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Biomedical subjects

Wei Wang

Publications and source records attributed to Wei Wang.

At least 19 recordsLinked to original sources

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age &#xf0b3;40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans

Gut microbiota-driven indole-3-propionic acid and kynurenine production is associated with improved metabolic adaptation in periparturient dairy cows.

BACKGROUND: Gastrointestinal microbes convert tryptophan into various bioactive metabolites that influence host energy metabolism; however, these mechanisms are not well understood in periparturient dairy cows, which experience marked metabolic challenges during this period. RESULTS: In this study, we used periparturient dairy cows with rumen and ileal cannulas as in vivo models. Blood, rumen fluid, ileal digesta, and fecal samples were collected at four time points during the periparturient period. By combining metagenome-assembled genomes (MAGs) and targeted metabolite quantification, we&#xa0;characterized microbial tryptophan metabolism and associated metabolite profiles during the periparturient period. The results showed that postpartum cows exhibited significantly increased serum concentrations of triglyceride (TG), aspartate aminotransferase (AST), &#x3b2;-hydroxybutyrate (BHBA), and total bilirubin (T-Bil) compared with prepartum cows, together with decreased levels of several tryptophan metabolites, including indole-3-propionic acid (IPA) and kynurenine (KYN), indicating that tryptophan deficiency might aggravate metabolic disturbances. Metagenomic analysis identified 578 high-quality MAGs, of which 461 contained genes involved in microbial tryptophan metabolic pathways. Among these, the ruminal taxon CAG-791 harbors acdA and contributes to IPA production, whereas the hindgut taxon Treponema_D harbors kynB and promotes KYN formation. Decreases in both taxa were consistent with the reduced levels of these metabolites observed above. In a follow-up in vivo trial with tryptophan supplementation, the abundance of CAG-791 and Treponema_D&#xa0;increased, along with tryptophan-derived metabolites (IPA and KYN), which further partially mitigated metabolic disturbances. CONCLUSIONS: These findings characterize spatial and temporal changes in tryptophan metabolites and gut microbial features in periparturient dairy cows, and provide integrated evidence that alterations in tryptophan metabolism are associated with postpartum metabolic adaptation, thereby supporting the potential of tryptophan-targeted nutritional strategies to improve metabolic health in dairy cows.

Gastrointestinal microbiome

The complete chloroplast genome sequence and phylogenetic analysis of Amorphophallus gigas.

We sequenced the complete chloroplast genome of Amorphophallus gigas, a perennial monocotyledonous herb in Araceae, using HiFi technology. The genome is 173,034 bp in length with a GC content of 34.96%. It exhibits a typical quadripartite structure: a large single-copy (LSC) region of 95,283 bp, a small single-copy (SSC) region of 15,675 bp, and a pair of inverted repeat (IR) regions of 31,038 bp each. It encodes 130 genes (85 protein-coding, 37 tRNA, 8 rRNA). Phylogenetic analysis revealed that A. gigas is closely related to A. titanum, forming a distinct clade. This study provides valuable genomic resources for understanding the evolution of Amorphophallus and Araceae.

Complete chloroplast genome

DNA hypermethylation of abscisic-acid-related genes helps enhance the cold tolerance of tetraploid rice.

Polyploid plants exhibit enhanced stress resistance and superior adaptability to extreme environments, but the underlying molecular mechanisms remain incompletely understood. Here we confirm that tetraploid rice exhibits stronger cold tolerance than diploid rice. This improved tolerance is mediated by reduced malondialdehyde accumulation, elevated antioxidant enzyme activity, and epigenetic regulation of genes involved in abscisic acid (ABA) biosynthesis and signaling. Under cold stress, tetraploid rice induces stress-responsive genes (especially in the ABA pathway) more rapidly and to higher levels than diploid rice. This enhanced gene expression coincides with increased endogenous ABA accumulation. Furthermore, polyploidization and cold stress synergistically induce high methylation at CG, CHG, and CHH sites in genes and transposons (TEs). Notably, the methylation level of class II TEs in tetraploid rice is significantly higher than in diploid rice under low temperatures. To suppress TE activation in gene promoter regions under cold stress, tetraploid rice enhances the methylation level of ABA pathway-related gene promoters, thereby silencing TEs and maintaining genome stability. Collectively, these results enrich the theoretical understanding of the strong stress tolerance in polyploid plants and provide theoretical support for breeding cold-tolerant polyploid rice varieties.

ABA

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals

T2T and chromosome-level genome assemblies provide insights into the genetic basis of bioactive compound biosynthesis and environmental adaptation in licorice.

Licorice is an important medicinal herb worldwide, including three Chinese Pharmacopoeia species (Glycyrrhiza uralensis, G. inflata, G. glabra), with bioactive compounds crucial for disease treatment and industrial applications. However, the genetic mechanisms underlying the biosynthesis, diversification, and environmental adaptation of bioactive compounds in Glycyrrhiza species have long remained unclear. Herein, we assembled a gapless telomere-to-telomere (T2T) genome of G. uralensis with resolved telomeres and centromeres and three significantly improved high-quality chromosome-level Glycyrrhiza genomes, alongside a variation map of 188 wild accessions. Population analysis revealed evolutionary divergence among species, with selection signals linked to medicinal compound pathways. We identified 4CL5 as a key gene for stress response and compound synthesis. GWAS validation highlighted the GiPHL1-Gi4CL5 module's role in licochalcone A accumulation and enhanced stress adaptation in G. inflata. This study provides the first T2T Glycyrrhiza genome and insights into medicinal compound biosynthesis and environmental adaptation.

Glycyrrhiza

Host metadherin coordinates hepatic lipid metabolism and CD8+ T cell immunity to promote tumor progression.

Cancer progression is systemically influenced by distant organ dysfunction induced by primary tumors, yet how long-distance tumor-organ crosstalk regulates antitumor immunity remains unclear. Here, we identify host metadherin (MTDH) as a critical regulator of tumor-induced immunosuppression and metabolic reprogramming via tumor-liver interactions. Using Mtdh knockout mouse models, we show that concurrent MTDH loss in hepatocytes and CD8+ T cells enhances effector T cell function and suppresses tumor growth and metastasis. Mechanistically, tumor-derived extracellular vesicles and particles (EVPs) activate Kupffer cells to secrete tumor necrosis factor &#x3b1; (TNF-&#x3b1;) and TGF-&#x3b2;, which suppress hepatic PPAR&#x3b1;-mediated lipid oxidation via nuclear factor &#x3ba;B (NF-&#x3ba;B) signaling. MTDH loss restores hepatic lipid catabolism, reduces systemic lipid levels, and promotes mitochondrial metabolic reprogramming in CD8+ T cells under lipid-reduced conditions, thereby boosting antitumor immunity. Genetic or pharmacological targeting of MTDH synergizes with anti-PD-1 therapy. These findings establish host MTDH as a key mediator of tumor-liver crosstalk through metabolic and immune interactions, driving systemic cancer progression.

CD8(+) T cells

Human periodontal ligament stem cells promote oral ulcer healing in rats through modulation of TGF-&#x3b2;1/smad signaling.

BACKGROUND: Oral ulcers (OU) often present with prolonged healing, recurrent episodes, and scar formation, posing challenges for clinical management. Human periodontal ligament stem cells (hPDLSCs) have shown potential in oral tissue repair, but further research is needed to clarify their mechanism of action in OU healing. This study aims to elucidate the molecular mechanisms by which hPDLSCs promote oral ulcer healing. METHOD: To identify key regulatory genes, the OU-associated microarray dataset GSE37265 was integrated with hPDLSC genomic data for differential expression analysis. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify functional modules associated with OU healing. In vivo, hPDLSCs were locally administered into a rat ulcer model, and therapeutic efficacy was assessed by ulcer closure rates and histological evaluation (HE and Masson's trichrome staining). Furthermore, RNA-sequencing (RNA-seq) was performed on oral mucosal tissues to delineate the underlying molecular landscape and critical signaling pathways. The involvement of the TGF-&#x3b2; signaling pathway was confirmed by real-time quantitative PCR (RT-qPCR) and Western blotting (WB) analyses. RESULTS: Bioinformatics analysis identified 92 key genes in hPDLSCs-mediated treatment of OU, highlighting the central role of the TGF-&#x3b2;1/Smad pathway. As shown by the animal studies, hPDLSCs therapy increased the healing rate to 97% by day 8 (vs. 70% in the model). Furthermore, the therapy significantly reduced inflammatory cell infiltration and abnormal collagen deposition while promoting regular collagen arrangement. Transcriptomic and molecular experiments further showed that hPDLSCs simultaneously inhibit TGF-&#x3b2;1/Smad and extracellular signal-regulated kinase (ERK) signaling pathways, thereby alleviating inflammatory responses and suppressing mucosal fibrosis. CONCLUSION: In this study, we reveal a novel role for hPDLSCs in promoting oral ulcer healing. The findings indicate that hPDLSCs suppress inflammation and fibrosis via the TGF-&#x3b2;1/Smad pathway, offering a promising therapeutic strategy for OU and other fibrotic conditions.

TGF-&#x3b2;1

Repeated Cross-Sectional Surveillance and ORF5-Based Molecular Epidemiology of Porcine Reproductive and Respiratory Syndrome Virus in Anhui Province, China, 2019-2024.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major threat to swine production, and its circulation after the African swine fever outbreak requires continued surveillance. This study investigated the temporal, regional, and genetic characteristics of PRRSV in Anhui Province from September 2019 to November 2024. Ten rounds of repeated cross-sectional surveillance were conducted at 147 slaughterhouses and 21 rendering plants. Tissue samples were collected by random, cluster, or risk-based sampling, pooled in groups of five, and tested by RT-qPCR. Representative positive samples with Ct values < 25 underwent ORF5 amplification, Sanger sequencing, and phylogenetic analysis. A total of 994 site visits yielded 18,733 tissue samples. No positive samples were detected in autumn 2020 or spring 2021, whereas PRRSV was detected again from autumn 2021 and subsequently fluctuated. The highest site-level positivity was 41.18% in autumn 2023, and the highest estimated individual-level positivity was 4.66% in spring 2023. Regional differences were statistically significant, with the highest site-level positivity in northern Anhui, and pooled-sample positivity was higher in rendering plants than in slaughterhouses. All 24 ORF5 sequences belonged to PRRSV-2 and mainly clustered with NADC30-like, NADC34-like, or MLV/classical strains. These findings demonstrate temporal fluctuations and lineage coexistence, supporting continued multisource surveillance and broader genomic and antigenic evaluation.

NADC30-like

Alternative tandem transcription initiation links noncoding variants to human disease through translational control.

Alternative tandem transcription initiation is a pervasive mechanism of gene regulation, yet its genetic impact on human disease remains largely unknown. Here, we systematically quantify the genetic regulation of alternative tandem transcription initiation across 25,859 samples from 49 normal human&#xa0;tissues and 33 tumor tissues. We identify approximately 0.4 million genetic variants associated with alternative transcription initiation in 5295 genes, with 32% operating independently of gene expression. Moreover, we discover 2238 multi-tissue alternative tandem transcription initiation outliers enriched for rare deleterious promoter and 5' UTR variants, demonstrating that both common and rare variants modulate transcription initiation. Strikingly, 74% of disease variants that colocalize with genetic variants regulating alternative transcription initiation cannot be identified through expression quantitative trait loci. Transcriptome-wide association studies identify 614 disease susceptibility genes associated with alternative transcription initiation, including known cancer drivers such as MAFF and MLLT10. Functional validation uncovers OSGEP as a breast cancer risk gene, where the alternative allele lengthens the 5' UTR and reduces protein abundance through upstream open reading frame-mediated translation repression, and suppresses breast cancer cell proliferation. Our findings establish alternative transcription initiation as a major, underappreciated mechanism associating noncoding variation with disease, providing a critical resource for interpreting disease risk loci.

Humans

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

Humans

Bergamottin, a bioactive component of bergamot: dual inhibition of Japanese encephalitis virus internalization and genome replication.

Japanese encephalitis virus (JEV) is associated with high mortality and severe neurological sequelae, and existing prevention and control strategies remain insufficient. Therefore, the development of novel antiviral agents is of critical public health importance. This study systematically evaluated the antiviral activity and underlying mechanism of bergamottin, a natural product. Bergamottin exhibited significant dose-dependent inhibitory effects against JEV in multiple cell lines, including BHK-21, HuH-7, and Vero cells, demonstrating potent antiviral efficacy. Mechanistic investigations revealed that bergamottin primarily targeted the internalization and replication stages of the JEV life cycle, thereby effectively suppressing viral proliferation. Additionally, adaptive mutation screening indicated that the D389G mutation in envelope protein E confers drug resistance by potentially changing E protein conformation or reducing endocytic efficiency. In vivo experiment, bergamottin significantly reduced viral loads in mouse brain tissue and effectively improved the survival rate of infected mice. Our findings indicated that bergamottin exerted antiviral activity by dual targeting of key steps in the viral life cycle, making it a highly promising candidate for anti-JEV therapy. Further exploration of the antiviral properties of bergamottin is expected to facilitate its clinical development as a treatment for JEV infection.

Animals

CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis.

Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b+ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8+ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.

Humans

Canine cholecystitis in the presence of Hammondia spp. infection.

Biliary protozoal infections are becoming increasingly recognized in dogs. Sarcocystidae protozoal infections (i.e Toxoplasma, Neospora, Hammondia, Besnoitia, and Sarcocystis spp.) are uncommon and host-specific. Diagnosis is traditionally dependent on tissue or serologic evaluation; sensitivity and specificity for these techniques can vary. PCR amplification and genetic sequencing provide a technique to expedite diagnosis and species identification in clinical biliary protozoal infections. Bile samples were collected percutaneously from two dogs presented to a referral hospital with mixed hepatopathies and hyperbilirubinemia. Diagnostic imaging revealed changes consistent with hepatobiliary inflammation, and tachyzoites were identified via bile cytology. Sera were positive for anti-Toxoplasma sp. (n&#xa0;=&#xa0;1/2) and anti-Neospora sp. (n&#xa0;=&#xa0;2/2) antibodies. Genomic isolation from bile and pan-Sarcocystidae (18S rRNA) PCR amplification were consistent with Hammondia spp. Additional 28S rRNA (LSU), alpha-tubulin (aTUB) and cytochrome b (CytB) gene-specific fragments were PCR amplified and sequenced. Phylogenetic analysis of LSU DNA fragment (584&#xa0;bp) suggested both patients were infected with Hammondia spp. closely related to H. heydorni. Sequencing of aTUB (234&#xa0;bp) and CytB (344&#xa0;bp) revealed Patient 1 Hammondia spp. was more closely related to H. triffittae, while Patient 2 was more similar to H. heydorni. Treatment with clindamycin, and in one case additional enrofloxacin, resolved clinical and clinicopathologic changes in both dogs. This report highlights the importance of multilocus sequencing in protozoal identification in atypical infections, clinical manifestations of canine hepatobiliary hammondiasis, and need for regional Sarcocystidae prevalence studies.

Animals

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans

RADX protects against intestinal inflammation by restraining IFI16-mediated innate immunity.

Genomic instability is increased in patients with inflammatory bowel disease (IBD), yet whether it contributes directly to disease pathogenesis remains unclear. Here, we identify RADX, a structural antagonist to RAD51 and a key regulator of replication fork stability, as a critical suppressor of intestinal inflammation by limiting innate immune sensing of replication-associated DNA damage. RADX deficiency exacerbates experimental colitis, with macrophages serving as the principal mediators of this phenotype. Mechanistically, RADX competes with the DNA sensor IFI16 for binding to single-stranded DNA (ssDNA). Loss of RADX promotes ssDNA accumulation, triggering IFI16-dependent activation of NF-&#x3ba;B signaling and inflammasome assembly, thereby driving intestinal inflammation. Consistent with these findings, two RADX variants identified in patients with IBD associate with reduced RADX protein expression, increased DNA damage signaling, and elevated IL-1&#x3b2; levels. Pharmacological inhibition of RAD51 with RI-1 alleviated colitis in both wild-type and Radx-deficient mice. Together, these findings establish a mechanistic link between genome instability and intestinal inflammation, identify a RADX-IFI16 checkpoint that restrains pathogenic innate immune activation, and nominate modulation of replication stress as a therapeutic strategy for IBD.

Animals

Identifying the regulatory network of the key lipid metabolism transcription factor peroxisome proliferator-activated receptor in oysters.

Rising seawater temperatures driven by global warming have led to summer mass mortality events that pose significant challenges for the oyster industry. Peroxisome proliferator-activated receptor (PPAR) serves as a key transcriptional regulator of lipid metabolism and plays an essential role in thermal adaptation. However, the upstream regulatory mechanisms of PPAR remain poorly understood in marine organisms. In this study, we identified two PPAR subtypes (PPAR&#x3b1; and PPAR&#x3b2;/&#x3b4;) in oysters and compared transcriptomic data in different tissues and under various environmental stressors, with PPAR&#x3b1; exhibiting higher expression levels and responsiveness to environmental stresses. We observed significantly higher PPAR&#x3b1; gene expression levels and promoter activity in the relatively cold-tolerant Crassostrea gigas compared to C. angulata. The low expression of the inhibitory transcription factor CTNNB1 in C. gigas may contribute to higher gene expression of PPAR&#x3b1;. Additionally, the expression genome-wide association study (eGWAS) identified 9 significant SNPs and 124 candidate regulatory genes associated with PPAR&#x3b1; expression, including ubiquitination, phosphorylation, signaling pathways, lipid metabolism, and glucose metabolism. We provided the first experimental validation of the PPAR&#x3b1; ubiquitination-degradation pathway in marine organisms via Co-IP, which was mediated by the E3 ligase RFWD3. The protein kinase SNF1 and signaling-related proteins PIKA and KCNK2 indirectly modulated PPAR&#x3b1; downstream pathway activation to varying degrees. This study presents the first systematic investigation of PPAR&#x3b1; expression regulation in marine organisms. It identifies key molecular regulators and provides novel insights into lipid metabolic regulation and molecular targets for genetic improvement of heat tolerance in oysters under global warming.

Animals

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584&#xa0;mM (OXD) and 0.1498&#xa0;mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10&#xa0;ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines