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PubMed2026

Multi-omics insights into the physiological mechanisms of bile acid accumulation in the gallbladder in brumation-like snakes.

Hibernation/brumation represents an important physiological adaptation for animals to cope with seasonal environmental changes. Field observations suggested increased gallbladder weight in the Five-pacer viper (Deinagkistrodon acutus) during brumation, and our quantitative measurements confirmed this increase together with bile acid accumulation. By integrating a multi-omic approach, this study elucidates the regulatory mechanisms of bile acid accumulation in the gallbladder during brumation. Results showed that taurocholic acid (TCA) and taurodeoxycholic acid (TDCA) were the major components in the gallbladder of the brumation-like group, with significantly elevated concentrations of bile acids, whereas bile acid concentrations in serum and intestinal contents were markedly reduced, indicating suppression of the enterohepatic circulation and consequent accumulation of bile acids in the gallbladder. Hepatic transcriptomic analysis revealed significant downregulation of bile acid synthesis and regulatory genes in brumation-like snakes. In contrast, the alternative synthesis pathway gene sterol 27-hydroxylase (CYP27A1) and some transporter genes were slightly upregulated. Further, some modification genes and regulatory genes showed no significant differences between active and brumation-like states. Gut microbiota analysis demonstrated Akkermansia muciniphila, Bacteroides fragilis, and Citrobacter freundii were more enriched in the active group, which were common microbes related to bile acid metabolism, and the correlation analysis confirmed this relationship. Taken together, these findings indicate that the "physiological bile acid accumulation" observed in snakes during brumation-like state is jointly driven by suppressed hepatic synthesis, reduced enterohepatic circulation, and remodeled microbial community structure. The study provides novel comparative physiological insights into extreme metabolic homeostasis in animals.

Animals↗

PubMed2026

Dissociable neural mechanisms of cognitive enhancement through transcranial stimulation and behavioral training.

BACKGROUND: Transcranial direct current stimulation (tDCS) and adaptive working memory (WM) training are promising cognitive enhancement approaches; however, their neural mechanisms and potential synergies remain poorly understood. OBJECTIVE: We directly compared how tDCS and WM training modulate neural oscillations during WM performance and examined whether combining both interventions produces additive effects. METHODS: We randomized 112 healthy adults into four groups: control (sham tDCS + non-adaptive 1-back), tDCS-only (active tDCS + non-adaptive 1-back), training-only (sham tDCS + adaptive n-back training), or combined (active tDCS + adaptive training). Participants underwent five daily intervention sessions. We recorded high-density EEG during transfer n-back tasks at baseline, post-intervention, and one-week follow-up. RESULTS: All active interventions improved WM performance relative to the control group, with the combined group showing the largest gains (n-back accuracy: +15.6% vs. + 10.1% tDCS-only, +9.7% training-only, +0.7% control; all p < 0.001). Critically, tDCS selectively increased gamma-band (30-50 Hz) power in the frontal and parietal regions (cluster p = 0.018, d > 1.0), whereas WM training enhanced frontal theta-band (4-8 Hz) power and theta-gamma phase-amplitude coupling (both cluster p < 0.012, d > 0.85). The combined group exhibited both neural signatures. Brain-behavior correlations revealed dissociable relationships: gamma increases predicted n-back accuracy improvements (r = 0.61, p < 0.001), whereas theta enhancements correlated with operation span gains (r = 0.58, p = 0.002). CONCLUSIONS: tDCS and WM training enhance cognition through distinct yet complementary neural mechanisms: tDCS via gamma-mediated cortical excitability and WM training via theta-mediated cognitive control. These findings provide neurophysiological evidence for multimodal enhancement strategies that target parallel pathways within WM networks.

Humans↗

PubMed2026

Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.

Advanced maternal age is a well-established risk factor for adverse reproductive outcomes due to increased rates of aneuploidy. However, emerging evidence indicates that the genetic consequences of maternal aging extend well beyond chromosome mis-segregation. Aging oocytes acquire a broad spectrum of genetic abnormalities, including maternally derived nuclear de novo mutations (DNMs) and mitochondrial DNA mutations, together with epigenetic dysregulation of DNA methylation and post-translational modification levels. These changes reflect the unique biology of the female germline in which oocytes remain arrested in meiotic prophase I for decades. Age-related deterioration of key processes, such as erosion of cohesion complexes, altered meiotic recombination, and weakened spindle assembly checkpoint surveillance collectively destabilize meiotic chromosome architecture, directly driving chromosome mis-segregation. At the same time, accumulation of endogenous DNA damage and declining DNA damage and repair processes increase the chances of transmitting lesions that can be converted into sequence-level mutations during the earliest embryonic divisions, when genome maintenance relies exclusively on maternal factors. High-resolution sequencing studies further demonstrate that maternal aging is associated with increased DNMs burden in both nuclear and mitochondrial DNA. Together, these findings support a model in which maternal aging is a driver of genome-wide instability that links aneuploidy and mutagenesis through shared defects in meiotic surveillance, declining DNA repair efficiency, and mitochondrial function. This framework positions delayed childbearing as a multifaceted genetic risk factor that extend beyond aneuploidy to include mutations and other genomic alterations that can impact intergenerational genetic risk.

Aneuploidy↗

PubMed2026

Ageing effects on chemical, physical, mechanical, and morphological properties of clear aligners - a systematic review.

BACKGROUND: Clear aligner (CA) therapy has experienced rapid use over the past two decades to treat orthodontic malocclusions. However, evidence on CA material degradation in the oral environment remains limited and often focuses on single brands or isolated material properties. OBJECTIVES: To investigate CA ageing characteristics across different materials and brands and evaluate the chemical, physical, mechanical, and morphological changes following simulated or intraoral ageing. SEARCH METHODS: Five databases (PubMed, Web of Science, MEDLINE [Ovid], ProQuest, and Scopus) were searched to 18 March 2026, with no restrictions. ELIGIBILITY CRITERIA: Studies assessing CA properties after intraoral use or simulated ageing (thermocycling, cyclic loading, or liquid immersion) were included. DATA COLLECTION AND ANALYSIS: Study selection followed PRISMA 2020. RoB was assessed using QUIN for purely in vitro studies, JBI for cohort in vivo studies, and Cochrane RoB 2 for RCTs. Results were synthesised narratively and organised by property domain, as substantial methodological heterogeneity precluded formal meta-analysis. Where protocols were comparable, a simple pooled weighted mean was calculated and presented graphically. RESULTS: Ninety-five studies were included. RoB was low in eight studies, moderate in sixty-two, and high in twenty-five. Chemical composition remained largely stable during ageing, though some brands showed trace elemental release. Physical, mechanical, and morphological properties showed material-dependent deterioration. Pooled discolouration was greatest with coffee (weighted mean ΔE = 70.9), versus tea (ΔE = 18.4) and red wine (ΔE = 11.5), with Invisalign® consistently exceeding the clinically perceptible threshold. Force decay of 40-90% typically occurred within 48 h. Thermoplastic polyurethane (TPU)-based and directly printed aligners (DPAs) generally showed greater susceptibility than polyethylene terephthalate glycol-modified (PETG)-based aligners, though findings on hardness, roughness, and stiffness were inconsistent. CONCLUSIONS: CA materials undergo clinically relevant degradation during use, particularly in TPU-based and DPAs aligners. Clinicians may need to prioritise material-specific protocols, reinforce dietary and cleaning instructions, and consider force decay when determining aligner replacement intervals. PROSPERO number: CRD420251110248.

Humans↗

PubMed2026

Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard®) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n = 53) or an untreated control group (n = 51). Clinical evaluations were performed on Days 0, 15 (±2), 30 (±2), and 45 (±2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p < .001), with large effect sizes at the final visit for all outcomes (r = 0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals↗

PubMed2026

Mechanisms of high-humidity hot air impingement blanching (HHAIB) on microbial counts, functional properties, phenolic profile transformation, and volatile compounds in celery stalks (Apium graveolens L.).

In this study, celery stalks were pretreated with different durations (0-150 s) of high-humidity hot air impingement blanching (HHAIB), followed by far-infrared radiation assisted pulsed vacuum freeze-drying (FIR-PVFD) at 60, 65, and 70 °C. The effects of HHAIB on the physicochemical properties, composition and transformation of phenolic compounds, volatile components, and antioxidant capacity of FIR-PVFD-dried celery stalks were systematically investigated. The results showed that HHAIB not only effectively reduced the counts of total mesophilic aerobic bacteria (TMAB) and total yeast and mold (TYM), but also decreased the relative activities of polyphenol oxidase (PPO) and lipoxygenase (LOX) by more than 91% after 90 s of treatment. HHAIB altered the cellular structure of celery stalks, shortened the drying time by 29.33-41.43%, and improved their hydration properties. HHAIB pretreatment promoted the conversion of bound phenolics to free phenolics in celery stalks, with significant increases in the contents of p-coumaric acid, apigenin, graveobioside A, and other components. The total free phenolic content increased by 56.99%, thus HHAIB enhanced the antioxidant activity. An electronic nose and sensory evaluation revealed that HHAIB-pretreated celery stalks better retained the characteristic herbal and pungent notes. GC-MS results indicated that HHAIB treatment optimized the aroma profile by regulating the contents and composition of terpenes, aldehydes, ketones, alcohols, and aromatic compounds.

Apium↗

PubMed2026

Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced ∼10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.

Nonsense Mediated mRNA Decay↗

PubMed2026

Engineering copper ferrite (CuFe2O4) nanocomposites for enhanced eco-friendly photocatalysis: a systematic critical review on mechanisms, performance, and environmental applications.

Water pollution caused by organic and inorganic contaminants, particularly dyes and pharmaceuticals, represents a major environmental challenge. Advanced oxidation processes based on photocatalysts have emerged as efficient and sustainable approaches for water and wastewater treatment. Copper ferrite (CuFe2O4) is considered a promising photocatalyst owing to its narrow bandgap, visible-light activity, chemical stability, and magnetic properties. Despite extensive experimental investigations, a comprehensive systematic comparison of CuFe2O4-based photocatalysts under diverse operational conditions has remained limited. In this study, a systematic review following PRISMA guidelines was conducted using studies published between January 2014 and November 2025 indexed in Scopus, PubMed, Web of Science, and ScienceDirect. From an initial pool of 397 studies, 98 articles met the inclusion criteria. Key parameters - including pollutant type, pH, catalyst dosage, initial pollutant concentration, irradiation time, light source, and degradation efficiency - were quantitatively compared to identify performance trends and operational optima. The results demonstrate that CuFe2O4-based nanocomposites, particularly heterojunction, Z-scheme, and S-scheme architectures combined with TiO2, g-C3N4, graphene, and metal oxides, achieve high degradation efficiencies (often >90 %) for a wide range of organic pollutants and selected inorganic contaminants (e.g., Cr(VI)). Enhanced charge separation and suppressed electron-hole recombination were identified as the primary factors contributing to improved photocatalytic activity. In addition, the intrinsic magnetic properties of these nanocomposites enable facile catalyst recovery and reuse. In conclusion, CuFe2O4-based nanocomposites, especially those incorporating advanced heterojunction architectures, emerge as highly efficient and magnetically recoverable photocatalytic platforms for sustainable water and wastewater treatment, with strong potential for scalable implementation and real-wastewater applications.

Catalysis↗

PubMed2026

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

Autophagy activation in granulosa cells as a mechanism of astaxanthin action: evidence from a pilot randomised trial in PMOS-associated infertility.

Astaxanthin (AST) has been reported to influence oxidative stress, endoplasmic reticulum stress, and apoptosis in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), but its effects on granulosa-cell (GC) autophagy remain unclear. Given the central role of autophagy in follicular development, this triple-blind, placebo-controlled pilot randomised trial evaluated whether AST modulates autophagy-related signalling in GCs and how these molecular effects relate to ovarian response. Fifty women with PMOS-related anovulatory infertility were enrolled between November 2023 and September 2024 and received AST (12 mg/day) or placebo for six weeks prior to oocyte retrieval; forty-four completed the study (21 AST, 23 placebo). Primary exploratory endpoints were molecular markers of adenosine monophosphate-activated protein kinase (AMPK)-autophagy signalling, and primary clinical outcomes included ovarian response indicators and cleavage stage embryo quality. AST supplementation increased autophagy-related gene 7 (ATG7) expression, enhanced autophagy flux, reduced apoptosis, and showed a trend toward increased AMPK activation. Before adjustment, AST improved oocyte maturity rate (OMR) and increased mature (metaphase II; MII) oocyte yield. After adjusting for age, body mass index, and anti-mullerian hormone level, total oocyte and MII oocyte yields remained significantly higher with AST, while OMR became non-significant. Among embryology outcomes, both the top-ranking embryo rate and the number of embryos suitable for cryopreservation were significantly higher with AST after adjustment. Pregnancy outcomes were numerically higher but not statistically significant. This pilot trial suggests that AST activates autophagy- and apoptosis-related pathways in GCs and may enhance oocyte competence and embryo quality in PMOS. Larger studies are needed to confirm these mechanistic and clinical effects.

Female↗

PubMed2026

Mechanisms of impact of mental health peer support in high-, middle- and low-income settings: mediation analysis of the UPSIDES randomised controlled trial.

AIMS: While there is growing evidence for the effectiveness of peer support (PS) in improving psychosocial outcomes among individuals with severe mental health conditions, the mechanisms through which these effects occur remain insufficiently understood. This study examines whether social inclusion, hope and empowerment mediate the relationship between PS, personal recovery and health and social functioning. METHODS: Data were collected from 565 adults with severe mental health conditions who participated in the multicentre UPSIDES randomised controlled trial across six sites in Germany, Uganda, Tanzania, India and Israel. Participants in the intervention group received structured PS from trained peer workers over a 6- to 8-month period. Standardised, self-report measures of social inclusion, hope, empowerment and personal recovery, as well as clinician-rated health and social functioning, were administered at baseline, 4 months, end of intervention (8 months) and 12-month follow-up. Cross-lagged panel modelling was used to explore longitudinal associations and mediating pathways. RESULTS: The cross-lagged models showed strong autoregressive effects across all variables, indicating high temporal stability. There were no significant direct effects of PS on recovery or health and social functioning. However, mediation analysis identified significant indirect effects of PS on personal recovery via social inclusion (β = 0.114, 95% confidence interval [CI] [0.049, 0.194], P < 0.05) and hope (β = 0.037, 95% CI [0.001, 0.086], P < 0.05). Similar indirect effects were observed for health and social functioning (via social inclusion: β = -0.035, 95% CI [-0.064, -0.013]; via hope: β = -0.026, 95% CI [-0.052, -0.006]; both P < 0.05). CONCLUSIONS: Findings suggest that PS affects recovery-related outcomes primarily through intermediate mechanisms of enhanced hope and social inclusion. These results support theoretical models positing indirect pathways of change in PS interventions and highlight the value of targeting social and psychological domains when designing and implementing PS in mental health services. Individuals with lower baseline levels of hope and social inclusion may particularly benefit from PS.

Humans↗

PubMed2026

O'nyong-nyong virus adaptive mutations in non-structural protein 1 and 3 enhance RNA replication and overcome FHL1 requirement.

Arthritogenic alphaviruses, like o'nyong-nyong virus (ONNV), cause debilitating musculoskeletal diseases and are geographically expanding. To predict their emergence, we seek to better understand evolutionary mechanisms that enable changes in virus tropism. Here, we identify adaptive mutations in the ONNV non-structural proteins (nsPs) that arose during cellular serial passaging and enabled ONNV to infect non-permissive Lunet cells. Using shotgun proteomics, we show that this human hepatoma cell line lacks the four-and-a-half-LIM domain protein 1 (FHL1), an essential host factor in ONNV RNA replication. Individual single nucleotide mutations in the nsP1 ring-aperture membrane-binding and oligomerization domain, the nsP3 macrodomain, and the nsP3 opal stop codon overcome FHL1 deficiency in Lunet cells by enhanced RNA replication. These findings demonstrate how subtle genomic changes in nsPs can profoundly influence alphavirus replication and tropism.

LIM Domain Proteins↗

PubMed2026

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation on Abdominal Pain in Patients With Functional Dyspepsia and Irritable Bowel Syndrome.

BACKGROUND: Patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) often experience abdominal pain and reduced quality of life and need effective treatments. This exploratory study aimed to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) could improve abdominal pain and quality of life in patients with FD and IBS, and whether the effects were mediated via the autonomic mechanisms. METHODS: A total of 64 patients with abdominal pain (43 FD and 21 IBS) with a pain score of 3 out of 10 or higher were randomized to receive 2 weeks of taVNS or sham-taVNS treatment. The primary outcome was numeric rating scale (NRS) for abdominal pain. The dyspeptic symptom scales (DSS), IBS symptom severity scale score (IBS-SSS), anxiety and depression scores, and the SF36 quality of life scale were assessed before and after the treatment. The electrocardiogram was also recorded for the assessment of autonomic function at baseline and after the treatment. KEY RESULTS: (1) taVNS reduced the abdominal pain score (p < 0.001 for both FD and IBS), the frequency of abdominal pain (p < 0.001 for both FD and IBS), and overall symptom scores in both FD patients and IBS patients (p < 0.001 for FD and IBS). There was no significant difference in the effect of taVNS on abdominal pain between FD and IBS patients. (2) taVNS improved quality of life compared with baseline in both FD and IBS patients. (3) taVNS decreased anxiety (p < 0.001) and depression (p < 0.001). (4) taVNS increased vagal activity. At the end of the taVNS treatment, the vagal activity was negatively correlated with the pain score (r = -0.491, p = 0.004). CONCLUSIONS: Non-invasive taVNS improves abdominal pain, quality of life, and anxiety and depression in patients with FD and patients with IBS, possibly attributed to the enhancement of vagal activity. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2400085697.

Humans↗

PubMed2026

Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2026

Accelerated Biological Aging Increases the Risk of Head and Neck Cancer: Insights From Genetic Instruments of Epigenetic Clocks.

Epigenetic clocks are robust biomarkers of biological aging and have been associated with cancer susceptibility. However, the relationship between genetically predicted epigenetic age acceleration and head and neck cancer risk remains unclear. Using a large case-control study of 2189 head and neck squamous cell carcinoma (HNSCC) cases and 2189 age- and sex-matched controls, we investigated the associations between polygenic scores (PGSs) for multiple epigenetic clocks and HNSCC risk, and evaluated their potential causal roles using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) associated with four epigenetic clocks (HannumAge, HorvathAge, GrimAge, and PhenoAge) were used to construct clock-specific PGSs. Logistic regression models were applied to assess associations between PGSs and HNSCC risk, while MR analyses, including inverse-variance weighted (IVW), weighted median, and MR-Egger methods, were used to infer potential causal relationships. Among the 48 epigenetic clock-associated SNPs, 12 showed nominal associations with HNSCC risk, and one variant (rs2275558 in PBX1) remained significant after Bonferroni correction (OR = 0.67, 95% CI: 0.60-0.76). PGSs for all four epigenetic clocks were higher in cases than in controls. In logistic regression analyses, each standard deviation increase in HannumAge PGS was associated with a 25% higher risk of HNSCC (OR = 1.25, 95% CI: 1.10-1.41), whereas HorvathAge, GrimAge, and PhenoAge PGSs showed weaker positive associations (ORs ranging from 1.06 to 1.10). Individuals in the highest PGS quartile for all four epigenetic clocks exhibiting 14%-25% higher risk than those in the lower three quartiles. MR analyses supported potential causal effects of genetically predicted HannumAge (IVW OR = 1.24 per SD increase, 95% CI: 1.09-1.42) and GrimAge (IVW OR = 1.23 per SD increase, 95% CI: 0.98-1.56) on HNSCC risk, with consistent estimates in weighted median analyses. Our results highlight biological aging as a potential etiologic mechanism for HNSCC and suggest that epigenetic clock-related genetic profiles may improve HNSCC risk stratification.

Humans↗

PubMed2026

Stage-specific ROMO1 in rheumatoid arthritis: predictive immune insights into the MIF pathway and HLA-DR/IL2RA axis via integrated GWAS, transcriptomic, single-cell, and spatial profiling.

Emerging evidence links reactive oxygen species modulator 1 (ROMO1), a key mitochondrial ROS regulator, to rheumatoid arthritis (RA) pathogenesis. However, its exact mechanism remains elusive given the conflicting evidence about its specific function. We used a four-level integrative framework combining multi-omics data and literature‑supported mechanistic inference. At the genetic level, Mendelian randomization (MR) was performed to explore potential causal relationships between ROMO1, IL2RA, HLA-DR, MIF, and RA risk, followed by differential expression analysis and machine learning-based feature selection to identify key mROS genes. The temporal expression dynamics of ROMO1 were assessed in RA progression. At the cellular and tissue levels, we integrated single-cell RNA sequencing and spatial transcriptomics to map cell-type-specific expression and synovial localization of ROMO1-related immune cells and pathways. Finally, our multi-omics findings were contextualized with literature-supported mechanistic inference. (1) MR results were consistent with a potential protective effect of ROMO1 on RA (OR = 0.52) and its potential regulation of risk factors IL2RA (OR = 0.46) and HLA-DR (OR = 0.40). Conversely, IL2RA (OR = 1.42), HLA-DR (OR = 1.88), and MIF (OR = 1.17) were positively associated with RA risk. Additionally, ROMO1 was identified as a top candidate diagnostic predictor with stage-specific dynamics: downregulated in the early but upregulated in the late/remission stages. (2) Single-cell RNA sequencing showed ROMO1's cell-specific expression in CD14+ HLA-DR+ CD74+ monocytes and CD4+ IL2RA+ T cells. Cell communication analysis further suggested that these cells may participate in MIF pathway regulation. Spatial transcriptomics subsequently identified that ROMO1-related cells localized to synovial pathological regions, with MIF pathway changes correlated with RA progression. (3) Finally, literature-supported mechanistic inference suggests that ROMO1 may modulate mROS levels to promote anti-inflammatory M2 macrophage polarization, which could theoretically contribute to reduced systemic inflammation and the alleviation of multi-organ decline in RA. This integrated multi-omics investigation, supported by literature-based mechanistic inference, suggests ROMO1 as a stage-dependent biomarker candidate and potential immune regulator in RA.

Humans↗