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
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
Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has d Show more
Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has demonstrated clinical benefit in stabilizing atherosclerotic plaques, yet its molecular mechanisms are not fully defined. This research sought to elucidate the protective effects exerted by SHTL on AS progression. To investigate the impact of SHTL on macrophage function and plaque stability, we utilized ApoE SHTL markedly attenuated the progression of AS, demonstrated by reduced plaque formation within both the aortic root and aorta, diminished plasma lipid concentrations, and suppressed inflammatory responses. SHTL demonstrates significant anti-inflammatory and lipid-regulatory effects, attenuating AS progression through the PPARγ/Mfge8 pathway, thereby enhancing macrophage efferocytosis. These findings highlight a novel mechanism by which SHTL may contribute to preventing and treating atherosclerotic diseases. 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
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
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
Oocyte maturation-coupled mRNA post-transcriptional regulation is essential for the establishment of developmental potential. Previously, oocyte mRNA translation efficiencies focused on the trans-regu Show more
Oocyte maturation-coupled mRNA post-transcriptional regulation is essential for the establishment of developmental potential. Previously, oocyte mRNA translation efficiencies focused on the trans-regulation of key RNA-binding protein (RBPs), rarely related to RNA structure. RNA G-quadruplexes (rG4s) are four-stranded RNA secondary structures involved in many different aspects of RNA metabolism. In this study, we have developed a low-input technique for rG4 detection (G4-LACE-seq) in mouse oocytes and found that rG4s were widely distributed in maternal transcripts, with enrichment in untranslated regions, and they underwent transcriptome-wide removal during meiotic maturation. The rG4-selective small-molecule ligand BYBX stabilized rG4s in the oocyte transcriptome and impaired spindle assembly and meiotic cell cycle progression. The proteomic spectrum results revealed that rG4 accumulation weakened the binding of a large number of RBPs to mRNAs, especially those associated with translational initiation. Ribosomal immunoprecipitation and translational reporter assays further proved that rG4s in the untranslated regions negatively affected the translational efficiency of key maternal mRNAs. Overexpression DEAH/RHA family helicase-36 partially reverses BYBX-induced oocyte developmental defects, suggesting its importance in rG4 regulation. Collectively, this study describes the distribution, dynamic changes, and regulation of rG4s in the mouse maternal transcriptome. Before meiosis resumption, a large number of rG4s in oocytes are necessary to maintain the translatome at a low level, and DHX36-mediated rG4 removal promotes a translational switch and is required for successful maternal-to-zygotic transition. 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
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
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
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-κB 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
Amyloid deposition of human islet amyloid polypeptide (hIAPP) is closely linked to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Developing effective inhibitors to suppress hIAP Show more
Amyloid deposition of human islet amyloid polypeptide (hIAPP) is closely linked to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Developing effective inhibitors to suppress hIAPP aggregation holds significant therapeutic potential for the prevention and treatment of T2DM. Recent researches indicate that both heme and lithospermic acid (LPA) can inhibit hIAPP aggregation. However, heme is prone to induce protein damage under oxidative stress, while LPA exhibits limited inhibitory efficacy despite its antioxidant properties. To overcome these limitations, we aimed to develop a dual-component inhibitor comprising heme and LPA. thioflavin T (ThT) fluorescence, transmission electron microscopy (TEM), circular dichroism (CD) and gel electrophoresis were combined to observe the inhibitory efficacy of heme-LPA co-formulation on hIAPP aggregation. The results demonstrate that LPA and heme can synergistically inhibit hIAPP aggregation. The inhibitory effect of heme-LPA co-formulation on hIAPP aggregation is significantly stronger than that of either component alone. The heme-LPA not only prevents the complete conversion of hIAPP into β-sheet fibrillar structures but also maintains its active monomeric conformation for extended periods. Furthermore, peroxidase activity assays revealed that the presence of LPA significantly reduces the peroxidase activity of heme in a concentration-dependent manner and attenuates peptide nitration damage under H₂O₂-NO₂ 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
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
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
Alzheimer's disease (AD) is a chronic neurodegenerative disorder predominantly affecting the elderly population. The pathogenesis of AD involves the production of highly neurotoxic amyloid-β peptide 1 Show more
Alzheimer's disease (AD) is a chronic neurodegenerative disorder predominantly affecting the elderly population. The pathogenesis of AD involves the production of highly neurotoxic amyloid-β peptide 1-42 (Aβ 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
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
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 6 908 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441 016 and 12 321 875 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
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
We have designed the first antigen-less pro-vaccine, named 8206, for treating autoimmune diseases. Composed of dexamethasone, rapamycin, and R848 at a mass ratio of 8:20:6, 8206 is a complete toleroge Show more
We have designed the first antigen-less pro-vaccine, named 8206, for treating autoimmune diseases. Composed of dexamethasone, rapamycin, and R848 at a mass ratio of 8:20:6, 8206 is a complete tolerogenic adjuvant that acts systemically to form an active vaccine in situ with endogenous pathogenic autoantigens. This active vaccine suppresses autoimmunity by expanding antigen-specific Treg cells in affected tissues. In a mouse model of atherosclerosis, 8206 successfully targeted all three analyzed pathogenic autoantigens (ApoB, HSP60, and HMGB1) and inhibited disease progression. These findings suggest that 8206 can potentially serve as a universal treatment vaccine for autoimmune diseases by eliminating the need for exogenous immunogens, with implications for broad applications in immunotherapy. Show less
By various assessments, the previous study has unequivocally concluded functional apoB and MTTP (microsomal triglyceride transfer protein) for VLDL production in chicken ovaries. The present study sou Show more
By various assessments, the previous study has unequivocally concluded functional apoB and MTTP (microsomal triglyceride transfer protein) for VLDL production in chicken ovaries. The present study sought to use whole tissue culture to define the role of VLDL secretion by small yellow follicles (SYFs) along their development under normal and heat stress (HS) conditions. Under thermoneutral conditions (39 °C), chicken SYFs increased MTTP activity, apoB expression and VLDL secretion, while underwent cell apoptosis along the time course. Despite relieved ER stress and protein ubiquitinylation, inhibition of VLDL secretion by Lomitapide and Mipomersen greatly increased triglyceride accumulation, impaired estradiol production and cell proliferation, and accelerated cell apoptosis in accordance with upregulated caspase 3/7 activity, JNK activation, protein carbonylation, and MDA accumulation. Exposure to HS at 44 °C boosted cell apoptosis in a duration-dependent manner. Acute HS for 3 h enhanced VLDL secretion, impaired estradiol production and cell proliferation, and promoted IL-1b production, oxidative damages, and cell apoptosis, whereas except MDA content and cell proliferation, the detrimental effects were halted after 13 h recovery. Lomitapide and Mipomersen augmented lipid accumulation, oxidative stress, inflammatory response, and exacerbated transient impairment of estradiol secretion and cell proliferation in SYFs under 3 h HS and after recovery, but failed to rescue cell viability despite relieved ER and proteostatic stress. In conclusion, routine secretion of VLDL by SYFs serves as an intrinsic mechanism to sustain cell viability and functions to support the whole program required for follicle development, while under HS, this mechanism provisionally rescues steroidogenesis and cell proliferation. 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 investigate the key regulatory genes and pathways related to growth traits in the Dongtingking crucian carp (Carassius auratus indigentiaus), the transcriptomes of brain, intestine, and muscle tiss Show more
To investigate the key regulatory genes and pathways related to growth traits in the Dongtingking crucian carp (Carassius auratus indigentiaus), the transcriptomes of brain, intestine, and muscle tissues were sequenced at early juvenile stage using RNA-Seq from two groups with extreme growth rates (fast-growing and slow-growing). A total of 65, 184, and 130 differentially expressed genes (DEGs) were detected in the brain, intestine, and muscle, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted that the PPAR signaling pathway, Insulin/PI3K/Akt/mTOR/FoxO/AMPK pathway, and Protein digestion and absorption pathways are crucial for growth in this species. Based on the transcriptome data, 32 key DEGs were identified, mainly participating in processes such as cell proliferation and differentiation, growth, development, and metabolism. Prominent examples are cyclic AMP-responsive element-binding protein 5 (creb5b), forkhead box protein O1-A (foxo1a), transcription factor AP-1-like (jun), lipoprotein lipase-like (lpl), angiopoietin-like 4 (angptl4), and egl nine homolog 3-like (egln3). This study enhances the understanding of the genetic factors and regulatory mechanisms responsible for variations in growth rates and provides a valuable basis for further studies on the regulatory mechanisms of growth in C. auratus indigentiaus. Show less
Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims Show more
Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers. A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.5 mg) and once-weekly administration for 2 weeks to reach target doses (5, 10 and 15 mg) by titration. A total of 40 volunteers received at least one dose of BGM0504 or placebo. The PK profile of BGM0504 was investigated over a wide dose range and supported once-weekly administration. It was observed that C BGM0504 was generally safe and well tolerated with favourable PK profile and potential role in weight loss was also confirmed. These findings support subsequent development of BGM0504 for type 2 diabetes mellitus (T2DM) and obesity. Show less
Endothelial-to-mesenchymal transition (EndMT) is a biological process that converts endothelial cells to mesenchymal cells with increased proliferative and migrative abilities. EndMT has been implicat Show more
Endothelial-to-mesenchymal transition (EndMT) is a biological process that converts endothelial cells to mesenchymal cells with increased proliferative and migrative abilities. EndMT has been implicated in the development of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), a fatal and progressive lung vascular disease. Transforming growth factor β Show less