Intramuscular fat (IMF) content in beef cattle is a critical determinant of beef meat quality, as it positively influences juiciness, tenderness, and palatability. In China, the crossbreeding of Wagyu Show more
Intramuscular fat (IMF) content in beef cattle is a critical determinant of beef meat quality, as it positively influences juiciness, tenderness, and palatability. In China, the crossbreeding of Wagyu and Angus is a prevalent method for achieving a better marbling level. However, the molecular mechanisms governing IMF regulation in these crossbreeds remain poorly understood. To elucidate the mechanism of IMF deposition in these crossbred cattle, we conducted a comparative transcriptomic analysis of Show less
Currently, understanding of the nonlinear relationship between age and hepatocellular carcinoma (HCC) prognosis is insufficient. Thus, this study aimed to analyze the relationship between age at HCC d Show more
Currently, understanding of the nonlinear relationship between age and hepatocellular carcinoma (HCC) prognosis is insufficient. Thus, this study aimed to analyze the relationship between age at HCC diagnosis and overall survival (OS) and identify possible influencing mechanisms. Clinical data from the TCGA public database were analyzed. Restricted cubic spline and segmented logistic regression were employed to explore the nonlinear relationship between age at diagnosis and mortality risk following hepatectomy. Furthermore, bioinformatics methods were employed to understand the possible mechanisms of this nonlinear relationship at the genetic level. The results indicated a nonlinear relationship between age at diagnosis and OS, with the age of 60 years identified as a critical point. Segmented regression showed that age ≥60 years is an unfavorable prognostic factor. The "DNA mismatch repair" pathway was considerably enriched in patients aged <60 years. However, the gene mutation rate of "APOB," "MUC16," "ALB," and "PCLO" and the median tumor mutation burden were relatively more evident in patients aged ≥60 years. MGEA12 was more highly expressed in tumor tissues than in normal ones, particularly in patients aged ≥60 years. The survival rate of the high-expression group was lower than that of the low-expression group. At the mRNA level, the MGEA12 expression in Huh-7 and SUN449 was higher than that in the HSC-LX2 cell line. A nonlinear relationship was found between age at HCC diagnosis and OS, with the age of 60 years being the critical point. MGEA12 may affect the prognosis of elderly people. Show less
Gastrointestinal (GI) cancers exhibit aberrant lipid metabolism, yet the causal mechanisms remain elusive. Here, we integrated Mendelian randomization (MR) and multi-omics data to dissect metabolic dr Show more
Gastrointestinal (GI) cancers exhibit aberrant lipid metabolism, yet the causal mechanisms remain elusive. Here, we integrated Mendelian randomization (MR) and multi-omics data to dissect metabolic drivers of 20 GI diseases. Focusing on colorectal (CC) and esophageal cancer (EC), we identified five metabolites (e.g., 1,2-di-palmitoyl-sn-glycero-3-phosphocholine) and arachidonic acid ethyl ester as causal drivers. Summary-data-based MR and colocalization analysis (PP.H4 > 0.75) revealed FADS1 as a master regulator of these metabolites, with genetic variants exhibiting tissue-specific lipidomic effects. Functional validation using FADS1-knockout cell lines and mouse models demonstrated that FADS1 inhibition suppresses tumor cell proliferation, migration, and invasion while promoting apoptosis. In vivo, FADS1 deletion reduced chemically induced CC/EC tumor burden by 62-75%, accompanied by decreased Ki-67/MMP-9 expression and inflammatory infiltration. Mechanistically, FADS1 ablation disrupted lipid metabolism (reduced linoleic acid and arachidonic acid) and attenuated PI3K/AKT and MAPK signaling. Multi-omics integration further corroborated FADS1-mediated epigenetic regulation (e.g., mQTL-driven DNA methylation). This study establishes FADS1 as a pivotal orchestrator of GI carcinogenesis via metabolic reprogramming and signaling dysregulation, offering a compelling therapeutic target for precision oncology in CC and EC. Regulatory mechanisms of FADS1 in CC and EC. Show less
Health literacy plays an important role in disease prevention and control. The aim of this study is to explore the health literacy patterns and associated factors among residents in Zhejiang Province. Show more
Health literacy plays an important role in disease prevention and control. The aim of this study is to explore the health literacy patterns and associated factors among residents in Zhejiang Province. This study included 56,863 residents aged 15-69 years from the 2024 Zhejiang Province Health Literacy Survey. Latent Profile Analysis (LPA) was used to investigate health literacy patterns, and multinomial logistic regression analysis was employed to identify associated factors. Dominance analysis was performed to compare the relative contribution of the main variables associated with health literacy. The analysis identified three distinct health literacy profiles: low literacy (15.13%), moderate literacy (32.24%), and relatively high literacy (52.63%). The low literacy group was characterized by an older demographic (with an average age of 58.71 years), lower educational attainment (20.72% had no formal education), a higher proportion of farmers (52.93%), and a significant share of low-income individuals (40.98%). Multinomial logistic regression and dominance analysis revealed that education level, age, and occupation were the most important associated factors of health literacy. The study findings highlighted the heterogeneity in health literacy among various population groups and emphasized the need for targeted interventions. This study provides empirical evidence to inform precision health promotion strategies in developed regions of China. Show less
As inflammatory processes may be involved in the pathogenesis of diabetic distal sensorimotor polyneuropathy (DSPN), the first aim of the present study was to determine the clinical characteristics of Show more
As inflammatory processes may be involved in the pathogenesis of diabetic distal sensorimotor polyneuropathy (DSPN), the first aim of the present study was to determine the clinical characteristics of type 2 diabetes mellitus (T2DM) with distal sensorimotor polyneuorpathy (DSPN). Next goal was to investigate inflammatory biomarkers, insulin-like growth factor- 1 and lipid profile in these patients. Finally, we aimed to compare the renal function in these patients. In a cross-sectional study, we included 160 patients diagnosed with T2DM. The control group was included 22 non-diabetic healthy subjects (HC). The patients with diabetes were divided into four groups, absent (n = 74), mild (n = 38), moderate (n = 24), and severe (n = 24) using a nomogram based on the MNSI features for a DSPN severity grading probability. Patients with moderate and severe DSPN were a little older and had longer duration of diabetes compared to patients with absent and mild DSPNS (p < 0.05). Serum levels of interferon-gamma (INF-γ), interleukin (IL)-1β, IL-4, IL- 6 levels in patients with severe DSPN were significantly higher than HC, absent, mild and moderate of DSPN (p < 0.05). The circulating levels of insulin-like growth factor-1 (IGF-1) were significantly lower in patients with severe DSPN (p < 0.05) compared to absent, mild and moderate of DSPN and HC. Diabetic patients with moderate DSPN showed increased circulating levels of TC, LDL-C, APOB (p < 0.05) compared to HC and patients with absent, mild and severe DSPN. Moreover, APO-A1/APOB was significantly lower in patients with diabetes compared to HC. In addition, patients with severe DSPN showed increased Cystatin C (p < 0.05) compared to HC and absent, mild, and moderate DSPN. Multivariate ordered logistic regression analysis showed that the levels of IL-6 (OR = 3.166, 95%CI 1.461-6.860, p = 0.003, IL-1β(OR = 1.148, 95%CI 1.070-2.232; p = 0.000), TC (OR = 1.174, 95%CI 1.011-1.364; p = 0.035), LDL-C (OR = 1.246, 95%CI 1.098-3.618; p = 0.003), Cystatin C (OR = 1.867, 95%CI 1.245-3.434; p = 0.004), ages (OR = 1.043, 95%CI 1.009-1.078; p = 0.012), and duration of diabetes (OR = 1.157, 95%CI 1.049-1.277; p = 0.004) were positively associated with increasing the odds ration of DSPN in T2DM. Conversely, the level of IGF-1 (OR = 0.922, 95%CI 0.961-0.982; p = 0.000) and ratio of APO-A1/APOB (OR = 0.212, 95%CI 0.078-0.567; p = 0.002) were significantly associated with decreasing the odds ratio of DSPN in T2DM. The levels of inflammatory biomarkers such as INF-γ, IL-1β, IL-4, IL- 6 were increased in patients with severe DSPN in T2DM. Ages, duration of diabetes as well as high circulating levels of IL-6, IL-1β, TC, LDL-C and Cystatin C were positively associated with DSPN in T2DM. Conversely, the level of IGF-1 and the ratio of APOA1/APOB were independent protective factors for DSPN in T2DM. Our results emphasize the importance of addressing issues related to inflammatory biomarkers, lipids and early impaired renal function in T2DM with DSPN, as these may be of potential relevance for deteriorating DSPN. Show less
Accumulation of various genetics and epigenetics alterations are accepted to result in the initiation and progression of hepatocellular carcinoma (HCC), and its high metastasis is viewed as a critical Show more
Accumulation of various genetics and epigenetics alterations are accepted to result in the initiation and progression of hepatocellular carcinoma (HCC), and its high metastasis is viewed as a critical bottleneck leading to its treatment failure. Amongst them, the microRNAs arising from the lack of the antioxidant transcription factor Nrf2 lead to cancer metastasis. However, much less is known about the regulation of microRNAs by Nrf1, even though it acts as an essential determinon of cell homoeostasis by governing the transcriptional expression of those driver genes contributing to the EMT involved in its metastasis. In this study, distinct EMT phenotypes resulted from specific knockouts of Nrf1 and Nrf2 in HepG2 cells, as accompanied by their differential migratory and invasive capabilities. The Show less
Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is resp Show more
Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is responsible for a significant number of cancer-related deaths worldwide. Targeted drugs have been used for anti-liver cancer treatment in the advanced stage, while their efficacy is greatly compromised by development of drug resistance. Drug resistance is a complicated process regulated by intrinsic and extrinsic signals and has been associated with poorer prognosis in cancer patients. In the current study, online available dataset analysis uncovered that angiopoietin-like protein 3 (ANGPTL3) manifested lower expression in sorafenib-resistant liver cancer cell lines. Additionally, ANGPTL3 was downregulated in HCC tissues, with its expression positively correlated with good prognosis. Functionally, ectopic expression of ANGPTL3 re-sensitized sorafenib-resistant cells, enhancing the sorafenib-induced reduction in cell viability and migration by suppressing zinc finger protein SNAI1 (SNAI1) expression and the protein stability of carnitine O-palmitoyltransferase 1, liver isoform (CPT1A). Clinical correlation analysis revealed that ANGPTL3 was negatively associated with SNAI1 expression. In conclusion, we identify a novel association between ANGPTL3, SNAI1 and CPT1A on sorafenib therapeutic response. Targeting ANGPTL3/SNAI1/CPT1A axis may serve as a therapeutic approach to improve prognosis of liver cancer patients with sorafenib resistance. Show less
Sudden cardiac arrest (SCA) is a leading cause of death in pediatric hypertrophic cardiomyopathy (HCM). The study sought to analyze the clinical and genetic characteristics of pediatric HCM and assess Show more
Sudden cardiac arrest (SCA) is a leading cause of death in pediatric hypertrophic cardiomyopathy (HCM). The study sought to analyze the clinical and genetic characteristics of pediatric HCM and assess the applicability of current SCA risk prediction models. We enrolled individuals diagnosed as HCM before 20 years of age, between 2000 and 2020, excluding those secondary to hemodynamic causes and those associated with genetic syndromes other than RASopathies. Among 91 patients (31 female, 60 male), SCA occurred in 13 (14.3%) patients, with 6 (46%) cases presenting as the initial symptom. These 6 patients were older and had lower left ventricular mass In pediatric HCM, SCA is notably associated with sarcomere gene pathogenic variants. While newer risk scoring systems, if incorporated with genetic information, effectively predict SCA in this Asia cohort, a challenge remains: nearly half of SCA cases present as the initial clinical manifestation. Show less
The extensive co-occurrence of cardiovascular diseases (CVDs), as evidenced by epidemiological studies, is supported by positive genetic correlations identified in comprehensive genetic investigations Show more
The extensive co-occurrence of cardiovascular diseases (CVDs), as evidenced by epidemiological studies, is supported by positive genetic correlations identified in comprehensive genetic investigations, suggesting a shared genetic basis. However, the precise genetic mechanisms underlying these associations remain elusive. By assessing genetic correlations, genetic overlap, and causal connections, we aim to shed light on common genetic underpinnings among major CVDs. Employing multi-trait analysis, we pursue diverse strategies to unveil shared genetic elements, encompassing SNPs, genes, gene sets, and functional categories with pleiotropic implications. Our study systematically quantifies genetic overlap beyond genome-wide genetic correlations across CVDs, while identifying a putative causal relationship between coronary artery disease (CAD) and heart failure (HF). We then pinpointed 38 genomic loci with pleiotropic influence across CVDs, of which the most influential pleiotropic locus is located at the LPA gene. Notably, 12 loci present high evidence of multi-trait colocalization and display congruent directional effects. Examination of genes and gene sets linked to these loci unveiled robust associations with circulatory system development processes. Intriguingly, distinct patterns predominantly driven by atrial fibrillation, coronary artery disease, and venous thromboembolism underscore the significant disparities between clinically defined CVD classifications and underlying shared biological mechanisms, according to functional annotation findings. Show less
This review aims to explore the epidemiology of lipoprotein(a) [Lp(a)] by its structural and genetic make-up variation amongst ancestry groups. Lipoprotein(a) [Lp(a)] is a genetically determined lipop Show more
This review aims to explore the epidemiology of lipoprotein(a) [Lp(a)] by its structural and genetic make-up variation amongst ancestry groups. Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle, causally implicated in atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Given its genetic basis, studies have shown marked ancestry-related differences in different races and ethnicities. Lp(a) plasma concentrations vary by more than 100-fold among individuals, primarily due to LPA gene polymorphisms and the number of kringle-IV type 2 (KIV2) repeats, which define apolipoprotein(a) [apo(a)] isoform size. Individuals of African descent have the highest median concentrations, followed by South Asians, with Hispanics/Latinos and East Asians having lower levels. Admixed populations display heterogeneity reflecting genetic ancestry. Despite differences in absolute levels, the relative ASCVD risk per unit increase in Lp(a) is consistent across groups, highlighting the universal atherogenicity of elevated Lp(a). Small apo(a) isoforms are associated with higher Lp(a) concentrations and risk, though isoform size is mainly a surrogate for Lp(a) burden. Despite a strong genetic basis and disproportionate burden in some populations, ancestry-specific testing guidelines are limited and testing rates remain low. Therapies targeting LPA transcription are in development, with outcome trials underway. Integrating ancestry-informed perspectives with universal risk principles is essential for equitable prevention and treatment. Routine, one-time Lp(a) testing enables cost-effective early risk stratification as Lp(a)-directed therapies emerge. Show less
This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability Show more
This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability in young and middle-aged patients after percutaneous coronary intervention (PCI). A cross-sectional study was conducted among 129 post-PCI patients from a single center in China. Participants completed the Medical Coping Modes Questionnaire (MCMQ), the Social Support Rating Scale (SSRS), and the Social Disability Screening Schedule (SDSS). Latent profile analysis (LPA) was used to identify distinct coping patterns. The moderation effect of social support was tested using the Johnson-Neyman technique. Two distinct coping profiles were identified via LPA: "Adaptive Copers" (55.1%), characterized by higher confrontation and lower avoidance/resignation, and "Maladaptive Copers" (44.9%), showing the opposite pattern. A counterintuitive finding emerged, with the Maladaptive Copers reporting significantly lower social disability scores. Furthermore, beyond this profile differentiation, social support demonstrated a significant U-shaped moderating effect in the coping-disability relationship. Its moderating role was statistically significant only at very low (<39.884) and very high (>52.924) levels of support. This study reveals two key findings: first, post-PCI patients are heterogeneous in coping, comprising adaptive and maladaptive subgroups; second, the impact of these coping styles on social disability is non-linearly moderated by social support. Clinicians should assess both coping profiles and social support levels to tailor interventions effectively. 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
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutriti Show more
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutritional strategies. This study examined the potential of stevia chlorogenic acid (SCGA), a bioactive byproduct of stevia processing, to alleviate intestinal injury, gut microbiota dysbiosis, and lipid metabolism disorders induced by oxidized fish oil in turbot. Four diets with equal nitrogen and lipid contents were formulated: a control diet (PC) containing 5 % fresh fish oil, an oxidized fish oil diet (OFO) comprising 5 % oxidized fish oil, and two additional OFO diets supplemented with 200 mg/kg (OFO200) or 400 mg/kg (OFO400) of SCGA. Each dietary treatment was randomly assigned to three replicates, each containing 40 fish weighing approximately 16.99 ± 0.01 g, and administered over a 10-week period. Fish fed the OFO diet exhibited significantly compromised growth performance, as indicated by decreased WGR and SGR, along with reduced serum immune indices (IgM, C3, and C4) and lipid parameters (TC, HDL, LDL), and elevated serum D-LA levels (P < 0.05). Moreover, dietary OFO markedly suppressed antioxidant enzyme activities (serum SOD; intestinal SOD, GSH-Px, and CAT) and elevated MDA concentrations (P < 0.05). Additionally, OFO reduced intestinal expression of tight junction-associated genes (Claudin-4, Claudin-7, Occludin) while increasing expression levels of MLCK, Keap1, inflammatory mediators (IL-6, IL-1β, TNF-α2, NF-κB, IFN-γ), and Caspase7 (P < 0.05). Notably, the TLR signaling pathway-related genes were upregulated, accompanied by pronounced shifts in gut microbiota composition (P < 0.05). In hepatic tissue, lipogenesis-associated genes (FAS, ACC) were significantly increased, while key genes involved in lipid transport and β-oxidation (CD36, LPL, ACOX1, PPARγ) exhibited reduced expression (P < 0.05). Dietary supplementation with 200 and 400 mg/kg SCGA effectively mitigated these detrimental impacts. SCGA restored growth performance, serum immune parameters, and antioxidant enzyme activities to levels comparable to the PC group. It also normalized gene expression related to intestinal barrier function, inflammation, apoptosis, and hepatic lipid metabolism. Furthermore, SCGA supplementation modulated gut microbiota structure by increasing beneficial genera and decreasing potential pathogens. In conclusion, SCGA effectively improves growth performance, alleviates OFO-induced intestinal injury and microbial dysbiosis, and regulates lipid metabolism in turbot. These findings provide theoretical insights and technical support for the application of SCGA in aquaculture. Show less
Some individuals are more susceptible to developing or suffering from pain states than others. However, the brain mechanisms underlying the susceptibility to pain responses are unknown. In this study, Show more
Some individuals are more susceptible to developing or suffering from pain states than others. However, the brain mechanisms underlying the susceptibility to pain responses are unknown. In this study, we defined pain susceptibility by recapitulating inter-individual differences in pain responses in mice exposed to a paradigm of socially transferred allodynia (STA), and with a combination of chemogenetic, molecular, pharmacological and electrophysiological approaches, we identified GABA-ergic neurons in the dorsal raphe nucleus (DRN) as a cellular target for the development and maintenance of STA susceptibility. We showed that DRN GABA-ergic neurons were selectively activated in STA-susceptible mice when compared with the unsusceptible (resilient) or control mice. Chemogenetic activation of DRN GABA-ergic neurons promoted STA susceptibility; whereas inhibiting these neurons prevented the development of STA susceptibility and reversed established STA. In in vitro slice electrophysiological analysis, we demonstrated that melanocortin 4 receptor (MC4R) enriched in DRN GABA-ergic neurons was a molecular target for regulating pain susceptibility, possibly by affecting DRN GABA-ergic neuronal activity. These results establish the DRN GABA-ergic neurons as an essential target for controlling pain susceptibility, thus providing important information for developing conceptually innovative and more accurate analgesic strategies. Show less
Yu Gan, Kangning Wang, Xiang Chen+4 more · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) in renal tissues plays an important role in the Show more
Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) in renal tissues plays an important role in the development of renal fibrosis. Eliminating senescent TECs has been proven to effectively reduce renal fibrosis. Procyanidin C1 (PCC1) plays a senolytic role by specifically eliminating senescent cells and extending its overall lifespan. However, whether PCC1 can alleviate unilateral ureteral obstruction (UUO)-induced renal fibrosis and the associated therapeutic mechanisms remains unclear. Here, we observed a marked increase in senescent TECs within obstructed human renal tissue and demonstrated the positive correlation between the accumulation of senescent TECs and renal fibrosis in UUO-induced renal fibrosis in mice. We found that PCC1 reduced the number of senescent TECs, restored the regenerative phenotype in kidneys with reduced fibrosis, and improved tubular repair after UUO-induced injury. In vitro, PCC1 effectively cleared senescent HK2 cells by inducing apoptosis via ANGPTL4/NOX4 signaling. Incubation with culture medium from senescent HK2 cells promoted fibroblast activation, whereas PCC1 impeded profibrotic effects by downregulating senescence-associated secretory phenotype (SASP) factors from senescent HK2 cells. Therefore, PCC1 alleviated interstitial renal fibrosis not only by clearing senescent TECs and improving tubular repair but also by indirectly attenuating myofibroblast activation by reducing the level of SASP. In summary, PCC1 may be a novel therapeutic senolytic agent for treating renal fibrosis. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health issue due to its high prevalence, yet the impact of accelerometer-measured physical activity on clinical outcomes re Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health issue due to its high prevalence, yet the impact of accelerometer-measured physical activity on clinical outcomes remains unclear. This study aims to examine the associations of physical activity with the risk of liver cirrhosis, cancer, cardiovascular disease (CVD) incidence and mortality. 32 681 MASLD participants with accelerometer-derived physical activity data from the UK Biobank were analysed. Physical activity intensity was categorised into light (LPA), moderate (MPA) and vigorous (VPA) intensity. Cox proportional hazard and acceleration failure models were employed to assess associations between physical activity duration and outcomes. During a median follow-up of 7.5-7.9 years, 1883 deaths, 151 liver cirrhosis, 3312 cancers and 6657 CVD events were recorded. Physical activity, regardless of intensity, was consistently associated with a reduced risk of liver cirrhosis, CVD and all-cause mortality. Compared with non-MASLD individuals, our analysis indicates that longer duration of physical activity, specifically >1945 min/week of LPA or >383 min/week of MPA may theoretically eliminate the excess risk of mortality associated with MASLD. Among MASLD individuals, longer physical activity duration, regardless of intensity, was associated with reduced risks of liver cirrhosis and mortality. MPA and VPA were associated with lower CVD risk, while VPA was associated with reduced cancer risk, highlighting the potential benefits of increasing the intensity and duration of physical activity in MASLD management. Show less
Breast cancer has seriously affected women's physical and mental health. This investigation aims at screening differentially expressed genes (DEGs) in breast cancer and illuminating the potential biol Show more
Breast cancer has seriously affected women's physical and mental health. This investigation aims at screening differentially expressed genes (DEGs) in breast cancer and illuminating the potential biological functions of Leiomodin 1 (LMOD1) and its behind mechanisms against breast cancer. The common DEGs (co-DEGs) between the GSE22820 and GSE29431 data sets and pivotal genes were screened out using bioinformatics methods. The biological roles of LMOD1 overexpression on malignant phenotypes were validated by functional assays and the impact on fatty acid synthesis was also elucidated in breast cancer cell lines. Additionally, colivelin, a STAT3 activator, was applied for further investigating the role of LMOD1 on the JAK2/STAT3 pathway in vitro. A total of 208 co-DEGs and 5 focal genes were screened through bioinformatics analysis, and 5 focal genes were downregulated in breast cancer cell lines. LMOD1 overexpression retarded proliferative, migratory, invasive capabilities of breast cancer cells. LMOD1 overexpression suppressed fatty acid synthesis. Furthermore, the inhibitory effects on malignant phenotypes of breast cancer cells with LMOD1 overexpression were partially abolished after colivelin treatment. Additionally, LMOD1 could impede fatty acid synthesis in breast cancer cells. Our study highlighted LMOD1 exerted as a tumor-suppressive role in breast cancer, which was correlated with restraining the JAK2/STAT3 pathway activation. Show less
For workers in the industry, occupational exposure to indium compounds induces pulmonary disorders, such as interstitial pneumonia. Moreover, lung cancer has been reported in both humans and rodents e Show more
For workers in the industry, occupational exposure to indium compounds induces pulmonary disorders, such as interstitial pneumonia. Moreover, lung cancer has been reported in both humans and rodents exposed to indium compounds by inhalation. However, the biological mechanism underlying indium-induced disorders is poorly understood. Epithelial-mesenchymal transition (EMT)-the cellular process of losing epithelial and acquiring mesenchymal characteristics-is linked to fibrosis and cancer progression. Therefore, we examined whether indium exposure elicits EMT in vitro. A549 human alveolar epithelial cells treated with indium chloride at doses of 0-500 μg/mL for 24 h were used to analyze EMT marker expression and cytoarchitecture. Significant downregulation of CDH1 mRNA expression as an epithelial marker after treatments at 125, 250, and 500 μg/mL occurred dose-dependently; conversely, the mesenchymal marker SNAI1 was upregulated. Consistent with mRNAs, the expression levels of EMT marker proteins (i.e., E-cadherin, ZO1, SNAIL, and Vimentin) were changed significantly by treatment. While NF-κB signaling was activated in treated cells, indium-dependent changes of CDH1 and SNAI1 mRNA expression were not affected by BAY 11-7082, an NF-κB inhibitor, suggesting that NF-κB activation may be dispensable for indium-induced EMT. Fibroblast-like morphological characteristics, such as actin stress fiber formation and cell elongation, along with deconstruction of cell-cell adhesion complexes, were observed in treated cells. Overall, our study is the first to demonstrate that EMT is caused by indium compounds. This will contribute biologically to understanding the mechanism of EMT induction and clinically to unveiling the pathophysiology of indium lung disease. Show less
Alzheimer's disease (AD) is a chronic neurodegenerative disorder predominantly affecting the elderly population. The pathogenesis of AD involves the production of highly neurotoxic amyloid-β peptide 1 Show more
Alzheimer's disease (AD) is a chronic neurodegenerative disorder predominantly affecting the elderly population. The pathogenesis of AD involves the production of highly neurotoxic amyloid-β peptide 1-42 (Aβ Show less
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive Show more
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive of its therapeutic potential against T2DM. In this study, we evaluated the protective effects of KA against apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (LDL) (AC3RL)-induced β-cell apoptosis and its underlying mechanism of action. ApoE Show less
Cranial neural crest cells (CNCs) play a critical role in craniofacial bone morphogenesis, engaging in intricate interactions with various molecular signals to ensure proper development, yet the molec Show more
Cranial neural crest cells (CNCs) play a critical role in craniofacial bone morphogenesis, engaging in intricate interactions with various molecular signals to ensure proper development, yet the molecular scaffolds coordinating these processes remain incompletely defined. Here, we identify neurofibromin 2 (Nf2) as a critical regulator to direct CNC-derived skull morphogenesis. Genetic ablation of Nf2 in murine CNCs causes severe craniofacial anomalies, featuring declined proliferation and increased apoptosis in osteoprogenitors, impaired type I collagen biosynthesis and trafficking, and aberrant osteogenic mineralization. Mechanistically, we uncover that Nf2 serves as a molecular linker that individually interacts with FGF receptor 1 (FGFR1) and Akt through spatially segregated phosphor-sites, and structural modeling and mutagenesis identified Ser10 and Thr230 as essential residues, with Thr230 mutation selectively ablating Akt binding while preserving FGFR1 association. Strikingly, Akt inhibition phenocopied Nf2 deficiency, reducing collagen production and Nf2 phosphorylation, whereas phospho-mimetic Nf2 (T230D) rescued CNC-derived osteogenic defects in Nf2-mutant animals. Our findings underscore the physiological significance of Nf2 as a phosphorylation-operated scaffold licensing the FGFR1/AKT axis to regulate collagen type I biogenesis and trafficking, ensuring normal CNC-derived osteogenesis and craniofacial bone development, thus exposing the Nf2/FGFR1/AKT signaling axis as a therapeutic target and promising advancements in treatment of craniofacial anomalies. Show less
Demyelination diseases are characterized by injury to large (A-type) myelinated nerve fibers, and by secondary damage to small (C-type) sensory fibers, which leads to chronic pain symptoms, such as al Show more
Demyelination diseases are characterized by injury to large (A-type) myelinated nerve fibers, and by secondary damage to small (C-type) sensory fibers, which leads to chronic pain symptoms, such as allodynia. The mechanisms underlying the interactions between the two fiber types are not clear. This study aims to investigate the role of lysophosphatidic acid (LPA) signaling in satellite glial cells (SGCs) within the dorsal root ganglia (DRG) in demyelination-induced chronic pain. A demyelination model was established by injecting cobra venom into the tibial nerve of 8-10-week-old Sprague-Dawley rats to selectively damage A-fiber myelin. Myelin morphology was observed via transmission electron microscopy (TEM) at 1, 3, 7, and 14 days post-injection. Pain behaviors (mechanical hypersensitivity, thermal hyperalgesia, and spontaneous pain) were assessed to evaluate progression. In vivo electrophysiology was performed to analyze sensory conduction and excitability changes in A- and C-type neurons. Immunofluorescence staining assessed SGC activation, LPA1 receptor (LPA1R) expression, and connexin 43 (Cx43) dynamics in the L4 DRG over time. Pharmacological interventions targeting LPA1R and SGC activation were applied to evaluate their effects on pain behaviors, cytokine release, and neuronal excitability using RT-PCR, ELISA, and spinal electrophysiology. Cobra venom induced a selective A-fiber demyelination and persistent pain in rats. It also upregulated the expression of LPA1R on SGCs that surround large DRG neurons, which normally mediate non-noxious input, and increased gap junction-mediated coupling via Cx43, leading to the activation of SGCs surrounding small nociceptive neurons. The activated SGCs released inflammatory mediators that increased nociceptive neuron excitability, driving chronic pain. In support of these results, pharmacological inhibition of LPA1R-mediated SGCs activation reversed this process. Our study demonstrates that LPA-LPA1R signaling in SGCs drives A-fiber demyelination-induced neuropathic pain by promoting Cx43-mediated SGC-neuron crosstalk and cytokine release. Targeting this pathway may represent a promising strategy to alleviate demyelination-associated chronic pain. Show less
Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining Show more
Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining heart health by draining fluids and immune cells. However, their involvement in HFpEF remains largely unexplored. We examined cardiac lymphatic alterations in mice with HFpEF with comorbid obesity and hypertension, and in heart tissues from patients with HFpEF. Using genetically engineered mouse models and various cellular and molecular techniques, we investigated the role of cardiac lymphatics in HFpEF and the underlying mechanisms. In mice with HFpEF, cardiac lymphatics displayed substantial structural and functional anomalies, including decreased lymphatic endothelial cell (LEC) density, vessel fragmentation, reduced branch connections, and impaired capacity to drain fluids and immune cells. LEC numbers and marker expression levels were also decreased in heart tissues from patients with HFpEF. Stimulating lymphangiogenesis with an adeno-associated virus expressing an engineered variant of vascular endothelial growth factor C (VEGFC Our study provides evidence that cardiac lymphatic disruption, driven by impaired BCAA catabolism in LECs, is a key factor contributing to HFpEF. These findings unravel the crucial role of BCAA catabolism in modulating lymphatic biology, and suggest that preserving cardiac lymphatic integrity may present a novel therapeutic strategy for HFpEF. Show less
FGFR1 amplification and FGFR1/2 activating mutations have been associated with antiestrogen resistance in estrogen receptor-positive (ER+) breast cancer. However, there are no approved FGFR1-targeted Show more
FGFR1 amplification and FGFR1/2 activating mutations have been associated with antiestrogen resistance in estrogen receptor-positive (ER+) breast cancer. However, there are no approved FGFR1-targeted therapies for breast cancers harboring these alterations. In this study, we investigated the selective degradation of FGFR1/2 using the proteolysis-targeting chimera (PROTAC) DGY-09-192 as a novel therapeutic strategy in ER + breast cancers harboring FGFR1/2 somatic alterations. Treatment of ER+/FGFR1-amplified breast cancer cells and patient-derived xenografts with DGY-09-192 resulted in sustained degradation of FGFR1 in a proteasome-dependent manner and suppressed downstream signal transduction. The combination of DGY-09-192 and the ERα degrader fulvestrant resulted in complete cell growth arrest and tumor regression of ER+/FGFR1-amplified patients-derived xenografts. In addition, we tested the effect of DGY-09-192 on breast cancer cells expressing FGFR1 Show less
Jia Min Chen, Yan Wang, Yan Shi · 2025 · Clinical, cosmetic and investigational dermatology · added 2026-04-24
Omega-3 polyunsaturated fatty acids (PUFAs) are potential targets for the treatment of skin diseases due to their anti-inflammatory and immunomodulatory effects. By leveraging a genetic approach known Show more
Omega-3 polyunsaturated fatty acids (PUFAs) are potential targets for the treatment of skin diseases due to their anti-inflammatory and immunomodulatory effects. By leveraging a genetic approach known as Mendelian randomization (MR), we sought to determine the causal impact of PUFAs on the likelihood of developing skin diseases among individuals of European ancestry. We integrated GWAS data from the CHARGE consortium and UK Biobank to identify genetic instruments for omega-3 PUFAs and desaturase activity, using two-sample MR to assess their associations with six skin diseases. Elevated levels of omega-3 fatty acids were found to substantially lower the probability of experiencing atopic dermatitis (0.92, [0.85,0.98]), while increased DPA levels correlated with a substantial increase in the probability of squamous cell carcinoma occurrence (2.25, [1.29,3.92]). Increased DHA levels were also associated with a reduced risk of atopic dermatitis (0.90, [0.84,0.96]) but increased the risk of solar dermatitis (1.38, [1.09,1.73]). In addition, tissue-type specific MR analysis revealed that elevated FADS1 expression in fibroblasts significantly inhibited atopic dermatitis development (β = -0.181, [-0.276,-0.0853]), while elevated FADS2 expression in non-sun-exposed skin tissues was associated with a reduced risk of squamous cell carcinoma (β = -0.562, [-0.833,-0.029]). Conversely, heightened FADS2 expression was strongly linked to a greater likelihood of developing atopic dermatitis in both sun-exposed and sun-protected skin areas (β = 0.107, [0.0348,0.179]; β = 0.192, [0.114,0.0270], respectively). This study reveals the causal role of omega-3 PUFAs and FADS expression in specific tissues and blood in skin diseases. These findings underscore the potential of PUFA biosynthesis pathways as therapeutic targets for skin disease interventions. Show less
This study aimed to elucidate the correlations among dyslipidemia, immune function, and clinical outcomes in patients with acute-on-chronic liver failure (ACLF), with particular emphasis on the clinic Show more
This study aimed to elucidate the correlations among dyslipidemia, immune function, and clinical outcomes in patients with acute-on-chronic liver failure (ACLF), with particular emphasis on the clinical significance of lipid metabolism and cellular immune parameters in hepatitis B virus-associated ACLF (HBV-ACLF). A retrospective analysis was conducted on 803 patients with HBV-ACLF admitted to the Shanghai Public Health Clinical Center from January 2014 to January 2024. Patients were stratified into deceased (n = 414) and survival (n = 389) groups based on clinical outcomes. Clinical baseline data, lipid metabolic indices, and cellular immune parameters were collected. The Spearman correlation coefficient was utilized to assess the correlation between lipid metabolic indices and cellular immune parameters, and a multivariate Cox proportional hazards model was applied to analyze risk factors for mortality. Compared to the survival group, lipid metabolism indices in the deceased group were significantly reduced (P < 0.05). Lipid metabolism indices, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), total cholesterol (TC), and triglycerides (TG), demonstrated significant negative correlations with the severity of liver failure (P < 0.05). Correlation analysis with lymphocyte subset counts revealed positive correlations between low-density lipoprotein, TG, TC, APOB, and CD3 + T cells, CD4 + T cells, CD8 + T cells, and CD45 + T cells (P < 0.05). APOA1 and HDL-C were positively correlated with B cells and NK cells (P < 0.05). TG and APOB showed significant negative correlations with the CD4/CD8 ratio (P < 0.05). Multivariate Cox analysis identified age, creatinine, total bilirubin, international normalized ratio (INR), hepatic encephalopathy, and hepatorenal syndrome as independent risk factors affecting the short-term prognosis of HBV-ACLF, while sodium, APOA1, and APOB were identified as independent protective factors for ACLF (HR = 0.984, 95% CI: 0.974-0.995, P < 0.001, HR = 0.267,95% CI: 0.120-0.596, P = 0.001, HR = 0.486, 95% CI: 0.282-0.838, P = 0.010). Patients with HBV-ACLF exhibit decreased levels of TC, TG, LDL-C, HDL-C, APOA1, and APOB. These alterations in serum lipid profiles are associated with immune dysfunction and disease progression in HBV-ACLF. Notably, APOA1 and APOB serve as protective factors against 90-day mortality in hospitalized ACLF patients. Further investigation is warranted to elucidate the relationship between lipid metabolism disturbances and peripheral immunity in ACLF. Show less