Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In Show more
Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In this study, we investigated the therapeutic potential of clinical-grade human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) for treating refractory moderate-to-severe intrauterine adhesion (IUA). In a rabbit IUA model, sub-endometrial injection of IMRCs significantly reduced fibrosis and enhanced endometrial angiogenesis, outperforming uterine perfusion. Transcriptomic analysis revealed distinct pro-angiogenic gene expression profiles between the two delivery routes. In vitro, IMRCs co-cultured with endometrial stromal cells (ESCs) markedly enhanced angiogenic potential compared to either cell type alone. Protein array analysis of the co-culture supernatant showed elevated levels of angiogenic factors, with functional assays confirming that inhibition of ANGPTL4, a non-canonical pro-angiogenic mediator, impaired angiogenesis. In a first-in-human, single-center, phase 1 dose-escalation trial involving 18 patients with refractory IUA, high-dose sub-endometrial IMRC injection promoted angiogenesis, reduced uterine scarring, and improved pregnancy outcomes, with no safety concerns observed over 3 years of follow-up. These findings highlight the translational promise of IMRCs as a novel therapeutic strategy for endometrial regeneration in severe IUA. Show less
The combination of Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma (Baizhu-Cangzhu, BC) is a commonly used couplet medicine suitable for strengthening spleen function in the clinic. The co Show more
The combination of Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma (Baizhu-Cangzhu, BC) is a commonly used couplet medicine suitable for strengthening spleen function in the clinic. The combination of BC originates from the ancient Chinese medical text Zhang's Medical Expert. Ancient Chinese doctors often used a combination of these two drugs or their different processed products to supplement the spleen and resolve dampness and treat hyperlipidemia (HLP). However, no further research has been conducted on the characteristics of the effects of different combinations of its raw drug and processed products. The present study aimed to elucidate the regulatory effect of raw BC, stir-frying BC with bran, and their different combinations on HLP and the therapeutic characteristics of each sample, and promote their application in the treatment of HLP and related diseases. A HLP model was induced by feeding mice with a high-fat diet (HFD) for six weeks. Serum biochemical indicators levels were measured using a fully automatic blood biochemistry analyzer. HE staining was used to observe the pathological changes of liver and small intestine tissues, Oil-Red O staining and Masson staining was used to observe the lipid and collagen deposition in the liver tissue, respectively. The levels of inflammatory cytokines, gastrointestinal hormones, and lipid metabolism-related indicators in the serum were detected by ELISA. The expression of aquaporins (AQPs) in liver tissues and MUC2 in small intestinal tissues were detected by immunohistochemistry. The protein expression levels of AQPs in liver tissues and tight junction proteins in small intestinal tissues were measured by Western blotting. The expression and localization of ZO-1 protein in small intestinal tissues were detected by immunofluorescence. The BC group significantly reduced serum TC and LDL-C levels (P < 0.005). FBFC treatment lowered serum AST levels (P < 0.05) and increased CETP and PLTP levels (P < 0.05). IL-6 and AQP9 levels were reduced in all treatment groups (P < 0.05). In liver tissue, AQP3 expression was upregulated in the BC and FBC groups, while AQP8 expression increased in the BFC and FBC groups (P < 0.05). In small intestine tissue, AQP3 expression was elevated in the BC and BFC groups, and AQP8 was increased in the BFC, FBC, and FBFC groups (P < 0.05). ZO-1 expression was enhanced in the BFC, FBC, and FBFC groups, while Claudin-1 expression was higher in the BC and FBFC groups (P < 0.05). MUC2 expression was increased in the FBFC group (P < 0.05). Our findings demonstrated that BC, stir-frying BC with bran, and their various combinations exert distinct therapeutic characteristics in improving spleen deficiency and lowering lipid levels in HFD-induced HLP mice. The raw products showed stronger lipid-lowering effects, whereas the processed products were more effective in improving liver enzyme profiles, regulating gastrointestinal hormones, and repairing intestinal barrier dysfunction. Show less
COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise ant Show more
COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise anti-inflammatory mechanisms and its potential to ameliorate depression-like behaviors remain incompletely understood. This study investigated the effects of COG133 in mouse models of depression induced by lipopolysaccharide (LPS), chronic social defeat stress (CSDS), and corticosterone (CORT), as well as in LPS-stimulated BV-2 microglial cells. We found that COG133 treatment significantly alleviated depression-like phenotypes and suppressed hippocampal neuroinflammation by inhibiting microglial overactivation. Using RNA sequencing (RNA-seq) and biochemical validation, we identified the MKK3/6-p38-ATF2 signaling axis as a central mechanism underlying the anti-inflammatory effects of COG133. Pharmacological modulation of p38 MAPK further confirmed that this pathway is essential for COG133-mediated behavioral and cellular recovery. Together, these findings identify COG133 as a promising peptide candidate for the treatment of depression through modulation of the p38 MAPK-mediated neuroinflammation axis. Show less
Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in th Show more
Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in the development and recovery of tracheal injury from septic shock. Nine New Zealand white rabbits were randomized to control (CON), septic shock model (SS), and septic shock norepinephrine treatment (SSNE) groups (each group n = 3). The SS and SSNE groups were injected with lipopolysaccharide to induce septic shock. The SSNE group was administered Ringer lactate with norepinephrine to maintain normal blood pressure. All animals underwent cuffed endotracheal intubation for 2 h. The injured tracheal segment was harvested. RNA sequencing was performed to identify the DEGs, followed by bioinformatics analysis, and pathological staining (both HE and Masson) was performed for pathological evaluation. Bioinformatics analysis included principal component analysis (PCA), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) network construction. Key findings were validated by qRT-PCR and immunohistochemistry. We obtained 124 upregulated and 28 downregulated DEGs in SS vs. CON groups, along with 60 upregulated and 178 downregulated DEGs in SSNE vs. SS groups. The pathological score showed that trachea tissue in the SS group had the highest score. The protein-protein interaction (PPI) prediction identified APOB and CD36 as the hub genes. The molecular experiments further confirmed that at mRNA and protein levels, APOB was significantly upregulated, while CD36 was significantly downregulated. Subsequent qRT-PCR and immunohistochemical analyses confirmed that APOB expression was significantly upregulated while CD36 was downregulated in the septic shock group, a trend partially reversed by norepinephrine treatment. Our study results suggest that APOB and CD36 may be involved in the pathogenesis of tracheal injury recovery in septic shock patients treated with NE. Not applicable. Show less
Acute kidney injury (AKI), a critical clinical syndrome marked by high incidence and mortality, is currently diagnosed mainly by serum creatinine (SCr) and blood urea nitrogen (BUN), which have high m Show more
Acute kidney injury (AKI), a critical clinical syndrome marked by high incidence and mortality, is currently diagnosed mainly by serum creatinine (SCr) and blood urea nitrogen (BUN), which have high miss rates. This study innovatively proposes using urinary hydrogen peroxide (H Show less
Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key g Show more
Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key genes in Koi Carp responding to S. aureus from human rhinitis remain unclear. In this study, we established an intraperitoneal infection model in koi carp (Cyprinus carpio) using an S. aureus isolate from patients with rhinitis and integrated RNA-seq, qPCR, and ELISA to dissect the host response. Our findings reveal a dual-module immune evasion strategy employed by S. aureus in koi carp. Module I: The pathogen down-regulated the entire complement coagulation cascade (C3, C9, CFH, F7/9/10) and apolipoprotein-mediated opsonins (APOA1, APOB, APOC1/2), thereby crippling innate clearance. Module II: The host mounted a restricted but potent counter-response, characterized by type I IFN signalling (gvin1, MHC-I), NK/T-cell co-stimulation (CD244, SLAMF5), and the selective induction of IL-8 and IL-1β, while IL-6, IL-10, and TNF-α remained unchanged. Functionally, serum superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM) activities surged, confirming an oxidative burst, whereas splenic CD22R protein decreased, indicating B-cell disinhibition. These results establish a molecular basis for understanding the interaction between human-derived S. aureus and the immune system of aquatic organisms. Show less
Fear of progression (FoP) is a prevalent psychological issue among stroke patients. Previous studies failing to distinguish characteristics of patient groups with varying FoP levels. Latent profile an Show more
Fear of progression (FoP) is a prevalent psychological issue among stroke patients. Previous studies failing to distinguish characteristics of patient groups with varying FoP levels. Latent profile analysis (LPA) classifies individuals into distinct subgroups via continuous FoP indicators, boosting classification accuracy by accounting for variable uncertainty. Given FoP's heterogeneity, investigating FoP profiles and their influencing factors in stroke patients is clinically significant for personalized psychological care and improved patient quality of life. A total of 366 stroke patients were selected as study subjects through convenience sampling, and a cross-sectional survey was conducted. FoP was assessed using the Fear of Progression Questionnaire-Short Form (FoP-Q-SF, 2 dimensions, 12 items). Independent variables included demographic characteristics, clinical indicators, the Recurrence Risk Perception Scale for Stroke patients (RRPSS), and the Medical Coping Modes Questionnaire (MCMQ). LPA was performed on the FoP-Q-SF items to identify subgroups. The R3STEP method was used to analyze influencing factors of subgroup membership, and the BCH method was applied to compare differences in distal outcomes across subgroups. Statistical significance was set at The study sample had a mean age of 63.93 ± 10.58 years, with 70.5% males and 65.0% first-ever stroke patients. Two latent profiles were identified: Low-FoP Adaptive Type (C1, 48.6%) and High-FoP Sustained Type (C2, 51.4%). The R3STEP showed that age 18-59 years (OR = 0.476, 95%CI = 0.245-0.924, This study revealed significant heterogeneity in FoP among stroke patients. Age, hypertension comorbidity, excessive recurrence risk perception, MCMQ-confrontation, and MCMQ-avoidance were associated with high FoP. Healthcare providers should prioritize identifying high-risk individuals and develop tailored interventions to reduce FoP and improve rehabilitation outcomes. Show less
Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, d Show more
Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, death. The global incidence of AD is projected to increase significantly, with late-onset AD being predominantly sporadic in nature. Over the past three decades, the Apolipoprotein E (APOE) gene has been recognized as the most important single genetic determinant of sporadic AD risk. The APOE4 allele is a major risk factor for AD and is known to exacerbate the pathological process for AD. Identifying protective variants that may reduce the risk or delay the onset of AD is of great significance for the development of effective treatments. This review comprehensively examines the protective effects of APOE and its related protective mutations. It also explores the impact of these unique protective variants at the cellular level during the pathological progression of AD. Furthermore, the review compiles new insights for AD treatment offered by these protective mutations, exploring the potential applications of APOE and its related protective variants in advanced therapeutic strategies, including gene editing, RNA editing, and stem cell therapy. Show less
Aberrant fibroblast growth factor receptor 3 (FGFR3) activation drives bladder carcinogenesis in humans, but currently approved pan-FGFR inhibitors lack FGFR3 isoform selectivity and fail to counter c Show more
Aberrant fibroblast growth factor receptor 3 (FGFR3) activation drives bladder carcinogenesis in humans, but currently approved pan-FGFR inhibitors lack FGFR3 isoform selectivity and fail to counter clinically acquired resistance mutations (e.g., FGFR3 V555M/L). Herein, we report the structure-based drug design of 4-(1-methyl-1 Show less
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To addre Show more
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To address this, we performed multi-tissue metabolomic profiling (liver, heart, and serum) in apolipoprotein E-deficient (ApoE-/-) mice subjected to CR. Metabolomic analyses of the multiple tissues revealed that glycerophospholipid metabolism pathway was consistently modulated by CR. To explore its relevance in vascular diseases, we performed serum metabolomic profiling in an abdominal aortic aneurysm (AAA) model induced by angiotensin Ⅱ (AngⅡ) infusion in ApoE-/- mice. The level of lysophosphatidylethanolamine (LPE) (16:0/0:0), a metabolite in the glycerophospholipid metabolism pathway, was elevated during AAA progression and significantly reduced by CR intervention, suggesting its potential as a vascular disease risk factor. Notably, glycerophospholipid metabolism and LPE (16:0) were significantly associated with vascular diseases and aging-related indicators in human multi-omics data, including public transcriptomic and lipidomic, and our serum multi-omics profiling of 76 healthy aged individuals. Collectively, our findings establish glycerophospholipid metabolism and LPE (16:0) as systemic signatures of CR with diagnostic potential. They highlight a crucial link between systemic metabolism and vascular remodeling and remodeling-associated vascular diseases, while also functioning as indicators of systemic aging. Show less
Myocardial hypertrophy is one of the most prominent features of heart failure. SET domain-containing protein 7 (Setd7), a catalytic enzyme responsible for histone H3K4 methylation, has been implicated Show more
Myocardial hypertrophy is one of the most prominent features of heart failure. SET domain-containing protein 7 (Setd7), a catalytic enzyme responsible for histone H3K4 methylation, has been implicated in various cardiac diseases. In this study we investigated whether Setd7 contributed to the development of cardiac hypertrophy. Male mice were subjected to a hypobaric hypoxic environment for 8 weeks; neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia for 6 h. We showed that hypoxic stimulation significantly upregulated the expression levels of Setd7 along with the expression of hypertrophic markers ANP and BNP in NRCMs. By conducting loss- and gain-of-function assays, we demonstrated that Setd7 modulated the hypertrophic and inflammatory markers in hypoxic cardiomyocytes. We further revealed that Setd7-mediated activation of E2F1 (E2 promoter binding factor 1) triggered the expression of E3 ubiquitin protein ligases WWP2, which catalyzed the ubiquitination and degradation of glutathione peroxidase 4 (GPx4), a critical lipid peroxide-reducing enzyme. This degradation drove extensive lipid peroxidation, thereby exacerbating pathological cardiac hypertrophy. Notably, GPx4 inhibition by ras-selective lethal small molecule 3 (RSL3) abolished the antihypertrophic effects of Setd7 knockdown in cardiomyocytes, underscoring the pivotal role of lipid peroxidation in Setd7-mediated hypertrophic responses. In summary, Setd7 promotes hypoxia-induced cardiac hypertrophy through the Setd7-E2F1-WWP2-GPx4 signaling pathway, suggesting that targeting Setd7 is a promising therapeutic strategy to alleviate hypoxia-induced myocardial hypertrophy. Show less
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible Show more
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible mechanism by which TUG1 inhibits neural repair subsequent to ICH through adjusting miR-381-3p/brain-derived neurotrophic factor (BDNF). After the ICH model was created, miR-381-3p agomir and pcDNA-TUG1 were injected. The neural function of rats was estimated using the modified neurological severity score. To quantify the expression of genes and proteins, western blotting, immunohistochemistry, and qRT-PCR were used. To confirm the interaction between TUG1 and miR-381-3p and between miR-381-3p and BDNF mRNA, a luciferase reporter assay was employed. In rats treated with miR-381-3p agomir, a trend of improvement in neurological dysfunction was observed, while the pcDNA-TUG1-treated ones showed deterioration. Furthermore, miR-381-3p agomir increased, while pcDNA-TUG1 reduced the expression level of BDNF in ICH rats. TUG1 and BDNF mRNA were validated to attach directly to miR-381-3p. Overexpressing TUG1 inhibited the level of BDNF by sponging miR-381-3p and antagonized its protective effect on neural repair in ICH rats. Our study suggests that TUG1 can sponge miR-381-3p to downregulate BDNF expression and inhibit neural repair following ICH, demonstrating a potential signaling pathway that is conducive to a better understanding of the pathological mechanisms of ICH. Show less
Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEA Show more
Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEAD) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains insufficiently studied. Given the overlapping metabolic disturbances in both conditions, such as insulin resistance and lipid abnormalities, a potential relationship between Lp(a) and peripheral vascular injury in MASLD is biologically plausible. This study aimed to investigate the cross-sectional association between circulating Lp(a) concentrations and the presence of LEAD in a well-characterized MASLD population. A total of 468 MASLD patients undergoing routine health check-ups were included. Lp(a) levels were stratified into three categories: <10 mg/dL, 10–30 mg/dL, and ≥ 30 mg/dL. LEAD was diagnosed using duplex ultrasonography. Multivariable logistic regression models were used to assess the relationship between Lp(a) levels and the presence of LEAD, with adjustments for demographic variables, metabolic conditions, and lipid-related parameters. Subgroup analyses were conducted to assess potential effect modification. LEAD was diagnosed in 61.5% ( Elevated Lp(a) levels were associated with a higher prevalence of LEAD in patients with MASLD. Although the magnitude of association per unit increase was modest, higher Lp(a) concentrations were associated with greater LEAD prevalence. These findings should be interpreted cautiously and viewed as hypothesis-generating, particularly with respect to subgroup analyses. Prospective studies are needed to clarify causality and clinical relevance. The online version contains supplementary material available at 10.1186/s12872-026-05600-7. Show less
Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non- Show more
Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non-foamy macrophages (NFMs). MicroRNAs are key regulators of macrophage function; for instance, The role of Unlike FMs, NFMs are primarily located in the plaque core and show higher Show less
Early-life stress is a critical determinant of vulnerability to later-life affective and cognitive dysfunction, yet the mechanisms through which adolescent adversity enhances adult stress susceptibili Show more
Early-life stress is a critical determinant of vulnerability to later-life affective and cognitive dysfunction, yet the mechanisms through which adolescent adversity enhances adult stress susceptibility remain incompletely understood. Here, we employed a two-hit model combining adolescent social isolation stress (SIS) with adult chronic restraint stress (CRS) to examine how developmental stress interacts with adult stress exposure. SIS alone or CRS alone exerted minimal behavioral effects, whereas SIS followed by CRS markedly potentiated depression-like behaviors and impaired spatial and object recognition memory. Two-hit stress produced robust hippocampal neuroinflammatory responses, including increased astrocytic and microglial activation and elevated TNF-α, IL-1β, IL-6, and IL-17A levels. These inflammatory alterations were accompanied by pronounced suppression of the BDNF/TrkB/p-CREB signaling cascade, reduced synaptic protein expression, and diminished dendritic spine density and branching complexity in CA1 pyramidal neurons. Notably, light treatment (LT) administered during CRS exposure significantly reversed two-hit induced behavioral deficits, attenuated glial activation and cytokine upregulation, enhanced BDNF/TrkB and p-CREB signaling, and restored synaptic and structural plasticity. Together, these findings indicate that adolescent SIS primes the hippocampus for exaggerated neuroinflammatory and neuroplastic impairments following adult stress, thereby amplifying stress vulnerability. Furthermore, LT emerges as a safe non-pharmacological intervention capable of mitigating combined stress-induced emotional and cognitive dysfunction by targeting neuroinflammatory and neurotrophic pathways. Show less
This study aimed to integrate network pharmacology, bioinformatics analysis, molecular docking, and experimental validation to construct a "component-target-pathway" multidimensional network model, sy Show more
This study aimed to integrate network pharmacology, bioinformatics analysis, molecular docking, and experimental validation to construct a "component-target-pathway" multidimensional network model, systematically elucidate the potential mechanisms underlying the therapeutic effects of the extract of Potentilla freyniana Bornm. (PFB) on hepatocellular carcinoma (HCC), and thereby clarify its pharmacological basis. HCC datasets were retrieved from GEO and TCGA databases, and the DEGs were screened. The active components of the n-butanol extract of PFB were obtained by UHPLC-MS/MS, and the candidate target genes were predicted by the SwissTargetPrediction, Similarity Ensemble Approach, and SuperPred databases. The overlapping target genes were selected by GO and KEGG enrichment analysis, and the key target genes were screened by the SVM and RF algorithms. The verification of differentially expressed target genes and ROC analysis of key target genes were performed. Molecular docking was performed using CB-Dock2. We investigated the parameters of proliferation, migration, invasion, and apoptosis in the n-butanol extract of PFB treated HCC, and we verified the expressions of key proteins in HCC by Western blot. Toxicity experiments showed that the n-butanol extract of PFB did not cause significant toxic damage to the mice heart, liver, and kidney. CCK8 assays detected that the n-butanol extract of PFB had inhibitory effects on HCC. Through network pharmacology, we obtained a total of 17 overlapping genes and finally screened out 6 key target genes by SVM and RF algorithm analyses. Molecular docking and molecular dynamics results showed that the active components of PFB, such as ellagic acid, luteolin, berberrubine, procyanidin B1, and adenosine, had better affinity with these key target genes. By qPCR and Western blot assays, we verified that the expressions of CDK1 and EZH2 and the key factors of the MPAK signaling pathway were significantly down-regulated in HCC. This study demonstrated that the n-butanol extract of PFB exhibits a strong inhibitory effect on the proliferation of HepG2 cells and clarifies the underlying molecular mechanisms involved. By precisely modulating the expression levels of critical signaling molecules - including CDK1, PDGFRB, AKT1, FGFR1, MAPK1, and EZH2 - the n-butanol extract of PFB robustly disrupts cancer cell cycle progression and perturbs the activity of associated signaling pathways, thereby significantly curtailing the aberrant proliferation of tumor cells. This study not only elucidated the effects of the n-butanol extract of PFB on the aforementioned targets but also established a theoretical and experimental basis for further investigating their application in the treatment of HCC. Furthermore, it offers novel insights and research directions for the development of innovative therapeutic strategies derived from natural products, particularly those centered on multi-target synergistic approaches for liver cancer treatment. Show less
Wenjie Li, Chen Li, Xing Li+1 more · 2026 · The aging male : the official journal of the International Society for the Study of the Aging Male · Taylor & Francis · added 2026-04-24
Prostate cancer (PCa) is a leading cause of male cancer-related death globally. While the gut microbiota is linked to PCa, its genetic association remains unclear. We screened genetic instruments rela Show more
Prostate cancer (PCa) is a leading cause of male cancer-related death globally. While the gut microbiota is linked to PCa, its genetic association remains unclear. We screened genetic instruments related to the gut microbiota and paired them with PCa genome-wide association study data to conduct Mendelian randomization (MR) analysis. Positive MR findings were then subjected to colocalization analysis. Subsequently, we utilized the Gene Expression Omnibus (GEO) dataset to perform differential expression analysis, aiming to identify differentially expressed associated genes (DEAGs). We determined the importance scores of these DEAGs through four machine learning models and constructed a nomogram based on these findings, and then validated it in another group of the GEO dataset. MR analysis found 16 gut bacteria causally linked to PCa (7 risk, 9 protective), with 144 related genes. PLCL1, VSNL1, ROR2, NRXN3, and TEAD1 were identified as feature genes for constructing a nomogram that provides a quantitative prediction of the risk of PCa onset. This study indicates that there are causal links between the gut microbiota and PCa. Feature genes may affect the occurrence of PCa by inhibiting the epithelial-mesenchymal transition, proliferation, migration, and invasion of cells. Show less
Prednisone is used clinically during pregnancy. This study investigates whether prenatal prednisone exposure (PPE) affects susceptibility to high-fat diet (HFD)-induced metabolic dysfunction-associate Show more
Prednisone is used clinically during pregnancy. This study investigates whether prenatal prednisone exposure (PPE) affects susceptibility to high-fat diet (HFD)-induced metabolic dysfunction-associated fatty liver disease (MAFLD) in adult offspring and explores underlying mechanisms. Pregnant Kunming mice were administered prednisone (0.25 or 1 mg/kg; PPE-L or PPE-H) or vehicle control (5% carboxymethyl cellulose; Ctrl) by daily gavage from gestational days 0-18. Offspring were assessed metabolically, histologically, and via RNA-Seq. Primary hepatocytes were treated with fatty acids with or without the epigenetic inhibitors to evaluate Nr1h3 expression and lipid deposition. Offspring body weight was similar in PPE-L vs Ctrl, but was reduced in PPE-H group followed by delayed growth. After 6-week HFD feeding, PPE-L offspring showed mild metabolic issues, while PPE-H males exhibited significant glucose/lipid disorders and hepatic steatosis compared to controls. RNA-Seq showed upregulation of hepatic lipid pathways in the PPE-H male offspring when challenged by HFD. The liver X receptor alpha (LXRα)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway and the expression of genes involved in de novo fatty acid synthesis were increased in PPE-H offspring under HFD. A485 significantly downregulated the expression of Nr1h3 in primary hepatocytes from male PPE-H offspring and alleviated lipid deposition in these hepatocytes treated with fatty acids. The H3K27ac level in the Nr1h3 promoter in the PPE-H offspring's liver was significantly upregulated. PPE-L impairs offspring glucose/lipid homeostasis, whereas PPE-H increase MAFLD risk of the offspring by epigenetic programming of the hepatic LXRα-SREBP1 pathway, especially in the males. Show less
ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since human cathelicidin LL-37 binds to ApoB-100 in this pathological context Show more
ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since human cathelicidin LL-37 binds to ApoB-100 in this pathological context, we investigated whether the circulating LL-37-ApoB-100 complex could serve as a biomarker for CAD. We performed surface plasmon resonance and protein-protein docking to demonstrate the direct LL-37-ApoB-100 interaction. We developed a specific polyclonal antibody against the complex and measured its levels in human atherosclerotic plaques and plasma, as well as in We identified that LL-37 directly interacted with multiple distinct binding sites on ApoB-100. Plasma levels of LL-37-ApoB-100 complex were significantly elevated in human patients with atherosclerosis. Consistently, levels of this complex were positively correlated with atherosclerotic plaque area in Circulating LL-37-ApoB-100 levels are strongly associated with angiographically documented CAD, highlighting LL-37-ApoB-100 as an independent predictor for CAD. Show less
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the Show more
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the associations between PF, RMS, and cognitive function among community-dwelling older adults in China, analyzing interactions with APOE Ɛ4 and the mediating effect of serum total bilirubin. About 1,081 Hubei Memory and Aging Cohort (HMACS) participants underwent PF (PEF, FEV1 and FVC), RMS (MIP and MEP) assessment, cognitive tests, APOE genotyping, and bilirubin measurement. Multivariate logistic regression and general linear regression were used to analyze associations. Among 1,081 participants (mean age 70.52 ± 5.55 years), 26.1% had cognitive impairment. Lower PF and RMS scores were associated with cognitive impairment. Higher comprehensive PF (c-PF) and RMS indices protected against cognitive impairment (eg, c-PF: OR = 0.482-0.609, PF (especially PEF) and RMS (especially MEP) indices are significantly associated with cognitive function and impairment in older adults, independent of APOE Ɛ4 status. These findings provide biomarkers for assessing cognitive health risk and a basis for interventions targeting PF and RMS to preserve cognitive function. Show less
This study aimed to investigate the current status of career calling among novice nurses, to identify potential subtypes and their population characteristics, and to further explore the factors associ Show more
This study aimed to investigate the current status of career calling among novice nurses, to identify potential subtypes and their population characteristics, and to further explore the factors associated with the different subtypes. A cross-sectional descriptive study was used. From January to February 2024, 845 novice nurses from 11 hospitals in Shanxi Province were selected for an online questionnaire survey using convenience sampling. The demographic questionnaire, transition shock of newly graduated nurses scale, medical staff resilience scale, and career calling scale were used as study instruments. Latent profile analysis (LPA) was used to explore the subtypes of novice nurses' career calling, and multifactorial logistic regression was used to analyze the related factors of novice nurses' career calling. Three subtypes of career calling of novice nurses in this study were identified, namely, lacking-calling group (10.3%), stable-calling group (50.0%), and sufficient-calling group (39.7%). Education, weekly working hours, weekly frequency of night shifts, reasons for choosing nursing, level of transition shock, and level of resilience were significantly associated with the three latent profiles of career calling of novice nurses in this study. Novice nurses' career calling presents 3 latent profiles and is heterogeneous in this study. Nursing administrators could pay attention to the differences in the level of career calling of novice nurses and adopt targeted management strategies based on the type of characteristics of the population in order to improve the level of career calling of novice nurses, help them develop their careers, and stabilize the nursing workforce. Show less
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key Show more
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key genes involved in KC development and in anoikis and endoplasmic reticulum (ER) stress. KC and control datasets from the GEO database were analyzed to identify differentially expressed genes (DEGs). These were cross-referenced with anoikis and ER stress-related genes from Genecards. Functional enrichment, immune infiltration analysis, and machine learning techniques (LASSO, Random Forest) were used to identify candidate molecular signatures, which were then validated in an animal model. We identified 46 DEGs associated with anoikis and 41 DEGs related to ER stress. Functional analysis linked them to apoptosis and IL-17 signaling. Five key molecular signatures were identified: CDKN1A, MCL1, PTGS2, PTHLH, and ANGPTL4. The expression of ANGPTL4, CDKN1A, and MCL1 was consistent in the animal model. These genes are associated with inflammatory and oxidative stress responses. Twelve potential therapeutic drugs were predicted. This study identifies five candidate molecular signatures for KC related to anoikis and ER stress, offering insights into KC pathogenesis and potential targeted therapies. Show less
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morronisid Show more
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morroniside (Mor), an iridoid glycoside compound in Cornus officinalis, is one of the effective active components. The effects of Mor on antioxidant stress, antiapoptosis, and nerve repair function have been widely studied, but the mechanism of Mor in AD treatment remains unclear. To study the neuroprotective effects of Mor and elucidate the molecular mechanisms underlying its improvement of AD symptoms, we used ApoE4 transgenic mice and ApoE4-transfected BV2 cells as models of AD, focusing on microglia phenotype, function, and neuroinflammation. The 10-month-old mice were randomly divided into the ApoE3 control group (ApoE3 + Veh), the ApoE4 model group (ApoE4 + Veh), and the ApoE4 + Mor 10, 20, and 40 mg/kg groups as in vivo models. The in vitro BV2-ApoE model was constructed via lentiviral transfection. The effects of Mor on cognitive function of AD models were assessed through behavioral tests, western blot, immunofluorescence staining, and ELISA to measure changes of related pathological and inflammatory factors. Mor improved the cognitive function of ApoE4 transgenic mice by reducing Aβ plaques in the brain, improving the structural lesions of hippocampal neurons, and increasing synaptic plasticity in the brain of AD mice. In addition, Mor promoted the transformation of microglia from the M1 to the M2 phenotype, inhibited the activation of the CX3CR1/PU.1 signaling axis, and alleviated the dysfunction of microglia both in vitro and in vivo. CX3CR1 siRNA and PU.1 siRNA were used further to verify the regulatory effect of Mor on microglia phenotype. Our findings indicate that Mor can inhibit neuroinflammation, reduce Aβ accumulation, and improve synaptic damage in ApoE4 mice via the CX3CL1/CX3CR1/PU.1 pathway regulating the phenotype and function of microglia. This study provides a new therapeutic candidate for the prevention and treatment of AD. Show less
Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet a Show more
Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet addiction and psychosocial maladjustment. This study aims to explore the transition patterns of internet addiction and its associations with emotional and interpersonal problems over time. A one-year longitudinal survey was conducted among 782 middle school students in rural China. Latent Profile Analysis (LPA) was conducted to identify internet addiction profiles at two time points. Latent Profile Transition Analysis (LPTA) was then used to examine the transition patterns between profiles over time. Subsequently, statistical analyses were conducted to explore how these transitions were associated with emotional and interpersonal problems. Three profiles of internet addiction were identified: minimal-internet addiction, low-internet addiction, and high-internet addiction. Based on LPTA, most adolescents with higher internet addiction at T1 shifted to lower-severity profiles over time (high → minimal: 35.3%; low → minimal: 39.8%; high → low: 33.3%), while some with initially lower levels transitioned to more severe profiles (minimal → high: 6.9%; low → high: 12.2%; minimal → low: 25.7%). Transition into higher addiction profiles predicted increased depression, anxiety, and poorer relationships with parents, peers, and teachers. Conversely, reductions in addiction were linked to improved depressive symptoms. Changes in internet addiction have an impact on adolescent psychosocial maladjustment. Early detection and flexible interventions are essential in rural settings. Show less
We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431- Show more
We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431-fold signal enhancement), and specific lysosome-targeting capability. QV-S allows for not only real-time monitoring of lysosomal viscosity changes in inflammatory and foam cells but also the precise imaging of atherosclerotic plaques in the aortas of ApoE Show less
The poor efficacy of chemotherapy for glioma is mainly due to the difficulty of drug penetration through the blood-brain barrier (BBB), as well as the difficulty of drug concentration in the tumor tis Show more
The poor efficacy of chemotherapy for glioma is mainly due to the difficulty of drug penetration through the blood-brain barrier (BBB), as well as the difficulty of drug concentration in the tumor tissue to reach the effective therapeutic level. The emerging tumor-targeted delivery technology can facilitate the precise enrichment of drugs in the tumor site. Apolipoprotein E (ApoE(159-167) Show less