Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac h Show more
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac hypertrophy. SMURF2 (SMAD-specific E3 ubiquitin ligase 2) is an important member of NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) family of HECT E3 ubiquitin ligases. In this study we investigated the regulatory role of SMURF2 in cardiac hypertrophy. Experiment models were established in mice by transverse aortic constriction (TAC) in vivo, as well as in neonatal rat cardiomyocytes (NRCMs) by treatment with angiotensin II (Ang II, 1 μM) in vitro. We showed that the expression levels of SMURF2 were significantly elevated in cardiac tissues from patients with cardiac hypertrophy and the two experiment models. In NRCMs, SMURF2 knockdown or treatment with a specific SMURF2 inhibitor heclin (8 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, evidenced by reduced mRNA levels of Anp, Bnp and β-Mhc as well as cell surface. Prophylactic or therapeutic administration of heclin (10 mg·kg Show less
Miao Sun, Yan Liu, Maolin Liu+5 more · 2025 · Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · Taylor & Francis · added 2026-04-24
Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutatio Show more
Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutations in more than 50 genes. We aimed to conduct an etiological analysis of a CHH Chinese family and summarize the clinical presentations and genetic changes of reported similar cases. Whole-exome sequencing (WES) was performed to identify the molecular cause in the proband. In silico tools were employed to analyze the pathogenicity of the variants. Reported cases with similar clinical features and associated genes were summarized by searching through PubMed/MEDLINE using keywords 'FGFR1,' 'CHH,' and 'Kallmann syndrome (KS).' Genetic analysis revealed a novel likely pathogenic deletion mutation in the FGFR1 gene (NM₀₂₃₁₁₀.3: c.263₂₆₄del (Val88Alafs*22)) in a Chinese family exhibiting micropenis and underdeveloped testes. A total of 38 cases with CHH or KS have been previously reported. This study identified a novel FGFR1 deletion variant responsible for CHH, expanding the known mutational spectrum of FGFR1. Typical manifestations include delayed puberty and diverse presentations. The genotype-phenotype correlation in CHH remains unclear and may involve oligogenic effects and epigenetic regulation. Show less
Obesity is a major global public health issue linked to a wide range of chronic diseases. Understanding its complex causal pathways requires robust analytical methods. Mendelian randomization (MR), wh Show more
Obesity is a major global public health issue linked to a wide range of chronic diseases. Understanding its complex causal pathways requires robust analytical methods. Mendelian randomization (MR), which employs genetic variants as instrumental variables, effectively addresses confounding and reverse causation and has become a key tool in obesity research. This review summarizes the development of MR methodologies, from single-sample to multivariable, mediation, and time-series models, and highlights key findings from the past decade. MR studies have revealed causal associations between obesity and nine major disease categories, including cardiovascular, metabolic, cancer, psychiatric, respiratory, renal, reproductive, musculoskeletal, and dermatological disorders. Obesity influences disease risk through mechanisms involving energy metabolism, hormonal regulation, and inflammation, with heterogeneity by age, sex, and fat distribution. Key genes such as Show less
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompl Show more
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompletely defined. Here, we found that BAF60a functions as a chromatin regulator that sustains biphasic GSIS and preserves β cell function under metabolic stress conditions. BAF60a was downregulated in β cells from obese and diabetic mice, monkeys, and humans. β cell-specific inactivation of BAF60a in adult mice impaired GSIS, leading to hyperglycemia and glucose intolerance. Conversely, restoring BAF60a expression improved β cell function and systemic glucose homeostasis. Mechanistically, BAF60a physically interacted with Nkx6.1 to selectively modulate chromatin accessibility and transcriptional activity of target genes critical for GSIS coupling in islet β cells. A BAF60a V278M mutation associated with decreased β cell GSIS function was identified in human donors. Mice carrying this mutation, which disrupted the interaction between BAF60a and Nkx6.1, displayed β cell dysfunction and impaired glucose homeostasis. In addition, GLP-1R and GIPR expression was significantly reduced in BAF60a-deficient islets, attenuating the insulinotropic effect of GLP-1R agonists. Together, these findings support a role for BAF60a as a component of the epigenetic machinery that shapes the chromatin landscape in β cells critical for glucose sensing and insulin secretion. Show less
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contr Show more
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contributing to stroke remains poorly understood. This study aims to investigate the association between the apoB/apoA1 ratio and intracranial or extracranial atherosclerosis. We enrolled 408 patients with acute ischemic stroke who had never been treated with statins or fibrates. Based on the images from computed tomography angiography (CTA), the patients were categorized into four groups: intracranial atherosclerosis stenosis (ICAS, n = 136), extracranial carotid atherosclerosis stenosis (ECAS, n = 45), combined intracranial and extracranial atherosclerosis stenosis (COAS, n = 73), and non-cerebral atherosclerosis stenosis (NCAS, n = 154). Demographic characteristics, clinical factors, and serum lipid levels were collected and then compared across groups. The apoB/apoA1 ratio was significantly higher in patients with ICAS, ECAS and COAS compared to those in the NCAS group. Multivariable logistic regression analysis demonstrated that the ApoB/ApoA1 ratio was independently associated with ICAS, but not with ECAS. ROC curve analysis showed that the ApoB/ApoA1 ratio had a good diagnostic ability for ICAS, with an area under the curve (AUC) of 0.764, an optimal cut-off value of 0.8122, a sensitivity of 81.3%, and a specificity of 59.8%. An higher apoB/apoA1 ratio is associated with ICAS in ischemic stroke patients. Show less
This study aimed to investigate the anti-tumour effect and the possible molecular mechanism of Tianma granules on colorectal cancer (CRC). The therapeutic effect of Tianma granules on CRC cell lines ( Show more
This study aimed to investigate the anti-tumour effect and the possible molecular mechanism of Tianma granules on colorectal cancer (CRC). The therapeutic effect of Tianma granules on CRC cell lines (HT116 and SW480) and AOM/DSS-induced CRC mouse models was evaluated. Tianma granules can attenuate weight loss and increase the survival rate of CRC mice, restore reduced colon length, reduce tumour numbers and increase goblet cell numbers in CRC mice. Tianma granules also downregulated the level of CRC-specific markers (COX2 and MUC2), inhibited the inflammation (decreased TNF-α, IL-1β, IL-6 levels and increased INF-γ level), and promoted apoptosis (decreased TUNEL positive cell rate; decreased Bax and Cleaved caspase3 protein levels and increased Bcl2 level) in CRC mice. In vitro, Tianma granules can inhibit the viability, proliferation, migration and invasion of CRC cells, while promoting cell apoptosis, cell cycle arrest and cell senescence. Tianma granules promoted AXIN1 protein levels and inhibited p-GSK-3β, β-catenin, Wnt5a and Cyclin D1 and c-Myc protein levels. Moreover, the network pharmacology analysis and in vitro validation revealed berberine might be the key compound responsible for Tianma granules' pharmacological actions. In conclusion, Tianma granules can inhibit inflammation and tumour progression in AOM/DSS-induced CRC mice, as well as inhibit CRC cell malignant phenotype. The protection of Tianma granules against CRC may be achieved by inhibiting the Wnt signalling pathway. Show less
Min Xiao, Ying-Ying Chen, Juan Yu · 2025 · The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · Taylor & Francis · added 2026-04-24
The research on Apolipoprotein A-1 (ApoA-1), Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) ratio, and preterm birth was limited to the first and second trimesters. No studies have been conducted i Show more
The research on Apolipoprotein A-1 (ApoA-1), Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) ratio, and preterm birth was limited to the first and second trimesters. No studies have been conducted in the third trimester, and thus this study aimed to investigate the association between ApoA-1, ApoB/ApoA-1 ratio, and preterm birth in patients with gestational diabetes mellitus (GDM) in the third trimester. This study collected the data of single pregnant women of age at pregnancy 16-49 years with GDM who were in the third trimester and gave birth in the Obstetrics department, Hangzhou Linping District Women & Children Hospital from December 1, 2023, to April 20, 2024. The patients were divided into preterm birth group and term birth group according to whether they had preterm birth or not. The restricted cubic spline analysis was used to explore whether there was a linear relationship between ApoA-1, ApoB/ApoA-1 ratio, and preterm birth. The relationship between ApoA-1, ApoB/ApoA-1 ratio, and preterm birth in patients with GDM was explored using trend analysis. The receiver operating characteristic and Decision Curve Analysis were conducted to evaluate the predictive efficacy and clinical benefits of ApoA-1, ApoB/ApoA-1 ratio in predicting preterm birth in patients with GDM. There was a linear relationship between ApoA-1, ApoB/ApoA-1 ratio, and preterm birth. The higher the ApoA-1 level, the lower the risk of preterm birth; the higher the ApoB/ApoA-1 ratio, the higher the risk of preterm birth. ApoA-1, ApoB/ApoA-1 ratio in pregnant women with GDM in the third trimester were associated with preterm birth. Show less
Atherosclerosis (AS), a chronic inflammatory disease linked to oxidative stress and lipid imbalance, remains a major cardiovascular threat. Traditional herbs Salvia miltiorrhiza and Carthamus tinctori Show more
Atherosclerosis (AS), a chronic inflammatory disease linked to oxidative stress and lipid imbalance, remains a major cardiovascular threat. Traditional herbs Salvia miltiorrhiza and Carthamus tinctorius exhibit multi-target anti-AS potential, yet their compositional complexity limits clinical translation. This study aimed to systematically identify core anti-AS components from these herbs and enhance their anti-AS efficacy via machine learning-aided screening and nanotechnology-driven codelivery. We initially pioneered a machine learning-aided hybrid strategy integrating network pharmacology and quantitative activity relationship (QSAR) modeling to identify four core anti-AS polyphenols (i.e., salvianic acid A, salvianolic acid B, protocatechuic acid, and hydroxysafflor yellow A). Subsequently, a quaternary metal-phenolic network (SSPH-MPN) was engineered for plaque-targeted codelivery, optimized via the median-effect principle for achieving a synergistic effect based on ROS scavenging efficacy. The optimized SSPH-MPN was characterized by a series of studies, including molecular dynamics simulations, UV, DLS, TEM, FTIR, XPS, and ICP-MS. The anti-AS effect of the optimized SSPH-MPN was evaluated by monitoring oxidative status (ROS levels, antioxidant enzymes SOD, GSH-Px, MDA, T-AOC), inflammatory markers (IL-1β, IL-6, TNF-α), lipid metabolism (DiI-oxLDL uptake, cholesterol efflux, blood lipid levels, lipid accumulation), and plaque areas. The results demonstrated that the optimized SSPH-MPN showed great efficiency in inhibiting lipid uptake and accumulation, and mediating cholesterol efflux in RAW 264.7 cells, and exhibited improved lipid metabolism, attenuated oxidative stress and inflammation, thus acquired diminished plaque area in apoE Show less
Diabetic retinopathy (DR) is the main cause of blindness worldwide, and its prevalence rate is constantly rising. More in-depth exploration of its risk factors and pathogenic mechanisms is needed. Thi Show more
Diabetic retinopathy (DR) is the main cause of blindness worldwide, and its prevalence rate is constantly rising. More in-depth exploration of its risk factors and pathogenic mechanisms is needed. This study systematically identified potential therapeutic targets for DR by evaluating causal effects of 16,989 genes and 2,923 proteins on DR/subtypes via two-sample Mendelian randomization (MR), validated with colocalization/Summary-data-based Mendelian randomization (SMR). National Health and Nutrition Examination Survey (NHANES) 1999-2010 cross-sectional data (weighted logistic/Restricted cubic spline (RCS)) pinpointed key risk factors; MR explored their links to DR subtypes. Bioinformatics (bulk and single-cell transcriptomics) analyzed molecular mechanisms of shared targets (gene expression, immune infiltration, pathway enrichment). Machine learning selected key targets for models. Finally, two-step mediation MR examined how targets regulate DR via risk factors. This study identified 64 core targets with causal links to DR. Subtype analysis revealed 2,128 causal genes and subtype-specific targets (e.g. 52 for background DR, 66 for proliferative DR). SMR validated these findings. NHANES data highlighted body mass index (BMI), stroke, hypertension (HBP), and C-reactive protein (CRP) as key DR risk factors, confirmed by MR. Transcriptomics identified 29 differentially expressed genes associated with both risk factors and DR, linked to immune cell regulation. Machine learning selected core targets (LY9, WWP2, etc.) and built a nomogram for DR risk prediction. Functional enrichment showed these targets enriched in chemokine/cytokine and immune-inflammatory pathways. Two-step mediation MR further revealed LY9, ARHGAP1, and WWP2 influence DR subtypes via regulating BMI, CRP, and HBP. This study systematically elucidates the key risk factors, potential molecular mechanisms, and core regulatory targets of DR through multi-omics integration, causal inference, and bioinformatics approaches. The results indicate that inflammation, immune dysregulation, and metabolic disorders play crucial roles in the pathogenesis of DR. Key genes such as LY9, ARHGAP1, and WWP2 could serve as potential intervention targets, offering theoretical foundations and strategic support for early warning and precision treatment of DR. Show less
In Traditional Chinese Medicine (TCM), dampness is a pathogenic factor arising from impaired production and transportation of bodily fluids. While Fuling Zexie decoction (FLZXD) has demonstrated thera Show more
In Traditional Chinese Medicine (TCM), dampness is a pathogenic factor arising from impaired production and transportation of bodily fluids. While Fuling Zexie decoction (FLZXD) has demonstrated therapeutic efficacy in dampness constitution (DC) treatment, the material basis underlying its constitutional modulatory effects remains unclear. This study proposes objective indicators for the differentiation and therapeutic evaluation of DC and elucidates the material basis of FLZXD in DC treatment. Serum exosome proteomic profiling was conducted across two independent cohorts to identify DC-related indicators and assess the therapeutic efficacy of FLZXD in DC-associated hyperlipidemia (DC-hyperlipidemia). The bioactive compounds of FLZXD were prioritized through a comprehensive analysis of patent documentation and network pharmacology, with subsequent validation of DC-related targets using enzyme-linked immunosorbent assay (ELISA). Proteomic analysis of serum exosomes revealed signatures that differentiate individuals with a balanced constitution (BC) from those with DC. The differentially expressed proteins (DEPs) were enriched predominantly in pathways related to the complement cascade and cardiovascular diseases. FLZXD demonstrated therapeutic efficacy against DC-hyperlipidemia, as evidenced by the reversal of DEPs expression following treatment, which was supported by the patentable findings and network pharmacology analysis. Through experimental validation and pharmacological evidence, the active herbs of FLZXD (Fuling, Zexie and Baizhu, collectively referred to as FZB) were identified, and a total of 73 putative therapeutic targets involved in the dampness-resolving effects of FZB were revealed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment further confirmed that FLZXD exerts its anti-dampness effects primarily through regulation of the complement and coagulation cascades. Among eight candidate indicators specifically associated with DC, four proteins were validated via ELISA, indicating potential utility for the differentiation of DC. The sensitivity (%), specificity (%), fold change (FC), p-value, and area under the curve (AUC) for each indicator were as follows: apolipoprotein B-100 (APOB) (100.00, 80.00, 0.63, 0.0051, 0.94), complement factor H-related protein 1 (CFHR1) (90.00, 100.00, 0.55, 0.0001, 0.98), alpha-1-acid glycoprotein 1 (ORM1) (100.00, 80.00, 0.71, 0.0043, 0.92), and pigment epithelium-derived factor (SERPINF1) (90.00, 70.00, 0.66, 0.0002, 0.87). The integrative approach, combining proteomic profiling, network pharmacology analysis, and clinical validation, establishes an integrative approach for research on TCM constitutions. This approach provides (1) molecular insights into the differentiation of DC, (2) a foundation for mechanism-based, targeted therapeutic strategies, and (3) enhanced patient stratification to support personalized treatment approaches. Show less
The efficacy and mechanism of Fufang Danshen dripping pills (FFDS) in the secondary prevention of stable coronary heart disease (SCHD) is currently undetermined. This study aims to investigate the eff Show more
The efficacy and mechanism of Fufang Danshen dripping pills (FFDS) in the secondary prevention of stable coronary heart disease (SCHD) is currently undetermined. This study aims to investigate the efficacy and preliminary mechanism by which FFDS may impact the progression of SCHD. Based on randomization, we administered oral FFDS to 30 patients with SCHD in addition to conventional treatment for 30 days. After treatment, three-months major adverse cardiovascular events (MACE) were assessed as the primary outcome. Additionally, we evaluated the patients' Seattle Angina Questionnaire score, blood pressure, circulating levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, platelets, alanine aminotransferase, aspartate aminotransferase, serum creatinine, and fasting blood glucose as the secondary outcomes. Furthermore, we utilized mass spectrometry analysis, network pharmacology, and lipidomics to predict the potential mechanisms of FFDS in the treatment of SCHD. Following treatment, FFDS demonstrated significant improvements in serum triglyceride levels ( In individuals with SCHD, the administration of FFDS has been shown to effectively reduce circulating triglyceride levels and decrease the frequency of angina episodes. This therapeutic effect is likely due to the active components of FFDS targeting key proteins: LPL, CD36, FABPpm, L-FABP, LCAT, and CEPT. https://www.chictr.org.cn/, identifier (ChiCTR2400080149). Show less
Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population Show more
Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives. We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of a statin plus blood pressure lowering). The Lp(a) testing intervention was compared to standard of care. The primary analyses were conducted from the Australian and UK healthcare perspectives in 2023AUD/GBP. A cost adaptation method estimated cost-effectiveness in multiple European countries, Canada, and the USA. Among 10,000 individuals, 1,807 had their treatment modified from Lp(a) testing. This led to 217 and 255 quality-adjusted life years gained in Australia and the UK, respectively, with corresponding incremental cost-effectiveness ratios of 12,134 (cost-effective) and -3,491 (cost-saving). From a societal perspective, Lp(a) testing saved $85 and £263 per person in Australia and the UK, respectively. Lp(a) testing was cost-saving among all countries tested in the cost adaptation analysis. Lp(a) testing in the primary prevention population to reclassify CVD risk and treatment is cost-saving and warranted to prevent CVD. Show less
This study aimed to investigate serum inflammatory factor levels of polycystic ovary syndrome (PCOS) in female patients with bipolar disorder (BD) to explore the related inflammatory molecular mechani Show more
This study aimed to investigate serum inflammatory factor levels of polycystic ovary syndrome (PCOS) in female patients with bipolar disorder (BD) to explore the related inflammatory molecular mechanisms preliminarily. The study recruited 72 female drug-naïve patients with BD and 98 female healthy controls (HCs). Demographic information, menstrual cycles, sex hormone levels, and ovarian ultrasound data were collected from them. Additionally, their serum inflammatory factor levels and the proteomics of peripheral blood mononuclear cells were analyzed. The levels of interleukin (IL)-8 and IL-13 were significantly higher in patients with BD than in HCs (p < 0.05), and the IL-8 level was higher in BD patients with PCOS than in those without (adjusted p = 0.07). Bioinformatics analysis revealed that downregulated genes with significant differences between the two groups were all involved in immune-inflammatory-related pathways, and the expression of downregulated genes BTN3A2, MAP2K5, JCHAIN-B, and DMAP1 showed substantial differences and consistent trends between the two groups. IL-8-related chronic inflammatory response is closely associated with PCOS in BD patients, and genes such as BTN3A2 may mediate this chronic inflammatory response by negatively regulating the abnormal differentiation of T helper 17 cells, serving as one of the mechanisms underlying its pathogenesis. Show less
The study aimed to investigate the role of carbohydrate-responsive element-binding protein (ChREBP) in the pathogenesis of pulmonary fibrosis (PF) by assessing its impact on fibrotic protein expressio Show more
The study aimed to investigate the role of carbohydrate-responsive element-binding protein (ChREBP) in the pathogenesis of pulmonary fibrosis (PF) by assessing its impact on fibrotic protein expression, fibroblast proliferation, and apoptosis in lung tissues. The PF model was established using bleomycin, and pathological changes in lung tissues were assessed through histopathological analysis. Expression levels of inflammatory markers and fibrotic proteins, including ChREBP, were measured using Western blot and ELISA. Additionally, human embryonic lung fibroblasts (MRC-5) were transfected with ChREBP overexpression or silencing vectors following TGF-β1 induction to examine changes in cellular behavior, including viability, apoptosis, and fibrotic protein expression. The PF model group showed significant alveolar structural abnormalities and elevated levels of TNF-α, MMP-7 and TGF-β1. ChREBP expression was markedly increased in fibrotic tissues (P < 0.05). In vitro, ChREBP overexpression in MRC-5 cells enhanced fibrotic protein levels, increased cell viability, and reduced apoptosis rates. Conversely, silencing ChREBP reduced fibrotic protein expression, inhibited fibroblast proliferation, and increased apoptosis (P < 0.05). These findings suggest that ChREBP plays a key role in modulating fibrosis-related pathways in PF. ChREBP is substantially upregulated in PF and plays a key role in promoting fibroblast proliferation and inhibiting apoptosis. These findings suggest that targeting ChREBP may present a novel therapeutic strategy for treating pulmonary fibrosis by modulating fibrotic and apoptotic pathways. Show less
While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposi Show more
While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposition underlying suicidal behaviors in diverse populations. This study aimed to conduct a large-scale investigation of the suicidality spectrum (SP) to generate new insights into its biology and epidemiology. Leveraging ancestrally diverse participants (SI N This study provides convergent genetic evidence for both shared and phenotype-specific components of suicidal behaviors and delineates their associated factors spanning from proximal clinical and behavioral traits to more distal social determinants. These findings refine our understanding of the etiology of suicidal behaviors and may inform targeted strategies for suicide prevention in both clinical and public health settings. Show less
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection te Show more
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB-ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G') increases over time, reaching about 1000 Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB-ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB-ECM treatment. Overall, this new injectable hydrogel based on FSB-ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure. Show less
Alterations in the fibroblast growth factor receptor 3 (FGFR3) gene have been noted in human diseases, including bladder cancer and urothelial carcinoma (UC). Erdafitinib was approved for the treatmen Show more
Alterations in the fibroblast growth factor receptor 3 (FGFR3) gene have been noted in human diseases, including bladder cancer and urothelial carcinoma (UC). Erdafitinib was approved for the treatment of UC but is limited by the progression of on-target gatekeeper resistance mutations. Several heterobifunctional FGFR degraders have been developed as potential therapeutic agents to block FGFR1 or FGFR2 signaling. However, to date, none of the FGFR3-active degraders have been identified. Herein, we report the discovery of LC-MF-4, the first efficient FGFR3 degrader, for the treatment of cancers harboring FGFR3 alterations. Proteomic analysis revealed that LC-MF-4 exhibits exceptional proteomic selectivity for FGFR3 degradation. In FGFR3-TACC3 fusion-positive cells, LC-MF-4 exerted its effects by suppressing the expression of genes involved in mitochondrial biogenesis and ATP synthesis. This study demonstrated robust antitumor activity of LC-MF-4 in the Ba/F3-FGFR3-TACC3 xenograft model, highlighting its potential for the treatment of FGFR3-altered cancers. Show less
2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is a common environmental contaminant and widely detected in aquatic surroundings, while only a few reports exist on the hazard mechanism in economic aquati Show more
2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is a common environmental contaminant and widely detected in aquatic surroundings, while only a few reports exist on the hazard mechanism in economic aquatic animals. It has been shown that 40 and 4000 ng/g of BDE-47 dietary exposure over 42 days significantly increased the levels of blood triglycerides, glucose, and liver glycogen in carp ( Show less
Postmenopausal women are at elevated risk for osteoporosis and dysregulated lipid metabolism. While the relationship between conventional lipid markers and bone mineral density (BMD) remains controver Show more
Postmenopausal women are at elevated risk for osteoporosis and dysregulated lipid metabolism. While the relationship between conventional lipid markers and bone mineral density (BMD) remains controversial, the association between apolipoprotein B-100 (ApoB-100) (an established independent predictor of atherosclerosis) and bone metabolism in postmenopausal women remains poorly understood. This study investigated the relationship between ApoB-100 and lumbar BMD in postmenopausal women, with specific focus on potential inflammatory and platelet-mediated pathways. We conducted a cross-sectional study of 1,429 postmenopausal women who underwent health screening at the First Affiliated Hospital of Xinxiang Medical University between January 2022 and December 2024. ApoB-100 levels were measured by immunoturbidimetry, and lumbar BMD was assessed using low-dose chest CT imaging. Participants were stratified into tertiles based on ApoB-100 levels. We employed univariate and multivariate regression analyses to evaluate the relationship between lumbar BMD and ApoB-100. Generalized additive models with smooth curve fitting were used to characterize the linear relationship. Subgroup analyses assessed the consistency of associations across different populations, while mediation models quantified the intermediary roles of the neutrophil-to-lymphocyte ratio (NLR) and platelet count. After multivariate adjustment, ApoB-100 demonstrated a significant independent negative correlation with lumbar BMD (β=-6.37, 95%CI: -9.26 to -3.49). This association was more pronounced in women younger than 60 years (β=-10.18, 95%CI: -13.94 to -6.42), those with BMI≥28kg/m² (β=-10.73, 95%CI: -15.31 to -0.86), and those without hypertension (β=-7.3, 95%CI: -10.42 to -4.19). Mediation analysis revealed that NLR accounted for 8.17% of the negative association between ApoB-100 and lumbar BMD, while platelet count showed a suppressive indirect association (20.60%). ApoB-100 exhibits an independent negative association with lumbar BMD in postmenopausal women, partially mediated through inflammatory and platelet pathways. These findings support the potential utility of ApoB-100 as a biomarker for osteoporosis risk assessment in postmenopausal women, particularly within specific high-risk subgroups. Show less
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, infla Show more
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, inflammatory factors, and GSD remain unclear. The aim of this study is to explore the causal relationships among these 3 factors. This study employed 2-sample Mendelian Randomization (TSMR) and 2-step MR to investigate the causal relationships and potential mediation effects among 91 inflammatory factors, 6 lipid metabolism-related molecules (HDL-C, LDL-C, TG, total cholesterol, ApoA1, and ApoB), and GSD. We opted for 4 distinct MR analysis methods including inverse variance weighted method, weighted median method, MR-Egger regression method and MR-PRESSO analysis. Sensitivity analyses included MR-Egger intercept tests, Cochran's Q statistic, Steiger tests, and leave-one-out analyses. Product of coefficients method was used to estimate mediation proportion. TSMR analysis revealed that every 1-unit increase in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), the risk of GSD decreased by 16.5%, 10.2%, 8.4%, and 13.1%, respectively. Inflammatory factors such as Natural killer cell receptor 2B4 (CD244), Macrophage colony-stimulating factor 1 (CSF-1), and interleukin-18 receptor 1 (IL-18R1) were identified as risk factors for GSD, while Fibroblast growth factor 19 levels (FGF19), Interleukin-1-alpha levels (IL-1α), and Interleukin-8 levels (IL-8) were found to be protective. Mediation analysis through 2-step MR identified potential pathways involving ApoA1--IL-8--GSD (P = .084) and IL-1α--ApoB--GSD (P = .117). This study provides robust evidence of causal links between specific lipid metabolites and GSD, as well as suggestive causal associations for several inflammatory factors. However, mediation analysis did not support significant roles for lipids or inflammatory factors as mediators in GSD pathogenesis. Future research could be further pursued in areas such as drug target intervention and mechanistic studies. Show less
Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated intera Show more
Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated interactions among the individual responsive parts restrict the advanced design of multimodal responsive photonic materials. Inspired by stimuli-responsive color change in chameleon skin, a simple and effective photo-crosslinking strategy is proposed to construct hydroxypropyl cellulose (HPC) based hydrogels with multiple responsive structured colors. By controlling UV exposure time, the structural color of HPC hydrogels can be effectively controlled in a full-color spectrum. At the same time, HPC hydrogels showcase temperature and mechanical dual-responsive structural colors. In particular, the microstructure of HPC hydrogels undergoes a transition from the chiral nematic phase to the nematic phase under the action of external stretching, leading to a significant reflection of circularly polarized light (CPL) to linearly polarized light (LPL). Given the diverse responsiveness exhibited by HPC hydrogels and their unique structural transition properties under external forces, we have explored their potential applications as dynamic anti-counterfeiting labels and optical skins. This work reveals the great possibility of using structural colored cellulose hydrogels in multi-sensing and optical displays, opening up a new path for the exploration of next-generation flexible photonic devices. Show less
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Al Show more
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Although the RNA moiety of most R-loops originates from linear transcripts, circular RNAs (circRNAs), outputs from back-splicing, can also hybridize with the complementary strand of a DNA duplex. However, how circRNA-associated R-loops (ciR-loops) are monitored remains elusive. Here, we identify the DEAD-box RNA helicase Brr2 as an evolutionarily-conserved ciR-loop repressor with dual roles in inhibiting circRNA generation and resolving harmful ciR-loops. Accumulation of ciR-loops caused by loss-of-function of this dual-action factor induces antisense transcription and premature transcription termination for many genes and generates significant DNA damage, which further leads to a series of defects in DNA replication, cell division and cell proliferation. We propose that functional integration of multilayered regulation by a single protein can be an efficient double protection against genome instability. Show less
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of Show more
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of chlorogenic acid (CHA), a multifunctional natural active compound, in AD therapy by developing a trifunctional nanocarrier (MC-H/R/si). CHA was effectively conjugated with iron-based metal-organic frameworks (MIL/Fe-100) through chelation interaction. The resulting nanocomplex (MC) not only enhances the bioavailability of CHA but also facilitates a synergistic antioxidant effect between CHA and MIL/Fe-100. Importantly, CHA can chelate Zn Show less
Abnormal glymphatic system may play a critical role in amyloid-β (Aβ) accumulation in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients. This study aims to use diffusion tensor ima Show more
Abnormal glymphatic system may play a critical role in amyloid-β (Aβ) accumulation in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients. This study aims to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) and perivascular space volume fraction (PVSVF) to investigate the aberrant glymphatic functions and the association between Aβ deposition and clinical symptoms in AD spectrum. The ALPS index was significantly lower in AD patients compared to MCI and normal controls (NC) groups. Additionally, the AD group showed a significantly higher PVSVF in hippocampus (HP) compared to NC group. No notable variations were observed in the ALPS index or PVSVF across various regions when comparing the MCI group to the NC group. Apolloprotein E (APOE) ε4 + group showed significantly higher PVSVF-HP and PVSVF in basal ganglia compared to APOE ε4 − group. All participants’ HP volume, lower cognitive scores, and higher Our findings demonstrate that glymphatic dysfunction is associated with cognitive decline, underscoring the critical roles of Aβ pathology and the APOE genotype in mediating this relationship. Further exploration of glymphatic function holds significantly promise for advancing research on AD pathogenesis. The online version contains supplementary material available at 10.1186/s13550-025-01339-y. Show less
People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, a Show more
People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, and the increased risk of MCI and AD is associated with the lack of estrogen during menopause. Previous studies have shown that Tiao Geng Decoction (TGD) may have antioxidant and anti apoptotic properties, which may prevent neurodegenerative diseases. However, whether TGD is effective in improving mild cognitive impairment due to postmenopausal estrogen deficiency and its potential pharmacological mechanisms remain unclear. The aim of this study was to investigate the possible pharmacological mechanisms of TGD in preventing postmenopausal MCI. We utilized RNA-seq technology to screen for differentially expressed genes (DEGs) and enrichment pathways in the hippocampal tissue of different groups of mice. Additionally, we adopted single-cell sequencing technology to study the cell types of Alzheimer's disease (AD) group and Normal Control (NC) group, the differential marker genes of each cell subgroup, and the GO enrichment analysis of each cell type. Both RNA sequencing and single-cell sequencing results showed a significant correlation between TGD and NF-κb pathway in improving mild cognitive impairment in postmenopausal women. The experimental verification results showed that the spatial learning and memory abilities of APP/PS1 model mice were weakened after ovariectomy, and the reproductive cycle on vaginal smears was in the interphase of diestrus. The levels of serum E2, and P-tau181 in mice were significantly down regulated, while the levels of brain tissue homogenate A β 42, IL-1 β, and IL-18 were significantly up-regulated, indicating successful modeling. Combining Western blotting, RT-qPCR, and transmission electron microscopy analyses, it was found that the low estrogen environment induced by oophorectomy can activate the NF-κb signaling pathway, activate the expression of NLRP3 inflammasome and A β secretase BACE1, and induce neuroinflammatory damage in hippocampal astrocytes. These results conform to the modeling characteristics of MCI. After TGD intervention, the spatial learning and memory abilities of MCI mice were significantly improved. The pharmacological validation results indicated that high concentration doses of TGD had a more significant effect on MCI. Subsequently, we used high concentration TGD (0.32 g/ml) as the traditional Chinese medicine group for further validation, protein blotting and RT-qPCR results indicated that TGD can effectively stimulate the secretion of ER α and ER β, inhibit the NF-κb pathway, downregulate BACE1, and inhibit the expression of NLRP3 inflammasome related proteins. In addition, the immunofluorescence results of hippocampal astrocytes showed that TGD can effectively facilitate the expression of AQP1 and significantly lower the sedimentation of A β compared with the model group. Our research suggests that there is a high correlation between a low estrogen environment and the occurrence and development of MCI. TGD may regulate the ERs/NF - κ b/AQP1 signaling pathway, promote estrogen secretion, activate AQP1, reduce A β deposition, reverse MCI neuroinflammatory injury, improve mild cognitive impairment, and prevent the occurrence of AD. This study revealed for the first time that TGD may be a potential new alternative drug for preventing and improving menopausal MCI. Show less
Thrombosis is a life-threatening complication in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study aims to conduct a statistical analysis of the incidence of blood clo Show more
Thrombosis is a life-threatening complication in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study aims to conduct a statistical analysis of the incidence of blood clots and lipid concentrations, and to examine the networks of oxylipins in hospitalised patients with SARS-CoV-2. Serum samples of 1731 hospitalised patients with SARS-COV-2 were used to measure six lipid parameters: total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (apoA), and apolipoprotein B (apoB). Additionally, the lipid profiles and oxidative lipidomics characteristics were examined via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) in SARS-COV-2-positive patients with and without thrombosis. The mortality rate in the SARS-COV-2 thrombosis group was significantly higher at 29.6% compared to the SARS-COV-2 non-thrombosis group at 12.1% (P < 0.0001). The levels of the lipid parameters were closely associated with both thrombosis and SARS-COV-2 severity. Patients with SARS-COV-2 admitted to the hospital exhibited significant changes in oxidative lipid metabolites, specifically in the arachidonic acid (ARA) and docosahexaenoic acid (DHA) classes, compared with those in the control group. Among the thrombus group, 28 oxidative lipid metabolites were found to be differentially expressed compared to the non-thrombus group, and with the most notable variations observed in 20-hydroxyPGF2α and 14(15)-EpETE. Enrichment analysis using KEGG revealed that differential oxidized lipid metabolites mainly concentrated in the ARA and serotonergic synapses metabolism signaling pathway. Our findings indicate a close association between lipid mediators and both SARS-COV-2 and thrombi. Specifically, ARA and serotonergic synapses metabolism signaling pathway may be an important pathogenic factor for thrombosis caused by SARS-COV-2. Furthermore, 20-hydroxyPGF2α and 14(15)-EpETE show promise as potential biomarkers for SARS-CoV-2-induced thrombosis. 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
Yunqi Xie, Haochen Wang, Yajie Zhang+5 more · 2025 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24
Smoking is harmful to health. Cigarette smoke (CS) contains a variety of toxic substances. Studies have found that nicotine, tar, polycyclic aromatic hydrocarbons, etc. in CS can pass through the bloo Show more
Smoking is harmful to health. Cigarette smoke (CS) contains a variety of toxic substances. Studies have found that nicotine, tar, polycyclic aromatic hydrocarbons, etc. in CS can pass through the blood-brain barrier and enter the brain to exert their effects. Moreover, some existing studies have pointed out that CS exposure is closely related to the accelerated pathology of Alzheimer's disease (AD). Transgenic mice with the five familial AD mutations (5xFAD), which are 1-month-old, were used for chronic CS exposure for 100 days. Subsequently, cognitive function and behavioral changes were evaluated through morris water maze and new object recognition tests. The acceleration of pathological changes due to CS exposure was assessed by HE, Tunel and Aβ immunohistochemical staining. Differential expression proteins and metabolites were screened through hippocampal proteomics and metabolomics analyses. Finally, the expression levels of key proteins were verified by Western blot. Compared with unexposed 5xFAD mice, the behavioral results of mice showed that FAD mice after CS exposure exhibited poorer cognitive abilities, with longer latencies in the Morris water maze, and decreased time spent and entries in the target quadrant. The results of pathological sections indicated that the total nuclei density in the DG and CA3 regions of the hippocampus of 5xFAD mice decreased significantly after chronic CS exposure, the number of TUNEL-positive cells increased, and the expression of Aβ42 increased. Multi - omics analysis revealed that CS exposure up - regulated the expression of 46 proteins and down - regulated the expression of 80 proteins in the hippocampus of 5xFAD mice, and caused changes in 92 metabolites. Analysis of the correlation between differential proteins and differential metabolites revealed six key cross-node proteins: Kng1, Hbb-b1, Fabp3, Apoa1, Ilk, and Apoa4. CS exposure may accelerate pathological changes and cognitive impairment in 5xFAD mice by affecting energy metabolism through the PPAR signaling pathway. Show less