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BACKGROUND: Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. METHODS AND RESULTS: In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow-up of 12.5 years. The within-participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Grays competing risk model, adjusting for confounding factors and participant-specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03-1.08], P

Abstract Background This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers’ caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals. Methods We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi’s seven-step analysis method. Results We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support. Conclusion There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers’ awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception.

Abstract Objective Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene‐1 (IRG1) and the IRG1–itaconic acid–NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4‐octyl itaconate (4‐OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute‐onset NMOSD and to investigate the inhibitory effects of 4‐OI on NLRP3 inflammasome activation via the IRG1–itaconic acid–NLRP3 pathway in monocytes and macrophages by using in vitro models. Methods Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3‐related inflammatory factors. Subsequently, the effects of 4‐OI on the IRG1–itaconic acid–NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP‐1 cells) via in vitro experiments. Results Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4‐OI inhibited the activation of the IRG1–itaconic acid–NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. Interpretation 4‐OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD‐derived PBMCs and in a human macrophage model. Thus, 4‐OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

Abstract Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole‐induced PCOS‐related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p

The changes that COVID-19 pandemic has brought upon the world are unprecedented. Its impact on students' learning is equally profound, making it critical to heed students' academic achievement effects that may derive from these alterations. Therefore, the present study explored an integrative model of mental health, self-regulated learning and academic achievement among adolescents during the pandemic. Participants were 1001 senior high school students (M[-subscript age] = 17.00, SD[subscript age] = 0.78, 48.7% female) from China. Results showed that the degree to which students were mentally healthy was not significantly related to academic achievement, whereas academic achievement and mental health were positively associated with self-regulated learning. Following structural equation modelling analysis, the effect of mental health on academic achievement was fully mediated by self-regulated learning. Taken together, the findings emphasised the necessity of developing self-regulated learning strategies during public health emergencies and have clinical and educational implications for planning psychological interventions in order to improve mental health and academic performance as well.

Objectives: Non-tuberculous mycobacteria (NTM) frequently colonize the airways of patients with bronchiectasis; however, there has been limited research into airway microbiota composition and predisposing factors for NTM detection during acute bronchiectasis exacerbations. Methods: This study enrolled 34 patients with bronchiectasis experiencing acute exacerbations. Metagenomic next-generation sequencing was used to detect microbiota in bronchoalveolar lavage fluid (BALF), and bioinformatics methods were used for the comparative analysis of meaningful microbiota in the BALF of patients with acute exacerbations of bronchiectasis. A correlation analysis was conducted to identify susceptibility factors for NTM in patients with bronchiectasis. Results: Compared with patients with community-acquired pneumonia, patients with bronchiectasis had higher detection rates of NTM (38.2%), Pseudomonas aeruginosa, and Haemophilus influenzae. Patients with NTM-positive bronchiectasis had lower body mass index and lipid profiles than patients who were NTM-negative. Metagenomic next-generation sequencing of BALF revealed patients who were NTM-positive had increased relative abundance of Rothia and other anaerobic genera compared with patients who were NTM-negative. Patients who were NTM-positive also showed higher levels of Streptococcus parasanguinis at the species level. Elevated Rothia mucilaginosa and S. parasanguinis correlated with decreased percentages of clusters of differentiation 3+ T lymphocytes and clusters of differentiation 3+ T-cell subgroups in peripheral blood. Conclusions: NTM colonization increases the risk of acute bronchiectasis exacerbations. Low body mass index, lipid levels, and isolation of R. mucilaginosa and S. parasanguinis in BALF are susceptibility factors for NTM colonization in patients with bronchiectasis.

ObjectiveWe investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic.MethodsThis retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records.ResultsThe overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p

ObjectiveTo investigate the pathogenesis of Primary Angle-Closure Glaucoma (PACG) and its relationship with the anatomical structure of the anterior segment by obtaining biometric parameters using the IOL-Master 700.MethodsA retrospective case–control study was conducted. Clinical data from 39 PACG patients and 40 normal controls treated at the Aier Eye Hospital affiliated with Wuhan University from January to December 2022 were collected. Anterior chamber depth (AC), white-to-white (WTW), lens thickness (LT), central corneal thickness (CCT), axial length (AL), corneal curvature (K1), corneal curvature (K2), and lens position (LP) were measured using the IOL-Master 700 to analyze the characteristics and differences in the anterior segment structure of both groups. Statistical methods included independent sample t-tests and logistic regression analysis.ResultsSignificant differences were found in the anterior segment biometric parameters between PACG patients and normal controls (p

IntroductionWorkplace violence against healthcare workers has become a serious global public health problem. The incidence of workplace violence towards Psychiatric nurses is higher than in all other medical institutions, up to 84.2% per year. It not only negatively affects many aspects of healthcare workers’ lives, but also destroys the harmony of the nurse–patient relationship and reduces the quality of nursing care. The number of psychiatric nurses in China was approximately 96,000, far lower than most other countries and unable to meet the growing demand for mental health. However, the increase in workplace violence has future exacerbates the current shortage of nurses. Therefore, it is necessary to develop effective strategies to prevent psychiatric nurses from suffering from workplace violence, thereby to reduce nurse turnover and improve the quality of nursing care. A comprehensive understanding of psychiatric nurses’ preferences and priorities for preventing workplace violence is an important prerequisite before formulating strategies and taking measures. Unfortunately, to date, no research has investigated the psychiatric nurses’ preferences. Therefore, a discrete choice experiment (DCE) is conducting to explore the psychiatric nurses’ preferences for workplace violence prevention. This article reports on methodological details of the DCE.Methods and analysisSix attributes were developed through a literature review, one-on-one interviews and focus group discussions. D-efficient design in NGENE was used to generate choice sets. SPSS 24.0 will be used for descriptive analysis of social Demography, and Stata 16.0 will be used for analysis of DCE data. A multinomial logit model will be used to preliminarily explore trade-offs between workplace violence prevention characteristics included in the choice tasks. Then, in a mixed logit model, we plan to choose some arbitrarily defined base violence prevention program and will use the nlcom command to evaluate the probability of an alternative violence prevention program.Ethics and disseminationThe study was approved by the relevant ethics committees. Our findings will emphasize priority intervention areas based on the preferences of psychiatric nurses and provide references for hospitals to develop and improve workplace violence prevention strategies. The results will be shared through seminars, policy briefs, peer-reviewed journal articles and online blogs.

Gastrodia elata Blume (G. elata), listed as one of the 34 precious Chinese medicines, servers a dual purpose as both a medicinal herb and a food source. Polysaccharide is the main active ingredient in G. elata, which has pharmacological activities such as immune regulation, anti-oxidation, anti-cancer, anti-aging, neuroprotection and antibacterial activity and so on. The biological activities of G. elata polysaccharide (GPs) is closely related to its chemical structures. However, no a review has synthetically summarized the chemical structures and pharmacological activities of GPs. This study delves into the chemical structures, pharmacological action of GPs, offering insights for the future development an application of these compounds.

Abstract Based on the research progress and traditional usage with whole herbal of the TCM "Tianma", chemical studies herein on the flower branch of Gastrodia elata were carried out in-depth and got 13 compounds including the gastrodinols (1–4), the flavonoid morins (5–8, 11–12), together with the specialist mulberrofurans (9, 13) and gastrodiamide (10) for the first time from the species. The antibacterial and cholinesterase inhibitory activities were then evaluated and the results showed that compounds 5, 11, 12, 13 have good activity against anti-methicillin-resistant Staphylococcus aureus, and compounds 9, 13 had good acetylcholinesterase inhibitory activity. All these results provide new chemical composition for better understanding the traditional application of "Tianma" and for exploring new pharmacological ingredients. Graphical Abstract

Abstract Background The quality of transitional care is closely related to the health outcomes of patients, and understanding the status of transitional care for patients is crucial to improving the health outcomes of patients. Therefore, this study aims to investigate the quality of transitional care in elderly patients with chronic diseases and analyze its influencing factors, to provide a basis for improving transitional care services. Methods This is a cross-sectional study. We used the Chinese version of the Partners at Care Transitions Measure (PACT-M) to survey patients with chronic diseases aged 60 years and older who were about to be discharged from five tertiary hospitals in Henan and Shanxi provinces. We used the mean ± standard deviation to describe the quality of transitional care, t-test or one-way ANOVA, and regression analysis to explore the factors affecting the quality of transitional care for patients. Results 182 elderly patients with chronic diseases aged ≥ 60 years completed the PACT-M survey. The scores of PACT-M1 and PACT-M2 were (30.69 ± 7.87) and (25.59 ± 7.14) points, respectively. The results of the t-test or one-way ANOVA showed that the patient’s marital status, ethnicity, religion, educational level, preretirement occupation, residence, household income per month, and living situation had an impact on the quality of transitional care for elderly patients with chronic diseases (P

Abstract Aim This study aimed to assess inclusive leadership and presenteeism among clinical nurses and to examine the moderating effect of perceived organizational support on presenteeism related to the inclusive leadership among nurses. Background Nurses’ presenteeism has become common. In hospitals, inclusive leadership is an acknowledged leadership style that has a positive influence on nurses. However, little emphasis has been paid to research on their relationships and moderating effect. Methods A cross-sectional study was undertaken to assess 2222 nurses using a general information questionnaire, Stanford Presenteeism Scale (SPS-6), Perceived Organisational Support Scale, and Inclusive Leadership Scale. Study variables were analyzed using descriptive statistics, correlation, and structural equation modelling (SEM). Results Presenteeism was relatively severe among clinical nurses. There were correlations between inclusive leadership, perceived organizational support and presenteeism. Perceived organizational support moderated the relationship between inclusive leadership and presenteeism. Discussion and conclusion Nursing managers should actively adopt an inclusive leadership style and improve nurses' sense of perceived organizational support to improve clinical nurses' presenteeism behaviors. Implications for nursing policy and practice Healthcare organizations and nursing managers should pay attention to the psychological needs of their nurses, provide complete understanding and support, encourage staff to actively participate in their work and contribute new ideas and opinions, reduce the incidence of presenteeism, and improve nurses' sense of well-being at work.

Abstract The epithelial–mesenchymal transition (EMT) is a critical tumor invasion and metastasis process. EMT enables tumor cells to migrate, detach from their original location, enter the circulation, circulate within it, and eventually exit from blood arteries to colonize in foreign sites, leading to the development of overt metastases, ultimately resulting in death. EMT is intimately tied to stromal cells around the tumor and is controlled by a range of cytokines secreted by stromal cells. This review summarizes recent research on stromal cell-mediated EMT in tumor invasion and metastasis. We also discuss the effects of various stromal cells on EMT induction and focus on the molecular mechanisms by which several significant stromal cells convert from foes to friends of cancer cells to fuel EMT processes via their secretions in the tumor microenvironment (TME). As a result, a better knowledge of the role of stromal cells in cancer cells’ EMT may pave the path to cancer eradication.

AbstractPlatelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP’s bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP’s IL-1β levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

Abstract Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy‐saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide‐induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

Enhancing learning engagement is a critical challenge in online education. While previous research underscores the importance of feedback, recent studies have shifted focus to students’ perceptions of feedback, which significantly impact learning performance. However, empirical evidence on how these perceptions affect online learning outcomes is limited. Drawing on Self-Determination Theory, this study addresses this gap by employing SEM to analyze the relationships among feedback perception, academic self-efficacy, test anxiety, and online learning engagement. A total of 402 Chinese vocational college students (ages 18–19) completed questionnaires, with statistical analysis conducted using SPSS and Mplus. The study found that perception of feedback directly influences online learning engagement and indirectly affects it through academic self-efficacy and test anxiety, with a total effect value of 0.416. The findings offer valuable insights for educators and suggest directions for future research on feedback perception and online learning engagement.

(1) Background: In lung cancer, the use of small-molecule inhibitors, chemotherapy and immunotherapy has led to unprecedented survival benefits in selected patients. Considering most patients will experience a relapse within a short period of time due to single drug resistance, combination therapy is also particularly important to improve patient prognosis. Therefore, more robust biomarkers to predict responses to immunotherapy, targeted therapy, chemotherapy and rationally drug combination therapies may be helpful in clinical treatment choices. (2) Methods: We defined tumor-specific T cells (TSTs) and their features (TSTGs) by single-cell RNA sequencing. We applied LASSO regression to filter out the most survival-relevant TSTGs to form the Tumor-specific T cell score (TSTS). Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low TSTS groups. (3) Results: We identified six clusters of T cells as TSTs in lung cancer, and four most robust genes from 9 feature genes expressed only on tumor-specific T cells were screened to construct a tumor-specific T cells score (TSTS). TSTS was positively correlated with immune infiltration and angiogenesis and negatively correlated with malignant cell proliferation. Moreover, potential vascular-immune crosstalk in lung cancer provides the theoretical basis for combined anti-angiogenic and immunotherapy. Noticeable, patients in high TSTS had better response to ICB and targeted therapy and patients in the low TSTS group often benefit from chemotherapy. (4) Conclusion: The proposed TSTS is a promising indicator to predict immunotherapy, targeted therapy and chemotherapy responses in lung cancer patients for helping clinical treatment choices.

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.

Abstract Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Abstract Background Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. Methods Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein–protein interactions, and related signaling pathways, etc. Results The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. Conclusion Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

Abstract Background Psoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles. Methods Plasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models. Results Males suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline. Conclusions Sex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.

Abstract The present study endeavors to unveil the progression of research subjects within the realm of China’s ecotranslatology studies through the examination of journal papers in the databases of China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) from 2001 to 2022, utilizing CiteSpace software for mapping and analyzing cooccurrences among authors, institutions, and keywords. The findings indicate that within ecotranslatology studies, a prominent theory-founding research group represented by Hu Gengshen has been established, yet no comparable clusters have been identified among scholars engaged in debate or applied studies. Additionally, a lack of effective cooperation and diversity among research entities as well as inadequate responses to questions and concerns have been observed. Furthermore, research focuses have undergone a shift, progressing from theory founding studies (2001–2008) to confirmation and verification studies (2009–2014) and finally to revision and applied studies (since 2015). Additionally, research topics have transitioned from grand, abstract theoretical foundations to subtle, specific theory revisions and applied translation studies, yet a dearth of quantitative research, comparative studies, or field studies have been conducted. In conclusion, it is suggested that future ecotranslatology studies should be more responsive to doubts and questions, cultivate diverse research entities, and place greater emphasis on field investigation within qualitative research.

Abstract Immune cell infiltration in response to myocyte death regulates extracellular matrix remodeling and scar formation after myocardial infarction (MI). Caspase-recruitment domain family member 9 (CARD9) acts as an adapter that mediates the transduction of pro-inflammatory signaling cascades in innate immunity; however, its role in cardiac injury and repair post-MI remains unclear. We found that Card9 was one of the most upregulated Card genes in the ischemic myocardium of mice. CARD9 expression increased considerably 1 day post-MI and declined by day 7 post-MI. Moreover, CARD9 was mainly expressed in F4/80-positive macrophages. Card9 knockout (KO) led to left ventricular function improvement and infarct scar size reduction in mice 28 days post-MI. Additionally, Card9 KO suppressed cardiomyocyte apoptosis in the border region and attenuated matrix metalloproteinase (MMP) expression. RNA sequencing revealed that Card9 KO significantly suppressed lipocalin 2 (Lcn2) expression post-MI. Both LCN2 and the receptor solute carrier family 22 member 17 (SL22A17) were detected in macrophages. Subsequently, we demonstrated that Card9 overexpression increased LCN2 expression, while Card9 KO inhibited necrotic cell-induced LCN2 upregulation in macrophages, likely through NF-κB. Lcn2 KO showed beneficial effects post-MI, and recombinant LCN2 diminished the protective effects of Card9 KO in vivo. Lcn2 KO reduced MMP9 post-MI, and Lcn2 overexpression increased Mmp9 expression in macrophages. Slc22a17 knockdown in macrophages reduced MMP9 release with recombinant LCN2 treatment. In conclusion, our results demonstrate that macrophage CARD9 mediates the deterioration of cardiac function and adverse remodeling post-MI via LCN2.

AIM: To report a novel splicing mutation in the RPGR gene (encoding retinitis pigmentosa GTPase regulator) in a three-generation Chinese family with X-linked retinitis pigmentosa (XLRP). METHODS: Comprehensive ophthalmic examinations including best corrected visual acuity, fundus photography, vision field, and pattern-visual evoked potential were performed to identify the disease phenotype of a six-year-old boy from the family (proband). Genomic DNA was extracted from peripheral blood of five available members of the pedigree. Whole-exome sequencing (WES), Sanger sequencing, and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR. Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants. RESULTS: The proband was diagnosed as having retinitis pigmentosa (RP). He had severe symptoms with early onset. A novel splicing mutation, c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing. Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped, leading to the subsequent deletion of 623 correct amino acids (c.529_619del p.Val177Glnfs*16). CONCLUSION: We identify a novel splice donor site mutation causing aberrant splicing of RPGR. Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

Accurate and reliable estimation of actual evapotranspiration (AET) is essential for various hydrological studies, including drought prediction, water resource management, and the analysis of atmospheric–terrestrial carbon exchanges. Gridded AET products offer potential for application in ungauged areas, but their uncertainties may be significant, making it difficult to identify the best products for specific regions. While in situ data directly estimate gridded ET products, their applicability is limited in ungauged areas that require FLUXNET data. This paper employs an Extended Triple Collocation (ETC) method to estimate the uncertainty of Global Land Evaporation Amsterdam Model (GLEAM), Famine Early Warning Systems Network (FLDAS), and Maximum Entropy Production (MEP) AET product without requiring prior information. Subsequently, a merged ET product is generated by combining ET estimates from three original products. Furthermore, the study quantifies the uncertainty of each individual product across different vegetation covers and then compares three original products and the Merged ET with data from 645 in situ sites. The results indicate that GLEAM covers the largest area, accounting for 39.1% based on the correlation coefficient criterion and 39.9% based on the error variation criterion. Meanwhile, FLDAS and MEP exhibit similar performance characteristics. The merged ET derived from the ETC method demonstrates the ability to mitigate uncertainty in ET estimates in North American (NA) and European (EU) regions, as well as tundra, forest, grassland, and shrubland areas. This merged ET could be effectively utilized to reduce uncertainty in AET estimates from multiple products for ungauged areas.