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PubMed2026

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans↗

PubMed2026

Effects of continuous isomaltulose-containing gummy intake on interstitial glucose and salivary hormones during an 18-hole golf round: a randomized, double-blind controlled pilot study.

BACKGROUND: Golf is a prolonged, moderate-intensity sport requiring sustained physiological stability to manage cumulative stress and maintain performance. Although carbohydrate intake is commonly used to reduce fatigue, rapidly absorbed sugar-induced rapid blood glucose fluctuations may induce volatile arousal and latent metabolic stress. Isomaltulose, a slow-digesting disaccharide, provides a steadier glucose supply compared with sucrose. This exploratory pilot study examined the effects of isomaltulose intake on physiological stress markers, glycemic dynamics, and subjective responses during a competitive 18-hole golf round. METHODS: Twenty-three male collegiate golfers were randomized to either the isomaltulose group (ISO; n = 12) or the sucrose group (CON; n = 11) in a double-blind controlled trial. Participants consumed gummies containing isomaltulose or sucrose immediately after each hole (12.1 g carbohydrate per hole; total carbohydrate intake: 217.5 g). Primary outcomes were salivary stress markers [cortisol, testosterone, and dehydroepiandrosterone sulfate (DHEAS)] levels. Secondary outcomes included interstitial glucose concentration measured via continuous glucose monitoring, subjective assessments (i.e. sleepiness, relaxation, and concentration), and golf performance (18-hole score). Between-group comparisons at each time point were conducted using planned Welch's t-tests. RESULTS: No significant between-group differences were observed for 18-hole score (p = 0.38) or mean interstitial glucose concentration (p = 0.20). However, exploratory analyses revealed distinct hormonal variations; salivary DHEAS and testosterone levels were higher in the ISO group during the latter half of the round (p < 0.05), whereas both declined in the CON group. Regarding glycemic variability, the ISO group demonstrated a more stable glucose profile with a medium effect size for lower standard deviation (ISO: 14.7 ± 1.9 vs. CON: 16.7 ± 4.6 mg/dL; d = 0.58), although this difference was not significant. Conversely, subjective outcomes diverged; the CON group reported significantly greater subjective arousal (wakefulness and relaxation) (p < 0.01) relative to the ISO group. CONCLUSIONS: In conclusion, continuous intake of isomaltulose-containing gummies during an 18-hole golf round was associated with differences in selected physiological markers, including DHEAS and testosterone concentrations. However, these findings were not accompanied by improvements in objective golf performance outcomes compared with sucrose-containing gummies. Isomaltulose may influence glycemic dynamics and hormonal responses during prolonged golf play; however, the practical significance of these effects remains exploratory. Further studies with larger sample sizes and appropriate repeated-measures frameworks are needed to determine whether such physiological changes translate into meaningful performance or recovery benefits.

Humans↗

PubMed2026

Molecular mechanisms underlying umami taste perception: A DIA-based proteomic analysis of Agrocybe aegerita peptides.

The mechanisms underlying the modulation of the salivary perception of umami peptides remain poorly understood. Herein, three umami peptides (DDL, DEL, and ENG) obtained from Agrocybe aegerita were used to investigate the regulatory role of saliva in umami taste perception via a combined approach involving sensory evaluation and proteomics analysis based on 4D-DIA technology. The results revealed that umami intensity peaked at 10 s after ingestion and was accompanied by a significant increase in saliva secretion (p < 0.05). Further proteomics analysis revealed that lactotransferrin and proline-rich proteins are closely associated with the sensory perception of umami peptides. Differentially expressed proteins were mainly enriched in pathways related to saliva secretion and proteasome function. This study provides new insights from the perspectives of salivary proteomics and dynamic salivary secretion, contributing to a deeper understanding of the mechanisms by which saliva regulates umami perception.

Humans↗

PubMed2026

The return of measles: a dangerous comeback.

PURPOSE OF REVIEW: Measles has reemerged as a significant global public health threat, with increasing morbidity and mortality associated with declining vaccination rates. This review summarizes current global outbreaks, history of measles, vaccination and elimination status, vaccine hesitancy, and outbreak response and lessons learned highlighting different novel digital epidemiological tools. RECENT FINDINGS: Measles continues to surge worldwide with an estimated 11 million infections in 2024, which is more than prepandemic levels. Developing and developed countries are both facing measles outbreaks, with the United States at risk of losing measles elimination status. Recent studies have showed that worldwide percentages of two-dose measles vaccination were lower than 95% that is required to interrupt measles transmission in all WHO regions. Novel epidemiological tools such as interactive simulators, real-time use of dynamic models, serosurveillance, and others are transforming measles outbreak response and enable earlier outbreak detection, tracking, and targeted public health interventions. SUMMARY: Vaccine hesitancy is one of the top global health threats and developing a tailored evidence-based approach is necessary to establish and maintain measles elimination.

Humans↗

PubMed2026

Control of foreign DNA: emerging roles of xenogeneic silencers.

Bacteria continuously acquire foreign DNA through horizontal gene transfer, yet its successful integration depends on regulatory mechanisms that balance genome protection with evolutionary innovation. Xenogeneic silencers are central to this process: they preferentially bind AT-rich DNA, a common feature of many horizontally acquired genetic elements, and repress its transcription. Recent studies, however, reveal a much broader regulatory repertoire. Beyond transcriptional repression, these proteins contribute to chromosome organization by forming higher-order nucleoprotein complexes and phase-separated condensates that shape bacterial nucleoid architecture. Furthermore, they play roles in regulating bacteriophage infection cycles, including mechanisms by which phages hijack host silencing activities for their own benefit. Their extensive regulatory reach, spanning virulence genes, biofilm formation, specialized metabolite production, and mobile genetic elements (MGEs), underscores their central role in connecting environmental signals, including fluctuations in the second messenger c-di-GMP, with gene expression, and genome organization. The diversification of xenogeneic silencers across bacterial chromosomes, plasmids, phages, and other MGEs highlights their evolutionary significance. Together, these recent findings position xenogeneic silencers as dynamic regulatory modules that shape the fate of foreign DNA across the horizontal gene transfer network.

Gene Transfer, Horizontal↗

PubMed2026

Epigenetic drift and LINE-1 activation in aging brain: Implications for neurodegenerative disease.

Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.

Humans↗

PubMed2026

Self-healing materials for food packaging: Design principles, activation mechanisms and implications for food safety.

Self-healing materials (SHMs), originally developed to restore mechanical integrity, have recently attracted growing interest in food packaging. By autonomously repairing physical damage, SHMs help preserve packaging integrity, barrier performance, food safety, and shelf-life during storage and transportation. This review summarizes recent advances in the design principles, activation mechanisms, material systems and food packaging applications of SHMs. Key healing strategies, including microencapsulation, dynamic covalent bond exchange, reversible non-covalent interactions and responsiveness to external stimuli such as temperature, pH, and humidity, are discussed. Representative material systems, including biopolymer-based films, hydrogels, nanocomposites, and stimuli-responsive polymers are evaluated with respect to their relevance to packaging animal-derived foods, fruits, and vegetables. Performance evaluation methods, sustainability implications, and food-contact safety concerns are addressed. Despite promising healing efficiency and mechanical resilience, challenges remain regarding production cost, food-grade safety, migration risks, trigger compatibility and stability under fluctuating environmental conditions. Future research should focus on scalable manufacturing, standardized evaluation protocols, repeated damage-healing safety assessment, regulatory compliance, and integration with intelligent packaging technologies.

Food Packaging↗

PubMed2026

Oxidative potential of fresh vs. O₃-aged PM2.5 across urban and rural sources in China.

Fine particulate matter (PM2.5) is a major health risk, yet its impacts are still largely assessed using mass concentration, which does not capture toxicity. Recently, oxidative potential (OP) has emerged as a more relevant metric, reflecting the ability of particles to generate reactive oxygen species. A current challenge, especially in China, is understanding how emission sources and ozone (O3) aging affect PM2.5 toxicity, given that O3 is an increasingly important pollutant there. A work by Ma and co-workers published in J. Environ. Sci. (doi.org/10.1016/j.jes.2024.04.023) addressed this by evaluating the OP of fresh and O3-aged PM2.5 from multiple sources in China using the dithiothreitol (DTT) assay. Biomass burning particles exhibited the highest OP, up to 35 times greater than suburban PM2.5, driven by water-soluble organics and transition metals. While O3 aging generally reduced OP, it also induced complex chemical transformations. These findings highlight that PM2.5 toxicity is dynamic and source-dependent, underscoring the need to move beyond mass-based air quality metrics.

Particulate Matter↗

PubMed2026

Predictive evolutionary genomics: principles, validation, and practice.

Climate change and habitat loss are driving rapid evolutionary responses in populations world-wide, which creates an urgent need for evolutionary forecasting in conservation and agriculture. Such forecasting can be categorized into three time scales: trait-based models that use multivariate quantitative genetic equations to project correlated phenotypic responses up to c. 20 generations, allele-based analyses that model allele frequency dynamics up to 100 generations, and composite adaptation scores that aggregate many small effects to yield predictions across longer horizons. However, these approaches have remained largely disconnected. Here, we present a Bayesian framework that integrates these three complementary approaches for evolutionary prediction. Our framework combines genomic, phenotypic, and environmental data to yield probabilistic predictions with explicit uncertainty. We show how predictive evolutionary forecasts can be validated with experimental evolution, field experimentation, historical specimens, and reciprocal transplants. These validated forecasts can help advance conservation and agricultural programmes by helping predict which populations are at risk of future extinction, optimizing breeding programmes for future climates, and planning ecosystem management under environmental change. By supporting a shift towards more predictive approaches in evolutionary biology, this framework may help improve our ability to manage biodiversity and food security in a changing world.

Genomics↗

PubMed2026

Deciphering CD8+ T cell exhaustion in human cancers through single-cell and spatial transcriptomics.

Exhausted CD8+ T cells (Tex) within the tumor microenvironment (TME) represents a critical barrier limiting anti-tumor immune responses. Tex cells are characterized by upregulated inhibitory immune checkpoint receptors, reduced cytotoxicity, and functional heterogeneity. Their genomic features and regulatory networks remain poorly defined, and only a minority of patients respond to immune checkpoint blockade (ICB) therapy. Single-cell RNA sequencing (scRNA-seq), through high-resolution transcriptomic profiling, has revealed diverse Tex subpopulations, identified subpopulation-specific marker genes and regulatory pathways. Spatial transcriptomics has further mapped the spatial distribution of Tex and their interaction networks with immune cells, tumor cells, and stromal cells, elucidating the impact of spatial heterogeneity on Tex functionality. Current studies indicate that the exhausted state of Tex is dynamic and modifiable, with functional differences among subpopulations closely associated with tumor progression and therapeutic response. However, the genomic characteristics, epigenetic regulation, and spatial interaction mechanisms of Tex require further exploration. This review summarizes recent advances in high-resolution omics technologies for precisely dissecting Tex heterogeneity, functional features, and interactions with other cells. It emphasizes the central value of optimizing Tex-targeted tumor immunotherapy strategies, providing theoretical foundations and directional guidance for developing more effective anti-tumor immunotherapies.

Humans↗

PubMed2025

Depth-dependent multi-kingdom microbial interactions and biogeochemical cycling genes in eutrophic shallow lake sediments.

Microorganisms are pivotal to lake ecosystem biogeochemical cycles, yet existing research often focuses on single microbial kingdoms or surface sediments, neglecting multi-kingdom interactions and depth-resolved dynamics. To address these gaps, we used metagenomic sequencing to characterize microbial communities and their functional associations across overlying water and 0-45 cm sediments in four shallow lakes of the middle Yangtze River basin, China. Despite increasing bacterial and fungal diversity with depth, the 0-9 cm surface sediments exhibited the strongest multi-kingdom network connectivity and the greatest microbial stability. Functional genes exhibited clear depth-dependent patterns: nitrogen cycling genes, including those involved in dissimilatory nitrate reduction to ammonium, were most enriched in the upper 0-9 cm of sediment; methane cycling genes were positively correlated with depth; phosphorus cycling genes and some sulfur cycling genes, such as assimilatory sulphate reduction, declined with depth. Sediment microbial assembly was dominated by deterministic processes, in which the vertical distribution of functional genes was primarily dictated by heavy metals and conventional environmental indicators. These findings highlight depth-specific multi-kingdom microbial interactions and their associations with biogeochemical cycling, advancing lacustrine microbial ecology understanding and providing references for lake conservation under environmental change.

Lakes↗

PubMed2026

Genomic history of the Caucasus: A systematic review and meta-analysis of ancient DNA studies.

The Caucasus region represents a unique natural laboratory for paleogenetic research due to its complex topography, long-standing role as a migratory corridor and glacial refugium, and exceptional preservation conditions for ancient DNA. This review synthesizes recent genome-wide studies to reconstruct the demographic history shaping the distinctive genetic landscape of modern Caucasus populations. The analysis reveals a deep pattern of continuity, isolation, and periodic admixture. Early genetic differentiation emerged in the Neolithic and Chalcolithic, forming distinct steppe and mountain population clusters. The Bronze Age was a pivotal period marked by large-scale gene flow from the Eurasian Steppe, particularly linked to the Yamnaya expansion, and interactions with Iranian and Anatolian-related groups. Despite these influences, many populations demonstrate remarkable genetic continuity from the Bronze Age to the present day. Significant knowledge gaps persist, particularly for the Paleolithic, Mesolithic, and Neolithic of the North Caucasus, as well as for the Late Medieval and Early Modern periods across the entire region. Addressing these gaps through targeted archaeogenomic studies is crucial for understanding the fine-scale processes that formed the hierarchical structure and high linguistic diversity of Caucasus populations, offering a powerful model for studying human adaptation, interaction, and language-genetics dynamics in a mountainous environment.

Humans↗

PubMed2026

Longitudinal associations between family factors and the neurodevelopmental and psychosocial outcomes of children with congenital heart disease: A systematic review.

Family factors have been gaining increased attention in understanding adverse neurodevelopmental and psychosocial outcomes for children with congenital heart disease (CHD). To clarify relevance, we undertook a systematic review of only longitudinal studies which assessed such associations. Comparisons with the contribution of disease/surgical factors were also made where included studies considered such. We included longitudinal studies which assessed dynamic family factors (e.g. parent mental health, attachment, family functioning) and later child outcomes. Searches were conducted across CINAHL, Medline-Pubmed, PsychInfo and SCOPUS Web of Science. The NIH Quality Assessment Tool was used to evaluate study quality and risk of bias. Eighteen studies, utilizing data from 11 study samples and 2109 participants, met inclusion criteria. These studies included samples from infancy, with follow-up periods stretching into young adulthood, and with various degrees of CHD severity. The quality of studies was "good" to "fair", with key limitations of attrition and limited sociocultural diversity in samples. Findings suggested that family factors predicted later child psychosocial outcomes and more consistently than severity of disease indicators. This contrasted with a much smaller number of studies examining family factors and child neurodevelopmental outcomes, where no reliable conclusions could be reached. Findings highlight the importance of screening and family focused interventions for this population.

Child↗

PubMed2026

Engineering bubble structures as Cas12a activators for highly sensitive monitoring of WRN helicase function.

The Werner syndrome helicase (WRN) is a critical synthetic lethal target in microsatellite instability cancers, essential for resolving complex genomic structures like replication bubbles and R-loops. However, strategies to simultaneously discriminate WRN activity on DNA versus DNA-RNA substrates in living cells are lacking. Here, we developed a structure-specific CRISPR/Cas12a biosensing strategy to visualize WRN functional activity by engineering bubble-structure probes. These probes were rationally designed to structurally mimic DNA replication bubbles and R-loop associated DNA-RNA hybrids. Upon specific unwinding by WRN, the probes release a sequestered activator strand that triggers Cas12a trans-cleavage, effectively converting the unwinding event into an amplified fluorescent signal. This assay achieves low picomolar sensitivity (LODs: 5.6-6.0 pM) and exceptional selectivity against homologous RecQ helicases. Uniquely, this strategy enables the parallel quantification of WRN activity on both substrate types, providing insights into distinct WRN-mediated pathways for resolving genomic stress. We further demonstrated the strategy's utility by visualizing endogenous WRN dynamics in living cells and profiling the efficacy of small-molecule inhibitors. This work offers a powerful molecular toolkit for dissecting WRN biology and facilitating high-throughput drug screening in targeted cancer therapy.

Werner Syndrome Helicase↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

A systematic review of human avoidance learning: Cognition, computation, and methods.

Avoidance behaviour is fundamental for survival but can become maladaptive in clinical conditions. A large body of literature has accumulated on the dynamics of human avoidance learning. However, current theories and overviews do not provide an exhaustive account of this evidence. In this systematic review, we identify N = 116 studies on human avoidance learning. We analyse these studies with the goal of distilling robust empirical phenomena as a basis for theory-building, and examine their diagnostic value in differentiating between competing theories. We find that the evidence is difficult to reconcile with foundational two-factor and classical safety-signal accounts, and most strongly supports expectancy- and inference-based views, in which avoidance responses are selected with respect to represented consequences. At the same time, no current framework provides a complete account of the evidence: several findings point to an additional role for operant valuation, Pavlovian influences, and contextual or latent-state control over the expression of avoidance. Methodologically, we observe that the problem setting in the most common experimental paradigms is radically simpler than real-world avoidance and therefore unlikely to expose the limits of inferential or reflective mechanisms. Consequently, we argue that paradigms with greater computational demands and more realistic action affordances are required to identify the mechanisms underlying avoidance learning. Collectively, these insights provide a foundation for theoretical refinement, computational modelling, and methodological innovation, with implications for advancing interventions targeting maladaptive avoidance.

Humans↗

PubMed2026

Uncovering hidden complexity in the Apis mellifera mitotranscriptome: a polyadenylation-centered perspective.

Mitochondrial transcription is gaining increasing attention as researchers seek to better understand the full coding potential of mitochondrial DNA (mtDNA). Emerging evidence suggests that mtDNA may encode additional elements beyond classical oxidative phosphorylation genes, pointing to a more complex transcriptional architecture than previously recognized. In this study, we explored the mitochondrial transcriptome of Apis mellifera (Insecta: Hymenoptera), with a particular focus on polyadenylation-associated features. Our analysis revealed that both sense and antisense transcripts undergo polyadenylation, although transcript abundance and poly(A) tail lengths varied markedly across mitochondrial genes. Several transcripts exhibited alternative isoforms, either extended or truncated, frequently including intergenic regions. These regions may represent functional non-coding elements or structural variants rather than conventional untranslated regions (UTRs). Interestingly, some transcripts also contained non-templated nucleotide additions particularly cytosine residues immediately upstream of the poly(A) tails. Monocistronic units that included portions of downstream intergenic regions were among the most abundantly represented, suggesting a possible regulatory role for these sequences. To experimentally validate our in silico findings, we performed RT-qPCR to assess relative gene expression and applied 3' RACE-PCR to define transcript boundaries. These approaches confirmed the presence of multiple transcript isoforms and supported the involvement of polyadenylation in shaping mitochondrial RNA diversity. Together, our findings reveal a previously underappreciated level of complexity in the A. mellifera mitochondrial transcriptome and highlight the potential regulatory significance of polyadenylation dynamics and intergenic region transcription.

Animals↗

PubMed2026

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals↗