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The present study aimed to investigate the combined impact of lipoprotein (a) [Lp(a)] and low-density lipoprotein (LDL) subfractions on cardiovascular outcomes in patients with acute coronary syndrome (ACS). The study enrolled 2061 ACS patients from Tianjin Chest Hospital. Participants were categorized into 4 groups based on their Lp(a) and the concentration of the sixth component particles of LDL(LDL-P6). The primary endpoint was the occurrence of major adverse cardiovascular events (MACE). The relationship between LDL-P6, Lp(a), and MACE was evaluated. Over a mean follow-up period of 5.4 years, 456 (22.1%) patients experienced MACE. Multivariate analysis identified both LDL-P6 and Lp(a) as significant independent predictors of MACE in ACS patients. Those in the highest-risk group had a substantially higher incidence of MACE compared with the lowest-risk group (HR 5.718; 95% CI 3.703-8.829; Show less

Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to investigate the combined effect of elevated Lp(a) and DM on survival outcomes in CAD patients. This study included 65 547 CAD patients (62.6 ± 10.7 years, 27.7% female) from CIN-II and RED-CARPET cohorts. Patients were stratified into four groups by Lp(a) levels (< or ≥ 30 mg/dL) and DM status. Multivariable Cox regression models estimated associations with cardiovascular and all-cause mortality, examining additive and multiplicative interactions. During a median follow-up of 5.5 years, 10 686 (16.3%) patients died from all causes and 5106 (7.8%) died from cardiovascular causes. Patients with Lp(a) ≥ 30 mg/dL and DM were independently associated with cardiovascular mortality (adjusted hazard ratio [aHR]: 1.28, 95% CI: 1.20-1.35; aHR: 1.53, 95% CI: 1.44-1.62, all p < 0.001, respectively). Compared to patients with Lp(a) < 30 mg/dL without DM, the aHRs were 1.26 (95% CI: 1.16-1.36, p < 0.001), 1.51 (95% CI: 1.40-1.62, p < 0.001) and 2.00 (95% CI: 1.83-2.18, p < 0.001) for those with Lp(a) ≥ 30 mg/dL without DM, Lp(a) < 30 mg/dL with DM and Lp(a) ≥ 30 mg/dL with DM, respectively. Significant additive interaction between elevated Lp(a) and DM on cardiovascular mortality was observed, with 12% of the excess risk attributed. Similar associations were observed in all-cause mortality. In patients with CAD, elevated Lp(a) and DM act synergistically to increase the risk of cardiovascular and all-cause mortality, suggesting that both risks should be considered to integrate management. Show less

This study aimed to evaluate serum brain-derived neurotrophic factor levels, stress, and quality of life in leprosy patients, and to explore their interrelations. A cross-sectional study was conducted from September 2024 to May 2025 at 3 hospitals in Medan, Indonesia, involving 45 leprosy patients aged ≥ 18 years who met inclusion criteria. Serum brain-derived neurotrophic factor levels were measured using ELISA, stress was assessed using the Perceived Stress Scale-10, and quality of life was evaluated through the WHOQOL-BREF questionnaire. Descriptive statistics, Shapiro-Wilk normality test, and Spearman's rank correlation were used for analysis. The mean serum brain-derived neurotrophic factor level was 7.38±3.37 ng/mL. Patients with multibacillary leprosy without reaction had higher brain-derived neurotrophic factor levels than those with type 1 or type 2 reactions. Stress levels were mild in 42.22% and severe in 28.89% of patients. Quality of life scores varied widely. A strong negative correlation was found between brain-derived neurotrophic factor and stress (r=-0.953, p< 0.0001), and a strong positive correlation between brain-derived neurotrophic factor and quality of life (r=0.962, p< 0.0001). These findings suggest that serum brain-derived neurotrophic factor levels are associated with psychological well-being in leprosy patients and may serve as a potential biomarker for mental health monitoring in this population. Show less

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by repetitive behaviors, social deficits, and comorbid phenotypes, with rising prevalence. Its unclear pathogenesis and symptom heterogeneity hinder therapy development. Chrysin, a flavone from bee products and plants, shows diverse biological effects but limited ASD studies. Therefore, this study examines chrysin's impact on ASD behaviors and comorbidities. Pregnant Wistar rats received 600 mg/kg valproic acid (VPA) on Embryonic day (ED) 12.5 intraperitoneally to induce ASD phenotypes. Neurodevelopmental milestones were evaluated on postnatal day (PND) 3-20. Twenty-seven male offspring were used for the study. The control (n = 9 ), the VPA-exposed offspring were randomly divided into two groups: a VPA + vehicle group (n = 9) and a VPA + chrysin treatment group (n = 9). The animals received distilled water or chrysin (100 mg/kg p.o) from PND21-42. Typical and atypical baseline behaviours were done on PND21 and repeated on PND42. Serum corticosterone, prefrontal cortex (pFC), and hippocampal (HPC) neurotransmitters, Histone deacetylase (HDAC), BDNF, and caspase-3 were evaluated with ELISA, while Shank3, p-AKT, and pS6 were evaluated with immunohistochemistry and Western blot. Data were analysed using One-way or Two-way ANOVA at α < 0.05. The VPA-exposed pups exhibit signs of developmental delay compared to the controls. Chrysin also ameliorated hyperalgesia (2.659 ± 0.2628vs4.257 ± 0.3272), depressive-like behaviour (68.86 ± 3.912vs138.5 ± 9.526), and anxiety (189.6 ± 20.58vs95.10 ± 7.716). Autistic-like, sociability (0.46 ± 0.039vs0.28 ± 0.06), and social novelty (0.77 ± 0.08vs-0.28 ± 0.19) were improved by Chrysin. Chrysin increased the level of serum corticosterone (22.45 ± 1.77vs13.90 ± 0.49) when compared to VPA-only. In the prefrontal cortex and hippocampus, the levels of serotonin, GABA, and dopamine increased, while glutamate levels decreased. The levels of HDAC (1.28 ± 0.12vs2.56 ± 0.10; 1.22 ± 0.11vs1.35 ± 0.18), and Caspase3 (10.33 ± 0.72vs16.79 ± 0.85; 4.50 ± 0.53vs6.45 ± 0.78) were reduced compared to VPA-only, while increasing the levels of BDNF (21.25 ± 0.63vs14.73 ± 0.57; 17.86 ± 1.23vs7.39 ± 0.56). Chrysin increased the expression of SHANK3(1.43 ± 0.1311vs0.6588 ± 0.02533; 0.8895 ± 0.1092 vs. 0.1961 ± 0.1401), p-AKT (0.8923 ± 0.04518vs0.2493 ± 0.03399; 1.011 ± 0.09692vs0.4969 ± 0.08145), and pS6 in the pFC and HPC. Chrysin may have ameliorated valproic acid-induced Autistic-like behaviours by upregulating epigenetic and translational control of scaffolding protein synthesis, and preserving neurotrophic signalling, in male Wistar rats exposed to VPA in utero. Show less

The incidence of multiple sclerosis (MS) has increased in recent years. Its pathogenesis involves the interaction between various elements, with interleukin 27 (IL-27) playing a key role in autoimmunity. The presence of the IL-27 receptor on astrocytes emphasizes its involvement in the disease's progression. The study aims to investigate possible associations between IL27 rs181206, serum level of IL27, and the development of MS. The study comprised 70 MS patients and 70 seemingly healthy controls. They were genotyped for IL27 rs181206 using the Taqman allelic discrimination approach, and their serum IL27 levels were estimated using ELISA. The frequency of TT genotype, T allele, and IL27 serum level were significantly higher among MS patients compared to controls. There was no significant difference between IL27 serum levels among different genotypes in both MS patients and controls; however, individuals with TT genotype showed higher levels of IL27 than those with CC genotype. TT genotype and T allele can increase the risk of developing MS. On the other hand, carrying the C allele may be associated with a lower risk of MS development. Understanding IL27 genetics and epistatic interactions can help clarify IL27's role in MS pathogenesis and utilize it as a therapeutic target. Show less

As a result of individual genetic variations, some patients show no response to initial antidepressant medications. This study aims to investigate the association between specific genetic polymorphisms and the efficacy of antidepressant drugs and to improve the accuracy and effectiveness of treatment under the guidance of genetic testing. A retrospective screening was conducted on medical records from, Suixian People's Hospital between January 2022 and December 2024. A total 202 patients with depression carrying the CYP2C19 gene were selected after the application of exclusion criteria. They were assigned to three groups in accordance with their genetic metabolism types: the rapid metabolism group (Group A, n = 65), the intermediate metabolism group (Group B, n = 94) and the poor metabolism group (Group C, n = 43). All three groups were treated with sertraline for a six-week treatment cycle. The observation indicators included scores on the Hamilton Depression Scale (HAMD); onset time of drug effect; rates of response and remission; scores on the Clinical Global Impression-Improvement (CGI-I) scale; levels of the neurotransmitter factors 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA) and brain-derived neurotrophic factor (BDNF); incidence of adverse events; and scores on the Morisky Medication Adherence Scale-8 (MMAS-8). The baseline data of the three groups of patients were comparable before medication (p > 0.05). Compared with those in Groups A and B, patients in Group C showed a significantly greater reduction in HAMD scores (all p < 0.05), along with higher response rates (all p < 0.05) and remission rates (all p < 0.05). Amongst the three groups, Group C had a shorter onset time of drug effect (all p < 0.05); more significant improvement in CGI-I scores (all p < 0.05); and more prominent upregulation of neurotransmitter factors, namely, 5-HT (all p < 0.05), GABA (all p < 0.05) and BDNF (all p < 0.05). Regarding the incidence of adverse events, Group C had the highest rate, whereas Group A had the lowest (10.8% vs. 24.5% vs. 41.9%). Compared with other groups, Group B exhibited a more significant increase in MMAS-8 scores (all p < 0.05). Metabolic phenotype exerts substantial effects on the therapeutic outcome of sertraline in patients with depression carrying the CYP2C19 gene. Amongst groups, Group C showed better therapeutic efficacy but an elevated incidence of adverse events and lower medication adherence; Group A had relatively poor efficacy; and Group B demonstrated superior adherence. In clinical practice, individualised treatment can be implemented on the basis of CYP2C19 metabolic typing to improve therapeutic efficacy and reduce adverse events and medical burden. Show less

Interleukin 1 receptor-associated kinase 1, 4 (IRAK 1/4) inhibitor exerts anti-inflammatory and immuno-modulatory effects; however, its role in high-fat diet-induced vascular dysfunction and cognitive impairment is not known, and therefore investigated in the present study. Animals were fed either a high-fat diet (60% Kcal fat) or a chow diet (10% Kcal fat) for 12 weeks to induce hyperlipidemia and weight gain. High-fat diet-fed animals were then treated with vehicle, IRAK1/4 inhibitor (2.2 mg/kg, i.p.) and a reference drug, Orlistat (20 mg/kg, oral gavage), for 4 additional weeks. Protein levels were assessed by ELISA or Western blotting, and mRNA by RT-PCR. IRAK1/4 inhibitor and reference drug, Orlistat treatment, prevented HFD-induced increase in body weight gain, fasting blood glucose and plasma lipids, improved discrimination between the familiar and the novel arm in the Y-Maze test, alleviated percent avoidance in two-way active avoidance, and freezing percent in contextual fear conditioning test. The treatments attenuated the levels of systemic inflammatory cytokines IL-1β, CRP, as well as TNF-α, IL-6 and protein expression of Iba-1, GFAP, HIF-1α, and restored the BDNF levels in the pre-frontal cortex of HFD-fed treated mice. IRAK 1/4 inhibitor exerted these effects by blocking proteasomal degradation of IκB-α protein in the pre-frontal cortex of HFD-treated mice. In addition, the treatments prevented HFD-induced increase in vascular ICAM-1, VCAM-1, MCP-1, COX-1 and COX-2 mRNA expression, and restored vascular eNOS mRNA levels as well as the Acetylcholine (300 ρM-300 μM) induced relaxations of PE (1 µM) pre-contracted aortic rings. IRAK1/4 inhibitor attenuates HFD-induced inflammation, vascular dysfunction and cognitive impairment in obese mice. Show less

This study aimed to investigate changes in brain structure and function of hippocampus in aged type 2 diabetes mellitus (T2DM) rats and the effects of tea polyphenol (TP) intervention using magnetic resonance imaging (MRI) and tissue-level molecular analyses. Rats were randomly assigned to six groups: Control, Aged, Aged T2DM, Aged T2DM + TP, Aged T2DM + rosiglitazone, and Aged T2DM + piracetam intervention groups. Anxiety- and depression-like behaviors were assessed using the open field test, the forced swimming test and elevated plus maze. Brain structure, blood flow and neuro-associated metabolites were evaluated via MRI. The number of nerve cells, neurons, microglia and astrocytes, the expression of BDNF/CREB/p-CREB protein, the levels of inflammatory factors, and the integrity of the myelin sheath in the hippocampus were evaluated. Relationships between behavioral, cellular and molecular changes and MRI-derived indicators were evaluated by Pearson correlation analysis. Aged T2DM rats exhibited severe anxiety- and depression-like behaviors accompanied by brain atrophy, reduced blood flow and decreased brain metabolites. At the microstructural level, the number of hippocampal neurons in the Aged T2DM group was significantly reduced, accompanied by increased counts of microglia and astrocytes. Meanwhile, the expression levels of hippocampal p-CREB and BDNF were decreased, the concentration of the inflammatory factor IL-1β, IL-6, TNF-α was elevated, and myelin integrity was impaired. Intervention with TP alleviated anxiety- and depression-like behavior, with MRI-detected abnormalities and in vitro histopathological molecular changes improved (except for myelin integrity). TP intervention mitigated alterations in brain structure and function as well as anxiety and depression-like behaviors in aged T2DM rats. Show less

Alzheimer's disease (AD) pathology disrupts functional brain connectivity long before symptoms emerge. African Americans face elevated AD risk, yet underlying mechanisms remain unclear. Genetic risk differs by ancestry: APOE-ε4 strongly predicts late-onset AD in European ancestry, whereas ABCA7 rs115550680 confers substantial risk in African ancestry. Yet, how these variants influence neural function in African Americans is unclear. The medial temporal lobe (MTL) is an early target of AD pathology and resting-state functional Magnetic Resonance Imaging (rs-fMRI) measures of dynamic network connectivity (hereafter "flexibility"), the brain's capacity to dynamically reconfigure connectivity, provide a sensitive metric of network adaptability, potentially preceding structural decline. However, comparative influence of APOE-ε4 and ABCA7 rs115550680 on MTL flexibility and subregional volumes in this population is unknown. 146 older African Americans (Mean Show less

Background With the prevalence of coronary artery diseases (CAD) on the rise, especially in the younger population, characterization of non-conventional risk factors remains essential, especially in the inherently predisposed Southeast Asian population. This study aimed at clinical and biochemical profiling in angiographically proven CAD in young Gujarati Indians without conventional risk factors such as tobacco/alcohol consumption. Methodology This single-center, descriptive, cross-sectional case series included consecutive Gujarati patients aged ≤45 years presenting with symptomatic, angiographically significant CAD over a 15-month period. Patients with tobacco or alcohol exposure and those with concomitant pre-existing diabetes mellitus and hypertension were excluded. Clinical characteristics, biochemical parameters (glycated hemoglobin, lipid profile, lipoprotein A (LpA), homocysteine, apolipoproteins), and coronary angiographic findings were recorded. Analyses were primarily descriptive, with limited exploratory comparisons. Results Overall, 2/4 obese patients (50%) and 3/4 obese patients (75%) were newly diagnosed with dysglycemia and dyslipidemia, respectively. Among patients with single-vessel disease (SVD; n = 16), eight (50%) patients presented with ST-segment elevation myocardial infarction, whereas among those with multi-vessel disease (MVD; n = 6), three (50%) patients presented with non-ST-segment elevation myocardial infarction. Elevated low-density lipoprotein cholesterol levels were observed in 8/16 (50%) patients with SVD and 3/6 (50%) patients with MVD. More than 5/6 (83.3%) patients with elevated LpA had SVD. Conclusions The study showed that non-conventional risk factors, such as obesity and family history of CAD, when combined with LpA and lipid profiles, can help in earlier identification of a predisposed individual in a high-risk population. Show less

The role of efferocytosis in chronic rhinosinusitis (CRS), particularly CRS with nasal polyps (CRSwNP), remains poorly understood. We comprehensively characterized efferocytosis in CRS and determined its association with inflammatory endotypes and clinical outcomes in CRSwNP. Efferocytosis-related marker expression between nasal polyps and healthy nasal mucosa was detected by quantitative real-time PCR and immunohistochemistry. Public single-cell RNA sequencing profiles of CRS were reanalyzed to dissect efferocytosis at single-cell resolution. Associations between efferocytosis and tissue inflammation were evaluated by Spearman correlation. Regression models and receiver operating characteristic analyses assessed the predictive capability of efferocytosis for CRSwNP recurrence. Compared with controls, CRSwNP exhibited widespread efferocytosis deficiency, including "find me" signals (CX3CR1, S1PRs, P2RY2, GPR132), "eat me" signals (ITGAV, MerTK, Tim1, ADGRB1), "don't eat me" signal CD300a, postengulfment signals (ABCA1, NR1H3/2, PPARδ/γ), and bridging molecule MFGE8. Macrophages, the principal efferocytic cells, shifted from homeostatic C3 Insufficient phagocytosis and increased antiphagocytosis activity are hallmarks of efferocytosis deficiency in CRS and are associated with the severity of inflammation and the clinical outcome of CRSwNP. Show less

The study explores the interconnection between the latent categories of mobile phone dependency and self-control in the sub-healthy urban older adults practicing Tai Chi. The findings aim to provide a reference for preventing mobile phone dependence, enhancing self-control and improving sub-health status in this population. A multi-stage cluster sampling method was employed to screen 560 sub-healthy urban older adults from 2,946 valid survey responses in Xuzhou City, Jiangsu Province. Sub-health status was verified using the SHMS V1.0 scale. Data were collected between September and October 2025. Latent profile analysis (LPA) was used to categorize mobile phone dependency and self-control. Pearson correlation analysis measured the relationship between these two variables. Additionally, chi-square test examined demographic differences across the identified latent profiles. Finally, multivariate logistic regression analyzed the associations between mobile phone dependency, self-control, and Tai Chi exercise. LPA identified four distinct profiles: Low dependency-Medium control (109 individuals, 19.5%), High dependency-No control (207 individuals, 37.0%), No dependency-High control (191 individuals, 34.1%), and Moderate dependency-Low control (53 individuals, 9.5%). These categories had statistically significant differences ( Tai Chi exercise exerts differential effects on urban sub-healthy older adults across distinct latent profiles of mobile phone dependency and self-control. Societal stakeholders should strengthen Tai Chi programs for these diverse categories to promote their physical and mental wellbeing. Show less

Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by the FMR1 premutation allele, is associated with brain degeneration, yet the mechanisms behind this neurodegeneration still need to be elucidated. Apoε polymorphism has been widely implicated in brain aging in cognitively healthy individuals and brain deterioration in Alzheimer's disease. This study aimed to examine the interaction of Apoε genotypes, FXTAS clinical symptoms, FMR1 molecular measures, and age, towards brain pathophysiology and cognitive functions. This longitudinal study includes MRI data collected from 205 male premutation carriers with and without FXTAS clinical symptoms and compared to 86 healthy male controls aged 40-85 years. The investigation includes FXTAS-related brain volumes, IQ, self-control behaviors, FMR1 molecular measures, and Apoε genotypes. In carriers with FXTAS, the presence of the Apoε2 allele showed a possible association with more favorable neuroimaging markers, such as reduced white matter hyperintensities, and lower incidence of the middle cerebellar peduncle sign, patterns that were not observed in carriers without FXTAS. Specifically, the presence of Apoε2 allele exhibited a potential protective effect on brain degeneration, and cognitive functions among FXTAS patients; on the contrary, the Apoε4 allele was associated with a worsening of brain volume and brain degeneration in carriers with no FXTAS symptoms. The identification of Apoε genotypes in FMR1 premutation carriers before any clinical symptoms of FXTAS are observed may improve symptomatic management leading to better outcomes for these individuals. Show less

Exercise-induced inflammation has been shown to influence iron metabolism. Conversely, ischemic preconditioning (IPC) has been proposed as a strategy to modulate post-exercise response, especially inflammation and neurotrophic factor secretion. In this study we analyzed the effects of a 14-days IPC intervention on the post-exercises changes of the selected Iron metabolism, inflammation and neurotrophic markers in the population of non-training healthy young man. Forty healthy, untrained young men voluntarily participated in this study and were randomly assigned to two groups: an IPC group (n = 20), which underwent a 14-day IPC intervention, and a placebo (SHAM) group (n = 20). Five participants from the IPC group and seven from the SHAM group did not complete the protocol and were excluded from the analyzes. Venous blood samples were collected at rest, immediately after and 2 h after the Wingate test. Selected inflammatory and neurotrophic markers were analyzed, including IL-6, IL-10, IL-15, LIF, BDNF, IGF-1, NGF, sAPPα, FSTL-1, and GDF-15. Additionally, serum levels of iron (Fe), hepcidin (Hpc), ferritin (Fer), erythroferrone (ERFE), and erythropoietin (EPO) were assessed. IPC increased resting ferritin (~ + 9%, p < 0.05), hepcidin (~ + 12%, p < 0.05), and erythroferrone (~ + 10%, p < 0.05) concentrations. The intervention also enhanced post-exercise IGF-1 (+ 8%, p = 0.03) and sAPPα (+ 10%, p = 0.04) release and reshaped cytokine profiles, with greater early elevations of GDF-15 and IL-15 (p < 0.05) and faster normalization of FSTL-1 within 2 h (p < 0.05). IPC further affected neurotrophic signaling, showing lower 2-h post-exercise BDNF levels (p < 0.05) and distinct IGF-1 kinetics (p < 0.01). Anaerobic performance remained unchanged (p > 0.05). Ischemic preconditioning induces coordinated alterations in iron metabolism and modulates inflammatory and neurotrophic responses to anaerobic exercise, without affecting physical performance in untrained individuals. Show less

Rapid advancements in artificial intelligence have magnified the inherent bottlenecks and energy inefficiencies of conventional von Neumann architecture. To address these limitations, processing information in a highly parallel, memory-integrated manner mimicking the human brain, neuromorphic devices have emerged as a cornerstone of next-generation computing. Among these, optical-neuromorphic devices are particularly promising. By using light, they offer transformative advantages, such as high speed, massive bandwidth, and minimal signal interference. Accordingly, we propose long-persistent luminescence (LPL) materials as novel substrates for optically operative artificial synapses. We utilize AGa Show less

Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospective UK Biobank cohort, we evaluated the bidirectional associations by time-varying Cox proportional hazards regression models and assessed shared genetic architecture using genome-wide association study summary statistics. Additionally, we employed collagen-induced arthritis (CIA) and chronic social defeat stress (CSDS) mouse models to investigate the relationship between rheumatoid arthritis (RA) and depression. Over 5,226,841 person-years of follow-up, 23,534 incident MDD cases were identified. The presence of any IMD was associated with higher MDD risk (hazard ratio [HR]: 1.95; 95% CI: 1.89-2.01). Conversely, 59,742 incident cases of IMD were documented. MDD was associated with increased IMD risk (HR: 1.47; 95% CI: 1.40-1.54). We observed significant global genetic correlations between IMDs and MDD (r Show less

Fear memory generalization is a fundamental hallmark of post-traumatic stress disorder (PTSD) that enables animals to use past experience to adapt to changing conditions. The infralimbic cortex (IL) is implicated in suppressing generalized fear, but the underlying molecular mechanisms remain unknown. Here, we demonstrate that S-nitrosylation of Dexras1 (SNO-Dexras1) in the IL drives fear generalization. Dexras1 is activated by nitric oxide (NO) donors as well as by N-methyl-D-aspartic acid (NMDA) receptor-stimulated NO synthesis in cortical neurons. It is found that the level of SNO-Dexras1 is significantly increased in the IL of generalized mice and downregulation of SNO-Dexras1 attenuates fear generalization. Mechanistically, inhibition of SNO-Dexras1 increases the expression of phosphorylated extracellular regulated protein kinases (pERK) and brain derived neurotrophic factor (BDNF), implicating synaptic remodeling in the IL. Our study reveals a key role of SNO-Dexras1 in the fear generalization, which may provide a potential therapeutic strategy for PTSD. Show less

Prior research has utilised person-centred approaches to identify parent feeding profiles distinguished by controlling and structure-based practices, but less research has examined autonomy support-based practices, or how social and family contextual factors differ between feeding profiles. This study aimed to identify profiles of parents with similar patterns of feeding practices and to examine whether profiles differ on family contextual factors. In 2022, 989 UK parents of children aged 3-6 years (M = 4.1 years) completed an online survey, which included the Comprehensive Feeding Practices Questionnaire (CFPQ), measuring parental feeding practices, and validated questionnaires capturing family contextual variables. Latent Profile Analysis (LPA) was conducted to identify parent feeding profiles using the CFPQ. A MANCOVA assessed differences in family contextual variables between profiles. LPA identified three profiles based on common model fit indices and theoretical considerations. Profile 1 'moderate control' (25.2%) showed moderate use of controlling practices and low use of structure-based and autonomy support-based practices. Profile 2 'structured and supportive' (29.6%) showed low use of controlling practices and high use of structure-based and autonomy support-based practices. Profile 3 'using everything' (45.2%) showed high use of all three types of feeding practices. Parents in the 'moderate control' profile had significantly lower parental wellbeing and reported more barriers of time and energy for meal planning compared to other profiles. In contrast, parents in the 'structured and supportive' profile had significantly lower household chaos and lower parental stress. Mothers had a higher proportion of membership to the 'structured and supportive' profile (33.9%) compared to other profiles, whereas fathers had a higher membership proportion to the 'using everything' profile (60.9%). Future interventions should be tailored to parent feeding practice profiles and associated family contextual factors. Show less

Neuroendocrine regulation of reproductive function represents a complex system based on the integration of signals between the central nervous system and peripheral organs. In recent years, particular attention has been given to the role of neuropeptides - such as kisspeptin, brain-derived neurotrophic factor (BDNF), and orexins - in the pathogenesis of disorders associated with menstrual irregularities. This review provides a detailed analysis of the molecular mechanisms underlying neuropeptide regulation in functional hypothalamic amenorrhea (FHA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS).Recent experimental studies are summarized, including stress-induced models of persistent estrous cycle arrest in laboratory animals and simulation of PCOS and POI using dietary and pharmacological interventions, respectively. Additionally, the review highlights publications demonstrating the significant role of impaired neuropeptide signaling in the development of reproductive disorders in women.The integration of fundamental research with clinical practice not only enhances our understanding of the pathophysiology of amenorrhea but also opens promising avenues for the development of novel therapeutic strategies, such as the use of kisspeptin agonists or other agents aimed at restoring reproductive function in women with various forms of menstrual dysfunction. Show less

Cardiovascular disease (CVD) is influenced by disturbances in lipoprotein composition and metabolism, including triglyceride-rich lipoproteins (TRLs) and elevated lipoprotein (a) (Lp(a)). While interactions between Lp(a) and very-low-density lipoproteins (VLDL) have been studied in hypertriglyceridemic and CVD populations, data in normotriglyceridemic individuals without CV events are limited. Seventy normotriglyceridemic adults with triglycerides < 150 mg/dL and no CV events were enrolled and divided into two groups based on Lp(a) concentration: <30 mg/dL and ≥30 mg/dL. VLDL was isolated by ultracentrifugation, and concentrations of Lp(a), lipids (triglycerides, cholesterol), and apolipoproteins (apo B, apo C-II, apo C-III, apo E) were measured in serum and VLDL. Serum lipid and apolipoprotein concentrations did not differ between the groups. Individuals with Lp(a) ≥ 30 mg/dL had significantly higher VLDL concentrations of triglycerides (+71%), cholesterol (+54%), apo B (+28%), apo C-II (+36%), and apo C-III (+33%). Ratios of lipids and apolipoproteins to apo B indicated unchanged VLDL particle composition, suggesting that differences reflected increased particle number rather than altered composition. In normotriglyceridemic subjects with Lp(a) ≥ 30 mg/dL, VLDL particles are more abundant but compositionally unchanged. Redistribution of lipids and apolipoproteins toward VLDL may contribute to VLDL residual cardiovascular risk, underscoring the need for further studies on VLDL-Lp(a) interactions. Show less

To investigate longitudinal changes in neuroimmune biomarkers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD), their modulation by standard therapy, and prognostic implications for 90-day outcomes. In a prospective cohort, 266 hospitalized AECOPD patients were stratified into worsened ( Compared with controls, AECOPD patients exhibited higher IL-6, TNF-α, PD-1, and MMP-9, alongside reduced BDNF and IL-10. Stable patients demonstrated partial biomarker normalization, whereas worsened patients retained a pro-inflammatory profile. Corticosteroids and antibiotics attenuated cytokine elevations, and oxygen therapy facilitated BDNF recovery. Low BDNF and high MMP-9 predicted spirometric decline, while elevated PD-1 and MMP-9 were associated with increased 90-day readmission risk. A dual-axis model incorporating neurotrophic and immune exhaustion markers outperformed GOLD classification for risk prediction. Neuroimmune biomarkers capture recovery heterogeneity in AECOPD. The proposed dual-axis model improves prognostic accuracy and may inform personalized management strategies. Show less

Near-infrared (NIR)-II fluorescence imaging at 1000-1700 nm is widely used for deep-tissue visualisation and disease theranostics in the brain, with NIR-II theranostics greatly improving imaging resolution, imaging depth, and therapeutic efficacy. However, the extreme lack of molecular design in NIR-II fluorophores has slowed the discovery of bright candidates and restricted their efficacious application in brain theranostics. Here, we develop a covalent bond locking (CBL) strategy that enables the feasible design of bright NIR-II fluorophores by effectively restricting the twisted intramolecular charge transfer state. These spirofluorophores incorporate terminally spiro-donor groups, which leads to a higher molar extinction coefficient and improved quantum yield than non-spirofluorophores do. With bright and stable NIR-II fluorescence advantages, we demonstrate that CBL nanoparticles (NPs) of spirofluorophores achieve multiscale high-resolution NIR-II angiography via one-photon fluorescence and two-photon fluorescence bioimaging simultaneously. With apolipoprotein E (ApoE) modification, CBL@ApoE NPs achieve enhanced blood-brain barrier permeability, facilitating superior brain glioma theranostics. This work proposes a CBL strategy to engineer highly bright NIR-II fluorescent fluorophores, providing a reliable nanoplatform for deep brain theranostics that can be effectively delivered across biological barriers to target brain tumors. Show less

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide, and an urgent need exists to discover new therapeutic strategies. Isolinderalactone (ISO) is a sesquiterpene compound derived from the Lindera aggregata root with significant anti-inflammatory effects. Given that atherosclerosis (AS) is a chronic inflammatory condition, the efficacy and mechanism of ISO on atherosclerotic disease are still unclear. The study aims to evaluate the therapeutic potential of ISO as an NLRP3 inhibitor in the management of AS. For in vivo study, ApoE Our data show that ISO reduced atherosclerotic plaque formation by inhibiting NLRP3 inflammasome activation and inflammatory responses. Network pharmacology analyses showed that ISO might alleviate AS by suppressing the NOD-like receptor (NLR) pathway, leading to reduced inflammatory mediators. ISO dose-dependently suppressed IL-1β secretion through inhibiting NLRP3 inflammasome activation, displaying an IC Collectively, ISO emerges as a novel NLRP3 inhibitor and a potential therapeutic candidate for atherosclerotic disease. Show less

This study explored the molecular mechanisms by which T7 peptide-modified liposomal irisin (T7@Lipo@Irisin) alleviates perioperative neurocognitive disorders (PND) via regulation of the AMPK/PGC-1α metabolic pathway. T7@Lipo@Irisin nanoparticles were prepared by thin-film hydration and ultrasonic dispersion and showed favorable physicochemical performance, with an encapsulation efficiency of approximately 85%. Serum analysis of healthy donors (n = 10) and PND patients (n = 6) showed higher IL-6 and TNF-α and lower brain-derived neurotrophic factor (BDNF) in PND. In vitro, T7@Lipo@Irisin restored mitochondrial membrane potential, reduced reactive oxygen species (ROS) accumulation, enhanced Neuro-2a hippocampal neuron viability, and activated the AMPK/PGC-1α axis under oxidative stress. In a PND mouse model, it improved Garcia neurological scores, preserved neuronal morphology, and decreased apoptosis. Multi-omic integration of scATAC-seq/scRNA-seq and TMT-based proteomics demonstrated enhanced neuro-glial crosstalk, epigenetic activation of metabolic/antioxidant genes (e.g., Sirt1, Nfe2l2), and upregulated pathways (mitochondrial function, NAD-dependent metabolism, synaptic homeostasis). Proteomics confirmed upregulation of SIRT1, NDUFS2, and BDNF, forming a network linked to energy metabolism and neural repair. Collectively, T7@Lipo@Irisin mitigates PND by activating AMPK/PGC-1α to enhance mitochondrial function and stabilize the neuro-microenvironment. Show less

The cytoplasmic fate of messenger RNAs (mRNAs) is dictated by the balance of translation and mRNA degradation, governed in part by the 3' poly-adenosine tail and cytoplasmic poly(A)-binding proteins (PABPCs). Deadenylases remove poly(A) to initiate mRNA decay, while sequence-specific RNA-binding factors, including Pumilio proteins (PUM1 and PUM2), modulate these processes. We investigated how human PUM1&2 repress target mRNAs by accelerating their degradation. We found that the poly(A) tail plays a central role in PUM repression, dependent on the interplay of deadenylases and PABPCs. PUM-mediated repression requires the CCR4-NOT deadenylase but not the poly(A) nuclease. PUMs associate with and require PABPC1 and PABPC4 to repress. In the absence of PABPCs, both PUM targets and non-targets become unstable, bypassing PUM control. Increasing PABPC inhibits PUM activity in a concentration-dependent manner by stabilizing poly(A) mRNAs. The results support a Goldilocks principle, wherein PABPC abundance tunes the response of mRNAs to PUM-mediated repression through protection of poly(A) from deadenylation. We propose that this principle may apply to other poly(A) dependent regulatory factors. Variation of PABPC levels across tissues and development suggests physiological relevance for this mechanism. Show less

Type II diabetes mellites (TIIDM) characterized by hyperglycemia, insulin resistance, insensitivity, and pancreatic β-cell atrophy has gained concern due to high rise in such cases globally. This study highlighted the therapeutic potency of a novel polyherbal formulation (PHF) of Phyllanthus urinaria and Adhatoda vasica Nees mice by in vitro, in vivo, and in silico analysis in high-fat diet (HFD)-streptozotocin (STZ)-induced Swiss albino. The findings showed significant inhibition of α-amylase and α-glucosidase activity of the PHF along with decreased blood glucose level, increased glycogen and serum insulin level, elevated mRNA expression of GIPR and GLP1R, GLUT2, GLUT4, INSR, INS1, INS2, TCF7L2, and Pdx1 in both low and high dose of PHF-treated mice as compared to HFD-STZ-induced diabetic mice. Western blot results also demonstrated augmented insulin protein level in both PHF-treated groups. Okanin and vomicine, identified from LCMS analysis as potent antidiabetic bioactive compounds bind to dipeptidyl peptidase 4 (DPP4) with a binding energy of -8.04 and -7.81 kcal/mol, respectively, as compared to standard drug metformin (-5.33 kcal/mol). Inhibition of DDP-4 by bioactives of PHF aids in enhanced secretion of incretion hormones leading to insulin secretion thereby established itself as a complementary and alternative therapeutics in the management of diet-induced TIIDM. Show less

Individuals with cancer often experience disrupted sleep, sedentary behavior, and reduced physical activity. This exploratory analysis examined the feasibility of continuous 24-h monitoring using wrist-worn accelerometers and characterized movement behaviors during a 12-week supervised resistance training program in individuals with cancer. We additionally aimed to evaluate whether daily movement behaviors (moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary time, and sleep) differed between exercise and non-exercise days. Thirty individuals with cancer wore Axivity accelerometers continuously while participating in supervised resistance training (2-3 sessions/week). Feasibility was assessed via wear-time compliance. Movement behaviors were analyzed descriptively across exercise and non-exercise days throughout the intervention. Participants demonstrated high adherence to continuous monitoring, with valid wear data on 70% of all days of the intervention. Within-person comparisons revealed significantly higher MVPA (+3.3 min) and LPA (+10.9 min) on exercise days. No significant changes were observed in sleep duration or sedentary time across the intervention or between exercise and non-exercise days. Continuous wrist-worn accelerometry is a feasible method for long-term behavioral monitoring in individuals with cancer. Supervised resistance training produced modest acute increases in physical activity but did not impact sleep or sedentary time. Show less