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The relationship between ambient air pollution and chronic liver disease (CLD), and whether physical activity (PA) modifies this association, remains unclear. We analyzed 17,708 middle-aged and older adults from the 2013 China Health and Retirement Longitudinal Study (CHARLS). Individual-level exposures to CO, O In fully adjusted models, higher pollutant levels were associated with increased CLD risk: CO (OR 1.13, 95% CI 1.04-1.19, p = 0.025), O Ambient CO, O Show less

This study aimed to assess the prognostic significance of serum lipoprotein(a) [Lp(a)] levels regarding overall survival (OS) and progression-free survival (PFS) among patients diagnosed with pancreatic cancer (PC). A retrospective cohort of 364 pathologically confirmed PC patients treated at the Affiliated Hospital of Qingdao University between January 2019 and December 2022 was analyzed. The optimal cutoff for Lp(a) was identified using X-tile software, allowing categorization into high and low Lp(a) groups. To minimize selection bias, propensity score matching (PSM) was utilized. Survival outcomes were compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were applied to identify independent prognostic variables affecting OS and PFS. Patients with high Lp(a) had significantly shorter OS and PFS both before and after PSM (post-PSM OS: 12.28 vs. 27.67 months, P = 0.003; PFS: 7.00 vs. 11.30 months, P = 0.002). Multivariate Cox analysis confirmed high Lp(a) as an independent predictor of poor OS [HR = 2.11 (1.17-3.81), P = 0.013] and PFS [HR = 2.14 (1.20-3.83), P = 0.010]. In the surgical subgroup (n = 215), high Lp(a) was also associated with worse OS (16.43 vs. 35.47 months, P = 0.02) and PFS (8.40 vs. 11.77 months, P = 0.036). Multivariate analysis in this subgroup showed that high Lp(a) remained an independent risk factor for OS [HR = 2.82 (1.36-5.87), P = 0.006] and PFS [HR = 2.01 (1.06-3.86), P = 0.034]. Elevated serum Lp(a) is an independent predictor of reduced OS and PFS in patients with pancreatic cancer. In contrast to conventional lipid profiles, the genetic stability of Lp(a) makes it a reliable baseline prognostic marker. Show less

Amyloid transthyretin (ATTR) amyloidosis is a rare, life-threatening disease frequently manifesting with cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN) or both (ATTR-mixed). We retrospectively analysed US electronic health records and claims data to provide up-to-date estimates of ATTR amyloidosis epidemiology (overall and by phenotype). Data were extracted from the Clarivate Real-World Data repository (2016-2023). Given the lack of established coding for ATTR amyloidosis, we used different combinations of diagnostic codes to obtain narrow and broad estimates of incident and prevalent cases in the USA in 2022. Temporal trends (2019-2022) were also assessed. Using narrow definitions, the 2022 estimated incidence of ATTR amyloidosis overall, ATTR-CM, ATTR-PN and ATTR-mixed was 16.6, 12.7, 3.5 and 1.9 cases per million people, respectively; the corresponding prevalence estimates were 59.8, 41.1, 15.1 and 9.8 cases per million people. Estimates were consistently lower with the narrow (vs broad) definitions. Over time, the incidence and prevalence of ATTR amyloidosis overall increased, driven by ATTR-CM cases. No major changes were reported for the other phenotypes. This study provides comprehensive and up-to-date epidemiological data for ATTR amyloidosis in the USA. Our findings corroborate the need for appropriate differential diagnostic coding and standardised criteria. Show less

Existing depression assessment tools inadequately detect rapid symptom changes after antidepressant treatments. This study aimed to translate, validate, and explore the clinical application of the Chinese version of the McIntyre and Rosenblat Rapid Response Scale (CMRRRS) for use during the treatment of rapid-onset depression. The McIntyre and Rosenblat Rapid Response Scale was translated and culturally adapted for use in Chinese settings. Briefly, 71 patients with major depressive disorder who were receiving intravenous esketamine were assessed using the CMRRRS and other validated scales. Properties were examined, including internal consistency, construct validity, and responsiveness to change. For patient classification, Latent Profile Analysis (LPA) and Kernel Density Estimation (KDE) curves were used. The Minimum Clinically Important Difference was computed to explore the smallest change related to clinical improvement. The CMRRRS showed high reliability and robust validity. Factor analysis explained over 60% of the total variance. LPA distinguished three patient classes, while KDE curves determined that a cut-off of 5 points was optimal for detecting clinically meaningful changes. The CMRRRS is a reliable, valid, and sensitive tool for monitoring rapid symptom changes in patients with depression treated with esketamine. It allows real-time symptom monitoring and personalized treatment adjustments. Further studies are warranted to explore its broader applicability. Show less

The objective of this study was to explore the longitudinal relationship between the volume and intensity of physical activity (PA) and their combined risk for cognitive impairment (CI). The study included 10,174 participants from the 2011-2018 CHARLS cohort. Pennsylvania and CI were assessed using self-reported questionnaires. Statistical analyses were performed using the Cox regression model. After adjusting for all covariates, the risk of CI was 14% lower in subjects with physical activity volume (PAV) ≥600 Metabolic Equivalent of Task (MET)-min/week compared to those with insufficient PA (HR: 0.86). The risk was reduced by 38% for subjects with PAV of 1800-2999 MET-min/week (HR: 0.62). Regarding the intensity of PA, the risk of CI was reduced by 25% for a proportion of 0.25-0.5 of (moderate to vigorous PA) MVPA to PAV (HR: 0.75) compared to a proportion of 0-0.25. Regardless of PAV, the risk of CI was lowest when the proportion of moderate to vigorous PA(MVPA) to PAV was 0.25-0.5, and 0.5-0.75 for the proportion of light-intensity physical activity (LPA) to PAV. The PAV 1800-2999 MET-min/week and maintaining a proportion of LPA to PAV of 0.5-0.75, or a proportion of MVPA to PAV of 0.25-0.5, are more effective in reducing the risk of CI. Policy implications should prioritize tailored physical activity strategies for individuals over 65, emphasizing low-intensity activities, safe high-intensity training, and the development of accessible urban facilities, in line with WHO guidelines. Show less

Exploring how different profiles of academic task values (ATVs) and academic achievement (AA) influence students' school satisfaction should enrich understanding of how school satisfaction develops in specific academic situations. This study aimed to identify profiles of ATV (attainment value [AV], utility value [UV]) and AA, as well as heterogeneous trajectories of school satisfaction, and then examine the joint predictive effects of ATV and AA on the development of school satisfaction. A total of 3548 Chinese elementary school students (M Data were collected through self-reports of ATVs and school satisfaction, while AA data were collected from final examination scores at the end of each semester. Latent profile analysis (LPA) and latent class growth analysis revealed six profiles of ATV and AA (i.e., congruent subgroups: congruent-low, congruent-high, congruent-moderate and incongruent subgroups: high ATV-low AA, lower UV-moderate AA, low ATV-moderate AA); and four heterogeneous trajectories of school satisfaction (i.e., high-decreasing, low-stable, high-stable, low-increasing). Latent transition analysis (LTA) indicated that students with congruent levels of AA and ATV were more likely to transition into the optimal school satisfaction groups (high-stable and low-increasing groups), whereas students with greater gaps between AA and ATV were more likely to transition into the adverse groups (i.e., low-stable and high-decreasing groups). These findings highlight the need for educators to tailor interventions to distinct groups to optimize students' school satisfaction. Show less

The influence of lactic acid bacteria (LAB) strains of various species isolated from Chinese traditional sourdough on the properties of rice sourdough and the textural and flavor qualities of steamed rice bread (SRB) was investigated. Show less

Relational aggression (RA) is characterised by social manipulation and covert harm, often involving fluid and overlapping experiences of both perpetration and victimisation. We used latent profile analysis (LPA) to identify subgroups of young Australian adults based on their self-reported experiences of RA and explore whether these RA typologies are associated with broader aggressive traits and behaviours. We used a community sample of Australian adults aged 18-25 ( Show less

This study integrates Self-Determination Theory with an emotion-cognition framework and uses a questionnaire-based design to examine individual differences in behavioral responses. A person-centered latent profile analysis (LPA) was conducted among 1596 Chinese participants (gender: 68.9% female; mean age: 18.25 years old) to identify distinct behavioral profiles in the context of negative life events. The results revealed that (1) four distinct profiles emerged among participants: a Self-Focused Group (33.65%), a Stress-Aggression Group (20.11%), an Ambivalent-Aggression Group (21.68%), and a Prosocial Group (24.56%); (2) significant differences were observed among these profiles in terms of empathic responses and psychological need satisfaction. By employing a person-centered analytical approach, this study contributes to a nuanced understanding of behavioral divergence under stress and offers insights for designing subgroup-specific psychological interventions. Show less

Problematic smartphone use (PSU) has become a growing concern among young populations, raising significant issues for their physical and psychological well-being. Guided by Compensatory Internet Use Theory and the Interaction of Person-Affect-Cognition-Execution (I-PACE) model, this study examined the associations between different forms of childhood trauma and PSU. Participants were 2717 college students (661 males, 22.49%; Mage = 19.81 years). Two chain mediation models were tested, and latent profile analysis (LPA) was employed to capture individual differences from a person-centred perspective. LPA revealed three distinct trauma profiles: low childhood trauma, moderate childhood abuse, and high childhood abuse. Across both variable-centred and person-centred ap-proaches, rumination and social anxiety were identified as mediators linking childhood trauma to PSU. These findings advance understanding of the pathways through which childhood trauma contributes to PSU in college students. By integrating variable- and person-centred approaches, the study highlights the importance of cognitive-emotional mechanisms and provides implications for targeted prevention and intervention strategies. 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

Calcific aortic stenosis (CAS) is frequently accompanied by systemic comorbidities, but their causal relationships and shared genetic architecture remain poorly defined. We aimed to map the multisystem comorbidity network of CAS and clarify underlying genetic mechanisms. In 467 484 participants from the UK Biobank, observational and polygenic phenome-wide association studies evaluated associations between CAS and 1571 phenotypes, integrating disease-trajectory analyses to visualise temporal patterns. Associations replicated across observational and polygenic analyses were tested using two-sample Mendelian randomisation (MR) based on 22 CAS-related variants from FinnGen. Polygenic risk score (PRS) analyses excluding specific genes assessed their contributions, particularly LPA and plasma lipoprotein(a) (Lp(a)) levels. CAS was associated with higher risks of 42 cardiovascular and non-cardiovascular conditions, most prominently metabolic, endocrine, haematological and respiratory disorders. Temporal analyses showed that circulatory and metabolic diseases typically precede other comorbidities in CAS trajectories. MR findings were consistent with causal effects of CAS on multiple cardiovascular diseases, iron-deficiency anaemia, mental disorders and pleural effusion. When LPA variants were removed from the CAS PRS or plasma Lp(a) concentration was adjusted for, most associations lost significance, indicating a shared LPA/Lp(a)-mediated genetic pathway. CAS is embedded within a broad multisystem comorbidity network, driven largely by genetic variation at LPA and elevated Lp(a). These findings highlight pleiotropic mechanisms linking valvular calcification with systemic disease and support LPA-targeted therapies as a promising avenue for reducing the multisystem burden of CAS. Show less

Cholesterol, an indispensable structural and signaling lipid, is fundamental to cellular membrane integrity, steroidogenesis, and developmental morphogen pathways. Its homeostasis hinges on the precise coordination of four interdependent metabolic modules: de novo biosynthesis, intestinal absorption, enzymatic conversion, and systemic clearance. This review delineates the molecular machinery governing these processes-from the Bloch/Kandutsch-Russell synthesis pathways and niemann-pick C1-like 1 (NPC1L1)-mediated cholesterol uptake to cholesterol 7α-hydroxylase (CYP7A1)-driven bile acid synthesis and HDL-dependent reverse transport. We further elucidate cholesterol's multifaceted roles in lipid raft assembly, Hedgehog signal transduction, and vitamin D/hormone production. Critically, dysregulation of cholesterol flux underpins pathogenesis in atherosclerosis, metabolic dysfunction-associated fatty liver disease (MAFLD), neurodegenerative disorders, and oncogenesis, with disrupted synthesis, efflux, or esterification cascades serving as key drivers. Emerging therapeutic strategies extend beyond conventional statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to include transformative modalities: CRISPR-based in vivo gene editing (e.g., VERVE-101 targeting PCSK9), small interfering RNA (siRNA) therapeutics (inclisiran), and microbiota-directed interventions. Pioneering approaches against targets Such as angiopoietin-like 3 (ANGPTL3), lipoprotein(a) [Lp(a)], and asialoglycoprotein receptor 1 (ASGR1)-alongside repurposed natural agents (berberine, probiotics)-offer promise for mitigating residual cardiovascular risk and advancing precision cardiometabolic medicine. By integrating mechanistic insights with clinical advancements, this review underscores the transition from broad-spectrum therapies to personalized, multi-target regimens, offering a roadmap for mitigating cholesterol-related diseases in the era of genomic and metabolic medicine. Show less

Cancer-related fatigue (CRF) is a multifaceted and subjective phenomenon that significantly impacts patients on physical, emotional, and mental levels. This study aims to identify specific subtypes of Cancer-related fatigue (CRF) in patients with Hepatocellular Carcinoma (HCC) and to explore the factors influencing each subtype. This cross-sectional study enrolled 220 participants from a tertiary cancer hospital. Latent Profile Analysis (LPA) and multinomial logistic regression were conducted to identify distinct fatigue profiles and to explore the influencing factors for different categories of CRF among the patients. The analysis revealed three potential categories of CRF severity: Physical balance -Low fatigue (20.1%); Physical imbalance -Moderate fatigue (69.6%); and Physical prominent -High fatigue (10.2%). It was found that the severe insomnia the greater the probability of patients belonging to the Physical prominent -High fatigue (OR = 1.299, 95%CI: 1.188-1.419). Has partner (OR = 5.171, 95%CI: 1.739-15.377), the severe financial stress (OR = 2.570, 95%CI: 1.209-5.463) and the moderate ISI (OR = 1.212, 95%CI: 1.136-1.292) were associated with the Physical imbalance - Moderate fatigue group. Protective factors for the Physical balance - Low fatigue group included higher scores in the physical activity Index (OR = 0.930, 95%CI: 0.870-0.995), Hope Index (OR = 0.647, 95%CI: 0.552-0.758), General self-efficacy (OR = 0.874, 95%CI: 0.793-0.965), Body Mass Index (OR = 0.799, 95%CI: 0.552-0.758), and Child-Pugh A classification (OR = 0.310, 95%CI: 0.119-0.808). CRF in patients with HCC demonstrates significant heterogeneity. It is conducive to the clinical identification of CRF risk characteristics and the design of personalized intervention measures. Show less

This study aims to identify heterogeneous subgroups of first-year residents experiencing transition shock using latent profile analysis (LPA) and to explore the predictive effects of various dimensions of professional identity on different transition shock types. A multi-center, cross-sectional design was employed. From September 2023 to August 2024, a total of 766 first-year residents were selected via cluster sampling from four national-level training bases in Hubei Province, China, for a cross-sectional survey. The survey was conducted using the revised Transition Shock Scale (Cronbach's A total of 574 valid questionnaires were returned. Latent profile analysis identified three latent classes: a low psychological-sociocultural shock group (13.41%, Transition shock among first-year residents exhibits significant heterogeneity. These findings provide evidence for developing targeted intervention strategies. Higher levels of professional cognition, commitment, and expectation are associated with lower levels of transition shock. However, a strong sense of professional values is associated with higher transition shock, a relationship potentially mediated by an idealism-reality gap. It is recommended that tiered competency-building interventions should be implemented for the high physical-knowledge/skill shock group, and a dual-track support system should be designed for Master of Medicine degree candidates. Show less

To examine the association between 24-hour movement behaviors and depressive symptoms in older adults using compositional data analysis, and to investigate the dose-response characteristics of time reallocations between movement behaviors in relation to depressive symptoms. A cross-sectional study was conducted among 1093 urban-dwelling older adults aged 60 years and above in selected communities of Jinan City, Shandong Province, China, between April 2024 and September 2024. The Chinese version of the International Physical Activity Questionnaire-Long Form (IPAQ-LF) was used to estimate time spent in moderate to vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), sedentary behavior (SB), and sleep (SLP) across a typical 24-hour day. The Chinese version of the Patient Health Questionnaire Depression Scale-9 item (PHQ-9) was applied to assess depressive symptoms. Compositional isotemporal substitution models were employed to explore the associations between time reallocations among 24-hour movement behaviors and depressive symptoms, accounting for the co-dependent nature of time-use data. (1) The geometric means of time spent in MVPA, LPA, SB, and SLP were 25.33 minutes, 141.26 minutes, 738.10 minutes, and 455.15 minutes, respectively. Variation matrix analysis revealed the highest log-ratio variance between MVPA and SB (0.168), and the lowest between SLP and SB (0.031). (2) The prevalence of screening-positive depressive symptoms was 16.29% among Chinese urban older adults. (3) Results from compositional linear regression models showed that time allocated to MVPA, LPA, and SLP (relative to the remaining movement behaviors) was negatively associated with depressive symptoms, while time spent in SB was positively associated. (4) Dose-response analysis further indicated that: (a) MVPA substitutions with other movement behaviors exhibited nonlinear and markedly asymmetric effects on depressive symptoms; (b) replacing MVPA with LPA, SB, or SLP resulted in increasingly larger changes in predicted scores as substitution duration increased, whereas the reverse substitution (MVPA for other movement behaviors) produced progressively smaller changes; and (c) substitutions between SB and LPA displayed linear and symmetrical effects. The findings provide evidence of an association between 24-hour movement behaviors and depressive symptoms in Chinese urban-dwelling older adults and reinforce the importance of achieving a balance between different types of movement behaviors over a 24-hour period for mental health. Show less

Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain tumor patients in Shanghai, China, using Latent Profile Analysis (LPA) to guide personalized diagnosis, treatment, and supportive care. A longitudinal study was conducted among 161 patients with primary brain tumors in Shanghai. Participants completed the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) at three intervals: the day of admission (T1), three days after surgery (T2), and two weeks after surgery (T3). Latent Profile Analysis (LPA) was used to identify subgroups with unique symptom patterns. Six distinct subgroups were identified (entropy = 0.964), ranging from low-burden to persistently severe patterns. Subgroup membership was partially associated with age, tumor grade, and diagnosis. These subgroups were: transient postoperative burden group, stable symptom with cognitive emergence group, distress-predominant, low burden group, elderly-high grade, persistently severe group, nausea-dominant recovery group, and distress-plus-nausea, younger urban group. Our findings reveal substantial heterogeneity in perioperative symptom experiences among brain tumor patients. Identifying subgroups with high and persistent symptom burden may help clinicians target interventions such as enhanced education, proactive monitoring, rehabilitation, psychological support, and antiemetic management. This subgroup-based approach may improve quality of life, reduce morbidity, and guide precision supportive care in neuro-oncology. Show less

Radiotherapy remains a valuable yet limited option for select colon cancer cases, with radioresistance representing a major clinical challenge. Lipidomics screening identified autotaxin (ATX), also known as ENPP2, as a key mediator of radiation-induced metabolic reprogramming. Radiation exposure upregulated ATX expression and its product lysophosphatidic acid (LPA), which activated the LPAR2-AKT signaling axis to support tumor cell survival. Pharmacological ATX inhibition with HA130 or genetic ATX knockdown enhanced radiosensitivity in vitro by suppressing proliferation and promoting apoptosis. In mouse models, both HA130 treatment and ATX knockdown significantly suppressed tumor growth and improved radiotherapy efficacy, as shown by reduced tumor volume, weight, and Ki67-positive cell counts. Clinically, elevated ATX-LPA pathway activity was associated with poor patient prognosis. These findings establish ATX as a promising therapeutic target for overcoming radioresistance in colon cancer, supporting the combination of ATX inhibition with radiotherapy to improve treatment outcomes. The online version contains supplementary material available at 10.1186/s12876-025-04578-4. Show less

Current conventions, partly derived from self-reported data, typically equate 1 minute of vigorous physical activity (VPA) to 2 minutes of moderate physical activity (MPA). Using accelerometer-derived intensity classification in 73,485 UK Biobank participants (mean follow-up: 8.0 [1.0] years), we assess the equivalence of light activity (LPA) and MPA to 1 minute of VPA for all-cause (ACM) and cardiovascular (CVD) mortality, major adverse cardiovascular events (MACE), type 2 diabetes, and cancer outcomes. For a standardised 5%-35% risk reduction, the median MPA equivalent per minute of VPA is 4.1 (ACM, 95% CI: 4.1-4.2), 7.8 (CVD mortality, 7.7-8.0), 5.4 (MACE, 5.3-5.5), 9.4 (type 2 diabetes, 9.3-9.6), and 3.5 (cancer mortality, 3.4-3.5) minutes. For non-cancer outcomes, the median LPA equivalent per 1 minute of VPA ranges from 53 (ACM) to 94 minutes (type 2 diabetes), reflecting generally weaker dose-response curves of LPA with all outcomes. These findings indicate a substantial departure from self-reported estimates and support integrating device-based equivalence into guidelines and wearables. Show less

Acute prolonged sitting increases blood pressure (BP) and arterial stiffness (AS). Both of these may be mitigated via light physical activity (LPA). Whether long COVID (LC), which partly manifests as vascular sequelae, predisposes a heightened sensitivity to sitting or diminished benefits from its interruption is unknown. The aims of this study were to identify whether individuals with LC: (i) exhibit a worse BP/AS response to uninterrupted sitting and (ii) a diminished mitigation of BP/AS response to sitting interrupted with LPA, compared to healthy controls. Thirty participants with LC and 15 controls completed 2 h of uninterrupted sitting and sitting interrupted with LPA. Central and peripheral systolic and diastolic BP and carotid-femoral pulse wave velocity (cfPWV) were determined pre and post sitting. Linear mixed-effects models demonstrated no three-way or two-way interactions for any variable. There was a significant main effect of time, with increases in central systolic (MD = 3.37 mmHg, SE = 0.93 mmHg, p < 0.001) and central diastolic (MD = 3.00 mmHg, SE = 0.58 mmHg, p < 0.001) BP. cfPWV was not altered in sitting in either group (MD = 0.13 m/s, SE = 0.09 m/s, p = 0.170). Uninterrupted sitting increases BP similarly, but AS is unchanged. Interrupting sitting with LPA did not mitigate sitting-induced increase in BP regardless of LC diagnosis. Show less

Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metabolic status in prediabetes, but their predictive value for cardiovascular mortality and stroke in this population remains unclear. We analyzed data from 74,678 White participants with prediabetes in the UK Biobank, defined by either HbA1c (5.7-6.4%) or fasting glucose (6.1-6.9 mmol/L). Follow-up continued until October 10, 2023. Cox regression was used to examine associations between LE8, phenotypic age (PhenoAge), cardiovascular biological age (CBA), and outcomes of cardiovascular (CVD) mortality and stroke. Restricted cubic spline (RCS) models identified biological age risk thresholds. Mediation analysis assessed whether proteins such as CST3, EFEMP1, FES, IGFBP2, IGFBP6, LPA, PCSK9, and TIMP1 mediated these effects. Over a median follow-up of 13.4 years, 2263 participants died from CVD causes. Each 1-year increase in CBA or PhenoAge was associated with a ~ 10% higher risk of CVD mortality (CBA aHR = 1.10; PhenoAge aHR = 1.09; both P < 0.001), while each 1-point increase in LE8 score was linked to a 3% lower risk (HR = 0.97, P < 0.001). The risk biological ages for these two indicators were also identified: PhenoAge ≥ 58.52 years and CBA ≥ 62.42 years. Similar trends were observed for stroke. Mediation analysis revealed that CST3, TIMP1, IGFBP2, and IGFBP6 contributed to the biological pathways between aging/lifestyle and CVD outcomes. The combined LE8 and PhenoAge model showed the strongest predictive performance for CVD mortality (AUC = 0.716) and stroke (AUC = 0.638) over 15 years. LE8 combined with phenotypic age provides prognostic value for CVD outcomes in prediabetes. These findings highlight the potential of lifestyle modification and delayed biological aging in reversing prediabetes and underscore comorbidity-related proteins as promising therapeutic targets. Show less

Lipoprotein (a) [Lp(a)] is a highly heterogeneous lipoprotein particle promoting panvascular disease. Structurally, it consists of an LDL-like core covalently bound to apolipoprotein (a) [apo(a)]. Molecular determinants linking various genetic variants of apo(a) constituent of Lp(a) to vascular pathology remain incompletely defined. We have built a model allowing dissection which variations in LPA gene are functional, and which are mere associates of these functional variations. Copy number changes in kringle IV type 2 (KIV-2), together with a spectrum of single nucleotide polymorphisms (SNPs), regulate apo(a) size, expression, and function. These variants can be broadly categorized into Lp(a)-increasing, Lp(a)-lowering, and null alleles, with distinct prevalence across populations. Notably, risk alleles such as rs10455872 and rs3798220 account for substantial variance in circulating Lp(a) and confer elevated susceptibility to coronary artery disease, whereas splice-altering and nonsense alleles markedly reduce Lp(a) concentrations. The therapeutic implications of modifying circulating Lp(a) levels are profound. While conventional lipid-lowering therapies exert little influence on Lp(a), antisense oligonucleotides (pelacarsen) and small interfering RNA agents (olpasiran, SLN360) achieve robust Lp(a) reductions. Integrating genetic insights with structural modeling provides a framework to disentangle functional from proxy associations within LPA and neutralize the cardiovascular hazard conferred by elevated levels of Lp(a). Show less

This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, and determine factors influencing different adaptability categories. CSNs play a vital role in treating and rehabilitating patients with cardiovascular conditions. However, the existing literature offers limited insights into the career adaptability of CSNs in China. A multicenter, cross-sectional survey involving 659 Chinese CSNs was conducted. LPA was utilized to classify career adaptability profiles based on responses to the Career Adaptation Abilities Scale Short Form (CAAS-SF). Influencing factors were assessed using the Conditions of Work Effectiveness Questionnaire-II (CWEQ-II) and the General Self-Efficacy Scale (GSES). Differences among identified profiles were analyzed through ANOVA, chi-square tests, and multinomial logistic regression to explore relevant socio-demographic characteristics and influencing variables. A four-profile model provided the best fit, identifying groups labeled as “high adaptability” (Class 4, These findings provide evidence to assist nursing administrators in developing training programs to enhance CSNs’ career adaptability. The variables identified as associated with profile membership may enable more tailored training strategies. Show less

Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. Human blastoids can be generated in large numbers, making them well-suited for high-throughput screening. However, automated methods for evaluating and characterizing blastoid morphology are lacking. We developed a deep-learning model-deepBlastoid-for automated classification of live human blastoids using only brightfield images. The model processes 273.6 images per second with an average accuracy of 87%, which is further improved to 97% by integrating a Confidence Rate metric. deepBlastoid outperformed human experts in throughput while matching accuracy in blastoid classification. We demonstrated the utility of the model in two use cases: (i) systematic assessment of the effect of lysophosphatidic acid (LPA) on blastoid formation and (ii) evaluating the impact of dimethyl sulfoxide (DMSO) on blastoid formation. The evaluation results of deepBlastoid using over 10,000 images were consistent with the known drug effects and showed subtle but significant effects that might have been overlooked in manual assessments. The publicly available deepBlastoid model enables researchers to train customized models based on their imaging and protocols, providing an efficient, automated tool for blastoid classification with broad applications in research, drug screening, and Show less

Bidirectional intergenerational support is linked to late-life mental health, yet the underlying mechanisms remain unclear. Guided by intergenerational solidarity and social support theories, we examined how distinct support profiles relate to mental health among Chinese older adults, testing self-rated health (SRH) as a mediator and social participation as a moderator. We analyzed 7,843 adults aged ≥60 from the 2020 China Longitudinal Aging Social Survey. Latent profile analysis (LPA) identified bidirectional support profiles; group differences in mental health were assessed using the Bolck-Croon-Hagenaars (BCH) approach, followed by mediation and moderated-mediation models with bootstrap inference (5,000 resamples). Four profiles emerged-High Support-High Interaction-High Closeness (HS-HI-HC; 47.02%), Child-High Support-Low Interaction-High Closeness (CS-LI-HC; 33.46%), Moderate Support-Moderate Interaction-Low Closeness (MS-MI-LC; 10.37%), and Low Support-Low Interaction-Moderate Closeness (LS-LI-MC; 9.16%). Mental health differed across different profiles, with HS-HI-HC showing the best mental health levels (the lowest scores). SRH partially mediated these associations (for instance, HS-HI-HC indirect effect = -0.186, 95% CI -0.245 to -0.131). Social participation attenuated benefits of high family support but buffered risks under low support. Bidirectional intergenerational support is heterogeneous in China; profiles characterized by reciprocity and closeness show the most favorable mental health. SRH accounts for a modest but meaningful share of these associations, and social participation can substitute for-or amplify-the benefits of family support depending on profile. Findings inform profile-tailored community and family interventions to promote healthy aging. Show less

Background Metabolic syndrome (MetS) is a major public-health concern that substantially increases the risk of cardiovascular disease and type 2 diabetes. Traditional lipid profiles may not fully capture the atherogenic burden in MetS, prompting investigation of novel lipid biomarkers, such as lipoprotein(a) (Lp(a)), apolipoproteins, and the Comprehensive Lipid Tetrad Index (CLTI). This study evaluated the association of these biomarkers with MetS in an Indian outpatient population. Methods In a cross-sectional study of 707 adults aged 25-75 years at a tertiary care hospital in Jamnagar, Gujarat, MetS was diagnosed using NCEP-ATP III criteria. Serum Lp(a), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and CLTI were measured using standard methods. Associations were tested using Chi-square analyses and logistic regression, and diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis. Results MetS was present in 397/707 (56.15%) participants, occurring in 197/332 (59.34%) of females and 200/375 (53.33%) of males. Elevated Lp(a), elevated Apo B, elevated CLTI, and reduced Apo A-I were all significantly associated with MetS (p < 0.001 for each). ROC analysis demonstrated the highest diagnostic accuracy for CLTI (area under the curve, or AUC = 0.835, 95% CI 0.806-0.862), followed by Lp(a) (AUC = 0.760, 95% CI 0.730-0.794), Apo B (AUC = 0.700, 95% CI 0.665-0.734), and Apo A-I (AUC = 0.620, 95% CI 0.584-0.657). Multivariable logistic regression identified elevated blood pressure, low high-density lipoprotein cholesterol, and elevated triglycerides as significant predictors of abnormal biomarker levels. Conclusion In this Indian outpatient cohort, CLTI and Lp(a) showed strong predictive value for MetS, and outperformed Apo A-I and Apo B when used alone. Incorporating CLTI and Lp(a) into clinical assessment may improve early detection and risk stratification in individuals at risk of MetS. Show less

To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a convenience sample of 411 older adults with disabilities was recruited from a tertiary hospital in Anhui Province, China. Data were collected using a general information questionnaire, the Chinese version of the Demoralization Scale, and the Active Aging Scale. Latent profile analysis (LPA) was performed based on demoralization subscale scores. Univariate and multinominal analyses were employed to investigate the influencing factors, and the Kruskal-Wallis The prevalence of demoralization syndrome was 49.1%. LPA identified three distinct profiles: the Well-Adapted Group (53.3%), the Disheartened-Helpless Group (23.8%), and the Fully Demoralized Group (22.9%). The Kruskal-Wallis Nearly half of the older adults with disabilities experienced demoralization, with heterogeneous subgroups identified. The active aging status of demoralized subgroups requires urgent attention. These findings suggest the need for targeted interventions tailored to the characteristics of each profile to improve mental health and promote active aging in this population. Show less

The pathways linking lipoprotein(a) (Lp[a]) to atherosclerotic cardiovascular disease (ASCVD) are unclear. This study aimed to discover Lp(a)-associated plasma proteins and estimate their associations with incident ASCVD. We analyzed 48,859 UK Biobank participants with measured Lp(a) and proteomic profiles, with replication in 9,416 individuals in the Atherosclerosis Risk in Communities (ARIC) study cohort utilizing a separate proteomic platform. Linear models assessed associations between Lp(a) and protein concentrations adjusted for age, sex, cigarette smoking, diabetes diagnosis, body mass index, systolic blood pressure, hypertension, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, statin prescription, and the first 10 components of genetic ancestry. Multiple testing correction was performed using the Benjamini-Hochberg FDR method (P < 0.05). We examined how the protein effect sizes from the primary analysis using the outcome of Lp(a) aligned with those for the outcomes of an LPA genetic risk score (GRS) and LDL-C. Cox proportional hazards models quantified hazard ratios (HRs) for protein associations with incident ASCVD. Participants were a mean age of 57 years (SD 8.22), 93.9% European, and 53.8% male, with median follow-up of 8.9 years (IQR 8.3-9.7). Of 1,459 circulating proteins, 164 were significantly associated with Lp(a) after FDR correction, with enrichment for lipid degradation, metabolism, and insulin secretion. In the ARIC study, 10 proteins were replicated with consistent effect estimates. Of these replicated proteins, there were no significant associations observed with an Using high-throughput proteomics, we discovered and replicated 10 proteins associated with circulating Lp(a), several of which were independent of genetically-predicted Lp(a). While Lp(a) is highly heritable, these atherogenic proteins represent a non-heritable Lp(a) axis. Show less