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Alzheimer's disease (AD) is moving toward earlier, biology-driven diagnosis, which increases the need for blood-based markers that are reliable, scalable, and interpretable across populations. This review integrates the AT(N) framework with a maturity model for circulating biomarkers. We first describe core and largely validated plasma measures, including LC-MS or automated immunoassay Aβ42/Aβ40 ratios, p tau217 and p tau231, glial fibrillary acidic protein (GFAP), and neurofilament light, and we relate them to recent multi-stakeholder recommendations on analytical performance and regulatory status. We then summarize replicated but context-dependent markers, such as soluble TREM receptors, CHI3L1, and MCP 1, which improve risk stratification when interpreted together with amyloid and tau. A separate section examines emerging readouts that capture central nervous system (CNS) processes indirectly, focusing on neuron-enriched extracellular vesicles (EVs) and EV-carried microRNA panels. These signatures are biologically plausible and often precede symptoms, although current datasets are small, Alzheimer's disease neuroimaging initiative (ADNI)-based, and require standardized pre-analytical handling and external validation before clinical triage can be recommended. We also discuss platform selection, comparing automated electrochemiluminescence (ECL) and single-molecule assays with LC-MS, and outline how composite plasma panels that include APOE genotype can support screen-confirm-monitor workflows in memory clinics. Finally, we propose a tiered implementation path in which genomic risk profiling and blood tests identify candidates for cerebrospinal fluid (CSF) or positron emission tomography (PET) studies. This shows how circulating and multi-omics biomarkers can be layered onto established plasma Amyloid beta (Aβ) and p tau assays to widen the measurable blood space in Alzheimer's disease. Show less

This cross-sectional study involved secondary data analysis to: (1) examine relationships between psychosocial factors (autonomous motivation for physical activity [PA], PA self-efficacy, social support for PA) and various levels of PA intensity (light PA [LPA], moderate PA [MPA], vigorous PA [VPA]), and moderate-to-vigorous PA [MVPA]) in adolescents aged 10-14 years in the U.S.; and (2) investigate the influence of demographic, physiological, and activity-related characteristics (age, sex, race/ethnicity, body mass index [BMI], annual family income, cardiorespiratory fitness [CRF; estimated maximal oxygen uptake: VO2 max], current sports or cheerleading team participation, and non-sport PA program participation) on various PA intensities. In 2022-2024, adolescents completed demographic and psychosocial surveys and wore accelerometers to assess PA. Of 935 adolescents enrolled, 623 (66.6%) provided valid accelerometer data (≥4 days). Structural equation modeling was used. MPA, VPA, and MVPA were positively associated with male sex, higher CRF, and sports or cheerleading team participation. Age and BMI z-score were negative predictors of MVPA and VPA. MPA was negatively associated with age, and LPA was negatively associated with annual family income. Social support for PA predicted autonomous motivation for PA and PA self-efficacy. Indirect effects of social support on the various levels of PA intensity via autonomous motivation or PA self-efficacy were not significant. Strengthening social support for PA may enhance adolescents' autonomous motivation for PA and PA self-efficacy to help them increase PA. However, indirect effects on the PA levels were not statistically significant. Findings underscore the promise and limitations of psychosocial pathways.ClinicalTrials.gov Identifier NCT04213014. Show less

Hyperlipidemia is highly prevalent worldwide and can affect cardiac pathophysiology. This study aimed to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the molecular mechanisms of myocardial stress and pathological remodeling in non-obese apolipoprotein E knockout ( Thirty-five 8-week-old male The HFD condition increased serum total cholesterol (TC) and triglyceride (TG) levels, but did not increase body weight, consistent with a lean hyperlipidemia model. Compared with the MICT condition, the HIIT condition demonstrated superior efficacy in reducing HFD-induced TC, TG and BNP levels ( In a non-obese, hypercholesterolemic Show less

To identify latent classes based on symptom clusters and to explore the association between these distinct symptom experience subtypes and social isolation in older adults with comorbid diabetes mellitus (DM) and coronary heart disease (CHD). A cross-sectional study was conducted among 337 older adults with DM and CHD recruited from the Department of Endocrinology and Cardiology of Nantong Sixth People's Hospital between February 2023 and October 2025. Data were collected using a general information questionnaire, the Chinese version of the Memorial Symptom Assessment Scale (MSAS), and the Lubben Social Network Scale-6 (LSNS-6). Exploratory factor analysis (EFA) was used to identify symptom clusters. Latent profile analysis (LPA) was then employed to classify patients into different symptom experience subtypes based on the symptom cluster scores. One-way ANOVA, Chi-square tests, and multiple linear regression were used to analyze the association between latent classes and social isolation. EFA extracted three symptom clusters (cardiopulmonary-fatigue, emotional-perceptual, and metabolic), accounting for 62.3% of the total variance. LPA identified three distinct latent classes: Class 1 "Low Burden-Balanced Pattern" (45.4%), Class 2 "Psycho-Somatic Co-dominant Pattern" (31.8%), and Class 3 "Metabolic-Physical Dominant Pattern" (22.8%). Univariate analysis revealed significant differences in social isolation scores (LSNS-6) across the three classes ( The findings reveal significant heterogeneity in symptom experiences among older adults with comorbid DM and CHD, which can be categorized into distinct latent classes. The subtype characterized by a Psycho-Somatic Co-dominant Pattern shows the strongest association with social isolation. In clinical practice, early identification of this high-burden subgroup may facilitate the provision of integrated interventions that address physical, psychological, and social dimensions. Show less

To identify latent profiles of proactive health behaviors in patients with hypertension, examine the category-specific influencing factors. Proactive health behavior, as an emerging concept, refers to a self-motivated approach to systematically managing health-related factors in order to actively maintain and promote one's health status. However, existing studies have largely focused on describing the overall level of such behaviors among patients with hypertension, with insufficient exploration of behavioral heterogeneity within this population. Moreover, there has been a lack of systematic integration of established behavioral theories to explain the multifactorial mechanisms underlying different behavioral patterns, which limits the development of precise nursing interventions. A cross-sectional study was performed, involving 352 patients with hypertension from 8 communities in Anhui Province from September to December 2025. The survey tools included self-designed demographic and clinical instrument, the Proactive Health Behavior Scale for Hypertensive Patients, the Self-Efficacy Scale for Hypertensive Patients, the Health Literacy Management Scale (HeLMS). Latent profile analysis (LPA) was used to identify subtypes of proactive health behavior among hypertension patients. Multinomial logistic regression analysis was applied to determine the factors associated with the identified subtypes. A total of 352 questionnaires were distributed, yielding 321 valid responses (a response rate of 91.2%). The total score of proactive health behavior was 89.57 ± 22.99 points. The LPA revealed four profiles of proactive health behavior: the positive proactive health behavior profile (Class 1, The proactive health behavior among hypertension patients was at a moderate level, revealing four distinct behavioral categories with significant differences. Guided by the Health Belief Model, profile-specific influencing factors were analyzed, which informed the development of tailored intervention strategies. Show less

Pine nut oil (PNO) is a candidate alternative to corn oil (CO) owing to comparable unsaturated fatty-acid profiles and enrichment in pinolenic acid (Δ5-18:3) and lipid-soluble micronutrients. We systematically compared extraction routes (solvent, supercritical CO₂, pressing), established solvent extraction as the optimal balance of yield and bioactive retention, and then characterized solvent-extracted oils from eight provenances using a weighted composite score to nominate Pinus tabuliformis for in vivo testing. In diet-induced obese mice (12-week Western diet, then 12-week intervention, n = 10 per group), replacing CO with PNO lowered body-mass gain and liver weight and improved serum lipids (triglycerides ↓ ∼ 28 %, total cholesterol ↓ ∼ 15 %, LDL-C ↓ ∼ 20 %) without affecting HDL-C or glucose; ALT and AST fell by ∼30 %, indicating hepatoprotection. Hepatic multi-omics revealed coherent remodeling toward PUFA-rich phospholipid species, activation of PPAR-centered peroxisomal/mitochondrial fatty-acid degradation and circadian pathways, and integrative correlations implicating Cyp4a10/14, Ehhadh, Slc27a2, Fgf21, Angptl4, and Plin5. Collectively, PNO reoriented hepatic lipid flux toward oxidation and membrane remodeling, supporting its development as a nutritionally advantaged culinary oil. Show less

Left pulmonary artery (LPA) sling is a rare congenital anomaly in which the LPA abnormally originates from the right pulmonary artery (RPA) and courses between the trachea and esophagus to reach the left pulmonary hilum. This anomaly is frequently associated with tracheobronchial and other cardiovascular anomalies and patients may manifest with varying airway and cardiovascular symptoms. Surgical repair is often required for symptomatic patients. Clinical outcomes largely depend on the extent and severity of coexisting anomalies, particularly tracheobronchial abnormalities. We report 2 autopsy cases of LPA sling, 1 pre- and 1 post-surgical repair. Comprehensive autopsy examination was crucial for confirmation of the clinical diagnoses and identification of a rare surgical complication. Show less

To identify latent profiles and influencing factors of toxic leadership behaviors of nurse managers experienced by staff nurses. Cross-sectional study. A total of 12 public hospitals in Guiyang and Zunyi city, Guizhou Province, China. From May 7, 2024 to December 31, 2024, a total of 900 nurses participated, and 868 valid questionnaires were collected with a validity rate of 96.44%. Data was collected via the Toxic Leadership Behaviors of Nurse Managers scale and a demographic questionnaire. Using latent profile analysis (LPA), distinct profiles of toxic leadership behaviors among nurse managers were identified. Univariate and multiple logistic regression analyses were performed to identify the factors associated with the toxic leadership behavior of nurse managers. The toxic leadership behaviors suffered by nurses were divided into four profiles: low toxic leadership behavior group (55.07%), moderate toxic leadership behavior group (16.71%), high toxic leadership behavior group (13.36%), and high Intemperate behavior group (14.86%). The results of multiple logistic regression analysis showed that nurses who are male, employed as non-permanent staff, or working in general hospitals are more susceptible to toxic leadership behaviors. This study used latent profile analysis to identify four distinct subgroups and found that male nurses, non-permanent staff, and nurses in general hospitals are more susceptible to toxic leadership behaviors. These results emphasize the need for developing strategies to address toxic leadership behaviors in order to promote nurses' wellbeing. Show less

Epstein-Barr virus (EBV) is an enveloped, double-stranded DNA virus that selectively infects primates. Periodontitis, a common inflammatory disease characterized by alveolar bone destruction, affects more than half of the global adult population. While EBV has been linked to periodontitis due to its pro-inflammatory effects and presence in the human periodontium, its effects on bone metabolism, particularly alveolar bone resorption, remain unclear. This study demonstrated that EBV infection in humanized mice induced osteoclast differentiation and alveolar bone resorption, resulting in sparse trabecular bone patterns and increased lacunae resorption. Extracellular vesicles (EVs) from EBV-infected cells contained M-CSF, essential for osteoclast differentiation, and increased CTSK and RANKL expression in osteoclast precursor cells after uptake. EBV infection increased the expression of group IIA-secreted phospholipase A Show less

Coronary artery calcification (CAC) signifies advanced atherosclerosis and portends increased cardiovascular risk. Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerosis; however, its association with in vivo lesion morphology and clinical outcomes in patients with symptomatic, advanced CAC remains incompletely characterized. This study aimed to investigate the association between elevated Lp(a) levels and both in vivo lesion morphology and clinical outcomes in this high-risk population. In this retrospective cohort, 292 patients with intravascular ultrasound(IVUS)-confirmed CAC were stratified into elevated (≥50 mg/dL,n = 77) or low (<50 mg/dL,n = 215) Lp(a) groups. The primary endpoint was major adverse cardiovascular events (MACEs). Associations were assessed via multivariable Cox models adjusted for clinical covariates. Patients in the elevated Lp(a) group presented a greater incidence of aortic valve calcification (p < 0.001). IVUS revealed constrictive remodeling with a smaller lumen and vessel dimensions. During a median follow-up of 17.2 months, the elevated Lp(a) cohort had a significantly higher MACE rate (37.7% vs. 15.8%; adjusted hazard ratio [aHR] 2.60, 95% CI 1.55-4.35, p < 0.001). Elevated Lp(a) independently predicted increased risks of ischemic stroke (aHR 7.14) and in-stent restenosis (aHR 2.78). In symptomatic patients with IVUS-confirmed CAC, elevated Lp(a) identifies a high-risk phenotype characterized by constrictive vascular remodeling and a markedly increased risk of MACEs, driven particularly by ischemic stroke and in-stent restenosis. These findings support the integration of routine Lp(a) testing into the risk stratification of patients with severe CAC, thereby identifying a precise high-risk phenotype that warrants intensified monitoring and represents an ideal target for emerging Lp(a)-lowering therapies. Show less

National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments. We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events. Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS). Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+. Show less

Cancer stem cells (CSCs) play a key role in the progression of colorectal cancer (CRC). The high heterogeneity of CSCs has hindered the clinical application of CSC-targeting therapies. Tetracyclines are drugs with therapeutic potentials beyond their antibiotic activity. We previously demonstrated the efficacy of tigecycline, a third-generation tetracycline, against a model of colitis-associated colorectal cancer, primarily focusing on its immunomodulatory role with a preliminary assessment of its impact on stemness. In this study we characterize the effects of tigecycline on colon CSCs in vitro and in a CRC xenograft model, with special attention on the signaling pathways involved and the modulation of the gut microbiota. We generated secondary colonospheres from two colon tumor cell lines HCT116 and CMT93, and evaluated the effect of tigecycline on CSCs properties. We showed that tigecycline (25, 50 μM) effectively reduced colon CD133 Show less

Achieving long persistent luminescence (LPL) in fully organic materials with both hour-level duration and high thermal stability remains a fundamental challenge attributable to rapid exciton quenching and poor resistance to thermal disturbances. Herein, a trap engineering strategy is reported based on rigidified triphenylamine derivatives and boronic ester functionalization embedded in recycled poly(ethylene terephthalate) (PET), enabling the first fully organic polymer-based LPL system that exhibits simultaneously ultralong LPL and exceptional thermal robustness. Molecular conformation locking and optimized donor-acceptor charge transfer lead to deep trap states (≈1.03 eV), resulting in ambient LPL lifetimes exceeding 12 h. Remarkably, the luminescence is thermally enhanced by over 56 times at 500 K, rivaling high-performance inorganic phosphors. In addition, 980 nm near-infrared photo excitation further amplifies the emission, showcasing strong photo-stimulated luminescence capability. Taking advantage of PET's processability, 3D-printed luminescent structures are fabricated that retain LPL functionality and enable spatially resolved thermal sensing and real-time damage detection. This work not only introduces a sustainable and scalable platform for advanced thermal imaging and optoelectronics, but also sets a new benchmark in the design of heat-resistant organic LPL materials, bridging the gap between high-performance functionality and environmental compatibility. Show less

Lysophosphatidic acid (LPA) is a cell-signaling lipid that has been proposed as an early-stage biomarker for ovarian cancer (OC). Diagnosing OC in Stage I is critical to improving patient outcomes, increasing the survival rate from 30% (when diagnosed in late stages of the disease) to over 90%. This significant improvement is due to the success of early interventions; however, current diagnostic methods are not as effective at early-stage detection, with only 15% of cases diagnosed in Stage I and over 70% diagnosed in Stage III or IV. There is a strong need for LPA detection that is sensitive, specific, rapid, low-cost, and automated to truly validate its effectiveness as a diagnostic characteristic for OC. We report the preliminary development and characterization of one such biosensor, which makes use of the advantages of magnetic particles and chemiluminescence for quick, sensitive detection of LPA. The sensor has proven to be viable, with a positive response to LPA concentration, a measurement time of 5 s after incubation, and an LOD of 3.5 nM. Show less

Exchangeable apolipoproteins, including apolipoprotein C-II (apo C-II), apolipoprotein C-III (apo C-III), and apolipoprotein E (apo E), play central roles in the modulation of cardiovascular disease (CVD) risk by readily transferring between anti-atherogenic high-density lipoprotein (HDL) and pro-atherogenic triglyceride-rich lipoproteins (TRL). High intra-pancreatic fat deposition (IPFD) has also emerged as a novel risk factor for CVD. This study aimed to investigate the associations of apo C-II, apo C-III, and apo E with IPFD, as well as with TRL and HDL subclasses. Abdominal magnetic resonance imaging at 3.0 T was used to quantify IPFD. Plasma levels of apo C-II, apo C-III, and apo E were measured. TRL and HDL subclasses were analysed, with TRL categorised into very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) subclasses (IDL-C, IDL-B, and IDL-A), and HDL into HDL-large, HDL-intermediate, and HDL-small subclasses. Univariate and multivariate linear regression analyses were performed to assess these associations. A total of 128 individuals were analysed. IPFD showed a significant inverse association with both apo C-II and apo C-III, consistent across all statistical models. In the most adjusted model, each unit increase in IPFD was associated with a 0.36-unit decrease in apo C-II (p = 0.001) and a 0.31-unit decrease in apo C-III (p = 0.004). Furthermore, apo C-II and apo C-III were significantly and inversely associated with all IDL subclasses (p < 0.02), but not with VLDL, across all models. No statistically significant association between apo E and IPFD or any IDL subclass was observed in the most adjusted model. Apo C-II and apo C-III, but not apo E, contribute to the previously observed positive relationship between IPFD and IDL. Show less

Nurses in traditional Chinese medicine (TCM) departments face significant sleep challenges associated with occupational stressors. However, person-centered analyses classifying these sleep patterns remain scarce. This study aimed to identify heterogeneous sleep disturbance subgroups via latent profile analysis (LPA) and evaluate the performance of explainable machine learning models in discriminating these subgroups based on demographic and occupational features. A cross-sectional survey enrolled 7721 nurses from 130 TCM healthcare institutions in Liaoning Province (December 2024). Data encompassed demographic, occupational, and psychological variables obtained via self-administered questionnaires, including the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance short form 8a. LPA was employed to categorize sleep disturbance patterns. Recursive feature elimination with random forest (RFE-RF) was used to select features associated with subgroup membership for five machine learning models. Models were trained on 70% of the data and evaluated on a 30% independent test set. The optimal classification model (XGBoost) underwent interpretability analysis using Shapley additive explanations (SHAP). LPA identified three subgroups: mild-stable (29.8%), moderate-fluctuating (60%), and severe-persistent (10.2%). Machine learning models achieved test AUCs of 0.71-0.84, with XGBoost demonstrating the highest discriminatory performance (AUC = 0.84, 95%CI: 0.83-0.85) in classifying subgroups. SHAP analysis indicated that monthly income, organizational support, hospital level, self-compassion, and resilience were the top five features contributing to the model's classification output. This study characterized three distinct sleep disturbance subgroups among TCM nurses, with the majority exhibiting moderate symptoms. The sequential application of LPA and explainable machine learning demonstrated robust performance in distinguishing sleep disturbance patterns. Identifying correlates-such as lower income and resilience-may assist nurse managers in stratifying risk and tailoring interventions for those most likely to fall into the severe subgroup. Future longitudinal studies are required to validate the stability of these subgroups and establish causal relationships. Show less

Accurate measurement of lipoprotein(a)-cholesterol [Lp(a)-C] may be useful in interpreting the traditional lipid panel, particularly in patients with high Lp(a). We developed and analytically validated a direct immunocapture ELISA in a Clinical Laboratory Improvement Amendments-certified laboratory for quantifying Lp(a)-C in human plasma using an apolipoprotein(a)-specific monoclonal antibody (LPA4) coupled to magnetic beads. The linearity of the assay was found to be excellent (R Show less

Perirenal fat deposition significantly impacts sheep carcass quality and economic efficiency. To elucidate the underlying genetic regulation, we performed a genome-wide association study (GWAS) on 556 Hu sheep and a comparative transcriptome analysis on 24 Hu sheep (12 with high- and 12 with low-perirenal fat deposition), all with accurate phenotypic records. Furthermore, hub genes and tissue-specific genes (TSGs) were discerned through weighted gene co-expression network analysis (WGCNA) and by leveraging RNA-Seq data from 12 tissues, respectively. qRT-PCR is used to validate the accuracy of RNA-Seq data. GWAS identified significant SNPs near genes including SETD4, TIMP2, SOCS3, and DNAH17. Comparative transcriptome analysis of HPF and LPF groups identified 2072 differentially expressed genes (DEGs), which were significantly associated with lipid storage (LPL), fatty acid homeostasis (APOE, GOT1), and biosynthesis (ACACA). A total of 2333 differential alternative splicing events were identified in 1169 genes, with skipped exons (SE, 30.65 %) being the most common. GO analysis of these SEs showed links to RNA splicing and lipid metabolism, with genes like BSCL2, DGAT1, PLIN5, and PNPLA2 involved in lipid droplet organization and triglyceride storage. WGCNA revealed key modules that were positively and negatively correlated with perirenal fat deposition, emphasizing hub genes (SAR1B, THRSP, ACSS2, KIF5B) associated with lipid droplet organization and metabolism. The integrated analysis of GWAS and RNA-seq identified TIMP2, SOCS3, and DNAH17 as potential key genes involved in regulating perirenal fat deposition in sheep. An association analysis of 372 Hu sheep populations identified significant links (P < 0.05) between perirenal fat deposition traits and mutations in the TIMP2 (g.9759169 G > A) and DNAH17 (g.9494469C > T) genes. Crucially, tissue-specific gene analysis across 12 tissues identified 448 perirenal fat TSGs, of which 75 were also differentially expressed genes (e.g., LPL, THRSP, LEP, ADRB3). In conclusion, our multi-omics study identified key genes influencing perirenal fat deposition in sheep. Notably, mutations in TIMP2 and DNAH17 could serve as candidate markers for enhancing carcass quality through marker-assisted selection. Show less

The presence of a blood-brain barrier (BBB) prevents the delivery of most drugs to the brain. This characteristic limitation poses a major challenge to effective pharmacological treatment for numerous neurodegenerative diseases, particularly Alzheimer's disease. Delivering small interfering RNA (siRNA) via nanoparticles represents a highly promising approach for treating Alzheimer's disease. Nevertheless, developing a safe and efficient siRNA delivery system remains challenging. To enhance brain targeting and therapeutic efficacy, we developed an siRNA nanocarrier system based on PAH-AM-PEG-ApoE (PAPA) nanoparticles (PAPA/siRNA NPs), which facilitates BBB penetration. In this study, an siRNA nanocarrier delivery system modified with ApoE peptide (PAPA/siRNA NPs) developed by our research team was employed to simultaneously encapsulate BACE1-siRNA and GSK3β-siRNA. The PAPA/siRNA NPs were prepared through self-assembly and electrostatic binding. The particle size distribution profile and zeta potential of the PAPA/siRNA NPs were analysed with dynamic light scattering, while its morphology was examined with transmission electron microscopy. For in vitro assessments, flow cytometry, confocal laser scanning microscopy, PCR, and Western blotting were employed to evaluate the cellular uptake, gene silencing capacity, and endosomal escape. The biodistribution was investigated by in vivo imaging technology, and the therapeutic effect on AD was verified in AD model mice. The prepared PAPA/siRNA NPs exhibited a regular spherical appearance with a uniform particle size distribution profile. In in vitro cell experiments, the PAPA/siRNA NPs demonstrated excellent cellular uptake ability and efficient endosomal escape. Meanwhile, the dual-loaded siRNA nanocarrier delivery system effectively inhibited the expression of GSK3β and BACE1 genes. In vivo experimental results showed that the siRNA could successfully cross the BBB and deliver to the brain. It not only significantly prolonged the half-life of siRNA but also greatly reduced the generation of pathological β-amyloid and phosphorylated microtubule-associated protein tau, showing excellent therapeutic effects in the treatment of AD. In this study, we successfully constructed a brain-targeted siRNA nanocarrier delivery system for double-gene knockdown. This system can efficiently overcome the obstacle of the BBB, markedly alleviating cognitive and memory deficits in AD mice. It paves the way for novel strategies in the clinical treatment of AD and is expected to bring new breakthroughs and changes to the conquest of this disease. Show less

This review overviewed the recent paradigm shifts in the diagnosis and management of Alzheimer's disease (AD), emphasizing the 2024 Alzheimer's Association (AA) revised criteria, advances in cerebrospinal fluid (CSF) and blood-based biomarkers (BBMs), and practical considerations for anti-amyloid monoclonal antibody therapy. We conducted a narrative appraisal of consensus frameworks (2018 National Institute on Aging-Alzheimer's Association [NIA-AA] amyloid, tau, and neurodegeneration [AT(N)] and the 2024 AA criteria), clinical practice guidance from AA released in 2025, regulatory status of CSF and BBMs. Intended-use settings (triage vs. confirmatory) of BBMs and implementation of anti-amyloid anti-body treatments (lecanemab or donanemab) in real-world practice in Korea were also reviewed. The 2024 AA criteria define AD biologically and designate A and T as core biomarkers; Core 1 biomarkers can establish AD irrespective of symptoms, whereas Core 2 biomarkers refine staging. A two-cutoff BBM strategy (positive/intermediate/negative) reduces misclassification and guides confirmatory CSF/positron emission tomography (PET) or retesting. BBMs now approach CSF/PET accuracy for amyloid detection, enable triage and, in selected settings, confirmation, and show utility for monitoring treatment response. Integration of clinical stages (1-6) with biological stages (A-D) clarifies syndrome-pathology discordance. Special scenarios-maintenance after induction, APOE ε4 homozygotes, Down syndrome, and serious mental illness-require individualized risk-benefit assessment. In South Korea, constrained access to tau PET and some BBMs necessitates Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision-anchored evaluation with selective biomarker testing. Biomarker-oriented diagnosis and anti-amyloid therapies are reshaping AD care. Priorities include rigorous validation of BBMs across populations, equitable access to core biomarkers, safety strategies, and real-world evidence to implement maintenance and special-population care pathways. Show less

Reliable prediction of reproductive toxicity remains a critical challenge in drug development and environmental safety. Here, a biomarker-integrated, fluorescent reporter-based reproductive organ-on-a-chip platform that recapitulates the multicellular composition, 3D architecture, endocrine signaling, and cyclic dynamics of the human menstrual cycle, is presented. The system is constructed using primary human theca, granulosa, endometrial stromal and stem cells, vascular endothelial cells, uterine macrophages, and myometrial smooth muscle cells, compartmentalized within collagen-hyaluronic acid hydrogels. Early-response toxicity biomarkers-ANGPTL4 (ovary) and SERPINB2 (endometrium)-are genetically linked to mCherry or GFP fluorescent reporters, enabling real-time, cell-type-specific visualization of toxicant-induced stress. Transcriptomic profiling, KEGG pathway enrichment, and gene knockdown studies confirm ANGPTL4 and SERPINB2 as functional mediators of toxic injury, not just passive indicators. Upon exposure to dioxin and other reproductive toxicants, the platform shows strong, region-specific fluorescent responses that preceded changes detected by conventional cytotoxicity assays. This system demonstrates high sensitivity, temporal precision, and mechanistic insight, offering a scalable and physiologically relevant tool for high-content reproductive toxicology screening. Furthermore, it supports endocrine crosstalk between the ovary and uterus, and dynamic responses across the menstrual cycle, enabling future applications in personalized toxicity prediction and preclinical safety evaluation. Show less

Acacetin, a natural flavonoid compound, exhibits anti-inflammatory, antioxidant, and lipid-lowering properties, indicating promising therapeutic potential for the prevention and treatment of cardiovascular diseases (CVD). However, the mechanisms underlying its therapeutic effects on atherosclerosis (AS) remain incompletely understood. This study aims to systematically elucidate the role and molecular mechanisms of Acacetin in the pathological progression of AS. First, network pharmacology was employed to predict the potential therapeutic targets of Acacetin in combating AS. Subsequently, both in vivo and in vitro experiments were established to investigate the underlying mechanisms. The in vivo AS model was generated by feeding apolipoprotein E knockout (ApoE Show less

Influenza vaccination coverage among older adults in China is low. We sought to identify latent vaccine-hesitancy profiles and their correlates. This community-based cross-sectional survey from May to July 2025 involved 1773 older adults from various areas in Jiangsu province. Data were collected via Wenjuanxing and included demographics, the Influenza Vaccine Hesitancy Scale, and the vaccine literacy scale. Group differences were examined using chi-square tests and one-way ANOVA; latent profile analysis (LPA) identified vaccine hesitancy subgroups, and multinomial logistic regression estimated correlates of profile membership. Three profiles emerged: Low Hesitancy (23.0%), Moderate Hesitancy (35.0%), and High Hesitancy (42.0%). Rural residence predicted Moderate (OR = 2.030) and High (OR = 2.993) hesitancy. Lower household income and chronic disease were associated with the Moderate Hesitancy profile, whereas male sex was associated with the High Hesitancy profile. Higher interactive (OR = 0.686) and critical (OR = 0.599) vaccine literacy were inversely associated with High hesitancy.Concerns about vaccine quality predicted both Moderate (OR = 1.433) and High (OR = 1.376) groups; knowledge gaps and fear of adverse reactions concentrated in the High group. Older adults show heterogeneous vaccine hesitancy phenotypes. Uptake efforts should move beyond one-size-fits-all messaging toward segmented strategies. These strategies should integrate cost-related measures with literacy-sensitive, trust-oriented communication, prioritizing rural residents, older men, and those with chronic conditions. The reported proportions of hesitancy profiles reflect our sample only and should not be viewed as nationally representative. Show less

Pulmonary artery sling (PAS) is a rare congenital vascular anomaly, in which the left pulmonary artery arises aberrantly from the right pulmonary artery and courses between the trachea and esophagus, often causing tracheobronchial compression. It is frequently considered within the spectrum of vascular rings. Prenatal diagnosis remains challenging yet crucial for optimizing perinatal management and neonatal outcomes. This case report illustrates the enhanced diagnostic capability achieved by integrating conventional two-dimensional (2D) ultrasound with spatiotemporal image correlation (STIC) technology for the accurate prenatal identification of PAS. A 33-year-old gravida 2 para 0 woman was referred for routine fetal assessment at 31 weeks of gestation. Initial 2D ultrasonography in the three-vessel tracheal view revealed an anomalous vascular configuration, suggesting the left pulmonary artery (LPA) originating from the right pulmonary artery (RPA). To confirm the diagnosis and delineate the vascular course, STIC technology was employed. The STIC volumetric acquisition and subsequent multi-planar reconstruction unequivocally demonstrated the LPA arising from the RPA and coursing posteriorly behind the trachea, thereby confirming the diagnosis of PAS. A comprehensive fetal echocardiogram excluded associated intracardiac anomalies. Following extensive parental counseling, the pregnancy continued uneventfully. The infant was delivered via elective cesarean section at 38 The synergistic use of routine 2D ultrasound and STIC technology provides a robust, clinically accessible method for the precise prenatal diagnosis of fetal PAS. This integrated imaging approach facilitates definitive diagnosis, enhances parental counseling, enables coordinated multidisciplinary perinatal planning, and ensures timely surgical intervention, all of which are pivotal for achieving favorable long-term outcomes in affected infants. Show less

This cross-sectional study aimed to examine the associations between the 24-h movement behaviors and mental health among university students in China, and to determine the optimal behavioral balance based on the top 5% of model-predicted mental health outcomes using compositional data analysis. A total of 6,084 university students aged 17–24 years in Southwest China self-reported their daily durations of moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), sedentary behavior (SED), and sleep (SLP). They were stratified by gender and then randomly and equally assigned to the “recommendation” group and the “validation” group. Using compositional data analysis, time-use compositions (MVPA, LPA, SED, SLP) were transformed into isometric log-ratios (with quadratic terms as needed) and subsequently used in regression models to predict the three mental health outcomes. All possible combinations of motion components were examined to determine the combination with the highest correlation (top 5%) for each outcome. Through research and analysis of the recommendation groups, the optimal combination of average (range) time usage is determined as follows: for males, MVPA 92 (60–110) min/day, LPA 361 (310–400) min/day, SED 372 (350–480) min/day, SLP 614 (530–680) min/day; for females, MVPA 58 (40–90) min/day, LPA 290 (180–390) min/day, SED 445 min (400–560), SLP 665 (580–740) min/day. The recommended durations served as benchmarks for the validation group. Participants who met the optimal 24-h movement behavior time showed significantly lower depression (males: β = –1.290, The optimal 24-h movement behavior time differs between men and women. Males tend to require a longer optimal MVPA duration than females, while females require a longer optimal SLP duration than males. The findings provide valuable reference for developing 24-h movement guidelines and promoting healthy and balanced lifestyles among university students. [Image: see text] The online version contains supplementary material available at 10.1186/s12889-026-26534-x. Show less

Congenital hypogonadotropic hypogonadism (CHH) is a genetically heterogeneous disorder, with multiple causative and candidate genes identified to date. To clarify underlying genetic factors involved in the development of CHH. We examined 88 Japanese patients with CHH using gene panel analysis (GPA) for 14 representative causative genes and whole-exome sequencing (WES) which was initially focused on 41 causative/candidate genes and subsequently expanded to other genes. We extracted rare variants (frequency of <0.01) and performed pathogenic assessment using refined American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria and registered information in ClinVar. Twenty-seven pathogenic/likely pathogenic variants were identified in 30 patients through GPA performed for all 88 patients and in 4 patients through WES performed for 58 patients in whom no obvious disease-causing variants were revealed by GPA. They resided in previously known ANOS1 (6 variants in 7 patients), CHD7 (3 variants in 3 patients), FGFR1 (14 variants in 15 patients), PROKR2 (2 variants in 8 patients), and SOX10 (1 variant in 1 patient), and a hitherto unrecognized ZNF462 (1 variant in 1 patient). One patient had 2 variants. Additionally, potentially CHH-related variants were detected in 12 genes including SEMA4D and CDH2 postulated on the CHH-related molecular network. Furthermore, in the 41 CHH-related genes, the frequency of oligogenicity was significantly higher and the number of rare variants per individual was significantly larger in 54 CHH patients with no discernible pathogenic/likely pathogenic variants than in 100 control individuals. The results support the notion that CHH occurs not only as a monogenic disorder but also as an oligogenic/multifactorial disorder, and suggest the involvement of ZNF462, SEMA4D, and CDH2 variants in the development of CHH. Show less

Alzheimer's Disease (AD), a leading cause of dementia, is a known neurodegenerative disorder. Affecting millions of people worldwide, AD pathogenesis involves diverse risk factors such as lifestyle, environmental, and metabolic conditions that accelerate sporadic AD. Very recently, backed with substantial evidence, herpes simplex virus-1 (HSV-1) has been recognized as a potential causative factor that may play a pivotal role in sporadic AD. Latent virus is estimated to activate key underlying pathways, preferably Aβ and p-tau, to cause AD. Additionally, Antivirals such as Valacyclovir have emerged to impart a potential neuroprotective role in AD. Present research aimed to explore the neuroprotective role and mechanism of Valacyclovir in the streptozotocin-induced Alzheimer's disease model in rats. A single dose of 3 mg/kg ICV (intracerebroventricular) Streptozotocin (STZ) was administered to induce AD in rats. Two doses of Valacyclovir, i.e., 100 mg/kg and 150 mg/kg were evaluated with Donepezil 5 mg/kg as standard. Post 21 days of treatment, Valacyclovir demonstrated dose-dependent improvement in neurobehavioral parameters. Further, AD-specific parameters i.e. Aβ1-40 and Aβ1-42, p-tau, and BACE-1 were significantly (p < 0.001) reduced with parallel reduction in inflammatory (p < 0.001) and oxidative stress markers. Additionally, Valacyclovir also increased the levels of amyloid clearance enzymes i.e., neprilysin (NEP) (p < 0.001) and insulin-degrading enzyme (IDE) (p < 0.001). Results suggest promising neuroprotective action of valacyclovir via reducing Aβ-amyloid protein, p-Tau, BACE-1, as well as demonstrating anti-inflammatory and antioxidant activity. Show less