Xiaokun Li, Zhiheng Rao, Wenhao Hu+2 more · 2025 · Obesity reviews : an official journal of the International Association for the Study of Obesity · Blackwell Publishing · added 2026-04-24
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, e Show more
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, excess deposition of lipids in hepatic lipid droplets. Despite the growing prevalence and serious risks it poses, including liver decompensation, the need for transplantation, and increased patient mortality, MASH currently faces no approved pharmacotherapy. Several promising treatment candidates have emerged from recent clinical trials, including analogs of FGF21 and agonists of the associated FGFR1-KLB complex. These agents were well-tolerated in trials and have demonstrated significant improvements in both histological and biochemical markers of liver fat content, inflammation, injury, and fibrosis in patients with MASH. Endocrine FGF21 plays a vital role in maintaining homeostasis of lipid, glucose, and energy metabolism. It achieves this through pathways that target lipids or lipid droplets in adipocytes and hepatocytes. Mechanistically, pharmacological FGF21 acts as a potent catabolic factor to promote lipid or lipid droplet lipolysis, fatty acid oxidation, mitochondrial catabolic flux, and heat-dissipating energy expenditure, leading to effective clearance of hepatic and systemic gluco-lipotoxicity and inflammatory stress, thereby preventing obesity, diabetes, and MASH pathologies. In this review, we aim to provide an update on the outcomes of clinical trials for several FGF21 mimetics. We compare these outcomes with preclinical studies and offer a lipid-centric perspective on the mechanisms underlying the clinical benefits of these agents for MASH. Show less
DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus i Show more
DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus in ducklings is limited. To dissect the molecular characteristics associated with pathobiology of ducklings to DHAV-3, we applied single-cell RNA-sequencing approach to profile the transcriptome of 1.4 million cells from 14 livers of DHAV-3 susceptible (S) and resistant (R) ducklings during viral infection and 4 uninfected healthy controls. We found that infected S ducks exhibited the activation of type I and II interferon pathways with elevated expression of interferon-stimulated genes (ISGs) compared to infected R ducks and healthy controls. DHAV-3 promoted proinflammatory phenotype and inhibited the cell apoptosis pathway of Kupffer cells of S ducks. Furthermore, we observed the elevated expression of host factor PLAC8 in S ducks and validated its ability to facilitate the infection of DHAV-3. We identified significant dysregulation of various genes in complement and coagulation cascades in hepatocytes2 exclusive to S ducks, together with over-secretion of ANGPTL4 from endothelial cells in S ducks which is confirmed to promote cellular migration, suggesting etiology of coagulopathic complications in ducks with severe DVH. Collectively, this study provides a rich resource for understanding the inflammatory immune signatures and cell communications underlying the pathogenesis of DHAV-3 infection, which may accelerate the development of better diagnostic methods and strategies for controlling this disease. Show less
Hui Wang, Timothy S Chang, Beth A Dombroski+64 more · 2025 · Movement disorders : official journal of the Movement Disorder Society · Wiley · added 2026-04-24
The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear pa Show more
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metaboli Show more
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metabolic status in prediabetes, but their predictive value for cardiovascular mortality and stroke in this population remains unclear. We analyzed data from 74,678 White participants with prediabetes in the UK Biobank, defined by either HbA1c (5.7-6.4%) or fasting glucose (6.1-6.9 mmol/L). Follow-up continued until October 10, 2023. Cox regression was used to examine associations between LE8, phenotypic age (PhenoAge), cardiovascular biological age (CBA), and outcomes of cardiovascular (CVD) mortality and stroke. Restricted cubic spline (RCS) models identified biological age risk thresholds. Mediation analysis assessed whether proteins such as CST3, EFEMP1, FES, IGFBP2, IGFBP6, LPA, PCSK9, and TIMP1 mediated these effects. Over a median follow-up of 13.4 years, 2263 participants died from CVD causes. Each 1-year increase in CBA or PhenoAge was associated with a ~ 10% higher risk of CVD mortality (CBA aHR = 1.10; PhenoAge aHR = 1.09; both P < 0.001), while each 1-point increase in LE8 score was linked to a 3% lower risk (HR = 0.97, P < 0.001). The risk biological ages for these two indicators were also identified: PhenoAge ≥ 58.52 years and CBA ≥ 62.42 years. Similar trends were observed for stroke. Mediation analysis revealed that CST3, TIMP1, IGFBP2, and IGFBP6 contributed to the biological pathways between aging/lifestyle and CVD outcomes. The combined LE8 and PhenoAge model showed the strongest predictive performance for CVD mortality (AUC = 0.716) and stroke (AUC = 0.638) over 15 years. LE8 combined with phenotypic age provides prognostic value for CVD outcomes in prediabetes. These findings highlight the potential of lifestyle modification and delayed biological aging in reversing prediabetes and underscore comorbidity-related proteins as promising therapeutic targets. Show less
The Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent appl Show more
The Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent application, the specific anti-osteoporotic mechanisms of RCRP remain to be elucidated. This study aims to elucidate the therapeutic mechanism of RCRP in the context of ovariectomy (OVX)-induced PMOP in rats. By employing an integrative approach, the research combines medicinal chemistry, gut microbiota (GM) profiling, metabolomics, MetOrigin traceability, network pharmacology, molecular docking, and molecular dynamics simulations to deliver a comprehensive analysis. Sprague-Dawley (SD) rats underwent bilateral OVX to establish a PMOP model. The therapeutic efficacy of RCRP was evaluated through bone metrics (BMD, bone strength, BV/TV, Tb.Sp), hematoxylin and eosin (H&E) histological assessment, and bone metabolism markers (OPG, BALP, TRACP-5b, β-CTX, RANKL). Fecal metabolomics and 16S rDNA sequencing were employed to assess the influence of RCRP on GM and metabolite profiles. Furthermore, MetOrigin facilitated the traceability analysis of relevant metabolites. Molecular docking identified potential RCRP compounds with anti-PMOP activity, while their stability and protein interactions were assessed through molecular dynamics simulations. Network pharmacology further confirms the targets of action. RCRP alleviated PMOP in rats, enhancing bone strength, cortical and trabecular BMD, BV/TV, and serum OPG levels, while reducing Tb.Sp, serum BALP, TRACP-5b, β-CTX, and RANKL concentrations. A total of twenty-six distinct metabolites were identified, of which ten-tribufos, sulfoacetic acid, betamethasone dipropionate, 9-oxooctadeca-10,12,15-trienoic acid, menatetrenone, piperlongumine, maltopentaose, enol-phenylpyruvate, catechol, pentaacetate, and (+)-2-methylpropanoic acid-exhibited correlations with six GM species: Turicibacter, Roseburia, Colidextribacter, Helicobacter, Odoribacter, and Lachnoclostridium, as determined by Spearman's correlation analysis. Notably, MetOrigin revealed the microbial metabolism of taurine and hypotaurine, along with host-specific steroid hormone synthesis. Computational docking studies demonstrated robust interactions between five RCRP-derived steroids (hydroxyecdysone, corticosterone, trilostane, 5α-androstan-3,6,17-trione, and cortisol) and key enzymes (estradiol 17α-dehydrogenase and UDP-glucuronosyltransferase), suggesting a potential enhancement of therapeutic efficacy against PMOP. Furthermore, molecular dynamics simulations indicated stable interactions between hydroxyecdysone and two proteins, with binding free energies of -67.427 kJ/mol and -156.948 kJ/mol, respectively. Through network pharmacology and molecular docking approaches, potential targets of these metabolites were identified, including estrogen receptors ESR1 and ESR2, dual specificity phosphatase 6 (DUSP6), sex hormone-binding globulin (SHBG), prostaglandin E receptor 4 (PTGER4), cannabinoid receptor 2 (CNR2), cathepsin K (CTSK), and androgen receptor (AR). RCRP effectively mitigates OVX-induced bone loss in PMOP rats by modulating GM and associated metabolites, along with their potential targets and key metabolic pathways, including taurine and hypotaurine metabolism, as well as steroid hormone biosynthesis. These findings offer new insights into the therapeutic mechanisms by which RCRP may alleviate PMOP. Show less
The Kruppel-like factor 15(KLF15) gene functions as a crucial transcriptional modulator involved in numerous cellular processes such as differentiation, proliferation, growth, and programmed cell deat Show more
The Kruppel-like factor 15(KLF15) gene functions as a crucial transcriptional modulator involved in numerous cellular processes such as differentiation, proliferation, growth, and programmed cell death. The epithelial-to-mesenchymal transition (EMT) provides malignant cells with the adaptability and movement necessary for tumor advancement and spread, with zinc finger E-box binding homeobox 1(ZEB1) playing a pivotal role as a transcriptional factor in EMT. This investigation initially examined the association between the KLF15 protein and EMT associated transcription factors such as ZEB1, Slug, and Snail, along with marker proteins like E-cadherin and β-catenin in bladder cancer. Furthermore, we explored their connections with clinicopathological attributes and conducted prognostic analyses. Immunohistochemical techniques were utilized to ascertain the presence of KLF15 protein and EMT-associated transcription factor proteins, along with their marker proteins in 110 specimens of bladder cancer tissues. Concurrently, clinicopathological data and postoperative survival statistics were amassed. The rates of KLF15 and Slug protein expression were linked with pathological differentiation, lymphatic involvement, and pTNM staging. The protein expression rates of ZEB1, Slug, Snail, E-cadherin, and β-catenin also showed associations with lymphatic metastasis and pTNM stages. Notably, the expression of KLF15, the coexpression of KLF15 and ZEB1, and lymphatic metastasis emerged as independent prognostic indicators for the overall survival rates in bladder cancer cases. EMT enhances the risk of tumor recurrence and reduces overall survival durations in bladder cancer cases. Furthermore, KLF15 is a significant contributor to the EMT pathway in bladder cancer, primarily through its interaction with the transcription factor ZEB1. KLF15 and ZEB1 might serve as key biomarkers for metastasis and prognosis, offering potential new targets for therapeutic intervention in bladder cancer. Show less
The intrinsic heterogeneity and invasiveness of diffuse gliomas complicate accurate prognosis. Existing approaches are largely constrained by subtype specificity or limited analytical dimensions. To a Show more
The intrinsic heterogeneity and invasiveness of diffuse gliomas complicate accurate prognosis. Existing approaches are largely constrained by subtype specificity or limited analytical dimensions. To address this gap, a multi- dimension-based prognostic framework encompassing the full glioma spectrum was developed, accompanied by an analysis of the associated immune microenvironment. A total of 3,323 glioma samples from the SEER (n = 2181), CGGA (n = 807), and TCGA (n = 335) datasets were integrated. Differentially expressed genes were screened using the limma package, and a Lasso-Cox-based prognostic signature (Glioma-GDPM) was established. Clinical variables such as age, grade, and IDH mutation status were harmonized through propensity score matching to construct a multi-omics prognostic model (Glioma-GCDPM). GSEA, CIBERSORT-based immune infiltration analysis, and TIDE scoring were used to investigate the biological characteristics of different risk subgroups. Eleven key prognostic genes (such as PRAMEF2 and FADS1) and four clinical factors (age, tumor grade, IDH mutation, and 1p/19q codeletion) were identified. Glioma-GCDPM demonstrated favorable predictive ability in both the internal test cohort (AUC 0.81-0.86) and external validation sets (AUC 0.59-0.83). High-risk tumors exhibited greater invasiveness, with significant enrichment in cell cycle and proliferation-associated pathways. Additionally, a suppressed immune microenvironment was observed, reflected by elevated M2 macrophage infiltration and increased T cell dysfunction scores. The multi-omics model established in this study enables precise stratification of prognostic risk in diffuse glioma patients and reveals immunosuppressive features in high-risk individuals, providing a new basis for personalized treatment strategies. Show less
Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Huma Show more
Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Human umbilical cord mesenchymal stem cells (hUC-MSCs) characterized by their abundant availability and low immunogenicity, have demonstrated significant therapeutic potential for AD in both preclinical studies and clinical trials. The use of exosomes can help mitigate the issues associated with cellular therapies. However, the clinical application of hUC-MSCs remains challenging due to their inability to effectively traverse the blood-brain barrier (BBB) and reach pathological sites. Therapeutic strategies utilizing exosomes derived from hUC-MSCs (Exos) have emerged as an effective approach for AD intervention. Here, we used ultrasound to construct multifunctional Exos (MsEVB@R/siRNA) for AD therapy. We obtained small interfering RNA for β-site precursor protein lyase-1 (BACE1 siRNA) and berberine for co-delivery into the brain. Berberine, a classical anti-inflammatory agent, effectively alleviates neuroinflammation in AD pathogenesis. BACE1 serves as the pivotal cleavage enzyme in amyloid β-protein (Aβ) formation, where silencing BACE1 synthesis through BACE1 siRNA significantly reduces Aβ production. In a 5xFAD mouse model, Exos selectively targeted microglial and neuronal cells after nasal delivery under the action of neural cell-targeting peptide rabies virus glycoprotein 29 (RVG29). BACE1 siRNA and berberine (BBR) loading enhanced the effectiveness of Exos in improving cognitive function, promoting nerve repair and regeneration, reducing inflammatory cytokine expression, and suppressing glial responses. BACE1 siRNA release was confirmed to reduce BACE1 expression and Aβ deposition. Concurrently, berberine effectively suppressed the release of inflammatory factors, thereby reducing neuroinflammation. In conclusion, the nasal delivery of engineered exosomes is a potentially effective method for treating AD. Show less
The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect Show more
The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect of 24-hour physical activities components on changing Life expectancy among patients with type 2 diabetes diagnosed. To address the abovementioned research gap, the study has a two-fold aims: first, to examine the mediation effect of 24-hour physical activities in type 2 diabetes and mortality; and second, to address how reallocating time on different daily activities would affect life expectancy. Analysis was conducted on the accelerometer data of 103,359 participants in the UK Biobank, with a median age of 57 years (range 39 to 70). Compositional mediation cox model was conducted to analyze the mediating effects of 24-hour physical activities. Additionally, the cohort Life table method was utilized to estimate the changes of Life-years over the next 10 years resulting from the substitution effect of different physical activities. During a mean follow-up of 13.95 (range 2.95-16.28) years, 2,649 deaths were recorded. Diabetes was significantly associated with increased time spent engaging in sedentary behavior (SB), and reduced time spent on moderate-to-vigorous physical activity (MVPA) and light-intensive physical activity (LPA), thereby demonstrating an association with higher mortality risk. The indirect effect of physical activity (HR = 1.27, 95% CI 1.23-1.30) accounted for 41.9% of the total effect of diabetes on mortality. Furthermore, the Life expectancy gains with a maximum of 1.32 years over the next 10 years was found when reallocating SB time to MVPA. The results revealed that 24-hour physical activities might mediate the association between diabetes and mortality. Therefore, promoting participation in MVPA and reducing sedentary activities among diabetes patients was expected to have a positive effect on Life expectancy over the next 10 years. Show less
Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanis Show more
Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanisms of carcinogenesis. Here, we developed geMER to identify candidate driver genes genome-wide by detecting mutation enrichment regions within coding and non-coding elements. We subsequently designed a pipeline to identify a core driver gene set (CDGS) that broadly promotes carcinogenesis across multiple cancers. CDGS comprising 25 genes for 25 cancers displayed instability in DNA aberrations. Variants within the TTN enrichment region may influence the folding of the I-set domain by altering local polarity or side-chain chemistry properties of amino acids, potentially disrupting its antigen-binding capacity in LUAD. Multi-omics analysis revealed that APOB emerged as a candidate oncogene in LIHC, whose genetic alterations within the enrichment region may activate key TFs, upregulate DNA methylation levels, modulate critical histone modifications, and enhance transcriptional activity in the HepG2 and A549 cell lines compared to Panc1. Additionally, CDGS mutation status was an independent prognostic factor for the pan-cancer cohort. High-risk patients tended to develop an immunosuppressive microenvironment and demonstrated a higher likelihood of responding to ICI therapy. Finally, we provided a user-friendly web interface to explore candidate driver genes using geMER ( http://bio-bigdata.hrbmu.edu.cn/geMER/ ). Show less
This study investigates the effect of angiopoietin-like 4 (ANGPTL4) on allergic rhinitis (AR) and explores the underlying mechanisms. A mouse model of AR was generated through ovalbumin (OVA) challeng Show more
This study investigates the effect of angiopoietin-like 4 (ANGPTL4) on allergic rhinitis (AR) and explores the underlying mechanisms. A mouse model of AR was generated through ovalbumin (OVA) challenge. The numbers of nasal rubbing and sneezing were counted and scored. Histological staining was conducted to analyze pathological alterations and inflammation in the mouse nasal mucosa. Inflammatory cytokines in serum and nasal lavage fluid (NALF) samples were analyzed using ELISA kits. Populations of regulatory T cells (Tregs) and Th17 cells in NALF or lymph nodes were analyzed using flow cytometry. Mice with AR were administered short hairpin (sh) RNAs targeting ANGPTL4. The effect of Notch pathway in AR severity was analyzed by gain- and loss-of-function assays. The consistent OVA challenge led to significant AR-like symptoms in mice, along with increased Notch signaling activation. Inhibiting this pathway using γ-secretase inhibitor (DAPT) markedly reduced the AR scores and alleviated inflammatory infiltration by improving Treg/Th17 cell balance. ANGPTL4 silencing significantly mitigated AR-related symptoms, Treg/Th17 cell imbalance, and inflammatory cascades in mice by inactivating the Notch signaling pathway. However, these alleviating effects of ANGPTL4 silencing on mice were negated by the administration of valproic acid, an agonist of the Notch signaling. This paper provides evidence that the ANGPTL4 knockdown shows significant therapeutic effects on AR by improving the Treg/Th17 cell balancing, effects achieved, at least in part, by blocking the Notch signaling pathway. Show less
Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagi Show more
Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagic pathway has emerged as an avenue for cancer therapy. In the present study, we identify apolipoprotein B100 (ApoB100), a key modulator of lipid metabolism, as a potential prognostic biomarker of ovarian cancer. ApoB100 functioned as a tumor suppressor in ovarian cancer, and the knockdown of ApoB100 promoted ovarian cancer progression in vivo. Moreover, ApoB100 blocked autophagic flux, which was dependent on interfering with the lipid accumulation/endoplasmic reticulum (ER) stress axis. The effects of LFG-500, a novel synthetic flavonoid, on ApoB100 induction were confirmed using proteomics and lipidomics analyses. Herein, LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100. Moreover, data from in vivo experiments further demonstrated that ApoB100, as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy, were responsible for the anti-tumor effects of LFG-500 on ovarian cancer. Hence, our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment. Show less
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from u Show more
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups. Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Show less
Mendelian randomization studies have identified that apolipoprotein B (ApoB) is the primary genetic determinant of ischemic stroke, rather than other lipid markers. However, its association with recur Show more
Mendelian randomization studies have identified that apolipoprotein B (ApoB) is the primary genetic determinant of ischemic stroke, rather than other lipid markers. However, its association with recurrent non-cardioembolic acute ischemic stroke (NCAIS) remains unclear. This study aimed to investigate this association. This study recruited 578 patients with acute ischemic stroke, excluding those with cardiogenic embolism. After a 3-year follow-up, a total of 428 patients completed the prospective cohort study. A Cox regression model was used to evaluate the association between ApoB levels at admission and the recurrence rate. Additionally, a nested case-control study was conducted by comparing blood samples collected at the time of recurrence from recurrent patients with those from non-recurrent patients. Binary logistic regression and ROC analysis were used to assess the association between serum ApoB, low-density lipoprotein cholesterol (LDL-C), and recurrent stroke at the time of recurrence. The Cox regression model demonstrated that ApoB levels at admission were independently associated with an increased risk of recurrent NCAIS (HR=6.697; 95%CI 2.581-17.374, P < 0.001). Recurrent stroke patients had significantly higher serum ApoB levels at admission than non-recurrent ones [0.85 g/L (IQR 0.21) vs. 0.63 g/L (IQR 0.15)]. In ROC analysis, ApoB (AUC = 0.732) showed a greater discriminatory ability for recurrent stroke than LDL-C (AUC = 0.685). Higher serum ApoB levels increased the risk of recurrence in patients with NCAIS, and ApoB demonstrated better discriminatory ability than LDL-C after therapy. These findings suggest that routine ApoB measurement may help improve secondary stroke risk assessment. Show less
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. W Show more
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 Show less
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treat Show more
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation. Show less
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emergi Show more
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emerging evidence has identified significant associations between CAVS and key biomarkers, including Lp(a) (lipoprotein [a]), low-density lipoprotein cholesterol, and PCSK9 (proprotein convertase subtilisin/kexin type 9). However, robust evidence from randomized controlled trials is still lacking to substantiate these associations. The EPISODE (Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis) trial is a prospective, evaluator-blinded, randomized controlled trial designed to assess the therapeutic efficacy of PCSK9 inhibitors in patients with CAVS. A total of 160 patients with mild-to-moderate or asymptomatic severe CAVS will be randomly assigned to receive either statin monotherapy or a combination of statins and PCSK9 inhibitors. Participants will undergo follow-up assessments at 3-month intervals for 24 months, including transthoracic ultrasonic cardiogram, computed tomography, and quality-of-life evaluations using the EuroQol-5 Dimension-3 Level questionnaire. The primary end point is the annualized change in peak aortic jet velocity, whereas secondary end points encompass changes in aortic valve area, calcification score, incidence of heart valve surgery, and quality of life. Safety end points include all-cause mortality and cardiovascular events. The trial aims to evaluate the efficacy of PCSK9 inhibitors in modulating disease progression, reducing adverse cardiovascular events, and improving clinical outcomes in patients with CAVS. The anticipated findings are expected to provide critical insights for developing novel therapeutic strategies for early intervention in CAVS. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04968509. Show less
Interleukin-27 (IL-27), an Interleukin-12 (IL-12) family heterodimeric cytokine, plays a central yet complex role in immunoregulation within the intestinal mucosa, where its context-dependent actions Show more
Interleukin-27 (IL-27), an Interleukin-12 (IL-12) family heterodimeric cytokine, plays a central yet complex role in immunoregulation within the intestinal mucosa, where its context-dependent actions can promote both protective and pathogenic outcomes. Although its cellular sources, receptor structure (IL-27Rα/gp130 complex), and involvement in regulating key immune cells (e.g., T-cell subsets, macrophages, neutrophils) and epithelial functions are established, the precise mechanisms underlying its paradoxical effects-balancing homeostasis with inflammation-remain incompletely resolved. This review synthesizes current understanding of IL-27 biology to clarify its multifaceted role. Crucial insights into these dual functions have emerged from preclinical models, including murine colitis (e.g., DSS-, TNBS-induced), enteric infection (e.g., Toxoplasma gondii, Citrobacter rodentium), and colorectal cancer models. These studies demonstrate that IL-27 critically orchestrates gut immunity, maintaining homeostasis through antimicrobial defense and barrier enhancement while suppressing immunopathology. Conversely, its dysregulation drives chronic inflammation and carcinogenesis. Clinically, IL-27 expression correlates with disease activity in inflammatory bowel disease (IBD), colorectal cancer (CRC), and infections, highlighting its biomarker potential. Consequently, targeting the IL-27 pathway presents promising therapeutic avenues: augmenting signaling may mitigate IBD hyperinflammation, while inhibition could bolster antitumor immunity or resolve infection-driven pathology. Future research must prioritize defining context-specific IL-27 functions, optimizing delivery strategies, and integrating IL-27 targeting with existing biologics to translate its immunomodulatory potential into novel therapies for intestinal diseases. Show less
The treatment and prognosis of cardiac amyloidosis (CA) depend heavily on the accurate identification of amyloid protein types. Histopathological methods are the most commonly used approach, but often Show more
The treatment and prognosis of cardiac amyloidosis (CA) depend heavily on the accurate identification of amyloid protein types. Histopathological methods are the most commonly used approach, but often produce inconclusive results. The application of mass spectrometry with laser microdissection mass spectrometry based on non-targeted proteomics in CA diagnosis is gradually being recognized, but it is expensive, time-consuming, and still in the early stages of scientific research applications. This study aims to establish a novel typing method based on targeted semi-quantitative proteomics to address the shortcomings of existing methods. Formalin-fixed, paraffin-embedded (FFPE) myocardial tissue samples from 52 CA and 52 hypertrophic cardiomyopathy (HCM) patients were analyzed. A semi-quantitative typing method was developed using triple quadrupole mass spectrometry, with laser microdissection mass spectrometry (LMD-MS) serving as the reference standard. A total of 52 peptides were analyzed. Key amyloid-associated proteins (AAPs) -apolipoprotein A-IV (apo A-IV), apolipoprotein E (apo E), and serum amyloid P component (SAP) - showed high diagnostic accuracy, with AUC values of 0.964, 0.999, and 0.923, respectively. Transthyretin (TTR), immunoglobulin light chains- κ (IGL - κ), and IGL-λ were semi-quantified using normalized scores (NS) adjusted for microdissection and peptide peak areas. An NS This targeted semi-quantitative mass spectrometry method has high consistency with non-targeted LMD-MS typing, with an accuracy higher than IHC (100 % vs. 30.8 %), while compensating for the shortcomings of non-targeted proteomics. It provides a practical method for CA typing in routine clinical laboratories and may help identify rare subtypes of amyloidosis in the future. Show less
Despite preclinical evidence for berberine's antidepressant potential, its pharmacological effects remain controversial.This study therefore systematically reviews animal research to clarify its mecha Show more
Despite preclinical evidence for berberine's antidepressant potential, its pharmacological effects remain controversial.This study therefore systematically reviews animal research to clarify its mechanisms and support future clinical trials. We searched PubMed, Embase, Web of Science, Cochrane Library, and OVID for studies on berberine in depression models up to March 20, 2025. Analysis used STATA 15.0 and Review Manager 5.4, with study quality assessed via SYRCLE's risk of bias tool. The meta-analysis included 18 studies (338animals). Overall, berberine significantly reduced depression-like behaviors in animal models.Specifically, BBR increased total locomotor activity in the open field test (SMD=2.79, 95% CI: 1.55, 4.02) and time spent in the center zone (SMD=2.49, 95% CI:1.61, 3.37), reduced immobility time in both the forced swim test and tail suspension test (SMD =-4.42, 95% CI:-5.77,-3.07; SMD=-4.46, 95% CI:-6.21, -2.71), increased sucrose intake in the sucrose preference test (SMD = 3.72, 95% CI: 2.37, 5.07), and reduced feeding latency in the novelty-suppressed feeding test (SMD=-5.72, 95% CI:-7.63, -3.82). However, BBR did not significantly alter the number of square crossings (SMD=1.36, 95%CI:-0.07 , 2.79) or rearing frequency (SMD=1.66, 95% CI: -0.29, 3.61) in the open field test. BBR also increased the levels of body weight, brain-derived neurotrophic factor, dopamine, serotonin, and norepinephrine,while reducing the levels of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. Preclinical studies suggest that berberine may represent a promising therapeutic agent for the treatment of depressive disorders. Its antidepressant effects appear to be closely associated with the modulation of neurotransmitter levels,reduction of oxidative stress, and inhibition of inflammatory responses.However, methodological limitations may constrain these findings. Larger, more rigorous preclinical studies are needed for confirmation. https://inplasy.com/inplasy-2025-6-0002, identifier INPLASY202560002. Show less
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is Show more
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure. Conversely, Hey2 depletion in adult mouse hearts and zebrafish enhances the expression of mitochondrial oxidation genes and cardiac function. Multifaceted genome-wide analyses reveal that HEY2 enriches at the promoters of genes known to regulate metabolism (including Ppargc1, Esrra and Cpt1) and colocalizes with HDAC1 to effectuate histone deacetylation and transcriptional repression. Consequently, restoration of PPARGC1A/ESRRA in Hey2- overexpressing zebrafish hearts or human cardiomyocyte-like cells rescues deficits in mitochondrial bioenergetics. Knockdown of Hey2 in adult mouse hearts protects against doxorubicin-induced cardiac dysfunction. These studies reveal an evolutionarily conserved HEY2/HDAC1-Ppargc1/Cpt transcriptional module that controls energy metabolism to preserve cardiac function. Show less
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and Show more
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and molecular pathological characteristics, of two patients harboring both Both patients were women aged 57 and 66 years. The two cases were diagnosed as invasive lung adenocarcinoma, and immunohistochemical staining showed that all tumor cells expressed CK7, Napsin A, TTF-1, and PD-L1. In Case 1, an Show less
Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 Show more
Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 nm NPs exposed group B, 5 ng·L Show less
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Show more
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear. This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved. The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE Show less
Diabetic retinopathy (DR) is a common complication of type II diabetes mellitus (T2DM) and a leading cause of blindness in the working population. Apolipoprotein levels have been reported to be associ Show more
Diabetic retinopathy (DR) is a common complication of type II diabetes mellitus (T2DM) and a leading cause of blindness in the working population. Apolipoprotein levels have been reported to be associated with the risk of DR. This study aimed to develop a predictive model for DR based on apolipoproteins (apoA and apoB) and menopausal status in Chinese Han women with T2DM and to evaluate the model's effectiveness. Data from 2339 T2DM women were collected between January 2018 and June 2022. Multilevel regression was used to explore the independent effect of apolipoproteins and interaction between apolipoproteins and menopausal status on DR and proliferative diabetic retinopathy (PDR). Receiver operating characteristic (ROC) analysis was performed to compare the fitting degree and predictive efficiency of different models. Results showed that both apoA and apoB were independent influencing factors for DR and PDR and interacted significantly with menopausal status. The interaction between apoA and menopausal status had a protective effect on DR [OR (95% CI) = 0.925 (0.858-0.996), P = 0.040] and PDR [OR (95% CI) = 0.937 (0.895-0.981), P = 0.006]. In contrast, the interaction between apoB and menopausal status was a risk factor for DR [OR (95% CI) = 1.684 (1.141-2.379), P = 0.008)] and PDR [OR (95% CI) = 3.377 (1.148-9.937), P = 0.027]. ROC analysis demonstrated that the interaction model outperformed models without interaction terms (P < 0.01). The area under the curve for the interaction model was 0.879 (95% CI 0.864-0.893) for DR and 0.930 (95% CI 0.915-0.945) for PDR. These findings suggest that the interaction model is highly efficient in predicting DR, particularly PDR, in Chinese Han women with T2DM. Show less
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. Ho Show more
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. However, existing materials mainly cover the 380-1540 nm range, with slight extension to the UV region, impeding their applications in solar-blind imaging, background-free tracking, concealed communication, etc. To address this challenge, here we propose guidelines for far-UVC (200-230 nm) optical design. Accordingly, we achieve multi-stimulated far-UVC luminescence at ~222 nm in Pr Show less