Category: 3. Business

Eleven crypto companies raised $99.6 million this week, according to DefiLlama data.

That brings the total funding for crypto companies to nearly $22 billion so far in 2025, far outpacing 2024’s total by over $11 billion.

Investors from Galaxy Ventures and Codebase expect it to go even higher, with investors expected to plough over $25 billion into the industry in 2025.

Despite the October deleveraging, the crypto fundraising environment remains stable, according to Mike Giampapa, General Partner of Galaxy Ventures.

Giampapa told DL News that while the crash broke records for the dollar amount leveraged traders lost, the fundamental view of the market remains the same.

“We are more confident than ever that financial services are going to be re-platformed onto blockchains and view shocks like this as a way to bulletproof the onchain financial systems of tomorrow.”

Karl-Martin Ahrend, co-founder of crypto M&A firm Areta, also pointed out that dealmaking takes months in advance and is typically conducted with a longer time horizon than market resets.

“So far sentiment and momentum continues to be strong with no notable downturn in interest,” Ahrend told DL News.

This week’s slate of deals was evidence of that.

On Tuesday, Coinbase acquired token fundraising platform Echo for $375 million, signalling renewed interest in the controversial initial coin offering.

FalconX also acquired crypto asset manager 21Shares on Wednesday in a bid to deepen its footprint in the fast-growing exchange-traded fund (ETF) sector.

Likewise, the development team behind the decentralised lending giant, Aave, acquired stablecoin savings startup Stable Finance.

Here are some other notable raises tracked by DefiLlama:

Pave Bank has raised $39 million in a Series A round to scale its programmable banking platform for fiat and digital assets.

The funding was led by Accel, with participation from Wintermute, Quona Capital, Helios Digital Ventures, and Tether Investments.

Licensed in Georgia, Pave Bank offers businesses real-time management of both fiat and crypto, automated treasury operations, and streamlined settlement infrastructure. CEO Salim Dhanani said the bank “merges the stability and oversight of traditional finance with the speed and intelligence of digital assets.”

Sign, a blockchain-based notary upstart targeting national governments as key clients, raised $26 million in a strategic round led by YZi Labs.

Backed by heavy hitters including venture capital firm Sequoia, stablecoin issuer Circle, and former Binance CEO Changpeng Zhao, Sign says it aims to provide governments with a “comprehensive digital asset infrastructure that preserves sovereign authority.”

By Charles Passy

A new survey points to a growing tipping backlash as 65% of Americans say they’re fed up with doling out those dollars

The tip screen has become a fact of life at many businesses – and customers aren’t crazy about it.

Have Americans reached a tipping point when it comes to tipping?

A new consumer survey from Popmenu, a technology company that services the restaurant industry, suggests as much. The key data point: 65% of Americans said they’re fed up with tipping – a notable increase from 2023, when 53% said they had reached that point.

Americans seem to be especially bothered by the fact so many businesses have their hand out for tips, from quick-serve restaurants to dog-grooming establishments and vehicle-repair shops. Consumers said that in the past year, they spent $150 on tips they felt were unnecessary, according to the survey.

“People are saying, ‘I don’t know what to tip for any more,’” Popmenu CEO Brendan Sweeney told MarketWatch.

On top of that, the suggested tip amounts shown on now-ubiquitous “tip screens” can be 30% of the purchase price, or even more in some instances, said etiquette expert Nick Leighton.

“The suggested amounts can sometimes be bonkers. A $1, $2 or $3 tip suggestion on a $3 cup of coffee is a 33%, 66% or 100% tip,” he said.

Add it up and we could be looking at the beginning of a consumer tipping backlash, if not a full-scale revolt, experts say.

“People are totally over it,” said Izzy Kharasch, president of Hospitality Works, a Chicago-based restaurant-consulting firm.

Kharasch is part of that change in behavior. He said he generally doesn’t leave tips when he’s ordering a coffee or a muffin at a quick-serve establishment. It’s what he describes as the new norm – being “tip choosy.”

Consumers said that in the past year, they spent $150 on tips they felt were unnecessary.

The tipping boom started a few years ago, according to hospitality experts and others. Part of it was fueled by new technology: point-of-sale systems that built tip screens into the checkout process.

Another part was the growing awareness of the financial and other challenges that service workers face. That became particularly evident during the pandemic, when such employees were often told to show up for their jobs despite the health risks.

Tipping was “a meaningful way to thank service workers during an incredibly difficult time,” said Deidre Popovich, associate professor of marketing at Texas Tech University.

But now that we’re a few years past the pandemic, that concern may not be as significant, experts say. In addition, inflationary pressures have prompted many businesses – restaurants especially – to raise prices. So if consumers are having to pay more for their purchase, they may be less inclined to tip.

It’s also possible the new “no tax on tips” deduction – something Donald Trump touted heavily during the presidential campaign – could result in some consumers deciding to tip less. Certainly, it’s a point that’s been raised on social media.

Finally, there are just those people, like Kharasch, who simply question if all services merit a tip of any kind, much less a sizable one.

“I’m so over tipping. It’s gone too far,” business owner Alitzah Stinson said in a TikTok video that has drawn hundreds of comments. Specifically, she addressed issues with tipping when ordering a breakfast smoothie – before she’s even tasted the drink and decided whether it was good or not.

“It’s a smoothie. It’s not like a sit-down restaurant,” she added, before sharing one of her new “rules” for tipping. “I am not tipping anywhere where they ask me to tip before I’ve experienced the service,” she said.

What might happen if the tipping backlash becomes more significant?

Experts say that merchants may have to adjust expectations of what people will tip and, at the very least, lower the suggested amounts on those tip screens. Or they can simply opt to charge more upfront and build the tip into the overall price.

The Popmenu survey suggested the latter option would be an appealing one for many consumers, with 62% saying they would rather spend more for food and drink if it enabled restaurants to provide higher wages for their employees and do away with tipping entirely.

The status quo may prevail, tip screens and all, but consumers may begin to decide whether they really want to tip 30% or if they will just skip the gratuity altogether, experts say. Or perhaps consumers will find a middle ground that feels comfortable.

Either way, it appears they may no longer tip without discretion, said Popmenu’s Sweeney.

“I think it will get to where people say, ‘I’m going to have my own rules,’” he said.

-Charles Passy

This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal.

  (END) Dow Jones Newswires

  10-25-25 1110ET
Copyright (c) 2025 Dow Jones & Company, Inc.

Story Continues

• Late-breaking positive Phase III data from ianalumab NEPTUNUS-1 and NEPTUNUS-2 trials in Sjögren’s disease to be presented
• Biomarker data informing use of investigational CAR-T cell therapy rapcabtagene autoleucel (YTB323) in systemic lupus erythematosus also to be presented
• Data underscore Novartis commitment to advance innovative medicines for complex, difficult-to-treat autoimmune diseases with high unmet need
• Novartis to hold virtual investor event following ACR highlighting immunology pipeline progress

Basel, October 25, 2025 – Novartis announced today plans to present data from 27 company- or investigator-sponsored abstracts across its Immunology portfolio and pipeline at the 2025 American College of Rheumatology (ACR) Convergence. Data to be presented include late-breaking pivotal Phase III results from the replicate NEPTUNUS-1 and NEPTUNUS-2 trials evaluating ianalumab in Sjögren’s disease¹. New biomarker data from an ongoing Phase 1/2 study of rapcabtagene autoleucel in severe refractory systemic lupus erythematosus will also be presented, along with Cosentyx data in multiple rheumatology indications^2,3.

“Our data at this year’s ACR demonstrate that Novartis is at the forefront of scientific innovation and is developing medicines for some of the most challenging autoimmune diseases, such as Sjögren’s,” said Angelika Jahreis, Global Head, Development, Immunology, Novartis. “Autoimmune diseases are often devastating and life-limiting. We are committed to developing new therapies with the potential to transform the standard of care for the millions who continue to suffer from rheumatic diseases.”

Ianalumab is an investigational medicine that has the potential to become the first targeted therapy for Sjögren’s disease, an area of high unmet need with no FDA-approved treatments^4,5. Sjögren’s disease affects millions of people globally and is the second most prevalent rheumatic disease⁶.

Additional presentations include data for rapcabtagene autoleucel, a novel one-time investigational CAR-T cell therapy being evaluated across several refractory autoimmune disease for its potential to induce an immune reset^7-9. Further presentations will feature real-world data on Cosentyx^® (secukinumab) in psoriatic arthritis, and new insights into the dual mode of action of ianalumab.

Investor call on Novartis Immunology pipeline 
Following the conclusion of ACR, Novartis will host a conference call for investors to provide updates on the company’s Immunology pipeline on Thursday, October 30, 2025, at 11:30 a.m. ET. Details can be found here.

Key abstracts accepted by ACR include:

Molecule/disease state	Abstract title	Abstract number/ presentation details
Ianalumab
Sjögren’s disease	Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren’s Disease: Efficacy and safety results from two global Phase 3, randomized, placebo-controlled double-blind studies (NEPTUNUS-1 and NEPTUNUS-2)	Abstract #LB24 Oral presentation Oct. 29, 9:15 am – 9:30 am CST
Sjögren’s disease	Evaluation of the dual mode of action of Ianalumab (VAY736) in the circulation and salivary gland tissue of patients with Sjögren’s Disease: Results from a Phase 2 mechanistic study	Abstract #2296 Poster presentation Oct. 28, 10:30 am – 12:30 pm CST
Sjögren’s disease	Ianalumab’s dual mode of action: targeting B cells through enhanced B cell depletion and blockade of B cell activating factor receptor signaling	Abstract #0903 Poster presentation Oct. 27, 10:30 am – 12:30 pm CST
Systemic lupus erythematosus	Achieving sustained lupus low disease activity state and remission with ianalumab (VAY736) in patients with systemic lupus erythematosus: A post hoc analysis from a phase II study	Abstract #0801 Oral presentation Oct. 26, 1:00 pm – 1:15pm CST
Rapcabtagene autoleucel
Systemic lupus erythematosus	Biomarker data from an open-label, Phase 1/2 Study for YTB323 (Rapcabtagene Autoleucel, a rapidly manufactured CD19 CAR-T therapy) suggest reset of the B Cell compartment in severe refractory SLE	Abstract #2696 Oral Presentation Oct. 29, 12:15pm – 12:30 pm CST
Cosentyx (secukinumab)
Psoriatic arthritis	Comparison of incidence of psoriatic arthritis in patients with psoriasis treated with interleukin-17 inhibitors vs interleukin-23 inhibitors, interleukin-12/23 inhibitors, and tumor necrosis factor inhibitors in real-world practice: a retrospective study	Abstract #2689 Oct. 29, 12:15pm – 12:30 pm CST

About Novartis Immunology 
At Novartis, we’re advancing bold science for autoimmune diseases, where meaningful therapeutic progress has long stalled.

With a growing legacy of first-in-class innovation across Rheumatology, Dermatology and Allergy, and a diverse industry-leading pipeline, we’re committed to shaping what’s next in Immunology. From small molecules to biologics and CAR-T cell therapy, our innovation is powered by cutting-edge science, focused on where we can have the greatest impact on patient outcomes and supported by strong collaboration across the healthcare ecosystem. 

We’re not just treating autoimmune diseases. We’re reimagining medicine, together.

Product information
For full prescribing information, including approved indications and important safety information about marketed products, please visit https://www.novartis.com/about/products

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis 
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.

References

1. Novartis. Data on file.
2. Morand E, et al. Biomarker Data From an Open-Label, Phase 1/2 Study for YTB323 (Rapcabtagene Autoleucel, a Rapidly Manufactured CD19 CAR-T Therapy) Suggest Reset of the B Cell Compartment in Severe Refractory SLE. Abstract presented at ACR Convergence 2025. Accessed September 19, 2025. https://acrabstracts.org/abstract/biomarker-data-from-an-open-label-phase-1-2-study-for-ytb323-rapcabtagene-autoleucel-a-rapidly-manufactured-cd19-car-t-therapy-suggest-reset-of-the-b-cell-compartment-in-severe-refractory-sle/
3. Armstrong A, et al. Comparison of Incidence of Psoriatic Arthritis in Patients With Psoriasis Treated With Interleukin-17 Inhibitors vs Interleukin-23 Inhibitors, Interleukin-12/23 Inhibitors, and Tumor Necrosis Factor Inhibitors in Real-World Practice: A Retrospective Study. Abstract presented at ACR Convergence 2025. Accessed September 19, 2025. https://acrabstracts.org/abstract/comparison-of-incidence-of-psoriatic-arthritis-in-patients-with-psoriasis-treated-with-interleukin-17-inhibitors-vs-interleukin-23-inhibitors-interleukin-12-23-inhibitors-and-tumor-necrosis-factor-i/
4. Dorner T, et al. Safety and Efficacy of ianalumab in patients with Sjogren’s disease: 52-week results from a randomized, placebo-controlled, phase 2b dose-ranging study. Arthritis and Rheumatology. 2025; 77(5):560-570
5. Negrini S, et al. Sjogren’s syndrome: a systemic autoimmune disease, Clin Exp Med. 2022; 22(1): 9-25
6. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Committee on Selected Immune Disorders and Disability. Sjogren’s Disease/Syndrome. Accessed September 11, 2025. https://www.ncbi.nlm.nih.gov/books/NBK584486/ 
7. ClinicalTrials.gov NCT05798117 [Last accessed: September 2025]
8. ClinicalTrials.gov NCT06665256 [Last accessed: September 2025]
9. ClinicalTrials.gov NCT06655896 [Last accessed: September 2025]

# # #

• Sustained improvements across stringent measures of disease in patients with psoriatic arthritis (PsA): One-year improvements were sustained to three years across measures of peripheral arthritis, dactylitis, enthesitis, skin psoriasis, and nail psoriasis – indicating sustained inflammation control
• Sustained clinical response to stringent endpoints in half of patients with axial spondyloarthritis (nr-axSpA and AS): From Week 16 to three years, 50% of patients never lost ASDAS low disease activity (LDA) (<2.1) status at any assessed visit – indicating sustained inflammation control
• First real-world findings demonstrate rapid quality of life (HRQoL) improvements in patients with PsA, nr-axSpA, and AS: Improvements in outcomes in routine clinical practice were reported at 24 weeks, with benefits as early as Week 2 in some patients

ATLANTA, Oct. 25, 2025 /PRNewswire/ — UCB, a global biopharmaceutical company, today announced new three-year data from Phase 3 trials, and their open-label extensions, investigating BIMZELX^® (bimekizumab-bkzx) in adults with active psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and ankylosing spondylitis (AS). BIMZELX, the first and only medicine approved to selectively inhibit both interleukin 17A (IL-17A) and interleukin 17F (IL-17F),¹ continued to demonstrate sustained control of inflammation and deep efficacy in patients living with PsA, nr-axSpA, and AS.^2-6

Sustained improvements across stringent measures of disease in patients with PsA²

“The diverse, multi-faceted nature of PsA can make it challenging to treat, as therapy should ideally address multiple disease domains,” said Professor Laura Coates, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Diseases, University of Oxford, United Kingdom. “These compelling data show sustained improvements over three years across key PsA disease domains. This demonstrates that bimekizumab has potential to benefit a broad range of patients, and may improve long-term inflammation control and prevent structural damage.”

In patients with PsA, one-year improvements were sustained to three years across the following GRAPPA domains:* peripheral arthritis, dactylitis, enthesitis, skin psoriasis and nail psoriasis.² Individual domain responses were consistent between bDMARD‑naïve and TNFi-IR patients.² Further, exposure-adjusted incidence rates per 100 patient years for uveitis and definite or probable adjudicated inflammatory bowel disease (IBD) to Week 156 were 0.2 (95% confidence interval 0.1, 0.6) and 0.3 (0.1, 0.7) in BE OPTIMAL and 0 and 0.1 (0.0, 0.6) in BE COMPLETE, respectively.² (See Appendix for further details).

Sustained clinical response to stringent endpoints in half of patients with nr-axSpA and AS

“In clinical practice, ASDAS LDA is an important treatment target for disease control for people living with axSpA, as it is a highly stringent measure of low disease activity,” said Professor Fabian Proft, Universitätsmedizin Berlin, Germany. “It is therefore meaningful that in this study of bimekizumab, half of the patients never lost their ASDAS LDA response at any assessed visit over three years, while over three quarters of patients maintained this response over three years. This suggests long-term disease control, which is paramount in treating both nr-axSpA and AS.”

A high proportion of BIMZELX-randomized patients who achieved clinical responses at Week 16 maintained these to Week 164 across the full disease spectrum of axSpA, including nr-axSpA and AS.⁴ From Week 16 through to Week 164, 50% of patients never lost their ASDAS LDA (<2.1) status at any assessed visit (MI), with a further 22.4% only losing their ASDAS LDA status at one visit, and 6.1% at two visits, respectively (MI).⁴ Of the 152 patients (43.6%; NRI) who achieved ASDAS LDA at Week 16, 78.8% still achieved ASDAS LDA at Week 164 (MI).*⁴ 

*Proportion of patients who achieved ASDAS LDA at Week 16 and Week 164 in patients randomized to BIMZELX 160 mg every four weeks (Q4W) at baseline. ⁴

Real-world findings demonstrate rapid HRQoL improvements in patients with PsA, nr-axSpA, and AS^5,6

Interim, post-hoc data analysis (observed case, OC) of patient-reported outcomes from the SPEAK study in routine clinical practice showed that:^5,6

For BIMZELX-treated patients with PsA, improvements in PsAID-12 total score were observed to 24 weeks, with mean (SD) change from baseline (CfB) at Week 24 of −1.9 (2.0).⁵ SF-36 PCS scores improved to Week 24 (mean [SD] CfB: +4.6 [7.9]), as did PGADA scores (mean [SD] CfB: −17.5 [23.8]).⁵ At Week 2, mean (SD) CfB in PsAID-12 total score and PGADA score were -0.8 (1.6) and -7.1 (19.3), respectively.⁵

For BIMZELX-treated patients with nr-axSpA and AS, improvements in ASAS HI score were observed to 24 weeks, with mean (SD) CfB at Week 24 of –1.6 (3.0).⁶ SF-36 PCS scores improved to Week 24 (mean [SD] CfB: +5.7 [7.3]), as did PGADA scores (mean [SD] CfB: –1.0 [2.5].⁶ At Week 2, mean (SD) change from baseline (CfB) in ASAS HI score and PGADA score were –0.7 (2.3) and –0.8 (2.1), respectively.⁶

“This data presented at ACR shows that bimekizumab continues to demonstrate long-term improvement in inflammation control and deep efficacy in patients living with PsA and axSpA, and emphasizes that this effect is consistent across a spectrum of patients with these diseases,” said Donatello Crocetta, Chief Medical Officer, UCB.

UCB will present 16 abstracts on BIMZELX at ACR 2025 in Chicago, October 24-29, across nr-axSpA, AS, PsA, and psoriasis. These will complement seven other presentations from UCB across their rheumatology portfolio. This data underscores UCB’s ambition to be a leader in rheumatology, commitment to advancing clinical research and innovation, and focus on developing meaningful solutions across the spectrum of rheumatic diseases.

*Core domains of PsA according to GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) recommendations.⁷

Study methodology

PsA abstract:² Included patients who were randomized to subcutaneous BIMZELX 160 mg or placebo every 4 weeks (Q4W) in BE OPTIMAL (biologic DMARD [bDMARD]‑naïve patients with PsA), BE COMPLETE (patients with PsA with inadequate response or intolerance to TNF inhibitors [TNFi‑IR]), BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS, i.e., radiographic axSpA).² From Week 16, all placebo-randomized patients received BIMZELX 160 mg Q4W.² Week 52/16 BE OPTIMAL/BE COMPLETE completers were eligible for BE VITAL open-label extension; BE MOBILE 1 and 2 Week 52 completers could enter BE MOVING OLE.² 

AxSpA abstract:⁴ BE MOBILE 1 (nr-axSpA) and 2 (AS) from Week 16, all patients received subcutaneous BIMZELX 160 mg Q4W. At Week 52, eligible patients could enroll in the OLE (BE MOVING).⁴

Real-world study:^5,6 SPEAK is an ongoing 52-week, multi-country, observational study in Belgium, Czechia, France, Germany, Greece, Spain and the United Kingdom.^5,6 This planned interim analysis reports data to April 2, 2025 (approx. 50% enrollment).^5,6 Adult patients with active PsA, nr-axSpA, or AS who initiated BIMZELX in routine clinical practice could be included if receiving treatment per label (BIMZELX 160 mg Q4W).^5,6

Notes to Editors

• ASAS40 responder rate: Assessment in SpondyloArthritis international Society ≥40% improvement⁴
• ASAS HI: Assessment of SpondyloArthritis international Society Health Index⁶
• ASDAS LDA: axSpA Disease Activity Score (ASDAS) low disease activity (LDA; <2.1)^4,8
• Dactylitis: Inflammation of a finger or toe⁹
• Enthesitis: Inflammation where the tendons and ligaments insert into bones¹⁰
• GRAPPA domains: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-based treatment recommendations focus on six core domains and the PsA-related conditions, uveitis and IBD. The six core domains are: peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis and nail psoriasis^2,7
• IBD: Inflammatory Bowel Disease
• LDI: Leeds Dactylitis Index
• LEI: Leeds Enthesitis Index
• MI: Multiple imputation²
• mNAPSI: Modified nail psoriasis severity index²
• mNRI: Modified NRI²
• NRI: Non-responder imputation²
• PASI 100: 100% improvement from baseline in Psoriasis Area and Severity Index²
• PGADA: Patient Global Assessment of Disease Activity^5,6
• PsAID-12: 12-item PsA Impact of Disease questionnaire⁵
• SF-36 PCS: Short Form 36-item Health Survey Physical Component Summary^5,6
• SJC: Swollen joint count²
• TNFi-IR: Inadequate response or intolerance to tumor necrosis factor inhibitors²
• Uveitis: Inflammation of the middle layer of the eyeball called the uvea¹¹

Appendix

Further detail from 3-year PsA data across GRAPPA domains²

For the majority of GRAPPA domains, 1-year improvements were sustained to 3 years across all studies.² These include stringent measures of disease within the disease domains, for example, complete resolution of the following:²

Table adapted from data extracted from abstract table for nail psoriasis, peripheral arthritis, enthesitis, dactylitis, skin psoriasis, axial disease.

About Psoriatic Arthritis

Psoriatic arthritis is a serious, highly heterogeneous, chronic, systemic inflammatory condition affecting both the joints and skin with a prevalence of 0.02 percent to 0.25 percent of the population.¹² Psoriatic arthritis affects approximately 30 percent of people living with psoriasis.¹³ It manifests as joint pain and stiffness, skin plaques, swollen toes and fingers (dactylitis) and inflammation of the sites where tendons or ligaments insert into the bone (enthesitis).¹⁴ The burden on those living with PsA extends beyond physical discomfort to reduced quality of life, with comorbidities including hypertension, cardiovascular disease, anxiety, and depression.¹⁵ In PsA, uncontrolled active disease can lead to long-term, irreversible structural damage.¹⁶

About BE OPTIMAL and BE COMPLETE

BE OPTIMAL and BE COMPLETE were two Phase 3 studies evaluating the efficacy and safety of BIMZELX in the treatment of psoriatic arthritis.^17,18 The primary endpoint in both studies was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at Week 16.^17,18 BE OPTIMAL (bDMARD-naïve) and BE COMPLETE (TNFi-IR) assessed subcutaneous BIMZELX 160 mg every four weeks (Q4W) in patients with PsA; both studies were placebo-controlled to Week 16, after which placebo patients switched to BIMZELX.^17,18

BE OPTIMAL Week 52 and BE COMPLETE Week 16 completers were eligible for BE VITAL open-label extension.^17,18

About Axial Spondyloarthritis

Axial spondyloarthritis (axSpA), which includes both non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis (AS), is a chronic, immune-mediated, inflammatory disease.¹⁹ nr-axSpA is defined clinically by the absence of definitive x-ray evidence of structural damage to the sacroiliac joints.¹⁹ axSpA is a painful condition that primarily affects the spine and the joints linking the pelvis and lower spine (sacroiliac joints).¹⁹ The leading symptom of axSpA in a majority of patients is inflammatory back pain that improves with exercise, but not with rest.¹⁹ Other common clinical features frequently include anterior uveitis, enthesitis, peripheral arthritis, psoriasis, inflammatory bowel disease, and dactylitis.¹⁹ The overall prevalence of axSpA is 0.3 percent to 1.4 percent of adults.^20,21 Approximately half of all patients with axSpA are patients with nr-axSpA.¹⁹ axSpA onset usually occurs before the age of 45.¹⁹ Approximately 10 to 40 percent of patients with nr-axSpA progress to ankylosing spondylitis over 2 to 10 years.¹⁹

About BE MOBILE 1 and BE MOBILE 2

BE MOBILE 1 and BE MOBILE 2 were two Phase 3 studies evaluating the efficacy and safety of BIMZELX in the treatment of nr-axSpA and AS, respectively.²² The primary endpoint in both studies was the Assessment of SpondyloArthritis international Society 40 percent (ASAS40) response at Week 16.²² BE MOBILE 1 and BE MOBILE 2 comprised a 16-week double-blind treatment period followed by a 36-week maintenance period.²² In BE MOBILE 1 and BE MOBILE 2, patients were randomized to BIMZELX (160 mg Q4W; N=128 for BE MOBILE 1 and N=221 for BE MOBILE 2) or to placebo (N=126 for BE MOBILE 1 and N=111 for BE MOBILE 2). Patients initially randomized to placebo were switched to BIMZELX (160 mg Q4W) at Week 16.²² BE MOBILE 1 and BE MOBILE 2 Week 52 completers were eligible for BE MOVING open-label extension.²²

About BIMZELX^® (bimekizumab-bkzx)
BIMZELX is a humanized monoclonal IgG1 antibody that is designed to selectively inhibit both interleukin 17A (IL-17A) and interleukin 17F (IL-17F), two key cytokines driving inflammatory processes.¹ IL-17A and IL-17F are key contributors of chronic inflammation and damage across multiple tissues, with IL-17F increasing over time.^1,23-25 IL-17F is over-expressed in skin and highly elevated in the serum of patients with psoriasis (PSO), psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA), ankylosing spondylitis (AS), and hidradenitis suppurativa (HS).^1,23-26

The approved indications for BIMZELX in the U.S. are:¹

• Plaque psoriasis: BIMZELX is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
• Psoriatic arthritis: BIMZELX is indicated for the treatment of adult patients with active psoriatic arthritis
• Non-radiographic axial spondyloarthritis: BIMZELX is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation
• Ankylosing spondylitis: BIMZELX is indicated for the treatment of adult patients with active ankylosing spondylitis
• Hidradenitis suppurativa: BIMZELX is indicated for the treatment of adults with moderate- to-severe hidradenitis suppurativa

BIMZELX U.S. IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

Suicidal Ideation and Behavior
BIMZELX (bimekizumab-bkzx) may increase the risk of suicidal ideation and behavior (SI/B). A causal association between treatment with BIMZELX and increased risk of SI/B has not been definitively established. Prescribers should weigh the potential risks and benefits before using BIMZELX in patients with a history of severe depression or SI/B. Advise monitoring for the emergence or worsening of depression, suicidal ideation, or other mood changes. If such changes occur, instruct to promptly seek medical attention, refer to a mental health professional as appropriate, and re- evaluate the risks and benefits of continuing treatment.

Infections
BIMZELX may increase the risk of infections, including serious infections. Do not initiate treatment with BIMZELX in patients with any clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing BIMZELX. Instruct patients to seek medical advice if signs or symptoms suggestive of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, monitor the patient closely and do not administer BIMZELX until the infection resolves.

Tuberculosis
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with BIMZELX. Avoid the use of BIMZELX in patients with active TB infection. Initiate treatment of latent TB prior to administering BIMZELX. Consider anti-TB therapy prior to initiation of BIMZELX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Closely monitor patients for signs and symptoms of active TB during and after treatment.

Liver Biochemical Abnormalities
Elevated serum transaminases were reported in clinical trials with BIMZELX. Test liver enzymes, alkaline phosphatase, and bilirubin at baseline, periodically during treatment with BIMZELX, and according to routine patient management. If treatment-related increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt BIMZELX until a diagnosis of liver injury is excluded. Permanently discontinue use of BIMZELX in patients with causally associated combined elevations of transaminases and bilirubin. Avoid use of BIMZELX in patients with acute liver disease or cirrhosis.

Inflammatory Bowel Disease
Cases of inflammatory bowel disease (IBD) have been reported in patients treated with IL-17 inhibitors, including BIMZELX. Avoid use of BIMZELX in patients with active IBD. During BIMZELX treatment, monitor patients for signs and symptoms of IBD and discontinue treatment if new onset or worsening of signs and symptoms occurs.

Immunizations
Prior to initiating therapy with BIMZELX, complete all age-appropriate vaccinations according to current immunization guidelines. Avoid the use of live vaccines in patients treated with BIMZELX.

Most Common Adverse Reactions
Most common (≥ 1%) adverse reactions in plaque psoriasis and hidradenitis suppurativa include upper respiratory tract infections, oral candidiasis, headache, injection site reactions, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other candida infections, and fatigue.

Most common (≥ 2%) adverse reactions in psoriatic arthritis include upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infections.

Most common (≥ 2%) adverse reactions in non-radiographic axial spondyloarthritis include upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, transaminase increase, and urinary tract infections.

Most common (≥ 2%) adverse reactions in ankylosing spondylitis include upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection site pain, rash, and vulvovaginal mycotic infection.

Please see Important Safety Information below and full U.S. Prescribing Information at www.UCB- USA.com/Innovation/Products/BIMZELX.

For further information, contact UCB:

Investor Relations
Antje Witte
T +32.2.559.94.14
email [email protected]

Brand Communications
Nicole Herga 
T +1.773.960.5349 
email: [email protected] 

About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9,000 people in approximately 40 countries, the company generated revenue of €6.1 billion in 2024. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter:@UCBUSA.

Forward looking statements
This document contains forward-looking statements, including, without limitation, statements containing the words “potential”, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will”, “continue” and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guaranteeing future performance and are subject to known and unknown risks, uncertainties, and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to be materially different from any future results, performance, or achievements expressed or implied by such forward-looking statements contained in this document.

Important factors that could result in such differences include but are not limited to: global spread and impacts of wars, pandemics and terrorism, the general geopolitical environment, climate change, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues, supply chain disruption and business continuity risks; potential or actual data security and data privacy breaches, or disruptions of UCB’s information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars or disruptive technologies/business models, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in laws and/or rules pertaining to tax and duties or the administration of such laws and/or rules, and hiring, retention and compliance of employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB’s efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB’s products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB’s data and systems.

Given these uncertainties, the public is cautioned not to place any undue reliance on such forward-looking statements. These forward- looking statements are made only as of the date of this document, and do not reflect any potential impacts from the evolving event or risk as mentioned above as well as any other adversity, unless indicated otherwise. The company continues to follow the development diligently to assess the financial significance of these events, as the case may be, to UCB.

UCB expressly disclaims any obligation to update any forward-looking statements in this document, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations.

References

1. BIMZELX^® (bimekizumab-bkzx) U.S. Prescribing Information. https://www.ucb-usa.com/Innovation/Products/BIMZELX.
2. Merola J. Sustained Efficacy up to 3 Years with Bimekizumab Treatment Across GRAPPA Core Domains in Patients with Psoriatic Arthritis: Long-Term Results from Two Phase 3 Trials [abstract]. ACR 2025. #2129566.
3. Rudwaleit M. Long-Term Uveitis Rates with Bimekizumab Treatment Across Pooled Phase 2b and Phase 3 Studies in Patients with Axial Spondyloarthritis or Psoriatic Arthritis: 3-Year Update [abstract]. ACR 2025. #2129301.
4. Proft F. Bimekizumab Treatment Resulted in Patients with Axial Spondyloarthritis Maintaining Their Clinical Responses Over 3 Years: Results from Two Phase 3 Studies and Their Open-Label Extension [abstract].ACR 2025. #2129239.
5. Baraliakos X. An Interim Analysis of Health-Related Quality of Life Outcomes from an International Multicentre Observational Study in Patients with Psoriatic Arthritis Initiating Bimekizumab in Real-World Clinical Practice [abstract]. ACR 2025. #2127676.
6. Baraliakos X. An Interim Analysis of Health-Related Quality of Life Outcomes from an International Multicentre Observational Study in Patients with Axial Spondyloarthritis Initiating Bimekizumab in Real-World Clinical Practice. [abstract]. ACR 2025. #2127714.
7. Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): Updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol. 2022;18(8):465–79.
8. Garcia-Magallón B et al. Is the new ASDAS nomenclature in agreement with therapeutic decision making in patients with axial spondyloarthritis? Semin Arthritis and Rheum. 2020;50(5):854-57.
9. Hamard A, Burns R, Miquel A, et al. Dactylitis: A pictorial review of key symptoms. Diagn Interv Imaging. 2020;101(4):193-207.
10. Sudoł-Szopińska I, Kwiatkowska B, Prochorec-Sobieszek M, et al. Enthesopathies and enthesitis. Part 1. Etiopathogenesis. J Ultrason. 2015;15(60):72-84.
11. Maghsoudlou P, Epps SJ, Guly CM, et al. Uveitis in adults: a review. JAMA. 2025;334(5):419-434.
12. Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheum Dis Clin North Am. 2015;41(4):545–68.
13. Mease PJ, Gladman DD, Papp KA, et al. Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol. 2013;69(5):729-735.
14. Mease PJ, Armstrong A. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014;74(4):423–41.
15. Lee S, Mendelsohn A, Sarnes E. The burden of psoriatic arthritis: A literature review from a global health systems perspective. P T. 2010;35(12):680–89.
16. Kwok T, Sutton M, Cook R, et al. Musculoskeletal Surgery in Psoriatic Arthritis: Prevalence and Risk Factors. J Rheumatol. 2023;50(4):497–503.
17. Ritchlin C, Coates L, McInnes I, et al. Bimekizumab treatment in biologic DMARD-naïve patients with active psoriatic arthritis: 52-week efficacy and safety results from the phase III, randomised, placebo-controlled, active reference BE OPTIMAL study. Ann Rheum Dis. 2023;82(11);1404–14.
18. Coates L, Landewé R, McInnes I, et al. Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL. RMD Open. 2024;10(1):e003855.
19. Deodhar A. Understanding Axial Spondyloarthritis: A Primer for Managed Care. Am J Manag Care. 2019;25(1):S319–30.
20. Reveille J, Witter J, Weisman M. Prevalence of axial spondyloarthritis in the United States: estimates from a cross- sectional survey. Arthritis Care Res (Hoboken). 2012;64(6):905–10.
21. Hamilton L, Macgregor A, Toms A, et al. The prevalence of axial spondyloarthritis in the UK: a cross-sectional cohort study. BMC Musculoskelet Disord. 2015;16:392.
22. Baraliakos X, Deodhar A, van der Heijde D, et al. Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies. Ann Rheum Dis. 2024;83(2):199–213.
23. Glatt S, Baeten D, Baker T et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. 2018;77:523–32.
24. Gordon KB, Foley P, Krueger JG, et al. Bimekizumab efficacy and safety in moderate-to-severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet. 2021;397(10273):475-486.
25. Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the treatment of moderate-to-severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial. Lancet. 2021;397(10273):487-498.
26. Rumberger BE, Boarder EL, Owens SL, et al. Transcriptomic analysis of hidradenitis suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis. Inflamm Res. 2020;69(10):967-973.

US-BK-2501221 
Date of preparation: October 2025
BIMZELX^® is a registered trademark of the UCB Group of Companies. 
©2025 UCB, Inc., Smyrna, GA 30080. All rights reserved

SOURCE UCB

BEIJING, Oct. 25 (Xinhua) — China saw 48,921 newly established foreign-invested firms in the first three quarters of 2025, a year-on-year increase of 16.2 percent, according to data released Saturday by the Ministry of Commerce.

During the same period, the actual foreign direct investment (FDI) inflow totaled 573.75 billion yuan (80.89 billion U.S. dollars), down 10.4 percent year on year. However, FDI in September alone rose 11.2 percent year on year, the data showed.

By sector, manufacturing attracted 150.09 billion yuan in actual FDI during the period, while the services sector drew 410.93 billion yuan.

Notably, investment from Japan, the United Arab Emirates, the UK and Switzerland surged by 55.5 percent, 48.7 percent, 21.1 percent, and 19.7 percent year on year, respectively, during the same period, the data showed.  ■

• Vera Therapeutics announced that its ORIGIN Phase 3 trial of atacicept for IgA nephropathy met its primary endpoint, showing statistically significant and clinically meaningful reductions in proteinuria and a safety profile comparable to placebo, with results presented at ASN Kidney Week 2025.

• Atacicept has also received FDA Breakthrough Therapy Designation, underlining its potential as an innovative treatment for autoimmune kidney diseases.

• We’ll explore what the positive ORIGIN Phase 3 data and Breakthrough Therapy Designation mean for Vera Therapeutics’ investment narrative.

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For shareholders, the core belief revolves around Vera Therapeutics’ ability to successfully bring atacicept to market as an innovative therapy for IgA nephropathy, potentially transforming its clinical and financial trajectory. The recent announcement that the ORIGIN Phase 3 trial met its primary endpoint and achieved a robust reduction in proteinuria, coupled with Breakthrough Therapy Designation, serves as a significant validation of the company’s clinical direction. Previously, the main short-term catalyst centered on regulatory data disclosures and regulatory progress for atacicept. With the latest data now in the spotlight at ASN Kidney Week 2025, the path toward regulatory submission and possible approval is clearer, elevating expectations around these near-term milestones. However, the company’s lack of revenue and ongoing quarterly losses remain major risks, as does future dilution from recent and potential equity offerings. Market interest may increase given the new efficacy data, but execution risk and financing needs persist for Vera despite the promising clinical results.

Otherwise, investors should not overlook the risk of continued operating losses and share dilution. Despite retreating, Vera Therapeutics’ shares might still be trading above their fair value and there could be some more downside. Discover how much.

Across the Simply Wall St Community, fair value estimates for Vera Therapeutics vary widely, spanning from US$72.29 to a very large US$722.93 based on five distinct analyses. While opinions differ on valuation, the company’s breakthrough trial results could shift these perspectives further given the heightened focus on near-term regulatory approval and continued funding requirements. Explore these broader viewpoints to better understand how varying investor expectations shape Vera’s share performance.

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This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include VERA.

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

Introduction

Asthma is a heterogeneous respiratory disease, generally classified into Type 2 (T2) and non-Type 2 (non-T2) subtypes, characterized by chest tightness, cough, wheezing, and shortness of breath, affecting approximately 1–18% of the global population.^1–3 Previous studies have shown that airway epithelial damage plays a crucial role in asthma pathogenesis.^4,5 Despite continual advancements in clinical guidelines and therapeutic strategies, a substantial proportion of patients fail to achieve adequate disease control. This leads to frequent exacerbations and progressive decline in pulmonary function,⁶ underscoring the urgent need for highly sensitive and specific biomarkers to enhance diagnostic accuracy and optimize management strategies. Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation,⁷ which can trigger inflammatory cascades through the release of damage-associated molecular patterns (DAMPs) like reactive oxygen species (ROS).⁸ Earlier studies have shown that ferroptosis in airway epithelial cells contributes to the inflammatory response and plays a key role in the pathological progression of asthma.^9,10 Nevertheless, it remains unclear whether ferroptosis-related genes (FRGs) have diagnostic or therapeutic value in asthma.

The CRYAB gene encodes αB-crystallin, a small heat shock protein that functions as a molecular chaperone and modulates multiple intracellular signaling pathways, thereby influencing cellular proliferation and apoptosis.^11,12 Emerging evidence suggests that novel therapeutic strategies targeting CRYAB or its interacting proteins—by selectively inducing apoptosis or disrupting metastatic processes—can improve outcomes in patients with metastatic disease.^13,14 Although CRYAB has been implicated in the pathogenesis and progression of various disorders, its specific role in asthma remains unclear, as does its involvement in the regulation of ferroptosis.

Machine learning algorithms such as LASSO and SVM have shown significant potential in identifying disease biomarkers by selecting key feature genes from large datasets.^15,16 Zhang et al found that STUA1 and SLC27A3 are valuable diagnostic biomarkers for chronic obstructive pulmonary disease (COPD) and affect the mechanism of COPD to a certain extent through the combined LASSO and SVM algorithms.¹⁷ Previous studies have demonstrated that exposure to house dust mites disrupts systemic iron homeostasis, exacerbates lipid peroxidation, and activates ferritinophagy in asthma, ultimately inducing ferroptosis in airway epithelial cells and amplifying inflammatory responses.¹⁸ Consistent with these findings, both asthma animal models and cell models exhibit markedly elevated levels of Fe²⁺, malondialdehyde (MDA), and reactive oxygen species (ROS), accompanied by reduced glutathione (GSH) levels—hallmarks of enhanced ferroptosis—which further accelerate asthma progression.¹⁹ Based on this body of evidence, we hypothesize that CRYAB, as a pivotal component of the ferroptosis regulatory network, may play a critical role in the pathophysiological processes of asthma. In the present study, we employed an integrated approach combining LASSO and SVM algorithms to systematically identify FRGs associated with asthma from the GEO database. Candidate FRGs were subsequently validated using clinical specimens, followed by functional experiments involving CRYAB overexpression or silencing in airway epithelial cells to elucidate its biological roles. Collectively, our findings not only reveal a potential mechanistic link between FRGs-particularly CRYAB-and immune regulatory networks but also provide a theoretical framework for developing precision diagnostic biomarkers as well as novel therapeutics targeting ferroptosis-related pathways for improved management of asthma.

Materials and Methods

Data Collection

The GEO (Gene Expression Omnibus) database (https://www.ncbi.nlm.nih.gov/geo/) is an open-access repository that archives high-throughput gene expression data submitted by research groups worldwide.²⁰ Based on our research objectives, we identified and included three microarray datasets for further analysis: GSE137268 (54 asthma patients and 15 healthy controls), GSE148004 (9 asthma patients and 10 healthy controls), and GSE4302 (42 asthma patients and 28 healthy controls). We grouped these datasets as follows: GSE137268 and GSE148004 were designated as the experimental cohorts for mining disease-specific gene expression profiles, while GSE4302 served as an independent validation cohort to assess the accuracy of our findings.

Screening of DEGs

In this study, we used the “Limma” package in R to identify DEGs. The screening criteria were set as follows: |Log2 Fold Change (Log2FC)|> 0.5, and an adjusted P-value (adjust P.Val) < 0.05. Initially, we compared asthma samples with healthy controls within the experimental group to obtain the set of DEGs.

Enrichment Analysis of DEGs

Disease Ontology (DO) enrichment analysis was conducted using the DOSE package to further investigate disease mechanisms and support novel drug development,²¹ with p < 0.05 set as the threshold for significance.

Screening and Validation of Candidate Biomarkers

FRGs were downloaded from the FerrDb database and intersected with the previously identified DEGs to generate a list of candidate diagnostic biomarkers. Feature selection was performed using LASSO and SVM-RFE algorithms to identify potential diagnostic biomarkers from asthma patients, with p < 0.05 considered statistically significant. The predictive value of these FRGs for asthma was assessed using receiver operating characteristic (ROC) curve analysis, and their diagnostic performance was further validated using the GSE4302 dataset.

Immune Cell Infiltration Analysis

To investigate the role of immune cells in the pathogenesis of asthma, we performed single-sample Gene Set Enrichment Analysis (ssGSEA) using the “GSVA” package in R.

Sample Collection

For this study, lung lobe and segmental bronchial specimens were collected from patients undergoing lobectomy who met the inclusion criteria. A total of 12 specimens were obtained, including 6 from non-asthmatic patients and 6 from asthmatic patients. All participants provided written informed consent prior to sample collection. The study protocol was approved by the Ethics Committee of Henan Provincial People’s Hospital (No. 2024–077-01).

Cell Culture

The human bronchial epithelial cell line BEAS-2B was purchased from FuHeng (FH0319, Shanghai, China). Cells were cultured in DMEM supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 37°C, CO2 incubator.

Western Blot

Total protein was extracted from lung tissue or cells using RIPA lysis buffer (Jingcai Bio, Xian, China) and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, protein bands in the gel were transferred onto polyvinylidene difluoride (PVDF) membranes. The membranes were blocked with 5% non-fat milk and incubated with primary anti-CRYAB overnight at 4°C, followed by incubation with IRDye 680RD Goat anti-Rabbit for 1 hour at room temperature. The relative expression of protein was measured using Image J, with β-actin/GAPDH serving as the loading control.

Quantitative Real-Time PCR (RT-qPCR)

Total RNA was isolated from human lung tissue or cells using TRIzol reagent (Invitrogen, USA) according to the manufacturer’s protocol. Use a reverse transcription kit (Servicebio, Wuhan, China) to reverse transcribe RNA into cDNA. RT-qPCR was carried out on an ABI 7500 qPCR system using the 2× SYBR Green qPCR Master Mix (Vazyme, Nanjing, China) reagent. The endogenous reference gene primers for β-actin, as well as other RT-qPCR primers, are listed in Table 1, all of which were obtained from Sangon Biotech (Shanghai, China). All experiments were repeated three times. The relative expression level was calculated using the 2^−ΔΔCt method, with β-actin mRNA serving as an internal control for normalization.

Table 1 Primers Used in the RT-qPCR Reaction

Plasmid Transfection and RNA Interference

When cells reached 50–70% confluence in complete growth medium, they were transfected with either siRNAs or plasmids. The siRNAs and pcDNA3.1 constructs were synthesized by Sangon Biotech (Shanghai, China). Ferroptosis was induced by exposing the transfected cells with 10 μM erastin (MCE, USA) for 24 hours. All experiments were performed 48 hours after transfection.

ROS Detection

Intracellular ROS levels were measured using the ROS Assay Kit (Solarbio, Beijing, China). BEAS-2B cells were seeded at a density of 2×10⁵ cells per well in a 12-well plate. Following transfection with siRNA or pcDNA3.1 for 24 hours, cells were washed and incubated with PBS. The medium was then replaced with 500 μL of working solution containing 10 μM H₂DCFDA, and the cells were incubated at 37°C for 30 minutes. After washing twice with serum-free medium, ROS fluorescence was visualized and imaged using a laser confocal microscope (ZEISS LSM800, Oberkochen, Germany).

Cell Proliferation Assay

BEAS-2B cells were seeded at a density of 5×10³ cells per well in a 96-well plate. After transfection with siRNA or pcDNA3.1 plasmids, cell viability was assessed at 24, 48, and 72 hours using the CCK-8 assay (MCE, USA). CCK-8 solution was added to each well and incubated for an additional 1.5 hours. Absorbance was then measured at 450 nm using a microplate reader (Thermo Scientific, USA).

GSH and MDA Measurement

Reduced GSH levels were measured using the GSH Content Assay Kit (Jiancheng, Nanjing, China), and MDA levels were assessed with the Lipid Peroxidation MDA Assay Kit (Beyotime, Shanghai, China), following the manufacturers’ protocols. Cell preparation was performed as described for ROS detection.

Statistical Analysis of Data

All data are presented as mean ± standard deviation (SD) and were analyzed using GraphPad Prism 9.0 software (USA). Comparisons between two groups were made using an unpaired Student’s t-test; for variables not conforming to a normal distribution, the Mann–Whitney test was applied. p < 0.05 was considered statistically significant.

Results

Results of Differential Analysis and DO Analysis

After performing differential analysis on the experimental group dataset, a total of 213 DEGs were identified, including 39 downregulated and 174 upregulated genes. These DEGs were further visualized using heatmaps and volcano plots, as shown in Figure 1a and b. DO analysis refers to the enrichment analysis of differentially expressed or target gene sets using the DO database, in order to elucidate their potential roles in diseases such as asthma and other respiratory disorders.²² The results of this analysis (Figure 1c and d) indicated that the primary diseases significantly enriched among these DEGs included asthma, obstructive pulmonary disease, bronchial disease, and other respiratory system diseases. Therefore, this study preliminarily suggests that these DEGs are closely associated with the occurrence and development of asthma, thereby providing new insights into its diagnosis and treatment.

Figure 1 Analysis of DEGs and disease ontology enrichment in asthma samples. (a) Heatmap of DEGs. (b) Volcano map of DEGs. (c) Bar chart of DO analysis results. (d) Bubble chart of DO analysis results.

LASSO and SVM-RFE Analysis for Screening FRGs in Asthma

To investigate the role of ferroptosis in the pathogenesis of asthma, we retrieved a list of FRGs from the FerrDb database. Differentially expressed FRGs were identified using Venn diagram analysis, resulting in five candidate genes: TFRC, ACO1, CRYAB, SLC7A11, and GCLM (Figure 2a). To further determine which of these may serve as asthma-specific signature genes, we employed two machine learning algorithms: LASSO and SVM-RFE. LASSO regression identified four hub genes (TFRC, CRYAB, SLC7A11, and GCLM), while SVM-RFE selected five genes (TFRC, ACO1, CRYAB, SLC7A11, and GCLM), To enhance specificity, the intersection of both algorithms was taken. Ultimately, four FRGs—TFRC, CRYAB, SLC7A11, and GCLM—were identified as potential signature genes for asthma, as shown in Figure 2b–d.

Figure 2 Analysis results of FRGs in asthma. (a) Venn diagram showing the identification of differentially expressed FRGs. (b) LASSO regression analysis plot. (c) SVM-RFE algorithm analysis plot. (d) Venn diagram depicting the final selection of signature genes.

Diagnostic Value and Validation of Signature FRGs in Asthma

To determine the specificity and diagnostic value of the identified signature FRGs for asthma, ROC curve analysis was performed to assess their performance. The results showed (Figure 3a–d) that the areas under the curves (AUCs) of these four signature genes were 0.767 (CRYAB), 0.726 (GCLM), 0.722 (SLC7A11), and 0.756 (TFRC). Notably, both CRYAB and TFRC exhibited AUC values greater than 0.75, suggesting superior clinical utility as diagnostic biomarkers in asthma. Furthermore, we analyzed the expression levels of TFRC and CRYAB in an independent validation cohort (GSE4302). The results revealed CRYAB expression was significantly upregulated in patients with asthma, whereas TFRC expression was significantly downregulated compared to controls (Figure 3e and f). To further validate their diagnostic potential, ROC analyses were conducted based on their expression levels in the validation group, and AUC values were calculated as 0.659 for CRYAB and 0.629 for TFRC (Figure 3g and h). Taken together, results from both discovery and validation cohorts indicate that altered expression levels of CRYAB and TFRC may serve as promising diagnostic biomarkers or potential therapeutic targets for asthma.

Figure 3 Diagnostic value and validation of signature FRGs in asthma. (a–d). ROC curve graphs of the diagnostic efficacy of CRYAB, GCLM, SLC7A11, and TFRC for asthma. (e and f). Bar plots showing the expression levels of CRYAB and TFRC. (g and h). ROC curve graphs of the diagnostic efficacy of CRYAB and TFRC for asthma in the validation dataset. Notes: AUC > 0.7 is considered indicative of acceptable diagnostic value. Con = healthy control samples, Treat = asthma samples.

The Level of Immune Cell Infiltration and Its Relationship with Signature FRGs in Asthma

Immune cells play a crucial role in the pathological process of asthma, particularly in mediating inflammatory responses and airway remodeling. To investigate differences in immune cell infiltration between asthmatic patients and healthy controls, ssGSEA was performed on the experimental dataset. As shown in Figure 4a, the analysis revealed significantly increased infiltration of activated B cells, activated dendritic cells, myeloid-derived suppressor cells (MDSCs), macrophages, and mast cells in the peripheral blood of asthma patients compared to controls.

Figure 4 Analysis of immune cell infiltration. (a) Diagram of the differences in the infiltration of 28 types of immune cells between asthma and normal control samples. (b) Correlation diagram of CRYAB and TFRC with the abundance of immune cell infiltration. *p<0.05, **p<0.01, ***p<0.001.

To further elucidate their roles, we analyzed correlations between these hub genes and immune cell abundance. The results demonstrated that CRYAB expression was positively correlated with plasmacytoid dendritic cells, neutrophils, mast cells, eosinophils, activated dendritic cells, activated CD4 T cells, and activated B cells. Additionally, TFRC expression showed a positive correlation with immature dendritic cells but negative correlations with monocytes, macrophages, effector memory CD8 T cells and activated B cells (Figure 4b). Collectively, these findings suggest that CRYAB and TFRC may influence asthma pathophysiology through modulation of immune cell activity.

Validation of CRYAB Expression in Lung Tissues from Asthma Patients

To further verify the differential expression of CRYAB in clinical samples, we assessed its mRNA and protein levels in lung tissues from asthma patients and non-asthmatic controls using RT-qPCR and WB, respectively. As shown in Figure 5a and b, CRYAB expression was significantly upregulated in the asthma group compared to controls, while TFRC expression showed no significant difference between groups. Consistently, Western blot analysis confirmed increased CRYAB protein levels in asthmatic lung tissues (Figure 5c and d). As CRYAB is a FRG implicated in asthma, we speculate that it may contribute to disease pathogenesis by modulating ferroptosis.

Figure 5 Expression of CRYAB in patients with asthma and non-asthma controls. (a) Histogram of CRYAB mRNA expression in the two groups. (b) Histogram of TFRC mRNA expression in the two groups. (c and d) Representative WB analysis and quantification of CRYAB protein expression in both groups. **p<0.01, ***p<0.001.

Overexpression of CRYAB Attenuates Ferroptosis in BEAS-2B Cells

CRYAB, a key heat shock protein, is known to confer protection against oxidative stress-induced apoptosis, but its impact on ferroptosis in BEAS-2B cells remains unknown. To elucidate this, we performed siRNA-mediated knockdown and pcDNA3.1-mediated overexpression of CRYAB in BEAS-2B cells. RT-qPCR and Western blot analyses demonstrated effective knockdown by all three siRNAs (si-CRYAB-1/2/3), with si-CRYAB-3 exhibiting the highest silencing efficiency and thus selected for subsequent experiments (Figure 6a–c). Conversely, transfection with pcDNA3.1-CRYAB significantly increased both mRNA and protein levels of CRYAB compared to negative control (Figure 6d–f). Furthermore, erastin-induced ferroptosis resulted in a significant downregulation of CRYAB expression at both mRNA and protein levels (Figure 6g–i).

Figure 6 Expression of CRYAB during ferroptosis. (a–c) siRNA-mediated knockdown of CRYAB significantly reduced its mRNA and protein expression levels. (d–f) pcDNA3.1-mediated overexpression markedly increased CRYAB mRNA and protein expression. (g–i) Downregulation of CRYAB mRNA and protein expression during ferroptosis induction. **p<0.01, ***p<0.001.

To investigate whether CRYAB participates in ferroptosis by affecting the lipid peroxidation and antioxidant systems in human bronchial epithelial cells, we employed reagent kits to measure the levels of MDA and GSH. As shown in Figure 7a–d, erastin significantly elevated MDA levels while reducing GSH content in BEAS-2B cells, similar changes were observed upon CRYAB knockdown. In contrast, overexpression of CRYAB decreased MDA accumulation and increased GSH levels relative to controls. Additionally, intracellular ROS levels and cell viability were evaluated: overexpression of CRYAB reduced ROS accumulation and improved cell viability compared to the silenced group, which exhibited enhanced ROS production and decreased viability (Figure 7e–h). Collectively, these results suggested that CRYAB upregulation attenuates ferroptosis by maintaining redox homeostasis and reducing lipid peroxidation in airway epithelial cells. This highlights its potential protective role in the pathogenesis of asthma through regulation of ferroptotic pathways.

Figure 7 Effects of CRYAB knockdown or overexpression on ferroptosis-related markers in BEAS-2B cells. (a and b) Bar charts of GSH and MDA levels following CRYAB knockdown. (c and d) Bar charts of GSH and MDA levels following CRYAB overexpression. (e) Immunofluorescence images showing ROS accumulation after modulation of CRYAB expression. (f and g) Histograms of ROS immunofluorescence intensity. (h) Line charts of relative viability of BEAS-2B cells with altered CRYAB expression. *p<0.05, **p<0.01, ***p<0.001.

Discussion

Asthma is one of the most common chronic diseases worldwide, with a continuously increasing prevalence and affecting over 300 million people globally. Regardless of economic development status, asthma remains a significant public health challenge in most countries.^23–25 The pronounced heterogeneity of asthma often limits the effectiveness of conventional treatments; therefore, guiding diagnostic and therapeutic decisions based on specific molecular mechanisms, rather than relying solely on clinical manifestations, has become a central tenet of contemporary precision medicine. Ferroptosis, an iron-dependent form of regulated cell death, has recently been demonstrated to be closely associated with asthma.^26,27 Additionally, algorithmic tools such as LASSO and SVM-RFE have provided greater convenience for disease analysis.²⁸ In this study, we sought to explore the diagnostic value of FRGs in asthma and determine their expression levels in asthma patients as well as their role in ferroptosis within bronchial epithelial cells, thereby providing new biomarkers and drug targets for the diagnosis and treatment of asthma.

In this study, we identified 213 DEGs in the asthma group, with upregulated genes predominating. DO enrichment analysis further demonstrated that these DEGs are significantly associated with respiratory diseases, particularly asthma, obstructive pulmonary disease, and bronchial disorders. These findings underscore their potential involvement in the pathogenesis of asthma. To further elucidate specific mechanisms underlying asthma development, we focused on FRGs, given growing evidence linking ferroptosis to asthma. Using LASSO and SVM-RFE algorithms, we narrowed down potential diagnostic biomarkers to four hub FRGs: TFRC, CRYAB, SLC7A11, and GCLM. Previous studies have demonstrated that TFRC, CRYAB, SLC7A11, and GCLM play pivotal regulatory roles in key biological processes of ferroptosis, particularly in the regulation of intracellular iron metabolism and maintenance of redox homeostasis.^12,29–31 The identification of these FRGs as putative signature genes for asthma not only provides novel insights into disease mechanisms but also offers promising targets for biomarker development or therapeutic intervention. This lays the foundation for future clinical validation and functional studies aimed at improving diagnosis and management strategies for patients with asthma.

Our study systematically evaluated the diagnostic potential of four FRGs in asthma. Among them, TFRC and CRYAB exhibited consistent expression patterns and demonstrated significant diagnostic value. Specifically, CRYAB was significantly upregulated while TFRC was downregulated in asthma patients compared to controls. These results suggest that altered expression of CRYAB and TFRC may serve as reliable molecular biomarkers for asthma diagnosis across diverse patient populations and implicate their involvement in ferroptosis-associated disease mechanisms. Previous research has shown that activation of TFRC mediates ROS generation and promotes cellular iron accumulation; conversely, inhibition of the TFRC pathway can suppress lung cancer cell growth, indicating its potential as a therapeutic target.^32,33 Additionally, high CRYAB protein expression is clinically and pathologically relevant to the disease, including TNM stage and overall survival rate, playing a crucial role in the biology of non-small cell lung cancer.¹⁴ In summary, our findings highlight CRYAB and TFRC as promising candidate biomarkers or therapeutic targets related to ferroptosis pathways underlying asthma pathogenesis. Notably, their roles in asthma have not been previously reported, offering novel directions for future investigation.

To better understand the role of immune cells in asthma, we utilized the ssGSEA algorithm to assess the infiltration of 28 immune cell types in asthma samples. The analysis revealed significant differences in peripheral immune cell composition between asthmatic patients and healthy controls, with marked increases in activated B cells, dendritic cells, MDSCs, macrophages, and mast cells among asthma patients. These findings are consistent with previous reports emphasizing the involvement of both innate and adaptive immune components in airway inflammation and remodeling associated with asthma.^34–36 Furthermore, expression levels of CRYAB and TFRC were correlated with several pro-inflammatory cell types, suggesting that these genes may influence asthma pathophysiology by modulating distinct immune cell populations. These findings further demonstrate the importance of FRGs in immune responses and immune cell infiltration, and better support their potential as therapeutic targets for asthma.

To further elucidate the expression levels and potential mechanisms of TFRC and CRYAB in asthma, we conducted a comprehensive analysis of lung tissue specimens from asthmatic patients and non-asthmatic controls. Compared with controls, CRYAB expression was significantly increased in asthmatic lung tissue, which not only corroborates our bioinformatic findings but also underscores its potential relevance to asthma pathogenesis. In contrast, TFRC expression did not show significant differences at the tissue level. Previous studies have demonstrated that CRYAB is induced by heat shock, pro-inflammatory cytokines, and oxidative stress, playing a role in cell growth, migration, differentiation, and development.^37,38 Moreover, CRYAB has been implicated in inflammatory diseases by modulating the TNF-α signaling pathway through its antioxidant properties and regulation of TAK-1 activity.³⁸ Research has established that the antioxidant capacity of Hsp27 is closely associated with airway inflammation in asthma, particularly in bronchial epithelial damage. Increased expression of Hsp27 in the bronchial epithelium of asthmatic subjects has been observed, which helps mitigate oxidative stress caused by chronic inflammation.³⁹ Our research results are consistent with these findings. Therefore, we speculate that CRYAB may be involved in the pathogenesis of asthma by affecting ferroptosis in bronchial epithelial cells.

To investigate the potential involvement of CRYAB in asthma pathogenesis via the ferroptosis pathway, we performed an in vitro study using BEAS-2B cells. MDA is one of the final products of lipid peroxidation triggered by free radicals, while GSH is an important intracellular antioxidant that can remove ROS and protect cells from oxidative damage,⁴⁰ both of which play an important role in ferroptosis. We observed that CRYAB expression was downregulated upon treatment with erastin, a classical ferroptosis inducer. Overexpression of CRYAB reduced intracellular ROS and MDA levels while increasing GSH content, thereby attenuating erastin-induced ferroptosis in BEAS-2B cells. We conclude that overexpression of CRYAB significantly reduces lipid peroxide levels and enhances antioxidant capacity, thus protecting BEAS-2B cells from ferroptosis. Previous studies have shown that phosphorylated CRYAB promotes NRF2 upregulation and nuclear translocation, alleviating ferroptosis in cardiomyocytes through transcriptional regulation,⁴¹ consistent with our findings. Furthermore, we observed that overexpression of CRYAB increased bronchial epithelial cell survival rates under oxidative stress conditions. Other researchers have similarly found that overexpression of CRYAB reduces CSE-induced apoptosis and enhances cell survival.⁴² Our results suggest that CRYAB plays a pivotal role in asthma progression by regulating ferroptosis in bronchial epithelial cells through modulation of antioxidant and lipid peroxidation pathways, potentially serving as a biomarker and molecular therapeutic target for asthma in the future.

Previous studies have shown that in certain asthma phenotypes—particularly neutrophilic asthma—ferroptosis plays an important role. For example, the ferroptosis inhibitor Liproxstatin‑1 (Lip‑1) has been demonstrated to effectively attenuate pulmonary pathological changes in models of neutrophilic asthma, with its mechanism closely associated with the significant upregulation of key ferroptosis‑regulating factors SLC7A11 and GPX4.⁴³ Notably, excessive accumulation of reactive oxygen species (ROS) not only induces ferroptosis but also contributes to oxidative damage in neutrophilic asthma.⁴⁴ In our study, we confirmed that upregulation of CRYAB expression in bronchial epithelial cells can effectively enhance antioxidant defenses and suppress lipid peroxidation, thereby markedly alleviating ferroptosis. The present findings provide a new perspective and potential therapeutic targets for understanding the regulation of ferroptosis in neutrophilic asthma. We propose that targeting CRYAB or its regulatory pathways may represent an effective strategy to mitigate ferroptosis and associated inflammatory injury in neutrophilic asthma. Therefore, future research will further explore the impact of CRYAB overexpression or inhibition on core inflammatory responses in neutrophilic asthma and elucidate its specific underlying mechanisms.

In conclusion, this study integrated bioinformatics analysis with clinical sample validation and in vitro experiments to identify CRYAB as a potential diagnostic biomarker with immunological relevance in asthma. Our findings demonstrate that CRYAB overexpression attenuates ferroptosis in bronchial epithelial cells, suggesting its role in modulating disease pathophysiology. However, current conclusions remain preliminary, primarily due to limitations including exploratory database mining without multi-cohort stratified validation, and bench-derived experiments constrained by modest sample sizes that lack endotype-specific mechanistic dissection. Future investigations should focus on deploying larger-scale independent cohorts for robust confirmatory validation; executing targeted mechanistic studies, including both cellular and animal models, to clarify the functional integration of CRYAB activity within ferroptosis regulatory networks across Th2 and non-Th2 asthma, and performing preclinical evaluations aimed at assessing translational viability prior to clinical application.

Data Sharing Statement

All data used and/or analyzed during this study are included in this article. And the data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

This study was performed in accordance with the Helsinki declaration. All patients obtained informed consent and were approved by the Ethics Committee of Henan Provincial People’s Hospital (No. 2024-077-01).

Acknowledgments

We would like to extend our sincere gratitude to the public databases GEO and FerrDb for providing data for our research.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by the Provincial-Ministerial Joint Construction Project of Henan Province Medical Science and Technology Tackling Plan (SBGJ202302003).

Disclosure

The authors declare no competing interests in this work.

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Companies discussed in this article include ETOR.

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