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To investigate the genetic causality between Human blood cell (HBC) traits and sporadic lymphangioleiomyomatosis (sLAM) by mediation joint multi-omics and eQTL Mendelian randomization analysis. Quality control processes were followed to select eligible instrumental variables strongly associated with 35 kinds of HBC traits. Independent cohort of European ancestry with sLAM and lung function genome-wide association study (GWAS) summary statistics were used separately. We utilized a two-step MR approach to explore potential mediators and evaluate the proportion of effect mediated in the associations linking HBC trait candidates to sLAM. Finally MR analysis integrating single cell expression quantitative trait loci (sc-eQTL) from 14 immune cell types with GWAS of sLAM was conducted. Increased level of basophil count was positively associated with higher risk of sLAM (BASO#; OR = 3.878, 95%CI:1.137–13.221, For the first time, this study leverages mediation analysis and multi-omics MR integrated with sc-eQTL data to elucidate the roles of HBC traits, immune cells, inflammatory proteins, VEGF-related proteins and immune cell-specific genes in the pathogenesis of sLAM among the European populations. The online version contains supplementary material available at 10.1186/s13023-026-04224-6. Show less

This study aimed to identify latent profiles of spiritual orientation (SO) and psychological well-being (PWB) among female healthcare workers and to examine how demographic factors predict profile membership. A total of 104 female healthcare professionals from two hospitals in eastern Türkiye were recruited using purposive criterion sampling. Participants completed validated self-report measures assessing SO and PWB. Latent Profile Analysis (LPA) with varying means, equal variances, and covariances fixed to zero (Model 1) was conducted to uncover distinct profiles based on standardized mean scores. Four profiles were identified: “Low Spirituality-Low Well-Being” (5.8%), “Moderate Spirituality-Low Well-Being” (13.5%), “High Spirituality–High Well-Being” (61.5%), and “Low Spirituality-High Well-Being” (19.2%). The four-class solution demonstrated superior fit indices (BIC = 1737.0, entropy = 0.956) compared to alternative models. Multinomial logistic regression analysis revealed that education level, tenure, and marital status standing significantly predicted membership in the more adaptive profiles, particularly the “High Spirituality–High Well-Being” group. Notably, a moderate positive correlation ( Show less

Pelvic radiation therapy is an essential treatment for several pelvic malignancies, but it can lead to radiation cystitis (RC), a severe progressive inflammatory bladder disorder lacking effective diagnosis and therapeutic options. RC evolves through acute, latent, and chronic phases, ultimately resulting in bladder fibrosis, vascular damage, and hematuria. Here, we characterize the molecular and immunological features associated with RC progression using a preclinical mouse model. Building on a prior analysis of the acute and chronic phases, we examined the previously unanalyzed latent phase and integrated transcriptomics, immune cell profiling, inflammatory protein measurements, and bladder function assessments across all stages. Acute radiation injury was marked by the strong activation of apoptotic pathways, whereas latent and chronic phases were dominated by inflammatory signaling with distinct cytokine and chemokine signatures. The persistent upregulation of Cdkn1a (P21) was consistent with sustained senescence-associated signaling, while reductions in IL-27 and shifts in the granulocyte-lymphocyte-enriched immune population during the latent phase were consistent with altered immune regulatory states. At chronic stages, increased SASP-associated proteins and matrix remodeling mediators coincided with bladder functional decline. Together, these findings support a model in which radiation-induced senescence, coupled with immune dysregulation during the latent phase, are coordinated features accompanying inflammation, tissue remodeling, and bladder dysfunction in RC. Show less

To ascertain the level of psychological resilience, examine the latent profiles of individuals within infertile couples who experience recurrent implantation failure (RIF), identify the relevant influencing factors, and lay a foundation for developing customized intervention strategies. Convenience sampling was adopted in this study. Participants were selected from individuals in infertile couples with RIF who attended the Second West China Hospital of Sichuan University between November 2024 and July 2025. Data were collected via a general information questionnaire and validated scales assessing psychological resilience, social support, sleep quality, family adaptability and cohesion, anxiety, and depression. Latent profile analysis (LPA) was performed to explore the psychological resilience profiles of individuals with RIF, while univariate analysis and multivariate Logistic regression analyses were employed to identify the influencing factors associated with different profile categories. A total of 303 valid questionnaires were collected, including 194 from females and 109 from males. The overall psychological resilience score was (26.66 ± 6.319). Latent profile analysis categorized psychological resilience into three subgroups: the low tenacity-low strength subgroup (31.4%), the moderate tenacity-moderate strength subgroup (53.1%), and the high tenacity-high strength subgroup (15.5%); Multivariate Logistic regression analysis indicated that gender, family adaptability and depression severity (all Marked interindividual heterogeneity exists in the psychological resilience of individuals with RIF. Gender, family adaptability and depression severity serve as the core influencing factors. In clinical practice, stratified and targeted interventions should be delivered according to distinct psychological resilience subgroups. It yields clinical implications for an association between improved psychological resilience among individuals from couples with RIF and enhanced treatment adherence. Show less

Recent advances in molecular pathology have transformed the diagnostic landscape and management of human cancer. Increasingly, integration of genomic and epigenomic data with conventional histopathology has improved tumor classification, refined prognostic assessment, and revealed previously unsuspected therapeutic targets. High-throughput techniques such as next-generation sequencing, gene fusion panels, and methylation arrays have expanded applicability to formalin-fixed tissue and enabled simultaneous evaluation of multiple cancer-defining alterations/genetic drivers. In optic nerve gliomas, MAPK pathway activation through BRAF or FGFR1 alterations, or NF1 inactivation, is a basic biological feature with diagnostic implications, while MEK inhibitors may be of clinical benefit in selected patients. Optic nerve sheath/orbital meningiomas demonstrate divergent molecular landscapes depending on location, with NF2-driven and non-NF2-driven pathways informing recurrence risk and behavior. In the orbit, characteristic genetic drivers facilitate diagnosis of mesenchymal tumors such as solitary fibrous tumor (NAB2::STAT6) and alveolar rhabdomyosarcoma (PAX3/7::FOXO1), while molecular profiling assists in distinguishing challenging peripheral nerve and melanocytic lesions. Similarly, lacrimal gland neoplasms parallel salivary gland counterparts, with recurrent fusions such as PLAG1, HMGA2, and MYB::NFIB of great diagnostic utility. These advances underscore the growing role of molecular diagnostics in improving accuracy, guiding prognostication, and refining the classification of rare ocular tumors. As high-throughput techniques continue to mature, integration with evolving spatial and single-cell-based approaches promises to expand our understanding and further personalize diagnostic and therapeutic strategies. Show less

Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut-lung axis and improve respiratory innate immunity in a mouse model of Three strains of Only strain LAFF998 significantly reduced pulmonary bacterial loads, prevented bacteremia, and attenuated lung injury. This protective effect was associated with selective modulation of respiratory immunity, characterized by reduced neutrophilic inflammation, increased lymphocyte recruitment, and enhanced activation of alveolar macrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages from LAFF998-treated mice exhibited a primed phenotype with heightened cytokine responses to pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to confer protection or significantly modulate respiratory immune responses. These findings demonstrate a strict strain-dependent effect among porcine 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

The 2025 update of the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines on dyslipidemia introduce important innovations based on new evidence. The risk assessment is now conducted using the systematic coronary risk evaluation 2 (SCORE2) and SCORE2-OP (older persons), which enable improved stratification, particularly in older individuals. In addition, risk modifiers, such as family history, ethnicity, comorbidities and the biomarkers elevated highly sensitive C‑reactive protein (hs-CRP) or lipoprotein(a) (Lpa), have been introduced. Risk categories have been refined while low-density lipoprotein cholesterol (LDL-C) target values and the principle of stepwise treatment remain unchanged. A major focus is on the acute coronary syndrome: the immediate initiation of high-intensity statin treatment, mostly in combination with ezetimibe is recommended. Increasingly more important are elevated Lp(a) levels and special subgroups: in people with human immunodeficiency virus (HIV), statin treatment is recommended over the age of 40 years regardless of the LDL‑C as well as in high-risk patients undergoing anthracycline treatment. The use of dietary supplements and vitamins for prevention, however, are discouraged. The update reinforces the principle of risk-adapted LDL‑C target values, expands the treatment options and emphasizes the need for early, consistent lipid-lowering with practical recommendations. Show less

Early diagnosis of pediatric sepsis is difficult because of the lack of specific clinical signs and limitations of standard biomarkers. Proteomics is a promising approach because it can identify disease-specific protein signatures. To systematically evaluate the current literature on the application of proteomics in pediatric sepsis, review and evaluate the current evidence on proteomic biomarkers for diagnosing and predicting pediatric sepsis. This is a systematic review with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-informed, structured search and transparent study-selection reporting. A structured literature search was conducted in PubMed, Scopus, and Web of Science up to January 2025. Studies involving pediatric patients (ages 0-18) with sepsis that used proteomic platforms and reported diagnostic or prognostic outcomes were included. Four studies met the inclusion criteria. Identified biomarkers included interleukin-27, signal transducer and activator of transcription 3, haptoglobin, serum amyloid A 1/2, soluble CD25, and leucine-rich alpha-2-glycoprotein 1. Sensitivities ranged from 60% to 86%, and specificities ranged from 75% to 92%. Multi-marker panels demonstrated superior diagnostic performance compared to single markers. Biomarkers were detectable within 2-6 hours of symptom onset. The analytical methods used varied and included enzyme-linked immunosorbent assays, liquid chromatography-tandem mass spectrometry, and SOMAscan. Most studies were exploratory and lacked external validation; they also used small, heterogeneous cohorts. Proteomics shows promise for earlier and more precise diagnostics of pediatric sepsis, but clinical translation is limited by small, single-center cohorts; age-dependent variability without developmental reference ranges; scarce longitudinal profiling; and minimal external validation. The priority now is multicenter, age-stratified, longitudinal studies with real-world comparators. 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

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

Autistic youth experience high rates of emotion dysregulation, which can significantly impact functioning and quality of life. Despite its clinical significance, emotion dysregulation remains understudied and misunderstood, with few validated measures for use in autistic youth. This study aimed to further validate the Emotion Dysregulation Inventory (EDI) and explore its utility in understanding emotion dysregulation, its relationship with autism symptoms, and its associations with treatment-relevant factors. Caregivers of autistic youth aged 6-11, recruited through the SPARK initiative, completed questionnaires on child behaviors, emotions, and experiences. A total of 320 families were included, with oversampling of minoritized racial and ethnic backgrounds. Structural equation modeling was used to confirm the EDI's two-factor structure and measurement invariance across diverse groups. Latent profile analysis (LPA) and the R3STEP procedure were used to identify subgroups based on emotion dysregulation and autism symptom severity and examine associations with child and family factors. The EDI demonstrated robust psychometric properties, with measurement invariance supporting its use across diverse racial and ethnic groups, as well as for youth with or without a history of language disorder. LPA identified three phenotypic subgroups, each showing meaningful associations with child and family characteristics, including behavioral problems, parental stress, and sleep disturbances. This study contributes to our understanding of emotion dysregulation in autism by supporting the EDI's validity in diverse samples and highlighting associations with autism symptoms, comorbidities, and other challenges. Integrating emotion dysregulation into clinical conceptualizations can improve the quality of care for autistic youth. 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

Allostatic load (AL), an index of cumulative physiological dysregulation from chronic stress, may contribute to Alzheimer's disease (AD) pathophysiology by accelerating brain aging. Higher AL has been associated with AD-related biomarkers, suggesting a mechanistic connection. Lifestyle factors influence both AL and AD vulnerability, but their moderating role in AL-AD biomarker associations remains unclear. We included 111 cognitively unimpaired older adults from the baseline visit of the Age-Well trial. AL was computed as a composite score of 18 biomarkers spanning neuroendocrine, immune, metabolic, cardiovascular-respiratory, and anthropometric systems. Plasma biomarkers included amyloid beta (Aβ)42, Aβ40, phosphorylated-tau (p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Physical activity, Mediterranean diet adherence, and cognitive activity were assessed using validated questionnaires. Multiple linear regressions tested associations between AL and (1) AD-related biomarkers and (2) lifestyle factors, as well as their interactions, controlling for age, sex, education, apolipoprotein E ε4 (APOE ε4) status, and glomerular filtration rate (GFR). Higher AL was associated with higher Aβ42/Aβ40 ratio ( Regular physical activity was associated with a weaker relationship between AL and early AD-related biomarkers in this cross-sectional sample. Longitudinal studies should confirm whether maintaining physical activity attenuates stress-related physiological dysregulation and reduces AD vulnerability. Show less

Precise toxicological mechanism of atherosclerosis (AS) induced by environmental hazardous substance nicotine exposure remains unclear, impeding its prevention strategies and antagonist development. Additionally, it is yet unknown whether Dendrobium officinale's active components can antagonize nicotine-induced AS. This study aimed to elucidate nicotine exposure-induced AS toxicological mechanisms and identify Dendrobium officinale's active components-derived antagonists. Firstly, using ApoE Show less

Apolipoprotein E (ApoE) is a key regulator of lipid metabolism that binds to lipid nanoparticle (LNP) surfaces to mediate cellular interactions. However, the ApoE-LNP behavior is highly dependent on the LNP composition, and the underlying mechanisms remain unclear. Here, we show that subtle alterations in LNP surface lipids profoundly reshape the ApoE-LNP structure and intracellular trafficking. Using cryogenic electron microscopy and live-cell imaging, we demonstrate that replacing 10 mol % 1,2-distearoyl- Show less

The precise mechanism of sodium glucose co-transporter 2 (SGLT2) inhibitor on reno-protective effect has been still unclear. In this study, we hypothesised that SGLT2 inhibitor prevents diabetic kidney disease via reduction of hypoxia-induced factors. In this multicenter, prospective, randomised, double blinded clinical trial, people with type 2 diabetes and microalbuminuria were randomised equally to empagliflozin (10 mg/day) (n = 40) and placebo (n = 39) and followed 24 weeks. The primary endpoint was change in urinary albumin creatinine ratio (ACR) and urinary liver type fatty acid binding protein (L-FABP) excretion from baseline to 24 weeks. Major secondary outcome was change in serum vascular endothelial growth factor (VEGF), angiopoietin-like proteins 2 (ANGPTL2), angiopoietin-like proteins 4 (ANGPTL4), and adrenomedullin (AM) levels. Although the reduction of ACR was significantly greater in the empagliflozin group than the placebo group at 4 and 12 weeks, the difference of change at 24 weeks between the two groups was not statistically significant (Empagliflozin group-Placebo group: -0.3643, 95% CI: -0.7571 to 0.0285, p = 0.0686). There was no difference in urinary L-FABP excretion between the empagliflozin and placebo groups. Serum VEGF and ANGPTL2 decreased significantly more in the empagliflozin group, whereas there were no significant differences in AM and ANGPTL4. These results demonstrated that empagliflozin partially suppressed the hypoxia-induced angiogenic factors overproduction in addition to a declining trend in ACR in the early stage of diabetic kidney disease, which might contribute to the mechanisms of reno-protective effects of this agent (jRCTs051200147). Show less

Parental history of dementia is associated with increased dementia risk. We investigated whether having a parent with dementia is associated with increased peripheral inflammation in middle-aged adults. Participants were from the Offspring Study (n = 1204). Parental dementia status was determined by a diagnostic consensus conference. Plasma chemokine and cytokine concentrations were assayed with Luminex technology. Parental history of dementia was associated with higher levels of eotaxin and lower levels of granulocyte colony-stimulating factor, vascular endothelial growth factor A, and interleukin (IL)-27. IL-18 and epidermal growth factor levels were higher in Black individuals with a parental history of dementia compared to Hispanic individuals with the same history. Women with a parental history of dementia had higher levels of interferon-alpha 2, IL-12p70, soluble CD40 ligand, and IL-18 compared to men with the same history. Parental history of dementia is associated with elevated markers of peripheral inflammation. These associations vary across sex, race, and ethnicity. 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

In this study, we evaluated a dual non-viable microbial therapeutic strategy combining prophylactic immune priming with heat-killed LpCFS did not directly alter cytokine or chemokine production by BAL macrophage-enriched adherent cells, indicating the absence of intrinsic immunostimulatory activity. However, therapeutic aerosol administration of LpCFS significantly reduced pulmonary and systemic PaS and PaR loads, attenuated lung damage, and modulated the inflammatory response by decreasing pro-inflammatory cytokines while increasing IL-10 during infections. Prophylactic administration of HK1505 effectively primed BAL macrophage-enriched adherent cells, enhancing their production of IL-1β, IL-6, IFN-γ, and IL-27 while reducing TNF-α and chemokine expression (CCL2, CXCL2, and CXCL10), thereby promoting efficient bacterial clearance with limited immunopathology. In this set of experiments HK1505 was compared with the live Our findings demonstrate that a non-viable probiotic-based strategy integrating prophylactic immune priming with HK1505 and therapeutic antibiofilm intervention with LpCFS effectively protects against antibiotic-resistant 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

Muscle satellite cells (SCs), essential for skeletal muscle regeneration, decline in number and function with age, contributing to sarcopenia. A fully defined viscoelastic hydrogel that preserves SC-myofiber interactions and supports tunable densities of fibronectin-derived RGD ligands was used to investigate age-related defects in extracellular matrix sensing by SCs. Elevating RGD density increased the number of activating and proliferating SCs on myofibers from young mice, whereas SCs from aged mice were unresponsive. Loss of FGF receptor 1 signaling in SCs from aged mice abrogated the coordinated Syndecan-4 and Integrin-β1 matrix response observed in SCs from young mice. Activating Integrin-β1 promoted asymmetric division and self-renewal in SCs from young mice whereas combined FGFR1 and Integrin-β1 signaling drove symmetric expansion. In SCs from aged mice, FGFR1 dysfunction disrupted this balance, impairing asymmetric division, but constitutive FGFR1 activation restored receptor co-localization, self-renewal, and fibronectin responsiveness. Therefore, FGFR1 integrates matrix and growth factor signals, suggesting that targeting the FGFR1-Integrin-β1 axis may enhance SC regenerative potential in aging organisms. Show less

FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms remain incompletely understood. Here, we report that cerebral FURIN-deficient mice exhibit cognitive decline and neurodegeneration. Lipid droplets (LDs) that are preferentially accumulated in astrocytes correlate with an increase of the LD markers PLIN2 and PLIN3, and conversely a decreased level of autophagic proteins including ATG5, BECN1 and MAP1LC3/LC3 as well as LAMP1. Accordingly, silencing of Show less

Based on epidemiological and genetic studies in recent decades, lipoprotein(a) (Lp(a)) has been accepted as a causal risk factor for atherosclerotic cardiovascular disease and aortic stenosis. Although inter-ethnic differences exist, Lp(a) level ≥50 mg/dL is commonly reported to indicate elevated cardiovascular risk. Blood Lp(a) levels are largely determined based on genetic background, and the kringle IV type 2 repeat variant is a major factor. Lp(a) is structurally similar to low-density lipoprotein (LDL) but also contains apolipoprotein(a) (apo(a)), which includes kringle domains associated with diverse effects depending on particles and individuals. The LDL-like property of Lp(a) and effect of apo(a) on vascular cells can promote atherosclerosis. Apo(a) competes with plasminogen and can inhibit the role of plasmin during fibrinolysis. Furthermore, oxidized phospholipids on apo(a) may induce oxidative stress to enhance atherosclerosis and can affect valve calcification. Trials on new therapeutics targeting Lp(a) RNA, including antisense oligonucleotide (e.g., pelacarsen), siRNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and small molecules (e.g., muvalaplin), are under way. Depending on the study or dose, these agents lowered Lp(a) levels by 80-100% compared with the control; however, results of clinical outcomes have yet to be reported. Show less

Alzheimer's disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), and regional vulnerability was assessed with a composite vulnerability score (CVS) derived from associations between diffusion features and AD severity across clinical traits in each of the four sex-APOE groups (female or male, with or without APOE4). Brain parcellation with the Eve atlas revealed regions consistently affected across sex-APOE groups (e.g., parahippocampal and superior temporal gyri) and regions specific to individual groups (e.g., the cingulum in females with APOE4 and the middle frontal gyrus in males without APOE4). Gene co-expression network analysis of the matched blood expression data identified gene subnetworks linked to group-specific regional vulnerability, including a muscle tissue morphogenesis module regulated by NEURL1B and HIST1H2BN associated with middle frontal gyrus vulnerability. These findings demonstrate that sex and APOE genotype jointly shape region-specific WM vulnerability and its molecular signatures in AD. Understanding these interactions provides novel mechanistic insights and may inform precision approaches to drug development, biomarker discovery, and clinical trial design for AD. Show less

Generation of specific antibodies against peptides by immunization requires their covalent conjugation to protein carriers to override their inherently weak immunogenicity. The vast majority of bioconjugation approaches to achieve peptide-protein constructs rely on thiol-maleimide chemistry and capitalize on a wide array of commercial maleimide-functionalized protein carriers. Disulfide-rich peptides (DRPs) possess a rigid, constrained structure that makes them ideal for designing synthetic mimics of protein regions/domains. For bioconjugation purposes, the introduction of a single spare thiol moiety into a linear peptide antigen is straightforward, while DRPs' disulfide bonds are prone to intramolecular thiophilic attack by the reactive thiolate. This unintended reactivity competes with the desired Michael addition to the maleimide moiety, ultimately disrupting the native disulfide bridging framework. As a result, DRP's tertiary structure will be altered, affording an immunogen that is a poor mimic of the native target. Although a few studies have explored the late-stage introduction of thiol-containing cross-linkers into DRP antigens for their conjugation onto protein carriers, the stability of DRPs' disulfide pattern in the presence of an extra thiol has never been examined. In this study, we systematically evaluated the influence of different spacers in "DRP-spacer-thiol" constructs under thiol-maleimide reaction conditions. Our results highlight how both linker length and flexibility are key to maintaining DRP disulfides unaltered, providing a general approach to achieve DRP bioconjugation by thiol-maleimide chemistry. We have applied our approach to a small DRP predicted to closely mimic a surface-accessible epitope of the full LINGO-1 protein and obtained a very specific antibody response upon immunization; the resulting polyclonal IgG was able to selectively bind the full-length protein in a cellular context, with stringent selectivity across its four homologs. Show less

Colorectal cancer (CRC) remains a major global health challenge, underscoring the need for reliable biomarkers to improve prognosis and therapeutic stratification. In this study, we comprehensively investigated the expression pattern, clinical significance, molecular functions, and immunological implications of LINGO1 in CRC. Integrative analyses of TCGA and GEO datasets, together with validation in 72 clinical CRC samples, demonstrated that LINGO1 is markedly overexpressed in tumors and strongly associated with advanced clinicopathological features and poor patient outcomes. Functional experiments revealed that both knockdown of LINGO1 in SW480 and LoVo cells and overexpression of LINGO1 in HCT116 cells significantly modulate malignant phenotypes, including proliferation, migration, invasion, and angiogenic capacity. Transcriptome-wide and pathway enrichment analyses further indicated that high LINGO1 expression is linked to epithelial-mesenchymal transition, angiogenesis, Wnt/β-catenin signaling, and other oncogenic pathways. Immunogenomic profiling, supported by multiplex immunofluorescence staining, showed that elevated LINGO1 is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T-cell infiltration and diminished GZMB expression, alongside upregulation of multiple immune checkpoint molecules. Collectively, our findings identify LINGO1 as a novel oncogenic driver and immune-modulatory biomarker in colorectal cancer, with potential value for prognosis and therapeutic targeting. Show less

For a long time, noncoding RNAs (ncRNAs) were considered irrelevant fragments of the genome, dismissed as genetic noise. However, recent breakthroughs have unveiled their crucial Role in regulating gene expression, influencing fundamental biological processes such as chromatin remodeling, epigenetic modifications, and cellular communication. Among them, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have drawn considerable attention due to their strong association with neurodegenerative disorders and cardiovascular diseases (CVDs). Despite their apparent differences, these conditions share molecular regulatory networks that ncRNAs help orchestrate. LncRNAs, like ANRIL and MEG3, play a Role in vascular integrity and cardiac fibrosis, while MIAT and MALAT1 are implicated in heart failure and ischemic injury. In Alzheimer's disease, BACE1-AS and BC200 contribute to the buildup of amyloid plaques and tau protein tangles, worsening cognitive decline. The ability of ncRNAs to act as molecular sponges-binding to miRNAs and modulating gene expression-demonstrates their intricate Role in disease progression. With advances in sequencing technologies and computational biology, ncRNAs are emerging as promising biomarkers and therapeutic targets. New approaches, including CRISPR-based gene editing and RNA therapeutics, present exciting possibilities for intervention. However, challenges such as stability, precise delivery, and potential side effects must be addressed before these treatments can be translated into clinical practice. This chapter delves into the expanding field of ncRNA research, highlighting its potential to reshape the future of precision medicine and targeted therapies. Show less