👤 Huizhen Huang

This study employed a latent profile analysis (LPA) to identify distinct subgroups of learned helplessness among Chinese breast cancer chemotherapy patients and examined influencing factors. Through convenience sampling, 260 breast cancer chemotherapy patients aged 18-74 years from a tertiary hospital in Henan Province were recruited between May 2024 and January 2025. Data were collected using a general demographic questionnaire, the Learned Helplessness Scale, the Brief Illness Perception Questionnaire, the Social Support Rating Scale, and the General Self-Efficacy Scale. An LPA was applied to classify learned helplessness patterns, followed by a multivariate logistic regression to determine the influencing factors. The latent profile analysis revealed three distinct profiles of learned helplessness among breast cancer patients undergoing chemotherapy: a "low helplessness-low hopelessness stable profile" (17.0%), a "moderate helplessness-moderate hopelessness fluctuating profile" (52.0%), and a "high helplessness-high hopelessness profile" (31.0%). The multivariable logistic regression revealed that age range 18-44 years, low monthly household income per capita, fatigue, and illness perception were significantly associated with the "high helplessness-high hopelessness profile" (P < 0.05). Conversely, the age range 45-59 years was significantly associated with the "moderate helplessness-moderate hopelessness fluctuating profile" (P < 0.001). Furthermore, experiencing ≤2 chemotherapy-related side effects, a higher level of perceived social support, and greater self-efficacy were significant predictors of membership in the "low helplessness-low hopelessness profile" (P < 0.05). Breast cancer chemotherapy patients were categorized into three distinct subgroups, which were influenced by age, income, fatigue, treatment side effects, illness perception, self-efficacy, and social support. Show less

This study aims to identify the latent profiles of sense of coherence (SOC) in patients with advanced cancer and explore its influencing factors encompassing sociodemographic and clinical characteristics, and generalized resistance resources (GRRs). A cross-sectional study of 262 patients with advanced cancer was conducted by convenience sampling in Guangzhou, China, from September 2023 to July 2024. Data were collected including sociodemographic and clinical characteristics, SOC-13, Revised Life Orientation Test (LOT-R), Rosenberg Self-Esteem Scale (RSES), Inner Peace State Scale (IPSS), Gratitude Questionnaire-6 (GQ-6), and Social Support Rating Scale (SSRS). Statistical analysis was performed using latent profile analysis (LPA) and multivariate logistic regression analysis. Three latent profiles of SOC were identified: low SOC and low comprehensibility group (29.01%), moderate SOC and high meaningfulness group (40.08%), and high SOC and high manageability group (30.91%). This study found that SOC was impacted by self-perceived severity of the disease and GRRs including optimism, self-esteem, and inner peace ( SOC in patients with advanced cancer exhibited different characteristics. Enhancing positive disease perception and GRRs including optimism, self-esteem, and inner peace may be effective strategies for improving their SOC. Healthcare professionals can formulate strategies such as tailored health education, symptom management, and positive psychological interventions to enhance SOC in patients with advanced cancer. Show less

Elevated lipoprotein(a) [Lp(a)] is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD), yet testing remains low. As our health system has expanded its efforts to increase Lp(a) awareness, we evaluated testing rates and their impact on care. Lp(a) testing rates were collected through electronic health record queries between 1/1/2022 to 12/31/2024. Baseline demographics, ASCVD status, Lp(a) testing rates by specialty, lipid lowering therapy (LLT) prescriptions and number of cardiology referrals were collected. 450,412 outpatients had ≥1 lipid panel order and 3.7 % ( While Lp(a) testing was low, it increased substantially over time. High risk Lp(a) levels were found irrespective of ASCVD status and were associated with more aggressive treatment. Systematic strategies to increase Lp(a) awareness and testing are warranted to mitigate cardiovascular risk. Show less

Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfunction, therefore, the development of alternative therapies is critical due to the global shortage of donor corneas. In our previous study, we confirmed that corneal stromal cells (CSCs) secretion can promote corneal endothelial cells (CEnCs) proliferation. This effect can be enhanced by treatment with lysophosphatidic acid (LPA), a bioactive phospholipid. Nevertheless, the components involved in CSC secretion remain to be elucidated. In this study, we investigated the therapeutic potential of CSC-derived exosomes and exosomal microRNAs (miRNAs) for enhancing CEnCs proliferation and corneal endothelial healing. CSC exosomes were characterized via nanoparticle tracking (NTA), transmission electron microscopy (TEM), and immunoassays. The miRNA expression profiles of CSC exosomes were identified via RNA sequencing, revealing a total of 767 distinct miRNAs. The proliferative effects of CSC exosomes and exosomal miR-221-3p were increased by LPA. Ectopic expression of miR-221-3p further increased CEnC proliferation and suppressed the expression of the CDK inhibitor p27 Show less

This study aimed to investigate the latent profiles of clinical nurse preceptors (CNPs)' compassion fatigue (CF), identify the influencing factors, and examine their association with work alienation. Between July and August 2025, 340 nurse preceptors from a tertiary grade A general hospital in Zhejiang Province were recruited as participants using convenience sampling. The Chinese version of the Professional Quality of Life Scale Version 5 (ProQOL-5) and the Work Alienation Scale (WAS) were used to assess compassion fatigue and work alienation, respectively. Demographic information was also collected from the participants. Latent Profile Analysis (LPA) was employed to identify potential profiles of compassion fatigue. After screening variables through univariate analysis and multicollinearity tests, multinomial logistic regression was used to assess the influencing factors. Furthermore, a one-way ANOVA was conducted to examine differences in work alienation among different potential profiles, and the results were interpreted based on the job demands-resources (JD-R) model theoretical framework. A total of 320 CNPs were included in the final analysis. The findings of the latent profile analysis indicated that three latent profiles of CNPs' compassion fatigue were identified: high-satisfaction-low-exhaustion group (n = 56, 17.5%), moderate compassion fatigue group (n = 160, 50%), and severe exhaustion group (n = 104, 32.5%). Multinomial logistic regression analysis showed that age, marital status, education, years of preceptorship, experience, employment type, and professional title were significant predictors of compassion fatigue among CNPs. There were statistically significant differences in the work alienation scores among the three latent profiles (P < 0.001). CNPs' compassion fatigue can be categorised into three types, with significant heterogeneity observed among them. Notable differences exist in work alienation among CNPs with different compassion fatigue types. These findings suggest that clinical managers and educators should develop targeted interventions and support systems based on these circumstances. Therefore, formulating such management strategies is crucial for alleviating work alienation among CNPs and will help improve nurse retention rates and the quality of clinical education. Show less

The associations between 24-h movement behaviours (24 h MBs) and emotional and behavioural problems (EBPs) in early years are not well understood. This study examined these associations in a nationally representative sample of Chinese preschoolers. As part of the Chinese cohort of the SUNRISE International Study of Movement Behaviors in the Early Years main study, this research recruited 1316 children aged 3-4 years through multistage stratified cluster sampling in urban and rural areas across seven major administrative regions in China. Moderate- to vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA) and sedentary behaviour (SED) were measured using 24-h accelerometry over five consecutive days. Sleep duration was parent-reported. EBPs were evaluated using the parent-rated Strengths and Difficulties Questionnaire (SDQ), which assesses total difficulties, internalising problems, externalising problems and prosocial behaviour. Compositional multiple linear regression was employed to analyse the relationships between 24 h MBs and EBPs. Compositional isotemporal substitution was also utilised to predict changes in EBPs due to reallocating time among 24 h MBs. Isotemporal substitution analyses revealed that replacing as little as 1 min of MVPA, LPA or SED with sleep was associated with significant reductions in total difficulties (β Increasing LPA by reducing MVPA or SED was significantly associated with improvements in internalising and conduct problems, whereas increasing sleep to decrease MVPA or SED-even by small amounts-was consistently associated with improvements in EBPs across all SDQ subscales. However, increasing LPA at the expense of sleep exacerbates total difficulties and externalising problems. Promoting diverse LPA opportunities alongside sufficient sleep, while maintaining a balance between them, is essential for supporting preschoolers' emotional and behavioural development. Show less

Lupus nephritis (LN) is a severe autoimmune disease often complicated by steroid resistance (SR), leading to treatment failure and poor prognosis like atherosclerosis (AS). Our study found that Panax notoginseng saponins (PNS) improve lipid metabolism and prevent AS in steroid-resistant LN by up-regulating PPARγ, though mechanisms are unclear. Recent research highlights the roles of macrophages, with M1 Mø promoting inflammation and M2 Mø providing protection, as PPARγ influences Mø's polarization, linking it to inflammation and M2 polarization, necessitating further investigation. Therefore, we conduct this study to investigate the regulatory effect of PNS on the "Mø M2 polarization-PPARγ" positive regulation, endeavoring to elucidate its therapeutic potential of delaying AS and reversing SR in LN. PPARγ expression in polarized Mø was measured via PCR and WB, while M1/M2 biomarkers and cytokines, influenced by PPARγ modulation, were assessed using flow cytometry and ELISA. In mouse Mø treated with PNS, IL-4, or both, PPARγ and cytokines were measured. ICR and MRL/lpr mice were used to establish an in vivo SR model to confirm PNS's role in M2 polarization of Mø and AS protection by analyzing blood lipid levels, iNOS, Lp(a), and apoptosis rates through WB, immunohistochemistry, HE-staining, and TUNEL. PNS's efficacy in renal protection and SR reversal was evaluated through Scr, BUN, urine protein, renal pathology, and P-gp; MDR1 expression was assessed via biochemical detection, HE-staining, flow cytometry, and WB. This study confirmed that PNS upregulates PPARγ and promotes M2 polarization, improving abdominal aorta pathology and delaying AS. It also enhances renal function and reverses SR by reducing P-gp and MDR1. This study shows that PNS promotes Mø polarization to M2 and enhances PPARγ expression, effectively preventing AS, improving renal function, and reversing SR in LN, offering insights for LN treatment and expanding PNS's therapeutic benefits for future research. 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

The COVID-19 pandemic has significantly disrupted educational style, potentially affecting the learning adaptation of nursing freshmen who are integral to the future nursing workforce. This study aimed to identify distinct subgroups of nursing freshmen based on their bioecological attributes related to learning adaptation during the pandemic. A multicenter, cross-sectional study was conducted of 1170 first-year nursing students from six higher education institutions in China. Learning adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction, were investigated. Latent Profile Analysis (LPA) was utilized to identify distinct profiles. Descriptive statistics indicated a positive level of learning adaptation among participants, with an overall mean score of 3.51 ± 0.57. LPA revealed four distinct profiles: 'Struggling Learners' (5.47%), 'Moderate Engagers' (70.60%), 'Adaptable Strivers' (18.29%), and 'Optimal Adapters' (5.64%), which demonstrated significant differences in adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction tendencies (P < 0.05). The study's findings emphasize the heterogeneity in learning adaptation among nursing freshmen and the importance of considering bioecological attributes when developing educational interventions during crisis. Recognizing these profiles can guide the development of targeted strategies to enhance student adaptation and academic achievement. Show less

This study explored how minority stress and social safety jointly shape mental health among Taiwanese sexual minority men (SMM) through the identification of psychosocial profiles and their associations with depression. Between April and May 2023, 415 Taiwanese SMM completed an online cross-sectional survey. Latent profile analysis (LPA) identified groups based on minority stress (sexuality-related discrimination, acceptance concerns, internalized homonegativity) and social safety (identity affirmation, family support, community connectedness) indicators. Multinomial logistic regression examined sociodemographic correlates of profile membership, and linear and binary logistic regressions assessed associations with depressive symptom severity (DSS) and major depressive disorder (MDD). LPA identified three distinct profiles: "Moderate Minority Stress-Low Social Safety" (MMS-LSS; These findings revealed diverse experiences of minority stress and social safety among Taiwanese SMM and their implications for depression, supporting culturally responsive interventions. Show less

BackgroundLogopenic primary progressive aphasia (LPA) is often associated with Alzheimer's disease (AD) pathology. However, few studies have compared cortical atrophy patterns in LPA and AD and their association with cognitive performance.ObjectiveTo identify atrophy patterns specific to LPA and determine whether those patterns relate to deficits in specific cognitive domains.MethodsElectronic health records from 2014-2024 were retrospectively reviewed to identify patients with LPA who had undergone MRI and neuropsychological (NP) examinations. Patients with LPA (n = 26) were matched in terms of age, sex, education, and symptom duration to patients with amnestic mild cognitive impairment (aMCI; n = 13). Logistic regression was used to assess group differences in MRI measures of cortical volume and thickness. Cluster analysis was used to identify patterns of atrophy that were associated with specific cognitive domains.ResultsThe LPA group performed significantly worse than the aMCI group on NP measures assessing verbal learning, attention/working memory, language, and executive functioning (p < 0.05). Compared to the aMCI group, the LPA group demonstrated both smaller and thinner cortex in the left lateral aspect of the superior temporal gyrus, superior temporal sulcus, and fusiform gyrus (p < 0.05), with the left superior temporal sulcus providing the most accurate measure of discrimination. Severity of language related cognitive deficits was not associated with a specific cluster in the LPA group.ConclusionsPatients with LPA demonstrate specific patterns of cortical atrophy that are distinguishable from atrophy due to aMCI and may be useful for diagnostic purposes. Show less

This study aimed to assess the knowledge, attitudes, and practices (KAP) of patients with lower limb arteriosclerosis obliterans (ASO) toward their disease. This cross-sectional study was conducted at 3 tertiary hospitals in Chengdu between August 2023 and January 2024 and included patients with lower limb ASO. Data were collected using an interviewer-administered questionnaire that captured demographic information and KAP scores. A latent profile analysis (LPA) was used to identify the KAP patterns among participants. A total of 515 nonproblematic questionnaires were collected, yielding an effective response rate of 95.72%. Among the respondents, 395 (76.85%) were male, with a disease course of 15.96 ± 17.55 months. The knowledge, attitude, and practice scores were 5.27 ± 4.69 (possible range: 0-22), 17.65 ± 2.86 (possible range: 5-25), and 107.63 ± 17.15 (possible range: 33-165), respectively. LPA identified 4 participant profiles: Profile 1 (high attitude, low practice), Profile 2 (low attitude, high practice), Profile 3 (low attitude, low practice), and Profile 4 (high attitude, high practice). Significant differences were found among profiles in residence (P = 0.028), medical insurance (P = 0.043), self-efficacy (P < 0.001), and patient activation (P < 0.001). Patients with lower limb ASO demonstrated inadequate knowledge but moderate levels of attitude and practice. Residence, medical insurance, self-efficacy, and patient activation may affect the KAP patterns of the patients. These findings suggest that tailored interventions targeting distinct patient profiles, while considering broader social determinants of health, may be critical to improving self-management and outcomes. Show less

Acetyl-CoA synthetase 2 (ACSS2) is the obligatory gatekeeper for converting rumen-derived acetate into acetyl-CoA in ruminants. However, whether ACSS2 actively regulates the transcriptional networks governing lactation, beyond its catalytic role, remains unclear. This study aimed to elucidate the molecular characteristics of buffalo ACSS2 and investigate its function as a central node in the metabolic-transcriptional circuitry of buffalo mammary epithelial cells (BuMECs). The complete coding sequence of buffalo ACSS2 was characterized, and its expression was analyzed across lactation stages. Subcellular localization was determined via high-resolution confocal microscopy. We utilized siRNA-mediated knockdown in BuMECs to assess cell viability, triglyceride (TAG) content, and the expression of core metabolic and regulatory genes to dissect the underlying molecular mechanisms. ACSS2 expression was highly enriched in lactating mammary tissue, and the protein exhibited a dual nucleocytoplasmic distribution. ACSS2 knockdown induced a "dual collapse" of cellular function: it severely impaired lipogenesis (significantly reducing intracellular TAG and downregulating FASN, ACACA, SCD, CD36, LPL, FABP3, DGAT1, DGAT2 and AGPAT6) and arrested cell proliferation (downregulating the G1/S phase regulators CCND1, CCNE1, CDK2 and CDK4). Mechanistically, ACSS2 depletion dismantled the transcriptional machinery itself, suppressing the mRNA levels of master regulators SREBF1 and PPARG. Crucially, this collapse was accompanied by the paradoxical upregulation of the SREBP1-inhibitor INSIG1, suggesting that metabolic stress triggers an INSIG1-mediated blockade of the feedback loop. This study establishes ACSS2 as a critical metabolic checkpoint in the buffalo mammary gland, rather than a passive enzyme. We propose a model where ACSS2 maintains a reciprocal positive feedback loop with SREBP1 and PPARG. By ensuring sufficient acetyl-CoA to suppress INSIG1 and support histone acetylation (implied by nuclear localization), ACSS2 couples substrate availability to the stability of the lipogenic program and cell cycle progression. These findings reveal an evolutionarily conserved metabolic-epigenetic axis essential for high-efficiency lactation in ruminants. Show less

Although glass-based long-persistent luminescence (LPL) materials offer superior transparency and integration capability compared with conventional phosphors, their emission has been predominantly restricted to the blue-green region, leaving warm-color LPL largely unexplored. In this work, Mn Show less

Backfat thickness, a key selection trait in pig-breeding programmes, has traditionally been measured as a homogeneous layer. However, backfat is anatomically structured into three distinct layers, and each layer likely contributes differently to carcass quality. In addition, previous studies have shown that the deposition of the third layer of backfat is phenotypically correlated with intramuscular fat (IMF). Therefore, targeted selection for specific backfat layers, particularly the third layer, represents a potential strategy to increase IMF content while maintaining a high lean meat percentage. However, the genetic architecture of these distinct porcine backfat layers remains poorly understood. The aim of this study was to estimate the genetic parameters and identify key candidate genes underlying the three backfat layers. We collected B-mode ultrasound images from 561 Landrace pigs to measure individual layer thickness, followed by DNA extraction, genotyping, genetic parameter estimation, and a genome-wide association study (GWAS). Our measurements showed that the first layer of backfat (FBF) is the thickest, followed by the second (SBF) and the third (TBF) layers. Genetic parameter estimation yielded heritability estimates of 0.37, 0.42, 0.38, 0.34, 0.32, 0.24, and 0.21 for total backfat (BF), FBF, FBF/BF, SBF, SBF/BF, TBF, and TBF/BF, respectively. Through integrated analysis of GWAS, Bayesian fine-mapping, and gene annotation, we identified 15 non-redundant candidate genes associated with different backfat layers. These included two genes (SOAT1 and ACBD6) shared by BF and SBF, LPL for BF and FBF, and CAND1 for TBF and TBF/BF. Additionally, SERPINA12 and SERPINA6 were associated with BF; PRKAG1 and PRDM16 with FBF; EPRS1 and SLC39A10 with FBF/BF; PTGES and CRAT with SBF; and ACLY, CAVIN1, and PDZRN3 with SBF/BF. Our results indicate that each layer is governed by a distinct set of genes, which advances our understanding of the genetic basis of backfat layers in pigs. Show less

This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify the pathogenic cause, and provide a basis for the clinical diagnosis, treatment, and genetic counseling of affected children. Clinical data were collected from family members. High-throughput sequencing was performed to identify pathogenic variants in genes associated with HS and FCS in the proband. Suspected pathogenic mutations were confirmed in family members via PCR-Sanger sequencing. Bioinformatics analysis and three-dimensional protein structure prediction were also conducted. The proband presented with severe anemia, splenomegaly, and jaundice. Genetic testing revealed a heterozygous mutation, c.6005G>A (p.Trp2002*), in the spectrin beta chain ( The heterozygous mutations Show less

Organic and organic-inorganic hybrid materials exhibiting room-temperature phosphorescence (RTP) and long persistent luminescence (LPL) materials have attracted growing attention for various time-resolved optoelectronic applications. To date, realizing intrinsically distinct RTP and LPL emissions within a single material system remains elusive, yet it is crucial for unlocking multifunctional applications such as multilevel optical encryption. Here, a Mn Show less

We aimed to investigate whether maternal and fetal genetic predispositions to insulin deficiency and resistance affect offspring fetal growth through distinct pathways in multi-ethnic populations. In 5065 multi-ethnic mother-infant pairs, we examined the conditional associations of maternal and fetal partitioned polygenic risk scores (pPRSs) for type 2 diabetes-related pathways with fetal growth outcomes, including birthweight, sum of skinfold thicknesses (SSF), large-for-gestational-age (LGA) births and small-for-gestational-age (SGA) births. Two-sample Mendelian randomisation (2SMR) in Europeans was performed for triangulation. Exposures were eight type 2 diabetes-related pathways (n=1,812,017), eight beta cell function indices (n=26,356) and two insulin sensitivity indices (n=53,657). Outcomes were maternal and fetal genetically determined birthweight (n=406,063). Mediation analysis was used to assess the mediation effects of maternal glucose levels and BMI on maternal genetic effects and of cord blood C-peptide on fetal genetic effects. Co-localisation analyses were performed to test for shared causal variants. Fetal type 2 diabetes polygenic risk score (PRS) and pPRSs for lipodystrophy-related insulin resistance and impaired fasting glucose (IFG)-related insulin deficiency were associated with lower birthweight and SSF, while maternal type 2 diabetes PRS and pPRSs for IFG-related insulin deficiency and obesity-related insulin resistance were associated with higher offspring birthweight, SSF and LGA. These associations were consistent across five ethnic groups. Maternal post-load hyperglycaemia mediated 44.2% and 34.2% of the effects of type 2 diabetes PRS and IFG pPRS, respectively, while maternal BMI mediated 43.4% of the effect of Obesity pPRS. 2SMR found consistent results in Europeans and further revealed that fetal insulin sensitivity index and corrected insulin response were associated with higher birthweight. Some loci with shared causal variants acted through multiple pathways, including CDKAL1, TCF7L2, ADCY5 and MACF1. Reduced fetal growth may be driven by lipodystrophy-related insulin resistance and IFG-related insulin deficiency pathways. Targeting pregnant women with high type 2 diabetes PRS/pPRS and prescribing interventions to reduce their post-load hyperglycaemia and BMI may help reduce offspring risk of LGA. Show less

Renal tubulointerstitial fibrosis (TIF) is a hallmark pathological feature of diabetic kidney disease (DKD). This study investigates the role and molecular mechanisms of retinol saturase (RetSat) in DKD-associated TIF. RetSat expression was assessed in renal tissues from DKD patients and mice and correlated with the severity of TIF. Functional experiments were conducted RetSat expression was significantly up regulated in the renal tissues of both DKD patients and mice, correlating with the deterioration of TIF. These findings indicate that RetSat promotes TIF in DKD by disrupting the Smurf2-ChREBP ubiquitination axis, highlighting RetSat as a promising therapeutic target for DKD. Show less

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the primary indication for heart transplantation. The intricate and poorly elucidated pathogenesis of genetic DCM, coupled with the paucity of effective therapeutic options, imposes a substantial burden on both patients and their families. In this study, we identified a novel MYBPC3 mutation (c.194C > T) in a patient diagnosed with DCM and established a patient-specific human induced pluripotent stem cell (hiPSC) model. Cardiomyocytes derived from these patient-specific hiPSCs (hiPSC-CMs) exhibited hallmark features of DCM, including cell enlargement, aberrant distribution of sarcomeric α-actinin, and dysregulated calcium ion homeostasis, as compared to control hiPSC-CMs derived from a healthy individual. RNA sequencing analysis revealed a significant upregulation of CASQ2, which encodes calsequestrin, a protein that binds to Ryanodine receptor 2 (RyR2). Notably, treatment with the RyR2 inhibitor ryanodine effectively restored the abnormal calcium transients observed in DCM-hiPSC-CMs. In summary, our findings provide compelling evidence that the c.194 C > T mutation of MYBPC3 plays a definitive pathogenic role in DCM, and that modulation of the RyR2 receptor may alleviate calcium dysregulation in affected cardiomyocytes. These insights enhance our understanding of the molecular mechanisms underlying DCM and offer a promising therapeutic strategy for patients with calcium ion dysregulation associated with this condition. Show less

Radiotherapy (RT) for breast cancer may increase atrial fibrillation (AF) risk. This study explored the association between RT and expression of AF-related genes in breast tumor tissues. A total of 1094 breast cancer patients (RT group: 1020; non-RT group: 74) were included based on inclusion criteria. Clinical data and RNA-seq profiles (TPM) were retrieved. Six AF-related genes (MYBPC3, LMNA, PKP2, FAM189A2, KDM5B, MYL4) were analyzed. Gene expression was compared using Wilcoxon rank-sum test after Log2(TPM + 1) transformation. Subgroup analyses were conducted by AJCC stage (I–III), laterality (left/right), age (< 65/≥65 years), clinical subtype (Luminal, HER2-positive, Triple-negative), and PAM50 molecular subtype (Basal, Her2, LumA, LumB, Normal). Multivariate linear regression was applied to evaluate RT’s independent effect on gene expression. In tumor tissues, expression levels of MYBPC3, LMNA, and MYL4 were significantly higher in the RT group compared to the non-RT group.Subgroup analysis revealed higher MYBPC3 expression in the RT group specifically in Stage III tumors, but lower expression in left-sided tumors and in patients < 65 years old. LMNA expression was higher in the RT group in Stage III tumors. MYL4 expression was higher in the RT group in Stage II tumors, in both left and right-sided tumors, and in both age groups (< 65 and ≥ 65 years). No significant differences were found across clinical or molecular subtypes for any gene.Multivariate regression confirmed RT as an independent predictor of increased MYL4 expression (β = 0.204), but not for MYBPC3 or LMNA expression. Sensitivity analysis in the 45–65 age subgroup supports the above findings. Based on tumor tissue analysis, breast cancer radiotherapy is associated with altered expression of AF-related genes (particularly MYL4) in tumor tissues, suggesting a potential molecular link worthy of further exploration in relation to atrial fibrillation. These findings warrant future validation in cardiac or circulatory tissues. The online version contains supplementary material available at 10.1007/s12672-026-04468-5. Show less

Rodents are widely used in immunology but do not always recapitulate human immune functions. The tree shrew (Tupaia belangeri) is phylogenetically closer to primates than rodents and may help bridge this gap, yet its immune system has not been comprehensively characterised at single-cell resolution. Here, we present a single-cell transcriptomic atlas of the tree shrew immune system, profiling 39 cell types across 12 tissues. We uncover human-like tonsillar structures and two transcriptionally distinct splenic macrophage subsets: an NR1H3 Show less

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a clinically heterogeneous disease lacking approved therapies. To assess genetic susceptibility toward a specific metabolic phenotype, we performed a genome-wide association study on plasma biomarker levels (mGWAS) in patients with ME/CFS ( Show less

Regulation of mRNA translation is essential for cellular homeostasis, and its dysregulation contributes to cancer, neurodegeneration, and developmental disorders. Stress granules are cytosolic condensates that form during stress-induced translation arrest and are enriched in mRNAs, translation factors, and RNA-binding proteins, but how stress granule proteins modulate translation remains poorly understood. Here, we identify the stress granule components Proline-Rich Coiled-Coil A, B, and C (PRRC2 proteins) as translation regulators. PRRC2 proteins are large, intrinsically disordered paralogs conserved across jawed vertebrates. Functional proteomics revealed that all PRRC2 proteins associate with the 48S translation initiation complex (PIC), whereas PRRC2B additionally interacts with nuclear proteins. Under stress, the proximal interaction network of PRRC2 proteins undergoes dynamic remodeling, including increased interactions with the stress granule scaffold G3BP1. Genetic perturbation shows that the PRRC2 proteins influence stress granule assembly in a context-specific manner, and are collectively required for cell growth in basal conditions due to their essential role in translation. Cells with reduced PRRC2 proteins exhibit a significant reduction in the abundance of more than half of the proteome, with a bias toward translational targets of eIF3d and eIF4G2. Interaction domain mapping and AlphaFold3 modeling revealed that an α helix within the putative coiled-coil domain of PRRC2C mediates interactions with the eIF3 core complex. This modeling places the PRRC2C α helix in a previously unassigned region of a published cryo-EM density map, validating the protein interaction and the mechanistic role of PRRC2C in translation control. Together, these findings establish PRRC2 proteins as components of the translation initiation machinery that regulate translation through their interactions with the eIF3 complex and other components of the 48S PIC factors, providing a direct mechanistic link between stress granule proteins and translational control. Show less

Colorectal cancer (CRC) is a highly aggressive malignancy prone to liver metastasis, which significantly worsens prognosis of patients. Autophagy supports tumor cell survival by meeting metabolic demands and evading programmed cell death. This study aimed to develop a prognostic risk signature for CRC patients by integrating autophagy- and metastasis-related genes and to investigate its association with the tumor immune microenvironment and implications for immunotherapy. Weighted gene co-expression network analysis (WGCNA) identified candidate genes related to autophagy and liver metastasis. Univariate Cox and LASSO regression analyses were employed to develop a risk signature in the TCGA cohort, which was subsequently validated using an independent GEO cohort. Functional enrichment, immune infiltration, the heterogeneity and dynamics of macrophages and A prognostic risk signature incorporating six biomarkers ( In our study, we developed and validated a novel autophagy- and liver metastasis-associated prognostic signature for CRC. The risk signature effectively predicts alterations in the tumor immune microenvironment, immunotherapy, chemotherapy sensitivity and intercellular communication across different risk groups. Importantly, our findings reveal that autophagy and liver metastasis synergistically foster an immunosuppressive microenvironment, highlighting a potential target for therapeutic intervention. Show less

Thoracic aortic dissection (TAD) is a life-threatening acute vascular condition with high morbidity and mortality. Endothelial cells (ECs) are critical for maintaining vascular homeostasis, yet the role of endothelial-to-mesenchymal transition (EndoMT), a key cell-fate process in vascular development and disease, in TAD remains poorly defined. Furthermore, the functional role of PDK4 (pyruvate dehydrogenase kinase 4) as a driver of this pathological cell-fate transition has not been elucidated. To delineate the mechanistic contribution of EndoMT to TAD, we integrated transcriptomic profiling and immunofluorescence analysis in human aortic specimens and a β-aminopropionitrile-induced murine model. Following the identification of PDK4 as a critical downstream effector of EndoMT signaling via RNA-sequencing and chromatin immunoprecipitation assays, its functional role was validated using conditional EC-specific knockout mice and adeno-associated virus-mediated endothelial gene modulation. Serum samples were collected, and ELISA was used to measure levels of endothelial injury markers for assessing EC-dysfunction. In addition, therapeutic potential was assessed using dichloroacetate, a small-molecule PDK4 inhibitor. A robust activation of the EndoMT gene program was observed in both human TAD specimens and murine aortic tissues, characterized by the loss of endothelial identity and acquisition of mesenchymal traits. Transcriptomic screening pinpointed PDK4 as a critical mediator upregulated during EndoMT. Mechanistically, we demonstrated that the transcription factor Our findings demonstrate that the pathological EndoMT program is activated in ECs by PDK4, which aggravates TAD development in β-aminopropionitrile-induced mouse models, highlighting PDK4 as a promising therapeutic target for TAD. Show less