Amyloid cerebrovascular disease, primarily driven by the accumulation of amyloid-beta (Aβ) peptides, is intricately linked to neurodegenerative disorders like Alzheimer's disease. BACE1 (beta-site amy Show more
Amyloid cerebrovascular disease, primarily driven by the accumulation of amyloid-beta (Aβ) peptides, is intricately linked to neurodegenerative disorders like Alzheimer's disease. BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) plays a critical role in the production of Aβ, making it a key therapeutic target. In the current work, a CNS library of ChemDiv database containing 44085 compounds was screened against the BACE1 protein. Initially, a structure-based pharmacophore hypothesis was constructed, followed by virtual screening, with the screened hits docked to the BACE1 protein to determine the optimal binding modes. The docking results were examined using the glide gscore and chemical interactions of the docked molecules. The cutoff value of -5 kcal/mol was used to select hits with high binding affinities. A total of seven hits were chosen based on the glide g score. Furthermore, the possible binding mechanisms of the docked ligands were investigated, and it was discovered that all seven selected ligands occupied the same site in the predicted binding pocket of protein. The bioactivity scores of the compounds demonstrated that the chosen compounds possess the features of lead compounds. The toxicity risks and ADMET features of the selected hits were anticipated, and four compounds, J032-0080, SC13-0774, V030-0915, and V006-5608 were chosen for stability analysis. The selected hits were extremely stable and strongly bound to the BACE1 pocket, and conformational changes caused by RMSD, RMSF, and protein-ligand interactions were assessed using MD modeling. Similarly, principal component analysis revealed a large static number of hydrogen bonds. The MM/GBSA binding free energies maps revealed a significant energy contribution in the binding of selected hits to BACE1. The binding free energy landscapes indicated that the hits were bound with a high binding affinity. Thus, the hits could serve as lead compounds in biophysical investigations to limit the biological activity of the BACE1 protein. Show less
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metaboli Show more
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metabolic status in prediabetes, but their predictive value for cardiovascular mortality and stroke in this population remains unclear. We analyzed data from 74,678 White participants with prediabetes in the UK Biobank, defined by either HbA1c (5.7-6.4%) or fasting glucose (6.1-6.9 mmol/L). Follow-up continued until October 10, 2023. Cox regression was used to examine associations between LE8, phenotypic age (PhenoAge), cardiovascular biological age (CBA), and outcomes of cardiovascular (CVD) mortality and stroke. Restricted cubic spline (RCS) models identified biological age risk thresholds. Mediation analysis assessed whether proteins such as CST3, EFEMP1, FES, IGFBP2, IGFBP6, LPA, PCSK9, and TIMP1 mediated these effects. Over a median follow-up of 13.4 years, 2263 participants died from CVD causes. Each 1-year increase in CBA or PhenoAge was associated with a ~ 10% higher risk of CVD mortality (CBA aHR = 1.10; PhenoAge aHR = 1.09; both P < 0.001), while each 1-point increase in LE8 score was linked to a 3% lower risk (HR = 0.97, P < 0.001). The risk biological ages for these two indicators were also identified: PhenoAge ≥ 58.52 years and CBA ≥ 62.42 years. Similar trends were observed for stroke. Mediation analysis revealed that CST3, TIMP1, IGFBP2, and IGFBP6 contributed to the biological pathways between aging/lifestyle and CVD outcomes. The combined LE8 and PhenoAge model showed the strongest predictive performance for CVD mortality (AUC = 0.716) and stroke (AUC = 0.638) over 15 years. LE8 combined with phenotypic age provides prognostic value for CVD outcomes in prediabetes. These findings highlight the potential of lifestyle modification and delayed biological aging in reversing prediabetes and underscore comorbidity-related proteins as promising therapeutic targets. Show less
Pediatric primary cardiomyopathies (PCMs) are rare diseases with complex causes and nonspecific treatment. The influence of electrolytes and amino acids (AAs) on cardiomyopathies has not been extensiv Show more
Pediatric primary cardiomyopathies (PCMs) are rare diseases with complex causes and nonspecific treatment. The influence of electrolytes and amino acids (AAs) on cardiomyopathies has not been extensively studied. This study aimed to explore clinical characteristics and the usage of electrolytes and AAs in children with PCMs. Children diagnosed with PCMs who had genetic test reports were included. Relevant information was collected and processed, and clinical characteristics and mutated genes were clarified. Gene databases were searched to explore related electrolytes and AAs in the treatment of PCMs. The effect of calcium was explored in children with DCM. Paired samples T tests and nonparametric Wilcoxon signed-rank tests were performed for comparison between before and after using calcium. In this study, 27 children with gene test results were enrolled to perform gene-related analysis. The median age was 2.5 years old. Mutated genes were collected, including pathogenic, likely pathogenic, uncertain significance, and other mutations. The most frequently mutated genes related to dilated cardiomyopathy (DCM) were For children with DCM, calcium supplements may be beneficial. AAs, including serine, cysteine, and arginine, could be used for supplementary treatment in children with DCM and HCM. 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
Many patients are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complications. Trimethylamine N-oxide (TMAO), derived from gut microbes, is a key u Show more
Many patients are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complications. Trimethylamine N-oxide (TMAO), derived from gut microbes, is a key unconventional contributor to the development of atherosclerosis. Here we present a strategy performed by orally administered nano-functionalized probiotics (PDMF@LGG) to inhibit TMAO through the gut microbiota-trimethylamine (TMA)-TMAO axis. PDMF@LGG, composed of polydopamine-coated Lacticaseibacillus rhamnosus GG and nanoparticles based on a reactive oxygen species (ROS)-responsive polymeric prodrug of fluoromethylcholine (FMC), can promote the retention of probiotics and nanoparticles in the intestine to persistently scavenge elevated ROS and release drugs. This process suppresses TMA production and absorption, lowering plasma TMAO levels. The therapeutic effects on male ApoE Show less
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study aimed to identify key genes involved in HCC development and elucidate their molecular mech Show more
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms, with a particular focus on mitochondrial function and apoptosis. Differential expression analyses were performed across three datasets-The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), GSE36076, and GSE95698-to identify overlapping differentially expressed genes (DEGs). A prognostic risk model was then constructed. Cysteine/serine-rich nuclear protein 1 ( A six-gene prognostic model was established, comprising downregulated genes ( Show less
Intramuscular fat (IMF) content in beef cattle is a critical determinant of beef meat quality, as it positively influences juiciness, tenderness, and palatability. In China, the crossbreeding of Wagyu Show more
Intramuscular fat (IMF) content in beef cattle is a critical determinant of beef meat quality, as it positively influences juiciness, tenderness, and palatability. In China, the crossbreeding of Wagyu and Angus is a prevalent method for achieving a better marbling level. However, the molecular mechanisms governing IMF regulation in these crossbreeds remain poorly understood. To elucidate the mechanism of IMF deposition in these crossbred cattle, we conducted a comparative transcriptomic analysis of 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
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
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
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
Hyperlipidemia is a common metabolic disorder and a risk factor for cardiovascular disease. The traditional medicine herb, Hippophae rhamnoides L., known as sea buckthorn, has anti-obesity and lipid-l Show more
Hyperlipidemia is a common metabolic disorder and a risk factor for cardiovascular disease. The traditional medicine herb, Hippophae rhamnoides L., known as sea buckthorn, has anti-obesity and lipid-lowering effects, while Silybum marianum (L.) Gaertn, known as milk thistle, has hepatoprotective properties and exhibits antioxidant effects. To evaluate the effect of sea buckthorn and milk thistle solid beverage (H-S solid beverage) in alleviating hyperlipidemia in rats and explore the underlying mechanisms by analyzing plasma and liver metabolomics, lipidomics, and liver transcriptomics. A hyperlipidemic rat model was established after 2 weeks of high-fat diet (HFD) feeding in Sprague Dawley rats. The administered doses of H-S solid beverage were 0.30 g/kg/d, 0.15 g/kg/d and 0.075 g/kg/d. Serum biochemical parameter detection, histopathological section analysis, untargeted plasma and liver metabolomics, lipidomics, and liver transcriptomics were performed to determine the therapeutic effects of H-S solid beverage and predict the related pathways in rats with hyperlipidemia. Changes in genes and proteins related to lipid metabolism were detected using real-time quantitative polymerase chain reaction and western blotting. Eighty-nine components were identified in H-S solid beverage using ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry, with flavonoids being the major constituents. The H-S solid beverage significantly reduced body weight, liver index, body fat percentage, lipid accumulation, and liver injury in HFD-fed rats. Fatty acids (FA), bile acid, phosphatidyl ethanolamine, phosphatidylcholine, triglyceride, cholesterol ester, diglyceride and phosphatidylinositol levels were significantly altered in the liver and plasma. Moreover, the transcriptomic analysis suggested that H-S solid beverage significantly altered the hepatic gene expression of cholesterol synthesis (Pdk4, Hmgcs1, and Dhcr24), lipogenesis (Scd, Angptl4, and Angptl8), and FA β-oxidation (Cpt1α, Pparδ, Acsl, Pgc-1α, and Pla2g2d). The solid beverage of sea buckthorn and milk thistle was firstly demonstrated to ameliorate HFD-induced hyperlipidemia. The lipid-lowering and hepatoprotective effects of H-S solid beverage significantly regulated cholesterol synthesis and de novo lipogenesis, as well as FA β-oxidation. In summary, this study highlights the potential of H-S solid beverages for the treatment of hyperlipidemia. 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
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
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
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
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
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
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
Apolipoprotein B (apoB) can be measured directly and accurately, and better predicts atherogenic risk than conventional lipid profiles. We aimed to investigate whether total and regional (trunk or leg Show more
Apolipoprotein B (apoB) can be measured directly and accurately, and better predicts atherogenic risk than conventional lipid profiles. We aimed to investigate whether total and regional (trunk or leg) fat deposits are associated with apoB levels in general US adults. 4585 participants were enrolled from the US National Health and Nutritional Surveys from 2011 to 2016. Overall and regional body fat were measured using dual-energy X-ray absorptiometry. The associations of total and regional fat with apoB levels were evaluated using linear regression models. Following adjustment for demographic, lifestyle, and clinical risk factors, whole-body fat percentage was positively associated with apoB levels. Additionally, percent trunk fat was positively associated (highest vs. lowest tertile beta = 17.73 for men and 14.89 for women, respectively), whereas percent leg fat was inversely associated (highest vs. lowest tertile beta = - 4.84 for men and - 6.55 for women, respectively) with apoB levels in both sexes. The association for trunk fat and leg fat remained significant after further adjustment for body mass index or waist circumference. Higher percent trunk fat combined with lower percent leg fat was associated with particularly higher apoB. In conclusion, among general US adults, both elevated trunk fat and reduced leg fat are associated with higher levels of apoB. Further research is required to elucidate the underlying pathophysiological mechanisms. Show less
Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines it Show more
Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines its major pathological process. However, current treatments have limited efficacy and may even cause serious complications. Remote ischemic conditioning (RIC), through repeated transient mechanical occlusion of limb blood vessels, has been confirmed to promote blood-brain barrier integrity after stroke, but its role in BRB disruption has not been elucidated. This study aimed to investigate the protective effects of RIC on the BRB in diabetic rats and its potential mechanisms. 48 Sprague-Dawley rats were randomly assigned to the Sham group, Sham + RIC group, diabetes mellitus (DM) group and DM+RIC group. The diabetic model was successfully induced by intraperitoneal injection of streptozotocin. RIC treatment was administered daily and lasted for 9 weeks. In functional analysis, RIC improved the retinal function based on electroretinogram data and reduced the leakage of BRB in diabetic rats. In proteomic analysis, tight junction pathway was enriched after RIC treatment, in which Patj gene was significantly increased. We also found that RIC increased mRNA levels of Patj, claudin-1 and zonula occludens (ZO)-1, protein expression of claudin-1 when compared with diabetic models. In conclusion, RIC slowed BRB damage in diabetic rats, which may be related to the preservation of tight junction proteins. RIC may be a promising protective strategy for the treatment of DR. 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
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
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
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
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