👤 Juanhua Zhu

Steroid-refractory (SR) disease develops in a substantial fraction of patients with grade II-IV acute graft-versus-host disease (aGvHD) and is associated with poor long-term survival. Improved mechanistic insight is needed to identify reliable predictors of steroid resistance. We retrospectively profiled peripheral blood collected prior to glucocorticoid treatment from allogeneic hematopoietic cell transplantation recipients without aGvHD, with steroid-sensitive aGvHD, and with SR-aGvHD using an integrated multi-omics approach, and validated findings in an independent multicenter cohort. Mass cytometry revealed expansion of activated CD28+ CD8+ effector-memory T (Tem) cells in SR-aGvHD. Absolute counts of these cells at neutrophil engraftment predicted subsequent steroid resistance in the multicenter cohort and performed comparably to established clinical classifiers. This phenotype was associated with a proinflammatory milieu enriched for IL-2, IL-27, and IFN-γ. Single-cell RNA sequencing and functional assays implicated a STAT1-glucocorticoid receptor (GR) regulatory axis in which inflammatory cytokines induce STAT1 phosphorylation and suppress GR expression, consistent with intrinsic glucocorticoid resistance. JAK inhibition rescued cytokine-induced steroid resistance in vitro, while in SR-aGvHD patients, clinical response to ruxolitinib was accompanied by reduced STAT1 activation, restoration of GR expression, and contraction of the expanded CD8+ Tem pool. These findings identify immune dysregulation at SR-aGvHD centered on CD8+ Tem cells with a STAT1-dependent GR deficit and support a mechanistic link to steroid refractoriness. CD28+ CD8+ Tem cell counts may serve as a biomarker of SR-aGvHD and inform development of pre-emptive, pathway-targeted strategies. Show less

Interleukin-27 (IL-27) is an immunoregulatory cytokine, but its role in B-cell haematopoiesis and B-cell acute lymphoblastic leukaemia (B-ALL) within the bone marrow (BM) niche remains unclear. IL-27 was delivered in vivo using adeno-associated virus. B-cell reconstitution, mixed BM chimeras, and an N-myc-driven B-ALL model were analysed by flow cytometry, transcriptional profiling, and survival studies. Group comparisons were assessed using Student's t-test, and survival was evaluated by Kaplan-Meier analysis with log-rank tests. Sustained IL-27 expression selectively impaired B-cell reconstitution while preserving overall haematopoietic recovery, with marked reductions in CLPs and early B-cell subsets. IL-27 directly inhibited early B-lineage differentiation and concurrently remodelled the BM microenvironment by downregulating VCAM-1, ICAM-2, CXCL12, and IGF-1. These niche alterations were associated with reduced BM-resident B-ALL burden, enhanced chemotherapy efficacy, and improved survival in B-ALL-bearing mice. IL-27 showed no direct cytotoxicity toward B-ALL cells, supporting an indirect, niche-mediated mechanism. IL-27 constrains B-cell haematopoiesis and B-ALL progression through coordinated progenitor inhibition and BM niche remodelling, revealing a cytokine-driven strategy with the potential to enhance leukaemia therapy. This work was supported by the National Key R&D Program of China (Grant No. 2021YFA1100800 to A.-B.L.) and the National Natural Science Foundation of China (Grant No. 82100180). Show less

The signaling pathways of inflammatory pain are widely explored, but practical clinical approaches to ameliorate pain remain inadequate. Quantitative PCR (qPCR) and ELISA methods were applied to measure the concentration of interleukin (IL)-27 in the inflammatory pain mouse model. Flow cytometry was conducted to identify the source of IL-27. Bone marrow-derived macrophages were stimulated by IL-27, IL-4, lipopolysaccharide, and/or interferon-gamma, followed by qPCR to assess pro-inflammatory and pro-resolving markers' dynamic expression. Then, the molecule profiling of IL-27-primed macrophages was determined using transcriptomic and proteomic sequencing. The Agilent Seahorse XF analyzer calculated energy metabolism indicators. The adoptive cell transfer method was used to verify that forkhead box class O3 (FoxO3) mediates alternatively activated macrophage differentiation induced by IL-27-Ucp2, contributing to alleviating pain sensation in mice. IL-27 is highly expressed centrally and peripherally in rodent pain models. Selective downregulation of IL-27 intensifies pain sensitivity in mice. In macrophages, IL-27 promotes the secretion of anti-inflammatory molecules, such as Arginase-1. Further, transcriptome, energy metabolic examination, and proteome analyses identified that IL-27 restructures the metabolism in macrophages, which is mediated by uncoupling protein 2 (Ucp2) and subsequently activates transcription factor FoxO3. Conditional knockdown of FoxO3 (si-FoxO3) in macrophages refrains the production of anti-inflammatory genes These findings reveal that the IL-27-Ucp2-FoxO3 axis regulates macrophage plasticity distinct from the canonical IL-4-mediated pathway through metabolic rewiring and facilitates alleviating Inflammatory pain. Show less

Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available studies. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of IL-27 in identifying TPE. In addition, we also compared the diagnostic accuracy of IL-27 and adenosine deaminase (ADA) with a head-to-head meta-analysis. We searched the PubMed and Web of Science databases to identify diagnostic test accuracy studies evaluating the accuracy of IL-27 for diagnosing TPE. The last search date was September 2025. We extracted data from the eligible studies and constructed a two-by-two table with true positives (TP), false positives (FP), true negatives (FN), and false negatives (FN). The QUADAS-2 tool was used to assess the quality of eligible studies. A bivariate model was applied to pool sensitivity and specificity, and a summary receiver operating characteristic (sROC) curve with the area under the curve (AUC) was generated to estimate the overall diagnostic accuracy of IL-27 and ADA. A Deeks funnel plot asymmetry test was used to evaluate publication bias. Nine studies encompassing ten cohorts were included, involving 1573 patients (429 with TPE and 1144 with non-TPE). The reported AUCs for IL-27 ranged from approximately 0.73 to 0.99 across eligible studies. The pooled sensitivity and specificity were 0.94 (95% CI, 0.83-0.98) and 0.96 (95% CI, 0.89-0.98), respectively. The AUC for sROC was 0.99 (95% CI, 0.97-0.99). The pooled positive likelihood ratio was 21.97 (95% CI, 7.95-60.69), the negative likelihood ratio was 0.07 (95% CI, 0.02-0.18), and the diagnostic odds ratio (DOR) was 329 (95% CI, 72-1506). Significant heterogeneity was observed in both sensitivity (I IL-27 is a promising diagnostic marker for TPE, and its diagnostic accuracy is comparable to that of ADA. IL-27 should be used as a complementary diagnostic marker to ADA for TPE. Show less

Dietary fibre is an important regulator of the gut microbiome and is associated with many health benefits. However, high levels of fibre intake have also been reported to exacerbate some diseases. Here, we show that mice fed semi-synthetic diets supplemented with purified inulin fibre develop chronic infections with the parasitic whipworm Trichuris muris, concomitant with dysregulated innate antimicrobial defences, exacerbated mucosal inflammation, and altered tryptophan metabolism. Inhibition of tryptophan catabolism or neutralizing either IL-27 or IL-18 restored infection resistance. Inulin-fed mice developed gut microbiota dysbiosis during parasite infection, with Proteobacteria becoming dominant. However, despite drastic differences in gut microbiota compositions in control- and inulin-fed mice, microbiota transfer and depletion experiments demonstrated that dietary inulin triggered chronic T. muris infection in a microbiota-independent manner. Importantly, removing inulin from the diet within a critical immune development window rapidly restored anti-parasite immunity, indicating direct, time-dependent modulation of mucosal immune responses. These data reveal T. muris-induced dysbiosis as a consequence rather than a causative factor of diet-driven changes in host susceptibility, and establish a direct link between dietary fibre and host defence at mucosal surfaces. Video Abstract. Show less

Lung adenocarcinoma (LUAD) exhibits substantial heterogeneity in tumor immune microenvironment (TIME) composition, shaping disease progression and therapeutic response. Here, we integrated transcriptomic and clinical data from TCGA-LUAD to develop a TIME-associated prognostic model. LASSO Cox regression identified eight key genes-S100P, CPLX2, CD200R1, LINC01857, CLEC7A, CLEC17A, COL6A5, and CX3CR1- that yielded a risk score separating patients into two groups with distinct immune states. High-risk tumors were characterized by diminished CD4 Show less

The aim of this study was to investigate the impact of interleukin-27 (IL- 27) gene polymorphism and additional interactions with environmental factors on non-small cell lung cancer (NSCLC) risk based on a Chinese population. SNPStats online software ( http://bioinfo.iconcologia.net/SNPstats ) was used for Hardy-Weinberg equilibrium (HWE) testing. Stratified analysis was performed by logistic regression model to examine the impact of IL- 27 gene SNPs and environmental factors, and additional gene-environment interaction on NSCLC risk. Logistic regression analysis showed a significant association between rs153109, rs181206 and increased NSCLC risk. However, no significant relationship was found between NSCLC risk and rs17855750 or rs40837 genotype with minor allele. Logistic regression also indicated a significant association between smoking status or alcohol consumption and NSCLC risk in this study. We performed crossover analysis to investigate the interaction between two SNPs (rs153109 and rs181206) and two environmental factors (smoking status and alcohol consumption) using logistic regression. We found that ever or current smokers with rs153109- AG or GG genotype have the highest NSCLC risk, compared with never smokers with the AA genotype after covariate adjustment, OR (95%CI) = 3.02 (1.97-5.12), p = 0.012. However, no significant interaction effect was found between rs153109 and alcohol consumption, rs181206 and smoking, rs181206 and alcohol consumption. Our results support an important association of the IL- 27 gene rs153109, rs181206, smoking and alcohol consumption with increased NSCLC risk. We also found a significant impact of an interaction between rs153109 minor allele and ever or current smoking on NSCLC risk. Show less

Opicinumab, a human monoclonal antibody against LINGO-1, is hypothesized to promote remyelination by enhancing the differentiation of oligodendrocyte progenitor cells. The objective of the study is to investigate the efficacy and safety of opicinumab as an add-on therapy to anti-inflammatory disease-modifying therapies (DMTs) in participants with relapsing multiple sclerosis (RMS). Participants with RMS aged 18-58 years, with disease duration up to 20 years, were randomized 1:1 to receive intravenous infusions of placebo or opicinumab every 4 weeks for 72 weeks. Primary endpoint was Overall Disability Response Score (ODRS) over 72 weeks. The study enrolled 263 participants. Adjusted mean difference (95% confidence interval (CI)) on ODRS was 0.15 (-0.05 to 0.35; Although the AFFINITY study did not show significant difference in mean ODRS between opicinumab and placebo groups, data from AFFINITY interpreted with the previous SYNERGY study may inform the design of future remyelination trials. gov identifier:(NCT03222973). Show less

Aortic aneurysm (AA) is a life-threatening vascular disease with high fatality upon rupture. While physical activity (PA) reduces cardiovascular risk, its role in AA prevention remains uncertain, particularly when assessed objectively. We analyzed 93,165 UK Biobank participants (56% women; median age 57 years) with valid 7-day wrist-worn accelerometer data. PA was categorized as light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA). Diagnosed AA was ascertained through linked hospital, death, and primary care records. Cox models estimated hazard ratios (HRs) for AA across quartiles and per-standard deviation (SD) increments, with adjustment for demographic, lifestyle, and cardiometabolic factors. Over a median 7.9-year follow-up, 499 clinically recorded AA cases occurred. Higher accelerometer-measured PA was inversely associated with AA risk. Per-SD increments in total PA, MPA, VPA, and MVPA corresponded to 17%, 22%, 19%, and 23% lower risks, respectively. Compared with the lowest quartile, the highest MVPA quartile had a 44% lower AA risk (HR = 0.56, 95% CI 0.42-0.76). Subtype analyses revealed stronger protective effects for abdominal aortic aneurysm (AAA) than thoracic aortic aneurysm (TAA), while LPA was not significantly associated. These findings demonstrate that higher levels of accelerometer-measured MVPA are robustly associated with a decreased risk of clinically detected AA in a dose-dependent manner. The associations were particularly pronounced for AAA. This study provides objective evidence supporting the potential benefits of MVPA for aortic health. Show less

Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, including circulating monocytes and tissue-resident macrophages, and integrates with host genomes to form stable viral reservoirs. To achieve a functional HIV cure, latency-promoting agents (LPAs) have been developed for the "block-and-lock" strategy to reinforce deep HIV-1 latency and permanently silence proviruses. However, most LPAs have been tested mainly in CD4 Show less

To explore the associations between accelerometer-measured physical activity patterns and cardiovascular diseases (CVD), CVD-cause mortality, and all-cause mortality in people with osteoarthritis (OA). OA participants from the UK biobank with ≥36 h of accelerometer data, collected over one-week, were analyzed. Moderate to vigorous physical activity (MVPA) patterns were classified as: 'weekend warriors' (≥150 min/week, >50% on 1-2 days), active regular (>150 min/week), or inactive (<150 min/week). Mean min per week of light physical activity (LPA) were categorized into quartiles based on the distribution in the analytical sample. Among 10 210 study participants (mean age 58.1 ± 7.1 years; 64.5% female) followed for a median of 6.9 years, there were 1,538 incident cases of CVD, and 358 deaths, including 90 from CVD. Compared with inactive MVPA, both weekend warrior (adjusted hazard ratio, aHR (95% CIs); 0.73 (0.64-0.82)) and active regular MVPA (0.75 (0.65-0.87)) significantly lowered the risks of incident CVD. Notably, only the weekend warrior group showed significant reductions in CVD-cause mortality (0.55, 0.33-0.92), and all-cause mortality (0.75 (0.59-0.96)). Higher levels of LPA may link to lower CVD, CVD-cause mortality, and all-cause mortality risks in a dose-response manner. Subgroup analysis indicated that more prominent associations were found in individuals with a body mass index >30 or those aged over 60. Engaging in a weekend warrior pattern may confer unique survival benefits for OA patients, especially among older adults and those with obesity. LPA may have dose-dependent protective effects for CVD and mortality risk in OA patients. Show less

Capillary zone electrophoresis (CZE)-mass spectrometry (MS) has attracted tremendous attention in top-down proteomics (TDP). However, its reproducibility and long-term repeatability for TDP remain concerns, most likely due to capillary coating. Here, we present an improved procedure for making linear polyacrylamide (LPA) coating, the most widely used coating in CE-MS-based proteomics, to boost the reproducibility and long-term repeatability of CZE-MS-based TDP. We focused on the step of degassing the polymerization solution, a critical step for achieving consistent LPA coating quality. The CZE-MS system using LPA-coated capillaries prepared with the optimal degassing procedure produced excellent reproducibility and repeatability for proteoform analysis. The 210 CZE-MS runs of three protein samples (a standard protein mixture, an Show less

This study aims to identify distinct mindfulness profiles among young and middle-aged lymphoma patients and to examine the mediating role of psychological resilience in the relationship between these mindfulness profiles and social function deficits. From November 2024 to June 2025, a total of 324 young and middle-aged lymphoma patients were recruited using convenience sampling from a tertiary cancer hospital in Urumqi, Xinjiang, China. Participants completed the Mindful Attention Awareness Scale, the 10-item Connor-Davidson Resilience Scale, and the Social Dysfunction Screening Scale. We used latent profile analysis (LPA) to identify distinct mindfulness profiles and tested the mediating role of psychological resilience with the Bootstrap method. Latent profile analysis identified three distinct mindfulness profiles among the patients: a low mindfulness type (29.3%), a moderate mindfulness type (40.1%), and a high mindfulness type (30.6%). Furthermore, psychological resilience partially mediated the relationship between these mindfulness profiles and social function deficits. Young and middle-aged lymphoma patients exhibit heterogeneous mindfulness profiles. Higher mindfulness can enhance psychological resilience, which in turn alleviates social function deficits. Therefore, healthcare providers should develop personalized interventions targeting psychological resilience based on patients' specific mindfulness profiles to improve their social function. Show less

This study aimed to investigate the current status of career calling among novice nurses, to identify potential subtypes and their population characteristics, and to further explore the factors associated with the different subtypes. A cross-sectional descriptive study was used. From January to February 2024, 845 novice nurses from 11 hospitals in Shanxi Province were selected for an online questionnaire survey using convenience sampling. The demographic questionnaire, transition shock of newly graduated nurses scale, medical staff resilience scale, and career calling scale were used as study instruments. Latent profile analysis (LPA) was used to explore the subtypes of novice nurses' career calling, and multifactorial logistic regression was used to analyze the related factors of novice nurses' career calling. Three subtypes of career calling of novice nurses in this study were identified, namely, lacking-calling group (10.3%), stable-calling group (50.0%), and sufficient-calling group (39.7%). Education, weekly working hours, weekly frequency of night shifts, reasons for choosing nursing, level of transition shock, and level of resilience were significantly associated with the three latent profiles of career calling of novice nurses in this study. Novice nurses' career calling presents 3 latent profiles and is heterogeneous in this study. Nursing administrators could pay attention to the differences in the level of career calling of novice nurses and adopt targeted management strategies based on the type of characteristics of the population in order to improve the level of career calling of novice nurses, help them develop their careers, and stabilize the nursing workforce. Show less

Myopia is a critical public health issue; however, the roles of multidimensional psychological resources (i.e., resilience and emotion regulation) and potential gender differences remain underexplored. This cross-sectional study aimed to investigate the association between latent psychosocial profiles and myopia severity, and to examine the moderating role of gender in this association among adolescents. In total, 1008 Chinese seventh-grade students completed assessments of psychological resilience, emotion regulation, and depressive and anxiety symptoms. Myopia was measured as spherical equivalent refraction (SER). Latent profile analysis (LPA) was used to identify distinct psychological profiles, and moderation analysis tested gender's role in the profile-myopia association. LPA revealed three distinct psychosocial profiles: "Low-Resource", "Emotion-Driven", and "Balanced-Adaptive". The Low-Resource profile exhibited the highest levels of depression, anxiety, and myopia severity. A significant moderating effect of gender was found. Among females, both the Emotion-Driven and Balanced-Adaptive profiles were associated with significantly less myopia severity compared to the Low-Resource profile-an association not observed in males. Specific psychological resource profiles were linked to myopia severity, a relationship that was significantly moderated by gender and was prominent only in female adolescents. These findings highlight the importance of person-centered approaches and gender-specific considerations in understanding the psychosomatic pathways of myopia. Show less

Family members of patients with digestive tract cancer represent a high-risk population for cancer development due to shared genetic and lifestyle factors, yet their own disease self-monitoring behaviors remain largely uncharacterized. Understanding the typologies and determinants of these behaviors is essential for precision prevention. A cross-sectional study was conducted among 414 family members of hospitalized patients with esophageal, gastric, or colorectal cancer in Sichuan Province, China (March-October 2023). Self-reported data were collected using validated questionnaires assessing socio-demographics, cancer risk perception, and digestive tract cancer self-monitoring behaviors. Latent profile analysis (LPA) was applied to identify subgroups of monitoring behaviors, and multinomial logistic regression was used to determine influencing factors. LPA revealed three distinct behavioral profiles: poor behavior group (47.10%), average behavior group (38.16%), and good behavior group (14.74%). The mean total self-monitoring score was 2.76 ± 0.69. Multivariate analysis showed that low educational level, family per capita monthly income ≤ 2000 CNY, and not living with patient were significant risk factors for poor monitoring behaviors. Conversely, having existing chronic disease and higher cancer risk perception were strongly associated with better monitoring performance. Nearly half of family members of digestive tract cancer patients exhibit insufficient self-monitoring of early symptoms. Education level, family per capita monthly income, cohabitation, comorbidity, and cancer risk perception are key determinants of behavioral heterogeneity. Tailored, risk-profile-based interventions that enhance risk awareness and promote regular screening are urgently needed to strengthen family-centered cancer prevention. Show less

Fear of disease progression (FoP) is a common psychological concern among patients with unruptured intracranial aneurysms (UIAs). However, heterogeneity in FoP and the role of psychological resilience before treatment remain insufficiently understood. In this cross-sectional study, patients with UIAs scheduled for endovascular treatment were recruited. FoP was assessed using the Fear of Progression Questionnaire-Short Form (FoP-Q-12), and psychological resilience was measured with the Connor-Davidson Resilience Scale (CD-RISC-25). Latent profile analysis (LPA) was conducted to identify distinct FoP profiles. Least Absolute Shrinkage and Selection Operator (LASSO) regression followed by multinomial logistic regression were used to examine factors associated with profile membership. Five distinct FoP profiles were identified: Minimal Fear-Good Adjustment, Mild Emotionally Elevated Fear, Moderate Emotionally Reactive Fear, Moderate Functionally Concerned Fear, and High Pervasive Fear. Multinomial logistic regression showed that higher psychological resilience-particularly the tenacity dimension-was associated with lower odds of belonging to the Mild Emotionally Elevated Fear, Moderate Emotionally Reactive Fear, and Moderate Functionally Concerned Fear profiles, compared with the Minimal Fear-Good Adjustment profile. No significant association was observed between tenacity and the High Pervasive Fear profile. Sensitivity analyses using alternative resilience indicators yielded consistent results. Among patients with UIAs prior to endovascular treatment, FoP exhibits marked heterogeneity. Psychological resilience, especially tenacity, is differentially associated with specific FoP profiles. These findings support the value of profile-based psychological assessment to inform targeted psychosocial support during treatment planning. Show less

Identifying high-performing advanced practice nursing roles and understanding the factors that contribute to their effectiveness are critical for advancing professional development, optimizing workforce deployment, and ensuring long-term sustainability in nursing. This study aimed to (1) identify distinct latent profiles of advanced practice nursing among specialist nurses in mainland China, (2) quantitatively examine the individual and contextual factors associated with high performance, as characterized by these profiles, and (3) qualitatively confirm the significant factors using explanatory semistructured interviews in the high-performance groups. A mixed-methods sequential explanatory design was used, in which quantitative data were collected first and subsequently explained through qualitative interviews. Certified specialist nurses from 16 hospitals across urban and rural areas of Shanghai were included. Latent profile analysis (LPA) was conducted using the five domains from the Advanced Practice Role Delineation tool as manifest indicators to classify nurses into distinct performance profiles. Multinomial logistic regression was used to examine potential determinants (e.g., job position) of group membership. Additionally, a backpropagation neural network (BPNN) was developed to rank the importance of contributing factors. Specialist nurses identified as high performers in the quantitative phase were purposively sampled for explanatory semistructured qualitative interviews. Three latent profiles emerged: high performance (26.1%), moderate performance (46.3%), and low performance (27.6%). Compared to APNs, staff nurses had significantly lower odds of belonging to the high-performance group ( Identifying the profiles of advanced practice nursing roles provides valuable insights for optimizing APN performance and informing targeted management and policy strategies. High-performing specialist nurses are positioned at the nexus of individual capability, interdisciplinary collaboration, and institutional support. Show less

Serum lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease. However, whether hypertension modifies the association between Lp(a) and adverse outcomes in acute decompensated heart failure (ADHF) remains unclear. We investigated how hypertension status influences the relationship between Lp(a) and all-cause mortality in ADHF. We conducted a single-center retrospective observational study including 2610 patients hospitalized with ADHF. We normalized the distribution of Lp(a) by a logarithmic transformation and assessed the risk of all-cause mortality with Lp(a), using Cox regression with adjustment for potential confounders. Among 2610 patients (39.0% women; mean age, 68.8 years), 1606 (61.5%) had hypertension. Over 4.1 years (median), 1287 deaths occurred. In all patients, log-transformed Lp(a) was significantly associated with mortality (adjusted HR 1.21; 95% CI, 1.05-1.39; Increased admission Lp(a) levels were associated with a higher risk of all-cause mortality in ADHF patients with hypertension. Further studies are needed to explore the mechanistic links among Lp(a), hypertension and ADHF. 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

Late-life depression shows heterogeneous developmental trajectories. Prior studies in older Chinese populations have identified distinct depressive trajectories, yet the influence of family emotional support across the life course remains underexplored. We conceptualized intergenerational emotional interaction patterns as the combined configuration of early-life parental affection and later-life emotional support from adult children. This study identified late-life depressive trajectories and tested whether these patterns predict depressive trajectory among Chinese older adults. Using China Health and Retirement Longitudinal Study (CHARLS) data (2011-2020; n = 9888), this study identified depressive trajectories using Latent Class Growth Modeling (LCGM) and Latent Profile Analysis (LPA) was used to categorize participants into subgroups based on maternal/paternal affection and emotional support from adult children. Multinomial logistic regression and Chi-square tests assessed associations between profiles and trajectories. Four depressive trajectories emerged: "no depression" (56.3%), "deterioration" (22.4%), "alleviation" (12.3%), and "chronic depression" (9.1%). Three distinct intergenerational emotional interaction patterns were found: "emotional inheritance" (40.7%), "emotional compensatory" (17.4%), and "emotional mismatch" (41.9%). The "emotion inheritance" group was overrepresented in the "no depression" trajectory, whereas the "emotional compensatory" group faced elevated risks for being classified into "deterioration" and "chronic depression" trajectories. Intergenerational emotional interaction patterns are independently and jointly associated with depressive symptoms trajectories in later life. The strongest protective effects were observed for individuals with both high childhood parental affection and ongoing emotional support from children. Conversely, low parental affection-even when compensated by later-life support-was linked to worse mental health outcomes. Show less

Peripheral artery disease (PAD) is a major manifestation of systemic atherosclerosis and affects vascular health in older adults. Dyslipidaemia contributes significantly to PAD, but the predictive value of composite lipid indices remains unclear. The non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) reflects the balance between atherogenic and protective lipoproteins. This study aimed to explore the association between the NHHR and PAD among vascular surgery inpatients aged ≥50 years in Kunshan, China. This retrospective cross-sectional study included 3,532 patients (aged ≥ 50 years) hospitalized at the Affiliated Kunshan Hospital of Jiangsu University, Suzhou, from December 2017 to August 2024. NHHR, calculated as (total cholesterol - HDL-C)/HDL-C, was the exposure variable; PAD, defined as PAD-like symptoms with an ankle brachial index < 0.9, was the outcome. Covariates included age, sex, lipoprotein(a) level [Lp(a)], apolipoprotein A1 level (Apo A1), alanine aminotransferase (ALT) level, neutrophil count (NEUT), hypertension status, diabetes status, smoking status, and alcohol consumption status. Multivariate logistic regression, smooth curve fitting, and threshold analyses were performed. After adjustment for confounders, the NHHR was nonlinearly associated with PAD (OR = 0.77; 95% CI: 0.65-0.93; The NHHR was associated with the presence of PAD, with the evidence suggesting a nonlinear relationship and potential sex-specific differences. Given the retrospective cross-sectional design, this association does not support causal inference or strong predictive claims. The NHHR may help identify individuals who could benefit from further clinical evaluation for PAD, but prospective studies are needed to confirm its clinical relevance before its routine application. Show less

Massive open online courses (MOOCs) have transformed global education, yet their long-term effectiveness and evolving learner engagement remain underexplored. This study aims to comprehensively evaluate a nursing MOOC over six years, examining learner engagement, identifying distinct learner profiles, and assessing changes across different developmental stages to inform future MOOC design. A retrospective study was conducted on 4171 completers of the Medical Nursing MOOC on a Chinese MOOC platform, covering eleven semesters from 2018 to 2023. Latent profile analysis (LPA) categorized learners based on unit test scores, and profile distributions were compared across the MOOC's developmental stages. The Medical Nursing MOOC attracted 69,642 registrants with a 5.99% completion rate. Among the 4171 individuals who completed the course, latent profile analysis identified six distinct learner types, demonstrating significant differences in overall learning effect (H = 2823.604, P < 0.001). The chi-squared analysis revealed significant differences between the proportions of the six profiles regarding MOOC developmental stages (χ Findings highlight the evolving role of MOOCs in nursing education. Despite challenges in long-term engagement, the increasing proportion of highly engaged learners and declining dropout rates indicate growing effectiveness and sustainability. These insights provide evidence-based guidance for optimizing MOOC design and implementation. Show less

Oxypeucedanin (OPD) showed anti-allodynia against neuropathic pain (NeuP) in our previous study. In the present study, we aimed to further investigate whether lysophosphatidic acid receptor (LPAR) signaling mediated OPD-induced antinociception against NeuP models. Single OPD treatment dose-dependently reduced pain hypersensitivity, and repeated OPD treatment maintained sustained antinociception without the development of tolerance. Importantly, OPD exhibited a significant curative effect on different stages of NeuP. ROCK and RhoA agonists prevented the therapeutic effect of OPD, while the inhibitors of LPAR, ROCK, and RhoA mimicked OPD-induced antinociception. Notably, OPD treatment attenuated the increases of LPA content and protein expression of LPAR1, RhoA, and Show less

The Climate Change Anxiety Scale (CCAS) is an emerging psychometric instrument designed to assess climate change anxiety (CCA). This study aimed to preliminarily identify reference cutoff scores and core items of the CCAS in a Chinese adult population. We conducted an online cross-sectional survey in China between May and June 2024, recruiting 653 Chinese adults (mean age = 32.62 ± 7.40 years; 53.8% female) via Wenjuanxing. CCA was assessed using the CCAS. External variables included generalized anxiety (Chinese GAD-7), self-rated sleep quality (single-item, past week), and self-reported experience of meteorological disasters (yes/no). Latent profile analysis (LPA) and receiver operating characteristic (ROC) analyses were used to derive reference cutoff scores, and network analysis was applied to identify core items. LPA supported a two-profile solution and yielded an overall reference cutoff score of 27.5, above which participants were categorized as having elevated CCA risk. Participants classified as high risk reported higher generalized anxiety, poorer sleep quality, and a higher likelihood of meteorological disaster experience. Sex-stratified analyses indicated different optimal cutoffs: 28.5 for males (sensitivity = 1.000; specificity = 0.982) and 26.5 for females (sensitivity = 0.986; specificity = 0.986). Network analysis further suggested that the item Show less

l-Pipecolic acid (l-PA) and its hydroxylated derivatives (hydroxypipecolic acids, HPAs) are non-proteinogenic amino acids that serve as valuable chiral building blocks for pharmaceuticals, antibiotics, and natural products. Conventional chemical synthesis of these compounds often suffers from operational complexity, poor environmental compatibility, and insufficient stereochemical control, driving a shift toward biosynthetic approaches. This review covers recent advances in enzyme engineering and synthetic biology aimed at enabling sustainable and efficient production of l-PA and HPAs. For l-PA biosynthesis, various metabolic engineering strategies to enhance its production in microbes are introduced, and enzyme cascades, single enzyme strategy, and immobilized enzyme strategy involved in l-PA production are discussed. Regarding HPAs biosynthesis, which involves the regioselective hydroxylation of l-PA, their structural features, catalytic mechanisms, and recent progress in the biosynthesis of diverse HPAs, the protein engineering of proline hydroxylase is emphasized. Finally, we present future perspectives to accelerate the biosynthetic production of l-PA and HPAs. Show less

Sequence alignment is essential for genomic research and clinical diagnostics, yet detecting complex rearrangements such as inversions, duplications, and gene conversions remains challenging due to allele complexity and limitations of current methods. We introduce VACmap, a non-linear mapping approach to enhance the detection and representation of all genetic variations. VACmap improves duplication detection from 20% to 90% in the Challenging Medically-Relevant Genes (CMRG) benchmark and improves characterization of complex inversions in repetitive regions and gene conversion events. It improves resolving clinically significant loci, including the LPA gene (with repetitive KIV-2 units linked to coronary heart disease), GBA1 and STRC genes (risk factors for Parkinson's disease and hearing loss, respectively, affected by pseudogene recombination with GBAP1 and STRCP1). Here, we show that VACmap delivers better alignment accuracy and SV detection, providing a robust tool for genomic analysis and clinical insights, with potential to advance understanding of genetic diversity and disease mechanisms. Show less

The polyphenols in grains are highly active, but some polyphenols in highland barley are in a bound form and have extremely low bioavailability. Fermentation by lactic acid bacteria (LAB) is capable of altering the functionality of foods. This research investigated the effects of fermentation with different LAB, such as Lactobacillus acidophilus (LAC), Lactobacillus casei (LCA), Lactobacillus rhamnosus (LRH), Lactobacillus plantarum (LPL), and Lactobacillus bulgaricus (LBU), on the hypoglycemic activity and mechanism of polyphenols in highland barley. The hypoglycemic activity of the fermentation products was measured by in vitro antioxidant, enzyme activity, and glucose consumption experiments. Untargeted metabolomic analysis used UHPLC-Q Exactive HF-X/MS to reveal distinct metabolic profiles among the fermented groups. Molecular docking and western blot experiments were conducted to elucidate the mechanism underlying the hypoglycemic effect of fermentation products. Polyphenolic antioxidant activity in highland barley and its inhibitory activities against α-glucosidase and α-amylase were increased after LAC fermentation. Furthermore, the fermented extracts improved glucose consumption in HepG2 cells. The content determination and metabolomic analysis showed that fermented highland barley polyphenols were increased, and 113 differential phenolic metabolites were identified and annotated, among which 44 exhibited a significant upregulation compared with raw highland barley polyphenols. At the molecular level, the polyphenol extract upregulated PI3K and phosphorylated Akt expression in HepG2 cells. Overall, the results indicate that fermentation by LAC biotransformed highland barley polyphenols into smaller molecules with improved hypoglycemic activities, thereby enhancing their bioavailability. Show less

This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becomes a common issue of functional decline in the elderly. Utilizing bioinformatics analysis, this research identified 101 overlapping differentially expressed genes (DEGs) involved in both CR and endurance exercise. These genes are primarily enriched in key biological pathways related to longevity, Apelin signaling, AMPK signaling, FoxO signaling, and cGMP-PKG signaling pathways. Additionally, we identified 10 key genes (such as LPL, PPARGC1A, and IGF1), 4 transcription factors (FOXC1, POU2F2, GATA2, and STAT3), and 4 microRNAs (miR-155-5p, miR-124-3p, miR-1-3p, and miR-16-5p) interacting with these genes. Drug-gene interaction analysis identified carotuximab as a compound with potential relevance for future investigation in the context of muscle aging. These findings provide new insights into the molecular mechanisms underlying muscle functional decline in the elderly and propose potential targets and drugs for intervention development. Show less