Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understandin Show more
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understanding of the genetic basis of HF and more specific NICM subtype in the East Asian populations and evaluate the biological pathways underlying subclinical left ventricular dysfunction. We conducted a meta-analysis of genome-wide association studies (GWAS) for all-cause HF in the East Asian populations (N cases ~ 13,385) and a more precise definition of nonischemic cardiomyopathy (NICM) subtype in multi-ancestry populations (N cases~3,603). We identified a low-frequency East-Asian enriched coding variant near MYBPC3 and a NICM specific locus. Follow up analyses demonstrated male-specific HF association at the MYBPC3 locus, and highlighted SVIL as a candidate causal gene for NICM. Moreover, we demonstrated that SVIL deficiency aggravated cardiomyocyte hypertrophy, apoptosis and impaired cell viability in phenylephrine (PE)-treated H9C2 cells. In addition, the gene expression level of B-type natriuretic peptide (BNP) which was deemed as a hallmark for HF was further elevated by SVIL silencing in PE-stimulated H9C2 cells. RNA-sequencing analysis of H9C2 cells revealed that the function of SVIL might be mediated through pathways relevant to regulation and differentiation of heart muscle. These results enhance our understanding of the genetic architecture of HF in the East Asian populations, and provide important insight into the biological pathways underlying NICM and sex-specific relevance of the MYBPC3 locus that warrants further replication in another datasets. Show less
Cholesteryl ester transfer protein (CETP) mediates the exchange of triglycerides (TG) from apolipoprotein B (ApoB)-containing lipoproteins to high-density lipoproteins (HDL) and the reciprocal exchang Show more
Cholesteryl ester transfer protein (CETP) mediates the exchange of triglycerides (TG) from apolipoprotein B (ApoB)-containing lipoproteins to high-density lipoproteins (HDL) and the reciprocal exchange of cholesterol (C) from HDL to ApoB-containing lipoproteins. CETP inhibition increases HDL-C and decreases low-density lipoprotein cholesterol (LDL-C) while modestly decreasing TG. Considering that CETP inhibitors block removal of TG from TG-rich lipoproteins (TRL), it is interesting that CETP inhibition decreases TG concentrations. TG levels are largely regulated by lipoprotein lipase (LPL), the enzyme primarily responsible for hydrolyzing TG. The angiopoietin-like 3/8 complex (ANGPTL3/8) is the most potent circulating LPL inhibitor, while the TG-lowering apolipoprotein A5 (ApoA5) acts by suppressing ANGPTL3/8-mediated LPL inhibition. To better understand CETP biology, we studied the effects of CETP overexpression and CETP inhibition on the levels of ANGPTL3/8 and ApoA5 in circulation using dedicated immunoassays. CETP-overexpressing transgenic mice had increased TG and normal ANGPTL3/8 levels but manifested dramatically reduced ApoA5 concentrations. Administration of the CETP inhibitor evacetrapib had no effect on ANGPTL3/8 levels in CETP-overexpressing mice or in humans. However, evacetrapib administration increased ApoA5 concentrations in both species. In human subjects, evacetrapib treatment increased circulating ApoA5 levels in the late-stage ACCELERATE and ACCENTUATE studies by 160.1% and 204.7%, respectively. Our results uncover a previously unrecognized link between CETP and ApoA5 by showing that CETP overexpression reduces ApoA5 levels while CETP inhibition increases ApoA5 concentrations. Show less
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases Show more
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases such as obesity. Several randomized controlled trials (RCTs) targeting obese or overweight populations have found that individuals with different genotypes exhibit varying responses to the same lifestyle intervention (gene-lifestyle intervention interactions). To date, more than 20 genes, including Show less
Osteoglophonic Dysplasia (OGD) is an autosomal dominant skeletal dysplasia characterized by impaired bone growth resulting in short stature, severe craniofacial abnormalities, and in some patients FGF Show more
Osteoglophonic Dysplasia (OGD) is an autosomal dominant skeletal dysplasia characterized by impaired bone growth resulting in short stature, severe craniofacial abnormalities, and in some patients FGF23-mediated hypophosphatemia. It is caused by gain-of-function variants in FGFR1, particularly in or near the transmembrane domain of the receptor. We used CRISPR in mice to knock-in the FGFR1 p.N330I variant, chosen based on its association with FGF23 excess. Skeletal phenotyping of this Show less
This study aimed to collaboratively investigate the mechanism of variations in intramuscular fat (IMF) content in Wandong cattle using transcriptomics and metabolomics techniques. Longissimus dorsi (L Show more
This study aimed to collaboratively investigate the mechanism of variations in intramuscular fat (IMF) content in Wandong cattle using transcriptomics and metabolomics techniques. Longissimus dorsi (LD) muscle samples were collected from thirteen free-range Wandong cattle in Fengyang County, Anhui Province, China. From this initial cohort, eight animals closely matched in age and body weight were selected. Based on IMF content measured by Soxhlet extraction, these eight cattle were divided into two groups: the high-IMF (HF, n = 4) and low-IMF (LF, n = 4) groups. Subsequent analyses were performed on integrated datasets comprising the transcriptome, metabolome, and fatty acid profile. The results revealed a significant increase in IMF in the HF group compared to the LF group ( Show less
With the aging population in China, research on preventing frailty is crucial. This study aims to investigate the independent and combined associations of the Dietary inflammatory index (DII) and phys Show more
With the aging population in China, research on preventing frailty is crucial. This study aims to investigate the independent and combined associations of the Dietary inflammatory index (DII) and physical activity (PA) with frailty among Chinese older adults. A total of 285 participants aged ≥60 years with 87 males and 186 females were recruited from Hunan Province. Daily moderate physical activity (MPA), vigorous physical activity (VPA) and light physical activity (LPA) were objectively measured using a triaxial accelerometer. A Food Frequency Questionnaire 25 (FFQ25) was used to assess the participants' dietary patterns, and DII was calculated. Six combined exposure groups were formed based on PA and DII: pro-inflammatory diet and insufficient PA group, neutral diet and insufficient PA group, anti-inflammatory diet and insufficient PA group, pro-inflammatory diet and sufficient PA group, neutral diet and sufficient PA group, and anti-inflammatory diet and sufficient PA group. Frailty was assessed using the Frailty Phenotype (FP), logistic regression analyzed the associations between dietary patterns, PA, and frailty. A total of 285 older adults participants were initially recruited, but 12 were excluded due to missing data. Consequently, 273 participants were included in the final analysis. Compared to individuals with insufficient PA, those with sufficient PA were associated with significantly lower odds of frailty (OR = 0.468, 95%CI = 0.242-0.907). Participants following an anti-inflammatory diet had significantly lower odds of frailty compared with those following a pro-inflammatory diet (OR = 0.467, 95%CI = 0.221-0.988). In the combined groups, frailty prevalence was significantly lower the group with anti-inflammatory diet and sufficient PA group (OR = 0.204, 95%CI = 0.072-0.583), compared with pro-inflammatory diet and insufficient PA group. The sensitivity analysis showed that the associations between anti-inflammatory diet and sufficient PA with frailty remained statistically significant, with the direction of the associations unchanged. These findings suggest that the results are robust. Our study indicates that adhering to an anti-inflammatory diet and maintaining sufficient PA may be associated with a lower likelihood of frailty. Achieving an adequate amount of PA and following a healthy dietary pattern may serve as potential preventive measures against frailty. Show less
The Glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) are well-established drug targets for the treatment of diabetes and obesity. Studies Show more
The Glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) are well-established drug targets for the treatment of diabetes and obesity. Studies have linked GLP-1R agonist to cardiometabolic diseases (CMDs), while the therapeutic potential of the GIPR agonist remains a topic of debate. Using genetic variants as instrumental variables, we performed a two-sample Mendelian randomization (MR) analysis to investigate causal relationships between genetically proxied GIPR agonist and 23 CMD outcomes, and a two-step mediation analysis to identify mediating inflammatory biomarkers. The inverse variance weighted (IVW) method served as the primary analytical approach, supplemented by sensitivity analyses to validate robustness. The genetic mimicry of GIPR enhancement showed significant protective associations with 14 CMDs. Mediation analysis revealed that Fms-related tyrosine kinase 3 ligand (Flt3L) partially mediated the effects of GIPR agonist on angina (OR 0.997 [0.995-0.999], P = 0.0048) and myocardial infarction(MI) (OR 0.998 [0.996-0.999], P = 0.0077), accounting for 15.49% and 16.71% of the total risk reduction, respectively. Our study revealed that GIPR agonist lowers the risk of 14 CMDs. Flt3L is pinpointed as a key mediating factor in reducing angina and MI risk, suggesting a new therapeutic avenue. Show less
Atherosclerosis serves as the core pathological basis of cardiovascular, cerebrovascular, and peripheral arterial diseases, posing a serious threat to human health. However, current mainstream treatme Show more
Atherosclerosis serves as the core pathological basis of cardiovascular, cerebrovascular, and peripheral arterial diseases, posing a serious threat to human health. However, current mainstream treatments such as statin drugs and stent implantation are associated with significant side effects or limited efficacy, highlighting the urgent need for new therapeutic strategies. Pulsed electromagnetic fields (PEMFs), due to their noninvasive nature and anti-inflammatory properties, show potential in the treatment of atherosclerosis. This study utilized ApoE-/- mice, ApoE-/-NLRP3-/- knockout mice, human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), and human plasma samples for experiments, revealing significant endothelial cell (EC) inflammation and pyroptosis during the progression of atherosclerosis. PEMFs were found to effectively inhibit the activation of the NLRP3 inflammasome, reduce plaque formation, and delay the progression of atherosclerosis. Proteomic analysis of plasma from atherosclerosis patients further indicated elevated expression levels of proteins related to inflammation and pyroptosis, with particularly notable changes in membrane proteins. Mechanistic studies demonstrated that PEMFs improve mitochondrial dysfunction in ECs by regulating membrane tension and the mechanosensitive tension-mediated transient receptor potential vanilloid 4 (TRPV4) channels, thereby reducing pyroptosis. This discovery not only reveals a novel mechanobiological pathway but also provides a solid theoretical foundation for the development of PEMF-based therapies for atherosclerosis. Schematic diagram of the mechanism by which PEMFs treat atherosclerosis (created in BioRender). Wei, B. (2025) https://BioRender.com/undefined ). Show less
Pentadecanoic acid (PEA), an odd-chain fatty acid derived from diet by the gut microbiome, has garnered increasing attention for its systemic health-promoting properties. Its potential role in bladder Show more
Pentadecanoic acid (PEA), an odd-chain fatty acid derived from diet by the gut microbiome, has garnered increasing attention for its systemic health-promoting properties. Its potential role in bladder cancer (BC) occurrence and invasion, however, remains unclear. Large-scale cohorts' analyses were performed to assess the association between dietary PEA and BC occurrence and invasion. In vitro and in vivo experiments, including EJ and T24 BC cell assays and a BBN-induced mouse model, were conducted to experimentally assess the impact of PEA on BC. Serum proteomics, gut microbiome, and targeted fecal lipidomics analyses were employed to explore the underlying mechanisms. Dietary PEA was negatively associated with BC occurrence and invasion in cohort analyses. PEA suppressed EJ and T24 BC cell migration, invasion, and proliferation, while inhibiting BC development in a BBN-induced mouse model. In vivo serum proteomics identified differentially expressed lipid-related proteins (e.g., Apoe and Apob) following PEA treatment, implicating its modulation of lipid metabolism pathways. Considering the essential role of the gut-bladder axis, the gut microbiome analysis exhibited that PEA markedly altered bacteria (e.g., g_Alistipes) and fungi (e.g., o_Erysiphales, g_Teberdinia, and g_Gibberella), with concomitant lipid metabolism changes. Furthermore, targeted fecal lipidomics demonstrated the shifts in key lipids, such as phosphatidylethanolamines (PE) involved in essential lipid clusters, suggesting regulation by gut microbiome linked to BC development. Collectively, our findings demonstrate that PEA mitigates BC by reshaping the gut microbiome and modulating lipid metabolism, providing new insights into its molecular and therapeutic potential. Show less
Astrocytes are key regulators of neuroinflammation in multiple sclerosis (MS). Electroacupuncture (EA), a safe and cost-effective adjuvant therapy, has shown benefits in neurodegenerative diseases, bu Show more
Astrocytes are key regulators of neuroinflammation in multiple sclerosis (MS). Electroacupuncture (EA), a safe and cost-effective adjuvant therapy, has shown benefits in neurodegenerative diseases, but its astrocyte-related mechanisms remain unclear. Here, we demonstrated that EA at ST36 alleviated blood-brain barrier (BBB) disruption and neuroinflammation during the peak period of experimental autoimmune encephalomyelitis (EAE). Additionally, EA at ST36 upregulated the expression of α-melanocyte-stimulating hormone (α-MSH) and its receptor melanocortin-4 receptor (MC4R) in spinal astrocytes. Pharmacological studies showed that MC4R agonist RO27-3225 mimicked the therapeutic effects of EA, whereas MC4R antagonist TCMCB07 weakened EA-mediated BBB protection and neuroinflammation suppression. Moreover, astrocyte-specific silencing of MC4R via adeno-associated virus (AAV) weakened EA-mediated BBB protection and neuroinflammation suppression. RNA-sequencing (RNA-seq) and western blot (WB) revealed that EA exerts neuroprotective effects by activating MC4R to inhibit MAPK and NF-κB signaling pathways. Moreover, in MC4R-overexpressing astrocytes, α-MSH and RO27-3225 reduced inflammation responses, while TCMCB07 reversed the effects by MAPK/NF-κB signaling pathways. Collectively, our findings identify astrocytic MC4R as a critical mediator of EA-driven neuroprotection by suppressing MAPK/NF-κB signaling, providing mechanistic insight and a promising therapeutic target for EAE and other neuroinflammatory disorders. Show less
The Kruppel-like factor 15(KLF15) gene functions as a crucial transcriptional modulator involved in numerous cellular processes such as differentiation, proliferation, growth, and programmed cell deat Show more
The Kruppel-like factor 15(KLF15) gene functions as a crucial transcriptional modulator involved in numerous cellular processes such as differentiation, proliferation, growth, and programmed cell death. The epithelial-to-mesenchymal transition (EMT) provides malignant cells with the adaptability and movement necessary for tumor advancement and spread, with zinc finger E-box binding homeobox 1(ZEB1) playing a pivotal role as a transcriptional factor in EMT. This investigation initially examined the association between the KLF15 protein and EMT associated transcription factors such as ZEB1, Slug, and Snail, along with marker proteins like E-cadherin and β-catenin in bladder cancer. Furthermore, we explored their connections with clinicopathological attributes and conducted prognostic analyses. Immunohistochemical techniques were utilized to ascertain the presence of KLF15 protein and EMT-associated transcription factor proteins, along with their marker proteins in 110 specimens of bladder cancer tissues. Concurrently, clinicopathological data and postoperative survival statistics were amassed. The rates of KLF15 and Slug protein expression were linked with pathological differentiation, lymphatic involvement, and pTNM staging. The protein expression rates of ZEB1, Slug, Snail, E-cadherin, and β-catenin also showed associations with lymphatic metastasis and pTNM stages. Notably, the expression of KLF15, the coexpression of KLF15 and ZEB1, and lymphatic metastasis emerged as independent prognostic indicators for the overall survival rates in bladder cancer cases. EMT enhances the risk of tumor recurrence and reduces overall survival durations in bladder cancer cases. Furthermore, KLF15 is a significant contributor to the EMT pathway in bladder cancer, primarily through its interaction with the transcription factor ZEB1. KLF15 and ZEB1 might serve as key biomarkers for metastasis and prognosis, offering potential new targets for therapeutic intervention in bladder cancer. Show less
Xiaokun Li, Zhiheng Rao, Wenhao Hu+2 more · 2025 · Obesity reviews : an official journal of the International Association for the Study of Obesity · Blackwell Publishing · added 2026-04-24
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, e Show more
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, excess deposition of lipids in hepatic lipid droplets. Despite the growing prevalence and serious risks it poses, including liver decompensation, the need for transplantation, and increased patient mortality, MASH currently faces no approved pharmacotherapy. Several promising treatment candidates have emerged from recent clinical trials, including analogs of FGF21 and agonists of the associated FGFR1-KLB complex. These agents were well-tolerated in trials and have demonstrated significant improvements in both histological and biochemical markers of liver fat content, inflammation, injury, and fibrosis in patients with MASH. Endocrine FGF21 plays a vital role in maintaining homeostasis of lipid, glucose, and energy metabolism. It achieves this through pathways that target lipids or lipid droplets in adipocytes and hepatocytes. Mechanistically, pharmacological FGF21 acts as a potent catabolic factor to promote lipid or lipid droplet lipolysis, fatty acid oxidation, mitochondrial catabolic flux, and heat-dissipating energy expenditure, leading to effective clearance of hepatic and systemic gluco-lipotoxicity and inflammatory stress, thereby preventing obesity, diabetes, and MASH pathologies. In this review, we aim to provide an update on the outcomes of clinical trials for several FGF21 mimetics. We compare these outcomes with preclinical studies and offer a lipid-centric perspective on the mechanisms underlying the clinical benefits of these agents for MASH. Show less
Tumor angiogenesis is required for the progression of non-small cell lung cancer (NSCLC), and anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab and multitarget tyrosine kinase i Show more
Tumor angiogenesis is required for the progression of non-small cell lung cancer (NSCLC), and anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab and multitarget tyrosine kinase inhibitor anlotinib are anti-cancer treatment options, the combined effect of which in NSCLC remains unclear. A vascularized microfluidic chip was applied to model angiogenesis, together with Bevacizumab plus anlotinib (B+A) inhibited angiogenesis, reducing vessel density to 10% of control values and also reducing diameter and green fluorescent protein (GFP) area ratio. B+A inhibited cell viability by 78%, colony formation by 90%, and invasion by 75% in NSCLC cell lines A549 and H1299; downregulated N-cadherin 5.34-fold, vimentin 6.46-fold, and α-SMA 4.35-fold; and upregulated E-cadherin 3.75-fold. The rates of apoptosis of A549 and H1299 cells were increased 3.85-fold. The phosphorylation of VEGFR2, PDGFRβ, and FGFR1 was also reduced. B+A reduced tumor volume 7.23-fold and weight 7.08-fold, decreased tumor cell density, and lowered Ki-67 expression in an HIF-1α inhibitor PX478 did not enhance the anti-tumor effects of B+A, but HIF-1α activator DMOG reversed them. In addition, the combination therapy enhanced CD4 Show less
Autophagy regulates intermittent hypoxia (IH)-induced obstructive sleep apnea-hypopnea syndrome (OSAHS). We investigated the effects of IH and its withdrawal on cognitive function, autophagy, and lyso Show more
Autophagy regulates intermittent hypoxia (IH)-induced obstructive sleep apnea-hypopnea syndrome (OSAHS). We investigated the effects of IH and its withdrawal on cognitive function, autophagy, and lysophagy in OSAHS. An OSAHS rat model was established, and rats were divided into five groups: normoxia control, IH-4w (4-week IH), IH-6w (6-week IH), IH-8w (8-week IH), and IH-8w + 4w (8-week IH and 4-week normoxia). The cognitive behavior; mitochondrial and lysosomal morphology of the hippocampal tissue; mitochondrial respiratory function, permeability, and membrane potential; lysosomal function; autophagy- and lysophagy-related protein levels; and hypoxia-associated autophagy gene expression in rats were assessed. The cognitive function of rats in the IH-4w, IH-6w, and IH-8w groups was significantly impaired. In IH-8w cells, mitochondrial function was damaged with swollen morphology and decreased quantity, respiration, permeability, and membrane potential, along with significantly increased mitophagy-related protein ATG5 and LC3II/LC3 levels and decreased p62 levels. Expression of hypoxia-associated autophagy genes Becn1, Hif1, Bnip3, Bnip3l, and Fundc1 was significantly higher in the IH-8w group. Significantly increased LAMP2, CTSB, and ACP2 levels in IH-8w cells further indicated impaired lysosomal function. Lysophagy-related protein LAMP1, LC3II/LC3I, and TFEB levels were significantly increased in the IH-8w group, whereas p62 level was significantly decreased. The above listed evidence indicated damage to the mitochondria and lysosomes, as well as stimulation of mitophagy and lysophagy in IH-treatment OSAHS rat model. After withdrawing IH and culturing for 4 weeks in normal conditions, the cognitive function of rats improved, and mitophagy and lysophagy decreased. Our findings indicate that IH impairs cognitive function and promotes mitophagy and lysophagy in an OSAHS rat model, and IH withdrawal recovered the above effects. Show less
Colorectal cancer (CRC) metastasis remains a major cause of mortality, driven by epithelial-to-mesenchymal transition (EMT) and invasion. Programmed cell death 4 (Pdcd4), a tumor suppressor, is known Show more
Colorectal cancer (CRC) metastasis remains a major cause of mortality, driven by epithelial-to-mesenchymal transition (EMT) and invasion. Programmed cell death 4 (Pdcd4), a tumor suppressor, is known to inhibit translation via interaction with eukaryotic initiation factor 4A (eIF4A). Previous studies have established that Pdcd4 suppresses stress-activated protein kinase 1-interacting protein 1 (Sin1) translation through the mTORC2-Akt axis, thereby downregulating Snail expression and EMT in CRC cells. However, whether Pdcd4 directly regulates Slug, another critical EMT transcription factor, remains unexplored. PDCD4 shRNA and SLUG siRNA were used to knock down Pdcd4 and Slug in colorectal cancer cells, respectively. The sucrose gradient fractionation was performed to determine SLUG translation. A luciferase reporter assay was used to determine the role of the SLUG 5' untranslated region (5'UTR) on Pdcd4 inhibition. The effect of Slug on promoting invasion was determined by Matrigel invasion assays. Knockdown of Pdcd4 in colorectal cancer cells increased Slug protein levels without altering SLUG mRNA abundance. Sucrose gradient fractionation revealed that Pdcd4 knockdown elevated the proportion of SLUG mRNA in polysome fractions, demonstrating Pdcd4-mediated suppression of SLUG translation. To validate the mechanism, the SLUG 5'UTR was cloned and fused to a luciferase reporter and named SLUG-5'UTR-Luc. Pdcd4 knockdown markedly enhanced SLUG-5'UTR-Luc activity; whereas, ectopic Pdcd4 expression suppressed it, indicating that the SLUG 5'UTR is critical for Pdcd4-mediated translational repression. Treatment with the eIF4A inhibitor silvestrol substantially reduced Slug protein levels and SLUG-5'UTR-Luc activity. In addition, Pdcd4 overexpression decreased Slug protein abundance and restored E-cadherin expression. Notably, Slug knockdown in Pdcd4-deficient cells rescued E-cadherin expression and abrogated the invasive phenotype. These findings suggest that up-regulation of Slug translation by Pdcd4 knockdown contributes to enhanced invasion. Pdcd4 suppresses colorectal cancer invasion by translationally downregulating Slug expression. Show less
Coronary heart disease (CHD) has a significant co-morbid association with chronic kidney disease (CKD), but identification tools for the risk of concomitant CKD in patients with CHD are still lacking. Show more
Coronary heart disease (CHD) has a significant co-morbid association with chronic kidney disease (CKD), but identification tools for the risk of concomitant CKD in patients with CHD are still lacking. The purpose of this research was to construct machine learning (ML) models for identifying undetected CKD in CHD patients. 1786 CHD patients undergoing coronary intervention were retrospectively included. Lasso regression and multifactor logistic regression were used to screen feature variables. Five ML models, ie, logistic regression (LR), support vector machine (SVM), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGBoost), were constructed. Participants were divided into the training set and validation set in a 7:3 ratio. The evaluation metrics included the area under the curve, calibration curve, and decision curve. Totally, 1786 CHD patients were enrolled and split into training (70%) and validation (30%) sets. The prevalence of CKD was 21.8% (390/1786). Multivariate logistic regression analysis showed that men, advanced age, hypertension, diabetes mellitus, history of atrial fibrillation (AF), high Gensini, low hemoglobin, low plateletcrit (PCT), high triglycerides (TG), high lipoprotein(a) (Lp(a)), hyperkalemia, high uric acid to albumin ratio (UAR), high systemic inflammation response index (SIRI), low lymphocyte to monocyte ratio (LMR), and high apolipoprotein B to apolipoprotein A1 (ApoB/ApoA1) ratio were the key clinical and laboratory test indicators of CKD. The XGBoost model performed optimally in the validation set (AUC=0.909, 95% CI 0.881 -0.937). SHapley Additive explanation analysis identified UAR, hypertension, Gensini score, age, and SIRI as the top 5 key features. The XGBoost model constructed on routine clinical data was effective in identifying CKD risk in CHD patients, with UAR as a novel strong predictor. Decision curve analysis confirmed the clinical utility of the model, indicating that it may be used to guide decisions for enhanced monitoring and early intervention over a wide range of risk thresholds. Show less
Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential Show more
Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs. Show less
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. Ho Show more
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. However, existing materials mainly cover the 380-1540 nm range, with slight extension to the UV region, impeding their applications in solar-blind imaging, background-free tracking, concealed communication, etc. To address this challenge, here we propose guidelines for far-UVC (200-230 nm) optical design. Accordingly, we achieve multi-stimulated far-UVC luminescence at ~222 nm in Pr Show less
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentia Show more
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis, protein-protein interaction analysis, gene function enrichment analysis, and comparative toxicology database analysis. Finally, the gene expression heat map was drawn, and miRNA information regulating core DEGs was retrieved. A total of 1151 DEGs were found, most of them focusing on systematic development, cell development, cell differentiation, regulation of multicellular biological processes, anatomical morphogenesis, MAPK signaling pathway, proteoglycans in cancer, fluid shear stress, and atherosclerosis. The core genes (MYL9, TAGLN, SMTN, CNN1, MYH11, MYLK, MYOCD, ACTC1, LMOD1, and TPM2) obtained in end are all lowly expressed in prostate cancer samples and are associated with hypertension, tumor metastasis, prostate tumors, and tumor aggressiveness. LMOD1 and SMTN are lowly expressed in prostate cancer and may be used as markers in prostate cancer nursing. Show less
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-se Show more
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-serving as promising reservoirs of such inhibitors. Nevertheless, comprehensive screening and mechanistic characterization of their inhibitory potential remain limited. This study sought to identify potent AChE inhibitors from YGE, investigate their mechanisms of action, and assess their therapeutic prospects for AD. Methodologically, an integrated approach was employed, combining ultrafiltration-liquid chromatography (UF-LC) for rapid inhibitor screening, molecular docking and dynamics simulations for mechanistic insight, two-stage high-speed countercurrent chromatography for compound isolation, enzyme kinetics to delineate inhibition modalities, and network pharmacology to uncover relevant AD-related targets. The findings identified seven active constituents with notable AChE inhibition, among which parishins A and G were obtained at high purity (98.26% and 97.26%, respectively) and exhibited mixed-type inhibition with low IC Show less
Perimenopause is a critical turning point in women's life cycle, and the issue of sleep disturbance during perimenopause not only affects individual health, but also has profound implications for fami Show more
Perimenopause is a critical turning point in women's life cycle, and the issue of sleep disturbance during perimenopause not only affects individual health, but also has profound implications for family functioning, socioeconomic status, and public health policies. Therefore, this study aims to explore different potential profiles of sleep quality in perimenopausal women in the community and analyze the influencing factors of different profiles. A cross-sectional study was conducted from July 2024 to December 2024, and a total of 281 perimenopausal women in the community were recruited from 4 communities in Bengbu by convenience sampling. The participants completed the pittsburgh sleep quality index (PSQI), and self-rating anxiety scale (SAS), self-rating depression scale (SDS) and simplified coping style questionnaire (SCSQ). Latent profile analysis(LPA) was employed to identify latent profiles of sleep quality of perimenopausal women in the community. The predictors of sleep quality in different latent profiles were assessed via multinomial logistic regression analysis. One-way ANOVA, chi-square test or Fisher exact test, and the Kruskal-Walis test were used to compare the PSQI scores of perimenopausal women in the community under different latent profile characteristics. The mean age of 281 perimenopausal women was 50.09 ± 5.08 years, and the prevalence of sleep disorders was 31.3%. The sleep quality of perimenopausal women in community could be divided into three different latent profiles: good sleep quality group (68.7%), falling sleep and maintenance difficulty group (24.2%), and poor sleep quality with sleep disorder group (7.1%). Taking the good sleep quality group as the reference group, drinking history (OR = 2.061), chronic disease history (OR = 2.154), spouse's health status (OR = 1.871) and anxiety (OR = 4.390) were the risk factors to predict the difficulty in falling asleep and maintaining sleep in community perimenopausal women (P < 0.05). Spouse's health status (OR = 2.139) and anxiety (OR = 19.029) were the risk factors for poor sleep quality and sleep disorders in community perimenopausal women (P < 0.05). There are three qualitatively different potential profile categories of sleep quality in perimenopausal women in the community, and drinking history, chronic disease, poor spouse health and anxiety have predictive effects on their profile categories. In the future, community nursing staff can take targeted interventions according to different categories of sleep quality in perimenopausal women to improve sleep quality and level of health promotion. Show less
Hyperlipidemia and its associated hepatic steatosis pose significant global health burdens, necessitating novel therapeutic strategies. High-fat diet (HFD)-fed C57BL/6 mice received TAC (2.5, 5.0, 10. Show more
Hyperlipidemia and its associated hepatic steatosis pose significant global health burdens, necessitating novel therapeutic strategies. High-fat diet (HFD)-fed C57BL/6 mice received TAC (2.5, 5.0, 10.0 g/L) or simvastatin for 2 weeks. Metabolic parameters, serum lipid profiles, hepatic function markers, and histopathology were systematically analyzed. Molecular pathways were interrogated through qPCR, Western blot, and pharmacological inhibition of AMPK (Compound C) and PPARα (GW6471). TAC treatment demonstrated significant dose-dependent improvements across multiple parameters. Compared to HFD controls, TAC reduced body weight by 21.3% and liver index by 18.7%, while lowering fasting blood glucose levels by 32.4%. Serum analyses showed substantial reductions in total cholesterol (46.2%), triglycerides (38.5%), and LDL-cholesterol (52.1%), accompanied by a 29.8% increase in HDL-cholesterol. Hepatic function improved markedly, with ALT and AST levels decreasing by 57.3% and 49.6% respectively. Histopathological examination revealed a 68.4% reduction in hepatic lipid accumulation. At the molecular level, TAC treatment resulted in a 2.7-fold increase in AMPK phosphorylation while significantly reducing HMGCR expression by 63.1% and nuclear SREBP-1c levels by 71.5%. Concurrently, TAC upregulated PPARα and LXRα expression by 3.1-fold and 2.4-fold respectively, leading to enhanced expression of lipolytic enzymes LPL and HL by 2.8-fold and 2.1-fold. These beneficial effects were completely abolished by co-treatment with pathway-specific inhibitors. TAC ameliorates hyperlipidemia and hepatic steatosis through dual modulation of AMPK/SREBP-1c-mediated lipid synthesis and PPARα/LXRα-driven lipolysis, presenting a multifaceted therapeutic approach for metabolic disorders. Show less
Mesenchymal cells constitute the primary structural support elements within endometriotic lesions, yet their pivotal roles in endometriotic pathogenesis remain largely uncharted. This study aimed to c Show more
Mesenchymal cells constitute the primary structural support elements within endometriotic lesions, yet their pivotal roles in endometriotic pathogenesis remain largely uncharted. This study aimed to construct a single-cell atlas of endometriosis using samples from three ovarian tissues affected by endometriosis and three normal ovarian tissues. Through the utilization of scRNA-seq, we have unveiled six distinct mesenchymal subclusters in normal and endometriosis-afflicted ovaries, elucidating the diverse functions of mesenchymal populations in endometriosis. Our comprehensive analysis has revealed that mesenchymal cells predominantly engage in three key functions: ribosome-mediated protein synthesis and processing, cell adhesion facilitating intercellular support and communication, and a range of metabolic processes. Furthermore, our findings have identified several pivotal differentially expressed genes (e.g. C3, FN1, COL3A1, COL1A1, NRXN3), primarily associated with the complement and coagulation cascades, extracellular matrix (ECM) regulation, ECM receptor interactions, and cell adhesion molecules. In essence, our study provides a comprehensive transcriptomic dataset and novel insights into adhesive molecule and integrin networks within mesenchymal subclusters in endometriosis. This, in effect, has deepened the understanding of the pathomechanisms governing this condition. Show less
G-patch domain-containing protein 2 (GPATCH2), a member of the G-patch domain-containing family, has been implicated in tumor cell growth, but the link between GPATCH2 and hepatocellular carcinoma (HC Show more
G-patch domain-containing protein 2 (GPATCH2), a member of the G-patch domain-containing family, has been implicated in tumor cell growth, but the link between GPATCH2 and hepatocellular carcinoma (HCC) remains uncertain. In the current study, comprehensive bioinformatics analysis revealed that GPATCH2 was markedly upregulated in HCC and positively correlated with aggressive clinicopathological features, including histologic grade, AFP, albumin level, and adjacent hepatic tissue inflammation, as well as miserable outcomes in HCC. GPATCH2 also has certain diagnostic value for HCC, histologic grade, and 1-, 3-, and 5-year survival outcomes. Functionally, loss-of-function experiments disclosed that silencing GPATCH2 suppressed HCC cell proliferation, migration, invasion, and xenograft tumor growth in the subcutaneous mouse model. Silencing GPATCH2 also resulted in an increase in the expression level of CDH1, while causing a decrease in the expression levels of FN1, TWIST1, SNAI1, and SNAI2. Rescue experiments further confirmed SNAI2 as a critical downstream effector mediating GPATCH2-driven oncogenic activity in HCC. Mechanistically, GPATCH2 was uncovered to be transcriptionally activated by the transcription factor Yin Yang 1 (YY1), and can mediate the role of YY1 in promoting HCC progression and elevating SNAI2 expression. Taken together, GPATCH2 is a YY1-regulated oncogenic driver that promotes HCC advancement through SNAI2, highlighting its potential as a diagnostic, prognostic, and therapeutic target for HCC. Show less
Understanding the adaptive evolution of brain function in extreme environments remains a central challenge in evolutionary biology. This study investigates the molecular mechanisms underlying cave ada Show more
Understanding the adaptive evolution of brain function in extreme environments remains a central challenge in evolutionary biology. This study investigates the molecular mechanisms underlying cave adaptation by comparing brain transcriptomes of sympatric cave-dwelling ( Show less
Renal clear cell carcinoma (RCC) is the most common type of kidney cancer, and its relationship with kidney fibrosis and inflammatory responses has attracted considerable attention. However, whether c Show more
Renal clear cell carcinoma (RCC) is the most common type of kidney cancer, and its relationship with kidney fibrosis and inflammatory responses has attracted considerable attention. However, whether causal relationships exist among these associations remains unclear, as traditional observational studies are susceptible to confounding factors. To evaluate causal relationships between kidney cancer, kidney fibrosis, and inflammatory factors using Mendelian randomization, and explore tumor microenvironment heterogeneity through single-cell analysis. Based on large-scale GWAS data, bidirectional Mendelian randomization analysis was performed to assess causal relationships between kidney cancer and kidney fibrosis, using MR Egger, inverse variance weighted (IVW), and weighted mode methods. Causal associations between kidney cancer and inflammatory factors including Axin-1, C-C motif chemokine 28, and interleukin-10 receptor subunit were analyzed. Single-cell RNA sequencing data from the GEO database (GSM4819725) was integrated for tumor microenvironment analysis. Bidirectional Mendelian randomization analysis revealed no significant causal relationship between kidney cancer and kidney fibrosis [kidney cancer→kidney fibrosis: IVW OR=0.992(95%CI: 0.913-1.077, P=0.842); kidney fibrosis→kidney cancer: IVW OR=0.922(95%CI: 0.824-1.030, P=0.151)]. However, significant positive causal associations were identified between kidney cancer and multiple inflammatory factors: Axin-1 levels [OR=1.448(95%CI: 1.107-1.894, P=0.007)], C-C motif chemokine 28 [OR=1.287(95%CI: 1.076-1.540, P=0.006)], and interleukin-10 receptor subunit [OR=1.135(95%CI: 1.032-1.248, P=0.009)]. Sensitivity analyses confirmed the robustness of results. Single-cell analysis revealed cellular heterogeneity in the tumor microenvironment, including various cell types such as immune cells, T cells, and NK cells, with pseudotime analysis demonstrating cell differentiation trajectories and dynamic gene expression changes. Mendelian randomization analysis provides genetic evidence for causal relationships between kidney cancer and inflammatory factors, while excluding direct causal associations between kidney cancer and kidney fibrosis. Show less
The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to Show more
The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to be fully characterized. The present investigation delves into the involvement of ANGPTL4 in the pathological progression of PD, both in vitro and in vivo. PD models were induced by intraperitoneal administration of MPTP and LPS in WT and ANGPTL4 The observations unveiled that ANGPTL4 deficiency exacerbated behavioral aberrations, intensified dopaminergic neuron loss, and stimulated microglial activation along with p21-dependent senescence. There was an elevation in the expression of proinflammatory cytokines in the PD model. Furthermore, the administration of rANGPTL4 protein reversed the observed phenotypes in ANGPTL4 Our findings posit a salutary role for ANGPTL4 in counteracting PD, rendering it a prospective therapeutic target for the development of innovative drugs aimed at treating neuroinflammation-associated neurological diseases, including PD. Show less
Programmed cell death protein 5 (PDCD5) is involved in apoptosis and is regarded as a tumor suppressor in various tumors. However, its role and underlying molecular mechanisms in hepatocellular carcin Show more
Programmed cell death protein 5 (PDCD5) is involved in apoptosis and is regarded as a tumor suppressor in various tumors. However, its role and underlying molecular mechanisms in hepatocellular carcinoma (HCC) remain unclear. PDCD5-overexpressing cell and xenograft tumor models were developed. Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine, wound healing, Transwell, flow cytometry, immunohistochemistry, and hematoxylin-eosin staining were employed to explore the effects of PDCD5 on HCC cell behaviors and tumor growth. The enzyme-linked immunosorbent assay and western blot were used to detect pyroptosis-related marker levels. The molecular mechanisms underlying PDCD5's role in HCC were investigated through transcriptome sequencing and coimmunoprecipitation. SRI-011381, a TGF-β signaling activator, was applied to evaluate the impact of PDCD5 in modulating the TGF-β/Smad2/3/Snail pathway. PDCD5 expression was reduced in HCC cells. Overexpression of PDCD5 inhibited HCC cell proliferation, migration, invasion, and xenograft tumor growth. Additionally, PDCD5 overexpression promoted apoptosis and pyroptosis, with corresponding increases in inflammatory factors and Caspase-1, GSDMD, and NLRP3 protein levels. Mechanistically, PDCD5 bound to receptor-regulated Smads (Smad2/3), inhibiting the TGF-β pathway. Treatment with the TGF-β pathway activator SRI-011381 significantly counteracted the inhibitory effects of PDCD5 overexpression on HCC progression. Our findings suggest that PDCD5 impedes the progression of HCC by promoting pyroptosis via regulation of TGF-β/Smad2/3/Snail pathway, which could be a possible therapeutic target for HCC. Show less