Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP Show more
Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP85, NUP107, or NUP133 in immortalized human podocytes activates CDC42, an important effector of SRNS pathogenesis. However, it is unknown whether or not loss of NUP160 dysregulates CDC42 in the podocytes. Here, we generated a podocyte-specific Nup160 knockout mouse model with double-fluorescent (mT/mG) Cre reporter genes using CRISPR/Cas9 and Cre/loxP technologies. We investigated nephrotic syndrome-associated phenotypes in the Nup160podo-/- mice, and performed single-cell transcriptomic and proteomic analysis of glomerular suspension cells and cultured primary podocytes, respectively. The Nup160podo-/- mice exhibited progressive proteinuria and fusion of podocyte foot processes. We found decreased Cdc42 protein and normal Cdc42 transcriptional level in the podocytes of the Nup160podo-/- mice using analysis of single-cell transcriptomes and proteomes. We subsequently observed that Cdc42 protein decreased in both kidney tissues and cultured primary podocytes of the Nup160podo-/- mice, although Cdc42 mRNA levels were elevated in the cultured primary podocytes of the Nup160podo-/- mice. We also found that Cdc42 activity was significantly reduced in the cultured primary podocytes of the Nup160podo-/- mice. In conclusion, loss of Nup160 dysregulated Cdc42 in the podocytes of the Nup160podo-/- mice with proteinuria and fusion of podocyte foot processes. Our findings suggest that the dysregulation of CDC42 may contribute to the pathogenesis of SRNS in patients with mutations in NUP160. Show less
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in medi Show more
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in mediating immune suppression. However, the precise mechanisms underlying PMN-MDSCs infiltration into the tumor immune microenvironment (TIME) and their immunosuppressive functions remain poorly understood. In this investigation, we observed that PMN-MDSCs were up-regulated during stomach carcinogenesis, with gastric cancer (GC) cells secreting CCL26 to promote the infiltration of PMN-MDSCs into the TIME via the CX3CR1 receptor. The infiltrating CX3CR1 Show less
Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti Show more
Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti-inflammatory activities, its clinical application is limited by a narrow therapeutic window. In the present study, we developed phosphatidylserine-exposing nanovesicles (Col@PSVs) that leverage the innate phagocytic capacity of macrophage-derived foam cells by presenting surface "eat-me" signals, thereby enabling targeted immune modulation. The synergistic collaboration between Col and PSVs allows low-dose Col to retain robust anti-inflammatory efficacy while mitigating dose-dependent toxicity. Mechanistically, Col@PSVs potently suppress CCR7-mediated NF-κB signaling activation in foam cells, leading to a marked downregulation of pro-inflammatory cytokine and disruption of inflammatory cascades. In ApoE Show less
Ruotong Li, Wenye Zhao, Jiaxin Zhang+7 more · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
The global increase in muscle weakness poses a critical public health concern. Nutritional interventions that improve muscular function hold promise as a therapeutic potential. Vitamin A (VA) and its Show more
The global increase in muscle weakness poses a critical public health concern. Nutritional interventions that improve muscular function hold promise as a therapeutic potential. Vitamin A (VA) and its active metabolites have been implicated in muscle development and the transformation of muscle fiber types. However, conventional VA formulations are restricted by poor stability and low bioavailability. In this study, a stable Nano VA was utilized to systematically evaluate its effects on muscle development and exercise performance in mice, as well as to explore its underlying mechanisms. A total of 44 male C57BL/6J mice were randomly divided into four groups: (i) normal control (NC), (ii) 5 mg/kg Nano VA (5 NVA), (iii) 10 mg/kg Nano VA (10 NVA), and (iv) 10 mg/kg VA (10 VA). The 10 NVA group demonstrated significantly improved muscle strength and swimming endurance, compared with the NC group. Further examination suggested a significant increase in myofiber diameter, cross-sectional area, and the content of fast-twitch fibers. Additionally, Nano VA treatment improved glucose tolerance and insulin sensitivity. To elucidate the mechanism by which Nano VA enhances muscle locomotor ability, transcriptomics and metabolomics data identified 111 differentially expressed genes and 253 differential metabolites. Of these, Angptl4, Ppp1r3a, and Cyp26b1 were identified as candidate regulators of muscle development and myofiber type transformation. In conclusion, Nano VA regulates muscle development and promotes muscle fiber type conversion, thus improving muscle strength and endurance in mice. Moreover, Nano VA facilitates mitigating and improving myasthenia gravis-related conditions. Show less
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contr Show more
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contributing to stroke remains poorly understood. This study aims to investigate the association between the apoB/apoA1 ratio and intracranial or extracranial atherosclerosis. We enrolled 408 patients with acute ischemic stroke who had never been treated with statins or fibrates. Based on the images from computed tomography angiography (CTA), the patients were categorized into four groups: intracranial atherosclerosis stenosis (ICAS, n = 136), extracranial carotid atherosclerosis stenosis (ECAS, n = 45), combined intracranial and extracranial atherosclerosis stenosis (COAS, n = 73), and non-cerebral atherosclerosis stenosis (NCAS, n = 154). Demographic characteristics, clinical factors, and serum lipid levels were collected and then compared across groups. The apoB/apoA1 ratio was significantly higher in patients with ICAS, ECAS and COAS compared to those in the NCAS group. Multivariable logistic regression analysis demonstrated that the ApoB/ApoA1 ratio was independently associated with ICAS, but not with ECAS. ROC curve analysis showed that the ApoB/ApoA1 ratio had a good diagnostic ability for ICAS, with an area under the curve (AUC) of 0.764, an optimal cut-off value of 0.8122, a sensitivity of 81.3%, and a specificity of 59.8%. An higher apoB/apoA1 ratio is associated with ICAS in ischemic stroke patients. Show less
Many patients are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complications. Trimethylamine N-oxide (TMAO), derived from gut microbes, is a key u Show more
Many patients are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complications. Trimethylamine N-oxide (TMAO), derived from gut microbes, is a key unconventional contributor to the development of atherosclerosis. Here we present a strategy performed by orally administered nano-functionalized probiotics (PDMF@LGG) to inhibit TMAO through the gut microbiota-trimethylamine (TMA)-TMAO axis. PDMF@LGG, composed of polydopamine-coated Lacticaseibacillus rhamnosus GG and nanoparticles based on a reactive oxygen species (ROS)-responsive polymeric prodrug of fluoromethylcholine (FMC), can promote the retention of probiotics and nanoparticles in the intestine to persistently scavenge elevated ROS and release drugs. This process suppresses TMA production and absorption, lowering plasma TMAO levels. The therapeutic effects on male ApoE Show less
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
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, infla Show more
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, inflammatory factors, and GSD remain unclear. The aim of this study is to explore the causal relationships among these 3 factors. This study employed 2-sample Mendelian Randomization (TSMR) and 2-step MR to investigate the causal relationships and potential mediation effects among 91 inflammatory factors, 6 lipid metabolism-related molecules (HDL-C, LDL-C, TG, total cholesterol, ApoA1, and ApoB), and GSD. We opted for 4 distinct MR analysis methods including inverse variance weighted method, weighted median method, MR-Egger regression method and MR-PRESSO analysis. Sensitivity analyses included MR-Egger intercept tests, Cochran's Q statistic, Steiger tests, and leave-one-out analyses. Product of coefficients method was used to estimate mediation proportion. TSMR analysis revealed that every 1-unit increase in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), the risk of GSD decreased by 16.5%, 10.2%, 8.4%, and 13.1%, respectively. Inflammatory factors such as Natural killer cell receptor 2B4 (CD244), Macrophage colony-stimulating factor 1 (CSF-1), and interleukin-18 receptor 1 (IL-18R1) were identified as risk factors for GSD, while Fibroblast growth factor 19 levels (FGF19), Interleukin-1-alpha levels (IL-1α), and Interleukin-8 levels (IL-8) were found to be protective. Mediation analysis through 2-step MR identified potential pathways involving ApoA1--IL-8--GSD (P = .084) and IL-1α--ApoB--GSD (P = .117). This study provides robust evidence of causal links between specific lipid metabolites and GSD, as well as suggestive causal associations for several inflammatory factors. However, mediation analysis did not support significant roles for lipids or inflammatory factors as mediators in GSD pathogenesis. Future research could be further pursued in areas such as drug target intervention and mechanistic studies. Show less
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
Insulin supply is the golden standard for type 1 diabetes mellitus (T1DM) therapy. Is there a drug-reduction application for reversing glucose metabolism disabled and diabetic neuropathy (DN), and is Show more
Insulin supply is the golden standard for type 1 diabetes mellitus (T1DM) therapy. Is there a drug-reduction application for reversing glucose metabolism disabled and diabetic neuropathy (DN), and is it suitable for the young and elderly populations? Reducing T1DM-associated DN, and maintaining glucose metabolism require using the anti-aging gene Klotho to regulate specific signaling cascades. This study applied five 16:8 intermittent fasting (16-h fasting, 8-h eating; 168if) protocols by different executing times to young and elderly diabetic mice to evaluate whether 168if is age-dependent and how it alters Klotho-related signaling molecules. Blood glucose levels were efficiently reduced when 168if was implemented in the early stage of T1DM onset (DNf group) of young and elderly mice. Another four groups failed to reduce blood sugar. However, the DNf protocol was unsuitable for diabetic elderly mice because it posed a higher mortality risk for this population. Young DNf mice exhibited reduced thermal hyperalgesia and mechanical allodynia and reversed Klotho downregulation and protein kinase C epsilon (PKCε) upregulation compared with DN mice. Furthermore, young DNf mice exhibited normalization of fibroblast growth factor receptor 1 (FGFR1) and nuclear factor κB (NF-κB) expression, which is involved in Klotho-related glucose metabolism and anti-inflammation. The expression densities of PKCε, Klotho, FGFR1, and NF-κB were linear to neuropathic manifestations. This study demonstrated the effectiveness of 168if application in the early stage of T1DM onset, a straightforward and convenient dietary control method, as a blood glucose control for achieving pharmaceutical reduction and relieving neuropathic pain in young T1DM patients. Show less
Fatty acid desaturase 1 (FADS1) is significantly and specifically upregulated following diabetic corneal injury. However, its role in diabetic keratopathy remains unclear. This study aimed to investig Show more
Fatty acid desaturase 1 (FADS1) is significantly and specifically upregulated following diabetic corneal injury. However, its role in diabetic keratopathy remains unclear. This study aimed to investigate the impact of FADS1 on wound healing and functional recovery of the diabetic corneal epithelium and explore its potential mechanisms. Using high-glucose-induced corneal epithelial cells and a streptozotocin-induced type 1 diabetic mouse model, FADS1 expression was suppressed via FADS1 small interfering RNA (siRNA). Cell migration was assessed using scratch and transwell assays. Wound healing and functional recovery of the corneal epithelium were evaluated using sodium fluorescein staining, anterior segment optical coherence tomography, hematoxylin and eosin staining, and immunofluorescence staining. FADS1 knockdown promoted wound healing and functional recovery of the diabetic corneal epithelium both in vivo and in vitro. Suppression of FADS1 enhanced high-glucose-induced corneal epithelial cell migration, which was dependent on elevated levels of the upstream metabolite γ-linolenic acid. This effect was mediated through the activation of the mitogen-activated protein kinase signaling pathway and the accumulation of autophagosomes. After diabetic corneal epithelial injury, FADS1 expression is specifically upregulated. Knockdown of FADS1 promotes wound healing and functional recovery, suggesting a novel therapeutic strategy for diabetic keratopathy. Show less
Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims Show more
Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers. A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.5 mg) and once-weekly administration for 2 weeks to reach target doses (5, 10 and 15 mg) by titration. A total of 40 volunteers received at least one dose of BGM0504 or placebo. The PK profile of BGM0504 was investigated over a wide dose range and supported once-weekly administration. It was observed that C BGM0504 was generally safe and well tolerated with favourable PK profile and potential role in weight loss was also confirmed. These findings support subsequent development of BGM0504 for type 2 diabetes mellitus (T2DM) and obesity. Show less
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
In recent years, accumulating evidence has highlighted the critical role of miR-627-5p in the occurrence and progression of various cancers. However, its specific role and mechanism in cervical cancer Show more
In recent years, accumulating evidence has highlighted the critical role of miR-627-5p in the occurrence and progression of various cancers. However, its specific role and mechanism in cervical cancer (CC) remain unclear. This study aimed to elucidate the mechanism by which miR-627-5p inhibits the malignant progression of CC and assess its potential clinical implications. In C33A cells, the mRNA expression levels of ANGPTL4 and miR-627-5p were analyzed using qRT-PCR. The miR-627-5p mimics and their control (miR-NC) were transfected into C33A cells to determine whether miR-627-5p directly regulates ANGPTL4 expression. A comprehensive suite of assays, including CCK-8, migration, transwell, flow cytometry, and Western blotting, was conducted to evaluate how miR-627-5p modulates the malignant biological behavior of CC cells. Rescue experiments were performed by overexpressing ANGPTL4. In C33A cells, miR-627-5p expression was reduced, whereas ANGPTL4 expression was elevated. Further analysis confirmed that miR-627-5p negatively regulates ANGPTL4 by directly targeting its 3'-UTR. Functional assays demonstrated that miR-627-5p inhibits proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) while promoting apoptosis and S-phase arrest in C33A cells, effects that were reversed by ANGPTL4 overexpression. These findings highlight the potential of miR-627-5p as both a biomarker and a therapeutic target for CC. By inhibiting EMT and regulating ANGPTL4 expression, miR-627-5p may provide a novel avenue for improving therapeutic strategies, particularly in advanced or metastatic CC. Moreover, miRNA-based therapies, supported by advanced delivery systems such as nanoparticle carriers, could enhance the stability and precision of miR-627-5p applications. This study lays the groundwork for future research integrating miR-627-5p into precision medicine approaches for CC treatment. Show less
Ursolic acid (UA) exhibits antitumor activity; however, its effects and mechanisms on triple-negative breast cancer (TNBC) cells are not well understood. The present study aimed to explore the anti- T Show more
Ursolic acid (UA) exhibits antitumor activity; however, its effects and mechanisms on triple-negative breast cancer (TNBC) cells are not well understood. The present study aimed to explore the anti- TNBC mechanisms of UA by network pharmacology and experimental validation. TNBC cell lines MDA-MB-231 and BT-549 cells were treated with UA. A CCK-8 assay was performed to detect cell growth, while flow cytometry assessed cell cycle arrest and apoptosis. The underlying mechanism and potential targets of UA for TNBC treatment were investigated by network pharmacology, including PharmMapper database, GO, KEGG enrichment, and PPI analysis. The protein expressions and phosphorylation levels of FGFR1, AKT, and ERK were measured by western blot. Pull-down assay, cellular thermal shift assay (CETSA), and molecular docking were used to analyze the interaction between UA and FGFR1. Xenograft models were established to examine the effect of UA on TNBC tumor growth. UA effectively reduced cell viability, induced apoptosis, and arrested cell cycle in TNBC cells. Moreover, UA significantly regulated the expression of Bcl-2 and Bax to induce apoptosis. The results of network pharmacology and western blot suggested that UA reduced FGFR1/AKT/ERK pathway. Furthermore, pull-down, CETSA, and molecular docking results revealed that UA directly bound to FGFR1. In the xenograft model, UA inhibited the growth by suppressing FGFR1. In this study, we employed network pharmacology and experimental approaches to elucidate the mechanism of UA on TNBC. The results demonstrated that UA targeted FGFR1 to inhibit TNBC via mediating FGFR1/AKT/ERK pathway. Our findings demonstrate that UA inhibits the FGFR1/AKT/ERK pathway by directly targeting FGFR1, thereby suppressing TNBC progression and supporting its potential as a therapeutic agent for TNBC treatment. Show less
Despite advancements in treatment, coronary artery disease (CAD) remains a significant global health concern. Although lipoprotein(a) [Lp(a)] is recognized as a crucial cardiovascular risk factor asso Show more
Despite advancements in treatment, coronary artery disease (CAD) remains a significant global health concern. Although lipoprotein(a) [Lp(a)] is recognized as a crucial cardiovascular risk factor associated with increased risk, the prognostic value of using Lp(a) levels in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains debatable. This review aimed to investigate the association between Lp(a) levels and recurrent ischemic events in patients with ACS undergoing PCI. This systematic review included studies with individuals aged ≥18 years diagnosed with ACS who underwent PCI and had Lp(a) measurements. The included studies were sourced from the PubMed database, with a focus on articles published between January 2020 and January 2025. Keywords related to Lp(a) and cardiovascular diseases were used in the search. Data extraction involved a review of titles and abstracts followed by quality assessment using the QUADAS-2 tool. The final analysis included 10 studies with a combined population of 20,896 patients from diverse regions, including Japan, India, Egypt, China, and South Korea. Key findings indicate that elevated Lp(a) levels are significantly associated with adverse cardiovascular outcomes, including myocardial infarction and mortality, both in hospital and during long-term follow-up. This review highlights Lp(a) as a critical biomarker for predicting recurrent cardiovascular events in ACS patients post-PCI. The consistent correlation between elevated Lp(a) levels and adverse outcomes underscores the necessity of routine monitoring and targeted management of Lp(a) to mitigate residual cardiovascular risk. Show less
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-se Show more
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-serving as promising reservoirs of such inhibitors. Nevertheless, comprehensive screening and mechanistic characterization of their inhibitory potential remain limited. This study sought to identify potent AChE inhibitors from YGE, investigate their mechanisms of action, and assess their therapeutic prospects for AD. Methodologically, an integrated approach was employed, combining ultrafiltration-liquid chromatography (UF-LC) for rapid inhibitor screening, molecular docking and dynamics simulations for mechanistic insight, two-stage high-speed countercurrent chromatography for compound isolation, enzyme kinetics to delineate inhibition modalities, and network pharmacology to uncover relevant AD-related targets. The findings identified seven active constituents with notable AChE inhibition, among which parishins A and G were obtained at high purity (98.26% and 97.26%, respectively) and exhibited mixed-type inhibition with low IC Show less
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and contr Show more
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and controversial. Mendelian randomization was applied to assess causal relationships between lipoproteins, circulating proteins, metabolites, and the risk of AAA. To test the hypothesis that elevated plasma TG levels accelerate AAA development, we used Mendelian randomization analyses integrating genetic, proteomic, and metabolomic data identified causal relationships between elevated TG-rich lipoproteins, TG metabolism-related proteins/metabolites, and AAA risk. In the angiotensin II infusion AAA model, most These findings identify hypertriglyceridemia as a key contributor to AAA pathogenesis and suggest that targeting TG-rich lipoproteins may be a promising therapeutic strategy for AAA. Show less
G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, yet the design of protein agonists and antagonists has been challenging as Show more
G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, yet the design of protein agonists and antagonists has been challenging as GPCRs are integral membrane proteins and conformationally dynamic. Here we describe computational Show less
People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, a Show more
People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, and the increased risk of MCI and AD is associated with the lack of estrogen during menopause. Previous studies have shown that Tiao Geng Decoction (TGD) may have antioxidant and anti apoptotic properties, which may prevent neurodegenerative diseases. However, whether TGD is effective in improving mild cognitive impairment due to postmenopausal estrogen deficiency and its potential pharmacological mechanisms remain unclear. The aim of this study was to investigate the possible pharmacological mechanisms of TGD in preventing postmenopausal MCI. We utilized RNA-seq technology to screen for differentially expressed genes (DEGs) and enrichment pathways in the hippocampal tissue of different groups of mice. Additionally, we adopted single-cell sequencing technology to study the cell types of Alzheimer's disease (AD) group and Normal Control (NC) group, the differential marker genes of each cell subgroup, and the GO enrichment analysis of each cell type. Both RNA sequencing and single-cell sequencing results showed a significant correlation between TGD and NF-κb pathway in improving mild cognitive impairment in postmenopausal women. The experimental verification results showed that the spatial learning and memory abilities of APP/PS1 model mice were weakened after ovariectomy, and the reproductive cycle on vaginal smears was in the interphase of diestrus. The levels of serum E2, and P-tau181 in mice were significantly down regulated, while the levels of brain tissue homogenate A β 42, IL-1 β, and IL-18 were significantly up-regulated, indicating successful modeling. Combining Western blotting, RT-qPCR, and transmission electron microscopy analyses, it was found that the low estrogen environment induced by oophorectomy can activate the NF-κb signaling pathway, activate the expression of NLRP3 inflammasome and A β secretase BACE1, and induce neuroinflammatory damage in hippocampal astrocytes. These results conform to the modeling characteristics of MCI. After TGD intervention, the spatial learning and memory abilities of MCI mice were significantly improved. The pharmacological validation results indicated that high concentration doses of TGD had a more significant effect on MCI. Subsequently, we used high concentration TGD (0.32 g/ml) as the traditional Chinese medicine group for further validation, protein blotting and RT-qPCR results indicated that TGD can effectively stimulate the secretion of ER α and ER β, inhibit the NF-κb pathway, downregulate BACE1, and inhibit the expression of NLRP3 inflammasome related proteins. In addition, the immunofluorescence results of hippocampal astrocytes showed that TGD can effectively facilitate the expression of AQP1 and significantly lower the sedimentation of A β compared with the model group. Our research suggests that there is a high correlation between a low estrogen environment and the occurrence and development of MCI. TGD may regulate the ERs/NF - κ b/AQP1 signaling pathway, promote estrogen secretion, activate AQP1, reduce A β deposition, reverse MCI neuroinflammatory injury, improve mild cognitive impairment, and prevent the occurrence of AD. This study revealed for the first time that TGD may be a potential new alternative drug for preventing and improving menopausal MCI. Show less
While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposi Show more
While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposition underlying suicidal behaviors in diverse populations. This study aimed to conduct a large-scale investigation of the suicidality spectrum (SP) to generate new insights into its biology and epidemiology. Leveraging ancestrally diverse participants (SI N This study provides convergent genetic evidence for both shared and phenotype-specific components of suicidal behaviors and delineates their associated factors spanning from proximal clinical and behavioral traits to more distal social determinants. These findings refine our understanding of the etiology of suicidal behaviors and may inform targeted strategies for suicide prevention in both clinical and public health settings. Show less
Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unident Show more
Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unidentified gene-FOS interactions. To identify genetic factors that interact with FOS to alter the circulating levels of PUFAs, we performed a multi-level genome-wide interaction study (GWIS) of FOS on 14 plasma measurements in 200,060 unrelated European-ancestry individuals from the UK Biobank. From our single-variant tests, we identified genome-wide significant interacting SNPs (p < 5 × 10 Show less
The Kirgiz, a Turkic-speaking ethnic group with a rich nomadic heritage, represent a pivotal population for understanding human migration and adaptation in Central Asia. However, their genetic origins Show more
The Kirgiz, a Turkic-speaking ethnic group with a rich nomadic heritage, represent a pivotal population for understanding human migration and adaptation in Central Asia. However, their genetic origins and admixture history remain largely unexplored. Here, we present the first comprehensive genomic study of Kirgiz populations from Xinjiang, China (XJ.KGZ, n = 36) and their counterparts in Kyrgyzstan (KRG), integrating genome-wide data of 2,406 global individuals. Our analyses reveal four primary ancestry components in XJ.KGZ: East Asian (41.7%), Siberian (25.6%), West Eurasian (25.2%), and South Asian (7.6%). Despite close genetic affinity (FST = 0.13%), XJ.KGZ and KRG diverged ∼447 years ago, with limited gene flow post-split. A two-wave admixture model elucidates their demographic history: an initial East-West Eurasian mixture ∼2,225 years ago, likely reflecting west-east contacts during the period of the Warring States and the Qin Dynasty, followed by secondary admixture events (∼875 to 425 years ago) linked to historical migrations under Mongol and post-Mongol rule. Local adaptation signatures implicate genes critical for cellular tight junction (e.g. PATJ), pathogen invasion (e.g. OR14I1), and cardiac functions (e.g. RYR2) with allele frequency deviations suggesting ancestry-specific selection. While no classical high-altitude adaptation genes (e.g. EPAS1) showed selection signals, RYR2 and C10orf67-implicated in hypoxia response in Tibetan fauna-displayed Western ancestry bias, hinting at convergent adaptation mechanisms. This study advances our understanding of the genetic makeup and admixture history of the Kirgiz people and provides novel insights into human dispersal in Central Asia. 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
This experiment investigated the response of carcass composition, digestive function, hepatic lipid metabolism, intestinal microbiota, and serum metabolomics to excessive or restrictive dietary energy Show more
This experiment investigated the response of carcass composition, digestive function, hepatic lipid metabolism, intestinal microbiota, and serum metabolomics to excessive or restrictive dietary energy in Ningxiang pigs. A total of 36 Ningxiang pigs (210 ± 2 d, 43.26 ± 3.21 kg) were randomly assigned to three treatments (6 pens of 2 piglets each) and fed a control diet (CON, digestive energy (DE) 13.02 MJ/kg,), excessive energy diet (EE, 15.22 MJ/kg), and restrictive energy diet (RE, DE 10.84 MJ/kg), respectively. Results showed that EE significantly increased the apparent digestibility of crude protein and total energy ( The findings suggest RE had no obvious negative effect on carcass traits of Ningxiang pigs. Apart from exacerbated body fat deposition, EE promoted fat accumulation in the liver by up-regulating the expression of lipogenic genes. Dietary energy changes affect hepatic bile acid metabolism, which may be mediated through the glycerophospholipid metabolism pathway, as well as disturbances in the gut microbiota. Show less
Human papillomavirus (HPV) infection is a global public health issue, and HPV-related stigma can affect cervical cancer prevention. But no validated tools exist to assess HPV stigma in Chinese adult w Show more
Human papillomavirus (HPV) infection is a global public health issue, and HPV-related stigma can affect cervical cancer prevention. But no validated tools exist to assess HPV stigma in Chinese adult women infected with HPV. This study aimed to adapt and validate the HPVsStigma scale (HPV-SS) in the Chinese context. A cross-sectional study was conducted from December 2024 to February 2025 among 501 HPV-infected women in Shenzhen, China. The HPV-SS was adapted from a 12-item HIV stigma scale. Demographic characteristics, HPV-related variables, and data on mental health were collected. Factor analyses (FA) were used to assess the scale's factorial structure, reliability, and validity. The bi-factor model was used to determine the score-reporting method of the scale. Item response theory (IRT) was employed to assess the relationship between participants' stigma levels and scale scores. Latent profile analysis (LPA) was conducted to classify the participants with different HPV stigma characteristics and determine the optimal cut-off value for HPV-SS. FA showed that the 3-factor model (personalized stigma, public-disclosure concerns, and negative self-image) had the best fit among the nested models, with good reliability and validity. The bi-factor model analysis indicated that the total scale score was more meaningful than dimension scores. IRT analysis confirmed that higher HPV-SS scores represented higher stigma levels. LPA identified a 2-class model as optimal, and the optimal cut-off value of the scale for high HPV stigma was 35. This study validated the 12-item HPV-SS for Chinese women infected with HPV, with good reliability and validity. The scale can be used to evaluate HPV stigma levels, facilitating targeted interventions to improve cervical cancer prevention and the psychological well-being of affected women. Show less
The dysregulation of T cell differentiation was associated with cognitive impairment. Recently, the peripheric β-secretase (BACE1) has been suggested as a regulator of T cell differentiation, which wa Show more
The dysregulation of T cell differentiation was associated with cognitive impairment. Recently, the peripheric β-secretase (BACE1) has been suggested as a regulator of T cell differentiation, which was increased in both cognitive impairment (CI) and type 2 diabetes mellitus (T2DM) in CI patients. However, the relationship between T cell dysfunction and CI remains unclear. To address this question, we measured T cell subtypes and BACE1 enzyme activity in a clinical cohort and 5xFAD mice. We found that both IFNγ+ Th1 and Tc1 cells were increased in the CI and T2DM-CI groups, which were associated with worsening cognitive function. The elevated IFNγ + Th1 and Tc1 cells were also observed in 8-month-old 5xFAD mice. The elevated BACE1-mediated INSR cleavage was associated with increased IFNγ + Th1 and Tc1 cells. These findings demonstrate the potential role of elevated BACE1 in IFNγ+ T cells and CI. 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