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Mechanistic insights into flavor deterioration in bitter sturgeon caviar: Evidence from lipidomics and metagenomics.

This study systematically compared the flavor and multi-omics differences between normal caviar and bitter caviar based on quantitative descriptive analysis (QDA), volatile compounds (VOCs) analysis, untargeted lipidomics, and metagenomics. The results showed that bitter caviar was characterized not only by increased bitterness, but also by decreased positive sensory attributes, including buttery, nutty, and marine fresh. VOCs analysis indicated that the volatile profile of bitter caviar was reorganized. Compounds such as 3-hydroxy-2-butanone, 1-octen-3-ol, and (E, Z)-2,6-nonadienal showed higher relative odor activity values (rOAVs); however, these changes did not improve its overall sensory experience. Untargeted lipidomics identified 492 differential lipids. These changes were mainly characterized by decreased PC and increased DG and LPC in bitter caviar. KEGG pathways analysis showed that these differential lipids were mainly associated with glycerophospholipid metabolism, choline metabolism in cancer, and retrograde endocannabinoid signaling. Metagenomic analysis showed that bacteria dominated the microbial community of caviar. Among them, Bacillus and Micromonospora showed relatively high abundance in the caviar microbiota. They were also closely associated with lipid metabolic changes involving PC, DG, and LPC, suggesting their potential as candidate targets for future microbiota-directed regulation of caviar quality. These findings provide new insights into the mechanisms underlying sensory deterioration and flavor formation in bitter caviar, and offer a theoretical basis for improving caviar quality in industrial production.

Animals

Sexual selection purges mutation load, but not overall genetic diversity, decreasing vulnerability to extinction.

Theory suggests sexual selection will enhance population viability by purging deleterious alleles. However, direct genomic evidence for this fundamental idea is scarce and contradictory. We combined long-term experimental evolution with whole-genome resequencing to directly test how sexual selection affects mutation load, genomic divergence, and extinction risk in small populations (maximum Ne = 40) of Tribolium castaneum. After 156 generations, populations evolving under strong sexual selection carried substantially fewer deleterious alleles than populations under weak sexual selection, based on both individual-level estimates of missense and nonsense variants and population-level Rxy analyses, indicating more efficient purging of deleterious alleles. In contrast, nucleotide diversity and runs of homozygosity were similar across treatments, indicating that purging acted most strongly on deleterious variation, and that reduced mutation load in these small populations under strong sexual selection was not explained by demographic effects. Importantly, population-level mutation load estimates best explained extinction risk under inbreeding, directly linking sexual selection to purging and population viability. Genome scans of high and low sexual selection populations revealed peaks of divergence, which included genes involved in courtship, sex discrimination, and seminal fluid proteins. Our results provide direct genomic evidence that sexual selection can reduce mutation load without eroding standing genetic diversity and thus adaptive potential, while driving adaptive divergence in reproductive traits. This beneficial purging may help explain the widespread prevalence of sexual reproduction in nature despite inherent costs and have important ramifications as to how we manage populations of conservation concern.

Animals

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 °C and 80 °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 °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

Genome-wide identification of the HSP70 superfamily in tropical sea cucumber Stichopus monotuberculatus and their expression analysis under low-salinity stress.

Heat shock proteins (HSPs) are a group of evolutionarily conserved molecular chaperones that serve as indispensable core regulators in preserving cellular homeostasis and orchestrating organismal stress responses. The tropical sea cucumber Stichopus monotuberculatus, a high-value aquaculture species, is sensitive to fluctuations in environmental salinity-a challenge that has emerged as a critical bottleneck limiting its large-scale commercial cultivation. However, no systematic investigation has been conducted to characterize the HSP70 superfamily in S. monotuberculatus and elucidate its functional roles in salinity adaptation. In the present study, we performed a comprehensive genome-wide scan and identified 19 HSP70 superfamily genes in the S. monotuberculatus genome, with the HSP70IV subfamily showing remarkable gene expansion, containing 8 distinct copies. Phylogenetic analysis, conserved motif identification, and gene structure characterization demonstrated high evolutionary conservation within each HSP subfamily. These genes were unevenly distributed across the chromosomes of S. monotuberculatus, and prediction of cis-acting elements revealed that their upstream regulatory regions were enriched with numerous functional elements associated with stress response and immune regulation. Salinity stress experiments revealed that under severe low-salinity conditions (18‰), the expression levels of SmHSPA14L and multiple HSP70IV subfamily members were significantly elevated, while SmHYOU1D was significantly downregulated; in contrast, only subtle changes were detected in the expression of most HSP70 genes under moderate low-salinity stress (24‰). These findings strongly suggest that HSP70 genes, particularly the expanded HSP70IV subfamily, may act as key modulators in the low-salinity stress response. This work provides valuable insight into the molecular mechanisms underlying salinity adaptation in tropical sea cucumbers.

Animals

How the microbiome shapes epigenetic trained memory in neuroinflammation: Implications for neurodegenerative diseases.

Neurodegenerative diseases are increasingly recognized as disorders involving immune dysregulation. However, the mechanisms underlying this dysfunction remain poorly characterized. Trained immunity has recently emerged as a potential contributor to immune dysregulation, particularly in neuroinflammation and neurodegenerative diseases, where trained immunity is the epigenetic reprogramming of innate immune responses following an initial inflammatory stimulus, which increases responses to subsequent exposures. In parallel, although the brain has traditionally been viewed as an immune-privileged organ, growing evidence indicates that peripheral immune activity exerts significant influence on neuroinflammation in the brain. A major driver of peripheral immunity is the microbiome. Therefore, this perspective aims to present a conceptual framework for a relationship between the microbiome, trained immunity, and neurodegenerative diseases. We first summarize evidence of trained immunity in the brain and its role in neurodegeneration. Next, we highlight the role of the microbiome in peripheral immune modulation and in trained immunity. Finally, we propose potential mechanisms through which the microbiome may induce or modulate trained immunity in the brain. These include: 1) immunogenic microbial metabolites that cross the blood-brain barrier and alter host cell epigenetics; 2) migration of peripherally trained myeloid cells into the brain; 3) viral infection-induced trained immunity that may predispose to neurodegeneration. Together, this perspective suggests that microbiome-induced trained immunity offers a novel mechanism linking peripheral immune regulation with neuroinflammation and neurodegeneration with implications for therapeutic targeting of epigenetic modification as a molecular prevention strategy for progression of neurodegeneration.

Humans

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans

Reprogrammed Komagataella phaffii for enhanced secretory expression of human lactoferrin.

Human lactoferrin (hLF) is a multifunctional glycoprotein of the transferrin family derived from milk and mucosal secretions, which exhibits antibacterial, anti-tumor, and immunomodulatory functions, and is an important component of infant formula. Conventional methods for lactoferrin expression are often inefficient, primarily due to inadequate protein synthesis capabilities and poor stability within microbial hosts. Herein, a Komagataella phaffii yeast strain capable of high-level secretory expression of hLF was constructed by reprogramming the endoplasmic reticulum (ER) and vacuole using CRISPR/Cas9 technology. A dual-expression cassette containing the AOX1 promoter, an α-secretion signal peptide, the hLF gene, and a terminator was integrated into three different sites of the K. phaffii genome. The stepwise strategy combining expansion of the ER membrane involved in protein synthesis with knockout of vacuolar proteases further enhanced hLF production. Subsequently, 0.1 g/L FeCl₃ was added to the medium to reduce the toxicity of hLF and improve its stability. After high-density cultivation of K. phaffii through optimization of cultivation conditions in shake flasks and a 5 L bioreactor, the secretory intact hLF titer reached 2214 mg/L, representing a 76.3-fold increase achieved through these engineering strategies. In addition, antibacterial experiments demonstrated that this secretory hLF had a significant inhibitory effect on Escherichia coli, Staphylococcus aureus, and yeast. Overall, the developed K. phaffii protein expression platform enabled efficient production of lactoferrin, demonstrating its potential for expressing other lactoproteins.

Lactoferrin

Effectiveness of Mobile-Delivered Exercise and Yoga Programs on Depressive Symptom Reduction in Employees: Randomized Controlled Trial.

BACKGROUND: Mental health challenges such as stress and depression are prevalent among employees. Mobile health platforms that deliver exercise or yoga interventions offer a promising approach to improve mental health outcomes in this population. OBJECTIVE: This study aimed to assess the effectiveness of 12-session adaptive moderate-intensity exercise and yoga programs delivered via a motion-detecting digital platform in reducing stress and depressive symptoms among employees. METHODS: This was an unblinded, 3-arm, parallel-group, randomized controlled trial conducted at Seoul National University Bundang Hospital and Boramae Medical Center between November 2023 and January 2024. Eligible participants were full-time employees. Seventy-five participants were randomly assigned to an exercise, a yoga, or a cognitive behavioral therapy-based self-care control group using computer-generated randomization. The exercise and yoga groups engaged in motion-detecting, adaptive physical activity training, whereas the control group accessed mobile-based, self-directed stress management educational materials. The intervention was largely automated, with no individualized therapeutic guidance provided. Allocation was concealed until trial entry. All recruitment and outcome assessments were conducted in person at the hospitals. The primary outcomes were perceived stress and depressive symptoms, whereas the secondary outcomes included posttraumatic stress, insomnia severity, cognitive stress response, occupational stress, and burnout. Physiological outcomes were assessed using heart rate variability and electroencephalography. Measurements were collected at baseline, immediately after the intervention, and at 4-week follow-up. Data were analyzed using a multivariate linear model to evaluate the main effects of time, group, and time&#xd7;group interactions. RESULTS: Of the 75 randomized participants (exercise: n=24, 32%; yoga: n=25, 33.3%; and control: n=26, 34.7%), 71 (94.7%) who completed at least 9 of the 12 sessions (&#x2265;40 min each) were included in the outcome analysis (exercise: n=21, 29.5%; yoga: n=24, 33.8%; and control: n=26, 36.6%). For the coprimary outcomes, the group&#xd7;time interaction for depressive symptoms (Patient Health Questionnaire-9) approached but did not reach the Bonferroni-corrected threshold (F4,136=2.71; P=.03; adjusted &#x3b1;=.025); however, planned pairwise comparisons revealed significantly greater improvement in the yoga group compared to the control group at 4-week follow-up (&#x3b2;=-3.67; adjusted P<.001). For the Perceived Stress Scale, the interaction was not significant (P=.29), although a significant main effect of time (P<.001) indicated overall stress reduction across all groups. For secondary outcomes, a significant group&#xd7;time interaction was found for the Cognitive Stress Responses Scale (P=.003), indicating differential trajectories of improvement. The yoga group showed a consistent linear decrease, whereas the exercise group showed immediate but less sustained gains. CONCLUSIONS: Digitally delivered adaptive yoga programs demonstrated superior and sustained improvements in depressive symptoms and Cognitive Stress Responses Scale scores compared with the active cognitive behavioral therapy-based self-care control group. However, the exercise program showed more modest and less sustained effects, warranting further investigation using larger samples.

Adult

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans

Metabolic and endocrine modulation of the gut-adipose tissue axis via pro-, pre-, and postbiotics in overweight dogs: A systematic review.

Canine obesity is a complex metabolic disorder driven by luminal dysbiosis, impaired gut barrier function, and metaflammation. Following PRISMA 2020 guidelines, this systematic review evaluated the efficacy of pro-, pre-, and postbiotics in modulating the gut-adipose tissue axis in overweight dogs (BCS &#x2265; 6/9) or diet-induced obesity models. Searches across PubMed and Dimensions (April 2026) identified seven eligible experimental trials. Results suggest that postbiotic Bifidobacterium animalis subsp. lactis CECT 8145 reduced postprandial glucose AUC by 6 % strictly during energy restriction. Pasteurized Akkermansia muciniphila postbiotics limited diet-induced weight gain, though glucoregulatory impacts were highly strain-specific (AKK2 reduced fasting glucose and insulin resistance indexes, whereas EB-AMDK19 exerted no significant effect). Specific probiotics (including Enterococcus faecium, Bifidobacterium lactis, Lactiplantibacillus plantarum and Bifidobacterium breve) attenuated fasting hyperinsulinemia and preserved circulating adiponectin, but lipid profile improvements (triglycerides and total cholesterol) were inconsistent across trials. In dogs, increased luminal short-chain fatty acids are not consistently mirrored by endocrine responses, so the coupling between microbial metabolites and incretin signaling remains incomplete. A critical lack of standardized reporting for species-validated insulin sensitivity metrics was identified. In conclusion, microbiome-targeted therapies, particularly inanimate postbiotics, may represent useful adjunctive strategies to mitigate metabolic dysregulation in obesogenic environments. However, clinical efficacy remains strictly strain-specific and dependent on host energy balance. Given the scarcity of high-certainty evidence, future trials must integrate dynamic physiological assessments with species-validated surrogate indexes alongside standardized dietary controls.

Animals

The global potential of freshwater microbes for plastic degradation.

Plastic pollution is becoming increasingly severe on a global scale, and the potential for biodegradation as a treatment method that is environmentally friendly merits greater attention. A significant number of genes that associated the degradation of plastic (PDAGs) have been identified, however, the distribution of these genes among microorganisms in global inland waters remains to be elucidated. A global-scale meta-analysis was conducted, incorporating approximately 1000 metagenome datasets of inland waters across seven continents. A total of 13,109 metagenome-assembled genomes (MAGs) were obtained by means of metagenomics binning, and 22,621 PDAGs were identified from these. Among these recognized PDAGs, phenylacetaldehyde dehydrogenase (PAD) was the most dominant (n = 16,664), followed by catalase (n = 5931). The predominant hosts for PAD and catalase were identified as Gamma-proteobacteria and Bacteroidia, respectively. The largest number of both PAD and catalase was found in MAGs from North America, while the average gene number in single MAG was highest in MAGs from Oceania. In accordance with the prediction of traits, PDAG-carrying MAGs from Europe demonstrated the fastest growth rate and the lowest optimal growth rate. Furthermore, 25 styrene monooxygenase (StyA) enzymes were identified, which were found to cluster into two distinct groups hosted by Alpha-proteobacteria and Gamma-proteobacteria, respectively. Moreover, 11 MAGs were observed to possess the complete pathway of polystyrene degradation. These results explored the potential of inland water microorganisms as a biological resource for plastic degradation and provided valuable microbial reference information that can be used to develop biological treatment technologies for mitigating plastics.

Plastics

Protein profiling and GC-MS product analysis provide insights into lignite solubilization and bioconversion by Lysinibacillus sphaericus strain SH19.

Lignite biosolubilization offers a mild route for valorizing low-rank coal, although the microbial processes that accompany solubilization remain incompletely defined. Here, an endogenous isolate designated Lysinibacillus sphaericus strain SH19 was evaluated using nitric-acid-pretreated Shengli lignite. Under the selected working conditions (4 M nitric-acid pretreatment, initial pH 8, 40&#xb0;C, and 16 days), the apparent solubilization rate reached 66.81%. Changes in A450, residual solid mass, culture pH, and extracellular protein concentration showed that chemical pretreatment and bacterial culture were both associated with the release of soluble lignite-derived material. SDS-PAGE and two-dimensional electrophoresis revealed treatment-associated differences in extracellular and intracellular protein patterns. LC-MS/MS analysis of excised protein spots yielded 85 candidate protein assignments; the revised supplementary table reports PEAKS scores, sequence coverage, peak area, and unique-peptide counts and highlights the limited support for several entries. GC-MS analysis produced 33 tentative library assignments in the solubilized fraction, but siloxane- and silyl-related signals were treated as possible analytical background, and no pathway was inferred from these assignments alone. Together, the data identify strain SH19 as a promising lignite-biosolubilizing isolate and provide candidate proteins and product signals for future validation. The proposed process model remains exploratory because direct enzyme assays, inhibitor experiments, carbon-balance measurements, transcriptomic or genetic validation, complete GC-MS blank subtraction, and authentic-standard confirmation were not available.

Bacillaceae

Advancing nursing education through social and emotional learning: A systematic review guided by the Collaborative for Academic, Social, and Emotional Learning framework.

BACKGROUND: With Generation Z entering the nursing workforce in growing numbers, strengthening social and emotional learning is critical for academic success, professional adaptation, and safe practice. However, the existing evidence remains fragmented because of varied interventions and inconsistent approaches. OBJECTIVES: This systematic review examined (1) the social and emotional learning essential for nursing students and nurses within the Collaborative for Academic, Social, and Emotional Learning framework, (2) their impact on educational and clinical outcomes, and (3) implications for advancing nursing education and practice. METHODS: Following Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, five international (PubMed, EMBASE, CINAHL, PsycINFO, Cochrane) and three Korean (RISS, KoreaMed, KMBASE) databases were searched up to June 2025. Eighteen studies involving 2,952 participants met the inclusion criteria, including quasi-experimental quantitative studies, descriptive quantitative studies, qualitative studies, and mixed-methods studies. The methodological quality of the included studies was appraised using the Mixed Methods Appraisal Tool. RESULTS: Within the Collaborative for Academic, Social, and Emotional Learning framework, relationship skills and self-management were the most frequently studied competencies, emphasizing teamwork, communication, and stress regulation. Self-awareness and social awareness were underexplored, despite their importance in empathy, resilience, and reflective practice. Responsible decision-making was the least studied competency, despite its importance in ethical reasoning. Social and emotional learning was consistently associated with enhanced adaptation, communication, leadership, relationships, and clinical performance. Effective strategies included blended learning, simulation, reflective activities, and mentorship, which are aligned with Generation Z's learning preferences. CONCLUSION: Although social and emotional learning integration is associated with improvements in educational and clinical outcomes in nursing, current research has largely centered on relational and stress-related competencies while underrepresenting responsible decision-making. To cultivate reflective, empathetic, and ethically grounded nurses, curricula should integrate social and emotional learning through a balanced and structured approach. REGISTRATION: This study was registered on PROSPERO (ID: CRD420251005683).

Humans

Protein persulfidation emerges as a conserved component of the redox response to DNA damage.

Genotoxic stress is frequently accompanied by alterations in cellular redox homeostasis; however, the mechanisms linking redox regulation to the DNA damage response (DDR) remain incompletely understood. Here, we investigated the early redox response to DNA damage induced by methyl methanesulfonate (MMS) in Saccharomyces cerevisiae, focusing on cysteine oxidative post-translational modifications (PTM). We show that activation of the DNA damage response is accompanied by rapid redox changes that occur in the absence of a generalized oxidative stress response. MMS exposure promotes selective remodeling of cysteine oxidative modifications, characterized by decreased free thiols, robust induction of protein persulfidation, and comparatively modest changes in sulfenylation. These alterations are accompanied by increased intracellular hydrogen sulfide levels, supporting the involvement of reactive sulfur species in the cellular response to DNA damage. Proteome-wide analyses revealed that cysteine oxidative modifications preferentially target proteins involved in central metabolism, nucleotide biosynthesis, and genome maintenance. Consistent with these observations, MMS-induced genotoxic stress promotes metabolic adaptation characterized by increased mitochondrial respiration, elevated ATP production, and mitochondrial morphological remodeling, linking bioenergetic adaptation to redox regulation. Importantly, perturbation of intracellular redox balance using N-acetylcysteine compromises survival under DNA-damaging conditions, supporting a functional role for redox signaling during the DDR. Finally, MMS treatment also induces protein persulfidation in mammalian cells. Moreover, exposure to etoposide, a mechanistically distinct genotoxic agent that induces DNA double-strand breaks through topoisomerase II inhibition, showed a similar trend, suggesting that protein persulfidation may not be restricted to alkylation-induced DNA damage. Together our findings identify protein persulfidation as a prominent component of the redox response to DNA damage and provide new insight into the functional interplay between mitochondrial metabolism, cysteine-based redox regulation, and genome maintenance.

Oxidation-Reduction

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2&#xd7; liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans

Integrated miRNA-mRNA profiling reveals candidate regulatory relationships associated with high-fat diet-induced muscle lipid deposition in black seabream (Acanthopagrus schlegelii).

High-fat diets are increasingly used in aquaculture due to their protein-sparing effects; however, the post-transcriptional regulatory mechanisms of fish muscle in response to high-fat diets (HFD) remain unclear. In this study, juvenile black seabream were fed either a normal-fat diet (NFD) or a HFD to investigate the miRNA-mRNA regulatory network associated with diet-induced muscle lipid deposition. Oil Red O staining and biochemical analysis showed that high-fat diet feeding markedly increased lipid droplet accumulation and crude lipid content in muscle, indicating significant induction of muscle lipid deposition. Integrated mRNA and miRNA expression profiling revealed substantial transcriptomic and post-transcriptional responses to high-fat diet challenge. A total of 271 differentially expressed genes were identified, including 120 upregulated and 151 downregulated genes. Through combined target prediction and expression correlation analysis, thirteen candidate inverse miRNA-mRNA relationships were subsequently identified, and RT-qPCR supported the expression patterns of selected miRNAs and mRNAs. These pairs included miR-499-x-dmgdh, miR-499-y-gatm, miR-727-y-ass1, miR-4649-x-foxo4, miR-9129-z-myl7, and several novel miRNA-mediated interactions involving adk, chst11, lypla2, frem2, kcnc4, wars1, bag2, and capn2. Functional analysis suggested that these regulatory pairs were mainly associated with metabolic adaptation, structural remodeling, and cellular stress responses. In particular, gatm, dmgdh, ass1, and adk were associated with energy metabolism-related processes, including pathways previously linked to Ampk regulation, whereas myl7, frem2, and kcnc4 may contribute to muscle structural maintenance and excitability regulation. Overall, this study provides candidate miRNA-mRNA regulatory relationships potentially involved in high-fat diet-induced muscle lipid deposition and adaptive remodeling in black seabream, offering a basis for future functional studies on muscle metabolism and quality regulation in marine fish.

Animals

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60&#xa0;days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals