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The laminins are a family of extracellular matrix proteins that regulate numerous cellular processes, including adhesion, neurite outgrowth, and axon guidance. However, it remains unclear whether laminin regulates axon guidance through local translation. Here, we show that laminin is necessary for local translation in axonal growth cones. Local translation is significantly increased in growth cones of embryonic day 17 mouse cortical neurons, either cultured on or acutely stimulated with soluble laminin 111, in the presence of BDNF. When cultured on laminin isoforms 211 or 221 in the presence of BDNF, there was a remarkable decrease in local translation in growth cones. Using a puromycin-proximity ligation assay to examine newly synthesized β-actin specifically, we find a significant increase in growth cones of neurons cultured on laminin 111 in the presence of BDNF. However, soluble laminin 111 alone results in a significant reduction in nascent β-actin protein synthesis. These results indicate that laminin isoforms can act in multiple ways, including synergistically with guidance cues and independently, to modulate local mRNA translation, thereby differentially influencing axon growth and guidance during development. Local translation in axons is critical for axon guidance. Laminin, a key component of the extracellular matrix, is necessary to induce local translation and thus mediate axon growth and guidance. Show less

Anorexia nervosa (AN) is a debilitating, often lethal, restrictive-type eating disorder without an effective cure. The underlying neural basis of AN has remained elusive without an animal model that has represented all typical AN symptoms. Here we show that aberrant activation of mediobasal hypothalamic (MBH) glutamatergic neurons led to lethal self-starvation, hyperactivity, anhedonia, social phobia, and increased anxiety, all of which represent typical symptoms of AN. These symptoms were selectively exhibited by targeted activation of MBH neurons expressing steroidogenic factor (SF1) and estrogen receptor alpha (ERa). Moreover, the elicited AN symptoms by activation of MBH glutamatergic or SF1/ERa neurons were rescued by removing release of glutamate or brain-derived neurotrophic factor (BDNF) from these neurons. Importantly, BDNF overexpression in SF1/ERa neurons promoted typical AN symptoms, which were suppressed by removing glutamate release. Thus, our findings identify aberrantly enhanced BDNF and consequent augmented glutamate release from SF1/ERa neurons as a neural basis underlying AN. Show less

Alcohol use disorder (AUD) is a significant medical problem and there is great need for developing effective treatment strategies. Brain-Derived Neurotrophic Factor (BDNF) has been shown to play a role in regulating numerous pharmacological and motivational effects of alcohol. We have shown that chronic alcohol-induced escalation of drinking is accompanied by a deficit in BDNF levels in medial prefrontal cortex (mPFC). This study examined whether exercise (wheel-running) attenuates excessive alcohol drinking via increased BDNF expression, thereby mitigating the deficit in mPFC. Adult male C57BL/6J mice were given scheduled (2-hr/day) access to a running wheel in the home-cage 1-hr following opportunity to drink alcohol for 2-hr/day. After six weeks, mice were further separated into groups that received chronic alcohol vapor or control (air) inhalation exposure. Results indicated that alcohol consumption did not alter wheel-running and exercise did not alter alcohol intake during the 6-week baseline. Exercise increased BDNF mRNA and protein expression in mPFC, reversed chronic alcohol-induced reduction in BDNF levels, and attenuated escalated alcohol drinking. Systemic administration of a TrkB receptor antagonist (ANA-12) reversed the beneficial effects of wheel-running in the model. Together, these data provide support for exercise as a potentially effective intervention strategy for treating AUD. Show less

Vitiligo is an autoimmune disorder characterized by the destruction of melanocytes. We performed a rank-based meta-analysis of six independent transcriptomic studies (115 samples) spanning microarray, bulk, and single-cell RNA-seq platforms to identify consensus signatures of lesional skin. Robust rank aggregation identified 108 downregulated and 6 upregulated genes. Pathway analysis revealed consistent suppression of melanin synthesis and neural development pathways in vitiligo, whereas immune response activation was heterogeneous across studies. Re-analysis of single-cell data from three studies confirmed melanocyte depletion. The 108 downregulated genes were expressed exclusively in melanocytes. These include neural development genes (PLP1, GPM6B, NRXN3), consistent with melanocytes' neural crest origin. We also identified candidate melanocyte markers, such as CYB561A3 and QPCT, with high melanocyte specificity and consistent downregulation in vitiligo. These findings reveal a robust melanocyte-loss signature in vitiligo, detectable across different studies. Study-dependent immune activation, possibly influenced by sampling method and disease characteristics, warrants further study. Show less

Patients with pulmonary arterial hypertension (PAH) experience long diagnostic delays, high functional class at diagnosis and poor prognosis. We aimed to study the differentiative and predictive value of 90 inflammatory and immunomodulatory related proteins in idiopathic and hereditary PAH (IPAH/HPAH) and systemic sclerosis-associated PAH (SSc-APAH). Cohort 1 comprised patients with SSc-APAH ( Show less

Genetic factors are thought to play an important role in antipsychotic-induced weight gain (AIWG). This study conducted a meta-analysis of current research of the pharmacogenetic associations of adult AIWG. The analysis included papers providing comparisons of weight gain across at least two allele combinations for at least one single nucleotide polymorphism (SNP). Inclusion criteria were, patients 18 years of age or older and had received a diagnosis of severe mental illness, for which antipsychotic medication was prescribed. The association with AIWG needed to be replicated across at least two papers reporting separate sample sets. Two hundred twenty-three papers were assessed for eligibility. Of the 223 papers, 148 were excluded, leaving 75 studies to be included. Six SNPs in six different genes were identified as having significant associations ( The study identified six SNPs that predispose adult individuals to AIWG, with Show less

Abdominal aortic aneurysm (AAA) has high mortality and enhanced oxidative stress; autophagy inhibition accelerates its formation. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 2 (NOX2) is responsible for generating reactive oxygen species (ROS). The aim is to clarify the mechanism of NOX2-mediated autophagy in AAA. Subcutaneous angiotensin II (AngII) infusion in ApoE Show less

With a rapidly aging population living with HIV that may face a double-hit of neuroHIV and Alzheimer's disease, the objective of this meta-analysis was to evaluate the impact of ε4 on cognitive performance in adults with HIV. The primary literature search was conducted with PubMed and other databases on studies published between 1997 and 2025. Searches were conducted from inception until June 2025. Out of 289 initial studies, 17 were identified for inclusion meeting pre-defined criteria. Data extraction was performed by two independent observers and followed established guidelines (PRISMA). Pooled data included a total of 2610 adults with HIV, including 765 ε4 carriers (age 45.3 ± 8.1 years, 62.1% male) and 1845 non-carriers (age 44.7 ± 9.2, 67.5% male). There was no significant difference between ε4 carriers and non-carriers in diagnosis of neurocognitive impairment (OR = 1.10, 95% CI 0.8 to 1.5 p = .563), nor in performance of any of the examined cognitive domains (Hedges gs<0.2, ps > 0.17). Meta-regression analysis suggested that less education was associated with increased risk of neurocognitive impairment in carriers (p = .0143). After controlling for the potential bias from "overrepresented" cohorts that appeared in multiple publications, this meta-analysis found no significant effects of ε4 on neurocognitive performance or impairment in adults with HIV, despite a weak and non-significant trend of low performance in memory and executive function in ε4 carriers. Factors such as a relatively young age may contribute to the null findings. Future studies with relatively older cohorts and more sensitive/interdisciplinary approaches are needed. Show less

Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms. Show less

Dietary diversity plays a crucial role in maintaining physical function. This study explored the association and potential mechanisms between dietary diversity and gait characteristics measured by wearable devices in older adults. This cross-sectional study included 861 older adults aged 60 years or above. Dietary diversity score (DDS) was assessed using a standard food frequency questionnaire. A multi-sensor gait system was used to measure periodic, kinetic, and spatiotemporal gait parameters during a 12-meter walking test. The coefficient of variation (CV) was calculated for each parameter to assess gait stability. Multivariable linear regression models were conducted to examine the relationship between DDS and gait parameters, adjusting for demographics, lifestyle factors, cognitive function, and comorbidities. Participants had a mean age of 70.25 ± 6.19 years, with 58.30% being female. After adjusting for all covariates, each 1-SD increase in DDS was positively associated with Z-scores of landing control force (β = 0.072, SE = 0.033, P = 0.033), foot-off angle (β = 0.076, SE = 0.033, P = 0.021), gait speed (β = 0.086, SE = 0.033, P = 0.008), step length (β = 0.068, SE = 0.031, P = 0.032), and stride length (β = 0.078, SE = 0.033, P = 0.013). Furthermore, higher DDS was negatively associated with the CVs of initial limb support time, step time, stride time, ground reaction force, landing control force, foot-off angle, gait speed, and step length (all P < 0.05). We also identified biomarkers simultaneously related to both DDS and gait characteristics, including albumin, leptin, myostatin, brain-derived neurotrophic factor, insulin-like growth factor-1, high-sensitivity C-reactive protein, interleukin-6, and glutathione reductase. Higher DDS is associated with superior kinetic and spatiotemporal gait vigor performance and enhanced gait stability. Pathways involving nutritional status, energy metabolism, inflammatory regulation, antioxidant defense, and neural function may underpin this association. Show less

Brusatol (BRU), a major bioactive quassinoid isolated from Brucea javanica, has shown potential in the treatment of inflammatory diseases. As mitochondrial dysfunction has been implicated in chronic inflammatory disorders, modulation of mitochondrial homeostasis may offer a potential approach for the treatment of rheumatoid arthritis (RA) and atherosclerosis (AS). To develop a novel BRU derivative through rational modification at the C11‑hydroxyl group and to compare the therapeutic effects of BRU and its derivative BRUD in experimental models of RA and AS, with particular focus on mitochondrial regulation and Drp1-associated signaling. This study combined in vivo and in vitro experiments to evaluate the pharmacological effects of BRU and BRUD and investigate the underlying mechanisms. The chemical constituents of BRU and BRUD were confirmed by HPLC and NMR spectroscopy ( In vivo studies demonstrated that both compounds ameliorated joint damage in CIA rats and reduced atherosclerotic lesion burden in ApoE These findings suggest that BRUD exhibits improved activity compared with BRU in RA and AS models, with protective effects associated with modulation of mitochondrial dysfunction, supporting its further evaluation as a lead compound. Show less

Atherosclerotic plaque rupture, driven by a vicious pathological cycle between endothelial-to-mesenchymal transition (EndMT) and chronic inflammation, represents a major therapeutic challenge in cardiovascular disease. Current clinical strategies, including statins and antiplatelet agents, fail to disrupt the EndMT-inflammation axis, while conventional TGF-β pathway inhibitors-critical for EndMT regulation-exhibit narrow therapeutic windows and systemic toxicity owing to the pleiotropic nature of TGF-β signaling. Here, we reported VRBPC, a VCAM-1-targeting, reactive oxygen species (ROS)-responsive baicalin-peptide conjugate that undergoes in situ self-assembly within atherosclerotic plaques to form a "molecular latch" that breaks the EndMT-inflammation loop. Upon VCAM-1-mediated endocytosis into activated endothelial cells, VRBPC responds to elevated ROS levels in the plaque microenvironment, triggering localized self-assembly that enhances baicalin retention and promotes its competitive binding to HSP90-a critical chaperone for TGF-β receptor stabilization. This mechanism inhibits Smad2/3 phosphorylation, reverses EndMT, and simultaneously suppresses inflammatory responses in macrophages. In vitro, VRBPC effectively restored endothelial phenotype, reduced aberrant migration, and diminished foam cell formation alongside pro-inflammatory cytokine secretion. In ApoE Show less

Pacific salmon (Oncorhynchus spp.) rely on olfactory information learned in their natal rivers to guide their homing migration. Although molecules associated with synaptic plasticity show marked changes in the olfactory system during periods linked to imprinting, the contribution of brain-derived neurotrophic factor (BDNF/Bdnf), a key regulator of neural development and plasticity, has not been fully examined in salmonids. In this study, we isolated the complete coding sequence of masu salmon (O. masou) pro-bdnf and analyzed its expression profile across the olfactory system using wild individuals at multiple developmental stages. The deduced amino acid sequence of masu salmon pro-Bdnf was highly conserved among vertebrates. Pro-bdnf mRNA was strongly expressed in under-yearling parr prior to smoltification, particularly in the olfactory rosette and olfactory bulb at the sensitive period for imprinting. In the telencephalon, a higher olfactory center homologous to the mammalian cerebrum, pro-bdnf expression remained stable across stages, consistent with ongoing neurogenesis in this region. These results provide molecular evidence that pro-bdnf expression mirrors developmental changes in the olfactory system and support the idea that Bdnf contributes to the formation and refinement of olfactory circuits essential for imprinting and homing in Pacific salmon. Show less

Numerous hypotheses have been proposed for the pathophysiology of bipolar disorder (BD). This study aimed to evaluate serum neuroserpin (NSP), tissue plasminogen activator (tPA), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), high-sensitivity C-reactive protein (hsCRP), and sedimentation levels in patients with BD, based on the inflammatory and fibrinolytic system hypothesis, to understand the etiopathogenesis of BD. The second aim of our study was to determine the risk of developing BD type 1 by examining the relationship between tPA and NSP in patients diagnosed with BD type 1. The study included 80 euthymic outpatients with BD type 1 and 80 healthy controls (HC). Individuals with a Hamilton Depression Rating Scale (HAM-D) score of less than 7 and a Young Mania Rating Scale (YMRS) score of less than 4 who did not show any symptoms of mania, depression, or hypomania for the last 6 months were included in the study. In both groups, serum levels of NSP, tPA, IL-6, BDNF, hsCRP, and sedimentation were measured. Compared to the healthy control group, the NSP and tPA levels were lower in the BD group (p<0.001). We found no linear relationship when we analyzed the relationship between tPA and NSP by excluding other variables. (p: 0.027). These findings suggest that tPA and NSP may serve as potential biomarkers for the euthymic period of BD type 1. These biomarkers may provide guidance in understanding the pathophysiology of bipolar disorder. Show less

Data are limited regarding national clinician awareness, testing, and treatment of lipoprotein(a) [Lp(a)]. We conducted a national survey of US clinicians to investigate these issues. An internet-based survey of awareness, testing and treatment of Lp(a) was administered by a medical survey company to clinicians who have been in practice ≥5 years in the US or its territories. 2002 clinicians completed the survey: 47 % were primary care, 35 % cardiology, 9 % endocrinology, and 9 % neurology. 28 % were female, 24 % Asian, 4 % Hispanic, and 3 % Black. Most clinicians agree knowing the Lp(a) level can improve risk assessment and patient engagement. Patients with premature or recurrent CVD events are most likely to be targeted for Lp(a) testing and for prescribing possible future Lp(a)-targeted therapies. Show less

Atherosclerosis currently lacks effective therapeutic strategies specifically targeting and inhibiting foam cell formation. In this study, we engineered a macrophage nanoparticle composite drug delivery system that utilizes macrophages for competitive lipid uptake, coupled with ROS-responsive statin nanoparticles aimed at inhibiting cholesterol synthesis. This integrated system embodies a "smart immunomodulatory" approach, leveraging the inherent activity and targeted capabilities of immune cells. Experimental results demonstrated that this system significantly reduced lipid accumulation within foam cells by inhibiting cholesterol uptake, promoting cholesterol efflux and inhibition of apoptosis. These effects were mediated through microenvironmental optimization and upregulation of ABCA-1 and SR-BI expression. In an APOE knockout mouse model of atherosclerosis, the system effectively lowered lipid levels, modulated inflammatory responses, and significantly reduced foam cell formation and atherosclerotic plaque development. The system enhanced Treg cell proliferation and TGF-β secretion. Moreover, the system demonstrated high biocompatibility and therapeutic efficacy, training macrophages to revert to a low-lipid and M2 phenotype. This targeted drug delivery system integrates multiple therapeutic mechanisms, including inhibition of cholesterol uptake, enhancement of cholesterol efflux, and immunomodulation, providing a promising new strategy for the treatment of atherosclerosis. Show less

Over 10 million patients undergoing non-cardiac surgery each year face major cardiovascular complications within 30 days, many due to destabilized atherosclerotic plaques. Reverse cholesterol transport (RCT), driven by HDL and Apoa1, protects against plaque progression, but the effects of surgical inflammation on this pathway remain unclear. Using an abdominal laparotomy model in ApoE Show less

Apolipoprotein C3 (apoC3) circulates primarily on triglyceride-rich lipoproteins and promotes atherosclerosis by fostering lipidemia and inflammation. Thus, apoC3 represents an important cardiovascular risk factor and is associated with cardiovascular events and mortality. Due to their dual nature as hemostatic and immunomodulatory effector cells, platelets play an important role in the development and progression of atherosclerosis and are responsible for thrombotic/thromboembolic events upon plaque rupture. We aimed to elucidate the impact of apoC3 on prothrombotic platelet functions. Platelets were isolated from healthy volunteers and the effect of apoC3 on their activation and aggregation was assessed by flow cytometry, ELISA, and light transmission and multiple electrode aggregometry. Platelet spreading and cytoskeletal remodeling were examined by immunofluorescence microscopy. In vivo relevance was confirmed in a murine model of FeCl ApoC3 strongly reduced platelet aggregation independently of the presence of plasma or other blood cells and impaired both α We identified apoC3 as lipoprotein-derived inhibitor of prothrombotic platelet functions, mediating antiaggregatory effects, likely via modulating AKT and VASP signaling and interfering with actin cytoskeleton remodeling to impair lamellipodia formation. Thus, apoC3 may counterbalance its proatherogenic properties on lipid metabolism and inflammation by dampening thrombotic risk in hyperlipidemia. Show less

Myocardial infarction (MI) is the most severe clinical manifestation of coronary artery diseases (CVD) and serves as a critical driver of sudden cardiac death and heart failure (HF). Its pathophysiology begins with the abrupt cessation of coronary blood flow, leading to severe ischemia and subsequent cardiomyocyte necrosis. This study aimed to investigate the molecular mechanisms by which METTL14 regulates the progression of MI in mice via the OTUD1/DUSP6 signaling axis. An MI mouse model was established by ligating the left anterior descending (LAD) coronary artery. The progression of MI was evaluated through echocardiography, HE staining, Masson's trichrome staining, TUNEL assay, and assessment of inflammatory cytokines. Mechanistically, Me-RIP, PAR-CLIP Co-IP, and protein stability assays were performed to dissect the interactions within the METTL14/OTUD1/DUSP6 axis. Our results demonstrated that METTL14 was highly expressed in the MI mouse model. Silencing METTL14 significantly reduced the left Ventricular Internal Diameter at end-diastole (LVIDd) and left Ventricular Internal Diameter at end-systole (LVIDs), increased ejection fraction (EF) and fractional shortening (FS), and attenuated histopathological damage, apoptosis, and the levels of inflammatory cytokines (TNF-α and IL-β). Further analysis revealed that METTL14 promotes OTUD1 mRNA stability and expression by modulating its m Show less

Pharmacological preconditioning of mesenchymal stem cells (MSCs) is a promising strategy to enhance their therapeutic efficacy for end-stage liver disease; however, maximizing this benefit remains a major clinical challenge. Senkyunolide H (SNH), a small-molecule compound derived from Angelica sinensis, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties. Nevertheless, its capacity to optimize MSCs-based therapy for liver disease has not been fully elucidated. Here, we demonstrate that SNH preconditioning significantly enhances the therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in a murine model of liver cirrhosis. Specifically, SNH-pretreated BMSCs markedly alleviated hepatocellular injury, promoted hepatocyte proliferation, and attenuated collagen deposition. Mechanistically, SNH augments the therapeutic potency of BMSCs by partly binding to macrophage erythroblast attacher (MAEA), a subunit of the E3 ubiquitin ligase complex. This interaction stabilizes MAEA, which in turn facilitates the ubiquitination and proteasomal degradation of dual specificity phosphatase 6 (DUSP6), thereby activating ERK/STAT3 signaling and upregulating the secretion of hepatocyte growth factor (HGF). Collectively, our findings highlight SNH preconditioning as a robust approach to enhance the paracrine function and therapeutic potential of BMSCs, and identify MAEA as a novel therapeutic target for BMSCs-based interventions in liver cirrhosis. Show less

Dual-specificity phosphatase 6 (DUSP6) is a phosphatase specific for extracellular signal-regulated kinase (ERK). Dusp6-knockout mice are resistant to diet-induced hepatic steatosis, which appears to be linked to the downregulation of cytochrome P450 4 A (CYP4A); however, its mechanism remains unclear. This study aimed to elucidate how DUSP6 regulates CYP4A11 in human hepatocyte-lineage cells by focusing on forkhead box O1 (FOXO1). HepG2 and HuH-7 cells were challenged with palmitic acid and oleic acid to induce lipid accumulation while manipulating the expression of DUSP6, FOXO1, CYP4A11, ERK, and/or AKT. Lipid accumulation was reduced by DUSP6 knockdown, resulting in decreased CYP4A11 expression despite elevated phosphorylated ERK, AKT, and FOXO1. Inhibition of ERK increased lipid accumulation, while simultaneous inhibition of ERK and AKT decreased it. Knockdown of FOXO1 or induced expression of DUSP6 increased CYP4A11 expression and lipid accumulation, whereas induced expression of FOXO1 decreased them. Chromatin-immunoprecipitation showed that FOXO1 bound to CYP4A11 promoter. Immunoprecipitations revealed that DUSP6 bound to and anchored FOXO1 in the cytoplasm. These results indicate that DUSP6 interferes with FOXO1's repressive activity towards CYP4A11 by sequestering it in the cytoplasm and preventing its nuclear translocation, which ultimately unleashes CYP4A11 and promotes lipid accumulation. Show less

Self-collection of biospecimens at-home, without specialized equipment or training, are increasingly being adopted in clinical practice due to convenience and patient preferences. However, sample instability during shipment means that remote access to common blood tests remains challenging. We hypothesized that the inaccuracy and imprecision in test results that develop because of sample instability could be modeled and controlled using knowledge of transit conditions captured by environmental sensors. We subjected 2685 blood samples from 65 participants to temperature cycles derived from real-world transit conditions. Training a model called Remote Control to predict change enabled accurate calibration of test results to approximate the time zero value at the point of collection, despite sample degradation. With calibration, unprocessed whole blood could be transported, for up to 9 days under ambient conditions and exposed to temperatures between 3.4 and 47.4 °C. Under these conditions, agreement with CLIA TEa ranged between 98.1 and 100%, with a |%bias| of 0.1-1.6%, a %CV of 2.2-4.9%, and a minimum sigma metric between 3 and 8.8σ for lipids (Cholesterol, HDL, LDL, Triglycerides, APO-A1, and APO-B). Performance was linear across measurement intervals (R Show less

Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. Therefore, effective treatment of NSCLC patients is very important. This study analyzes the impact of a nursing intervention of case management combined with cognitive-behavioral therapy on anxiety and depression and quality of life in postoperative NSCLC patients. A single-center, non-randomized controlled study in which 80 NSCLC patients from the Hospital were enrolled from May 2023 to January 2024, and were categorized into case management (CM) and cognitive-behavioral therapy (CBT) groups depending on treatment modalities, with case management care in both groups, and cognitive-behavioral therapy care added to the CM combined with CBT (CC) group. The Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), self-perception burden scale (SPBS), life qualities (QLQ-C30), neurotransmitter levels, and clinical effectiveness were primarily assessed in both groups post-treatment. Secondary outcomes included pain level (VAS score), nursing satisfaction, adverse events, and complications. After treatment, the indicators of both groups were significantly different from those of the pre-treatment. Post-treatment, the CC group demonstrated significantly lower scores than the CM group in HAMA (10.18 ± 2.10 vs. 16.04 ± 3.89), HAMD (11.94 ± 2.91 vs. 16.81 ± 3.19), and SPBS (25.52 ± 3.17 vs. 33.50 ± 5.61) (all P < 0.05). Conversely, the CC group showed significantly higher QLQ-C30 scores and levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). The nursing intervention of case management combined with cognitive behavioral therapy has a good improvement effect on the anxiety and depression status of NSCLC patients. It can improve the quality of life, which is worth promoting and using in the clinic. Show less

Adverse childhood experiences (ACEs) represent a strong influence on the developing brain and profoundly affect corticolimbic circuits, thereby contributing to vulnerability for mental disorders. Individual differences in resilience-related behavior, such as physical activity, may mitigate these effects. This retrospective study examined whether self-reported lifetime physical activity (LPA) modulates the relationship between ACEs and resting-state functional connectivity (rs-FC) of key limbic regions among 75 adults (mean age = 31.8 years, 82.7% female). Interaction models (ACE × LPA) were constructed for seed-to-voxel analyses, using the amygdala, hippocampus, and anterior cingulate cortex as seeds. Significant clusters were extracted and subjected to moderation analyses, and the Johnson-Neyman technique was used to determine sample-specific LPA ranges where the association between ACEs and connectivity became statistically significant. Significant ACE × LPA interactions were observed across all 3 seed regions, with robust clusters located in subcortical-cerebellar, visual association, and motor networks. Across clusters, greater ACE exposure was associated with reduced connectivity at lower LPA levels but increased connectivity at high levels, indicating a crossover moderation pattern. The Johnson-Neyman technique identified LPA ranges (∼150-390 min/wk) where ACE effects on connectivity were statistically significant. LPA moderated the association between ACEs and rs-FC within emotion- and sensorimotor-related networks. Higher activity levels were linked to connectivity profiles consistent with potential neural resilience to early adversity. These findings highlight physical activity as a modifiable lifestyle factor associated with neurobiological adaptation following early adversity. Show less

Lipoprotein(a) [Lp(a)] promotes atherosclerotic plaque vulnerability through pro-inflammatory and thrombogenic pathways, while the CatLet© angiographic score quantifies coronary lesion complexity. We hypothesized that their integration would improve prognostication in acute myocardial infarction (AMI) after emergency percutaneous coronary intervention (ePCI). In this retrospective cohort, 307 AMI patients undergoing successful ePCI (2020-2022) were stratified by 1-year major adverse cardiovascular/cerebrovascular events (MACCE). Serum Lp(a) and troponin I were measured post-admission. CatLet© and Gensini scores were assessed by blinded analysts. Multivariable logistic regression and ROC analyses evaluated predictive performance. MACCE patients (n = 78) exhibited higher Lp(a) (135.99 ± 33.07vs. 123.35 ± 42.70nmol/L, P = 0.0178) and CatLet© scores (33.58 ± 9.04vs. 30.80 ± 8.24, P = 0.0012) versus controls. Lp(a) (OR=2.339,95%CI:1.519-3.603, P <  0.001) and CatLet© score (OR=1.092, 95%CI:1.027-1.161, P = 0.005) independently predicted MACCE. The combined model Lp(a)≥70.70 nmol/L + CatLet© ≥ 18.6) significantly outperformed individual markers (AUC 0.862 [95%CI:0.83-0.96] vs. 0.780/0.833; DeLong's test confirmed the superiority of the combined model over individual predictors (P = 0.0089, Z = 2.64 vs. Lp(a); P = 0.034, Z = 2.12 vs. CatLet© score), with 88% sensitivity and 83% specificity. The Lp(a)-CatLet© synergy enhances MACCE risk stratification in ePCI-treated AMI, reflecting complementary pathobiological (Lp(a)-driven plaque vulnerability) and anatomical (CatLet©-quantified complexity) pathways. This dual-parameter approach could support post-PCI risk stratification and follow-up planning. Show less

Alzheimer's disease (AD) is a progressive disorder that affects the brain and leads to cognitive decline and memory loss, with postmenopausal women being unduly affected. Estrogen is believed to exert neuroprotective effects by influencing amyloid-beta accumulation, tau hyperphosphorylation, oxidative stress, synaptic function, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signalling. This review examines the role of estrogen in AD pathogenesis among postmenopausal women. A systematic literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included "estrogen", "Alzheimer's disease", "neuroprotection", "amyloid-beta," and "BDNF." Inclusion criteria were peer-reviewed studies from the past 10 years focusing on estrogen's effects on AD mechanisms, neurobiology, and therapeutic relevance. Articles were screened by title and abstract. Followed by a full-text review to ensure methodological rigour and relevance. Evidence indicates that estrogen reduces amyloid beta burden, inhibits tau phosphorylation, mitigates oxidative stress, preserves synaptic connectivity, and suppresses neuroinflammation. Estrogen also modulates ApoE-linked lipid metabolism and enhances BDNF signalling, supporting neuronal survival and cognitive resilience. Declining estrogen after menopause increases vulnerability to AD. Understanding estrogen's neuroprotective mechanisms may support targeted therapeutic strategies. Hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs) show potential, but further research is needed to optimise timing, dosage, and patient selection in postmenopausal AD prevention and management. Show less