Mitochondria are the body’s “energy factories,” and their proper function is essential for life. Inside mitochondria, a set of complexes called the oxidative phosphorylation (OxPhos) system acts like a biochemical assembly line, transforming oxygen and nutrients into usable energy.
Now, the study, led by the GENOXPHOS group at the Spanish National Centre for Cardiovascular Research (CNIC) and the Biomedical Research Networking Centre in the area of Frailty and Healthy Ageing (CIBERFES), and directed by Dr. José Antonio Enríquez, has revealed how this system evolved over millions of years-from the first vertebrates to modern humans. “Understanding this evolution helps explain why some genetic mutations cause rare but serious diseases that affect the OxPhos system,” say José Luis Cabrera the leading author of the study.
Published in Cell Genomics, the study describes the molecular evolutionary strategies of the OxPhos system, the main site of metabolic and energy integration in the cell. It also shows how this information can be used to identify mutations that cause disease.
Working in collaboration with Fátima Sánchez-Cabo, head of the CNIC Computational Systems Biomedicine group, the researchers analyzed the interaction between the two types of DNA that encode OxPhos proteins: nuclear DNA (inherited from both parents) and mitochondrial DNA (inherited only from the mother).
The OxPhos system, explains José Antonio Enríquez-head of the CNIC Functional Genetics of the Oxidative Phosphorylation System (GENOXPHOS) group-comprises five large protein complexes: four that transport electrons and one, called ATP synthase, that produces ATP, the cell’s molecular “fuel.”
These complexes can work individually or in combination, depending on the cell’s energy needs. Together, they are made up of 103 proteins encoded by two different genomes: nuclear and mitochondrial. While nuclear DNA changes slowly over time and gains variation through genetic mixing during reproduction, mitochondrial DNA evolves much more rapidly but is passed only through the maternal line.”
Dr. José Antonio Enríquez, GENOXPHOS Lab, CNIC
Dr. Cabrera adds that the proteins encoded by mitochondrial DNA form the core of the respiratory complexes, “so proper function depends on precise compatibility between the nuclear and mitochondrial components.”
The study also introduces an innovative new tool: ConScore, a predictive index that assesses the clinical relevance of mutations in the 103 OxPhos proteins. “ConScore is based on the evolutionary divergence of these proteins across vertebrates-including primates and other mammals-and complements human population genetic data,” says Enríquez.
The authors affirm that ConScore provides a new framework for interpreting potentially pathogenic mutations, opening the door to improved diagnosis and treatment of mitochondrial diseases.
Ultimately, the researchers conclude, this study not only advances our understanding of how human cells evolved, but also brings us closer to new solutions for patients with rare genetic diseases.
Source:
Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.)
Journal reference:
Cabrera-Alarcón, J. L., et al. (2025). Structural diversity and evolutionary constraints of oxidative phosphorylation. Cell Genomics. doi.org/10.1016/j.xgen.2025.100945.
Amazon Prime Day kicks off next week on Tuesday, July 8, but one of the best early mobile offers I’ve seen is already here. That’s right — you don’t need to be a Prime member to snag these savings, and this smartphone is already under $1,000.
The new Nothing Phone 3 just launched (seriously, our expert is still in London post-launch party), and Amazon already has a tempting preorder offer.
Also: The best Prime Day tech deals
If you preorder the Nothing Phone 3 on Amazon, you can scoop up the 512GB model for $799. That’s a $100 discount on the 16 + 512GB model, and a chance to swipe up double the storage for the same price as the 12+ 256GB model, which is also available for preorder for $799. You save $100, get twice the storage, and get the new Nothing Phone 3 when it ships on July 15.
Expert Prakhar Khanna says that Nothing’s new flagship phone is the brand’s most expensive and risky product yet. “At $799, the Nothing Phone 3 no longer undercuts its midrange competitors. Instead, the handset takes on the likes of the iPhone Pro, Pixel Pro, and Galaxy S phones of the world with a striking design, functional AI features, and fine software tuning,” he says.
Also:I tried the controversial Android phone that’s got the internet buzzing – and left impressed
Khanna got a first-look at the new device at Nothing’s launch party in London this week, and he says it’s “poised to make a splash” in a competitive mobile market.
The display on the Nothing Phone 3.
Prakhar Khanna/ZDNET
At 218 grams, Khanna says the new Phone 3 isn’t the heaviest flagship phone. It features flat sides with curved corners and a glass design that he says feels ergonomic to hold. It also supports IP68 dust and water resistance.
The phone features a 6.67-inch LTPS AMOLED display, which goes from 30Hz to 120Hz instead of going all the way down to 1Hz like LTPO panels. Khanna says the latter is more battery efficient, but that the Phone 3’s 5,150mAh battery should last a whole day.
Also:I’m a phone expert, and you won’t want to miss these July 4th phone deals
Unlike other flagships, the Nothing Phone 3 is powered by Qualcomm’s Snapdragon 8s Gen 4 chipset, which doesn’t have the new Oryon CPU cores. The Nothing flagship features three 50MP cameras on the back and a 50MP selfie camera on the front. The Nothing Phone 3 also supports TrueLens Engine 4, which is said to process photos 125% faster than the previous Phone 2. It also helps improve HDR performance, real-time scene segmentation, lower noise, and smoother motion.
It runs Android 15-based Nothing OS and is promised to get Android 16 later this year. Khanna says it’s also housing some handy AI features, like Essential Space, which holds everything that you record with the Essential Key, plus new features like Flip to Record, which records and transcribes audio recordings when you put the phone face down.
Intrigued by Nothing’s latest release? Preorder the Nothing Phone 3 for a double storage upgrade and $100 savings at Amazon while you can.
Looking for the next best product? Get expert reviews and editor favorites with ZDNET Recommends.
How I rated this deal
This $100 savings offer translates to 11% savings, which isn’t typically a great deal. However, this phone releases July 15 and is brand new to the market, so it’s a first-time discount on a freshly launched product. Plus, when you factor in that the phone is already under $1,000 and the larger, 512GB model is selling for $799, it’s a pretty good bargain. While the 256GB model isn’t on sale, you can take advantage of a double the storage offer by grabbing the 512GB model for the same $799 price, boosting your storage and essentially saving you $100. Due to these factors, I’ve bumped up this first-time offer to a 4/5 Editor’s deal rating.
While many sales events feature deals for a specific length of time, deals are on a limited-time basis, making them subject to expire anytime. ZDNET remains committed to finding, sharing, and updating the best offers to help you maximize your savings so you can feel as confident in your purchases as we feel in our recommendations. Our ZDNET team of experts constantly monitors the deals we feature to keep our stories up-to-date. If you missed out on this deal, don’t worry — we’re always sourcing new savings opportunities at ZDNET.com.
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In a recent lecture on RNA Biology by Dr. Fazal Adnan, the Head of the Department at Atta Ur Rahman School of Applied Biosciences in Islamabad, presented an intriguing illustration (see Figure 1), that truly ignited curiosity among all of us students. This captivating image not only piqued scientific curiosity but also inspired a deeper conversation about human molecular biology and its evolution. It made me reflect on both the incredible advancements we have made in the past and appreciate the journey of discovery that has brought us to where we are today.
It is a widely accepted practice to express gratitude to our ancestors for their contributions in advancing civilization and transforming our way of life. But what if I tell you that our bodies have a similar practice. Just like we honor those who came before us, our cells remember past infections through integrating invader sequences in our genome, helping our cells recognize and combat similar threats in the future. Isn’t that incredible? It’s a fascinating dance of human evolution alongside the evolution of microbes. So, who’s the smarter one in this partnership? Well, this is about the untold story of RNA biology that has revolutionized our understanding of molecular defense. Let’s dive into it.
A recent article published in Nature raised a critical question: Why is RNA structure so difficult to predict? While many bioinformatics platforms have successfully tackled protein analysis, they fall short in RNA prediction. This discrepancy highlights a significant challenge in our field, and we must delve into this question, as understanding RNA structure is key to advancing our knowledge in molecular biology and therapeutics.
For many years, RNA has served as an intermediary component within the framework of the central dogma of molecular biology. Then the discovery of ribozymes, the identification of RNA as a catalyst, and the understanding of the RNA world hypothesis have significantly heightened scholarly interest in the study of RNA.
The true importance of RNA began to shine through in 1974, when groundbreaking research unveiled its remarkable ability to self-modify. This unique trait allows RNA to carry out crucial functions that help safeguard the integrity of the cell and its entire cellular system. This process of regulation through inducing chemically modified tags annotates the sequence to functionalize and generate a desired product. The Accumulation of sequences from past generations has aided in the evolution of the genome to increase its fitness. This fascinating interplay reveals just how adaptable and vital RNA is to life itself.
This has led to the emergence of Epitrancriptomics, which encompasses post-transcriptional modifications that do not affect the base sequence. These modifications have significant implications for the final structure, stability, and translation efficiency of RNA molecules. These chemical modifications control gene expression beyond the DNA sequence.
Cracking The RNA Code: What Is Epitranscriptomics?
The genetic code can be likened to a language that narrates the experiences and resilience of human beings throughout their lives (see Figure 2). This code, composed of the four nucleotides adenine (A), uracil (U), guanine (G), and cytosine (C), conveys essential biological information. Furthermore, RNA modifications function as grammatical rules that enhance and clarify the meanings conveyed by the genetic sequence. To date, over 170 distinct types of RNA modifications have been identified across various forms of RNA, underscoring the intricate nature of genetic regulation. These modifications are not just static; they’re dynamic and reversible, tightly orchestrated by specialized enzymes. You can think of them as the storytellers in this biological tale: where “writers“(METTL3, METTL14) introduce transformative edits, “erasers“ (FTO, ALKBH5) refine them, and “readers” (YTHDF1, YTHDF2, IGF2BP1) interpret their significance. Embracing this complexity opens up a deeper understanding of the full spectrum of genetic expression.
Epitranscriptomics is an intriguing RNA editing mechanism that sets itself apart from epigenetics. While epigenetics focuses on how chemical modifications influence gene expression, epitranscriptomics delves into the realm of RNA itself. It’s a fascinating layer of gene regulation that actively transforms the RNA message, shaping its destiny in unique ways. Imagine the power of writing directly on RNA, altering its fate and function; this is the dynamic world of epitranscriptomics!
Many different chemical changes can happen to RNA, but N6-methyladenosine stands out as a very important molecular switch. This modification plays a critical role, allowing the cell to adapt to its dynamic needs.
On the other hand, alterations like acetylation and pseudouridylationimprove RNA’s regulatory capabilities even more. They increase the stability of the molecule, enhance its ability to fold, and maintain the integrity of its intricate two- and three-dimensional structures. Because of its crucial function in post-transcriptional control, this vast panorama of alterations highlights the immense complexity and distinctiveness of RNA. A relevant question is raised: might these RNA alterations play a significant role in clarifying the mechanisms behind aging, disease, and evolutionary processes? A pertinent inquiry arises: could these RNA modifications serve as key factors in elucidating the mechanisms underlying disease, aging, and evolutionary processes?
The Groundbreaking Discoveries That Changed RNA Biology
The epitranscriptomics and its application in research and development have opened new avenues and have answered some of the important questions on evolution and the role of molecular agents in it. The most significant application is the development of technology to map all the chemical modifications on the transcriptome, which can tell a lot about human health and disease and the adaptive trails a cell undergoes. For example, if we want to study cancer, we can check for RNA alterations, to seek specific modifications specific to that pathogenesis could help to develop novel targets for drug development and understanding how a cell undergoes dysfunction.
One of the most significant and potent examples is the development of the COVID-19 vaccine, where chemical alterations have been made to mRNA coding for the protein of interest, increasing the vaccine efficacy while minimizing the unwanted immune reactions. This is the way that understanding chemical modifications for safety profiles of many potent vaccines and therapeutic drugs accelerates the research advancement and provides a novel platform to tackle critical health concerns.
The Living and the Dead Li’s Elements
Historically, the epitranscriptomic encompasses the chemical changes such as methylation, acetylation, and pseudouridinylation, but now it has added some new modes of changes. Xiong et al reported that this region also includes RNA control by retrotransposition, which is assisted by the m6A alteration. These retrotransposons provide prospective targets for RNA modification.
A study by Dominissini et al distinguishes between “living” (retrotranspositionally competent) and “dead” (retrotranspositionally incompetent) L1 components where data indicates that m6A enhances the activity of functional “living” L1 sequences while simultaneously serving a significant role for “dead” L1 sequences. These “dead” L1 sequences can influence the host organism by inhibiting genes that typically suppress the transposition of “living” L1s. Moreover, these alterations exhibit non-random characteristics and are preserved, signifying that their involvement in retrotransposition represents a strategic framework designed to promote genomic stability and foster functional diversity.
VIP pass to tiny RNA molecules
Small RNAs, known for their existence in plants and traditional therapeutic practices, face considerable obstacles when they travel through the human digestive system. These small compounds are naturally delicate and have difficulty passing through the membranes, which causes their degradation through the body’s surveillance system, before they can induce their potential effects. Despite facing numerous challenges, the remarkable potential of these biomolecules to transform various aspects is truly promising and should not be overlooked.
Guo et al performed research on Ban Zhi Liana, a herb in traditional Chinese medicine where the isolated crude extract contains the specifically modified small RNAs. These are natural, particularly the two fascinating types: 2′-O-methylation (2′-O-Me) and N6-methyladenosine (m6A). Furthermore, the investigation has also found an additional modification known as 5-methylcytidine (m5C); however, this particular modification did not demonstrate the same exceptional advantages as the others. These findings offer a promising perspective on the potential of natural compounds to advance health and therapeutic applications.
The Next Frontier: Can We Hack RNA Modifications for Medicine?
In the above mentioned context, the field of epitranscriptomics is rapidly evolving, providing great opportunities for revealing previously unknown facts within scientific inquiry. Looking ahead, we may anticipate the development of novel instruments and assays, which will pave the way for further in-depth study in RNA biology, covering topics such as aging and cancer, allowing the detection of changes at the individual cell level. Such breakthroughs will allow us to monitor organ health with great accuracy. The advancement of knowledge and technologies to map all chemical changes in a transcriptome will enable the screening of lethal and healthy tags, and techniques to restore them. Here, CRISPR-based tools are transforming the utilization of chemical tags from diagnostics to therapeutics, allowing researchers to add or remove critical modifications with precision. This advancement is laying the groundwork for next-generation theragnostics, in which physicians may one day be able to address diseases by directly targeting RNA and making diagnostics more sensitive and precise.
We are just beginning to unlock the mysteries of RNA and its critical role in understanding how our bodies function. In the not-so-distant future, we will gain insights into how our bodies heal, all thanks to the fascinating world of RNA biology. It’s an exciting time to be part of this journey.
References
Bhat, S. S., Bielewicz, D., Jarmolowski, A., & Szweykowska-Kulinska, Z. (2018). N6-methyladenosine (m6A): Revisiting the Old with Focus on New, an Arabidopsis thaliana Centered Review. Genes, 9(12), 596. https://doi.org/10.3390/genes9120596
Cerneckis, J., Ming, G.-L., Song, H., He, C., & Shi, Y. (2024). The rise of epitranscriptomics: Recent developments and future directions. Trends in Pharmacological Sciences, 45(1), 24–38. https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(23)00254-7
Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., & Kupiec, M. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485(7397), 201–206. https://idp.nature.com/authorize/casa?redirect_uri=https://www.nature.com/articles/nature11112&casa_token=998Qh-5Va2cAAAAA:InO38ZnffREIuw_ScTtRKxGpwzFdbabgd0mQRmMDeDoJIkshEt5L39MG4Lc2K_sXGYe8FtxUM293sYqm0g
Guo, S., Li, Z., Li, X., Liang, Z., Zhao, D., Sun, N., Liu, J., Wang, X., Mei, S., & Qiao, X. (2025). 2′-O-methylation and N6-methyladenosine enhance the oral delivery of small RNAs in mice. Molecular Therapy Nucleic Acids. https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(25)00128-3
Kwon, D. (2025). RNA function follows form-why is it so hard to predict? Nature, 639(8056), 1106–1108. https://pubmed.ncbi.nlm.nih.gov/40128371/
Xiong, F., Wang, R., Lee, J.-H., Li, S., Chen, S.-F., Liao, Z., Hasani, L. A., Nguyen, P. T., Zhu, X., & Krakowiak, J. (2021). RNA m6A modification orchestrates a LINE-1–host interaction that facilitates retrotransposition and contributes to long gene vulnerability. Cell Research, 31(8), 861–885. https://www.nature.com/articles/s41422-021-00515-8
Microsoft has begun rolling out a long-awaited feature to Copilot for Windows 11 and Windows 10, allowing the AI assistant to search for files stored locally or synced via OneDrive. Previously, this feature was only available to Windows Insiders, but is now available to all Copilot users, reports Windows Latest.
Copilot’s File Search feature uses Windows Search indexing to find documents by name, type, or date. Microsoft Office formats (DOCX, XLSX, PPTX), PDF, text files, and more are supported. However, developer-specific extensions, such as .dart, are not currently supported.
By default, Copilot only has access to the Documents and Downloads folders, but the search scope can be customized in Windows permissions settings. To activate the feature, users need to enable it in Copilot settings. Microsoft deliberately did not enable it by default for privacy reasons.
Microsoft says the feature will be rolling out gradually over several weeks and does not require a Copilot Pro subscription. The company sees local file search as a natural extension of Copilot’s desktop integration, helping users quickly find and interact with documents without leaving the chat interface.
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Alanis Morissette’s headline show at the Lytham Festival has been cancelled due to 40mph winds being forecast on the Fylde coast, organisers have confirmed.
In a statement, organisers said the decision had been taken because of “adverse weather conditions”.
A TK Maxx presents Lytham Festival spokesperson said: “The safety of our customers, staff and artists is our priority and increasing high winds mean it would not be safe to go ahead.
“All customers will receive a full refund for tonight’s show. Please wait to hear from your ticket agent for further information.”
The four-day music festival at Lytham Green, which runs until Sunday, was headlined on Thursday by legendary singer-songwriter Stevie Wonder.
Rock band Kings of Leon had been due to open the festival, but had to cancel their appearance in May after lead singer Caleb Followill broke a bone in his heel in a “freak” accident.
Canadian singer-songwriter Morissette shot to fame with her 1995 album Jagged Little Pill, which contained hits including Ironic, You Oughta Know, and Hand In My Pocket.
Other acts who were due to play on Friday included Train – best known for their hit single Hey, Soul Sister – Greater Manchester indie band The Lottery Winners, and US singer Liz Phair.
Justin Timberlake is due to headline on Saturday while Sunday’s closing night will feature dual headline slots from Simple Minds and Texas.
Other acts booked for the four-day festival – expected to attract more than 100,000 music fans – include Corinne Bailey Rae, Jess Glynne and Cast.
There will also be a special tribute to Welsh musician, songwriter and cancer campaigner Mike Peters of The Alarm.
New research analyzing an online survey of 1,633 respondents found 15% recent use of doxycycline post- and pre-exposure prophylaxis (doxyPEP/PrEP) among men who have sex with men (MSM), transgender and gender diverse people in the Netherlands according to a recent study published by Eurosurveillance. These data highlight an increase in the informal use of doxyPEP/PrEP, with 65% of the participants intending to use it in the future. Currently, doxyPEP/PrEP is not recommended or actively promoted by healthcare professionals in the Netherlands. Informal use i.e. without a prescription by a healthcare professional, could contribute to antimicrobial resistance (AMR) and changes in the microbiome.
The use of doxyPEP has been shown to be an effective method in the prevention against sexually transmitted infections (STIs) in MSM, transgender and gender diverse persons. Clinical trials of doxyPEP have shown significant reductions in syphilis and chlamydia, with additional potential to reduce incidence of other bacterial STIs such as chlamydia and gonorrhea
However, the public health implications of the widespread use of doxyPEP are subject to current debate. The administration of doxyPEP to specific individuals could prevent a substantial number of STIs and lower antibiotic use, particularly among those who repeatedly have STIs.
Informal doxyPEP/PrEP use associated with HIV PrEP use, sexualized drug use and perception of safety
As highlighted by this paper and an accompanying editorial by Lyons et al., the prescription of doxyPEP to many sexually active individuals poses the risk of a substantial population-level increase in overall antibiotic consumption and an increase in AMR.
Teker et al. reviewed data from a cross-sectional study gathered from an online survey among MSM, transgender and gender diverse persons of 18 years of age or older. The survey focused on previous use of doxyPEP or doxyPrEP awareness and intention to use it. Participants were recruited through advertisements at the Centre for Sexual Health in Amsterdam, the Netherlands, as well as dating apps (Grindr), Instagram, Facebook, Facebook Messenger and targeted Instagram accounts.
In the study, 23% of participants reported having ever used doxyPEP/PrEP and 15% reported having used doxyPEP/PrEP in the six months prior to the survey. Respondents informing about recent use were more likely to report living with HIV or frequently using oral HIV PrEP in the six months before taking the survey. They were also more likely to report a history of bacterial STIs, having a higher number of sexual partners, and a higher frequency of engaging in chemsex and in group sex during that period.
Doxycycline was the most used antibiotic reported in this study, with 46% of the participants reporting using it recently as PEP, 29% of recent PEP users using it as PrEP and 25% using it as a combination of both.
Overall, the intention to use doxyPEP/PrEP was very high among the study population, with more than half of the participants (65%) expressing intention to use. More than two thirds of respondents (72%) were willing to pay for doxyPEP/PrEP if it became formally available, indicating a potential demand for the drug among the study population and beyond.
It was also found that doxyPEP/PrEP was primarily obtained from countries outside of the Netherlands or through prescriptions, with participants paying on average €30 for the drug.
Additional determinants for both informal use of doxyPEP/PrEP and high intention to use included using oral HIV PrEP or living with HIV, receiving advice from others to use doxyPEP/PrEP and perceiving doxyPEP/PrEP as an effective and safe method of STI prevention.
Potential antimicrobial resistance risks from lack of monitoring
The impact of prophylactic antibiotic use on AMR was highlighted in the study as there are uncertainties regarding the long-term adverse effects of doxyPEP/PrEP use. Teker et al. emphasize the potential harms of doxycycline effectiveness and AMR risks, as summarised in previous studies including in the United States.
They also cite its potential effects on the gut microbiome, which need to be studied further. If doxyPEP is implemented in country-wide clinical guidance, it would be vital to monitor both individual and population-level resistance to doxycycline.
Lack of awareness on the extent of informal use of doxyPEP/PrEP makes it difficult to monitor and implement appropriate public health stewardship. This leads to difficulties in detecting overuse, misuseand adverse effects including AMR development and effects on microbiome composition.
Source:
European Centre for Disease Prevention and Control (ECDC)
Journal reference:
Buhari, T., et al. (2025). Emergent informal use of doxycycline post- and pre-exposure prophylaxis among men who have sex with men and transgender and gender diverse people, the Netherlands, 2024. Eurosurveillance. doi.org/10.2807/1560-7917.ES.2025.30.26.2400707
Quantitative vessel tortuosity (QVT), a noninvasive, radiomics-based imaging biomarker, was able to detect the antiangiogenic mechanism of action of fruquintinib (Fruzaqla) in patients with metastatic colorectal cancer (mCRC), according to data from a retrospective analysis of the phase 3 FRESCO-2 trial (NCT04322539) presented during the 2025 ESMO Gastrointestinal Cancer Congress.
Results from the analysis demonstrated that patients in the fruquintinib group experienced a 70% decrease of vessel inflection in lung lesions from baseline to day 1 of cycle 3 (P < .0006). Additionally, patients in the fruquintinib arm experienced median reductions in vessel volume, torsion, curvature, and radius of 25% (P < .006), 15% (P < .05), 10% (P < .05), and 5% (P < .05), respectively, over the same time period. Conversely, patients in the placebo arm experienced a 30% increase in abnormal vessel branching at day 1 of cycle 3 compared with baseline (P < .05).
“Significant changes in QVT features between patients in the fruquintinib and placebo arms were observed during the first assessment, demonstrating the early antiangiogenic action of fruquintinib,” Sara Lonardi, MD, chief of the Oncology 3 Unit of Veneto Institute of Oncology in Padua, Italy, and her coauthors wrote in the poster. “The observed differences in Delta QVT radiomic features…quantify the ability of fruquintinib to prevent the formation of a twisted, heterogeneous vasculature.”
In November 2023, the FDA approved fruquintinib for the treatment of adult patients with mCRC who received previous treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.2 The regulatory decision was partially supported by prior data from FRESCO-2, which demonstrated that patients treated with the VEGFR inhibitor experienced a 34% reduction in the risk of death compared with those who received placebo (HR, 0.66; 95% CI, 0.55-0.80; P < .001).
FRESCO-2 Study Design and Retrospective Analysis Methods
FRESCO-2 was a global, double-blind study that enrolled adult patients with metastatic CRC.3 Patients were required to have experienced disease progression on or have been intolerant to trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga). Eligible patients also needed to have a body weight of at least 40 kg, an ECOG performance status of 0 or 1, measurable disease per RECIST 1.1 criteria, and an expected survival of over 12 weeks.
Patients were randomly assigned 2:1 to receive fruquintinib (n = 461) or placebo (n = 230) at 5 mg daily, both in combination with best supportive care.1 Treatment was administered in 28-day cycles for 3 weeks on, 1 week off. Treatment in both arms continued until disease progression or unacceptable toxicity.
The primary end point was overall survival (OS).3 Secondary end points included progression-free survival, objective response rate, disease control rate, duration of response, and safety.
This retrospective analysis included CT scans from 221 patients enrolled in FRESCO-2; 442 lesions were analyzed from 162 patients in the fruquintinib arm and 167 lesions were analyzed from 59 patients in the placebo arm.1 For each lesion, 909 QVT features were extracted to quantify peritumoral vascularity. The longitudinal change in QVT features was calculated as the percentage change in features from screening to day 1 of cycle 3.
Following CT scan image transfer, image processing and lesion selection occurred, followed by lesion annotation and segmentation. QVT features were then extracted and selected prior to data integration and analysis.
The presence of lung metastases was the primary objective of the retrospective analysis. Notably, primary colorectal lesions were not analyzed due to the high rate of resection prior to screening.
Additional Findings From the Retrospective Analysis
Additional data from the retrospective analysis revealed that a statistically significant difference in Delta QVT with fruquintinib vs placebo was observed in 11 of the 21 preselected QVT features. Treatment with fruquintinib also showed a clear normalizing effect on tumor-associated vasculature in lung metastases. Compared with placebo, treatment with fruquintinib led to decreases in mean vessel curve intensity (P = .02095), mean branch length (P = .04677), number of branches (P = .01460), mean torsion (P = .01939), torsion length-to-distance ratio (P = .00991), number of vessel inflection points (P = .00606), mean vessel radius (P = .01282), and vessel volume (P = .00606).
“These findings establish the value of QVT as a direct measure for fruquintinib-based antiangiogenic activity and support the use of this method as a potential tool to assess treatment effect based on the mechanism of action,” Lonardi and her coauthors wrote in their conclusion. “Further analyses are planned to include liver lesions and a predictive model of OS.”
Disclosures: Lonardi reported being on the advisory boards of Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol Myers Squibb, Astellas, GlaxoSmithKline, Takeda, Bayer, Rottapharm, BeiGene, Nimbus Therapeutics, and Helion. She has also been an invited speaker for Pierre Fabre, GlaxoSmithKline, Roche, Servier, Amgen, Bristol Myers Squibb, incyte, Lilly, Merck Serono, and AstraZeneca, as well as a coordinating primary investigator for Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, and Bristol Myers Squibb.
References
Lonardi S, Yardibi O, Dasari A, et al. A novel imaging biomarker, quantitative vessel tortuosity, captures the antiangiogenic effect of fruquintinib in metastatic colorectal cancer. Presented at: ESMO Gastrointestinal Cancers Congress 2025; July 2-5, 2025; Barcelona, Spain. Abstract 32P.
FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed July 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer
A study of efficacy and safety of fruquintinib (HMPL-013) in participants with metastatic colorectal cancer (FRESCO-2). ClinicalTrials.gov. Updated April 4, 2025. Accessed July 4, 2025. https://clinicaltrials.gov/study/NCT04322539
Xiaomi has introduced new smart glasses to the global market. The eyewear is called the Smart Audio Glasses and is currently available on AliExpress for $86.54. While that’s an affordable price tag, the feature set is not as extensive as some of the other options in the market.
To be specific, as the name somewhat suggests, the wearable is basically a pair of glasses with functionalities of Bluetooth earbuds. Of course, given the design, these smart glasses can be considered an alternative to open-ear headphones, and as Xiaomi highlights, there are sound leakage protections for enhanced privacy in public spaces.
The company also notes that the smart glasses feature an SLS0820 ultrasonic speaker and sound cavity structure algorithm. This combination allows the eyewear to offer “optimized sound quality” and deliver “rich, deep bass” along with “vibrant, clear treble.” The wearable has an echo-cancelling algorithm as well, which is said to lower distortion and ensure clear audio output.
Another highlight of the Xiaomi Smart Audio Glasses is the battery life. The company claims that in standby mode, the runtime can reach 11 days, while they are said to offer up to 10 hours of battery life when listening to audio. Regarding charging the built-in battery, the wearable relies on a magnetic pogo pin charger, similar to what most smartwatches come with.
Design-wise, Xiaomi highlights that the smart glasses have a frame that weighs 40 grams. With a comfort-forward temple curve and adjustable nose pads, the wearable is said to offer all-day comfort. Other highlights include a detachable hinge design for interchanging frames, an IP54 water and dust resistance rating, and touch controls.
Abid Ahsan Shanto – Senior Tech Writer – 1767 articles published on Notebookcheck since 2023
Abid’s journey as a technophile began when he first assembled his PC. Since then, his insatiable curiosity has driven him to delve into every aspect of this rapidly evolving technological landscape. And as a tech reporter, he prioritizes transparency, accuracy, and unbiasedness.
