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The objective of our investigation was to explore the features of gut microbiota dysbiosis and the concentrations of gut metabolites in relation to white matter injury (WMI). Furthermore, we sought to evaluate the influence of gut dysbiosis on neuroinflammation in WMI via intestinal metabolites, and its contribution to pathogenesis. A cerebral hypoxia-ischemia-induced WMI model was established in 3-day-old Sprague-Dawley rats. Liquid chromatography-mass spectrometry/gas chromatography-mass spectrometry analyses and 16S rRNA gene sequencing were undertaken to ascertain WMI biomarkers. Mechanistic experiments were used to analyse activation of the H3K9ac/BDNF/TrkB pathway and neuroinflammation. The analysis of 16S rRNA sequencing disclosed gut microbiota dysbiosis in WMI rats, quantified using linear discriminant analysis effect size. Overall, 341 differentially expressed metabolic markers between the WMI and Sham groups were discovered. The Kyoto Encyclopedia of Genes and Genomes network enhancement evaluation revealed significant downregulation of 20 metabolic processes in the WMI group, which is strongly related to changes in fecal microbial metabolites, and the synthesis process of unsaturated fatty acids was the most significant. Gut microbiota dysbiosis may influence WMI by downregulating metabolites such as eicosapentaenoic acid (EPA). Fecal microbiota transplantation increased EPA concentration in the brain tissue of WMI rats. Gut microbiota-derived EPA promoted H3K9ac and BDNF/TrkB expression and inhibited the transcription of pro-inflammatory TNF- WMI induces gut dysbiosis involving down-regulation of unsaturated fatty acid synthesis. Fecal microbiota transplantation leads to increased levels of EPA. Gut microbiota-derived EPA increases levels of acetylated histone H3K9ac, causes activation of the BDNF/TrkB pathway, reduces neuroinflammation, and improves WMI-associated myelination disorders. It provides a basis for targeted treatment of white matter injury in the future. Show less

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder in which numerous interconnected pathological processes, such as cholinergic deficits, Aβ and tau aggregation, oxidative stress, metal dyshomeostasis, mitochondrial dysfunction, and neuroinflammation, synergistically drive neuronal damage and cognitive decline. This heterogeneity has limited the effectiveness of the clinically available single-target therapies which only provide symptomatic relief and underscores the need for molecular frameworks capable of addressing multiple pathogenic pathways simultaneously to stop the progression of the disease. Hydrazones have emerged as highly versatile scaffolds in medicinal chemistry thanks to their straightforward synthesis, structural adaptability, and rich repertoire of interaction modes with different biological targets. In recent literature, an increasing number of hydrazone-based molecules have been designed as multitarget-directed ligands (MTDLs) to modulate key enzymes and pathological mechanisms relevant to AD. This review provides a comprehensive and critical overview of hydrazone-containing compounds reported over the last years (2020-2025) with potential application in AD therapy, highlighting their activity on classical targets, especially cholinesterases (ChEs), as well as emerging targets including carbonic anhydrase, BACE1, and α-glycosidase. Particular emphasis is placed on structure-activity relationships (SARs), multitarget profiles, and rational design strategies aimed at exploiting the hydrazone moiety to address the multifactorial nature of AD. Show less

A paternal high-fat diet (HFD) has been shown to affect the expression of peroxisome proliferator-activated receptors ( In this experimental study, adult male Wistar rats (F0) were fed for 60 days with one of the following four diets: control diets (C), control diets with trans fatty acids (CTH), diets containing vitamin E (E) and diets containing vitamin E and trans fatty acids (ETH). Then the male offspring (F1) were raised on standard chow, and their testicular tissue was later analyzed to assess the impact of paternal diet on gene expression, and the expression of the The data revealed that paternal HFD can suppress the expression of Our findings demonstrate the metabolic impact of paternal diet on offspring's, with focus on mechanisms related to altered lipid metabolism and reproductive health. Show less

Research indicates that impairment of instrumental activities of daily living (IADLs) leads to reduced physical activity (PA) in daily life. However, these studies often rely on subjective measures such as questionnaires and interviews to assess PA. This study examined the association between IADL frequency and objectively measured PA in stable individuals with cardiovascular disease (CVD). In this cross-sectional study, we included people with CVD who had been receiving outpatient care under stable conditions for at least 6 months. IADL frequency was assessed using the Frenchay Activities Index (FAI). PA was measured using accelerometers over 2 weeks to calculate the daily average number of steps, low-intensity PA (LPA), and moderate-to-vigorous-intensity PA (MVPA). A multivariate linear regression model analyzed the associations between the FAI scores (total and sub-items) and PA levels. This study included 1126 stable participants with CVD (median age, 74.0 years; 278 females). After adjusting for clinical confounding factors, a high FAI total score was significantly associated with higher levels of PA (number of steps per day, unstandardized coefficient [В] = 78.1, LPA per day, В = 0.7, and MVPA per day, В = 0.2). In the FAI subitems, 4 housework and 6 leisure activities were positively associated with the daily average number of steps and LPA, and 2 leisure activities were positively associated with daily MVPA. Greater IADL frequency was associated with higher objectively measured PA in stable participants with CVD. Leisure-related activities were associated with increased MVPA, suggesting that encouraging these activities may help promote meaningful PA engagement in this population. Show less

Hypertensive disorders of pregnancy (HDP) are associated with future cardiovascular disease but mechanisms are not well defined. We examined the association between HDP and atherosclerotic cardiovascular disease (ASCVD) biomarkers 5-10 years after childbirth. Secondary analysis of the NICHD MFMU Network Gestational Diabetes (GDM) Trial Follow-Up study. Participants were recruited and biospecimens obtained 5-10 years after the original trial of treatment for mild GDM. Patients were included if a biospecimen was available and their HDP status was known. We compared patients who experienced HDP to normotensive controls. Outcomes included unadjusted medians and mean concentrations of ASCVD serum biomarkers Apolipoprotein B (ApoB), high-sensitivity C-reactive protein (hs-CRP), and creatinine. Generalized linear models were used to compare concentrations between groups. Of 740 participants in this analysis, 78 had been diagnosed with HDP. Mean duration of follow up after delivery was 7.1 ± 1.3 years for both groups. Unadjusted means of each biomarker were not different between groups. After adjusting for obesity, mean serum creatinine was elevated in women who had been diagnosed with HDP (0.77 mg/dL 95%CI (0.72, 0.82)) compared to controls (0.71 mg/dL 95%CI (0.69, 0.72)), p = 0.02. Adjusted means for ApoB between women with HDP and controls were 64.2 mg/dL (95%CI (59.3, 69.5)) and 60.6 mg/dL (95%CI (58.9, 62.3)), (p = 0.18), and for hs-CRP mg/L were 14.6 (95%CI (11.4, 19.1)) and 14.5 mg/L (95%CI (13.3, 15.9)), (p = 0.91). In patients with HDP compared to normotensive controls, serum creatinine, but not ApoB or hs-CRP, was modestly elevated within 10 years of childbirth. Show less

To investigate the role of PINK1/Parkin-mediated mitophagy in regulating synaptic remodeling of neuronal cells in depression-like behaviors induced by nonylphenol (NP). In vitro experiments: HT-22 neuronal cells were exposed to NP, and mitophagy and Parkin expression were inhibited using specific inhibitors. The cells were categorized into the following groups: (1) control (C) and low-dose NP group (L: 2.5 µM), medium-dose NP group (M: 50 µM), and high-dose NP groups (H: 100 µM); (2) control (C), NP (100 µM), Mdivi-1 (5 µM), and Mdivi-1 + NP (5 µM Mdivi-1 +100 µM NP) groups; (3) control (C), NP (100 µM), AC220 (2 nM), and AC220 + NP (2 nM AC220 +100 µM NP) groups. In vivo experiments: a total of 48 mice, including 24 C57BL/6 wild-type mice and 24 PKRK2 gene-knockout mice, were randomly assigned to the following four groups: control (C), NP (100 mg/kg/day), PKRK2-knockout (KO), and PKRK2-knockout + NP (100 mg/kg/day, KH) groups, with 12 mice in each group. In vitro: With increasing NP concentration, the ATP content reduced and the expressions of synaptic remodeling-related proteins (i.e., PSD-95, BDNF, SYN) decreased. In contrast, the expressions of mitophagy-related proteins and those involved in the PINK1/Parkin-signaling pathway (such as p62, Beclin1, PINK1, Parkin) increased (P < 0.05). Inhibition of mitophagy with Mdivi-1 alleviated the NP-induced changes in synaptic, mitophagy-related, and PINK1/Parkin pathway-related proteins. Similarly, the inhibition of Parkin with AC220 mitigated NP-induced effects on synaptic, mitophagy-related, and PINK1/Parkin-signaling pathway-related proteins and mRNA expression. In vivo: PKRK2 gene-knockout mice exhibited improved NP-induced depression-like behaviors and decreased NP-induced synaptic morphology and mitochondrial ultrastructure changes. Moreover, the gene knockout alleviated the downregulation of synaptic remodeling-related proteins and inhibited the PINK1/Parkin-signaling pathway-mediated mitophagy activated by NP. Mitophagy inhibition or PKRK2 knockout can alleviate NP-induced downregulation of synaptic remodeling-related proteins, protect synaptic morphology and ultrastructure, and improve NP-induced depression-like behaviors. Show less

To compare a flow-independent, 3D isotropic non-contrast MRA (REACT), with time-resolved contrast-enhanced MRA (4D CE-MRA) for postoperative assessment of the pulmonary arteries in patients with congenital heart disease (CHD), with emphasis on different implant types. In this retrospective single-center study, 53 patients with CHD underwent clinically indicated cardiovascular magnetic resonance (CMR) including both 4D CE-MRA and REACT at 1.5T. Three radiologists independently scored image quality (IQ) as well as motion and susceptibility artifacts on 5-point Likert scales and measured the diameters of the pulmonary arteries (PAs) [main (MPA), left (LPA) and right pulmonary artery (RPA)]. Subgroup analysis was performed for stents, conduit/patch/valve (CPV), and no implant. Pooled across readers and PA segments, REACT achieved higher overall IQ than 4D CE-MRA (median 3.67 [3.00-4.17] vs. 3.00 [2.33-3.33]; p < 0.001) and provided significantly better motion scores (p < 0.001), whereas susceptibility scores were comparable between techniques. The proportion of fully diagnostic studies (3/3 segments) was similar (REACT 77.4%, 41/53; 4D CE-MRA 83.0%, 44/53; McNemar, p = 0.38). Diameter measurements showed excellent inter-reader agreement (ICC ≈ 0.89-0.95) and minimal bias between techniques; only the RPA yielded slightly smaller diameters in REACT (mean difference -0.85 ± 1.51mm, p < 0.001). In subgroup analysis, stented segments showed no IQ advantage of REACT (p > 0.99) with IQ being limited due to susceptibility artifacts in both 4D CE-MRA and REACT. In the CPV and the no implant group, REACT yielded a one point higher median IQ score (both p = 0.002) and one point less impaired by motion artifacts (CPV: p < 0.001; no implant: p = 0.002), while both techniques provided very high shares of diagnostic image quality (defined as IQ ≥ 2; both > 90%; p > 0.99). REACT enables robust, contrast-free postoperative imaging of the pulmonary arteries in patients with CHD with superior IQ and reduced motion artifacts compared to 4D CE-MRA, while maintaining highly reproducible diameter measurements. Stented segments remain a shared limitation. Show less

To retrospectively analyze the effects of Butylphthalide and Sodium Chloride Injection (BP-SC) combined with Argatroban (AG) on neurological deficits and hemorheology in progressive ischemic stroke (PIS) patients. A total of 123 PIS patients admitted to our hospital between April 2023 and April 2025 were retrospectively analyzed and divided into two groups according to the different treatment schemes: the control group (n=58; treated with AG) and the research group (n=65; treated with BP-SC and AG). Clinical efficacy, neurological deficits (assessed by the National Institutes of Health Stroke Scale [NIHSS]), neurological function (astrocyte-derived protein S100β, brain-derived neurotrophic factor [BDNF], and neuron-specific enolase [NSE]), hemorheology (fibrinogen [FIB], plasma viscosity [PV], whole blood low-shear viscosity [WBLSV]), vascular endothelial function (endothelin-1 [ET-1] and nitric oxide [NO]), inflammatory factors (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), adverse events (gingival bleeding, subcutaneous ecchymosis, nausea, abdominal distension, and vomiting), the 90-day post-operative modified Rankin Scale (mRS) score were compared between the two groups. Compared with the control group, the research group demonstrated significantly higher overall effective rate and favorable prognosis rate. The research group also showed greater post-treatment reductions in the NIHSS score and levels of S100-β and NSE, along with a more pronounced elevation in BDNF level, indicating improved neuronal function. Additionally, the combined treatment significantly improved multiple hemorheological indices and endothelial function as evidenced by reduced ET-1 level and elevated NO level. Moreover, levels of hs-CRP, IL-6, and TNF-α were significantly decreased. However, the total incidence of adverse events was comparable between the two groups. Combined treatment with BP-SC and AG exerts more significant improvements in neurological deficits and hemorheological parameters in PIS patients. Show less

To evaluate the preventive effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) on post-stroke cognitive impairment (PSCI) in patients with type 2 diabetes mellitus (T2DM) and concurrent acute ischemic stroke (AIS). A retrospective cohort study was conducted on 236 patients with T2DM+AIS recruited from April 2021 to October 2024. Patients were grouped based on DPP-4i use: an observation group (107 cases) with DPP-4i therapy and a control group (129 cases) without. Patients' baseline demographics, clinical features, laboratory indices, and follow-up data were extracted from the electronic medical record system. The primary outcome measure was the incidence of PSCI, defined as a Montreal Cognitive Assessment Scale (MoCA) score <26 at six months after AIS. Secondary outcomes included inflammatory cytokines, oxidative stress markers, neuroprotective factors (BDNF), glycemic metabolism indicators, and life quality [Barthel Index (BI), Functional Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL)]. At 6 months after AIS, the incidence of PSCI was significantly lower in the observation group than in the control group (P<0.05). Furthermore, inflammatory and oxidative stress marker levels were decreased whereas BDNF level was significantly elevated in the observation group compared to the control group (all P<0.05). According to the quality-of-life assessment, patients receiving DPP-4i had higher BI, FIM, and IADL scores (P<0.05), along with a lower all-cause readmission rate (P<0.05). Subgroup analysis indicated that different DPP-4i types (e.g., sitagliptin, saxagliptin) had consistent cognitive protective effects (P>0.05). DPP-4i can lower PSCI risk in T2DM+AIS patients. Its mechanism involves multi-dimensional effects like anti-inflammation, anti-oxidation, insulin sensitivity enhancement, and neuroprotection. Show less

Sepsis triggered by lipopolysaccharide (LPS) is a life-threatening condition. Inspired by the specific capture mechanism of innate proteins like LBP and CD14, we develop oxidized chitosan microspheres functionalized with hyperbranched polylysine (OCS-HBPL) as a sepsis detoxification agent. Isothermal titration calorimetry (ITC) reveals that HBPL-LPS binding is an enthalpy-driven process, distinct from the entropy-driven interaction of linear polylysine (LPL)-LPS. Validated by surface plasmon resonance (SPR), HBPL demonstrates superior affinity with a dissociation constant (K Show less

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Drug-eluting stents (DES) were developed to delay the progression of atherosclerosis. However, the diagnostic and prognostic value of Lp(a) in patients undergoing percutaneous coronary intervention (PCI) with DES remains unknown. We aim to evaluate the prognostic impact of serum Lp(a) level on cardiovascular outcomes and predictive value on repeat revascularization in patients undergoing PCI with DES. We conducted a literature search from the inception of PubMed to May 2025. Eligible studies include adult patients, with the majority (>90%) undergoing PCI with DES. Primary outcomes were the prognostic value of Lp(a) in predicting major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular (CV) mortality, and all-cause mortality. Secondary outcomes were the diagnostic value of Lp(a) for repeat revascularization, target vessel revascularization (TVR), and target lesion revascularization (TLR) evaluated in terms of sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Eleven cohorts were included, comprising a total of 27,618 patients (mean age 61 ± 10.2 years, mean follow-up 4.5 ± 1.98 years). For primary outcomes, high Lp(a) level was associated with increased risks of MACE (odds ratio [OR] 1.25, 95% CI 1.09-1.42), MI (OR 1.75, 95% CI 1.08-2.83), stroke (OR 1.28, 95% CI 1.04-1.59), CV mortality (OR 1.37, 95% CI 1.02-1.83), and all-cause mortality (OR 1.29, 95% CI 1.04-1.59). For secondary outcomes, high Lp(a) level showed sensitivity of 46%, 35%, and 39% and specificity of 64%, 74%, and 79% in predicting repeat revascularization, TLR, and TVR, respectively. The AUROC for repeat revascularization, TLR, and TVR were 0.527, 0.536, and 0.537, respectively. High Lp(a) level in patients who underwent PCI with DES was associated with poor prognosis; however, the predictive value of Lp(a) in this population remains inconclusive. Show less

This study aimed to identify novel key targets and mechanisms for repurposing strategies and mitigating sorafenib (SFB) resistance using the GEO transcriptomic dataset GSE94550 within a systems pharmacology framework. Potential counteracting molecules against SFB were retrieved from chemical repositories, followed by molecular docking tests (MDT), Kaplan-Meier survival analysis, and density functional theory (DFT) assessments to evaluate therapeutic potential. PPI networks were constructed using STRING and R to characterize the relationships between upregulated and downregulated genes. The most relevant signalling pathways associated with major targets were determined to elucidate the upstream regulatory mechanisms. Among the differentially expressed genes, APOB emerged as a pivotal regulator (log Show less

Aortic aneurysm (AA) is a life-threatening vascular disease with high fatality upon rupture. While physical activity (PA) reduces cardiovascular risk, its role in AA prevention remains uncertain, particularly when assessed objectively. We analyzed 93,165 UK Biobank participants (56% women; median age 57 years) with valid 7-day wrist-worn accelerometer data. PA was categorized as light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA). Diagnosed AA was ascertained through linked hospital, death, and primary care records. Cox models estimated hazard ratios (HRs) for AA across quartiles and per-standard deviation (SD) increments, with adjustment for demographic, lifestyle, and cardiometabolic factors. Over a median 7.9-year follow-up, 499 clinically recorded AA cases occurred. Higher accelerometer-measured PA was inversely associated with AA risk. Per-SD increments in total PA, MPA, VPA, and MVPA corresponded to 17%, 22%, 19%, and 23% lower risks, respectively. Compared with the lowest quartile, the highest MVPA quartile had a 44% lower AA risk (HR = 0.56, 95% CI 0.42-0.76). Subtype analyses revealed stronger protective effects for abdominal aortic aneurysm (AAA) than thoracic aortic aneurysm (TAA), while LPA was not significantly associated. These findings demonstrate that higher levels of accelerometer-measured MVPA are robustly associated with a decreased risk of clinically detected AA in a dose-dependent manner. The associations were particularly pronounced for AAA. This study provides objective evidence supporting the potential benefits of MVPA for aortic health. Show less

Pulmonary infections and fibrosis remain difficult to treat because current interventions target isolated pathways rather than the coupled axes of inflammation, barrier integrity, and tissue remodeling. Here, it is shown that inhalationally delivered, lung-targeted antisense oligonucleotides against angiopoietin-like 4 (Angptl4-ASO) attenuate both infectious and fibrotic lung disease. In murine models of bacterial and viral pneumonia, Angptl4-ASO reduces inflammatory cell infiltration, preserves alveolar architecture, and improves host defence. In bleomycin-induced fibrosis, treatment lowered Ashcroft scores, collagen deposition, and α-smooth muscle actin (SMA) expression, indicating broad efficacy across acute and chronic injury. Comparative transcriptomics reveal model-specific responses, immune and oxidative-stress programs in pneumonia versus extracellular matrix (ECM)-remodeling pathways in fibrosis, yet nearly half of all changes converge on a shared ANGPTL4-regulated network linking hypoxic, inflammatory, apoptotic, and stress response programs. This conserved signature suggests that ANGPTL4 functions as a central regulator of injury resolution regardless of the initiating insult. Mechanistically, Angptl4-ASO reinforced epithelial barrier integrity through coordinated regulation of tight junction and glycoprotein pathways. Longitudinal tracking of a Sulfo-Cyanine 5 (Cy5)-conjugated Angptl4-ASO confirmed a lung-retentive biodistribution, with sustained intrapulmonary localization and minimal systemic dissemination over a 144-hour window. Collectively, these findings position inhaled ANGPTL4-ASO as a host-directed, multi-axis therapeutic strategy that addresses shared and context-specific drivers of diverse pulmonary pathologies. Show less

BackgroundThe Montreal Cognitive Assessment (MoCA) is widely used for cognitive screening. Despite numerous studies showing that MoCA scores are affected by demographic variables including age, education, and race, the instrument is typically evaluated using a raw score or simple one-point education correction in clinical practice.ObjectiveIn this study, we comprehensively evaluate the diagnostic accuracy of the MoCA in a large cohort of individuals being evaluated for mild cognitive impairment or dementia.MethodsWe used data from the National Alzheimer's Coordinating Center (NACC) database to examine diagnostic accuracy of the MoCA, using both raw scores and Z-scores subject to non-linear demographic correction. We present comprehensive accuracy statistics, concordance with Show less

As an important interface between the peripheral environment and the central nervous system, the gut microbiota varies greatly between patients or animals with Alzheimer's disease (AD) and their respective non-AD counterparts; however, it remains unexplored whether the apolipoprotein E (APOE) genotype, age, and sex may interactively influence the characteristics of gut microbiota in AD animals. APOE genotype, age, and sex were enrolled as independent variables, with genotype distinguished into APOE3 and APOE4, age into 3 and 10 months, and sex into female and male. The composition, structure, and potential functions of gut microbiota were systematically analyzed by 16S rRNA gene amplicon sequencing to evaluate the individual and interactive effects of APOE genotype, age and sex. Significant interactions were observed among APOE genotypes, ages, and sexes, with different factor combinations exhibiting distinct effect on microbiotic composition and functional potential. APOE genotype exerted the most significant influence on gut microbiota, followed by age and sex with a relatively minor effect, highlighting the dominant role of host genetic background. Functional prediction analysis indicated that the functional profiles were mainly concentrated in basic metabolic pathways, including the biosynthesis of secondary metabolites and amino acids, and carbon metabolism. APOE genotype, age, and sex are jointly associated with the structure and potential function of the gut microbiota in AD model mice. These findings provide a perspective of multi-factor interaction into the alterations in gut microbiota in AD and offer new microecological evidence for understanding APOE4-related AD susceptibility, as well as a conceptual basis for future stratified microecological intervention studies. Show less

Psychosis in Alzheimer's disease (AD), including hallucinations and delusions, affects up to 50% of patients and is linked to faster cognitive decline. Delusions can occur across AD, with persecutory delusions early and misidentification delusions late, while hallucinations emerge in advanced stages and predict greater cognitive and functional decline. The APOE4 allele is the strongest genetic risk factor for late-onset AD, although its influence on neuropsychiatric symptoms, including psychosis, remains unclear. This study examined the interaction between APOE4 status, sex, EHT use, and psychosis symptoms in AD using data from participants in the National Alzheimer's Coordinating Center Uniform Data Set. Generalized Additive Models assessed nonlinear associations between predictors and psychosis outcomes, including the presence of delusions, hallucinations, and their visual and auditory subtypes. Analyses were stratified by sex (males: n = 13,841, females: n = 15,354). Predictor variables included APOE4 status, current use of estrogen hormone therapy (EHT) in females. Due to limited data availability, CSF biomarkers (Aβ1-42, p-tau181, t-tau) could not be included in the main models and were instead examined in a secondary sub analysis. APOE4 homozygosity was associated with significantly greater odds of delusions in the past month in both males and females, with a stronger effect in females (p<0.05). In females only, APOE4 homozygosity was significantly associated with hallucinations, with no effect in males (p<0.05). EHT was associated with lower risk of hallucinations in females (p<0.05). These findings underscore sex-specific genetic and biological contributors to psychosis in AD and support sex-stratified approaches to understanding and addressing psychosis symptoms in clinical settings. Show less

Metabolic and Bariatric Surgery (MBS) has evolved from being historically contraindicated for pediatric special needs populations to be an evidence-based standard of care. As obesity acts as a morbidity multiplier within this cohort, success with MBS is dependent on the strength of support ecosystems available to caregivers of these patients, rather than cognitive capacity. Although specific pathophysiology's such as intractable hyperphagia associated with Prader-Willi syndrome or complete MC4R deficiency may pose long-term durability challenges, many of these patients achieve weight loss and resolution of comorbidities comparable to their neurotypical peers. By applying a multidisciplinary ethical framework during the unique window of metabolic plasticity in children, clinicians can reverse life-threatening diseases prior to irreversible end organ damage occurs. This paradigm shift ensures that the most vulnerable patients are no longer denied transformative treatment based on underlying diagnoses alone. Show less

Given the limitations of current treatments for Alzheimer's disease (AD), this study aims to comprehensively evaluate the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) in AD mouse models through a systematic review and meta-analysis. Additionally, we explore the impact of transplantation dose and route on treatment outcomes to identify the optimal window for clinical application. In accordance with the PRISMA guidelines, we systematically searched four major databases to identify randomized controlled trials involving hUCMSCs in AD mouse models. We used the standardized mean difference (SMD) to synthesize effect sizes and performed subgroup analyses based on pre-defined transplantation routes and doses. A total of 13 studies were included in the analysis. The meta-analysis revealed that hUCMSCs transplantation significantly improved spatial learning and memory in AD model mice, with a marked reduction in escape latency (SMD = -2.55; 95% CI: -3.34 to -1.75; Human umbilical cord mesenchymal stem cells can improve behavioral and pathological outcomes in AD mouse models via multiple mechanisms of action. The intravenous route using medium to high doses emerges as a critical factor for achieving optimal effects, providing important evidence and informing future experimental design and clinical translational research. Show less

Lipoprotein(a) [Lp(a)] has emerged as a critical determinant of residual cardiovascular risk. However, its impact on plaque morphology remains underinvestigated. This study aimed to elucidate the relationship between the serum Lp(a) levels, coronary plaque vulnerability, and vascular remodeling characteristics by utilizing intravascular ultrasound (IVUS). We retrospectively enrolled 292 consecutive patients with coronary artery disease who underwent IVUS. Target lesions were classified into vulnerable (n = 83) or stable (n = 209) plaque groups based on the IVUS criteria. Multivariate binary logistic regression was performed to identify independent predictors. The morphological parameters were further compared between the high (＞18.8 mg/dL) and low (≤ 18.8 mg/dL) Lp(a) groups. The vulnerable plaque group exhibited significantly higher median serum Lp(a) levels than the stable group (14.56 vs. 11.04 mg/dL, P = 0.011). After adjusting for age, sex, LDL-C, smoking, diabetes, and hypertension, Lp(a) ＞18.8 mg/dL remained an independent predictor of plaque vulnerability (OR = 1.76; 95% CI: 1.00-3.07; P = 0.049). Notably, the LDL-C levels did not predict vulnerability in this cohort. Furthermore, the high Lp(a) group demonstrated significantly larger vascular dimensions (EEM CSA: 14.67±4.95 vs. 13.22±4.20 mm Elevated serum Lp(a) levels are independent predictors of coronary plaque vulnerability. The underlying mechanism involves Lp(a) promoting compensatory vascular enlargement, accompanied by an increased plaque volume. These findings underscore the necessity of Lp(a) screening to identify any residual risk, particularly in patients with effectively controlled low-density lipoprotein cholesterol (LDL-C). Show less

Lipoprotein(a) (Lp[a]) can refine atherosclerotic cardiovascular disease risk assessment and guide lipid-lowering therapy intensification (LLTI). However, the association between Lp(a) testing and LLTI across large health systems is not well characterized. Using Veterans Affairs electronic health record data, we conducted a retrospective cohort study of veterans undergoing lipid testing from January 1, 2017, to June 30, 2024. We first compared a 1:1 propensity-matched cohort with concurrent low-density lipoprotein cholesterol (LDL-C) and Lp(a) testing with those with LDL-C testing alone. We then compared veterans with elevated versus nonelevated Lp(a) (>50 versus <50 mg/dL). The primary outcome was LLTI within 12 months, defined as therapy initiation, dose escalation, or addition of another lipid-lowering agent. LDL-C goal attainment (<100 mg/dL primary prevention; <70 mg/dL secondary prevention) was assessed within 12 months. Multivariable logistic regression adjusted for sociodemographic and clinical factors. Among 6 941 840 veterans with LDL-C testing, 10 384 (0.1%) underwent Lp(a) testing. The propensity-matched cohort included 20 768 veterans (mean±SD age, 58.4±15.3 years; 12.4% women; 19.2% Black individuals). Elevated Lp(a) (>50 mg/dL) was present in 25% (n=2562). Lp(a) testing was associated with greater LLTI (odds ratio [OR], 2.11 [95% CI, 1.95-2.29]), LDL-C testing (OR, 1.27 [95% CI, 1.19-1.36]), and LDL-C goal attainment (OR, 1.22 [95% CI, 1.12-1.33]). Compared with Lp(a) <50 mg/dL, Lp(a) >50 mg/dL was associated with increased LLTI (OR, 1.73 [95% CI, 1.55-1.94]). Lp(a) >100 mg/dL was associated with lower LDL-C goal attainment (OR, 0.68 [95% CI, 0.56-0.84]). Lp(a) testing was associated with increased LLTI and LDL-C goal attainment. Elevated Lp(a) identified individuals more likely to undergo LLTI, suggesting testing may motivate preventive treatment optimization. Show less

Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 (IRF6) is a transcription factor that regulates the inflammatory response following injury. In this work, the LSS-induced AS model was induced by the partial ligation of the left carotid artery in high-fat diet-fed ApoE Show less

This study investigated the antifungal performance of copper-based antimicrobial coatings developed by Gencoa Ltd., previously validated against bacterial ESKAPE pathogens, alongside newly formulated titanium oxide coatings, against key agricultural fungal pathogens: Alternaria alternata, Botrytis cinerea, Cladosporium cucumerinum, and Fusarium oxysporum. Testing was conducted both in vitro and in field trials within an actively used polytunnel. In vitro assays included a modified ISO 846 agar plate protocol and a six-well plate fungal colonization assay simulating high humidity conditions. Field trials assessed coating performance under real-world exposure. Copper-containing coatings: pure copper, copper oxynitride, and copper-doped titanium oxide, consistently demonstrated significant antifungal activity, effectively reducing spore germination and colonization. Titanium oxide coatings without copper showed minimal effect, performing similarly to uncoated polyethylene. While copper-based coatings were highly effective, some susceptibility to surface degradation under prolonged moisture was observed. However, antifungal activity often persisted in degraded areas of samples with high copper content. Copper-based antimicrobial coatings offer strong potential for preventing fungal colonization on agricultural surfaces, outperforming titanium oxide formulations under both laboratory and field conditions. Optimization to enhance durability will further improve their suitability for long-term use in protected cultivation systems. Show less

Oxidative modification of apolipoprotein B-100 (apoB) containing particles and subsequent immune responses contribute to the pathogenesis of atherosclerosis. Circulating IgG and IgM apoB-containing immune complexes (apoB-IC) and autoantibodies to a malondialdehyde mimotope (anti-MDA-mimotope) serve as biomarkers of oxidative stress and immune activation in atherosclerotic cardiovascular disease. Elevated lipoprotein(a) [Lp(a)] is associated with increased oxidative burden and immune activation. To investigate the effect of lipid-lowering medications on IgG and IgM apoB-IC and IgG and IgM autoantibodies to an MDA-mimotope in individuals with elevated lipoprotein(a) [Lp(a)] concentrations. In this prospective study, patients (n = 70) with Lp(a) levels ≥ 75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). IgG and IgM apoB-IC and IgG and IgM anti-MDA-mimotope were measured at baseline and 3 months after treatment initiation. Patients had a mean age of 51 ± 15 years and 40% were male. Significant reductions in IgG apoB-IC levels were observed following treatment with high-intensity statins, add-on ezetimibe and add-on PCSK9i (by 18.3%, 17.5% and 25.5%, respectively, all p < 0.05). No significant changes in IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels were observed in any treatment group. In individuals with Lp(a) levels ≥ 75 nmol/L, high-intensity statins, add-on ezetimibe and add-on PCSK9i reduced IgG apoB-IC but did not affect IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels. The clinical significance of these findings warrants further investigation. Show less

Plozasiran (Redemplo), a novel small interfering RNA (siRNA) therapeutic targeting the hepatic biosynthesis of apolipoprotein C-III (APOC3), is approved by the US FDA for treating familial chylomicronemia syndrome (FCS), a disease of rare prevalence that presents with extremely elevated levels of serum triglycerides (TG) leading to a higher risk of acute pancreatitis. Plozasiran is also in Phase 3 development to treat the broader indication of severe hypertriglyceridemia. Population pharmacodynamic (PD) analysis of plozasiran was conducted on serially measured serum APOC3 and TG levels in the FCS patients participating in the pivotal Phase 3 study by employing a cascading kinetic-PD model that described the inhibitory effect of plozasiran on the synthesis of APOC3, which in turn decreases serum TG levels. The estimated IC Show less

Coronary artery disease (CAD) polygenic risk score (PRS), low-density-lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), and high-sensitivity C-reactive protein (hsCRP) are biomarkers that predict CAD. It is unclear whether integrating genomics with lipid and inflammatory biomarkers could complement traditional risk scores in identifying people at risk of CAD. This study assesses the predictive value of CAD PRS, LDL-C, Lp(a), and hsCRP for incident CAD across different age and sex groups. Participants (n = 215,695) from the UK Biobank aged 40 to 69 years with baseline CAD PRS, LDL-C, Lp(a), and hsCRP values were followed for 12 years to assess the incidence of CAD. We evaluated a multivariable-adjusted Cox model that included all 4 biomarkers, net reclassification index, C-statistics, and population attributable risk across different age and sex groups. Over a 12-year follow-up, 4,721 men and 2,425 women developed CAD. The HRs for incident CAD associated with each biomarker elevation were 1.79 (95% CI: 1.70-1.89) for CAD PRS, 1.60 (95% CI: 1.48-1.66) for LDL-C, 1.20 (95% CI: 1.12-1.29) for Lp(a), and 1.64 (95% CI: 1.57-1.72) for hsCRP. CAD PRS demonstrated a stronger association in men (HR per SD: 1.49; 95% CI: 1.45-1.54) than women (HR per SD: 1.37; 95% CI: 1.31-1.44; P-interaction ≤ 0.001). All biomarkers conferred greater HRs at younger ages (P < 0.0001). Individuals with all biomarkers elevated had a 4.65-fold increased risk of CAD compared with those with no elevated biomarkers. A combined 4-biomarker model had a higher C-statistic of 0.753 compared with the pooled cohort equations (C-statistic of 0.740). The C-statistic of the combined 4-biomarker model was also higher in younger individuals in both sexes and yielded a 32.0% continuous net reclassification index when compared with the pooled cohort equations. CAD PRS, LDL-C, hsCRP, and Lp(a) show independent age- and sex-specific associations with CAD. Measuring all 4 biomarkers may improve midlife CAD risk prediction for both male and female patients. Show less

Elevated lipoprotein(a) [Lp(a)] levels have been strongly related to cardiovascular (CV) risk. However, its association with Hypertension Mediated Organ Damage (HMOD) and CV events in the primary prevention setting remains unclear. To evaluate in these patients, the correlation between Lp(a) levels and: (i) heart, vessels and kidney HMOD and; (ii) CV events and all-cause mortality in a primary prevention setting. 747 low CV risk subjects were recruited between 2009 and 2014. HMOD was assessed through Pulse Wave Velocity, carotid Intima-Media Thickness (IMT), presence of carotid plaques, Left Ventricular Hypertrophy (LVH) and Ejection Fraction and glomerular filtration rate. All-cause mortality and CV events up to 2021 were retrieved by electronic health records, for a median follow-up time of 10 years (I-III quartiles 9.6-11.1). Mean age was 50.8 ± 13.0 years and 63.5% of the subjects were men. The prevalence of hypertension was 37.9%, dyslipidemia 67.2%, smoking 17.8%, and diabetes mellitus 8.7%. Median Lp(a) value was 17 mg/dL (5.9-56.0), and 26.5% of patients had values above 50 mg/dL. Regarding HMOD, 10.3% subjects had arterial stiffness, 7.2% increased IMT, 19.8% carotid plaques while only 0.7% had LVH. No significant correlation was found between Lp(a) levels and indices of subclinical HMOD. Furthermore, no relationship was found between CV events and all-cause mortality and Lp(a) levels. In this primary prevention cohort, elevated Lp(a) levels were not associated with significant structural damage to the heart, carotid arteries, or increased aortic stiffness and were not associated with CV events and all-cause mortality. Show less

Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease, but its impact on long-term coronary plaque progression remains unclear. This study synthesizes evidence from CCTA, IVUS, and OCT to clarify the relationship between high-risk Lp(a) and coronary plaque burden and high-risk plaque features. We conducted a comprehensive search of multiple databases up to July 2025 for studies evaluating Lp(a) and atherosclerotic plaque progression. Statistical analysis was performed using a random-effects model in RevMan 5.4, reporting odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). The protocol is registered in PROSPERO (CRD420251113955). Our final analysis included 16 studies comprising 19,822 participants with a mean age of 62 years and a median imaging follow-up ranging from 10 months to 10.2 years. On analysis, high-risk Lp(a) levels were significantly associated with the presence of coronary plaque (OR 1.53; 95% CI, 1.03-2.29; p = 0.04) compared with low Lp(a) levels. Additionally, patients with elevated Lp(a) exhibited significantly greater progression in percent atheroma volume (ΔPAV) than those with low levels (MD 4.31%; 95% CI, 1.08-7.53; p = 0.009). Subgroup analysis by plaque phenotype revealed a statistically significant increase in low-attenuation plaque (LAP) presence among individuals in the high-risk Lp(a) category (OR 1.92; 95% CI, 1.13-3.27; p = 0.02). High-risk Lp(a) is associated with greater coronary plaque prevalence, accelerated progression, and increased LAP. These findings underscore Lp(a) as a driver of high-risk, rupture-prone plaques and a critical biomarker and potential therapeutic target in cardiovascular risk management. Show less

The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing to its lipid-regulating and anti-inflammatory effects, paeoniflorin (Pae) inhibits VSMC phenotypic transformation, making it a promising candidate for AS treatment. Mouse aortic VSMCs were treated with oxidized low-density lipoprotein (ox-LDL) and Pae, and the effects on cell phenotype were examined. An AS model was established by feeding ApoE Pae reversed weight gain and elevated TG levels in the AS model. Oil Red O staining showed that Pae inhibited VSMC-derived foam cell formation in vitro and reduced aortic sinus plaque area, aortic wall lipid deposition, and hepatic steatosis in the AS model. Immunofluorescence staining of the aortic sinus revealed that Pae mitigated α-SMA overexpression and reversed ATP-binding cassette transporter A1 (ABCA1) downregulation. Western blotting analysis revealed that Pae inhibited ERK1/2 and p65 phosphorylation, curbed MMP2 overexpression, and restored downregulated ABCA1 expression. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, and wound healing assays demonstrated that Pae inhibited ox-LDL-induced VSMC proliferation and migration. Additionally, Pae significantly inhibited the expression of the inflammatory factors IL-6 and MCP-1 both in vivo and in vitro. Pae may treat AS by inhibiting VSMC phenotypic transformation. Show less

This study aimed to identify different symptom profiles of complicated grief/bereavement-related posttraumatic stress disorder (PTSD) and examine the associations with social life factors, posttraumatic growth, and quality of life in a sample of parents whose children died in Sewol ferry accident. A total of 272 bereaved parents affected by the Sewol ferry accident participated and completed self-report scales about traumatic loss-related symptoms. The latent profile analysis (LPA) of complicated grief and posttraumatic symptoms was classified. To examine the predictors (interpersonal stress/familial conflict/social support) and outcomes (posttraumatic growth/quality of life) of the traumatic loss symptom profiles, an automatic three-step approach was chosen. The LPA identified three symptom profiles of complicated grief and posttraumatic stress: low symptomatology group (30.4%), moderate symptomatology group (49.6%), and high symptomatology group (20.0%). Higher perceived interpersonal stress significantly increased the odds of moderate and high symptomatology, while higher family stress was a significant predictor for high symptomatology compared to both low and moderate symptomatology groups. In addition, higher perceived social support significantly decreased the odds of being in both moderate and high symptomatology groups compared to the low group. The low symptomatology group showed the highest quality of life, followed by the moderate and high groups. Posttraumatic growth was also significantly different between the classes, with the moderate symptomatology group reporting higher growth than the low symptomatology group. Our findings suggest that managing the mental health of people who have experienced a traumatic loss will be a critical component of their quality of life in the future. In addition, interventions to help reduce family conflict and interpersonal stress may be necessary to reduce difficulties associated with psychopathology. Show less