Pathological cardiac hypertrophy is an independent risk factor for heart failure (HF). Early identification and timely treatment are crucial for significantly delaying the progression of HF. Targeted Show more
Pathological cardiac hypertrophy is an independent risk factor for heart failure (HF). Early identification and timely treatment are crucial for significantly delaying the progression of HF. Targeted amino acid metabolomics and RNA sequencing (RNA-seq) were combined to explore the underlying mechanism. In vitro, H9c2 cells were stimulated with angiotensin II (Ang II) or were incubated with extra valine after Ang II stimulation. The branched chain alpha-ketoate dehydrogenase kinase (Bckdk) inhibitor 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) and rapamycin were utilized to confirm the role of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in this process. A significant accumulation of valine was detected within hypertrophic hearts from spontaneously hypertensive rats (SHR). When branched chain amino acid (BCAA) degradation was increased by BT2, the most pronounced decrease was observed in the valine level (Δ = 0.185 μmol/g, p < 0.001), and cardiac hypertrophy was ameliorated. The role of imbalanced mitochondrial quality control (MQC), including the suppression of mitophagy and excessive mitochondrial fission, was revealed in myocardial hypertrophy. In vitro, high concentrations of valine exacerbated cardiomyocyte hypertrophy stimulated by Any II, resulting in the accumulation of impaired mitochondria and respiratory chain dysfunction. BT2, rapamycin, and mitochondrial division inhibitor 1 (Mdivi-1) all ameliorated MQC imbalance, mitochondrial damage and oxidative stress in hypertensive models with high valine concentration. Valine exacerbated pathological cardiac hypertrophy by causing a MQC imbalance, probably as an early biomarker for cardiac hypertrophy under chronic hypertension. Show less
Osteoarthritis (OA) is a common progressive joint disorder marked by synovial inflammation, cartilage degeneration, the formation of osteophytes, though its underlying molecular mechanisms remain uncl Show more
Osteoarthritis (OA) is a common progressive joint disorder marked by synovial inflammation, cartilage degeneration, the formation of osteophytes, though its underlying molecular mechanisms remain unclear. This study integrated bioinformatics and experimental validation to identify key genes in OA synovium and their association with immune infiltration. Analysis of the GSE82107 dataset (10 OA, 7 controls) revealed 909 differentially expressed genes (525 upregulated, 384 downregulated). WGCNA identified the "midnightblue" module, and its intersection with DEGs yielded 122 genes enriched in cytokine-cytokine receptor interaction, JAK-STAT signaling, and autophagy pathways. Protein-protein interaction analysis highlighted FLT3LG, MC4R, CXCL10, CARTPT, and LHX2 as core genes (AUC 0.743-0.871). Immune infiltration analysis showed elevated M0 macrophages in OA, with CXCL10 showing a strong positive correlation with M1 macrophage infiltration (r = 0.74), and MC4R correlating with the presence of follicular helper T cells (r = 0.85). In vitro, OA-derived fibroblast-like synoviocytes exhibited CXCL10 upregulation, MC4R downregulation, and increased IL-6, IL-8, and TNF-α secretion, which were markedly reduced by CXCL10 knockdown or MC4R overexpression. Synovial tissue assays confirmed these expression patterns. CXCL10 and MC4R may represent promising diagnostic markers and therapeutic targets, offering new insights into OA immunopathogenesis and precision intervention. Show less
Yilin Chen, Xiaofeng Ding, Sonalika Ray+10 more · 2025 · bioRxiv : the preprint server for biology · Cold Spring Harbor Laboratory · added 2026-04-24
Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and a Show more
Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and aging-related comorbidities. To define the underlying mechanisms, we performed longitudinal transcriptomic profiling in peripheral blood mononuclear cells (PBMCs) from a cohort of simian immunodeficiency virus (SIV)-infected rhesus macaques spanning four key stages: pre-infection, acute infection, short-term ART, and long-term ART. Bulk RNA sequencing revealed dynamic immune remodeling across infection and treatment. Acute SIV infection induced robust antiviral and inflammatory programs, with upregulation of interferon-stimulated genes (ISGs), IL-27, JAK/STAT, and NF-ÎşB signaling, coupled with suppression of T- and B-cell activation pathways. Short-term ART effectively reversed these transcriptional perturbations, restoring adaptive immune gene expression and reducing innate antiviral responses to near-baseline levels. In contrast, chronic SIV infection on long-term ART maintained viral suppression but was characterized by reactivation of innate immune pathways, including TLR2/TLR4/MYD88, NF-ÎşB, and inflammasome (NLRP3/or NLRP12, caspase-1) signaling, along with sustained macrophage activation, platelet/coagulation signaling, and senescence-associated secretory phenotype. Protein analyses confirmed persistent CASPASE-1 and NF-ÎşB activation in spleen tissue. Pathologic evaluation of a carotid artery from an SIV-infected, long-term ART-treated macaque revealed macrophage-rich plaques with p21 Show less
Little is known about the association between physical activity and the risk of pre-sarcopenic obesity (pre-SO) among adolescents. Hence, this study aimed to examine the association between physical a Show more
Little is known about the association between physical activity and the risk of pre-sarcopenic obesity (pre-SO) among adolescents. Hence, this study aimed to examine the association between physical activity and pre-SO in a sample of 2143 adolescents aged 12 to 18 years from Yinchuan, China. The pre-SO was defined by three criteria: low skeletal muscle mass adjusted by weight (SMM/W) combined with body mass index (BMI), fat mass percentage (FMP), and waist circumference (WC). After adjusting for age, smoking, drinking, sleep time, and high-fat food consumption, participants with high physical activity (HPA) had a lower risk of pre-SO compared to those with low physical activity (LPA) according to the obesity criteria of FMP (OR   0.63, 95% CI, 0.48-0.83, P < 0.05), and WC (OR 0.71, 95% CI, 0.52-0.96, P < 0.05). Additionally, restricted cubic spline models showed a linear dose-response association between total physical activity (TPA) and pre-SO no matter what obesity criteria were adopted (all P overall trend < 0.05, all P non-linear > 0.50). Subgroup analyses revealed that individuals with higher TPA levels exhibited a decreased risk of pre-SO in boys according to the obesity criteria of FMP, and WC. In conclusion, HPA is associated with a reduced risk of pre-SO in adolescents, especially among boys. Show less
Hepatoid carcinoma of the ovary (HCO) is a highly uncommon and aggressive neoplasm originating from the surface epithelial cells of the ovary, characterized by hepatocyte-like differentiation. To date Show more
Hepatoid carcinoma of the ovary (HCO) is a highly uncommon and aggressive neoplasm originating from the surface epithelial cells of the ovary, characterized by hepatocyte-like differentiation. To date, most information on HCO is derived from case reports, with fewer than 50 documented cases globally. In this case report, we present a detailed account of the diagnosis, treatment, and prognosis of a patient diagnosed as having bilateral HCO, which is even rarer. Targeted next-generation sequencing revealed somatic mutations in PIK3C3 and TP53, with no BRCA1/2 alterations, and a molecular profile consistent with microsatellite stability and low tumor mutational burden. We also review the current literature to situate our findings within the broader context of existing knowledge. Given the rarity of bilateral HCO, our objective is to contribute to the existing body of knowledge by providing a comprehensive description of its clinical features, molecular characteristics, and treatment strategies. This effort may enhance understanding of this rare malignancy and offer insights to improve patient outcomes in clinical practice. Show less
Evidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically Show more
Evidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically identify Cpn's therapeutic targets and pathways in Western diet (WD)-induced obesity using integrated network pharmacology, transcriptomics, and experimental validation. A Western diet (WD)-induced mice model was used to evaluate the effectiveness of Cpn in ameliorating obesity. A network pharmacology analysis was then employed to identify the potential anti-obesity targets of Cpn. GO functional enrichment and KEGG pathway analysis were performed to elucidate the potential functions of the identified targets, followed by constructing a protein-protein interaction network to screen the core targets. Meanwhile, quantitative transcriptomics was conducted to validate and broaden the network pharmacology findings. Finally, molecular docking and quantitative real-time PCR assay were used for the core target validation. Cpn treatment effectively alleviated obesity-related symptoms in WD-induced mice. The metabolic pathway, insulin signaling pathway, HIF-1 signaling pathway, FoxO signaling pathway, lipid and atherosclerosis pathway, and core targets including CPS1, HRAS, MAPK14, PAH, ALDOB, AKT1, GSK3B, HSP90AA1, BHMT2, EGFR, CASP3, MAT1A, APOM, APOA2, APOC3, and APOA1 are involved in regulating the therapeutic effect of Cpn. This study comprehensively uncovers the potential mechanism of Cpn against obesity based on network pharmacology and quantitative transcriptomics, which provides evidence for revealing the pathogenesis of obesity, suggesting that Cpn is a possible lead compound for anti-obesity treatment. Show less
ObjectiveTo analyze the clinical characteristics, etiological composition, genetic variations, and survival outcomes of children with hypertrophic cardiomyopathy.Materials and methodsThis retrospectiv Show more
ObjectiveTo analyze the clinical characteristics, etiological composition, genetic variations, and survival outcomes of children with hypertrophic cardiomyopathy.Materials and methodsThis retrospective study included 41 pediatric patients diagnosed with hypertrophic cardiomyopathy at The First Affiliated Hospital of Guangxi Medical University from 2013 to 2024. Clinical data were reviewed, including symptoms, echocardiography, electrocardiography, genetic testing, and follow-up outcomes. Comparisons were made between patients with primary and secondary hypertrophic cardiomyopathy.ResultsAmong the 41 patients, 27 were men and 14 were women, with a median age at onset of 4 years and 3 months. Genetic testing was performed in 24 cases, identifying 13 cases of primary hypertrophic cardiomyopathy and 11 cases of secondary hypertrophic cardiomyopathy, most commonly associated with Noonan syndrome. The most frequent symptoms were fatigue (28.95%) and dyspnea (23.68%). Common pathogenic genes in primary hypertrophic cardiomyopathy included Show less
Existing depression assessment tools inadequately detect rapid symptom changes after antidepressant treatments. This study aimed to translate, validate, and explore the clinical application of the Chi Show more
Existing depression assessment tools inadequately detect rapid symptom changes after antidepressant treatments. This study aimed to translate, validate, and explore the clinical application of the Chinese version of the McIntyre and Rosenblat Rapid Response Scale (CMRRRS) for use during the treatment of rapid-onset depression. The McIntyre and Rosenblat Rapid Response Scale was translated and culturally adapted for use in Chinese settings. Briefly, 71 patients with major depressive disorder who were receiving intravenous esketamine were assessed using the CMRRRS and other validated scales. Properties were examined, including internal consistency, construct validity, and responsiveness to change. For patient classification, Latent Profile Analysis (LPA) and Kernel Density Estimation (KDE) curves were used. The Minimum Clinically Important Difference was computed to explore the smallest change related to clinical improvement. The CMRRRS showed high reliability and robust validity. Factor analysis explained over 60% of the total variance. LPA distinguished three patient classes, while KDE curves determined that a cut-off of 5 points was optimal for detecting clinically meaningful changes. The CMRRRS is a reliable, valid, and sensitive tool for monitoring rapid symptom changes in patients with depression treated with esketamine. It allows real-time symptom monitoring and personalized treatment adjustments. Further studies are warranted to explore its broader applicability. Show less
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between the Show more
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between these groups and depressive symptoms. A total of 521 adolescents aged 13-18 years from Wuhan and Changsha, China, were included. Bouts of physical activity (PA) and sedentary behavior (SED) were measured using accelerometers. The Center for Epidemiologic Studies Depression Scale was used to assess participants' depressive symptoms. Latent profile analysis was employed to identify distinct groups based on their activity patterns. Three distinct groups were identified: "Prolonged sitters" ( The synergistic effect of strategies to reduce total SED duration by limiting SED bouts to 30 min or less and increasing light physical activity (LPA) may also be effective in alleviating depressive symptoms in adolescents. Show less
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection te Show more
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB-ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G') increases over time, reaching about 1000Â Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB-ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB-ECM treatment. Overall, this new injectable hydrogel based on FSB-ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure. Show less
Limited identification of insulin resistance-associated loci hinders understanding of its role in cardiometabolic health, impeding therapeutic strategies. We apply three multivariate genome-wide assoc Show more
Limited identification of insulin resistance-associated loci hinders understanding of its role in cardiometabolic health, impeding therapeutic strategies. We apply three multivariate genome-wide association study approaches on homeostatic model assessment for insulin resistance, insulin resistance index, fasting insulin, and ratio of triglycerides to high-density lipoprotein cholesterol from MAGIC and UK Biobank to develop a comprehensive phenotype ('mvIR'), and identify 217 independent loci, including 24 novel loci. The mvIR is causally associated with higher risks of 17 cardiometabolic diseases and five aging phenotypes, independent of adiposity and sarcopenia. We outline 21 of 2644 druggable genes for insulin resistance by Mendelian randomization and colocalization, where six genes (AKT1, ERBB3, FCGR1A, FGFR1, LPL, NR1H3) encode targets for approved drugs with consistent directions in alleviating insulin resistance, with no significant side effects revealed by phenome-wide association study. This study uncovers novel loci and therapeutic targets to inform strategies promoting insulin resistance-centered cardiometabolic health and longevity. Show less
Primary membranous nephropathy (pMN) often progresses to end-stage renal disease (ESRD) in the absence of immunosuppressive therapy. The immunological mechanisms driving pMN progression remain insuffi Show more
Primary membranous nephropathy (pMN) often progresses to end-stage renal disease (ESRD) in the absence of immunosuppressive therapy. The immunological mechanisms driving pMN progression remain insufficiently understood. We developed a single-cell transcriptomic profile of peripheral blood mononuclear cells (PBMCs) from 11 newly-diagnosed pMN patients and 5 healthy donors. Through correlation analysis, we identified potential biomarkers for disease stratification and poor prognosis. Expression levels of several proinflammatory factors were significantly increased in patients compared to healthy donors, such as interleukins ( Our study provides insight into the immunological mechanism of pMN and identifies numerous biomarkers and signaling pathways as potential therapeutic targets for managing the progression of high-risk pMN. Show less
Family caregivers ('carers') bear the highest care burden during the postoperative survivorship period of pancreatic cancer, given its poor prognosis. Most carers report unmet needs when taking on car Show more
Family caregivers ('carers') bear the highest care burden during the postoperative survivorship period of pancreatic cancer, given its poor prognosis. Most carers report unmet needs when taking on caregiving responsibilities during this period. Thoroughly investigating carers' needs is essential for helping families address practical care challenges. However, this important topic remains underexplored. To assess the need levels and identify need subgroups among carers of patients with pancreatic cancer 6 months after surgery and demographic predictors contributing to heterogeneity. Cross-sectional study. Participants were recruited from the pancreas centres of four tertiary A-level comprehensive hospitals in Jiangsu Province, China. 240 patients with pancreatic cancer and their carers ('dyads') participated in the survey. Carers completed the Comprehensive Needs Assessment Tool in Cancer for Carers, the Activities of Daily Living Scale for patients, and the General Demographic Information Questionnaire for dyads. Latent profile analysis (LPA) was used to categorise carers' needs. Non-parametric and chi-square tests were used to examine differences in need scores and sociodemographic characteristics among subgroups. Multiple logistic regression (MLR) was used to analyse sociodemographic impacts. Six months post-surgery, the total carers' need score was 41.83 ± 22.65 points, indicating a moderate level, with the highest needs reported for healthcare personnel, information and knowledge, and facilities and services. The LPA results revealed that carers were divided into five distinct subgroups based on differing levels of need across the domains assessed by the Comprehensive Needs Assessment Tool in Cancer for Carers, with proportions of 8.8 %, 22.5 %, 8.3 %, 55 %, and 5.4 %. Subgroup membership was predicted by four factors: carers' sex (odds ratio [OR]: 11.08, 95 % confidence interval [CI]: 1.64, 74.99, We have highlighted the complex individualised needs of carers of patients with pancreatic cancer. Through LPA and MLR, we identified distinct need subgroups and their predictors. Healthcare professionals may be able to improve dyads' health by tailoring support to each subgroup's specific needs and issues. Registration number: ChiCTR2400079415, registered 03/01/2024, first recruitment 04/02/2024. Show less
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein in Show more
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein interactions. In this study, we investigate the role of the PALS1-associated tight junction protein (PATJ), which contains 10 PDZ domains, in the formation of IS and its subsequent impact on T cell activation. To elucidate the function of PATJ, we generated murine models with conditional T cell-specific knockout of We observed a rapid increase in PATJ expression during T cell activation. Conditional knockout of Our study reveals an important role of PATJ in the formation of IS and provides an approach to improve the efficacy of CAR-T therapy. Show less
Atherosclerosis (AS), a chronic inflammatory condition of the vasculature, is a major contributor to cardiovascular morbidity. Yaoshi Tongyuan Tablet (YTT) is a food-medicine homology (FMH) formulatio Show more
Atherosclerosis (AS), a chronic inflammatory condition of the vasculature, is a major contributor to cardiovascular morbidity. Yaoshi Tongyuan Tablet (YTT) is a food-medicine homology (FMH) formulation containing A combination of network pharmacology, ultra-performance liquid chromatography coupled with Q Exactive Orbitrap mass spectrometry (UPLC-QE-MS), and molecular docking was employed to predict potential bioactive compounds and their molecular targets. ApoE Integrated analyses revealed kaempferol, isorhamnetin, and quercetin as central bioactive molecules acting on AKT1, a key node within the PI3K/Akt signaling cascade. YTT ameliorates atherosclerosis by counteracting dyslipidemia and inflammation, primarily through modulation of the PI3K/Akt/NF-ÎşB pathway. This study offers novel integrative insights into the anti-atherogenic properties of YTT and pinpoint crucial bioactive constituents worthy of further pharmacological investigation. Show less
Derazantinib (DZB), a pan-fibroblast growth factor receptor (FGFR) inhibitor, exhibits potent activity against FGFR1-3 kinases and has been clinically approved for antitumor therapy. However, its anti Show more
Derazantinib (DZB), a pan-fibroblast growth factor receptor (FGFR) inhibitor, exhibits potent activity against FGFR1-3 kinases and has been clinically approved for antitumor therapy. However, its antibacterial properties remain unknown. Here, we demonstrated that DZB displays broad-spectrum activity against Show less
Integrated multi-omics analysis has revolutionized the investigation of plant-derived compounds for type 2 diabetes mellitus (T2DM). Solanesol, a bioactive constituent from Solanaceae plants, exhibits Show more
Integrated multi-omics analysis has revolutionized the investigation of plant-derived compounds for type 2 diabetes mellitus (T2DM). Solanesol, a bioactive constituent from Solanaceae plants, exhibits high oral bioavailability and translational potential for multi-target therapeutics. This study aimed to elucidate the multi-target mechanisms and multi-organ protective effects of solanesol in T2DM management through integrated multi-omics approaches, to bridge the gap between phytochemical discovery and clinical translation. In Lepr Solanesol improved glucose tolerance, insulin sensitivity, and reduced serum lipids, hepatic gluconeogenesis, uric acid, white adipose mass, pancreatic/hepatic inflammation, and renal fibrosis. Mechanistically, solanesol: 1) enriched beneficial gut microbiota (Alistipes, Anaerotruncus, and Parasutterella) and increased levels of long-chain unsaturated fatty acids; 2) rebalanced the dysfunctional mitochondrial oxidative phosphorylation​​ microenvironment by modulating the expression and the activities of respiratory chain Complexes I-V; 3) modulated hepatic lipid metabolism by ​inhibiting​​ de novo ​​lipogenesis​​ via the Acly-Acaca-Fasn pathway, promoting cholesterol efflux and fatty acid oxidation​​ through Abca1/Fabp5, and attenuating inflammation​​ via Lpl-PPARδ downregulation. Solanesol demonstrates multi-organ protective effects through gut microbiota-metabolite crosstalk and hepatic lipid/redox homeostasis regulation. Its multi-target efficacy and oral bioavailability position it as a novel, clinically translatable candidate for T2DM management. Show less
This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glu Show more
This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). A prospective cohort of 150 diet-controlled GDM patients and 150 pregnant women with NGT, all delivering at our hospital, were selected based on predefined criteria. Data on demographics, physical parameters, and perinatal outcomes were compiled. Blood samples for fasting plasma glucose (FPG), homocysteine (Hcy), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and apolipoprotein A1 (apoA1) were collected before delivery. GDM patients exhibited higher levels of FPG, Hcy, and the apoB/apoA1 ratio, but lower HDL-C and apoA1 levels compared to the NGT group. Adverse outcomes such as macrosomia, premature rupture of membranes, and postpartum hemorrhage were more prevalent in the GDM group. In GDM patients, neonatal birth weight positively correlated with FPG and TG levels. Stratified Hcy analysis in GDM showed no significant differences in perinatal outcomes. However, the third quartile of the apoB/apoA1 ratio had a lower incidence of macrosomia compared to the first quartile, and the second quartile showed a higher incidence of birth asphyxia. GDM patients demonstrated increased levels of Hcy, FPG, and the apoB/apoA1 ratio, correlating with more adverse perinatal outcomes than healthy pregnant individuals. The relationships between Hcy, lipids, and these outcomes remain inconclusive, highlighting the need for further research. Show less
Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poo Show more
Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poorly understood. Here, to address this issue, we induced injury and performed single-cell RNA sequencing on individual cells in skeletal muscle at different time points. Our analysis revealed a distinct macrophage subset that expressed high levels of Gpnmb and that coexpressed critical factors involved in macrophage-mediated muscle regeneration, including Igf1, Mertk and Nr1h3. Gpnmb gene knockout inhibited macrophage-mediated efferocytosis and impaired skeletal muscle regeneration. Functional studies demonstrated that GPNMB acts directly on muscle cells in vitro and improves muscle regeneration in vivo. These findings provide a comprehensive transcriptomic atlas of macrophages during muscle injury, highlighting the key role of the GPNMB macrophage subset in regenerative processes. Our findings suggest that modulating GPNMB signaling in macrophages may represent a promising avenue for future research into therapeutic strategies for enhancing skeletal muscle regeneration. Show less
The seven-transmembrane (7TM) receptors are the largest superfamily of cell-surface receptors and are involved in various physiological processes of vertebrate species. In our previous study, a new ch Show more
The seven-transmembrane (7TM) receptors are the largest superfamily of cell-surface receptors and are involved in various physiological processes of vertebrate species. In our previous study, a new chicken 7TM receptor (Ch-7TM) was discovered in mononuclear phagocytes (MNPs) derived from chicken peripheral blood mononuclear cells (PBMCs). To explore the functions of Ch-7TM, RNA interference (RNAi) was used to silence the Ch-7TM messenger RNA (mRNA) of MNPs, using small interfering RNA (siRNA) designed with BLOCK-iT™ RNAi Designer. Herein we demonstrated that silencing of the Ch-7TM mRNA induced apoptosis of MNPs, suggesting that Ch-7TM contributed to the survival of MNPs. Moreover, chicken sera could inhibit the Ch-7TM-silencing-induced apoptosis in MNPs. The survival factor presented in fraction 16 (F16) of chicken sera was highly protective against the Ch-7TM-silencing-induced apoptosis in MNPs. The proteins from F16 were identified as vitamin D-binding protein (DBP) and apolipoprotein A-IV (ApoA-IV), which might be potential candidates for survival factors. The protective effect of vitamin D and ApoA-IV indicated that Ch-7TM might involve the intracellular oxidation-reduction balance, although more evidence is needed to confirm this function. The siRNA screening serves as an excellent model for studying the functions of chicken MNPs receptors. Show less
Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency. Methionine (Met) is an essential amino acid required for feather follicle development; yet t Show more
Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency. Methionine (Met) is an essential amino acid required for feather follicle development; yet the exact mechanism involved remains insufficiently understood. A total of 180 1-day-old broilers were selected and randomly divided into 3 treatments: control group (0.45% Met), Met-deficiency group (0.25% Met), and Met-rescue group (0.45% Met in the pre-trial period and 0.25% Met in the post-trial period). The experimental period lasted for 56 d, with a pre-trial period of 1-28 d and a post-trial period of 29-56 d. In addition, Met-deficiency and Met-rescue models were constructed in feather follicle epidermal stem cell by controlling the supply of Met in the culture medium. Dietary Met-deficiency significantly (P < 0.05) reduced the ADG, ADFI and F/G, and inhibited feather follicle development. Met supplementation significantly (P < 0.05) improved growth performance and the feather growth in broilers. Met-rescue may promote feather growth in broilers by activating the Wnt/β-catenin signaling pathway (GSK-3β, CK1, Axin1, β-catenin, Active β-catenin, TCF4, and Cyclin D1). Compared with Met-deficiency group, Met-rescue significantly (P < 0.05) increased the activity of feather follicle epidermal stem cell and mitochondrial membrane potential, activated Wnt/β-catenin signaling pathway, and decreased the content of reactive oxygen species (P < 0.05). CO-IP confirmed that mitochondrial protein PGAM5 interacted with Axin1, the scaffold protein of the disruption complex of the Wnt/β-catenin signaling pathway, and directly mediated Met regulation of Wnt/β-catenin signaling pathway and feather follicle development. PGAM5 binding to Axin1 mediates the regulation of Wnt/β-catenin signaling pathway, and promotes feather follicle development and feather growth of broiler chickens through Met supplementation. These results provide theoretical support for the improvement of economic value and production efficiency of broiler chickens. Show less
The leopard coral grouper (Plectropomus leopardus), an increasingly important species in marine aquaculture, has garnered significant research interest due to its high market value. Despite extensive Show more
The leopard coral grouper (Plectropomus leopardus), an increasingly important species in marine aquaculture, has garnered significant research interest due to its high market value. Despite extensive research on ovarian growth and development in fish, the molecular mechanisms governing lipid droplet formation and lipid deposition in P. leopardus remain poorly understood. In this study, we conducted transcriptomic analyses of P. leopardus ovaries at three developmental stages: primary growth (PG), pre-vitellogenesis (PV), and mid-vitellogenesis (MV). A total of 534,847,090 raw reads were obtained from nine cDNA libraries, leading to the identification of 19,155 genes with 13,817 genes expressed at all stages. Differential analysis showed that 1012, 2609, and 4039 genes were up-regulated, while 168, 277, and 577 genes were down-regulated in the three comparisons, respectively. Functional enrichment analyses highlighting the critical roles of differentially expressed genes (DEGs) in lipid transport (such as fatp1, fatp4, fatp6, apoeb, lpl and fabps), fatty acid metabolism (such as elovl6, acsl1, dgat2 and gpat4) and phospholipid metabolism (such as ept1, chka and pla2g15). These findings underscore their contribution to lipid droplet formation and deposition. Furthermore, key signaling pathways, including Wnt, mTOR, PPAR and PI3K/Akt, were implicated in regulating these processes. The reliability of the RNA-seq data was confirmed through qPCR validation of 10 lipid-related genes. Based on these results, we propose a model for lipid droplet formation and lipid deposition during ovarian development in P. leopardus. This study advances our understanding of ovarian development in P. leopardus and provides a foundation for future research on marine fish reproduction, with potential applications in species conservation and aquaculture management. Show less
Maternal circulating lipid concentrations impact the risk of pregnancy complications and infant health outcomes. The associations between physical activity and circulating lipids during pregnancy rema Show more
Maternal circulating lipid concentrations impact the risk of pregnancy complications and infant health outcomes. The associations between physical activity and circulating lipids during pregnancy remain inadequately understood. A study was conducted from July 2024 to March 2025, involving the recruitment of 520 pregnant women in Wuhan, China. The Pregnancy Physical Activity Questionnaire (PPAQ) scores were evaluated in trimesters. Circulating lipid profiles, including total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), apolipoprotein A1 (APOA1) and apolipoprotein B (APOB) concentrations, were assessed at each trimester. The daily energy expenditure of physical activity (EEPA) during the first, second, and third trimesters was recorded as 11.35, 9.07, and 9.48 metabolic equivalents-hour/day (METs-h/d). The EEPA in the first trimester was significantly greater than that in the second ( This study suggests that increased physical activity during pregnancy is associated with lower lipid levels. Moreover, maternal age appears to have a significant impact on physical activity and the metabolism of circulating lipids during pregnancy. Show less
Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, Show more
Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut - brain - liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system. Show less
Adipose tissue metabolism plays a crucial role in sheep meat quality and the optimization of adipose tissue utilization. To reveal the molecular mechanisms of adipose tissue metabolism during growth i Show more
Adipose tissue metabolism plays a crucial role in sheep meat quality and the optimization of adipose tissue utilization. To reveal the molecular mechanisms of adipose tissue metabolism during growth in naturally grazing sheep, we investigated the mRNA and miRNA profiles in subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (Mth-6, Mth-18, and Mth-30). We identified 927 differentially expressed (DE) genes and 134 DE miRNAs in the SAT of sheep at different growth stages. Specifically, the expressions of Show less
High-grade serous ovarian cancer (HGSOC) is the most lethal type of gynecological cancer, and platinum-resistance is a serious challenge in its treatment. Long non-coding RNAs (lncRNAs) play critical Show more
High-grade serous ovarian cancer (HGSOC) is the most lethal type of gynecological cancer, and platinum-resistance is a serious challenge in its treatment. Long non-coding RNAs (lncRNAs) play critical regulatory roles in the occurrence and development of cancers. Here, using RNA sequencing of tumor small extracellular vesicles (sEVs) from HGSOC patients, the lncRNA CATED is identified as significantly upregulated in both tumors and tumor-derived sEVs in platinum-resistant HGSOC, and low CATED levels correlate with good prognosis. Functionally, CATED enhances cisplatin resistance by promoting cell proliferation and inhibiting apoptosis in vitro and in vivo. These effects could be transferred via CATED-overexpressing sEVs from donor cells and HGSOC tumor sEVs. Mechanistically, CATED binds to and upregulates DHX36 via PIAS1-mediated SUMOylation at the K105 site, and elevated DHX36 levels increase downstream RAP1A protein levels by enhancing RAP1A mRNA translation, consequently activating the MAPK pathway to promote platinum-resistance in HGSOC. Antisense oligonucleotide mediated knockdown of CATED reverse platinum-resistance in sEV-transmitted mouse models via the DHX36-RAP1A-MAPK pathway. This study newly identifies a sEV-transmitted lncRNA CATED in driving HGSOC platinum-resistance and elucidates the mechanism it regulates the interacting protein through SUMOylation. These findings also provide a novel strategy for improving chemotherapy in HGSOC by targeting CATED. Show less
The early detection of high-risk individuals is crucial to delay and reduce the incidence of type 2 diabetes. In this study, we aimed to explore the performance of a novel subgroup-specific biomarker Show more
The early detection of high-risk individuals is crucial to delay and reduce the incidence of type 2 diabetes. In this study, we aimed to explore the performance of a novel subgroup-specific biomarker strategy in the prediction of incident diabetes. In the Taiwan Lifestyle Cohort Study, adult subjects without diabetes were included and followed for the incidence of diabetes in 2006-2019. The biomarkers measured included blood secretogranin III (SCG3), vascular adhesion protein-1 (VAP-1), fibrinogen-like protein 1 (FGL1), angiopoietin-like protein 6 (ANGPTL6), and angiopoietin-like protein 4 (ANGPTL4). Among the 1,287 subjects, 12.2% developed diabetes during a 6 year follow-up. Blood VAP-1 was significantly associated with incident diabetes in the overall population (HR = 0.724, P < 0.05), participants under 65 years old (HR = 0.685, P < 0.05), those with a BMI of ≥24 kg/m Gender- and BMI-specific biomarker strategy can improve the prediction of incident diabetes. A subgroup-specific biomarker strategy is a novel approach in the prediction of incident diabetes. Show less
Angiopoietin-like protein 8 (ANGPTL8) forms complexes with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity, and decreased LPL activity is an established cardiovascular risk factor. S Show more
Angiopoietin-like protein 8 (ANGPTL8) forms complexes with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity, and decreased LPL activity is an established cardiovascular risk factor. Serum levels of ANGPTL4/8 and C-terminal domain-containing ANGPTL4 (CD-ANGPTL4) are positively associated with cardiovascular death, however, the underlying mechanisms remain incompletely understood. The present study investigated relationships of ANGPTL3, ANGPTL3/8, CD-ANGPTL4, and ANGPTL4/8 with coronary artery calcification (CAC) progression (using Agatston scores) and incident coronary events. ANGPTL3, ANGPTL3/8, CD-ANGPTL4, and ANGPTL4/8, were measured using dedicated immunoassays in participants of the Heinz Nixdorf Recall (HNR) study, an unselected, population-based cohort of subjects free from cardiovascular disease at baseline. CAC measurements were performed at baseline and after 5 years in 2887 participants, and there was follow-up for coronary events (median duration 18.8 years). Median Agatston scores increased over 5 years from 6.70 (t Associations of ANGPTL3 and ANGPTL3/8 with coronary atherosclerosis progression and incident coronary events were inconsistent, while CD-ANGPTL4 and ANGPTL4/8 were associated with both coronary atherosclerosis progression and incident coronary events. Associations of ANGPTL4/8 and CD-ANGPTL4 with cardiovascular events may reflect progression of coronary atherosclerosis conferred by diabetes, inflammation, or the potential intrinsic effects of CD-ANGPTL4 and ANGPTL4/8. Show less
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelia Show more
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelian randomization study. The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6Â 908Â 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441Â 016 and 12Â 321Â 875 genetic variants available for analysis. Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes. Thirteen lipid biomarkers, VA, and CRT. A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD. This MR study suggests unidirectional causality between TG and ApoE3 and the response to anti-VEGF treatment in patients with nAMD. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Show less