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Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals

Proteomic analysis of cisplatin-induced spermatogenesis defects in mice.

BACKGROUND: Cisplatin is a crucial chemotherapeutic agent used for treating various cancers; however, its excessive use can cause irreversible damage to the reproductive system, and the protein expression profile of cisplatin-induced testicular injury remains unclear. METHODS: Male C57BL/6 mice were treated with cisplatin at various doses, and testes were collected for histological, immunofluorescence, and proteomic analyses. Germ cell loss and apoptosis were assessed using H&E staining, TUNEL assays, and immunofluorescence for LIN28A, SYCP3, MVH, and CDK1. Label-free quantitative proteomics identified differentially expressed proteins, which were analyzed for functional enrichment and protein-protein interactions. RESULTS: We observed that cisplatin treatment led to smaller testes, reduced sperm count, and a significant decrease in the number of spermatocytes and spermatids in mice. Label-free quantitative proteomic analysis revealed that cisplatin significantly reduced the expression of cyclin-dependent kinase 1 (CDK1), a key spermatogenesis regulator, in the testes. Reduction in CDK1 expression is correlated with spermatogenic arrest, particularly in spermatocytes. CONCLUSION: These findings highlight the critical role of CDK1 in cisplatin-induced spermatogenic dysfunction and provide new insights into fertility preservation strategies for patients with cancer undergoing chemotherapy.

Animals

Simultaneously PYCR-1 and ALH-6 inhibition exacerbates 6-PPD quinone toxicity via disrupting proline and glutamate metabolisms and activating insulin signals in Caenorhabditis elegans.

Glutamate synthesized from the proline can serve as a precursor for key intermediate metabolites of citric acid cycle. Recently, we observed reduced glutamate content and expression of alh-6 controlling glutamate synthesis by 6-PPD quinone (6-PPDQ) in Caenorhabditis elegans. However, possible effect of 6-PPDQ on proline synthesis and the association with 6-PPDQ toxicity induction remain unclear. After 0.1-10 μg/L 6-PPDQ exposure, proline content was further reduced, and expression of pycr-1 governing proline biosynthesis was decreased. In 6-PPDQ exposed nematodes, RNA interference (RNAi) of pycr-1 decreased α-ketoglutarate content, enhanced mitochondrial dysfunction, reduced nicotinamide adenine dinucleotide (NADH) and reduced flavine adenine dinucleotide (FADH₂) contents, inhibited mitochondrial complex I/II activities, and decreased expressions of gas-1 and mev-1. Moreover, compared to single RNAi, double RNAi of pycr-1 and alh-6 exacerbated the 6-PPDQ toxicity in reducing α-ketoglutarate, NADH, and FADH₂ contents, and suppressing mitochondrial complex I/II activities and gas-1 and mev-1 expressions. Additionally, double RNAi of pycr-1 and alh-6 intensified toxicity of 6-PPDQ on longevity and caused upregulation of insulin ligand and receptor genes and downregulation of daf-16 and its targeted genes in 6-PPDQ exposed nematodes. Furthermore, after 6-PPDQ exposure, daf-16 RNAi suppressed pycr-1 and alh-6 expressions, suggesting formation of a regulatory feedback loop between pycr-1/alh-6 and daf-16. Our findings highlight involvement of disrupted proline and glutamate metabolisms in 6-PPDQ-induced mitochondrial dysfunction and reduced longevity.

Animals

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one‑carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals

Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8&#xa0;days to four thermal regimes: constant 18&#xa0;&#xb0;C (CT), constant 28&#xa0;&#xb0;C (HT), intermittent cooling from 18 to 8&#xa0;&#xb0;C followed by recovery to 18&#xa0;&#xb0;C (FL), and intermittent warming from 18 to 28&#xa0;&#xb0;C followed by recovery to 18&#xa0;&#xb0;C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P&#xa0;<&#xa0;0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2&#xa0;years) and the longer-lived cold-water Argopecten purpuratus (7-10&#xa0;years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56&#xa0;days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30&#xa0;days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56&#xa0;days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae

UNCX/SIN3A-Mediated H4K8 decrotonylation suppresses FOXO3 to drive TNBC progression and docetaxel resistance.

Triple-negative breast cancer (TNBC) remains a clinically challenging subtype characterized by aggressive behavior and limited treatment options. Though docetaxel remains a cornerstone chemotherapy for TNBC, the frequent emergence of resistance highlights the urgent need to identify novel therapeutic targets. In this study, we report that uncoordinated homeobox (UNCX) is upregulated in docetaxel-resistant breast cancer cells, genomically amplified in breast cancer, and associated with poor survival in breast carcinoma patients. Functional studies revealed that UNCX promotes breast cancer cell proliferation, migration and reduces the docetaxel sensitivity. Mechanistically, UNCX functions as a transcriptional repressor by recruiting the SIN3A complex. Genome-wide profiling indicated that the UNCX/SIN3A complex directly binds to the promoters of tumor-suppressor genes including FOXO3, and represses their transcription by removing histone H4K8 crotonylation (H4K8cr). Additionally, the UNCX/SIN3A complex enhances FOXO3 phosphorylation and inhibits its nuclear translocation, further inhibiting its activity. Notably, SIN3A knockdown, FOXO3 overexpression, or crotonylation restoration effectively reverses UNCX-induced malignant phenotypes. These findings collectively establish the UNCX/SIN3A-H4K8cr-FOXO3 axis as a pivotal epigenetic regulator of TNBC progression and chemoresistance, revealing new avenues for targeted therapeutic development against this aggressive breast cancer subtype.

Humans

Integrative multi-omics reveals a fibroblast-centered, ZFHX3-prioritized regulatory framework linking sick sinus syndrome and atrial fibrillation.

OBJECTIVE: To define shared genetic and multi-scale mechanisms underlying comorbidity between sick sinus syndrome (SSS) and atrial fibrillation (AF). METHODS: We integrated genome-wide association study (GWAS) summary statistics for SSS and AF with Genotype-Tissue Expression (GTEx) expression and splicing quantitative trait loci (eQTL/sQTL), atrial single-cell and spatial transcriptomics, and epigenomics. We identified trait-relevant tissues and pathways, prioritized shared cell types, quantified genome-wide and local genetic sharing, detected joint loci by cross-trait meta-analysis, and linked loci to regulatory programs via colocalization and cell-prioritized co-expression networks. RESULTS: Both traits showed strongest enrichment in cardiac tissue, especially Heart Atrial Appendage. Fibroblasts from the left atrial appendage were consistently prioritized as the key shared cell population. SSS and AF displayed significant positive genome-wide genetic correlation, with multiple locally shared regions, including six major loci. Cross-trait meta-analysis identified eight joint-phenotype SNPs implicating four susceptibility genes. ZFHX3 was the leading tissue-cell-gene candidate, acting as a hub in fibroblast co-expression modules and colocalizing with cardiac regulatory signals. CONCLUSION: Shared liability for SSS and AF is highly tissue- and cell-specific, converging on regulatory networks in atrial appendage fibroblasts, with ZFHX3 serving as a central mechanistic and biomarker node.

Humans

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44&#xa0;&#xb0;C) and compared with control conditions (27&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals

A pragmatic randomized controlled trial of self-directed online writing interventions for posttraumatic stress symptoms in a real-world digital setting.

Background: Public health and other large-scale crises, such as the COVID-19 pandemic, have intensified the global mental health burden, creating unprecedented demand for accessible interventions for posttraumatic stress symptoms (PTSS).Objective: We evaluated the feasibility and effectiveness of two self-directed online writing interventions embedded within China's WeChat ecosystem during the COVID-19 pandemic through a pragmatic randomised controlled trial.Methods: Between December 2021 and August 2022, 1,526 adults were screened for PTSS via a Tencent Medinfo Mini-Program. Eligible participants (n&#x2009;=&#x2009;211) were randomised to Guided Narrative Technique-Writing (GNT-W, n&#x2009;=&#x2009;100) or Expressive Writing (EW, n&#x2009;=&#x2009;111). Both interventions comprised three self-directed daily writing sessions delivered entirely online without human support. Primary outcome was PTSD symptom severity (PTSD Checklist-Short), assessed at baseline, post-intervention, 2-week, and 1-month follow-ups.Results: While initial engagement followed typical digital health patterns (64.5% overall attrition), participants who initiated treatment showed strong adherence (77% completion). Both interventions were associated with significant within-group reductions in PTSS severity (GNT-W: b&#x2009;=&#x2009;-0.43, p&#x2009;=&#x2009;.023, d&#x2009;=&#x2009;-0.43; EW: b&#x2009;=&#x2009;-0.60, p&#x2009;=&#x2009;.001, d&#x2009;=&#x2009;-0.58), with no significant between-group difference (group &#xd7; time: b&#x2009;=&#x2009;0.18, p&#x2009;=&#x2009;.48). GNT-W did not confer additional benefit over EW protocol on PTSS severity.Conclusions: Both self-directed writing interventions were associated with within-group reductions in PTSS; without an inactive control condition, however, these changes cannot be firmly attributed to the interventions. GNT-W showed no advantage over the simpler EW protocol. These findings offer preliminary support for embedding scalable, low-barrier writing interventions in widely used digital platforms.Chinese Clinical Trial Registry: ChiCTR2000034836.

Humans

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log&#x2081;&#x2080;(P)&#xa0;&#x2265;&#xa0;6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C&#xa0;>&#xa0;T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals

Metatranscriptomic analysis of viral sequences associated with Culex nigripalpus at an Alabama aquaculture site.

Mosquitoes associated with aquaculture habitats can harbor diverse viruses, yet the viromes of many locally abundant species remain poorly characterized. At an aquaculture-associated site in Auburn, Alabama, we surveyed mosquito populations and found Culex nigripalpus to be the dominant species collected. To characterize viruses associated with this mosquito, we performed RNA-seq on pooled female Cx. nigripalpus and compared complementary bioinformatic workflows for viral detection and genome recovery. One workflow removed host-associated reads by mapping to the closest available mosquito reference genome prior to assembly, whereas a second workflow used fully de novo assembly and viral database annotation. Additional protein-level filtering, cross-workflow comparison, and comparison of Trinity and rnaSPAdes assemblies were used to prioritize well-supported viral candidates. Across the original analyses, 16 submitted accessions corresponding to 12 collapsed virus/name groups were recovered, including Merida virus, Hubei mosquito virus 5, Zhejiang mosquito virus, Hubei virga-like virus 3, Rinkaby virus, Elemess virus, Qingnian mosquito virus, Serbia narna-like virus 2, XiangYun narna-levi-like virus 8, Ecclesville picorna-like virus, and baculovirus-like fragments. Several candidates were supported across multiple workflows, while others were recovered only under specific analytical conditions, indicating that candidate recovery was influenced by assembly and filtering choices. Selected viral contigs were independently supported by RT-PCR amplification. Overall, these results provide a first characterization of viral sequences associated with Cx. nigripalpus from an Alabama aquaculture-associated site and show that comparison across assembly and filtering strategies helped prioritize the most consistently supported viral candidates.

Animals

The gonadal matrisome and its correlation with sex change in the ricefield eel Monopterus albus.

The matrisome is a comprehensive list of genes in the genome of an organism, which encodes proteins constituting or interacting with the extracellular matrix (ECM). The gonadal ECM is important for folliculogenesis and spermatogenesis. This study characterized the composition of the matrisome and the expression of matrisome genes in the gonad of ricefield eel, a protogynous sex-changing teleost, during sex change. A total of 838 matrisome genes were identified in the genome of ricefield eel through an in-silico orthology-based approach, of which 482, 443, 429, and 570 matrisome genes were shown to be expressed in the gonads of female (F), early intersexual (EI), mid-intersexual (MI), and late intersexual (LI) fish, respectively. Differentially expressed matrisome genes (DEMGs) were observed across all the sexual stages as well as in each category of ECM components. Analysis of DEMGs in the comparison between EI and F revealed dramatic upregulation of adam8a, mmp9, and s100a11 while downregulation of col4a5, col15a1b, clec3ba, f13a1, and ccl44, which were further confirmed by qPCR analysis. Together, these findings revealed significant changes in the expression of many matrisome genes, particularly three regulator genes, adam8a, mmp9 and f13a1, as female ricefield eels initiate sex change, suggesting that gonadal tissues undergo dramatic remodeling involving the regression of ovarian tissues and the development of testicular tissues to facilitate this process. These data provide valuable resources for further unraveling the roles of matrisome genes in gonadal development of ricefield eel and other vertebrates.

Animals

Integrated physiological and transcriptomic analyses reveal coordinated gill responses to heat stress in pikeperch (Sander lucioperca).

Climate change-driven warming of aquatic environments has made thermal stress an increasingly important factor influencing fish physiological homeostasis. Given their central roles in respiration and osmoregulation, gills are particularly responsive to variations in ambient temperature. Histological examination, physiological measurements, and transcriptome profiling were integrated to investigate the mechanisms associated with heat stress-induced gill injury in pikeperch (Sander lucioperca). Histological analysis revealed that exposure to 29&#xa0;&#xb0;C directly caused structural damage to the gills of pikeperch. Oxidative status was evaluated by measuring malondialdehyde (MDA) levels and the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). MDA accumulation was significantly enhanced under heat stress, while antioxidant enzyme activities (SOD, POD, and CAT) displayed a transient increase followed by a subsequent decline. Transcriptome profiling showed marked enrichment of the protein processing in endoplasmic reticulum pathway after heat stress, suggesting activation of endoplasmic reticulum (ER) stress in pikeperch gills. With increasing stress duration, the unfolded protein response (UPR) appeared unable to re-establish ER homeostasis, shifting ire1 and atf6 toward a pro-apoptotic state. Protein-protein interaction (PPI) analysis further highlighted hub genes potentially involved in heat stress-induced ER stress and apoptosis. TUNEL staining and western blotting collectively confirmed that heat stress triggered apoptosis in pikeperch gill tissue. Overall, this study provides new insights into the physiological and molecular responses of pikeperch gills to heat stress and enhances our understanding of thermal stress adaptation in cold-water aquaculture species under climate change.

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&#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

Unraveling the c-Myc-CASC19/HDAC1-NPM1 epigenetic axis: A novel regulatory circuitry and therapeutic target in gastric carcinogenesis.

Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation.

Humans

Distinct molecular responses to acute cold exposure revealed by comparative transcriptomic and metabolomic profiling in the bay scallop Argopecten irradians.

Acute cold stress can elicit distinct molecular responses even when bay scallop populations show similar phenotypic outcomes. We compared a seventh-generation fast-growing bay scallop line (BS) with a commercial control population (CC) during a 72-h acute cold exposure at -1&#xa0;&#xb1;&#xa0;0.3&#xa0;&#xb0;C. RNA-seq was used as the discovery layer, representative BS cold-responsive genes were evaluated by qRT-PCR, and paired LC-MS profiles provided a comparative metabolic layer. At baseline, 138 genes differed between BS and CC; after cold exposure, 134 of these baseline differences disappeared and 61 of 65 cold-state differences newly emerged. BS showed a larger transcriptomic response magnitude than CC, with 1129 cold-responsive genes compared with 28 genes in CC, and this ordering remained robust across multiple sensitivity analyses. Survival after 72&#xa0;h was identical in BS and CC (83/90, 92.2% in each population). Biochemical responses were time-dependent and marker-specific: CAT, LZM, T-SOD and T-AOC showed population-by-time interactions, whereas GSH-Px and MDA did not, and the 72-h differences were not consistently favourable to BS. Metabolomic cold effects were strongly concordant between populations, and no feature showed a significant population-by-cold interaction. Features putatively assigned to arachidonic acid metabolism were enriched, but this provider-annotated pathway signal remains exploratory because authentic-standard confirmation was not performed. These findings indicate population-specific differences in molecular responsiveness but do not establish superior cold tolerance in BS.

Animals