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Vitamin D may play a role in cardiovascular health, particularly in lipid metabolism and atherosclerosis. This study examines the correlation between serum vitamin D levels with Apolipoprotein B (Apo B), and the Framingham Risk Score (FRS) and evaluates the impact of correcting severe vitamin D deficiency on Apo B levels and FRS among a group of Iraqi population. This two-phase study was conducted in Baghdad between November 2022 and October 2023 and included a cross-sectional phase examining the association between vitamin D, with Apo B, and the FRS, followed by a prospective phase assessing the impacts of vitamin D correction. A total of 201 participants were recruited, including 60 individuals with severe vitamin D deficiency (≤ 10 ng/ml) who received supplementation and 40 with sufficient vitamin D levels (≥ 30 ng/ml) serving as controls. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Apo B, and FRS were evaluated at baseline and after six months. The Thai Clinical Trials Registry (TCTR) has retrospectively registered and approved the study under the identification number TCTR20250301003 on the 1st of March 2025. Vitamin D levels correlated significantly with age (p < 0.001), Apo B (p = 0.007), and FRS (p = 0.003) in the cross-sectional phase. After supplementation TC (p = 0.004) and FRS (p = 0.007) significantly decreased in the treatment group, with no significant changes in Apo B. Males only showed significant decrease in FRS and TC. Vitamin D correction significantly decreased TC and FRS reinforcing its role in lipid metabolism and cardiovascular health. However, Apo B levels remained unchanged, suggesting that vitamin D may not directly influence Apo B metabolism in the short term. These findings emphasize the importance of correcting severe vitamin D deficiency before calculating FRS due to its impact on lipid parameters. Show less

Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one-third of cases. Even when a structural lesion is identified as the epileptogenic focus, understanding the underlying genetic causes is crucial to guide both counseling and treatment decisions. Both somatic and germline DNA variants may contribute to the lesion itself and/or influence the severity of symptoms. We therefore used whole exome sequencing (WES) to search for potentially pathogenic somatic DNA variants in brain samples from children with lesional epilepsy who underwent epilepsy surgery. WES was performed on 20 paired DNA samples extracted from both lesional brain tissue and reference tissue from the same patient, such as leukocytes or fibroblasts. The paired WES data were jointly analyzed using GATK Mutect2 to identify somatic single nucleotide variants (SNVs) or insertions/deletions (InDels), which were subsequently evaluated in silico for their disease-causing potential using MutationTaster2021. We identified known pathogenic somatic variants in five patients (25%) with variant allele frequencies (VAF) ranging from 3-35% in the genes Show less

Examining how hypoglycemic medications affect brain function is one of the best approaches to addressing cognitive impairment. In this study, trelagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, was utilized to assess memory loss in diabetic rats through fear conditioning tests. Trelagliptin restored fear memory in diabetic rats that had been disrupted over a relatively long period (24 h) or extended period (5 days). Moreover, trelagliptin treatment reduced the higher incidence of neuronal cell death in the cerebral cortex, as observed via Nissl or hematoxylin and eosin staining. Subsequent analyses revealed that diabetic rats exhibited elevated levels of inflammatory cytokines (p-IKKα and p-NFκB) and a trend toward oxidative damage, indicated by malondialdehyde (MDA), superoxide dismutase 2 (SOD2), and glutathione peroxidase 4 (GPX4) detection. However, administration of trelagliptin reversed these markers to baseline levels. Additionally, trelagliptin activated p-AMPK, p-AKT, and p-GSK-3β. Notably, trelagliptin upregulated the expression of postsynaptic density protein 95 (PSD95) and synaptotagmin 1 (SYT1) while downregulating amyloid precursor protein (APP) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). These findings suggest that trelagliptin alleviates cognitive impairment in diabetic rats, likely through AMPK-AKT-GSK-3β-mediated mitigation of oxidative stress, enhancement of synaptic plasticity, and reduction of Aβ accumulation. Show less

Metabolic syndrome (MetS), a cluster of cardiometabolic abnormalities including elevated blood pressure, impaired glucose regulation, dyslipidemia, and increased waist circumference is increasingly recognized as a condition linked to both physical and psychological health risks. This study aims to investigate genotype-specific differences in psychological distress between healthy individuals and those with metabolic disorders, as well as to examine potential gene metabolic status interactions. This study is a cross-sectional analysis conducted in Turkistan city in the Southern region of Kazakhstan. Participants (healthy and those with metabolic syndrome) were invited to take part in the study by random sampling from the Khoja Akhmet Yassawi Kazakh-Turkish International University Medical Center. Consenting individuals provided a genetic analysis. Psychosomatic indicators were assessed using the Perceived Stress Questionnaire (PSQ) and the Depression, Anxiety, and Stress Scale (DASS-21). A total of 200 individuals participated, with an approximately 3:1 ratio of women to men. The mean age in years was 50.4 ± 9.5 and 48.8 ± 7.7 for men and women, respectively. Preliminary analyses showed variations in cognitive and psychosomatic measures among individuals with metabolic syndrome, but no associations with genetic variants, and no significant group differences across key psychosomatic indicators when stratified by metabolic or genetic factors. However, a significant difference in LPL-Anxiety between genotypes GA-GG ( Variations in metabolic and genetic factors within the studied population were not associated with measurable differences in stress or depressive symptoms. Show less

Little is known about the association between physical activity and the risk of pre-sarcopenic obesity (pre-SO) among adolescents. Hence, this study aimed to examine the association between physical activity and pre-SO in a sample of 2143 adolescents aged 12 to 18 years from Yinchuan, China. The pre-SO was defined by three criteria: low skeletal muscle mass adjusted by weight (SMM/W) combined with body mass index (BMI), fat mass percentage (FMP), and waist circumference (WC). After adjusting for age, smoking, drinking, sleep time, and high-fat food consumption, participants with high physical activity (HPA) had a lower risk of pre-SO compared to those with low physical activity (LPA) according to the obesity criteria of FMP (OR   0.63, 95% CI, 0.48-0.83, P < 0.05), and WC (OR 0.71, 95% CI, 0.52-0.96, P < 0.05). Additionally, restricted cubic spline models showed a linear dose-response association between total physical activity (TPA) and pre-SO no matter what obesity criteria were adopted (all P overall trend < 0.05, all P non-linear > 0.50). Subgroup analyses revealed that individuals with higher TPA levels exhibited a decreased risk of pre-SO in boys according to the obesity criteria of FMP, and WC. In conclusion, HPA is associated with a reduced risk of pre-SO in adolescents, especially among boys. Show less

Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less

This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups. Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Show less

Good skin quality not only improved carcass quality but also increased consumer demand for fresh poultry meat. This study aimed to investigate the developmental changes in skin growth and quality of Pekin ducks during 1-6 weeks of age. The skin samples were collected from the breast, back, and thigh tissues of six male ducks at the end of each week. The skin strength, skin thickness, and collagen content as well as the related gene expressions were determined for the evaluation of skin quality. The results showed that the body weight, absolute skin weight, areas, and density, epidermal and dermal thickness (breast and thigh), shearing force, piercing force (back and thigh), and collagen content in Pekin ducks increased linearly and quadratically with age, reaching a plateau at 5-6 weeks of age (P < 0.05). The mRNA expressions of IGF-1 and FGFR1 related to cell proliferation were highest in breast, back, and thigh of ducks at 3 weeks of age, while the mRNA expression of FGF14 and EGF associated with collagen synthesis reached maximum values at 5 weeks of age. Additionally, the mRNA expressions of IGF1R and FGFR2 were upregulated in breast and thigh skins of ducks at 1 week old and in back skin of ducks at 3 weeks old compared with birds at other weeks old (P < 0.05). In conclusion, the developmental pattern of skin growth and structure of Pekin ducks in a linear manner with increased age. The skin quality was increased in a quadratic manner, which was associated with the changes in mRNA expression of target genes related to cell proliferation and collagen synthesis. Show less

Congenital hypogonadotropic hypogonadism (CHH) can cause delayed secondary sexual characteristics and contribute to juvenile osteoporosis, with multiple causative genes having been reported. We treated a 27-year-old man diagnosed with central hypogonadism, presenting with delayed secondary sexual characteristics and juvenile osteoporosis, using bone resorption inhibitors and testosterone therapy. Genetic testing revealed missense variants both in the fibroblast growth factor receptor 1 ( Show less

Maternal circulating lipid concentrations impact the risk of pregnancy complications and infant health outcomes. The associations between physical activity and circulating lipids during pregnancy remain inadequately understood. A study was conducted from July 2024 to March 2025, involving the recruitment of 520 pregnant women in Wuhan, China. The Pregnancy Physical Activity Questionnaire (PPAQ) scores were evaluated in trimesters. Circulating lipid profiles, including total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), apolipoprotein A1 (APOA1) and apolipoprotein B (APOB) concentrations, were assessed at each trimester. The daily energy expenditure of physical activity (EEPA) during the first, second, and third trimesters was recorded as 11.35, 9.07, and 9.48 metabolic equivalents-hour/day (METs-h/d). The EEPA in the first trimester was significantly greater than that in the second ( This study suggests that increased physical activity during pregnancy is associated with lower lipid levels. Moreover, maternal age appears to have a significant impact on physical activity and the metabolism of circulating lipids during pregnancy. Show less

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a leading cause of sudden cardiac death (SCD) in young adults and athletes. It exhibits marked clinical variability, which may be influenced by genetic background and environmental factors. Although Show less

Atherosclerosis is traditionally viewed as a disease triggered by lipid accumulation, but growing evidence underscores the crucial role of the plaque microenvironment in disease progression. This review explores recent advances in understanding how cellular and extracellular components of the plaque milieu drive atherosclerosis, with a focus on leveraging these microenvironmental factors for therapeutic intervention. This review highlights recent advances in cell-cell crosstalk and matrix remodeling, offering insights into innovative therapeutic strategies for atherosclerotic cardiovascular disease. While atherosclerosis begins with the subendothelial retention of apolipoprotein B (ApoB)-containing lipoproteins​, its progression is increasingly recognized as a consequence of complex cellular and extracellular dynamics within the plaque microenvironment. Soluble factors and extracellular matrix proteins shape mechanical properties and the biochemical landscape, directly influencing cell behavior and inflammatory signaling. For instance, the deposition of transitional matrix proteins, such as fibronectin, in regions of disturbed flow primes endothelial cells for inflammation​. Likewise, impaired clearance of dead cells and chronic extracellular matrix remodeling contribute to lesion expansion and instability, further exacerbating disease severity. Targeting the plaque microenvironment presents a promising avenue for stabilizing atherosclerotic lesions. Approaches that enhance beneficial cellular interactions, such as boosting macrophage efferocytosis to resolve inflammation while mitigating proatherogenic signals like integrin-mediated endothelial activation, may promote fibrous cap formation and reduce plaque vulnerability. Harnessing these mechanisms may lead to novel therapeutic approaches aimed at modifying the plaque microenvironment to combat atherosclerotic cardiovascular disease. Show less

The rapid detection of drug resistance in Mycobacterium tuberculosis is essential for managing drug-resistant tuberculosis (DR-TB). This study evaluated the performance of molecular assays compared to phenotypic drug susceptibility testing (pDST) and targeted next-generation sequencing (T-NGS). We retrospectively analyzed 40 presumptive pulmonary DR-TB cases in Rio de Janeiro from 2018 to 2022. Xpert MTB/RIF Ultra (Xpert Ultra) and Line Probe Assay (LPA; MTBDRplus = LPA-1, MTBDRsl = LPA-2) were performed directly on clinical respiratory specimens, with pDST serving as the reference standard. T-NGS was used to identify resistance mutations and clarify discordant results. Most samples (92.5%) were smear-positive. Xpert Ultra and LPA-1 demonstrated high sensitivity for detecting resistance to rifampicin (91.7% and 89.3%, respectively). However, LPA-1 exhibited lower sensitivity for isoniazid (81.5%). The performance of LPA-1 decreased in samples with cycle threshold (Ct) values ≥16, indicating low bacterial load (p = 0.001). T-NGS detected resistance to fluoroquinolones (22.5%) and injectables (15-20%) that was missed by LPA-2 and MGIT. Mixed infections were identified in 17.5% of samples and accounted for 27.8% of discordant results. Isoniazid heteroresistance was detected in 32.5% of samples by LPA-1 and in 7.5% by T-NGS. Xpert Ultra and LPA-1 are effective for the rapid detection of rifampicin resistance but have limitations for isoniazid and second-line drugs. T-NGS improved the detection of low-level resistance, heteroresistance, and mixed infections, supporting its implementation in reference laboratories for comprehensive DR-TB diagnosis. Show less

Squamous cell carcinoma is the second most prevalent type of non-small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines. A novel new lung squamous cell carcinoma cell line, OMUL-1, was developed from the primary lung cancer of a 74-year-old man. We assessed the characteristics and behavior of OMUL-1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT-PCR), and RNA sequencing and invasion assays. OMUL-1-an adherent cell line-resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF-1 was negative). An invasion assay demonstrated that OMUL-1 had a lower invasion ability compared to that of other developed cell lines. RT-PCR analysis and RNA sequencing indicated that OMUL-1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c-MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL-1 cells. Immunohistochemistry revealed that IGF1R and PD-L1 were expressed in both the primary and subcutaneous tumors. We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1. Show less

Approaches of promoting a neural milieu permissive for plasticity and resilience against neuronal injury are important strategies for the treatment of a range of neurological disorders. Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective against various mental diseases. However, the underlying molecular mechanisms remain elusive. Here, we report a study of the neuroprotective effects of FGF21 by promoting 5-HT Show less

Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has demonstrated clinical benefit in stabilizing atherosclerotic plaques, yet its molecular mechanisms are not fully defined. This research sought to elucidate the protective effects exerted by SHTL on AS progression. To investigate the impact of SHTL on macrophage function and plaque stability, we utilized ApoE SHTL markedly attenuated the progression of AS, demonstrated by reduced plaque formation within both the aortic root and aorta, diminished plasma lipid concentrations, and suppressed inflammatory responses. SHTL demonstrates significant anti-inflammatory and lipid-regulatory effects, attenuating AS progression through the PPARγ/Mfge8 pathway, thereby enhancing macrophage efferocytosis. These findings highlight a novel mechanism by which SHTL may contribute to preventing and treating atherosclerotic diseases. Show less

Lysophosphatidic acid (LPA) is a bioactive phospholipid that mediates a variety of biological actions through binding to G protein-coupled receptors known as LPA receptors (LPARs). In mammals, six LPAR subtypes (LPAR1-6) have been identified. This study aimed to determine the expression of LPAR4 in the developing mouse brain. Brains samples were prepared from mice in various stages of development and biochemical and immunohistochemical analyses were conducted using anti-LPAR4. Western blot analysis detected two LPAR4-immunoreactive species at ∼50 kDa and ∼42 kDa from embryonic day 16.5 (E16.5). The ∼50 kDa molecule increased during development, reaching a peak at postnatal day 3 (P3), and then gradually decreased through P22. In contrast, the ∼42 kDa molecule continued to increase up to P22. Immunohistochemical analyses demonstrated strong LPAR4 expression in neural cells in the intermediate zone and cortical plate of the E15.5 cerebral cortex, whereas neural progenitors in the ventricular and subventricular zones exhibited weaker expression. At P15, fiber-like staining resembling the apical dendrites of cortical neurons and hippocampal pyramidal cells was also observed. This study demonstrated dynamic, spatiotemporal changes of LPAR4 expression in the brain from embryonic to postnatal stages. These findings support a potential role for LPAR4 in neural development. Show less

Here, we identified a type of hypothetical T7SS effector in This alternative strategy facilitates effectors' delivery, even for fragmented substrates, highlighting its importance in ensuring the functionality of T7SS. Show less

Early diagnosis of Alzheimer's disease (AD), particularly during its preclinical and prodromal phases, remains a major challenge. Plasma biomarkers such as phosphorylated tau at threonine 217 (p-tau217), amyloid-β (Aβ) isoforms, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) show promise for early detection; however, their relationships with medial temporal lobe (MTL) subfield atrophy and potential inter-biomarker pathways remain unclear. This study aimed to address this gap by investigating the associations between plasma biomarkers and MTL subfield atrophy, and by assessing potential mediation pathways. We conducted a cross-sectional study using data from 330 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively normal (CN) and mild cognitive impairment (MCI) groups. High-resolution coronal T2-weighted MRI quantified MTL subfield volumes using the ASHS protocol. Plasma biomarkers were measured using ultrasensitive immunoassays. The cohort included 209 CN participants (mean age [SD] = 69.3 [6.9] years; 64.2% women; 24.4% APOE ε4 carriers) and 121 MCI participants (mean age [SD] = 71.3 [7.3] years; 48.8% women; 27.9% APOE ε4 carriers). MCI individuals showed significantly higher plasma concentrations of p-tau217, p-tau217/Aβ Show less

Macrophage-like phenotype switching of vascular smooth muscle cells (VSMCs) is a crucial mechanism driving atherogenesis. Inhibition of a phenotype switch to macrophage-like cells is a promising strategy to prevent atherosclerosis (AS), and targeted nanotherapeutics represent one approach for implementing this strategy. To this end, we designed immunosuppressive oligodeoxynucleotide A151 functionalized selenium nanoparticles with a spearhead LacNAc (LN-A151-SeNPs) that target macrophage-like VSMCs. Nano characterization showed that the uniformity and stability of nanoparticles were optimized by modification with LacNAc and A151, resulting in an average diameter of 88.90 ± 1.45 nm, Zeta potentials of -21.1 ± 1.5 mV, a A151:Se molar ratio of 1:60 and mass ratio of 1.68:1. The effects of LN-A151-SeNPs on inhibiting VSMCs phenotype switching and attenuation of AS were investigated using [Image: see text] The online version contains supplementary material available at 10.1186/s12951-025-03925-7. Show less

Cancer cells fulfil their energy requirements by acquiring fatty acids (FAs) through both de novo synthesis and exogenous uptake. Although studies have focused on de novo FAs synthesis in papillary thyroid cancer (PTC), research on exogenous FAs uptake is scarce. Lipoprotein lipase (LPL), which enhances cellular FAs uptake, serves as the focal point of this study, which explored the role of LPL-mediated exogenous FAs uptake and FAs synthase (FASN)-mediated endogenous FAs synthesis in PTC cell proliferation. The expression of LPL was analyzed using databases including GTEx, GEO, and TCGA. Furthermore, its expression in PTC tissue samples and cell lines was confirmed. To observe the impact of the lipoprotein-deficient medium on PTC cells, EdU and TUNEL staining assays were conducted. CCK-8, colony formation, and TUNEL assays were performed to assess the effect of down-regulating LPL and/or FASN expression in PTC cells. Bioinformatics analysis revealed the upregulation of LPL mRNA in thyroid cancer. LPL expression was significantly elevated in PTC tissues and cell lines. Lipoprotein-deficient medium inhibited PTC cell proliferation and induced apoptosis. Similarly, silencing either LPL or FASN led to comparable outcomes. The combined inhibition of both LPL and FASN had a synergistic effect, enhancing the inhibition of PTC cell proliferation and the increase in apoptosis. Both the de novo synthesis and exogenous uptake of FAs are important for PTC cell proliferation. The combined inhibition of LPL and FASN inhibitors shows promise for PTC treatment. Show less

With less than two years remaining from 2027-the year which the government has targeted to achieve zero Indigenous cases, we map the malaria indicators across the 700 + districts for five years between 2019 and 2023 using spatiotemporal maps and also assess the potential drivers of malaria transmission in different regions. We used the annual district-wise malaria data from the National Center for Vector Borne Disease Control Programme (NCVBDC) and the cross-sectional socio-economic data from the National Family Health Survey. We also collated the meteorological and land-use land-cover data from the MERRA-2 and Sentinel-LPA satellites, respectively. We then developed region-specific ensembles of spatiotemporal models that allowed us to identify the associated covariates while the regions were identified using the Getis-Ord Gi* statistics. With 0.33 million malaria cases in 2019, the COVID-19 pandemic led to a significant reduction in reported cases. The P. falciparum affected regions are widespread in North-eastern and Central India. However, after the pandemic, an emerging geographical expansion into the north-eastern parts is observed for the P. vivax, which is evident from the clusters and the spatiotemporal ensemble models. Population belonging to scheduled castes and scheduled tribes and those economically marginalised are among the most vulnerable, but lifestyle habits such as drinking water practices, maternal education, and healthcare accessibility are associated with malaria transmission. We also developed a digital dashboard that allows the general public and the stakeholders to track the malaria indicators for each district and the corresponding year. Show less

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. Lipoprotein (a) [Lp(a)] has emerged as an independent risk factor for CAD, but its role in predicting coronary severity in Vietnamese populations remains unclear. To evaluate the value of Lp(a) in predicting the severity of coronary artery stenosis in chronic CAD. This cross-sectional study was conducted at Tam Anh General Hospital from June 2024 to June 2025, including 138 patients diagnosed with chronic CAD. Demographic, clinical, laboratory, and coronary angiographic data were collected. CAD severity was assessed using the Gensini score. Logistic regression and ROC analysis were employed to evaluate the predicting value of Lp(a). Severe CAD (Gensini score >40) was present in 31.9% of the cohort. Patients with Lp(a) ≥30 mg/dL exhibited a significantly higher prevalence of severe CAD (72.5% vs. 8.0%). Lp(a) levels correlated strongly with the Gensini score. The optimal cut-off for predicting severe CAD was 30.6 mg/dL (AUC = 0.869). Multivariate analysis confirmed Lp(a) as an independent predictor. Lp(a) ≥30 mg/dL is strongly associated with severe coronary artery stenosis. Lp(a) is a valuable independent predictor of CAD severity and may serve as an essential tool for risk stratification in clinical practice. Show less

Intramuscular fat (IMF) critically governs beef sensory attributes (juiciness, tenderness, flavor). Previous studies have predominantly focused on genomics and transcriptomics, with limited proteomic data available. To gain a more comprehensive understanding of the mechanisms regulating IMF deposition, we integrated proteomic and metabolomic profiling of the Longissimus dorsi across three genetically distinct cattle breeds. A comprehensive analysis of 633 differentially abundant proteins (DAPs) and 1456 differential metabolites (DAMs) identified 20 potential protein regulators (e.g., ACAA1, ACACA, ADIPOQ, and HSD17B12) and 19 candidate metabolites (e.g., hexadecanoic acid, icosadienoic acid, oleic acid, and oxaloacetate) as key molecular markers. Furthermore, HSD17B12 was found to inhibit IMF cell proliferation while promoting differentiation and lipid accumulation. This integrated approach highlights HSD17B12 as a critical regulator in enhancing IMF content, providing a theoretical foundation for improving beef quality. Show less

Previous studies suggest that total screen time does not comprehensively predict health behavior. The effects on health behaviors vary by app type. This study examines the association of different app categories (social, entertainment, game, education) related to physical activity (PA) and sedentary behavior (SB) patterns among university students. This study followed 345 university students aged 18–22 for 7 days. Physical activity (PA), and sedentary behavior (SB) were objectively measured using the ActiGraph GT3X-BT accelerometer. Smartphone app usage was tracked via objective daily survey logs. After the 7-day tracking period, semi-structured interviews were conducted to gather detailed information on app usage and physical activity. Data analysis was performed using SPSS 26.0 and R software. In 248 participants (139 males, 109 females), Males had higher daily energy expenditure and more sedentary time (ST) compared to females, who spent more time in light-intensity physical activity (LPA) but less in vigorous-intensity physical activity (VPA). Males showed a positive correlation between entertainment app usage and ST ( Different smartphone app categories show distinct associations with physical activity and sedentary behavior, with social apps linked to more light activity and entertainment/gaming apps to more sedentary patterns, especially in males. Show less

Schiff bases derived from 3-acetyl-4-hydroxycoumarin represent a promising yet underexplored scaffold in medicinal chemistry. Here, we report the efficient synthesis of a series of bisimine derivatives (3a-j) through condensation with structurally diverse amines, achieving yields of 68-95%. Spectroscopic characterization (NMR, IR, MS) confirmed their unique architectures, with 3j emerging as a standout candidate exhibiting anticancer activity comparable to doxorubicin but with superior selectivity against MCF-7 and A549 cell lines. Among the tested derivatives, compound 3a exhibited the most potent antibacterial activity, with the lowest MIC values observed against Gram-positive strains. Notably, 3f (a thiourea analog) demonstrated broad-spectrum antifungal efficacy (MICs: 1.95-31.25 µg/mL), while 3c surpassed ascorbic acid in radical scavenging (96.7% DPPH inhibition). Molecular docking revealed robust interactions between lead compounds (3b, 3c, 3j) and key therapeutic targets (FGFR1, cIAP1-BIR3), suggesting a dual inhibitory mechanism. These findings underscore the potential of coumarin bisimines as versatile platforms for addressing antibiotic resistance and oxidative stress-related pathologies. Show less

Mutations in LRRK2, a leading genetic cause of Parkinson's disease (PD), are linked to immune dysregulation, but the immune profiles in the periphery and central nervous system (CNS) remain incompletely defined. This study utilized a large cohort of serum samples (n = 651) and matched CSF samples (n = 129) from LRRK2 mutation carriers and non-carriers, with and without PD, to assess immune regulators using Luminex immunoassay. After correction for multiple comparisons, LRRK2 mutations were associated with significantly elevated serum levels of SDF-1 alpha and TNF-RII, while CSF markers such as BAFF, CD40L, and IL-27 were nominally reduced. Regardless of LRRK2 status, PD was associated with nominally lower levels of inflammatory analytes in CSF, with minimal changes observed in serum. Correlation analyses revealed distinct immune profiles between serum and CSF, suggesting compartmentalized immune responses. These findings highlight immune alterations in LRRK2 mutation carriers and PD, providing potential serum markers for monitoring immune responses and avenues for mechanistic studies. Show less

Xylaria nigripes, is a rare medicinal fungus known as Wulingshen in China. It has a neutral and sweet nature and belongs to the heart and kidney meridians. Rich in a variety of bioactive ingredients, it serves as a nutrient-dense food and a therapeutic agent for disease prevention. Wuling powder, a fermented form of X. nigripes, leverages biotechnology to harness the fungus's health benefits, showing significant therapeutic efficacy clinically, offering patients a safer and more effective treatment option. This article reviews the recent progress in the biological characteristics, chemical constituents, and pharmacological effects of X. nigripes. Additionally, it evaluates the modern clinical applications of Wuling powder and the current state of product development, aiming to provide insights for its further development and utilization. Research materials were collected from databases including SciFinder, PubMed, and Web of Science, encompassing over 20 years of academic literature, including books, doctoral dissertations, and master's theses from 2004 to October 2024. The literature search integrated keywords related to "X. nigripes", "Wulingshen", "Leizhenzi", "Wuling powder", "biological characteristics", "pharmacological profile", "chemical constituents", and "clinical applications", used in both English and Chinese. This review highlights the chemical diversity and bioactivities of 82 compounds identified from X. nigripes between 2004 and October 2024. Among these, 26 compounds exhibit diverse pharmacological properties, including antioxidant, anti-inflammatory, neuroprotective, anti-tumor, and cholesteryl ester transfer protein (CETP) inhibitory activities. Both aqueous and ethanol extracts of X. nigripes demonstrate comparable bioactivities. Clinical studies have further validated the efficacy of Wuling powder (dried mycelium product of X. nigripes) in regulating mental health, alleviating insomnia, and treating related disorders. The review also explores the product development status and potential of X. nigripes, analyzing its market prospects. Furthermore, it addresses advancements in artificial cultivation and industrial production, emphasizing the importance of sustainable supply chains for ongoing research and commercial applications. X. nigripes, with its elusive specific ingredients, is recognized for its potential health benefits and has been extensively researched. Due to its notable bioactive effects on human health, X. nigripes and its application, Wuling powder, have garnered considerable attention and have undergone extensive research. Recent multidimensional and interdisciplinary research approaches have achieved a deeper understanding of the biochemical nature and pharmacological effects of X. nigripes. This has led to the accumulation of substantial practical experience in the clinical application of Wuling powder-based medicines. Concurrently, the development of health products, deep fermentation technology, artificial cultivation and deep fermentation technology of X. nigripes have been successfully achieved. It is anticipated that X. nigripes holds the potential to emerge as a pivotal resource for the development of novel pharmaceuticals and therapeutic strategies targeting various human ailments. Show less