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  • Skechers just can’t quit making crappy AI ads

    Skechers just can’t quit making crappy AI ads

    As AI becomes more accessible, it seems we’ve been plagued with an increasing number of AI ads. Lacking both quality and style, these sloppy marketing ploys are hard to ignore, but Skechers’ latest ad might just be the worst offender I’ve seen in some time.

    The best billboard ads are crafted to make us stop in our tracks, whether that’s with guerrilla marketing or ingenious design, but Skechers’ ad has caught attention for all the wrong reasons. Obviously AI to a painful degree, the abysmal ad is a troubling reflection of a looming future without AI regulation in advertising.


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  • Role of ILC2s as potential effector cells of IL25-mediated type 2 infl

    Role of ILC2s as potential effector cells of IL25-mediated type 2 infl

    Introduction

    Chronic rhinosinusitis (CRS) is a common disease marked by elevated levels of T helper (Th) cytokines, chronic rhinosinusitis with nasal polyps (CRSwNP) is closely associated with type 2 inflammation showing high concentrations of Th2 cytokines such as IL-5 and IL-13.1–3 Recent research suggests that these cytokines are produced not only by T cells but also by other immune cells, such as mast cells, basophils, and group 2 innate lymphoid cells (ILC2s).4–6 As a result, Th2 cytokines are now broadly referred to as type 2 cytokines. In Western countries, CRSwNP is predominantly associated with type 2 inflammation, characterized by pronounced eosinophilia and elevated levels of type 2 cytokines including IL-5 and IL-13.7 However, while less frequent, the occurrence of this type 2 inflammation in NPs is increasing among Asian patients as well.8,9

    Interleukin (IL)-25, which is a member of the IL-17 cytokine family and known as IL-17E, plays a key role in inducing and regulating type 2 inflammation.10–13 IL-25 is mainly produced by epithelial cells, Th2 cells, mast cells, eosinophils, macrophages, dendritic cells, and basophils.10,14–18 In mouse model, IL-25 has been shown to play an important role in the pathogenesis of CRSwNP.19 Targeting IL-25 neutralizing antibodies can reduce the number of polyps and inflammatory status in murine NPs.19 However, the role of IL-25 on NPs development in human is still controversial, and the expression of IL-25 in NPs is likely related to ethnicity. Research in the United States using a larger cohort found that IL-25 levels were nearly undetectable in NPs.20 In contrast, studies from Asian countries have reported elevated IL-25 levels in NPs, suggesting that IL-25 may be involved in the pathogenesis of eosinophilic NPs specifically in Asian populations.20 However, a recent study in the US found IL-25 in the NP is primarily produced by solitary chemosensory cells that is a subset of epithelial cells.21 This indicates that the quantity of these cells in NPs may influence IL-25 detection and suggests that IL-25 could play a role in NP pathogenesis even in Western populations. Further research is needed to clarify the role of IL-25 and its effector cells in the NPs from CRSwNP patients.

    ILC2s function as an important role in type 2 inflammation and can be activated to produce a large number of Th2 cytokines IL-4, IL-5 and IL-13 under the influence of upper dermal cytokines IL-25, IL-33 and thymic stromal lymphopoietin (TSLP), which are involved in the process of immune reaction.22–27 Research has shown that ILC2 were dominant and significantly elevated in NPs compared to PBMC, tonsil, and normal sinus tissue in CRSwNP patients.28 Our previous research has shown that IL-25 is able to regulate pathogenesis of asthma and allergic rhinitis primarily through ILC2s sorted from peripheral blood mononuclear cells.29 However, under IL-25 stimulation, the role of ILC2s in NPs from Chinese CRSwNP patients remains uninvestigated.

    Thus, this study aimed to examine the impact of IL-25 on the ILC2s isolated from NPs of Chinese CRSwNP patients in response to IL-25 stimulation. In vitro studies were used to investigate the potential signaling pathway involved in the effects of IL-25 on ILC2s in CRSwNP diseases.

    Methods

    Study Subjects

    The study was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (2024-KY-0405-002) in accordance with the Declaration of Helsinki. Written informed consent was obtained from 44 subjects (ages 16–65), including 37 patients with CRSwNP and 7 control patients with pituitary tumors but without CRS. All patients underwent endoscopic sinus surgery were diagnosed with CRSwNP according to EPOS 2020 guidelines and were refractory to standardized medical treatment.

    Inclusion Criteria for CRSwNP Patients

    1. All participants met the diagnostic criteria outlined in the 2012 European Position Paper on Sinusitis and Nasal Polyps (EPOS) and had a disease duration of more than 12 weeks with nasal polyps.

    2. Primary symptoms: Nasal congestion and/or sticky or purulent nasal discharge.

    3. Secondary symptoms: Facial swelling and a decreased or lost sense of smell. Diagnosis required at least two of the symptoms listed above.

    4. Nasal endoscopy findings: Presence of viscous or mucopurulent secretions in the middle nasal passage and olfactory fissure, along with nasal mucosa congestion, edema, or visible polyps.

    5. Imaging findings: CT scans showing inflammatory lesions of the ostiomeatal complex and/or sinus mucosa.

    Exclusion Criteria

    1. Use of nasal spray hormones or oral hormone therapy within the past month.

    2. Symptoms of acute upper respiratory tract infection within the past month.

    3. Pregnancy.

    4. Serious comorbid organ or systemic diseases (eg, heart, liver, kidney), immunodeficiency (eg, AIDS), abnormal coagulation function, or neoplastic diseases.

    Collection and Treatment of Specimens

    Samples were collected from the NPs and TM of CRSwNP patients, as well as from the TM of non-CRS pituitary tumor patients. Immunohistochemical methods were used to detect IL-25 levels in these tissues. The level of ILC2s was measured using flow cytometry after single-cell staining. NPs from CRSwNP patients were divided into two groups: one cultured with DMEM (Gibco, USA) alone and the other stimulated with DMEM plus IL-25 (Human IL-17E (IL-25) Recombinant Protein, PeproTech®) for 12 hours at 10 ng/mL. The levels of IL-5 and IL-13 in the supernatant were measured using the ELISA kits (Abcam, USA).

    Protein was extracted from the NPs to analyze the phosphorylation levels of STAT3, using Western blotting.

    Western Blot

    Western blot experiments were carried out by following the well-established protocols with modifications.19,29 Proteins were extracted from nanoparticles (NPs) subjected to various experimental conditions. An equal amount of protein (15 μg per lane) was loaded onto SDS-PAGE gels for electrophoretic separation, followed by transfer onto polyvinylidene difluoride (PVDF) membranes (Roche Diagnostics, Indianapolis, IN). Membranes were blocked using 10% nonfat dry milk, rinsed, and then incubated with primary antibodies against phosphorylated STAT3 (Tyr705) (D3A7) XP rabbit monoclonal antibody (1:500 dilution) and GAPDH mouse monoclonal antibody (1:10000 dilution). Following additional washes, membranes were treated with horseradish peroxidase (HRP)-conjugated secondary antibodies targeting rabbit or mouse IgG. Protein bands were visualized using Enhanced Chemiluminescence Plus detection reagent (Millipore Corporation, Billerica, MA). All antibodies used were sourced from Cell Signaling Technology (Danvers, MA).

    Enzyme-Linked Immunosorbent Assay (ELISA)

    The levels of human IL-5, IL-13 in the supernatants of extraction of nasal polys and ILC2s cell-culture were examined using commercially available ELISA kits (RayBiotech Inc, Norcross, GA for IL-5 and IL-13 in accordance with the manufacturer’s instructions. The detection limits were 2.74 pg/mL for IL-5, 0.15 pg/mL for IL-13. All values below the detection limits were set at 0.

    ILC2s Isolation and Cell Sorting from Human NP Tissue

    ILC2s were sorted from patients’ NPs with CRSwNP as previously described.30 Tissue samples were fragmented and incubated with 30 µg/mL DNase I and 1 mg/mL type I collagenase containing media at 4 °C overnight. Following this, tissues were minced using dissociator, and the cells were filtered through 70 -µm nylon mesh (BD Biosciences, San Jose, CA). Cells were then treated with red blood cell lysis solution (Miltenyi Biotec) before counting and staining for cell sorting. After the isolation, cells were first treated with Aqua LIVE/DEAD fixable dead cell staining reagent (Invitrogen, Carlsbad, CA) at room temperature in the dark. Cells were then blocked by Fc Block reagent and incubated with Human Hematopoietic Lineage FITC Cocktail (eBioscience, USA), Anti-Human Fc epsilon Receptor I alpha (FceR1) FITC (eBioscience, USA), PE-Cy7 Mouse Anti-Human CD127 (BD, USA) and PE Rat Anti-Human CD294 (CRTH2) (BD, USA) at 4 °C in the dark. We sorted ILC2s (Lin−FceR1−CRTH2+CD127+ lymphocytes) with a BD FACSAria SORP cell sorter.

    Cell Culture

    Sorted NPs ILC2s, were suspended in the RPMI medium supplemented with 25 IU/mL IL-2 (Prometheus, San Diego, CA), 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin, as previously described.30 ILC2s were stimulated with 100 ng/mL IL-25 (R&D Systems, Minneapolis, MN), with addition of limonin (stored in DMSO at 5 mM) at 100 μM for 30 minutes. After the centrifuge, the expression of IL-5 and IL-13 was quantified by ELISA kits (Abcam, USA). After the protein extraction, the phosphorylation of STAT3 was quantified by Western blot.

    Immunohistochemistry

    IHC of NPs and TM tissues was performed as previously reported with modifications.19 Immunohistochemical (IHC) staining was performed using the Polink-2 HRP Plus Broad DAB Detection System (Golden Bridge International Labs, Bothell, WA). After deparaffinization, the tissue sections were treated with 3% hydrogen peroxide to block endogenous peroxidase activity and subjected to heat-induced epitope retrieval in 10 mmol/L citrate buffer (pH 6.0) using a microwave. The sections were then incubated at room temperature for 60 minutes with a primary antibody, rabbit anti-human IL-25 (1:500, Abcam). Following this, incubation was carried out using a broad antibody enhancer, polymer-horseradish peroxidase (HRP), and staining with the DAB Detection System. Hematoxylin was used as a counterstain. Sequential IHC was performed using polymer-HRP and alkaline phosphatase kits to detect primary antibodies in human tissue, with Permanent Red and Emerald staining (Polink DS-MR-Hu C2 Kit, Golden Bridge International Labs) used to identify IL-25. Polymer mixtures were created by combining alkaline phosphatase polymer anti-mouse IgG and polymer-HRP anti-rabbit IgG in a 1:1 ratio and used as negative control.

    Flow-Cytometric Analysis

    Flow-cytometry was utilized to count ILC2s as previously described.30 Cells were first treated with Aqua dead cell staining reagent as a live/dead discriminator. Cells were then incubated with an Fc Block reagent (Miltenyi Biotec) for 10 min at 4 °C in the dark. Cells were stained with the following antibodies: Human Hematopoietic Lineage FITC Cocktail (eBioscience, USA), Anti-Human Fc epsilon Receptor I alpha (FceR1) FITC (eBioscience, USA), PE-Cy7 Mouse Anti-Human CD127 (BD, USA) and PE Rat Anti-Human CD294 (CRTH2) (BD, USA). Cells were stained for 30 min at 4 °C in the dark and washed with MACS buffer (Miltenyi Biotech). After washing, cells were fixed with a BD Cytofix/Cytoperm Kit (BD Biosciences), resuspended in MACS buffer, and stored at 4 °C in the dark before analysis on a CytoFLEX flow cytometer (Beckman Coulter, Indianapolis, IN). All analysis was performed with FlowJo software, version 10.1 (TreeStar, Ashland, OR), and the experimental method was established and verified with the proper single-stained control beads (BD Biosciences and eBiosciences).

    Statistical Analyses

    SPSS26 software was used for data analysis. The data were pre-sented as mean ± SEM. Statistical analyses were performed using paired or unpaired nonparametric tests (Mann–Whitney test, Krus-kal-Wallis test, Dunn’s multiple comparison test and Spearman rank correlation). P value less than 0.05 was considered statistically significant.

    Results

    Patient General Information

    A total of 44 subjects were included in the study as shown in Table 1, comprising 37 patients with CRSwNP, all diagnosed according to EPOS 2012 criteria. These patients were newly diagnosed and had no history of hormone use within the past month. The control group consisted of 7 patients with pituitary tumors without chronic sinusitis. The ages of the subjects ranged from 16 to 65 years, including 16 women and 21 men with CRSwNP, and 4 women and 3 men as controls. There was no significant difference in age and sex distribution between the CRSwNP patients and the controls.

    Table 1 Baseline Characteristics of the Participants’ Demographics, Blood Eosinophils Involved in This Study

    Regarding the incidence, 17 participants had unilateral sinus disease, while 20 participants had bilateral sinus disease. Notably, during functional endoscopic sinus surgery (FESS), 15 patients underwent full sinus opening surgery. The percentage of peripheral blood eosinophils was significantly higher in patients with CRSwNP (7.43 ± 5.33) compared to controls (1.78 ± 1.25) (P = 0.009).

    Increased Levels of IL-25 in NPs and TM Tissues of Patients with CRSwNP

    Samples of NPs and TM from CRSwNP patients, as well as TM from the control group (patients with pituitary tumors without chronic sinusitis), were collected. Immunohistochemical methods were employed to detect the expression and distribution of IL-25 in these tissues. The results showed that IL-25 expression was significantly increased in the TM (Figure 1A) and NPs (Figure 1B) of CRSwNP patients compared to the TM of the control group (Figure 1C). The negative control (Figure 1D) was immuno-stained with isotype IgG to confirm the non-specific binding is low.

    Figure 1 Expression of IL-25 in patients with CRSwNP and control patients. TM (A) and NP (B) tissues from patients with CRSwNP, and control TM from pituitary tumor patients without CRS (C) were immune-stained with IL-25 antibody. The negative control (D) was immunostained with isotype IgG. (E). Comparison of IL-25 expression levels in each tissue. **P < 0.01, ***P < 0.001.

    The percentage of the regional area of IL-25 in the TM was 1.52 ± 0.22 in the control group, 8.60 ± 1.04 in CRSwNP patients, and 12.32 ± 1.99 in the NPs of CRSwNP patients. This indicates that the IL-25 area percentage in both the TM andNPs of CRSwNP patients was significantly higher than that in the control group (Figure 1E, P < 0.001). Furthermore, the expression of IL-25 was significantly higher in the NPs than in the TM of CRSwNP patients (Figure 1E, P < 0.01).

    Increased STAT3 Phosphorylation and Elevated Levels of Th2 Cytokines IL-5 and IL-13 Were Observed in CRSwNP-NP Compared to Control-TM

    Nasal polyp (NP) tissues from CRSwNP patients and turbinate mucosa (TM) tissues from control subjects were subjected to protein extraction for p-STAT3 quantification. The levels of IL-5 and IL-13 in the extraction supernatant were measured by ELISA and compared between the CRSwNP and control groups.

    As shown in Figure 2A and Figure S1 (uncropped image), p-STAT3 levels in NP tissues were significantly elevated compared to control TM tissues. Similarly, the production of Th2 cytokines IL-5 and IL-13 was markedly increased in NP tissues relative to control TM (Figure 2B and Table S1). Given the observed upregulation of IL-25 in NP tissues, it is reasonable to speculate that IL-25 may promote p-STAT3 activation, thereby contributing to the increased production of Th2 cytokines IL-5 and IL-13.

    Figure 2 Phosphorylation of STAT3 and production of Th2 cytokines were elevated in CRSwNP-NP compared to control-TM. (A). Phosphorylation of STAT3 in NPs was upregulated compared to the control-TM. (B). The production of Th2 cytokines IL-5 and IL-13 in NPs were increased compared to the control-TM. **P < 0.01, ***P < 0.001.

    The Increasing Level of ILC2s in NPs and TM of CRSwNP Patients

    As a key effector cell of IL-25, ILC2s are characterized by the markers Lin−FceR1−CRTH2+CD127+ and play a crucial role in promoting type 2 inflammation.31 Our previous research has shown that ILC2s are predominantly responsible for the robust production of Th2 cytokine IL-5, IL-13 and IL-9 in asthma with allergic rhinitis patients, a typical Type 2 inflammation.29 And studies from Western countries suggest that ILC2s are highly elevated in eosinophilic NPs of CRSwNP patients.28 However, the ILC2s remain under-explored in NPs and TM of CRSwNP patients in China. Thus, flow cytometry was used to measure ILC2s levels in NPs and TM of CRSwNP patients, with TM from non-CRS pituitary tumor patients serving as controls. A significant increase in ILC2s populations was observed in the NPs (0.4761 ± 0.2989%) and TM (0.1683 ± 0.1022%) of CRSwNP patients, whereas ILC2s were almost undetectable in the TM of the control group (0.0048 ± 0.0064%) (Figure 3A and Table S2, Scheme S1–S3). Although the ILC2s content was higher in NPs of CRSwNP patients, there was no statistically significant difference between the TM and NPs (Figure 3B and Table S2). The strong correlation between elevated ILC2s levels and increased IL-25 in NPs and TM suggests that IL-25-activated ILC2s cells play a pivotal role in the type-2 inflammation of CRSwNP Chinese Patients.

    Figure 3 High ILC2s levels in CRSwNP patients in China. (A) Lymphocytes from nasal polyps (NP) and turbinate mucosa (TM) tissues were flow sorted, and ILC2s were defined as Lin−FceR1−CRTH2+CD127+ lymphocytes. Lineage-negative (CD2–, CD3–, CD14–, CD16–, CD19–, CD56–, CD235a–) FceR1– cells were gated and further assessed for co-expression of CD127 and CRTH2 for control (C), CRSwNP TM (D) and CRSwNP NP (E), gating strategy is shown in Scheme S1 – S3. (B) ILC2s levels were quantified flow cytometry in control (n = 5), CRSwNP TM (n = 6), CRSwNP NP (n = 6) patients. *P < 0.05, **P < 0.01, ***P < 0.001.

    ILC2s Sorted from NPs Contribute to the Over-Production of Th2 Cytokine IL-5 and IL-13 Under IL-25 Stimulation

    Although the proportion of ILC2s in NPs was higher than in the TM and control groups, they comprised less than 1% of total lymphocytes, making comprehensive cellular analysis challenging. ILC2s sorted from the NPs of six CRSwNP patients were collected and subjected to IL-25 stimulation and limonin treatment. As shown in Figure 4A, ILC2s exhibited the typical morphology of general lymphocytes. Upon IL-25 stimulation for 30 minutes, they increased in size (Figure 4B).

    Figure 4 IL-25 Induces Morphological Changes in ILC2s and Enhances IL-5 and IL-13 Production through STAT3 pathway. (A) The morphology of ILC2s sorted from NPs of CRSwNP patients. (B) Morphological changes in ILC2s induced by IL-25 stimulation (10 ng/mL). (C) The phosphorylation of STAT3 in ILC2s was stimulated by treatment of IL-25 and peaked at 30 minutes. (D and E) The phosphorylation of STAT3 in ILC2s was inhibited by addition of limonin at 100 µM. (F) IL-5 production levels in ILC2s following IL-25 treatment, with the addition of limonin at 100 µM. (G) IL-13 production levels in ILC2s following IL-25 treatment, along with limonin at 100 µM. **P < 0.01, ***P < 0.001.

    Phosphorylated STAT3 (p-STAT3) levels rose significantly within 15 minutes, peaked at 30 minutes, and declined after 60 minutes (Figure 4C and Figure S2 for uncropped image). Additionally, IL-25 stimulation led to a significant increase in IL-5 (Figure 4F) and IL-13 (Figure 4G) production compared to untreated ILC2s (Table S3). These cytokines play a crucial role in recruiting and activating other immune cells, such as eosinophils, and contribute to mucus production and airway hyperreactivity—hallmarks of type-2 inflammatory diseases.

    Limonin, a secondary metabolite found in citrus plants, has been widely studied for its anti-inflammatory properties.32,33 Emerging research indicates that limonin and its derivatives can suppress inflammation by inhibiting the JAK-STAT and NF-κB signaling pathways.34–37 Previous studies have shown that limonin can alleviate LPS-induced pulmonary dysfunction in mice by suppressing pro-inflammatory cytokine production through multiple signaling pathways, including activation of AMPKα/NRF2 and inhibition of NF-κB.38,39 These findings underscore its therapeutic potential in airway inflammatory diseases. In this study, limonin treatment effectively reversed the p-STAT3 activation (Figure 4D and Figure S3 for uncropped image, Figure 4E), and inhibited the upregulation of IL-5 (Figure 4F) and IL-13 (Figure 4G) due to the IL-25 stimulation (Table S3). These findings suggest that ILC2s drive IL-5 and IL-13 overproduction via STAT3 signaling in NPs, highlighting limonin as a potential therapeutic strategy for managing type-2 inflammation in CRSwNP patients. This is the first report showing that limonin modulates ILC2s function by downregulating type 2 cytokine production, thereby attenuating inflammation in CRSwNP. Future work will focus on elucidating the broader immunomodulatory effects of limonin to further evaluate its potential as an anti-inflammatory agent in CRS.

    Discussion

    Our previous research has demonstrated that in peripheral blood mononuclear cells (PBMCs), there is an increase in eosinophils, which positively correlates with ILC2s levels in patients with asthma and allergic rhinitis (AR).29 Study in the United States found that ILC2s are elevated in eosinophilic NPs but not in non-eosinophilic NPs and that the frequency of ILC2s positively correlates with eosinophils in NPs tissue.40 In this study, we found that the percentages of peripheral blood eosinophils also show a positively correlation with ILC2s in NPs in Chinese patients.

    IL-25, produced by infiltrating mast cells and nasal epithelial cells, plays a crucial role in the pathogenesis of type 2 inflammatory diseases such as asthma, atopic dermatitis, and CRSwNP.20,41 Our findings further confirmed that IL-25 is overexpressed in NPs and TM tissues from Chinese CRSwNP patients. Besides, p-STAT3 levels in NP tissues were significantly elevated compared to control TM tissues. Similarly, the production of Th2 cytokines IL-5 and IL-13 was markedly increased in NP tissues relative to control TM (Figure 2B). Given the observed upregulation of IL-25 in NP tissues, it is reasonable to speculate that IL-25 may promote p-STAT3 activation, thereby contributing to the increased production of Th2 cytokines IL-5 and IL-13.

    Various cell types, including ILC2s, macrophage cells and mast cells in human NPs, have shown a strong correlation with IL-25 expression.31,42,43 In this study, ILC2s were found to have increased abundance in the NPs and TM tissues of Chinese patients with CRSwNP. In contrast, TM tissues from patients with pituitary tumors exhibited a low content of ILC2s. The results suggest that ILC2s play a key role in regulating the inflammation in NPs from Chinese patients.

    Studies have shown that ILC2s are elevated in NPs and contribute to the type 2 inflammatory response induced by epithelial-derived innate cytokines.28 This study explored the role of ILC2s in NP tissues of Chinese CRSwNP patients in response to IL-25. In vitro stimulation with IL-25 increased ILC2 size and p-STAT3 levels, leading to the overexpression of IL-5 and IL-13. Notably, limonin inhibited STAT3 phosphorylation and reduced IL-5 and IL-13 production, highlighting ILC2s as key IL-25 effector cells in NPs and suggesting limonin as a potential therapeutic for CRSwNP by targeting p-STAT3. However, the low abundance of ILC2s in NPs presents challenges for systematic study. Future work will focus on collecting and analyzing ILC2s from NP tissues of Chinese CRSwNP patients to further investigate their role.

    In conclusion, this study identified ILC2s as key effector cells of IL-25 in NPs from Chinese CRSwNP patients. IL-25 and ILC2 levels were significantly elevated in the NPs and TM of these patients. Upon IL-25 stimulation, ILC2s in NPs contributed to the overexpression of Th2 cytokines IL-5 and IL-13 via the STAT signaling pathway. Notably, limonin inhibited STAT3 phosphorylation, thereby reducing IL-5 and IL-13 production, highlighting its potential as a therapeutic strategy for controlling type-2 inflammation in Chinese CRSwNP patients.

    Highlights

    1. IL-25 stimulates NPs tissues of Chinese CRSwNP patients to produce Th2 cytokines IL-5 and IL-13 through STAT3 pathway which are the key drivers for type 2 inflammation.

    2. ILC2s sorted from NPs of Chinese CRSwNP patients significantly produce IL-5 and IL-13 via STAT3 pathway.

    3. ILC2s function as potential effector cells of IL-25 in NPs in Chinese CRSwNP patients.

    4. Limonin can Inhibit the phosphorylation of STAT3 suppressing the production of Th2-type cytokines IL-5 and IL-13 in ILC2s, which demonstrate the potential to control the type 2 inflammation of CRSwNP.

    Data Sharing Statement

    Raw data of Western Blot, ELISA and gating strategy of flow cytometry analysis are in the supporting material. Original fcs files of flow cytometry are available upon reasonable request to the corresponding authors, Drs. Shaochi Wang ([email protected], [email protected]) and Yulin Zhao ([email protected]).

    Ethics Approval and Consent to Participate

    The study was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (2024-KY-0405-002). Written informed consent was obtained from 44 subjects (ages 16 – 65).

    Human Ethics Declaration

    This study was conducted in accordance with the ethical guidelines outlined in the Institutional Review Board (IRB), Ethics Committee of The First Affiliated Hospital of Zhengzhou University. Ethical approval was obtained from Ethics Committee of The First Affiliated Hospital of Zhengzhou University, and all research procedures adhered to the principles of the Declaration of Helsinki.

    Consent to Participate

    All participants were informed about the study’s objectives, procedures, potential risks, and benefits before participation. Written informed consent was obtained from all participants (or from their legal guardians if they were minors) before their involvement in the study. Participants were assured that their participation was voluntary and that they could withdraw at any time without any consequences.

    Consent for Publication

    All the authors have reviewed the manuscript and agreed to publish it.

    Acknowledgments

    The authors would like to express their gratitude to the participating patients and their families for their contributions to this important research.

    Funding

    This work was supported by Henan Province in 2023 Key Scientific Research Project Plan of Colleges and Universities (Grant No. 23A310029) to and The First Affiliated Hospital of Zhengzhou University Postdoctoral Research Start-up Fund (Grant No. 71783) Dr. Shaochi Wang.

    Disclosure

    The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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    24. Neill DR, Wong SH, Bellosi A, et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010;464(7293):1367–1370. doi:10.1038/nature08900

    25. Price AE, Liang H-E, Sullivan BM, et al. Systemically dispersed innate IL-13–expressing cells in type 2 immunity. Proc Natl Acad Sci. 2010;107(25):11489–11494. doi:10.1073/pnas.1003988107

    26. Barrett NA, Austen KFJI. Innate cells and T helper 2 cell immunity in airway inflammation. Immunity. 2009;31(3):425–437.

    27. Spits H, Di Santo JPJNI. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol. 2011;12(1):21–27. doi:10.1038/ni.1962

    28. Stevens WW, Kato A. Group 2 innate lymphoid cells in nasal polyposis. Ann Allergy Asthma Immunol. 2021;126(2):110–117. doi:10.1016/j.anai.2020.08.001

    29. Yu QN, Guo YB, Li X, et al. ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma. Allergy. 2018;73(9):1860–1870. doi:10.1111/all.13438

    30. Ogasawara N, Poposki JA, Klingler AI, et al. Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps. Mucosal Immunol. 2020;13(1):86–95. doi:10.1038/s41385-019-0215-8

    31. Bartemes KR, Kita H. Roles of innate lymphoid cells (ILCs) in allergic diseases: the 10-year anniversary for ILC2s. J Allergy Clin Immunol. 2021;147(5):1531–1547. doi:10.1016/j.jaci.2021.03.015

    32. Manners GD. Citrus limonoids: analysis, bioactivity, and biomedical prospects. J Agric Food Chem. 2007;55(21):8285–8294. doi:10.1021/jf071797h

    33. Wang S, Kuperman LL, Song Z, et al. An overview of limonoid synthetic derivatives as promising bioactive molecules. Eur J Med Chem. 2023;259:115704. doi:10.1016/j.ejmech.2023.115704

    34. Jin S, Wang J, Chen S, et al. A novel limonin derivate modulates inflammatory response by suppressing the TLR4/NF-kappaB signalling pathway. Biomed Pharmacother. 2018;100:501–508. doi:10.1016/j.biopha.2018.02.046

    35. Wang SC, Yang Y, Liu J, et al. Discovery of novel limonin derivatives as potent anti-inflammatory and analgesic agents. Chin J Nat Med. 2018;16(3):231–240. doi:10.1016/S1875-5364(18)30052-9

    36. Wang S, Han X, Yang Y, et al. A practical synthesis of amino limonin/deoxylimonin derivatives as effective mitigators against inflammation and nociception. RSC Med Chem. 2020;11(7):843–847. doi:10.1039/D0MD00117A

    37. Wang S, Han X, Yang Y, et al. Discovery of deoxylimonin delta-lactam derivative with favorable anti-inflammation and antinociception efficacy from chemical modified limonin/deoxylimonin analogs. Bioorg Chem. 2020;100:103886. doi:10.1016/j.bioorg.2020.103886

    38. Liang H, Liu G, Fan Q, Nie Z, Xie S, Zhang R. Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury. Int Immunopharmacol. 2023;122:110678. doi:10.1016/j.intimp.2023.110678

    39. Wang D, Zhang H, Fang J, Zhong Y, Yu C. Effects of limoninon on LPS-induced acute lung injury in mice. Chin J Clin Pharmacol Ther. 2018;23(1):8.

    40. Walford HH, Lund SJ, Baum RE, et al. Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness. Clin Immunol. 2014;155(1):126–135. doi:10.1016/j.clim.2014.09.007

    41. Yuan Q, Peng N, Xiao F, et al. New insights into the function of Interleukin-25 in disease pathogenesis. Biomark Res. 2023;11(1):36. doi:10.1186/s40364-023-00474-9

    42. Zhu Y, Sun X, Tan S, et al. M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps. Front Immunol. 2022;13:1047930. doi:10.3389/fimmu.2022.1047930

    43. Takabayashi T, Kato A, Peters AT, et al. Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2012;130(2):410–20e5. doi:10.1016/j.jaci.2012.02.046

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  • User Receives MSI RTX 5090 With GPU And VRAM Chips Torn Off PCB; Another Incident Of Fake GPUs Being Supplied To Amazon

    User Receives MSI RTX 5090 With GPU And VRAM Chips Torn Off PCB; Another Incident Of Fake GPUs Being Supplied To Amazon

    It appears that the GPU might have been sent to one of those Chinese Labs, where they rip the GPU and VRAM chips from the RTX 5090s.

    Redditor Orders MSI RTX 5090 Ventus 3X From Amazon but Finds No Tamper Seal; Further Investigation Revealed Ripped GPU Chip and VRAM From the PCB

    Once again, we are witnessing the supply of Fake GeForce RTX 5090 GPUs. It shouldn’t be surprising since we have seen and reported such fraud multiple times, but this one looks somewhat familiar with what we reported recently. The GeForce RTX 5090 has a huge demand, particularly for AI in Chinese markets. Due to an official ban in the country, the only way the GPU gets there is by smuggling.

    This Redditor seems to be a victim of such fraud, as his GPU didn’t have the components, which are usually ripped from the PCB in China. Reddit user u/Nice-Screen-4193 says that he bought a brand new GPU from Amazon FR, “sold and shipped by Amazon”, not just by any third-party seller. However, he became skeptical when he saw no tamper seal on one of the screws at the back. This means the GPU was opened before.

    Image Credit: Reddit

    The user still tried to give it a go before investigating further and reported a non-operational state of the GPU. He also states that the PCIe gold finger was looking dull and used. Using a flashlight, he was able to peek underneath the heatsink to find no memory chips under the thermal pads. So, after the disassembly, it was confirmed that not only was it missing the memory chips, but the entire GPU substrate was gone as well. What remained were just the soldering points on the PCB.

    Graphics card and cooling system with a cartoon character overlay in a tech setup.
    GPU chip and memory modules ripped from the MSI RTX 5090 Ventus 3X, Image Credit: Reddit

    This is a classic fraud, which could be linked to the Chinese labs where thousands of RTX 5090 go under transformation. They remove the GPU die and the VRAM chips to solder on another custom PCB for deployment in the AI servers. It appears that the empty GPU was sent back in the supply chain cleverly, and ended up with the Reddit user. So, apparently, not even the GPUs, which are sold and shipped by Amazon, are safe from such fraud, but it also shows how common it is.

    Order summary: MSI NVIDIA RTX 5090 graphics card, €1,994.73, dispatched July 2025.
    The GPU was sold and shipped by Amazon, Image Credit: Reddit

    The GeForce RTX 5090 reportedly doesn’t have any problems in being smuggled to China, and while it’s one thing to see RTX 5090 being converted into AI GPUs, it’s even a more serious problem to see fake RTX 5090s getting back into the supply chain.

    News Source: Reddit

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  • Apple @ Work: Device Management Service migration is going to elminate vendor lock-in on Apple fleets

    Apple @ Work: Device Management Service migration is going to elminate vendor lock-in on Apple fleets

    Apple @ Work is exclusively brought to you by Mosyle, the only Apple Unified Platform. Mosyle is the only solution that integrates in a single professional-grade platform all the solutions necessary to seamlessly and automatically deploy, manage & protect Apple devices at work. Over 45,000 organizations trust Mosyle to make millions of Apple devices work-ready with no effort and at an affordable cost. Request your EXTENDED TRIAL today and understand why Mosyle is everything you need to work with Apple.

    Migrating between Device Management Services (DMS) usually involved full device wipes, custom scripts, and hoping everything re-enrolled properly. Some vendors leaned into that pain. They’d offer bargain pricing in year one, then quietly ratchet it up over time. Because what were IT teams going to do? Switching DMS (previously MDM) vendors meant hours of manual work or rebuilding devices from scratch, and employees really wouldn’t see much difference.

    About Apple @ Work: Bradley Chambers managed an enterprise IT network from 2009 to 2021. Through his experience deploying and managing firewalls, switches, a mobile device management system, enterprise grade Wi-Fi, 1000s of Macs, and 1000s of iPads, Bradley will highlight ways in which Apple IT managers deploy Apple devices, build networks to support them, train users, stories from the trenches of IT management, and ways Apple could improve its products for IT departments.

    Apple is changing that with a new feature for the fall software updates inside Apple Business Manager and Apple School Manager built for device management migration. It solves a real problem that many IT teams have struggled with for years. More importantly, it puts pressure on vendors to keep delivering value at fair prices. When migration is easier, IT teams have more power to move to the best solution for their needs. That’s a win for the customers and vendors who aim to deliver value and not lock-in.

    How device management migration works

    Inside Apple Business Manager or Apple School Manager, IT admins can now reassign iPhone, iPad, and Mac devices to a new device management service. There’s even an option to set a migration deadline. Once a deadline is set, users will get a notification letting them know that they need to migrate. If they don’t take action, the migration kicks off automatically.

    During the migration process, the device removes the old configurations and installs the new ones. Using the bootstrap token, the new service can take over things like Activation Lock and FileVault key escrow. It’s a fairly clean handoff and makes switching to a new platform less of a hassle. It follows a trend in the enterprise I’ve seen Apple do over the last decade: take things that require a lot of hacks/workarounds and make them turn-key.

    App preservation is a big deal

    One of the most important parts of this new process is app preservation. Without it, every device would feel like a wipe and rebuild for managed apps. With app preservation, the device keeps managed apps installed through the transition. That includes both apps and their data, which makes the migration feel seamless to end users. Apple recommends using the await device configured step to ensure everything reinstalls properly before the user exits enrollment. This is especially critical for iPhone and iPad, where all of the apps are likely going to be managed.

    Things to keep in mind

    This isn’t a magic switch. There are still some gotchas to be aware of. One issue folks have seen in testing is when a Wi-Fi configuration profile is removed before the new one is applied. In that case, the device can get disconnected from the network during the transition. If it happens at the office, IT Teams will need to spin up an open network to allow folks to connect to finish the process. If they’re at home or somewhere with saved networks, it usually resolves itself.

    Apple also mentioned that there’s ongoing work around FileVault and Activation Lock during migration. The new service can rotate the FileVault key using the bootstrap token, but how that behaves in edge cases is still something to watch as the rollout continues.

    Wrap up

    This new feature from Apple solves a real problem for enterprises that use Apple at work. It helps customers avoid vendor lock-in, helps vendors compete on product quality instead of contracts and switching costs, and makes managing Apple devices a little less annoying for IT teams. There are still things to watch, like how FileVault keys behave or how Wi-Fi reconnects during the changeover, but overall, this is a big win for the entire industry.

    Apple @ Work is exclusively brought to you by Mosyle, the only Apple Unified Platform. Mosyle is the only solution that integrates in a single professional-grade platform all the solutions necessary to seamlessly and automatically deploy, manage & protect Apple devices at work. Over 45,000 organizations trust Mosyle to make millions of Apple devices work-ready with no effort and at an affordable cost. Request your EXTENDED TRIAL today and understand why Mosyle is everything you need to work with Apple.

    FTC: We use income earning auto affiliate links. More.

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  • Top Stories: iOS 26 Beta 5, Apple Watch Ultra 3 Rumors, and More

    Top Stories: iOS 26 Beta 5, Apple Watch Ultra 3 Rumors, and More

    The official unveiling of the iPhone 17 lineup and new Apple Watch models plus potentially a few more announcements is just a month away now, and the rumor cycle is in full swing for these final weeks.

    iOS 26 is also well into its beta testing cycle, with Apple putting the final touches on things over the next few weeks to be able to install it on the new iPhones before they ship, so read on below for all the details!

    Everything New in iOS 26 Beta 5

    Apple is continuing to make progress on refining iOS 26 and related major operating system updates that should see their official releases in September, pushing out the fifth developer betas and second public betas this week with some fresh changes in store.

    iOS 26 FeatureiOS 26 Feature
    The new Liquid Glass design seems to be firming up after several revisions in previous betas, while beta 5 introduces some new “bounciness” for transitions in places like Lock Screen passcode entry and switching between Control Center pages. There are other functional and visual tweaks for Camera, Mail, AirDrop, Wallet and more.

    iOS 26 Beta Reveals Apple Watch Ultra 3 Display Size

    It looks like the display on the Apple Watch Ultra 3 might be just a hint larger than on previous Ultra models, based on imagery discovered by MacRumors in the latest iOS 26 beta.

    ultra 2 prime dayultra 2 prime day
    It’s likely the slight increase in display size will be accommodated by shrinking the bezels around the display rather than increasing the casing size, but we’ll have to see once the next-generation Apple Watch Ultra is unveiled. The first substantial upgrade for the model in two years is likely to come next month alongside the iPhone 17 lineup.

    iPhone 17 Air Battery Allegedly 2.49mm – Half the Thickness of 17 Pro’s

    Over the weekend, photos surfaced of what was originally claimed to be the metal-encased battery for the upcoming ultra-thin “iPhone 17 Air,” although the original report was later corrected to note that the battery is for the iPhone 17 Pro.

    iphone 17 air battery vs proiphone 17 air battery vs pro
    It didn’t take long for photos of the actual iPhone 17 Air battery to surface, however, and they reveal that it measures just 2.49 mm thick, roughly half as thick as the iPhone 17 Pro battery. The iPhone 17 Air will reportedly have a battery capacity of 3,000 mAh or less, which will hamper battery life compared to thicker models. But between software optimizations and a rumored battery case, the majority of users will hopefully still be able to get a full day’s use out of a single charge.

    AirPods Pro 3 Could Be Just Weeks Away – Here’s What We Know

    Apple’s high-end AirPods Pro earbuds are due for an update, and it could be arriving as soon as September alongside the new iPhone and Apple Watch models.

    AirPods Pro 3 Mock FeatureAirPods Pro 3 Mock Feature
    We’re expecting some design tweaks for the earbuds and the case, performance upgrades in audio processing and active noise cancellation, in-ear heart-rate tracking, and perhaps some other improvements.

    New Apple TV Still Launching This Year

    The current Apple TV 4K model is coming up on three years old, but Apple is apparently on track to release an updated model later this year, according to a source speaking to MacRumors.

    Apple TV 2025 Thumb 3Apple TV 2025 Thumb 3
    We’re expecting a chip upgrade from the A15 Bionic found in the current model, Wi-Fi 7 support via a new Apple-designed Bluetooth/Wi-Fi chip, and additional enhancements.

    Google Makes Fun of Apple Intelligence Siri Delay in Ad Promoting Pixel 10

    Google this week used Apple’s Siri failure to attempt to lure customers to the upcoming Pixel 10 series, sharing an ad that calls out the delayed Apple Intelligence ‌Siri‌ functionality.

    google pixel 10 smartphonesgoogle pixel 10 smartphones
    “If you buy a new phone because of a feature that’s coming soon, but it’s been coming soon for a full year,” the teaser video begins, “you could change your definition of soon. Or you could just change your phone.”

    In an all-hands meeting for Apple employees late last week, Tim Cook defended the company’s AI efforts, noting that “we’ve rarely been first” to new technologies but that AI is “ours to grab” and the company “will make the investment to do it.”

    MacRumors Newsletter

    Each week, we publish an email newsletter like this highlighting the top Apple stories, making it a great way to get a bite-sized recap of the week hitting all of the major topics we’ve covered and tying together related stories for a big-picture view.

    So if you want to have top stories like the above recap delivered to your email inbox each week, subscribe to our newsletter!

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  • People’s Pharmacy: Is there a link between the herpes virus and Alzheimer’s disease?

    People’s Pharmacy: Is there a link between the herpes virus and Alzheimer’s disease?

    Q. I had chicken pox as a child and shingles as an adult. I have gotten the Shingrix vaccine. For an occasional cold sore, I use acyclovir, but I take L-lysine daily for prevention. Has anyone studied this as an alternative prevention against Alzheimer’s disease?

    As I understand it, the herpes virus might be a contributing factor. Since L-lysine is available without a prescription in the U.S., it could be an alternative to antiviral drugs for many people.

    A. The link between herpes virus infection and AD is tantalizing, but it has not yet been firmly established. What we know about L-lysine is that it can help reduce outbreaks of cold sores due to herpes (Viruses, June 2, 2023). According to the scientists, the effective dose of this dietary supplement is at least 1 gram per day. We found no studies of L-lysine being used to prevent AD.

    L-lysine is an essential amino acid. Another amino acid, arginine, counteracts the antiviral action of lysine. As a result, L-lysine appears to be more effective if people reduce their intake of arginine from sources such as legumes, nuts and meat like turkey, chicken or pork.

    It was smart of you to get vaccinated against shingles. The varicella zoster virus that causes both chicken pox and shingles has also been implicated in AD. Studies in Wales and Australia indicate that older people vaccinated against shingles are less likely to develop AD than their neighbors who were not vaccinated (Nature, April 2, 2025; JAMA, April 23, 2025).

    Q. I have read that there is now an epinephrine nasal spray called neffy for severe allergic reactions or even anaphylaxis. It requires a prescription and is pricey. Why not use over-the-counter Primatene Mist instead? It’s far less expensive.

    A. Anaphylaxis is a life-threatening allergic reaction. It must always be treated as a medical emergency.

    Epinephrine auto-injectors such as EpiPen or Adrenaclick deliver a specified dose of epinephrine immediately into the bloodstream. German scientists studied Primatene Mist to see if it could be used as a substitute treatment for anaphylaxis and found it is not suitable (Journal der Deutschen Dermatologischen Gesellschaft, May 2009).

    On the other hand, neffy was developed specifically to immediately provide an appropriate dose of epinephrine. Experimenting with a money-saving alternative may not be wise when the outcome could be death.

    In their column, Joe and Teresa Graedon answer letters from readers. Write to them in care of King Features, 628 Virginia Drive, Orlando, FL 32803, or email them via their website: www.PeoplesPharmacy.com. Their newest book is “Top Screwups Doctors Make and How to Avoid Them.”

    If you purchase a product or register for an account through a link on our site, we may receive compensation. By using this site, you consent to our User Agreement and agree that your clicks, interactions, and personal information may be collected, recorded, and/or stored by us and social media and other third-party partners in accordance with our Privacy Policy.

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  • Inhyuk Lee Brings Street-Level Fashion To The Marvel Universe With New Variant Covers

    Inhyuk Lee Brings Street-Level Fashion To The Marvel Universe With New Variant Covers

    Marvel, but make it fashion? As previously revealed at San Diego Comic-Con, artist Inhyuk Lee has designed a number of street-level fashion variant covers for November’s comics, all called “Street-Verse.”

    “I was honored to create the Street-Verse Variant Covers for Marvel,” Lee said via press release. “I started my career as a character designer at a game company 20 years ago, so I’m familiar with and enjoy designing characters and I’m interested in modern and practical design, so I was always drawn to techwear. Since the winter of 2021, I’ve been working on a personal project redesigning Spider-Man characters’ costumes in a modernized way. I’ve called it ‘Who is next?’ Marvel saw the series and approached me with this cover and mural project.”

    In the new covers, the classic superhero costumes are transformed into “techwear,” which includes future aesthetics while emphasizing “functionality.” The 20 covers range from Emma Frost, to Spider-Man, to Doctor Doom, and more.

    “This marks my 13th year working with Marvel,” Lee continued. “They’ve always known what I do best and have given me suggestions based on what I excel at. It’s a pleasure to work with Marvel, who recognize my strengths. I hope many people will enjoy these covers.”

    You can check out the covers (minus one to be revealed later), as well as solicit info, below.

    On Sale 11/5

    AMAZING SPIDER-MAN #15 STREET-VERSE VARIANT COVER BY INHYUK LEE

    AMAZING X-MEN #2 STREET-VERSE VARIANT COVER BY INHYUK LEE

    AVENGERS #32 STREET-VERSE VARIANT COVER BY INHYUK LEE

    MILES MORALES: SPIDER-MAN #40 STREET-VERSE VARIANT COVER BY INHYUK LEE

    PLANET SHE-HULK #1 STREET-VERSE VARIANT COVER BY INHYUK LEE

    On Sale 11/12

    EDDIE BROCK: CARNAGE #10 STREET-VERSE VARIANT COVER BY INHYUK LEE

    FANTASTIC FOUR #5 STREET-VERSE VARIANT COVER BY INHYUK LEE

    IRON & FROST #2 STREET-VERSE VARIANT COVER BY INHYUK LEE

    ROGUE STORM #2 STREET-VERSE VARIANT COVER BY INHYUK LEE

    UNBREAKABLE X-MEN #2 STREET-VERSE VARIANT COVER BY INHYUK LEE

    VENOM #251 STREET-VERSE VARIANT COVER BY INHYUK LEE

    On Sale 11/19

    ALL-NEW SPIDER-GWEN: THE GHOST-SPIDER #4 STREET-VERSE VARIANT COVER BY INHYUK LEE

    CAPTAIN AMERICA #5 STREET-VERSE VARIANT COVER BY INHYUK LEE

    ONE WORLD UNDER DOOM #9 STREET-VERSE VARIANT COVER BY INHYUK LEE

    THE LAST WOLVERINE #2 STREET-VERSE VARIANT COVER BY INHYUK LEE

    X-MEN: BOOK OF REVELATION #2 STREET-VERSE VARIANT COVER BY INHYUK LEE

    On Sale 11/26

    BLACK CAT #4 STREET-VERSE VARIANT COVER BY INHYUK LEE

    DAREDEVIL/PUNISHER: THE DEVIL’S TRIGGER #1 STREET-VERSE VARIANT COVER BY INHYUK LEE

    TBA #1 STREET-VERSE VARIANT COVER BY INHYUK LEE

    THOR #4 STREET-VERSE VARIANT COVER BY INHYUK LEE

    Comic Book Club Live Info:

    Want to watch Comic Book Club live? We stream every Tuesday at 7 p.m. ET on YouTube and Twitch. Come hang out, and ask questions of our guests (and us!). And you could potentially win a $25 gift card to Midtown Comics. You can check out a current list of upcoming guests and other live appearances on our Shows page.

    Discover more from Comic Book Club

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  • The Morning Habit That Could Be Harming Your Heart

    The Morning Habit That Could Be Harming Your Heart

    • Breakfast foods like bacon, sausages, muffins and bagels can be loaded with sodium.
    • Eaten regularly, their sodium could be hurting your heart health, says a cardiologist. 
    • Opt for foods high in fiber and lean protein, yet low in sodium and saturated fat.

    Despite all the social media messaging to move into your day in a calm, well-fed and happy way, mornings can be busy and chaotic. But there is one important reason to take the time to start the day on a strong, healthy note: Some of your go-to morning habits could be affecting your heart health. Like your breakfast. If it’s high in hidden sodium, it could be slowly chipping away at your heart health, says cardiologist Robert Segel, M.D.

    And we’re not just talking about salty bacon or sausages. Sodium is often hiding in many breakfast staples that don’t even taste salty, like bread, bagels, muffins, pastries and more.  Given that cardiovascular disease accounts for 1 in 3 deaths in the U.S., it’s worth stepping back and reevaluating what’s on your plate before you start your busy day. 

    Read on to learn why a high-sodium breakfast can spell trouble for your heart, plus morning habits to keep your heart in top shape.

    How a High-Sodium Breakfast May Be Harming Your Heart

    Can Raise Blood Pressure

    “High sodium intake causes fluid retention, raises blood pressure and increases the risk of heart failure,” says Segel. Sodium is so problematic that research has found that people who eat a high-sodium diet may be 19% more likely to develop cardiovascular disease than people who follow a low-sodium eating pattern. The reason? Excess sodium disrupts the function of the system that regulates your blood pressure (called the renin-angiotensin system) and makes your heart work harder to pump blood. 

    Most of us typically consume more than 3,300 milligrams of sodium every day. The American Heart Association recommends slashing that number by more than half to 1,500 mg per day for optimal heart health.

    May Be High in Saturated Fat

    If processed breakfast meats, like bacon and sausage, are your go-to morning protein sources, you aren’t just getting lots of gratuitous sodium. These meats are also high in cholesterol-raising saturated fat, delivering a double whammy when it comes to heart health. One study even found that eating slightly more than 5 ounces of processed meat weekly may increase the risk of major cardiovascular disease by as much as 46%.

    The good news is, there are plenty of less-processed breakfast staples that can give you the protein you need without all the sodium and saturated fat. Eggs, unsweetened yogurt and kefir, low-sodium cottage cheese and even tuna are all top choices. 

    What about turkey bacon or chicken sausage? As healthy as these may sound, they still fall under the processed meat umbrella, so steer clear.

    Linked to Type 2 Diabetes

    People with diabetes have double the risk of heart disease thanks to chronically high blood sugar, which damages the blood vessels.  So, maintaining healthy blood sugar levels can protect your heart. 

    Sugary breakfast treats, like doughnuts and pastries, aren’t the only foods to watch out for to reduce your diabetes risk. Research reveals that a high-sodium eating pattern can also be a culprit. For instance, one study found that people whose diets contained the most sodium were 80% more likely to develop diabetes than people who ate the least sodium.

    Frequently Low in Fiber

    Fiber is found in plant foods like fruits, vegetables, whole grains, legumes, nuts and seeds. While fiber is best known for keeping your digestive system regular, it also offers protection against heart disease and diabetes. Yet, most of us don’t come close to getting the roughly 28 grams we need per day. Catch is, there’s no fiber in bacon and sausage. And many breads, bagels and baked goods are also low in fiber, unless they’re made with lots of whole grains.

    While all fiber is a win, soluble fiber is the one you want for better heart health. This type of fiber binds to cholesterol in your intestine, ferrying it out of your body through your stool. To work more cholesterol-lowering soluble fiber into your morning, think oatmeal and fruits, like apples, pears, bananas and oranges.

    Morning Habits That Support Heart Health

    Reducing the sodium in your breakfast is a great start for heart health. Now the question is: What do you eat (and do) instead? Here are a few totally doable habits to consider:

    • Hydrate: Rather than having a coffee-first routine, Kiran Campbell, RDN, recommends starting your day with a glass of water. “Even mild dehydration can affect how hard your heart has to work,” she says. Getting H2O on board first helps support circulation, digestion and blood pressure regulation, she adds.
    • Add in some fiber: “Fiber helps lower total and LDL (“bad”) cholesterol and supports digestive and heart health,” says Campbell. She suggests aiming for at least 5 grams of fiber at breakfast. You can hit this quota by prioritizing fruits, vegetables and whole grains, she says.
    • Include high-quality protein: “[Protein] helps keep blood sugar stable, reduces cravings, supports muscle mass and improves satiety, making it easier to eat mindfully the rest of the day,” says Blair Persyn, M.S., RDN. She recommends starting your day with a breakfast that contains 20 to 30 grams of protein. 
    • Avoid added sugars: Excess intake of added sugars also increases the risk of stroke, heart failure and atrial fibrillation, says Campbell. Whole fruits can be a nice source of natural sweetness at breakfast. If you drink coffee and tea, skip the sugar.

    • Move your body: If you have the time, spending 10 to 15 minutes moving your body in the morning can help improve blood pressure and cholesterol levels and promote a healthy weight, says Campbell. That might be some yoga sun salutations, stretching or a walk outside. Bonus points if that walk happens after a meal, as it can also help lower blood sugar and improve digestion.
    • Build in some quiet time: Rushing to get ready is a given in many of our morning routines. But Persyn recommends slowing down, even if it’s for just a moment. “Stress management is often overlooked when it comes to heart health, but it matters,” she says. “Even just 60 seconds of deep breathing or a moment of mindfulness before jumping into your day can make a meaningful difference.” 
    • Seek out the sun: Morning light exposure has been found to help reduce blood pressure at night and may be an additional way to support heart health, research suggests. Start your day with a leisurely walk outside, and you’ll double up on exercise and quiet time, too.

    Heart-Healthy Breakfast Recipes to Try

    Our Expert Take

    Regularly eating a high-sodium breakfast could be harming your heart, according to a cardiologist. And many go-to breakfast foods like bacon, sausages, muffins, bagels and bread can be loaded with it. Not only can their sodium raise your blood pressure, it may also increase your risk of type 2 diabetes, which can double your risk of heart disease. If that weren’t trouble enough, many high-sodium breakfast staples are heavy in artery-clogging saturated fat, yet low in heart-friendly fiber. So, reach for a breakfast that’s rich in fiber and lean protein, yet low in added sugars and sodium. While you’re at it, add a few heart-healthy habits to your a.m., like moving your body, scheduling a few moments of mindfulness or getting out in the sunlight. You’ll start your day on a positive note and do good things for your heart in the process.

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  • Traders Are Fleeing Stocks Feared to Be Under Threat From AI

    Traders Are Fleeing Stocks Feared to Be Under Threat From AI

    (Bloomberg) — Artificial intelligence’s imprint on US financial markets is unmistakable. Nvidia Corp. is the most valuable company in the world at nearly $4.5 trillion. Startups from OpenAI to Anthropic have raised tens of billions of dollars.

    Most Read from Bloomberg

    But there’s a downside to the new technology that investors are increasingly taking note of: It threatens to upend industries much like the internet did before it. And investors have started placing bets on just where that disruption will occur next, ditching shares in companies some strategists expect will see falloffs in demand as AI applications become more widely adopted.

    Among them are web-development firms like Wix.com Ltd., digital-image company Shutterstock Inc. and software maker Adobe Inc. The trio are part of a basket of 26 companies Bank of America strategists identified as most at risk from AI. The group has underperformed the S&P 500 Index by about 22 percentage points since mid-May after more or less keeping pace with the market since ChatGPT’s debut in late 2022.

    “The disruption is real,” said Daniel Newman, chief executive officer of the Futurum Group. “We thought it would happen over five years. It seems like it is going to happen over two. Service-based businesses with a high headcount, those are going to be really vulnerable, even if they have robust businesses from the last era of tech.”

    So far, few companies have failed as a result of the proliferation of chatbots and so-called agents that can write software code, answer complex questions and produce photos and videos. But with tech giants like Microsoft Corp. and Meta Platforms Inc. pouring hundreds of billions into AI, investors have started to get more defensive.

    Wix.com and Shutterstock are down at least 33% in 2025, compared with a 8.6% advance for the broad benchmark. Adobe has fallen 23% amid concerns clients will look to AI platforms that can generate images and videos, as Coca-Cola has already done with an AI-generated ad. ManpowerGroup Inc., whose staffing services could be hurt by rising automation, is down 30% this year, while peer Robert Half Inc. has shed more than half its value, dropping to its lowest in more than five years.

    The souring sentiment among investors comes as AI is changing everything from the way people get information from the internet to how colleges function. Even companies at the vanguard of the technology’s development like Microsoft have been slashing jobs as productivity improves and to make way for more AI investments. To many tech-industry watchers, the time is nearing when AI becomes so pervasive that companies start going out of business.

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  • Pulmonologist reveals 5 habits that help improve sleep quality: Change pillow cover, no caffeine and more | Health

    Pulmonologist reveals 5 habits that help improve sleep quality: Change pillow cover, no caffeine and more | Health

    Updated on: Aug 09, 2025 06:28 pm IST

    It’s not just about the number of hours, you also need good quality sleep. If your sleep is light, know the essential habits that help get better quality sleep.

    Sleep is restorative for overall wellbeing, acting as the bedrock for good health. But when sleep gets compromised, the ripple effects can be felt throughout the body and mind. This is where your habits leading up to bedtime count. Sleep is more than just clocking in the recommended eight hours; the quality also matters, substantially.

    A good and comfotable sleep necessitates cummulative of habits that

    Despite getting the recommended hours of sleep, if you are still tossing and turning, changing sides, flipping pillows to the cold side, or counting sheep to fall asleep, then the quality of sleep may be poor. Let’s take a closer look at what may help you sleep better.

    ALSO READ: Pumpkin seeds for better sleep: A complete guide to their nutritional value and how to add to your diet

    Dr Waseem Ud Din, Consultant Pulmonologist at Ujala Cygnus Group of Hospitals, told HT Lifestyle about the value of sleep hygiene. He elaborated, “Sleep hygiene refers to the daily habits and environment that support deep, restorative sleep. It’s not just about getting eight hours, it’s about setting up your body and mind to sleep well. When sleep suffers, everything from focus and mood to immunity can take a hit.” Certain habits help in preparing the body and mind to achieve deep, restorative sleep.

    Dr Waseem shared 5 habits that you need to make a note of if you are seeking deep sleep:

    1. Regularly changing pillow covers and bedsheets

    Change your pillow cover to reduce skin discomfort.(Shutterstock)
    Change your pillow cover to reduce skin discomfort.(Shutterstock)
    • Clean your pillow cover and bedsheets every week to prevent the buildup of dust, sweat, and allergens.
    • These irritants can lead to skin discomfort and sinus problems that interrupt your sleep.
    • Keeping your bedding fresh not only feels better but also helps create a healthier sleep environment.

    2. Go to bed and wake up at same time

    • Go to bed and wake up at the same time every day, including weekends.
    • This consistent routine helps regulate your body’s internal clock and improves the quality of your sleep.

    3. No screen before bed

    • Blue light from phones, tablets, and TVs can disrupt melatonin production, making it harder to fall asleep.
    • Turn off screens at least one hour before going to bed.

    4. Turn your bedroom dark

    Turn your bedroom dark for restful sleep.(Shutterstock)
    Turn your bedroom dark for restful sleep.(Shutterstock)
    • Keep your bedroom dark, cool, quiet, and clutter-free.
    • Using blackout curtains or white noise machines can further promote restful sleep.

    5. Avoid caffeine or heavy meals before bed

    • Caffeine can stay in your system for hours.
    • Heavy food may cause gut discomfort that disrupts sleep.
    • Opt for lighter meals earlier in the evening.

    Note to readers: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.

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    News / Lifestyle / Health / Pulmonologist reveals 5 habits that help improve sleep quality: Change pillow cover, no caffeine and more

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