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Early detection of preclinical Alzheimer's disease (AD) could expand preventative care. Current biomarkers are costly, invasive, or lack generalizability. Driving and sensorimotor performance may reveal prodromal changes. We tested whether features from high-frequency driving trips detect preclinical AD and whether demographic, genetic, or sensorimotor data improve accuracy. Drivers aged ≥ 65 (n = 254) from Driving Real-World In-Vehicle Evaluation System (DRIVES) completed cerebrospinal fluid Aβ The top-performing model (driving, age, A high-frequency trip's driving telemetry, combined with age and Show less

Ttraumatic brain injury (TBI) induces oxidative stress, which contributes to neuronal damage and cognitive impairment. Apolipoprotein E (ApoE) plays a key role in neural repair and may modulate oxidative stress responses. However, the relationship between ApoE expression at different stages after TBI and oxidative stress markers, as well as its association with cognitive outcomes, remains unclear. A total of 126 patients with TBI were prospectively enrolled and stratified according to the Glasgow Coma Scale (GCS) score on admission into mild ( Serum ApoE levels peaked at 24 h and slightly decreased thereafter, with overall levels increasing in proportion to TBI severity ( ApoE exhibits an injury-severity-dependent increase during the early stage of TBI, and its levels are closely associated with oxidative stress imbalance and cognitive impairment. These findings suggest that ApoE may play a critical role in both the pathological progression and neural repair following TBI. Show less

This study aimed to identify phenotypes of subtle variation in multidomain cognitive performance and examine their longitudinal associations with Alzheimer's disease and related dementias (AD/ADRD) biomarkers and cognitive outcomes. Among 1192 cognitively unimpaired (CU) older adults from the Baltimore Longitudinal Study of Aging, latent profile analysis (LPA) identified phenotypes based on baseline patterns of neuropsychological test performance. Mixed-effects and Cox models examined longitudinal differences in cognitive status and AD/ADRD biomarkers (phosphorylated tau-181 [pTau181], amyloid-beta 42/40 ratio [Aβ42/Aβ40], neurofilament light [NfL], and glial fibrillary acidic protein [GFAP]) across phenotypes. LPA identified the following cognitive phenotypes: Subtle variations in neuropsychological performance among CU older adults have implications for long-term cognitive health and may help inform Alzheimer's disease and related dementias diagnosis and disease monitoring. Significant cognitive heterogeneity exists in CU older adults.LPA identified phenotypes based on cognitive performance.Personality and psychosocial characteristics differed by cognitive phenotype.Cognition over time and risk of cognitive impairment differed by cognitive phenotypes.The phenotype with greatest executive dysfunction had the fastest increase in NfL. Show less

To explore the dynamic evolution of symptom clusters in patients with gynecologic malignancies during the early postoperative period and identify key transition points and influencing factors, providing evidence for precision symptom management in clinical nursing. A longitudinal study was conducted among 324 patients using the MDASI-PeriOp-GYN on postoperative days 1 (T1), 5 (T2), and 7 (T3). Exploratory factor analysis identified symptom clusters at each time point, and growth mixture modeling (GMM) was applied to examine trajectory patterns. Latent profile analysis (LPA) and network analysis were performed at T2 to identify patient subgroups, influencing factors, and core symptoms. Five symptom clusters were identified: disease behavior, gastrointestinal, endocrine, neurological, and emotional. The emotional cluster, independent at T1 and T3, merged with the disease behavior cluster at T2. GMM indicated that all clusters declined from T1 to T2, followed by divergence after T2. LPA identified high- and low-symptom subgroups. Patients with ovarian cancer and those with KPS₁ were more likely to belong to the high-symptom group. Network analysis revealed "poor appetite" as the most central symptom at T2. Postoperative day 5 (T2) represents a critical transition point in symptom evolution. Ovarian and KPS₁ are at higher risk for severe symptoms, and "poor appetite" plays a key driving role. Targeted assessment and intervention at T2 may reduce symptom burden and improve recovery outcomes in patients with gynecologic malignancies. 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

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

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

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

Retirement is a major life transition that can alter patterns of movement behaviors (physical activity, sedentary behavior and sleep). While some studies indicate an increase in physical activity post-retirement, others report a rise in sedentary behavior. However, evidence is lacking on how individuals re-allocate time among movement behaviors, particularly using analytical approaches that account for the co-dependence of 24-hour time-use data. Furthermore, little is known about how pre-retirement occupational physical activity (OPA) levels influence physical activity after retirement. This study examined changes in the relative time spent in sleep, sedentary behavior (SB), light physical activity (LPA), and moderate-vigorous physical activity (MVPA) over retirement, and how these changes vary by pre-retirement OPA levels. Data were drawn from the Swedish Retirement Study, which followed 112 participants (47 men, 65 women; age: 60–72) at three timepoints during the retirement transition. Movement behavior and sleep data were collected over a week-long period using thigh-worn accelerometers and wrist-worn actigraphs. Compositional data analysis (CoDA) was employed to account for the co-dependent nature of 24-hour time-use data. Multivariable linear mixed models, adjusted for sociodemographic and health covariates, were used to evaluate the associations between retirement, OPA tertiles, and movement behaviors. In the overall sample, changes in movement behaviors mainly involved sleep. However, substantial variation was observed across OPA tertile groups. The sleep-to-wake time ratio increased in the high OPA group and, to a lesser extent, in the medium OPA group. Regarding physically active and sedentary time, a convergence between the high and low OPA groups was observed, as pre-retirement differences diminished. Specifically, the ratio of physically active time to SB decreased in the high OPA group and increased in the low OPA group. The findings indicate that pre-retirement OPA is a significant factor in understanding changes in movement behaviors during the retirement transition. The reduction in post-retirement physical activity among high-OPA workers may represent a healthier rebalancing rather than a decline, which aligns with the “physical activity paradox” and the “Sweet-Spot Hypothesis”. This evidence highlights the need for tailored interventions for retirees, particularly those from physically demanding occupations. The online version contains supplementary material available at 10.1186/s11556-025-00395-6. Show less

The scaffold protein IQGAP3 is highly upregulated in most epithelial cancers. While recent studies have highlighted its pivotal roles in cancer cell proliferation and metastasis, a deeper mechanistic understanding of IQGAP3 is currently lacking. We have here used TurboID to map IQGAP3 proximity partners and identified the Wnt signaling members Axin1 and CK1α as IQGAP3-interacting proteins. Our functional studies demonstrated that overexpression of IQGAP3 increases β-catenin levels, while IQGAP3 depletion reduces β-catenin levels in gastric cancer cells. Mechanistically, IQGAP3 disrupts Axin1-CK1α interaction, thereby inhibiting β-catenin phosphorylation and ultimately leading to its accumulation. Importantly, we discovered that IQGAP3 itself is regulated by Wnt signaling, suggesting its involvement in a positive feedback loop in Wnt/β-catenin signaling through interactions with Axin1 and CK1α. These findings identify IQGAP3 as a novel mediator of β-catenin stabilization and underscore its potential as a target for cancer therapy. Show less

Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and alopecia. Chemotherapy-induced alopecia severely impacts patients' quality of life and psychological well-being. Modified Huanjingjian (MHJJ), a traditional Chinese herbal formula, demonstrates clinical efficacy in alleviating chemotherapy-related side effects, yet its mechanisms against CTX-induced alopecia remain uncharacterized. And our main aim was to explore the efficacy and the mechanism of MHJJ in mice. UPLC-QE-Orbitrap-MS characterized MHJJ's chemical composition. A CTX-induced alopecia murine model was established. Systemic toxicity was evaluated through body weight monitoring, automated biochemical analysis (ALT/AST levels), and hematological profiling (WBC/PLT counts). Hair follicle histopathology was assessed via H&E staining. IHC and IF staining quantified proliferation markers and hair follicle stem cell (HFSC) biomarkers. Reduced representation bisulfite sequencing (RRBS) was used to map DNA methylation patterns. Wnt pathway dynamics were analyzed through qRT-PCR and IF staining. We identified 110 bioactive compounds in MHJJ. MHJJ intervention attenuated alopecia severity, restored follicular architecture, and increased follicular density compared to CTX monotherapy (p<0.05). HFSC proliferation markers (Ki67/CD34) showed significant upregulation, while apoptosis markers (Caspase-3) were suppressed. RRBS revealed MHJJ-mediated hypomethylation in differentially methylated regions, with gene body methylation constituting 60% of total methylation changes. Methylation-modulated genes predominantly localized to Wnt signaling pathways: MHJJ enhanced Wnt3/Wnt10a expression while suppressing Cer1/Axin1. Corresponding methylation reductions at promoter and gene body regions were confirmed at mRNA and protein levels. MHJJ mitigates CTX-induced alopecia through epigenetic regulation of HFSCs, specifically via DNA hypomethylation-mediated activation of Wnt3/Wnt10a and suppression of Cer1/Axin1. This mechanism promotes follicular regeneration by restoring Wnt signaling homeostasis, positioning MHJJ as a promising adjuvant for chemotherapy-induced alopecia management. Show less

Endothelial dysfunction is a key pathological mechanism in atherosclerotic cardiovascular disease, and methylglyoxal (MGO) has been identified as a major contributor to endothelial cell damage through its overabundance. In this study, the effects of MGO on atherosclerotic human endothelial cells were investigated. Human Umbilical Vein Endothelial cells (HUVECs) were first pre-treated with 1 mM palmitic acid (PA) for 24 h to induce lipotoxic conditions and then treated with 60 and 400 µM MGO for an additional 24 h. A total of six experimental groups were included: Control, 60 µM MGO, 400 µM MGO, PA, PA + 60 µM MGO, and PA + 400 µM MGO. Intracellular lipid accumulation was investigated using Oil-Red O staining. Apoptotic changes were assessed by flow cytometry, while nitric oxide (NO) levels were measured using the Griess assay. Gene expression patterns associated with angiogenesis, inflammation, lipoprotein, and cholesterol metabolism were investigated by real-time PCR. Based on findings, the distribution of lipid droplets was detected exclusively in the PA-treated group, while no such accumulation was observed in the MGO (60 and 400 µM)-treated groups. Furthermore, co-treatment with PA-MGO (60 and 400 µM) significantly reduced apoptosis, while PA with 60 µM MGO elevated NO levels (p < 0.05). HUVECs' exposure to MGO remarkably upregulated levels of LPL, LPA, IL-8, and IFN-γ (p < 0.05), whereas IL-6 levels were elevated only in the PA-MGO group (p < 0.05). The PA-MGO combination significantly altered the expression of angiogenesis-related genes (p < 0.05). MGO dose-dependently exacerbated the harmful effects of PA on HUVECs through increased inflammatory responses, impaired angiogenesis, and induction of nitrosative stress. Additionally, high concentrations of MGO altered the expression of genes related to lipid metabolism, including LPL and LP(a). Overall, the results indicate that MGO and PA may play a synergistic role in the occurrence of inflammation, lipid and angiogenesis disorders, and endothelial damage associated with CVDs. Show less

Adolescent psychological wellbeing is a critical determinant of lifelong health. Global data suggest a concerning decline in adolescent wellbeing. While the 24-hour movement behaviours, moderate to vigorous physical activity (MVPA), light physical activity (LPA), sedentary time, and sleep, have been linked to mental health outcomes; their associations with specific domains of adolescent psychological wellbeing remain underexplored. This study used compositional data analysis (CoDA) to examine how time-use relate to domain-specific wellbeing in Australian secondary school adolescents. Data were drawn from 124 adolescents (aged 13–17 years) participating in the TransformUs Secondary effectiveness trial. Wrist worn Actigraph GT9X accelerometer captured 24-hour movement behaviour over at least three valid days (≥ 16 h/day). Wellbeing was assessed using the EPOCH Measure of Adolescent Wellbeing, which includes five domains: engagement, perseverance, optimism, connectedness, and happiness. CoDA was used to examine associations between the composition of daily movement behaviours and EPOCH domains using isometric log-ratio (ILR) transformations. A compositional time reallocation analysis (30-minutes) was also performed to explore hypothetical associations with wellbeing outcomes. The average daily time-use composition was 680.9 min (47.3%) sedentary time, 473.0 min (32.8%) sleep, 250.7 min (17.4%) LPA, and 35.3 min (2.5%) MVPA. Greater time spent in LPA relative to other behaviours was significantly associated with higher happiness scores ( Adolescent daily movement behaviour composition was associated with domain-specific psychological wellbeing, particularly happiness. LPA was a potential contributor to positive psychological wellbeing. These findings suggest that even modest changes in daily routines, such as replacing sedentary time and LPA, may support adolescent flourishing. Future research should confirm these findings longitudinally and employ in intervention studies. The online version contains supplementary material available at 10.1186/s44167-025-00094-8. Show less

Mental health among college students represents a significant and growing public health concern. Negative bias in prospection is closely related to depression and anxiety. Prospection bias (PB) encompasses increased negativity, reduced positivity and overgeneralization, which exhibit intricate co-occurrence patterns and exert a complex influence on mental health. However, the presence of distinct patterns of PB and their impact on mental health remain unknown. We recruited 1,030 Chinese college students to complete assessments of PB, depression, anxiety, stress and resilience. Latent profile analysis (LPA) was used to identify distinct PB profiles. Linear regression was then applied to examine their effects on mental health outcomes. The results suggested six profiles: (1) high levels of increased negativity and overgeneralization but a low level of reduced positivity (contradictory overgeneralizers), (2) low PB, (3) moderate low PB, (4) a high level of increased negativity but low levels of reduced positivity and overgeneralization (simple contradictory), (5) high PB, and (6) moderate high PB. Regression analyses demonstrated that high prospection bias predicted more severe stress, depressive and anxious symptoms, as well as lower resilience. Additionally, the results implied that handling increased negativity and reduced positivity of prospection might be potential ways to improve mental health. These findings may facilitate the early detection of mental health issues among college students and contribute to the refinement of future interventions. The online version contains supplementary material available at 10.1186/s12888-025-07732-0. Show less

Diabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper metabolism is also implicated in diabetes and its complications. This study aims to identify copper metabolism-related biomarkers and potential drugs for DN. DN datasets and copper metabolism-related genes (CMGs) were obtained from Gene Expression Omnibus (GEO) and GeneCards. Differentially expressed CMGs (DE-CMGs) were identified using the limma package and the Venn algorithm. Functional enrichment analysis and protein-protein interaction (PPI) network were performed to identify candidate hub genes. The single gene with an area under the receiver operating characteristic (ROC) curve > 0.7 was identified as a potential diagnostic biomarker of DN. Finally, these biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in high-glucose-treated human proximal tubular (HK-2) cells. These validated hub genes were used to construct a combined prediction model, confirmed by additional GSE30528 and GSE30529 datasets. The correlation analysis between the expression level of the hub genes and the estimated glomerular filtration rate (eGFR) was carried out. Additionally, immune cell infiltration and potential target drugs were investigated for these biomarkers. Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN. Utilizing multiple biomarkers enhanced diagnostic accuracy and specificity. CD36, CCL2, and CASP3 correlated negatively with eGFR levels, while LPL and APOC3 correlated positively. Additionally, these hub genes were significantly linked to various immune cell types, including macrophages M1 and M2, T cells, gamma delta resting dendritic cells, neutrophils, and NK cells. Furthermore, 15 agents targeting these biomarkers were retrieved from the DrugBank database. Our study identified key genes possibly related to copper metabolism in the pathological mechanism of DN that could serve as novel targets for the diagnosis and therapy of DN. Show less

Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. Betaine, a natural methyl donor, has shown potential as a functional feed additive, but its comprehensive protective mechanisms under HF stress remain to be fully elucidated. Juvenile largemouth bass (Micropterus salmoides) were fed one of four isonitrogenous diets for 8 weeks: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. Growth performance, digestive enzyme activities, serum biochemical parameters, hepatic antioxidant capacity, and the expression of genes related to antioxidant defense, lipid metabolism, and inflammation were analyzed. The HF group exhibited significantly impaired growth, digestive function, and antioxidant capacity, along with elevated lipid peroxidation, dyslipidemia, and pro-inflammatory cytokine expression. Betaine supplementation restored growth performance and feed efficiency to control levels, ameliorated digestive enzyme activities (particularly enhancing lipase), and activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing enzyme activities. Betaine also improved serum lipid profiles, upregulated genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl), suppressed lipogenic genes (srebp-1, fas), and rebalanced inflammatory cytokines by reducing tnf-α and il-1β while increasing tgf-β1 and il-10. Dietary betaine effectively counteracts HF-induced metabolic stress in M. salmoides through coordinated multi-pathway regulation. It enhances antioxidant defense, reprograms hepatic lipid metabolism toward catabolism, and restores inflammatory homeostasis. These findings underscore betaine's role as a multi-functional feed additive capable of mitigating HF-related metabolic disorders and promoting overall health in carnivorous fish aquaculture. 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

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

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

To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatments (H1: 18:6, H2: 24:6, and H3: 30:6) were tested using agricultural unmanned aerial vehicles (AUAVs) for pollination assistance. The results showed that row-ratio had little effect on sterile line flowering dynamics. The index of flowers meeting (IFM) was 0.71-0.72 at Qionglai and 0.81-0.86 at Mianzhu, with 11 to 12 days of flowering duration. As the row-ratio increased, total pollen quantity in the panicle layer and grain filling rate (GFR) decreased, while grain infection rate (GIR) increased. The responses of grain blighted rate (GBR), grain empty rate (GER), and fertilization success rate (FSR) to row-ratio varied between sites. Pollen density and GFR followed the pattern of near region (NR) > central region (CR) > far region (FR). Within the panicle, pollen density was generally highest in the upper panicle layer (UPL), followed by the middle (MPL) and lower (LPL) layers, with partial exceptions observed in the H2 and H3 treatments at Mianzhu. The vertical distribution of GFR varied by site: at Qionglai, it was apical parts of panicle (APP) > median parts (MPP) > basal parts (BPP), whereas at Mianzhu the order was MPP > APP > BPP. With wider row-ratios, yield per unit area (YUA) and GFR declined (H1 > H2 > H3), while 1,000-grain weight increased or decreased and then increased. Under H1, yields reached 2,107.50 kg ha Show less

in the last decades, social networking sites (SNSs) use among adolescents has dramatically increased, feeding the adolescents' needs. However, younger users might be more vulnerable to problematic social networking. Scholar research increasingly highlighted the need to explore the underlying mechanisms of problematic use of SNSs. Difficulties in emotion regulation, general distress, experiences of shame, and specific motivations for SNSs use might represent risk factors for problematic social networking. On the contrary, other variables adolescence-related and potentially involved in problematic SNSs use (emptiness, boredom, emotional autonomy, and self-concept clarity) need further exploration. the present person-centered study aimed at profiling SNSs teen users (13-19 years) based on their (problematic) social networking, by comparing their SNSs-related behaviors and motivations, emotional dysregulation, distress symptoms, emptiness, boredom, shame, self-concept clarity, and emotional autonomy. the study involved 774 Italian adolescents (57% females; mean age = 15.74 ± 1.62 years) and four different profiles characterized by unique patterns of (problematic) social networking were identified through the latent profile analysis (LPA): (1) non-problematic SNSs users, (2) at-risk SNSs users, (3) problematic SNSs users, and (4) defended SNSs users (ntp=218; AIC=39125.44; BIC=39988.37; SSABIC=39296.00; entropy=.97; LMP-LRT p <.05; BLRT p <.05). concerning the emerging profiles, problematic and non-problematic SNSs users displayed the highest and lower levels of risk factors related to social networking, respectively. The so-called "Defended" profile might include participant adolescents who defensively avoided thinking about the psychological and emotional experiences of SNSs use, showing very low levels in all the variables exploring SNSs-related behaviors and motivations, and psychological risk. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle composed of apolipoprotein B-100 covalently linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The Lp(a) particle is enriched with oxidized phospholipids (OxPLs), which confer enhanced atherogenic and pro-inflammatory properties compared with low-density lipoprotein (LDL). Robust genetic and epidemiologic evidence demonstrates that elevated Lp(a) levels are independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. However, no pharmacologic therapy has yet been approved that specifically lower Lp(a) or to demonstrate a reduction in cardiovascular events. Antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and oral small-molecule Lp(a) inhibitors (e.g., muvalaplin) have demonstrated profound reductions in circulating Lp(a) concentrations, typically achieving decreases of 80-90%. In some studies, the reductions approached or achieved a near-complete suppression. Current genetic and modeling evidence suggests that an absolute reduction of at least 50 mg/dL in Lp(a) levels is required to achieve meaningful cardiovascular benefits. Large-scale outcome trials are now underway to assess the effects of these emerging therapies on cardiovascular and valvular outcomes. Early findings indicate favorable effects on oxidized phospholipids and vascular inflammation, suggesting broader anti-atherogenic potential. As these agents progress toward clinical use, routine Lp(a) measurement and risk stratification will become increasingly essential for personalized cardiovascular prevention. This review summarizes the molecular biology of Lp(a), highlights the limitations of current therapies, and discusses emerging RNA-based and small-molecule approaches with the potential to redefine the management of residual cardiovascular risk. Show less

Small ruminant lentivirus (SRLV) infections occur worldwide in goats and sheep and have negative impact on the production and welfare of animals. During recent years, many studies have focused on the host factors that determine the resistance of individual animals to SRLV infection; consideration of such factors would be an alternative to current control programmes based on culling seropositive animals. The aim of this study was to analyse the relationship between the expression of two previously selected goat genes, Primary fibroblast cultures obtained from the skin of goats with high SRLV proviral DNA load (HPL), low proviral load (LPL) or free of infection were inoculated with the A5 SRLV subtype circulating in the flock. The course of infection was observed based on cytopathic changes in cell cultures and the presence of SRLV A5 RNA, of which the level was monitored using a quantitative reverse-transcription PCR. The relative expression of the selected host genes following SRLV infection was analysed. The kinetics of SRLV replication differed, and distinctly higher numbers of SRLV particles were detected in cells derived from the HPL animal. The expression profiles of The observed relationship between expression of Show less

Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors, however, its function in osteosarcoma is unclear. This study aimed to explore the role of glycerolipid metabolism in osteosarcoma. We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and single-cell RNA sequencing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma. Tumor-associated macrophages (TAMs) and their interactions with immune cells were examined through single-cell analysis and co-culture experiments. Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6 (LPAR6) inhibitors. Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3 ( Show less

In quest of new and potent multitarget therapeutics for Alzheimer's disease (AD), a series of recently synthesized arylidene-hydrazinyl-thiazoles were repurposed as multitarget directed anti-AD agents. In total, 14 compounds were tested for their inhibitory activities against the key enzymes acetylcholinesterase (AChE), β-secretase 1 (BACE1), and butyrylcholinesterase (BChE). Derivatives Show less

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an RNA-binding protein known to play critical roles in metabolism, cell proliferation, and tumorigenesis. Although its involvement in muscle development has been documented in several species, the function of goose IGF2BP2 remains largely unexplored. In this study, we cloned and characterized the full-length cDNA and genomic DNA sequences of goose IGF2BP2. The cDNA is 2957 bp in length and contains a 1662 bp open reading frame encoding a 553-amino acid protein with five conserved RNA-binding domains. The genomic sequence spans 12,183 bp and consists of 12 exons and 11 introns. A total of 60 genetic variants were identified, including a deletion of a G base at position 2299 (g.2299delG) that results in a frameshift mutation. Expression analysis revealed high levels of IGF2BP2 mRNA in the liver, heart, and muscle tissues of female geese across embryonic (E25d), growing (A70d), and laying (L270d) stages, consistent with a potential role in muscle development ( Show less

Hypertrophic cardiomyopathies (HCMs) are among the most common genetic disorders; however, they might be underdiagnosed. Sequencing core sarcomere gene panels remain the main diagnostic tool. We present the results of HCM genetic testing performed at Lithuania's tertiary care center. All patients with diagnosed or clinically suspected HCM underwent next-generation panel sequencing. Of 204 patients, 34 (16.7%) received a genetic diagnosis. The most commonly affected genes were Show less