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
Protein arginine methyltransferase 5 (PRMT5) complexes with methylosome protein 50 (MEP50) play crucial roles in tumor progress. However, the regulatory mechanism of governing the PRMT5-MEP50 hetero-o Show more
Protein arginine methyltransferase 5 (PRMT5) complexes with methylosome protein 50 (MEP50) play crucial roles in tumor progress. However, the regulatory mechanism of governing the PRMT5-MEP50 hetero-octameric complex remains unclear. Here, we demonstrate that C6orf223, to our knowledge an uncharacterized protein, facilitates PRMT5-MEP50 multiprotein complex assembling, thereby promoting colorectal cancer (CRC) growth and metastasis. C6orf223 forms dimers through disulfide bonds, with its N-terminal arginine-enriched region binding to the C-terminal negatively charged groove of PRMT5, thus stabilizing PRMT5-MEP50 multiprotein and enhancing PRMT5 methyltransferase activity. Consequently, PRMT5-mediated H4R3me2s substantially decreases the expression of the tumor suppressor GATA5, leading to the upregulation of multiple oncogenic target genes including WWTR1, FGFR1, and CLU. Targeting C6orf223 using siRNAs encapsulated in ferritin protein shells effectively suppresses CRC tumor growth and metastasis. Collectively, our findings characterize the role of C6orf223 in facilitating PRMT5-MEP50 hetero-octameric complex assembling and suggest that C6orf223 could serve as a potential therapeutic target for CRC. Show less
Liver and lung are the most common metastatic sites in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a crucial role in the progression and metastasis of CRC. Understanding the Show more
Liver and lung are the most common metastatic sites in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a crucial role in the progression and metastasis of CRC. Understanding the interactions between various types of cells in the TME can suggest innovative therapeutic strategies. Using single-cell RNA sequencing (scRNA-Seq) and clinical samples, fibroblast growth factor-19 (FGF19, rodent FGF15) is found to mediate a significant interaction between CRC cells and cancer-associated fibroblasts (CAFs), activating the hepatic stellate cells (HSCs)-to-CAFs differentiation. In various CRC metastatic mouse models, it is shown that FGF15 has a more pronounced effect on liver metastasis compared to pulmonary metastasis. More importantly, the differentially expressed genes (DEGs) are also identified from the RNA-Seq dataset upon the activation of HSCs by FGF19 and compared the DEGs in matched primary and metastatic mRNA samples from patients with CRC liver metastasis (CRCLM), it is found that the ANGPTL4 gene is significantly associated with HSCs activation. Different mouse models also demonstrated the impact of the FGF19/ANGPTL4 axis on the severity of CRCLM. Importantly, disruption of this axis significantly inhibits CRCLM in vivo. This study is among the first to demonstrate the impact of the FGF19/ANGPTL4 axis on CRCLM, offering a novel therapeutic strategy. Show less
Prior research has consistently demonstrated that higher levels of digital health literacy contribute positively to improved mental health outcomes and overall quality of life among patients. Neverthe Show more
Prior research has consistently demonstrated that higher levels of digital health literacy contribute positively to improved mental health outcomes and overall quality of life among patients. Nevertheless, the interplay between digital health literacy and the experience of perceived stigma-particularly among burn patients-remains underexplored, and the potential heterogeneity within this relationship has not been adequately addressed. This cross-sectional study, conducted from June to July 2025, recruited 534 burn patients (mean age 31.05 ± 9.52 years; 61.0% male) from three tertiary hospitals in Sichuan Province, China. Participants completed validated scales assessing digital health literacy, social support, appearance anxiety, perceived stigma, and demographics. Data were analyzed using Pearson correlations, latent profile analysis (LPA) with fit indices, univariate analyses (chi-square tests and Digital health literacy was negatively correlated with perceived stigma ( This study confirms heterogeneity in digital health literacy and perceived stigma among burn patients, with social support and appearance anxiety as key influencers. Findings support targeted interventions to enhance digital health literacy and reduce perceived stigma, advancing precision psychological care for burn survivors. Show less
GLP-1 has become a prime target for medical treatment due to its significant therapeutic efficacy. However, the activation mechanisms of class B1 GPCRs, including glucagon-like peptides (GLP-1) and gl Show more
GLP-1 has become a prime target for medical treatment due to its significant therapeutic efficacy. However, the activation mechanisms of class B1 GPCRs, including glucagon-like peptides (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), remain poorly understood. This study focuses on understanding the activation mechanisms of the GLP-1 receptor (GLP-1R) by investigating its conformational changes from activated/inactivated to inactivated/activated states. By analyzing the dynamic conformational changes of the receptor during activation, a closure-open transition in the extracellular domain (ECD) and a movement trend of the transmembrane helices are observed, which indicates a similarity to the activation mechanism of class A GPCRs. Furthermore, the binding characteristics of a dual agonist Tirzepatide (LY3298176) is studied in detail and it is revealed that the conserved residues contribute in a similar fashion toward binding to both GLP-1R and GIPR. Mutations in non-conserved residues in Tirzepatide affect the binding affinity, with C-terminal mutations weakening the binding affinity toward GLP-1R, while N-terminal mutations enhancing the affinity to GIPR, resulting in a biased binding mode. These findings enriched our fundamental understanding of GLP-1R/GIPR activation and provided theoretical guidance for the design and development of future peptide-based agonists and offer insights into the optimization of other dual or multi-target agonists. Show less
Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder primarily linked with mutations in Exostosin-1 (EXT1) and Exostosin-2 (EXT2) genes. However, not all HME cases can be exp Show more
Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder primarily linked with mutations in Exostosin-1 (EXT1) and Exostosin-2 (EXT2) genes. However, not all HME cases can be explained by these mutations, and its pathogenic mechanisms are not fully understood. Herein, utilizing whole-exome sequencing and genetic screening with a family trio design, we identify two novel rare mutations co-segregating with HME in a Chinese family, including a nonsense mutation (c.204G>A, p.Trp68*) in EXT1 and a missense mutation (c.893T>G, p.Phe298Cys) in FUT7. Functional assays reveal that the FUT7 mutation affects the cellular localization of FUT7 protein and regulates cell proliferation. Notably, the simultaneous loss of fut7 and ext1 in a zebrafish model results in severe chondrodysplasia, indicating a functional link between FUT7 and EXT1 in chondrocyte regulation. Additionally, we unveil that FUT7 p.Phe298Cys reduces EXT1 expression through IL6/STAT3/SLUG axis at the transcription level and through ubiquitination-related proteasomal degradation at the protein level. Together, our findings not only identify novel germline mutations in FUT7 and EXT1 genes, but also highlight the critical interaction between these genes, suggesting a potential 'second-hit' mechanism over EXT1 mutations in HME pathogenesis. This insight enhances our understanding of the mechanisms underlying HME and opens new avenues for potential therapeutic interventions. 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
To develop and evaluate a predictive model for myocardial injury in patients with advanced gastric cancer treated with fluorouracil plus platinum-based chemotherapy, incorporating baseline characteris Show more
To develop and evaluate a predictive model for myocardial injury in patients with advanced gastric cancer treated with fluorouracil plus platinum-based chemotherapy, incorporating baseline characteristics and inflammatory, nutritional, and atherosclerotic factors. A total of 268 patients with advanced gastric cancer who received this treatment between April 2020 and September 2024 were selected and divided into a training set ( In the training set, 56 patients (29.79%) developed myocardial injury, while 23 patients (28.75%) in the validation set developed myocardial injury, with no statistically significant difference in the incidence or clinical characteristics between the two sets ( This predictive model aids in the early identification of myocardial injury, guiding clinical decision-making and improving prognosis. Show less
Previous researches have indicated the oncogenic effect of circCOL1A2 in several cancers, such as tongue squamous cell carcinoma, gastric cancer, and colorectal cancer. Regrettably, the functions and Show more
Previous researches have indicated the oncogenic effect of circCOL1A2 in several cancers, such as tongue squamous cell carcinoma, gastric cancer, and colorectal cancer. Regrettably, the functions and mechanisms of circCOL1A2 in lung cancer, a disease with the highest global incidence and mortality rates and with 85 % of cases classified as non-small cell lung cancer (NSCLC), remain largely unexplored. Hsa_circ₀₀₈₁₁₁₁ (circCOL1A2) was identified from GSE236879 dataset of Gene Expression Omnibus (GEO) database. Its expression was validated in 37 paired samples of cancerous and adjacent normal tissues from NSCLC patients, as well as in cell lines. The function of hsa_circ₀₀₈₁₁₁₁ was analyzed using CCK-8, Matrigel transwell, Western blot, and immunofluorescence assays in vitro, and by conducting subcutaneous xenograft experiments in mouse. The underlying mechanisms were explored using bioinformatics analysis, RNA pull-down experiments, and RNA immunoprecipitation. High expression of hsa_circ₀₀₈₁₁₁₁ was observed in NSCLC tissues and cell lines. This was positively correlated with the TNM stage and lymph node metastasis of NSCLC patients. Hsa_circ₀₀₈₁₁₁₁ overexpression promoted the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Conversely, its downregulation showed the opposite effects. In vivo studies revealed that silencing hsa_circ₀₀₈₁₁₁₁ inhibited tumor growth, EMT, and MMP9 expression in tumor tissues. Mechanically, hsa_circ₀₀₈₁₁₁₁ enhanced Slug mRNA stability by interacting with the RNA-binding protein IGF2BP2. Taken together, hsa_circ₀₀₈₁₁₁₁ is an oncogenic circRNA that promotes NSCLC malignancy by regulating IGF2BP2-mediated Slug mRNA stability. Hsa_circ₀₀₈₁₁₁₁ has the potential to be a diagnostic and therapeutic target for NSCLC. Show less
Foamy macrophages are pivotal contributors to the development and progression of atherosclerotic plaques, posing a substantial threat to human health. Presently, there is no pharmaceutical interventio Show more
Foamy macrophages are pivotal contributors to the development and progression of atherosclerotic plaques, posing a substantial threat to human health. Presently, there is no pharmaceutical intervention available to effectively eliminate foamy macrophages. In this study, we demonstrate that probiotic membrane vesicles (MVs) can induce atherosclerotic plaque regression by modulating foamy macrophages. MVs isolated from Lactobacillus rhamnosus exhibited a specific uptake by foamy macrophages. Near-infrared fluorescence (NIRF) imaging, aortic oil red O staining, and hematoxylin and eosin staining showed reductions in the plaque area following MVs treatment. Mechanistically, bioinformatics analysis provided insights into how MVs exert their effects, revealing that they promote lipid efflux and macrophage polarization. Notably, MVs treatment upregulated NR1H3, which in turn increased ABCA1 expression, facilitating lipid efflux from foamy macrophages. Moreover, MVs shifted macrophage polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, highlighting their potential to create a more protective environment against plaque progression. This study is significant as it introduces MVs as a novel therapeutic platform for the targeted delivery of anti-inflammatory agents to atherosclerotic sites. By specifically modulating macrophage function, MVs hold considerable potential for the treatment of atherosclerosis and related cardiovascular diseases, addressing an unmet need in current therapeutic strategies. Show less
Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have indep Show more
Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have independently evolved specialized musk-secreting glands, representing a striking case of convergent evolution. Through an integrated multi-omics approach, this study identified cyclopentadecanone as a shared key metabolic precursor in musk from both forest musk deer and muskrat, although downstream metabolite profiles diverged between the two lineages. Single-cell RNA sequencing revealed that these specialized apocrine glands possessed unique secretory architecture and exhibited transcriptional profiles associated with periodic musk production, distinct from those in conventional apocrine glands. Convergent features were evident at the cellular level, where acinar, ductal, and basal epithelial subtypes showed parallel molecular signatures across both taxa. Notably, acinar cells in both species expressed common genes involved in fatty acid and glycerolipid metabolism (e.g., Show less
Pesticides increase agricultural productivity, but with the widespread use of pesticides, concerns have arisen about their potential negative impacts on human health and aquatic organisms. Pydiflumeto Show more
Pesticides increase agricultural productivity, but with the widespread use of pesticides, concerns have arisen about their potential negative impacts on human health and aquatic organisms. Pydiflumetofen (PYD) is a novel chiral fungicide, and the potential environmental and health hazards of PYD and its chiral isomers are not sufficiently understood. In this work, zebrafish were employed as a model organism to study the toxicity of PYD, specifically investigating the developmental and cardiovascular toxicities in zebrafish exposed to 0.2 μg/mL of PYD for 72 h. The results showed that PYD severely impeded the development of zebrafish embryos, resulting in abnormal hatching rates, enlarged yolk sacs and shortened body length. In addition, PYD resulted in morphological and functional abnormalities of the embryonic heart and blood vessels, such as pericardial edema, linearization of the heart, impeded vascular production, slowed heart rate, and reduced erythrocyte flow rate. Mechanistically, we found that PYD caused oxidative stress, lipid accumulation and apoptosis in zebrafish. Simultaneously, the expression of genes associated with cardiac (nkx2.5, gata4, tbx5, hand2, has2) and vascular (vegfc, dll4, cdh5, hey2, and notch3) development was altered. Notably, our results indicate that (+)-R-PYD exhibits higher developmental and cardiovascular toxicity than (-)-S-PYD. This paper first reveals the cardiovascular toxicity of PYD and opens new avenues for assessing the environmental and health hazards caused by chiral fungicides. Show less
This study aims to investigate the roles of the EXT1 and FGFR3 genes in the development of osteochondromas, focusing specifically on their potential interactions in chondrocyte proliferation, differen Show more
This study aims to investigate the roles of the EXT1 and FGFR3 genes in the development of osteochondromas, focusing specifically on their potential interactions in chondrocyte proliferation, differentiation, and tumor formation. In vitro, the ATDC5 chondroprogenitor cell line was used to examine the effects of inactivation of both EXT1 and FGFR3. In vivo, a mouse model with dual gene knockout of Ext1 and Fgfr3 was constructed to further explore these genes' roles in tumor formation by observing the incidence and distribution patterns of osteochondromas. The in vitro experiments demonstrated that ATDC5 cells with reduced expression of EXT1 and FGFR3 genes exhibited enhanced chondrogenic differentiation. In vivo, Fgfr3 The EXT1 and FGFR3 genes play crucial regulatory roles in the development of osteochondromas. Deficiencies in Ext1 and Fgfr3 can induce the formation of osteochondromas. Show less
Branched-chain amino acids (BCAAs), including valine, leucine and isoleucine, are essential nutrient signals that influence mammalian animal metabolism. Many enzymes are involved in the metabolism of Show more
Branched-chain amino acids (BCAAs), including valine, leucine and isoleucine, are essential nutrient signals that influence mammalian animal metabolism. Many enzymes are involved in the metabolism of BCAAs, such as branched-chain amino acid transaminases (BCATs), branched-chain α-keto acid dehydrogenase (BCKDH), and BCKDH kinase (BCKDK). The aberrant expression of enzymes involved in BCAA metabolism and an imbalance in BCAA amino acid intake can lead to disordered metabolism. Aberrant BCAA metabolism can lead to several diseases, such as human ovarian disease, including ovarian cancer (OC), polycystic ovary syndrome (PCOS), and premature ovarian failure (POF), which are common gynaecological diseases. The overexpression of BCATs is found in OC, which promotes BCAA catalysis to provide a large amount of energy for tumorigenesis. However, BCKDK is overexpressed in epithelial ovarian cancer (EOC), which promotes proliferation and migration via MEK-ERK. In addition, several studies have reported that high levels of BCAAs are increased in the plasma of PCOS and POF patients. This review focuses on the role of BCAA metabolism and potential management methods for OC, PCOS and POF. Show less
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune sys Show more
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune system due to anti-inflammatory properties. Tigecycline, an antibiotic of the glycylcycline class, is commonly used for severe infections. This study aimed to investigate tigecycline's mechanism on the inflammatory response of sepsis to find new targets for sepsis treatment. The objective included (i) to observe the changes in inflammatory factors in LPS (lipopolysaccharide) induced septic mice after tigecycline administration, (ii) to detect the effect of tigecycline on macrophages NF-κB (nuclear factor kappa B) signalling. For LPS-induced sepsis in mice and intervention with tigecycline, mice were first injected with tigecycline (6.5 mg/kg) via tail vein followed by LPS (15 mg/kg). Luminex analysis was performed on 16 mediators. NF-κB signalling pathway antibody chip detected the expression of target sites in macrophages of the LPS group and tigecycline + LPS group. Tigecycline has inhibitory effects on LPS-induced inflammatory response in septic mice, decreasing the concentrations of IL (interleukin)-6, IL-27, TNF-α (tumour necrosis factor-α), TNF RII, IFN-γ (interferon-gamma), CCL5/RANTES (CC Motif Chemokine Ligand) while increasing IL-6Rα, IL-10, and TWEAK (TNF-related weak inducer of apoptosis). Tigecycline downregulated phosphorylation levels of key sites JNK (c-Jun N-terminal kinase)1/2/3, p-p65 (s468) and p-p105/p50 (s907) in NF-κB signalling. Tigecycline may inhibit the excessive immune response induced by LPS in sepsis, which may cause a potential protective effect on the host through immune regulation. Show less
Sijie Gu, Haoran Feng, Xiaomei Li+10 more · 2025 · Molecular therapy : the journal of the American Society of Gene Therapy · Elsevier · added 2026-04-24
Preventing the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a considerable clinical challenge. In this study, we elucidate the role of WNT5A in accelerating the A Show more
Preventing the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a considerable clinical challenge. In this study, we elucidate the role of WNT5A in accelerating the AKI-to-CKD transition and its underlying mechanisms. Renal biopsies from patients with AKI showed marked upregulation of WNT5A and its receptor, CD146, in proximal tubules, with higher expression in patients with CKD progression. In murine AKI models, Wnt5a knockdown attenuated CKD progression. Conversely, proximal tubular overexpression of Wnt5a exacerbated renal fibrosis in ischemia-reperfusion injury (IRI) mice, which was alleviated by Box5, a specific WNT5A antagonist. In vitro, WNT5A overexpression in transforming growth factor β (TGF-β)-stimulated HK-2 cells promoted CD146 upregulation, activated JNK phosphorylation, and enhanced SNAI1 expression. The genetic silencing of WNT5A/CD146 and JNK inhibition suppresses SNAI1 expression and attenuates fibrotic responses. Mechanistically, JNK-mediated c-JUN phosphorylation promoted its interaction with KLF5 at the SNAI1 promoter, driving renal fibrosis. Elevated serum levels of soluble CD146 correlated with renal function in patients with AKI and were higher in patients exhibiting CKD progression. Inhibition of WNT5A could serve as a therapeutic target for delaying renal fibrosis in AKI progression. Show less
To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a c Show more
To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a convenience sample of 411 older adults with disabilities was recruited from a tertiary hospital in Anhui Province, China. Data were collected using a general information questionnaire, the Chinese version of the Demoralization Scale, and the Active Aging Scale. Latent profile analysis (LPA) was performed based on demoralization subscale scores. Univariate and multinominal analyses were employed to investigate the influencing factors, and the Kruskal-Wallis The prevalence of demoralization syndrome was 49.1%. LPA identified three distinct profiles: the Well-Adapted Group (53.3%), the Disheartened-Helpless Group (23.8%), and the Fully Demoralized Group (22.9%). The Kruskal-Wallis Nearly half of the older adults with disabilities experienced demoralization, with heterogeneous subgroups identified. The active aging status of demoralized subgroups requires urgent attention. These findings suggest the need for targeted interventions tailored to the characteristics of each profile to improve mental health and promote active aging in this population. Show less
This study aimed to explore the molecular pathological mechanisms of the liver in metabolic disease-susceptible transgenic pigs via multiomics analysis. The triple-transgenic (PNPLA3 The TG2 pigs pres Show more
This study aimed to explore the molecular pathological mechanisms of the liver in metabolic disease-susceptible transgenic pigs via multiomics analysis. The triple-transgenic (PNPLA3 The TG2 pigs presented mild metaflammation and insulin resistance (IR) which was similar to WT12 pigs. Compared with the other three groups, the TG12 pigs presented severe hepatocyte ballooning, fat deposition, and portal area fibrosis. The transcriptome data suggested that the TG2 pigs presented upregulated gene expression in the extracellular matrix (ECM). The TG12 pigs presented more severe metaflammation and exhibited imbalanced glycolipid metabolism. Interestingly, genes such as ETNPPL, GABBR2, and BMP8B might be key regulatory targets for liver injury. The metabolome and lipidome suggested that long-chain polyunsaturated fatty acids (LCPUFAs) and phospholipids with corresponding LCPUFAs were remodelled. Importantly, bis(monoacylglycerol) phosphates (BMPs) and sulfatides (SLs) could be the key regulatory metabolites in liver injury. ETNPPL, GABBR2, and BMP8B might be potential therapeutic targets for liver injury. BMPs and SLs might be biomarkers for the diagnosis and treatment of liver diseases. Show less
Pharmaceutical and personal care products (PPCPs), as ubiquitous emerging contaminants, present undercharacterized neuropsychiatric hazards through environmental exposure. This investigation employs c Show more
Pharmaceutical and personal care products (PPCPs), as ubiquitous emerging contaminants, present undercharacterized neuropsychiatric hazards through environmental exposure. This investigation employs convergent multi-omics strategies - integrating toxicogenomic discovery, disease-associated genomic mapping, and transcriptomic profiling - to elucidate mechanistic linkages between PPCPs bioactivity and depressive pathogenesis. Through systematic analysis of Nanjing's aquatic chemical burden (prioritizing dimenhydrinate, ibuprofen, padimate-O, caffeine, and roxithromycin), we identified 3073 conserved molecular targets bridging PPCPs toxicity and depression etiology via Comparative Toxicogenomics Database and GeneCards interrogation. Functional ontology revealed dysregulated pathways encompassing lipidomic remodeling, IL-17-mediated neuroinflammation, and synaptic transmission deficits. Ensembled machine learning algorithms (Lasso regression, XGBoost, random forest) converged on seven high-fidelity candidate biomarkers (HSPA8, CBX1, CD59, CHAF1A, CUX1, ID2, RPL3) demonstrating stress-adaptive, chromatin regulatory, and immunomodulatory functions. Molecular docking predicted strong binding affinities between PPCPs and depression-related proteins, notably dimenhydrinate with CHAF1A (- 6.1 kcal/mol) and HSPA8 (- 6.1 kcal/mol), suggesting multi-target modulation. This work proposes a computational framework to map molecular interactions between specific PPCPs and depression-associated pathways. Candidate targets highlight testable hypotheses for future experimental validation. These findings suggest selected PPCPs with neuroactive properties may warrant further investigation as environmental modifiers of depression risk. Show less
To optimize livestock production of integrated farms, dietary crude fat levels are often increased, making efficient fat utilization crucial. Bile acids are known to improve fat utilization, but their Show more
To optimize livestock production of integrated farms, dietary crude fat levels are often increased, making efficient fat utilization crucial. Bile acids are known to improve fat utilization, but their impact on growth performance and breast muscle development in Zhijiang ducks remains unclear. In this study, a total of 360 twenty-day-old Zhijiang ducks with similar body weights were divided into three groups: the control group (CN) received a basal diet; the high-fat group (FA) received the basal diet plus 1.25 % rapeseed oil; and the high-fat plus bile acids compound (BA) group (FB) received the FA diet supplemented with 250 mg/kg BA for 30 days. Results indicated that the addition of rapeseed oil and BA significantly increased (P < 0.05) average daily gain (ADG) and reduced (P < 0.05) feed conversion ratio (FCR). Slaughter data showed that BA significantly enhanced (P < 0.05) breast muscle weight and percentage while decreasing (P < 0.05) abdominal fat weight. Additionally, BA increased (P < 0.05) the cross-sectional area of breast muscle fibers, total bile acid content, and levels of insulin-like growth factors 1/2 (IGF1/2). Transcriptomic analysis further revealed that BA significantly upregulated (P < 0.05) the levels of PPARα, CPT1α, NR1H4, and CETP in breast muscle. 16S rRNA analysis showed a significant increase (P < 0.05) in the relative abundances of genera Enorma, [Eubacterium nodatum group], Rikenellaceae RC9 gut group, and SP3-e08. Additionally, the Spearman correlation suggested a positive correlation between the genera Olsenella, SP3-e08, Enorma, Rikenellaceae_RC9_gut_group, and [Eubacterium_nodatum_group] with PPARα, CETP, NR1H4, and CPT1α. In contrast, the genera Christensenellaceae_R₇_group and Sutterella exhibited negative correlations with PPARα. These findings provide new insights into the role of BA in promoting growth performance and skeletal muscle development in Zhijiang ducks fed a high-fat diet, with this effect potentially linked to changes in the gut microbiota. Show less
Subjective cognitive decline (SCD) serves as an initial symptom of preclinical Alzheimer's disease (AD). The accumulation of amyloid-beta (Aβ) is acknowledged as a critical risk factor for the eventua Show more
Subjective cognitive decline (SCD) serves as an initial symptom of preclinical Alzheimer's disease (AD). The accumulation of amyloid-beta (Aβ) is acknowledged as a critical risk factor for the eventual progression to mild cognitive impairment or dementia in individuals with SCD, highlighting the necessity for early detection and intervention. Previous studies have identified the retina and choriocapillaris as potential biomarkers for AD; however, these investigations have not thoroughly examined large and medium-sized choroidal vessels. Ultra-wide swept-source optical coherence tomography angiography (SS-OCTA), an innovative noninvasive imaging modality, facilitates rapid and precise quantitative assessment of retinal and choroidal boundaries and vasculature through dynamic scanning, encompassing large and medium-sized choroidal vessels. This study aims to characterize the outer retinal and choroidal vasculature and structure in individuals with SCD, examine the correlation between altered choroidal vasculature parameters and amyloid burden, and the presence of the apolipoprotein E (APOE) ε4 allele in SCD participants, to identify potential ocular biomarkers for high-risk SCD screening. In this study, 57 individuals with SCD and 45 matched normal controls were enrolled. Ultra-wide SS-OCTA was employed to assess the thickness of the outer retina and choroid and the blood flow within the choriocapillaris and large, medium-sized choroidal vessels. Show less
The development of BACE-1 (β-site amyloid precursor protein cleaving enzyme 1) inhibitors is a crucial focus in exploring early treatments for Alzheimer's disease (AD). Recently, graph neural networks Show more
The development of BACE-1 (β-site amyloid precursor protein cleaving enzyme 1) inhibitors is a crucial focus in exploring early treatments for Alzheimer's disease (AD). Recently, graph neural networks (GNNs) have demonstrated significant advantages in predicting molecular activity. However, their reliance on graph structures alone often neglects explicit sequence-level semantic information. To address this limitation, we proposed a Graph and multi-level Sequence Fusion Learning (GSFL) model for predicting the molecular activity of BACE-1 inhibitors. Firstly, molecular graph structures generated from SMILES strings were encoded using GNNs with an atomic-level characteristic attention mechanism. Next, substrings at functional group, ion level, and atomic level substrings were extracted from SMILES strings and encoded using a BiLSTM-Transformer framework equipped with a hierarchical attention mechanism. Finally, these features were fused to predict the activity of BACE-1 inhibitors. A dataset of 1548 compounds with BACE-1 activity measurements was curated from the ChEMBL database. In the classification experiment, the model achieved an accuracy of 0.941 on the training set and 0.877 on the test set. For the test set, it delivered a sensitivity of 0.852, a specificity of 0.894, a MCC of 0.744, an F1-score of 0.872, a PRC of 0.869, and an AUC of 0.915. Compared to traditional computer-aided drug design methods and other machine learning algorithms, the proposed model can effectively improve the accuracy of the molecular activity prediction of BACE-1 inhibitors and has a potential application value. Show less
The objective of this study was to evaluate the effects of dietary fatty acids (FA) saturation and lysophospholipids supplementation on growth, meat quality, oxidative stability, FA profiles, and lipi Show more
The objective of this study was to evaluate the effects of dietary fatty acids (FA) saturation and lysophospholipids supplementation on growth, meat quality, oxidative stability, FA profiles, and lipid metabolism of finishing beef bulls. Thirty-two Angus bulls (initial body weight: 623 ± 22.6 kg; 21 ± 0.5 months of age) were used. The experiment was a completely randomized block design with a 2 × 2 factorial arrangement of treatments: 2 diets with FA of different degree of unsaturation [high saturated FA diet (HSFA) vs. high unsaturated FA diet (HUFA)] combined with (0.075%, dry matter basis) and without lysophospholipids supplementation. The bulls were fed a high-concentrate diet (forage to concentrate, 15:85) for 104 d including a 14-d adaptation period and a 90-d data and sample collection period. No interactions were observed between dietary FA and lysophospholipids supplementation for growth and meat quality parameters. A greater dietary ratio of unsaturated FA (UFA) to saturated FA (SFA) from 1:2 to 1:1 led to lower DM intake and backfat thickness, but did not affect growth performance and other carcass traits. Compared with HSFA, bulls fed HUFA had greater shear force in Longissimus thoracis (LT) muscle, but had lower intramuscular fat (IMF) content and SOD content in LT muscle. Compared with HUFA, feeding the HSFA diet up-regulated expression of ACC, FAS, PPARγ, and SCD1, but down-regulated expression of CPT1B. Compared with feeding HSFA, the HUFA diet led to greater concentrations of c9-C18:1 and other monounsaturated FA in LT muscle. Feeding HUFA also led to lower plasma concentrations of cholesterol, but there were no interactions between FA and lysophospholipids detected. Feeding lysophospholipids improved growth and feed conversion ratio and altered meat quality by increasing muscle pH Results indicated that supplementing a high-concentrate diet with lysophospholipids to beef bulls can enhance growth rate, feed efficiency, meat quality, and beneficial FA. Increasing the dietary ratio of UFA to SFA reduced DM intake and backfat thickness without compromising growth, suggesting potential improvements in feed efficiency. Show less
Yifei Dou, Ying Li, Meng Zhang · 2025 · Wei sheng yan jiu = Journal of hygiene research · added 2026-04-24
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 p Show more
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 police officers were selected using cluster random sampling in the Inner Mongolia Autonomous Region between September and December 2021. Participants completed a basic information questionnaire and the Pittsburgh sleep quality index(PSQI). Latent profile analysis(LPA) was employed to examine heterogeneity in sleep quality, and multinomial Logistic regression was used to identify associated factors of the latent profiles. The mean age of participants was(43.08±8.98) years. The sample comprised 920 males(79.2%) and 242 females(20.8%), 987(84.9%) were married and 175(15.1%) were single, 644(55.4%) had a high school education or below, and 518(44.6%) had college education or above. By department, 607(52.2%) worked in grassroots police stations, 200(17.2%) were criminal police, and 355(30.6%) served in other units. Significant heterogeneity in sleep quality was identified, revealing four distinct latent classes: good sleep group(n=821, 70.6%), moderate sleep group(n=46, 4.0%), sleep-disordered group(n=249, 21.4%), and medication-assisted sleep group(n=46, 4.0%). Using the good sleepers as the reference group, multinomial Logistic regression indicated that older age was a significant risk factor for belonging to the medication-assisted sleep group(OR=1.348, 95%CI 1.078-1.822). Higher education level was a protective factor against membership in the moderate sleep group(OR=4.101, 95%CI 1.304-12.893). Serving as a grassroots police station officer or criminal police officer was a significant risk factor for membership in both the moderate sleep group(OR = 3.329, 95%CI 1.338-8.284; OR=4.188, 95%CI 1.415-12.396) and sleep-disordered group(OR=1.701, 95%CI 1.196-2.420; OR=1.587, 95%CI 1.073-2.533). Sleep quality among police officers demonstrates significant heterogeneity. Age, police department assignment, and educational level are key associated factors of distinct latent classes of sleep quality. Show less
no PDFDOI: 10.19813/j.cnki.weishengyanjiu.2025.05.015
Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement Show more
Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement in bone marrow hematopoietic stem cells, resulting in the transformation of myeloid/lymphoid cells into neoplastic growths. The clinical and laboratory features of affected individuals are influenced by the specific partner genes. Purpose This article aims to report a case of MLN-FGFR1 involving a novel CNTRL::FGFR1 splicing variant and to discuss its clinicopathological characteristics and treatment challenges. Methods/Results We report a case of MLN-FGFR1 in a 35-year-old male patient presenting with leukocytosis, lymphadenopathy, hepatosplenomegaly, and a mixed population of B lymphoblasts, T lymphoblasts, and monoblasts in the bone marrow and lymph nodes. Comprehensive molecular profiling, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), targeted transcriptome sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing, identified a novel splicing variant of the CNTRL::FGFR1 fusion, resulting from a t(8;9)(p11;q33) translocation. This novel splicing variant involves an in-frame fusion between exon 38 of CNTRL and exon 11 of FGFR1, retaining the kinase domain of FGFR1 and leading to its constitutive activation. Despite multiple treatment regimens, the patient failed to achieve complete remission (CR). Conclusion The findings highlight the urgent need for targeted therapies, such as FGFR inhibitors, to improve outcomes in patients with FGFR1-rearranged malignancies. Show less
Mitochondria play an essential role in regulating various physiological functions including bioenergetics, calcium homeostasis, redox signaling, and lipid metabolism and also are involved in the patho Show more
Mitochondria play an essential role in regulating various physiological functions including bioenergetics, calcium homeostasis, redox signaling, and lipid metabolism and also are involved in the pathogenesis of cardiovascular diseases. However, the relationship between mitochondrial calcium homeostasis in vascular smooth muscle cells (VSMCs) and atherosclerosis remains poorly understood. Here, we demonstrate that cholesterol induces mitochondrial calcium overload and lipid accumulation in VSMCs, which is resulted from dysregulation of mitochondrial calcium uniporter (MCU), as evidenced by genetic and pharmacologic inhibition of MCU. Furthermore, MCU inhibitors alleviate Western diet-induced atherosclerosis in ApoE-/- mice. Mechanistically, high-fat and high-cholesterol diets induce the contact between mitochondria and the endoplasmic reticulum (ER) in VSMCs as indicated by transmission electron microscopy, proximity ligation assay and immunofluorescence staining, which increases the formation of mitochondria-associated membranes (MAMs), leading to Ca2 + release from the ER into the mitochondria and thus elevating Ca2 + in the mitochondria. Using mitochondrial calcium uptake 1 (MICU1) mutant and Ca2 + detection assay, we confirmed that this increased Ca2 + binds to MICU1, a blocker of MCU, to impair its ability to block MCU, thus enabling the MCU to remain open and resulting in mitochondrial calcium overload. Further, mitochondrial calcium overload dysregulates fatty acid β-oxidation by modulating medium-chain acyl-CoA dehydrogenase (ACADM), thereby leading to lipid deposition. The inhibition of MCU alleviates the pathological changes elecited by cholesterol. Our findings unveil the previously unrecognized role of MAM-MICU1-MCU axis in cholesterol-induced mitochondrial calcium overload and atherosclerosis, indicating that MCU represents a promising therapeutic target for the treatment of atherosclerosis. Show less