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Advanced mitigation strategies for acrylamide formation in foods: Mechanistic insights, emerging innovations, and future perspectives.

Acrylamide is a heat-induced contaminant formed predominantly in carbohydrate-rich foods during high-temperature processing, posing significant concerns due to its potential carcinogenic, neurotoxic, and genotoxic effects. This review critically examines the mechanisms of acrylamide formation, emphasizing the role of the Maillard reaction and key precursors such as asparagine and reducing sugars, along with the influence of processing conditions including temperature, time, pH, and moisture. Various mitigation strategies are comprehensively discussed, ranging from raw material selection and genetic approaches to enzymatic treatments such as asparaginase and the application of natural and chemical inhibitors. Advances in processing technologies, including optimization of conventional thermal methods and emerging non-thermal techniques such as cold plasma and ultrasound, are evaluated for their effectiveness. The review also highlights the role of food additives, functional ingredients, and fermentation in reducing acrylamide formation. Furthermore, recent developments in analytical techniques, including chromatographic methods, biosensors, and artificial intelligence-based predictive models, are explored for improved detection and control. Risk assessment, toxicological implications, and global regulatory frameworks are also examined. Finally, future perspectives focusing on genetic engineering, personalized nutrition, and digital technologies such as AI and blockchain are discussed to support sustainable and industry-applicable mitigation strategies.

Acrylamide

Mitochondrial dysfunction in muscle cells induced by snoring vibrations.

Snoring-related vibrations have been proposed as a pathogenic factor contributing to upper airway muscle dysfunction in patients with obstructive sleep apnea (OSA). To investigate whether exposure to snoring vibration is linked to muscle weakness, we used an in vitro vibration model to examine its effects on mitochondrial homeostasis in L6 muscle cells at 8, 12, 24, and 48 h. The findings were then compared with mitochondrial alterations in the upper airway muscles from snorers and patients with OSA. Proteomic analysis of L6 myoblasts revealed extensive remodeling of the mitochondrial proteome at 8 h, affecting pathways involved in oxidative phosphorylation, protein import, ribosome biogenesis, and RNA processing. Respiratory chain remodeling was subunit-specific, with increased abundance of selected components of Complexes I, IV, and V, including NDUFS4, COX5A, and ATP5PD. However, reductions in spliceosome-associated factors, such as SRSF2 and DDX46, along with alterations in mitochondrial ribosomal proteins, indicated impaired RNA processing and protein synthesis. Furthermore, both proteomic and transcriptomic analyses revealed activation of a mechanosensing-mechanotransduction axis, with early upregulation of integrin subunits and mechanosensitive ion channels, followed by transient activation of focal adhesion signaling. Despite transcriptional upregulation of selected Complex IV subunits Cox5a and Cox6a2, this response was accompanied by accumulation of unspliced pre-mRNA, indicating impaired RNA processing efficiency and a decoupling between transcript and protein levels. Real-time Seahorse assay revealed a collapse of mitochondrial respiration and glycolytic reserve at 8 h. Although mitochondrial oxygen consumption recovered after 48 h, the ability to dynamically upregulate glycolysis remained impaired. In patients, muscle capillarization was impaired, COX activity was reduced, and mitochondrial organization was disrupted. Moreover, transcription of Complex IV subunits COX5A and COX6A2 was, as in vibrated L6 cells, upregulated, suggesting a mismatch between transcript levels and protein expression. We conclude that snoring-induced vibrations are an unrecognized stressor that disrupts mitochondrial homeostasis in muscle by impairing RNA processing, protein synthesis, and mechanotransduction-driven mitochondrial remodeling, leading to transcript-protein uncoupling and likely muscle dysfunction.

Humans

Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.

BACKGROUND: Guanidinoacetic acid (GAA) supplementation has been reported to increase brain creatine content more effectively than creatine monohydrate (CrM). However, the effects on cognitive function are unclear. PURPOSE: The purpose of this proof-of-concept exploratory clinical trial was to determine whether GAA supplementation with and without CrM affects cognitive function and/or markers of health. METHODS: In a double-blind, randomized, and counterbalanced manner, 58 healthy and active adults (33 females, 35.5&#x2009;&#xb1;&#x2009;14 years, 76.2&#x2009;&#xb1;&#x2009;14 kg) ingested a PLA (PLA, 2 &#xd7; 6 g/d maltodextrin), GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;PLA (2 &#xd7; 5 g/d), or GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;CrM (2 &#xd7; 5 g/d) for six weeks. The participants donated fasting blood samples and completed a battery of tests and questionnaires assessing various aspects of function, mood, stress, sleep quality, and markers of health at baseline and after six weeks of supplementation. Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, and mean changes from baseline with 95% confidence intervals, and Chi-squared analysis, and considered significant when the probability of error was 0.05 or less, and approaching significance (p&#x2009;>&#x2009;0.05-p&#x2009;<&#x2009;0.10). RESULTS: GAA supplementation tended to improve overall reaction time (-241.8&#x2009;ms [-533, 50], p&#x2009;=&#x2009;0.10) while significant interaction effects were observed in overall reaction time (p&#x2009;=&#x2009;0.031-330 ms [-629, -31]) and YES reaction time (-290&#x2009;ms [-484, -96], p&#x2009;=&#x2009;0.004) while recalled correct reaction time (-178&#x2009;ms [-374, 21], p&#x2009;=&#x2009;0.078) and recalled correct YES (7.4 % [-1, 15.8], p&#x2009;=&#x2009;0.084) approached significance compared to PLA. Limited to no effects were observed on the Delayed Picture Recognition Task Test, Digit Vigilance Task Test, Corsi Block Task Test, or Stroop Color-Word Task Test. The amount of time engaged in moderate physical activity was significantly greater (p&#x2009;<&#x2009;0.05) in the GAA group compared to PLA. Participants in the GAA group reported a lower frequency of controlling irritations (p&#x2009;=&#x2009;0.036), and feeling like difficulties are mounting (p&#x2009;=&#x2009;0.053) on the Perceived Stress Scale. Some positive and potentially undesirable effects were observed in sleep quality assessments. The quality of life assessment revealed that participants in the GAA group reported less frequent feelings of being worn out (p&#x2009;=&#x2009;0.068) and that their health was excellent (p&#x2009;=&#x2009;0.092) while those in the GAA&#x2009;+&#x2009;CrM group reported more frequent limitations when bending, kneeling, or stooping (p&#x2009;=&#x2009;0.053), more often feeling full of life (p&#x2009;=&#x2009;0.081), and less frequency in feeling downhearted and depressed (p&#x2009;=&#x2009;0.066). No clinically meaningful changes were observed in blood markers or self-reported side effects among the groups. CONCLUSION: Dietary supplementation with GAA (2 g/d) and the combination of CrM (10 g/d&#x2009;+&#x2009;GAA 2 g/d) for six weeks improved delayed verbal episodic recognition memory and retrieval speed and some measures of perceived stress, sleep quality, and quality of life. However, most cognitive tests were not affected, particularly when comparing the GAA to the PLA group; there were some inconsistencies in the findings, and several differences only approached significance. Additional research is needed before conclusions can be drawn. Clinical trial registration: ISRCTN68542582.

Humans

Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cognitive-behavioral interventions (CBIs) delivered by nonspecialist providers (NSPs) on perinatal depressive (PND) and anxiety symptoms, and to narratively synthesize their implementation processes and reported implementation outcomes, including acceptability, feasibility, fidelity, cost, and sustainability. METHODS: We systematically searched eight databases from inception to April 8, 2025. Eligible studies were randomised controlled trials (RCTs) assessing CBIs delivered by NSPs for PND and/or anxiety. Two reviewers independently screened, extracted, and assessed trials. Meta-analyses employed random-effects models, with subgroup, sensitivity, meta-regression, and publication bias analyses conducted in Stata 18.0. Implementation processes and outcomes were reported as frequencies or percentages across trials. RESULTS: A total of 47 trials (11, 357 participants) were included in the systematic review, of which 37 trials (8,709 participants) were included for meta-analyses. CBIs were conducted in 12 countries. Nurses and midwives delivered 45% of CBIs. CBIs were associated with reduced PND post-intervention compared with control conditions (standardized mean difference [SMD] -0.49, 95% CI -0.63 to -0.35; I&#xb2; = 86.8%). Limited evidence from four trials suggested a small sustained effect at 12 months (SMD -0.14, 95% CI -0.27 to -0.02; I&#xb2; = 26.4%). Reductions in anxiety symptoms were observed immediately post-intervention (SMD, -0.45, 95% CI -0.65 to -0.25; I&#xb2;=81%), but evidence for longer-term effects was limited. Subgroup analyses confirmed consistent effects across diverse settings, populations, and intervention characteristics. Reporting of implementation processes (e.g., training, supervision, fidelity) was limited, with only 23.4% of trials assessing fidelity and 10.6% evaluating costs. CONCLUSIONS: NSP-delivered CBIs showed beneficial effects on PND and anxiety, with generally encouraging evidence for acceptability and feasibility. However, evidence for sustained effects beyond the immediate post-intervention period remains limited. Future studies should strengthen long-term follow-up and improve reporting of implementation processes and outcomes, particularly in rural and adolescent perinatal populations, to inform scalable and equitable task-sharing models.

Humans

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

A chromosomal gtrB homolog and dam differentially contribute to dry-heat and high hydrostatic pressure resistance in Salmonella enterica.

Salmonella enterica can persist in low-moisture foods and shows enhanced dry-heat resistance under low water activity, posing significant food safety challenges. However, the genetic basis of extreme dry-heat resistance and its relationship with other processing stresses remain unclear. In this study, twelve S. enterica strains were screened for dry-heat treatment at 60&#xa0;&#xb0;C and 80&#xa0;&#xb0;C, with S. Infantis CICC21649 identified as the most resistant strain. Comparative genomics and transcriptional analysis identified candidate genes related to envelope integrity and regulation, including gtrB and dam. Deletion of the chromosomal gtrB homolog reduced dry-heat resistance, producing an additional 0.91-log10 reduction relative to the parent strain at 80&#xa0;&#xb0;C. Deletion of dam caused broader stress sensitivity, reducing resistance to both dry heat and high hydrostatic pressure, with the stronger phenotype observed under high hydrostatic pressure. Proteomic analysis of the chromosomal gtrB homolog mutant revealed broad alterations in envelope-associated proteins, transport functions, oxidative stress pathways, and central metabolism under dry-heat stress. These findings indicate that the chromosomal gtrB homolog is an important contributor to extreme dry-heat resistance, whereas dam contributes to resistance against both dry-heat and high hydrostatic pressure, likely through a broader regulatory role in stress adaptation. These results reveal distinct structural and regulatory layers underlying stress adaptation in S. enterica and provide practical guidance for low-moisture food processing by highlighting the need to account for strain-dependent and stress-specific resistance during process validation.

Hydrostatic Pressure

Depth-dependent microbial succession and interspecies hydrogen transfer drive pit mud maturation in Chinese strong-flavor baijiu fermentation.

Microbial communities in fermentation pit mud play a key role in determining the quality of Chinese strong-flavor baijiu (CSFB). However, the ecological processes underlying pit mud maturation across spatial and temporal scales remain unclear. In this study, amplicon sequencing and metagenomic analyses were employed to investigate the taxonomic succession, community assembly, and metabolic functions of bacterial and archaeal communities during the transition from fresh pit mud (FPM) to new pit mud (NPM) and old pit mud (OPM). A pronounced depth-dependent succession pattern was observed, with 4&#xa0;cm representing a critical ecological boundary separating distinct community structures and maturation trajectories. During surface-layer maturation, community assembly shifted from stochastic to deterministic processes, accompanied by homogeneous selection and increasing network complexity. In contrast, stochastic processes remained dominant throughout deep-layer maturation. Metagenomic analyses revealed a functional transition from lactate and acetate production, primarily associated with Lactobacillus in FPM and NPM, to butyrate and caproate production associated with Clostridium and Caproiciproducens in OPM. This functional transition was accompanied by enhanced amino acid metabolism, which was associated with the enrichment of Proteiniphilum and Aminobacterium. Notably, methanogen-mediated interspecies hydrogen transfer (IHT) emerged as a key ecological feature during pit mud maturation. In OPM, IHT networks primarily involving Methanobacterium and Methanosarcina linked methanogenesis with reverse &#x3b2;-oxidation through diverse hydrogen-transfer pathways, reinforcing metabolic interactions underlying caproate production. These findings provide new insights into the ecological mechanisms underlying pit mud maturation and offer a theoretical basis for the directed cultivation of high-quality pit mud in CSFB production.

Hydrogen

Single-cell transcriptome revealed the aberrant keratinocytes activation in antigen presentation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD), a common chronic inflammatory skin disease, has been extensively studied using single-cell genomics. However, keratinocytes, as key effector cells in AD, have underlying mechanisms remain incompletely understood and require further investigation. METHODS: We integrated single-cell transcriptomic data from skin tissues of healthy controls, chronic active AD patients, spontaneously healed AD (SHAD) patients, and an ovalbumin-induced AD mouse model. The study particularly emphasized the gene expression and cellular dynamics of keratinocytes across the different groups, as well as their interactions with immune cells. RESULTS: Compared to healthy controls, we observed significant changes in the keratinocyte transcriptome, cellular state, and keratinocyte-immune cell ligand-receptor interactions in AD skin, particularly the marked activation of genes involved in antigen processing and presentation. Interestingly, such gene activation was not observed in keratinocytes from the ovalbumin-induced AD mouse model, despite its phenotype closely resembling human AD. Furthermore, in SHAD, we identified a recovery of both the ligand-receptor interaction patterns and antigen processing and presentation genes, accompanied by a notable shift in the transcriptome. This involved a significant downregulation of genes related to cytoplasmic transcription and oxidative phosphorylation. Notably, this pattern was not observed in the self-healing mouse model following the removal of ovalbumin stimulation. CONCLUSION: Our results suggest that the persistent activation of antigen processing and presentation pathways in keratinocytes may be a key driver of chronic inflammation in AD. Therefore, redirecting anti-allergic therapeutic strategies from solely targeting immune cells to targeting of keratinocyte-mediated antigen presentation may offer a more effective approach. Furthermore, we raise concerns about the use of ovalbumin-induced mouse models to recapitulate human chronic AD, as the underlying mechanisms may differ significantly.

Dermatitis, Atopic

Detoxifying biotransformation of chloramphenicol by Exiguobacterium sp. CAP4 and its bioaugmentation of chloramphenicol biodegradation in simulated wastewater.

The extensive use of chloramphenicol (CAP) in livestock leads the accumulation of CAP in livestock manures, threatening environmental and human health. Therefore, eliminating or reducing CAP concentration in manures before its re-utilization and application through microbial remediation is necessary. Exiguobacterium sp. CAP4, isolated from the plastisphere in duck manures, was capable of degrading CAP with the biodegradation efficiency of 97.8 % at initial CAP concentration of 5 mg/L within 4 days. A total of twenty-four biotransformation products were determined, including two novel transformation products, TP166 and TP203, enriched the integrity of CAP biodegradation pathways. Furthermore, the biotransformation process was proposed as a detoxifying process through biotransformation products toxicity evaluation. Notably, Exiguobacterium sp. CAP4 successfully colonized in the cow manures after inoculation, and bioaugmented the biodegradation of CAP in virgin cow manures. This study significantly extended our understanding of the CAP biotransformation fate, and provided a promising bacterial strain for bioremediation of CAP containing wastewater in situ.

Chloramphenicol

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (&#x394;CAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

A Critical Assessment of Evidence-Based Design's Knowledge Base and Inspiration: A Systematic Review.

PurposeThis study examines Evidence-Based Design (EBD) as an epistemological framework for guiding design research and practice, with a particular focus on its reliance on Evidence-Based Medicine (EBM) as a source of methodological inspiration.BackgroundOver the past two decades, EBD has been promoted as a way to strengthen design processes through the systematic use of scientific evidence. Its relationship to EBM, however, remains conceptually ambiguous: EBD draws legitimacy from EBM's hierarchical conception of "best evidence" while at the same time acknowledging the specificities of design practice, which do not easily fit such a model.MethodologyA systematic review was conducted on 31 publications in the design research literature that explicitly address the tension surrounding EBD's conception of "best evidence." The criticisms raised were coded and analyzed by main topics and subtopics.ResultsThe review highlights several reasons why EBM's hierarchical view of "best evidence" is an unsuitable epistemological foundation for EBD. It imposes scientifically inappropriate and practically ineffective methodological standards, devalues important sources of design knowledge, and fails to address central epistemic challenges intrinsic to design processes.ConclusionsBy bringing together critical yet fragmented insights from the literature, this study argues for the development of an updated epistemological framework for EBD. Constructing this framework will require sustained interdisciplinary dialogue between design research and philosophy of science.

Humans

Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene

Application of causal discovery of factors driving dissolved oxygen in estuarine environments.

Dissolved oxygen (DO) concentrations in estuarine bottom waters are a manifestation of multiple, interacting physical and biogeochemical processes, yet identifying their independent contributions remains challenging. Here, we analyze monthly water quality monitoring data from eight stations across Long Island Sound from 1994 to 2022 using a causal discovery framework (PCMCI+) and transformation of forcing variables. Our goal is to identify and isolate variables that causally influence bottom DO and improve predictive models by minimizing overfitting and multicollinearity. PCMCI+ reveals surface-layer temperature as the most important and consistent negative driver of bottom DO, followed by stratification. Wind events exhibit only brief relief by advection and mixing, while river discharge shows no direct causal link to DO, making it less influential than previously thought. Biogeochemical variables, including chlorophyll-a (Chl-a), nitrate and nitrite, and particulate carbon, influence DO through both contemporaneous and time-lagged pathways, often with signs that shift depending on the process. The derived models were evaluated by comparing skill scores, mean squared error, and Akaike Information Criterion. Both model types perform well, with coefficient of determination values exceeding 0.90 at multiple stations using only 3-5 predictors. Our analysis reveals that the best causal predictors are surface-layer temperature, stratification, Chl-a, and particle carbon. This approach provides a scalable framework for improving prediction models and understanding the mechanistic links that control the seasonal variability of DO in estuarine systems.

Estuaries

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7&#xa0;days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals

Microbial diversity, functional activities, and safety risks in fermented tea: a comprehensive review.

Microbial fermented teas are gaining global popularity due to their unique sensory profiles and health benefits. The quality and safety of these products are governed by complex microbial ecosystems that orchestrate the biotransformation of tea leaf components. This review addresses a critical paradox in the field: the same microbial activities that generate desirable bioactive metabolites, such as theabrownins and organic acids, also create ecological niches for mycotoxigenic fungi, posing significant health risks from contaminants like ochratoxin A, citrinin, and aflatoxins. While extensive research has cataloged the microbial diversity in these systems, a comprehensive framework linking processing environments to microbial community assembly, functional outcomes, and quantifiable safety risks remains elusive. This review systematically bridges this gap by synthesizing current knowledge on the microbial consortia-dominated by Aspergillus, Penicillium, Bacillus, and Lactiplantibacillus species-that drive tea fermentation. We critically analyze their functional roles in enhancing flavor, bioactivity, and potential probiotic activity while simultaneously evaluating the mechanisms of mycotoxin production and accumulation. By integrating microbial ecology, biochemistry, and food safety, we propose a forward-looking perspective focused on transitioning the industry from traditional, spontaneous fermentation to modern, controlled biotechnological processes. This approach, centered on the use of defined starter cultures, predictive modeling, and active biocontrol strategies, provides a roadmap for ensuring the consistent quality and safety of fermented tea products, ultimately unlocking their full potential as high-quality functional foods.

Tea

An Update on Inborn Errors of V(D)J Recombination.

V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte-specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical nonhomologous end joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEIs), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase [RAG1, RAG2, and the recently identified RAG cochaperone NudC domain-containing 3 (NUDCD3)], end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development.

Humans

Plasticity of hepatic metabolism in Arctic char (Salvelinus alpinus) in response to cyclic hypoxia.

The emergence of cyclic hypoxia puts aquatic organisms' homeostasis under significant strain. Energetic metabolism as well as protein synthesis and folding are particularly altered during hypoxia, while reoxygenation imposes an oxidative challenge. Currently, little is known about how hypoxia-sensitive organisms respond to large oxygen fluctuations. Our previous work on Arctic char revealed that this salmonid, despite being strongly affected by acute hypoxia and reoxygenation (H/R), can successfully reestablish homeostasis, notably through adjustments to hepatic mitochondrial metabolism. However, the mechanisms underlying this acclimation remain poorly understood. We hypothesized that Arctic char remodel their hepatic proteome to optimize energy metabolism, reorganize oxygen-demanding pathways, and maintain cellular homeostasis during repeated H/R cycles. By exposing Arctic char to two or fifteen days of diel cyclic hypoxia, we confirmed this species' limited capacity to respond to acute H/R. Nevertheless, after fifteen cycles, fish adjusted their energetic metabolism through coordinated regulation of carbohydrate and lipid pathways and upregulation of amino acid metabolism. Mitochondrial metabolism was strongly reorganized, particularly at the ubiquinone-Complex III interaction level, alongside adjustments in proline utilization and protein processing. Moreover, protein processing and folding pathways were stimulated in both mitochondria and the endoplasmic reticulum. However, chronic cyclic hypoxia may still promote non-mitochondrial ROS production, DNA replication stress, and impaired immune function. This study highlights how a hypoxia-sensitive fish progressively reorganizes its metabolism and oxygen-demanding pathways to establish a phenotype adapted to chronic cyclic hypoxia, while also revealing the physiological costs associated with this acclimation.

Animals

Bioactive peptides for meat quality and preservation: Integrating peptidomics and computational screening.

Bioactive peptides generated from meat proteins, fermented meat products, and slaughter by-products have attracted increasing attention as functional molecules for improving meat quality and preservation. In meat systems, peptides can be produced through endogenous postmortem proteolysis, microbial fermentation, gastrointestinal digestion, or controlled enzymatic hydrolysis of underutilized animal by-products. These peptides are closely associated with key meat science endpoints, including postmortem tenderization, oxidative stability, color retention, flavor development, microbial inhibition, and the valorization of processing by-products. However, although high-resolution peptidomics has greatly expanded the identification of meat-derived peptide sequences, their translation into practical meat applications remains limited by matrix interactions, processing stability, sensory constraints, safety concerns, and insufficient validation in real meat systems. This review synthesizes recent advances in meat-related peptidomics and computational screening, including sequence-based prediction, machine learning, molecular docking, molecular dynamics, stability assessment, and safety-oriented filtering. Particular attention is given to how these approaches can prioritize peptides with antioxidant, antimicrobial, flavor-modulating, and preservation-related functions under meat-specific technological constraints. By integrating peptide generation pathways, mass spectrometry-based identification, in silico prioritization, and meat quality endpoints, this review proposes a stage-gated framework for translating meat-derived bioactive peptides from discovery to application. Future research should strengthen matrix-specific validation, standardized peptidomic reporting, and safety assessment to support the use of bioactive peptides in meat quality improvement, clean-label preservation, and circular utilization of meat industry by-products.

Animals