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Dan-Dan Li,1,&ast; Xue Yang,1,&ast; Yang Yang,2,&ast; Li-Hua Zhao,1 Tian-Tian Zhang,3 Yi-Nan Wang,1 Jian-Bin Su,1 Li-Hua Wang,4 Hai-Yan Shi3 1Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 2Department of General Practice, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 4Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Hua Wang, Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email wlh512512@163.com Hai-Yan Shi, Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email 1198827119@qq.comBackground: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied.Methods: A total of 615 patients with T2D were selected by convenient sampling. The patients were investigated with the International Physical Activity Questionnaire (IPAQ-S). Moreover, biochemical indices were collected, and the progression of the body composition of the subjects was determined via dual-energy X-ray absorptiometry (DXA). The variables included lumbar bone mineral density (LSBMD), femoral neck bone mineral density (FNBMD), hip bone mineral density (HBMD), whole-body bone mineral density (TBMD), limb skeletal muscle mass index (ASMI), whole-body fat percentage (B-FAT) and trunk fat percentage (T-FAT). Moreover, the levels of physical activity (high level of physical activity [H-PA], medium level of physical activity [M-PA] and low level of physical activity [L-PA]) were divided into three groups to analyze the changes in patient body composition with changes in physical activity level.Results: One-way analysis of variance showed that β-CTX, TP1NP, HbA1c, B-FAT and T-FAT increased significantly (p< 0.05), while 25(OH)D, LSBMD, FNBMD, HBMD, TBMD and ASMI decreased significantly (p< 0.001) with the decrease of physical activity. However, there was no significant difference in serum lipids between lnHOMA-ir and lnHOMA-β (p> 0.05). Multiple linear regression model was established to gradually adjust for clinical confounding factors. It was found that physical activity level was independently positively correlated with LSBMD, FNBMD, HBMD, TBMD, and ASMI, and was independently negatively correlated with B-FAT and T-FAT in patients with type 2 diabetes.Conclusion: A lack of physical activity is an independent risk factor for decreased bone mineral density, decreased skeletal muscle content and increased fat content in patients with T2D.Keywords: type 2 diabetes, physical activity, body composition, correlation

Ding-Yun Feng,&ast; Jian-Xia Zhou,&ast; Xia Li, Wen-Bin Wu, Yu-Qi Zhou, Tian-Tuo Zhang Department of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Tuo Zhang, Department of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Tel +86-20-85252241, Fax +86-20-85253084, Email zhtituli@163.comPurpose: Acinetobacter baumannii is the most common microorganism in sputum cultures from long-term hospitalized patients and is often the cause of hospital-acquired pneumonia (HAP), which is usually associated with poor prognosis and high mortality. It is sometimes difficult to distinguish between A. baumannii infection and colonization. This study aimed to evaluate factors that differentiate infection from colonization and predict mortality in patients with nosocomial pneumonia caused by A. baumannii.Patients and Methods: The data used in this study were collected in our hospital between January 2018 and December 2020 from patients whose sputum cultures were positive for A. baumannii.Results: A total of 714 patients were included, with 571 in the infection group and 143 in the colonization group. The in-hospital mortality rate in the infection group was 20.5%. Univariate and multivariate logistic regression analyses showed that age, total number of inpatient departments, absolute neutrophil count, and C-reactive protein (CRP) level helped distinguish between infection and colonization. The area under the receiver operating characteristic curve (ROC) of the identification model was 0.694. In the infection group, age, Charlson comorbidity score, neutrophil-to-lymphocyte ratio, blood urea nitrogen/albumin ratio, CRP level, presence of multidrug resistance, and clinical pulmonary infection score (≥ 6) ratio were associated with in-hospital mortality. The area under the ROC curve for the prediction model was 0.828. The top three drug resistance rates in the infection group were 100% (cefazolin), 98.77% (ceftriaxone), and 71.8% (cefuroxime).Conclusion: The combination of common parameters helps identify A. baumannii respiratory tract infection or colonization. Several novel predictors can be used to predict the risk of death from A. baumannii pneumonia to reduce mortality. The drug resistance of A. baumannii remains high.Keywords: Acinetobacter baumannii, infection, colonization, mortality, drug resistance

Dong-mei Zhou,1,2,&ast; Jing Wei,2,&ast; Ting-ting Zhang,2 Feng-jie Shen,2 Jin-Kui Yang1 1Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China; 2Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin-Kui Yang, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China, Email jkyang@ccmu.edu.cnPurpose: To establish and validate the nomogram model for predicting diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) patients with proteinuria.Methods: A total of 102 patients with T2DM and proteinuria who underwent renal biopsy were included in this study. According to pathological classification of the kidney, the patients were divided into two groups, namely, a DN group (52 cases) and a non-diabetic renal disease (NDRD) group (50 cases). The clinical data were collected, and the factors associated with diabetic nephropathy (DN) were analyzed with multivariate logistic regression. A nomogram model for predicting DN risk was constructed by using R4.1 software. Receiver operator characteristic (ROC) curves were generated, and the K-fold cross-validation method was used for validation. A consistency test was performed by generating the correction curve.Results: Systolic blood pressure (SBP), diabetic retinopathy (DR), hemoglobin (Hb), fasting plasma glucose (FPG) and triglyceride/cystatin C (TG/Cys-C) ratio were independent factors for DN in T2DM patients with proteinuria (P< 0.05). The nomogram model had good prediction efficiency. If the total score of the nomogram exceeds 200, the probability of DN is as high as 95%. The area under the ROC curve was 0.9412 (95% confidence interval (CI) = 0.8981– 0.9842). The 10-fold cross-validation showed that the prediction accuracy of the model was 0.8427. The Hosmer-Lemeshow (H-L) test showed that there was no significant difference between the predicted value and the actual observed value (X2 = 6.725, P = 0.567). The calibration curve showed that the fitting degree of the DN nomogram prediction model was good.Conclusion: The nomogram model constructed in the present study improves the diagnostic efficiency of DN in T2DM patients with proteinuria, and it has a high clinical value.Keywords: diabetic nephropathy, non-diabetic renal disease, nomogram model, type 2 diabetes mellitus

Ding-Yun Feng,1,&ast; Yong Ren,2,&ast; Mi Zhou,3,&ast; Xiao-Ling Zou,1 Wen-Bin Wu,1 Hai-Ling Yang,1 Yu-Qi Zhou,1 Tian-Tuo Zhang1 1Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, People’s Republic of China; 3Department of Surgery Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Tuo Zhang; Yu-Qi ZhouDepartment of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaTel +86-20-85252241Email zhtituli@163.com; zzyyqqcj7605@163.comBackground: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Although there are many predictors of death for CAP, there are still some limitations. This study aimed to build a simple and accurate model based on available and common clinical-related feature variables for predicting CAP mortality by adopting machine learning techniques.Methods: This was a single-center retrospective study. The data used in this study were collected from all patients (≥ 18 years) with CAP admitted to research hospitals between January 2012 and April 2020. Each patient had 62 clinical-related features, including clinical diagnostic and treatment features. Patients were divided into two endpoints, and by using Tensorflow2.4.1 as the modeling framework, a three-layer fully connected neural network (FCNN) was built as a base model for classification. For a comprehensive comparison, seven classical machine learning methods and their integrated stacking patterns were introduced to model and compare the same training and test data.Results: A total of 3997 patients with CAP were included; 205 (5.12%) died in the hospital. After performing deep learning methods, this study established an ensemble FCNN model based on 12 FCNNs. By comparing with seven classical machine learning methods, the area under the curve of the ensemble FCNN was 0.975 when using deep learning algorithms to classify poor from good prognosis based on available and common clinical-related feature variables. The predicted outcome was poor prognosis if the ControlNet’s poor prognosis score was greater than the cutoff value of 0.50. To confirm the scientificity of the ensemble FCNN model, this study analyzed the weight of random forest features and found that mainstream prognostic features still held weight, although the model is perfect after integrating other factors considered less important by previous studies.Conclusion: This study used deep learning algorithms to classify prognosis based on available and common clinical-related feature variables in patients with CAP with high accuracy and good generalizability. Every clinical-related feature is important to the model.Keywords: deep learning, community-acquired pneumonia, mortality, predictor

Xiao-Ling Zou,1,&ast; Jin-Jie Wu,2,&ast; Hui-Xia Ye,3,&ast; Ding-Yun Feng,1,&ast; Ping Meng,1 Hai-Ling Yang,1 Wen-Bin Wu,1 Hong-Tao Li,1 Zhen He,2 Tian-Tuo Zhang1 1Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Tuo ZhangDepartment of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaEmail zhtituli@163.comZhen HeDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, People’s Republic of ChinaEmail hezh5@mail.sysu.edu.cnObjective: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma.Methods: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients.Results: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies.Conclusion: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.Keywords: asthma, phenotypes, gut microbiota, 16S rRNA next-generation sequencing, functional pathway

Ding-Yun Feng,* Xiao-Ling Zou,* Yu-Qi Zhou,* Wen-Bin Wu, Hai-Ling Yang, Tian-Tuo Zhang Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian-Tuo ZhangDepartment of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaTel +86-20-85252241Email zhtituli@163.comPurpose: Community-acquired pneumonia (CAP) is common among the elderly; it typically has a poor prognosis and high mortality. This study evaluated the factors predicting CAP-related in-hospital mortality in the elderly to identify a simpler and more accurate predictor.Patients and Methods: This was a single-center, retrospective study. The data used in this study was collected from all older patients (≥ 65) with CAP admitted to our hospital between January 2012 and April 2020.Results: A total of 2028 older patients with CAP were included; 121 (5.97%) died in hospital. Of the patients in the study, 1267 (62.5%) were men and 261 (12.9%) had a history of malignant tumors. After performing univariate and multivariate Cox regression analyses, sex, history of malignant tumor, CURB-65 score, neutrophil-to-lymphocyte ratio (NLR), hemoglobin level, and NLR*CURB-65 levels were associated with CAP mortality. By comparing the area under the receiver operating characteristic (ROC) curves of the predicted factors, the NLR*CURB-65 level used to predict CAP mortality in the elderly was 0.755, and was superior to other measurements. All included patients were then dichotomized into two groups based on NLR*CURB-65 level (≤ 9.06 and > 9.06) according to the ROC analysis. Patients with a high NLR*CURB-65 level had higher in-hospital mortality than those with a low NLR*CURB-65 level. The two divided groups showed significant differences in age, sex, smoking history, comorbidity, and laboratory findings. This indicates that NLR*CURB-65 is a predictive index that could reflect the comprehensive condition of older patients with CAP.Conclusion: NLR*CURB-65 is a simpler and more accurate predictor of CAP-related in-hospital mortality in the elderly.Keywords: NLR*CURB-65, community-acquired pneumonia, mortality, predictor

Ding-Yun Feng,1,* Yu-Qi Zhou,1,* Xiao-Ling Zou,1 Mi Zhou,2 Jia-Xin Zhu,1 Yan-Hong Wang,1 Tian-Tuo Zhang11Department of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Surgery Intensive Care Unit, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: Nosocomial pneumonia is a common nosocomial infection that includes hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia(VAP). It is an important cause of morbidity and mortality in hospitalized patients. This study aimed to evaluate the differences in microbial etiology and outcomes between HAP and VAP, particularly in related risk factors of multidrug-resistant organism (MDRO) causing HAP and VAP.Patients and methods: This single-center retrospective, observational study included patients with HAP/VAP. Clinical and epidemiological data of nosocomial pneumonia confirmed by microbial etiology that occurred in the Third Affiliated Hospital of Sun Yat-sen University, China, from January 2014 to December 2017 were obtained.Results: A total of 313 HAP cases and 106 VAP cases were included. The leading pathogens of HAP and VAP were similar, including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Antimicrobial susceptibility of the pathogens was low, and P. aeruginosa in VAP was less susceptible. In the multivariate logistic regression analysis, the risk factors associated with MDRO-HAP were chronic obstructive pulmonary disease, antibiotic therapy in the preceding 90 days, and prior endotracheal tracheostomy. The risk factor of MDRO-VAP was ≥5 days of hospitalization. The 30-day mortality rates of HAP and VAP were 18.5% and 42.5%.Conclusion: The leading pathogens were similar in both HAP and VAP, and antimicrobial susceptibility of the pathogens was low. The risk factors associated with MDRO infection in HAP and VAP have significant variability; hence, attention should be paid to improve prognosis. VAP was associated with poorer outcomes compared with HAP.Keywords: hospital-acquired pneumonia, ventilator-associated pneumonia, epidemiology, microbial etiology

Yu-Qi Zhou,1,2,* Ding-Yun Feng,1,2,* Wen-Juan Li,1,2 Hai-Ling Yang,1,2 Zhao-Ni Wang,3 Tian-Tuo Zhang,1,2 Zhuang-Gui Chen1,3 1Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, Guangdong, China; 2Department of Internal Medicine, Division of Respiratory Diseases, Guangzhou, Guangdong, China; 3Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China *These authors contributed equally to this work Background and purpose: Hospital-acquired pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. The emergence of multidrug resistant (MDR) Pseudomonas aeruginosa (PA) is of major concern. Our aim was to evaluate the risk factors and prognosis of HAP due to MDR-PA infection.Patients and methods: In a retrospective observational study, we collected data on all episodes of HAP caused by PA (PA-HAP) occurring from January 2013 to December 2016. Characteristics of patients with drug-sensitive PA were compared with those with MDR-PA. Data of demographic, underlying conditions, peripheral neutrophil-to-lymphocyte ratio (NLR), and clinical outcomes were collected and analyzed.Results: One hundred fifty-seven patients with PA-HAP were included, of which 69 (43.9%) patients were diagnosed with MDR-PA infection. There were significant differences between MDR-PA group and non-MDR-PA group on the following variables: initial inappropriate antibiotic therapy (P

Ding-Yun Feng,1,* Yu-Qi Zhou,1,* Yan-Fang Xing,2,* Chuang-Feng Li,3 Qing Lv,4 Jie Dong,5 Jie Qin,3 Yue-Fei Guo,3 Nan Jiang,6 Chencui Huang,7 Hai-Tao Hu,8 Xing-Hua Guo,9 Jie Chen,10 Liang-Hong Yin,11 Tian-Tuo Zhang,1 Xing Li12 1Department of Respiration, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 2Department of Nephrology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China; 3Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 4Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 5Department of Radiotherapy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 6Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 7The Associated Laboratory for AI, Cross-strait TsingHua Research Institute and Huiying Medical Technology, Dongsheng Science and Technology Park, HaiDian District, Beijing 100192, People’s Republic of China; 8Department of Surgery, ChanCheng District Center Hospital, Foshan 528000, People’s Republic of China; 9Department of Rheumatology, The LingNan Hospital of Sun Yat-sen University, Guangzhou 510000, People’s Republic of China; 10Department of Oncology, HengYang City Center Hospital, Hengyang 421001, People’s Republic of China; 11Department of Nephrology, The First Affiliated Hospital of JINAN University, Guangzhou 510630, People’s Republic of China; 12Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this work Purpose: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. Methods: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. Results: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%–60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. Conclusion: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy. Keywords: radiomics, connective tissue diseases, interstitial lung diseases, glucocorticoid

Xiao-ling Zou,1,2,* Zhuang-gui Chen,2,3,* Tian-tuo Zhang,1,2 Ding-yun Feng,1,2 Hong-tao Li,1,2 Hai-ling Yang1,2 1Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Institute of Respiratory Disease of Sun Yat-Sen University, 3Department of Pediatrics Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Background: Th17 and regulatory T cell (Treg) play crucial roles in the pathogenesis of asthma. However, the association between Th17/Treg homeostasis and asthma exacerbation remains unclear.Patients and methods: To investigate the role of Th17/Treg bias in asthma exacerbation, 49 asthma patients were enrolled in the current study, of whom 31 had acute asthma exacerbation (exacerbation group) and 18 did not (non-exacerbation group). Meanwhile, 17 healthy subjects were recruited as normal controls (control group). By measuring interleukin (IL)-4, IL-13, interferon (IFN)-γ, IL-10, and IL-17A levels in plasma using enzyme-linked immunosorbent assay (ELISA) and determining the mRNA expression of T-bet, GATA-3, forkhead/winged helix transcription factor (Foxp3), and receptor-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) by quantitative real-time PCR.Results: We found that IL-17A/IL-10 and RORγt/Foxp3 ratios were significantly increased in the exacerbation group compared with that in the non-exacerbation group, while IL-4/IFN-γ and GATA-3/T-bet ratios remained unchanged. Moreover, IL-17A/IL-10 and RORγt/Foxp3 ratios, but not IL-4/IFN-γ or GATA-3/T-bet ratios, negatively correlated with forced expiratory volume in the first second (FEV1)/FEV1pred and Asthma Control Test Questionnaire (ACT) scores in both exacerbation group and non-exacerbation group. In contrast, the IL-4/IFN-γ ratio was negatively correlated with FEV1/FEV1pred and ACT scores only in the non-exacerbation group but not in the exacerbation group, while the ratio of GATA-3/T-bet was correlated with neither FEV1/FEV1pred nor ACT scores in both groups with asthma.Conclusion: Our results suggest that the homeostasis of the Treg and Th17 cells is broken in asthma exacerbation and correlates with asthma severity and disease control status. The outcome has significant implication in understanding the progression of asthma and providing helpful information for physicians in the diagnosis and treatment of asthma patients. Keywords: bronchial asthma, exacerbation, T cell, Th17/Treg

Ai-Ling Liang,1–3,* Hai-Li Qian,4,* Ting-Ting Zhang,1–3 Ning Zhou,1–3 Hai-Juan Wang,4 Xi-Ting Men,4 Wei Qi,5 Ping-Ping Zhang,6 Ming Fu,4 Xiao Liang,4 Chen Lin,4 Yong-Jun Liu1–3 1Medical Molecular Diagnostics Key Laboratory of Guangdong, 2Department of Biochemistry and Molecular Biology, 3Department of Clinical Biochemistry, Guangdong Medical University, Dongguan, Guangdong, 4State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, 5Electroencephalogram Room, 6Department of Orthopedics, Guangdong Medical University Affiliated Hospital, Zhanjiang, Guangdong, People’s Republic of China *These authors contributed equally to this study Abstract: Breast cancer is the most common cancer and the leading cause of cancer-related death among women worldwide, with urgent need to develop new therapeutics. Targeted therapy is a promising strategy for breast cancer therapy. Stromal-derived factor-1/CXC chemokine receptor 4 (CXCR4) has been implicated in the metastasis of breast cancer, which renders it to be therapeutic target. This study aimed to evaluate the anticancer effect of fused TAT–DV1–BH3 polypeptide, an antagonist of CXCR4, and investigate the underlying mechanism for the cancer cell-killing effect in the treatment of breast cancer in vitro and in vivo. This results in a potent inhibitory effect of fused TAT–DV1–BH3 polypeptide on tumor growth and metastasis in nude mice bearing established MDA-MB-231 tumors. Fused TAT–DV1–BH3 polypeptide inhibited the proliferation of MDA-MB-231 and MCF-7 cells but did not affect that of HEK-293 cells. The fused TAT–DV1–BH3 polypeptide colocalized with mitochondria and exhibited a proapoptotic effect through the regulation of caspase-9 and -3. Furthermore, the fused TAT–DV1–BH3 polypeptide suppressed the migration and invasion of the highly metastatic breast cancer cell line MDA-MB-231 in a concentration-dependent manner. Notably, the DV1-mediated inhibition of the stromal-derived factor-1/CXCR4 pathway contributed to the antimetastasis effect, evident from the reduction in the level of phosphoinositide 3 kinase and matrix metalloproteinase 9 in MDA-MB-231 cells. Collectively, these results indicate that the apoptosis-inducing effect and migration- and invasion-suppressing effect explain the tumor regression and metastasis inhibition in vivo, with the involvement of caspase- and CXCR4-mediated signaling pathway. The data suggest that the fused TAT–DV1–BH3 polypeptide is a promising agent for the treatment of breast cancer, and more studies are warranted to fully elucidate the therapeutic targets and molecular mechanism. Keywords: bifunctional, fused polypeptide, CXCR4, breast cancer, apoptosis, transfer

Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.

Objectives: To investigate the pharmacokinetics of talipexole hydrochloride tablets and the potential influence of Madopar (benserazide and levodopa combination; co-beneldopa) tablets on talipexole's pharmacokinetics when the two tablets are coadministered orally to healthy Chinese volunteers. Methods: A sensitive liquid chromatographytandem mass spectrometry (LC-MS/MS) method was developed to measure talipexole concentration in human plasma in an open-label, randomized, two-way crossover, single-dose study, with 1-week washout period. Healthy Chinese volunteers were randomized to receive talipexole tablets either alone or together with Madopar tablets by oral administration after an overnight fast. Serial blood samples were collected for a period of 36 h after the administration. Pharmacokinetic parameters Cmax, tmax, t1/2z, mean residence time (MRT), AUC0-tau, AUC0-infinity, CLz/F and Vz/F were determined under the non-compartmental model. Pharmacokinetic values of talipexole administered alone to the subjects were compared with those administered simultaneously with Madopar to determine whether or not the differences were statistically significant. Results: The subjects experienced mild gastrointestinal irritation when talipexole was administered alone as well as together with Madopar. For talipexole hydrochloride, there were no significant differences in the pharmacokinetic values between the two administrations. No pharmacokinetic differences based on gender were observed either. Conclusion: A single oral dose of Madopar co-administered with talipexole does not significantly change talipexole's pharmacokinetics in human. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbance may impact response to psychological treatment for depression. Understanding how sleep disturbance changes during the course of psychological treatment, and identifying the risk factors for sleep disturbance response may inform clinical decision-making., Method: This analysis included 18,915 patients receiving high-intensity psychological therapy for depression from one of eight London-based Improving Access to Psychological Therapies (IAPT) services between 2011 and 2020. Distinct trajectories of change in sleep disturbance were identified using growth mixture modelling. The study also investigated associations between identified trajectory classes, pre-treatment patient characteristics, and eventual treatment outcomes from combined PHQ-9 and GAD-7 metrics used by the services., Results: Six distinct trajectories of sleep disturbance were identified: two demonstrated improvement, while one showed initial deterioration and the other three groups displayed only limited change in sleep disturbance, each with varying baseline sleep disturbance. Associations with trajectory class membership were found based on: gender, ethnicity, employment status, psychotropic medication use, long-term health condition status, severity of depressive symptoms, and functional impairment. Groups that showed improvement in sleep had the best eventual outcomes from depression treatment, followed by groups that consistently slept well., Limitation: Single item on sleep disturbance used, no data on treatment adherence., Conclusions: These findings reveal heterogeneity in the course of sleep disturbance during psychological treatment for depression. Closer monitoring of changes in sleep disturbance during treatment might inform treatment planning. This includes decisions about when to incorporate sleep management interventions, and whether to change or augment therapy with interventions to reduce sleep disturbance., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The relationship between sexual dysfunction and burnout among physicians remains unclear., Aim: To investigate the frequency of sexual dysfunction among physicians in primary hospital and explore the association between sexual dysfunction and burnout., Methods: This study was a cross-sectional survey conducted through a questionnaire. We used the Arizona Sexual Experience Scale and the Chinese version of the Maslach Burnout Inventory-Human Service Survey to assess sexual function and burnout among physicians in primary hospital. Considering the working environment of physicians, we also evaluated the doctor-patient relationship and sleep quality., Outcomes: Over one-third of physicians experience sexual dysfunction. Burnout is a significant factor to sexual dysfunction among medical professionals., Results: A total of 382 doctors participated in this survey, and the prevalence of sexual dysfunction was 33.51%. Sexual arousal and orgasm were the main sexual dysfunctions faced by male and female doctors, respectively. The prevalence of burnout among physicians was 43.72%. The prevalence of sexual dysfunction among physicians experiencing burnout (45.51%) was higher than that observed in physicians without burnout (24.19%). Physicians with burnout exhibited significantly higher total and individual scores on the Arizona Sexual Experience Scale as compared with physicians without burnout (all P values <.05). There was a significant positive correlation between depersonalization and sexual drive (r = 0.508, P < .001), sexual arousal (r = 0.521, P < .001), lubrication (r = 0.432, P < .001), orgasm/erection (r = 0.420, P < .001), and sexual satisfaction (r = 0.434, P < .001). Logistic regression analysis confirmed that-in addition to burnout-older age, dissatisfaction with income, a poor doctor-patient relationship, and poor sleep were significant contributors to sexual dysfunction among physicians in primary hospitals., Clinical Implications: Sexual health is an integral aspect of well-being. Prioritizing the sexual health of medical professionals can significantly contribute to improving their productivity., Strengths and Limitations: First, our sample size was small, and the impact of different specialties on sexual functioning was somewhat overlooked. Second, we lacked laboratory data (eg, testosterone and prolactin levels) that could provide substantial support to sexual identification. Finally, although we used logistic regression to establish causality, the relationship between sexual dysfunction and certain factors may be bidirectional., Conclusions: The issue of sexual dysfunction among doctors needs more attention. We should make targeted efforts to improve the quality of physicians' sexual lives., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.)

Background: Myocardial ischemia-reperfusion injury (MIRI) poses a prevalent challenge in current reperfusion therapies, with an absence of efficacious interventions to address the underlying causes., Aim: To investigate whether the extracellular vesicles (EVs) secreted by adipose mesenchymal stem cells (ADSCs) derived from subcutaneous inguinal adipose tissue (IAT) under γ-aminobutyric acid (GABA) induction (GABA-EVs IAT ) demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms., Methods: We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA. We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays. The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds. To explore the functional RNA diversity between EVs IAT and GABA-EVs IAT , we employed microRNA (miR) sequencing. Through a dual-luciferase reporter assay, we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein (TXNIP). Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction., Results: Our study demonstrates that, under the influence of GABA, ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs. Consequently, this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention, ultimately resulting in myocardial protection. On a molecular mechanism level, EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes., Conclusion: Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs, thereby regulating the expression of TXNIP. The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice., Results: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS., Conclusion: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Acute Stanford Type A Aortic Dissection (ATAAD) is a critical medical emergency characterized by significant morbidity and mortality. This study aims to identify specific gene expression patterns and RNA modification associated with ATAAD., Methods: The GSE153434 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted to identify differential expression genes (DEGs) associated with ATAAD. To validate the involvement of RNA modification in ATAAD, RNA modification-related genes (M6A, M1A, M5C, APA, A-to-I) were acquired from GeneCards, following by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. A gene prediction signature consisting of key genes was established, and Real-time PCR was used to validate the gene expression in clinical samples. The patients were then divided into high and low-risk groups, and subsequent enrichment analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and assessments of immune infiltration. A co-expression network analysis (WGCNA) was performed to explore gene-phenotype relationships and identify key genes., Results: A total of 45 RNA modification genes were acquired. Six gene signatures (YTHDC1, WTAP, CFI, ADARB1, ADARB2, TET3) were developed for ATAAD diagnosis and risk stratification. Enrichment analysis suggested the potential involvement of inflammation and extracellular matrix pathways in the progression of ATAAD. The incorporation of pertinent genes from the GSE147026 dataset into the six-gene signature further validated the model's effectiveness. A significant upregulation in WTAP, ADARB2, and TET3 expression, whereas YTHDC1 exhibited a noteworthy downregulation in the ATAAD group., Conclusion: Six-gene signature could serve as an efficient model for predicting the diagnosis of ATAAD., Competing Interests: None., (© 2024 JGC All rights reserved; www.jgc301.com.)

The aim of this work was to study the lymphatic absorption characteristics of gastric hydrolysates and intestinal hydrolysates of eicosapentaenoic acid-enriched phosphoethanolamine plasmalogen (EPA-pPE) with focusing on the fate of EPA and vinyl ether bonds in the lymph fluid using lymphatic intubation and lipidomics. The results showed that the EPA peak occurred earlier in the gastric (1.5 h) and intestinal (1 h) hydrolysates than in the EPA-pPE group (3 h) with EPA peak content being 2.03 and 1.46 times higher, suggesting pre-hydrolysis contributed to lymphatic absorption. Further, duodenal injection of gastric hydrolysates sn2 EPA-lysoPE produced higher levels of EPA-LPC, PC, PE, and PG. Meanwhile, intestinal hydrolysates free EPA and sn1 lyso-pPE enriched the sn1 + 2 + 3 TG (20:5&#95;20:5&#95;20:5) and increased the vinyl ether bond-containing lipids, such as PE (18:0p&#95;18:0) and PE (18:0p&#95;20:4). This study provides insight into dietary molecular structures of EPA and plasmalogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To explore the effects of canagliflozin on cardiac function and its regulation of ferroptosis in rats with heart failure with preserved ejection fraction (HFpEF). Methods: Thirty-two 7-week-old Dahl salt-sensitive rats were selected and randomly divided into four groups: the control group (fed with low-salt diet), the HFpEF group (fed with high-salt diet), the canagliflozin 20 group (fed with high-salt diet and 20 mg·kg -1 ·d -1 canagliflozin), and the canagliflozin 30 group (fed with high-salt diet and 30 mg·kg -1 ·day -1 canagliflozin). Body weight and blood pressure of the rats in each group were monitored. Metabolic cage tests were conducted at the10 th week of the experiment, and echocardiography was performed at the 12 th week, after which the rats were killed. Blood and left ventricular samples were collected. HE staining, Masson staining, Prussian blue iron staining, and reactive oxygen species staining were performed to observe the cardiomyocyte size and shape, degree of interstitial fibrosis, iron staining, reactive oxygen species production under optical microscope. The ultrastructure of cardiomyocytes was observed under electron microscope. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression levels of proteins and mRNA related to ferroptosis in left ventricular myocardial tissue of rats in each group. Results: After 1 week of adaptive feeding, all rats survived. Metabolic cage results showed that compared with control group, rats in the HFpEF group, canagliflozin 20 group and canagliflozin 30 group had more food intake, water intake and urine output, and lower body weight (all P <0.05). These changes were more pronounced in canagliflozin 20 group and canagliflozin 30 group than in HFPEF group, and only the body weight at the 12 th week showed a statistically significant difference between canagliflozin 20 group and canagliflozin 30 group ( P <0.05). The blood pressure of 6 th week and 12 th week, heart weight and left ventricular corrected mass of 12 th week of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while the ratio of early mitral valve peak velocity to late mitral valve peak velocity of 12 th week was lower (all P <0.05). HE and Masson staining showed that compared to control group, the myocardial fibers in the left ventricular myocardial tissue of rats in HFpEF group were disordered, with larger cell diameter ((0.032±0.004) mm vs. (0.023±0.003) mm, P <0.05), irregular shape, obvious proliferation of interstitial collagen fibers, and higher collagen volume fraction (0.168±0.028 vs. 0.118±0.013, P <0.05). Compared with HFpEF group, rats in the canagliflozin 20 group and canagliflozin 30 had more orderly arranged myocardial fibers, more regular cardiomyocyte shape, smaller cell diameter, and lower collagen volume fraction ( P <0.05). It was observed under electron microscopy that, compared to control group, most of the striated muscles in myocardial tissue of HFpEF group were broken, and the Z line and M line could not be clearly distinguished, some changes such as mitochondrial swelling, membrane thickening, cristae reduction or even disappearance occurred. In the canagliflozin 20 group and canagliflozin 30 group, the arrangement of striated muscles in the myocardial tissue of rats tended to be more regular, and the morphological changes of mitochondria were milder. Prussian blue iron staining results showed that the iron content in myocardial tissue of rats in HFpEF group was higher than that in control group, canagliflozin 20 group and canagliflozin 30 group. Reactive oxygen species staining results showed that the reactive oxygen species content in the myocardial tissue of rats in HFpEF group was higher than that of control group, canagliflozin 20 group and canagliflozin 30 group. Biochemical analysis of myocardial tissue showed that Fe 2+ and malondialdehyde content in myocardial tissue of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while glutathione content was lower (all P <0.05). Western blot and RT-qPCR detection results showed that compared to control group, rats in HFpEF group had higher expression levels of transferrin receptor 1 (protein relative expression level: 1.37±0.16 vs. 0.31±0.12), acyl-CoA synthetase long-chain family member 4 (protein relative expression level: 1.31±0.15 vs. 0.63±0.09) protein and mRNA, and lower expression levels of ferritin heavy chain 1 (protein relative expression level: 0.45±0.08 vs. 1.41±0.15) protein and mRNA (all P <0.05). There was no statistically significant difference in these indicators between canagliflozin 20 group and the canagliflozin 30 group (all P >0.05). There was no significant difference in levels of glutathione peroxidase 4 protein and mRNA expression in myocardial tissue of rats in four groups( P >0.05). Conclusion: Canagliflozin improves cardiac function in HFpEF rats by regulating the ferroptosis mechanism.

Prenyltransferases play a pivotal role in the isoprenoid biosynthesis and transfer in insects. In the current study, two classes of prenyltransferases (MhieFPPS1 and MhieFPPS2, MhiePFT-β and MhiePF/GGT-α) were identified in the leaf beetle, Monolepta hieroglyphica. Phylogenetic analysis revealed that MhieFPPS1, MhieFPPS2, MhiePFT-β and MhiePF/GGT-α were clustered in one clade with homologous in insects. Moreover, MhieFPPS2 lacked one aspartate-rich motif SARM. Molecular docking and kinetic analysis indicated that the (E)-GPP displayed higher affinity with MhieFPPS1 compared to DMAPP within the binding pocket containing metal binding sites (MG). The other class of prenyltransferases (MhiePFT-β and MhiePF/GGT-α) lack the aspartate-rich motif. Docking results indicated that binding site of MhiePFT-β involved divalent metal ions (Zn) and bound farnesyl or geranylgeranyl. In vitro, only recombiant MhieFPPS1 could catalyze the formation of (E)-farnesol against different combination of substrates, including IPP/DMAPP and IPP/(E)-GPP, highlighting the importance of SARM for enzyme activities. Kinetic analysis further indicated that MhiePFT-β operated via Zn 2+ -dependent substrate binding, while MhiePF/GGT-α stabilized the β-subunit during catalytic reaction. These findings contribute to a valuable insight in to understanding of the mechanisms involved in the biosynthesis and delivery of isoprenoid products in beetles., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or competing interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previous research has shown mixed results regarding the relationship between social class and children's prosocial behavior. The current study aims to further our understanding of these findings by exploring the relationship between social class and children's prosocial behavior in a moral context. Study 1 ( N = 833) found that when a target child pursued a morally negative goal and subsequently experienced misfortune, children from higher social class, compared to those from lower social class, experienced greater schadenfreude and exhibited less prosocial behavior. The relation between social class and prosocial behavior was mediated by schadenfreude. Study 2 ( N = 389) investigated whether the greater schadenfreude experienced by children from higher social class was due to a weaker empathic response to misfortune or a stronger sense of deservingness. The results revealed a sequential mediation effect of social class on prosocial behavior through deservingness and schadenfreude. These findings provide insight into the impact of social class on the development of children's moral judgment, emotions, and behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) are attractive approaches for solving the global problem of water pollution, due to the generation of highly-active reactive oxygen species (ROS). Therefore, highly-efficient PMS activation is crucial for promoting the catalytic degradation of environmental pollutants. Here, bimetallic CoGeO 2 (OH) 2 nanosheets with abundant surface hydroxyl groups (CGH) were synthesized via a simple hydrothermal route for PMS activation and degradation of various organic contaminants for the first time. The abundant surface hydroxyl groups (≡Co-OH/≡Ge-OH) could promptly initiate PMS to generate highly-active species: singlet oxygen ( 1 O 2 ), sulfate radicals (SO 4 · - ) and hydroxyl radicals (HO • ), while the asymmetric electron distribution among Co-O-Ge bonds derived from the higher electronegativity of Ge than Co further enhances the quick electron transfer to promote the redox cycle of Co 2+ /Co 3+ and Ge 2+ /Ge 4+ , thereby achieving an outstanding catalytic capability. The optimal catalyst exhibits nearly 100 % catalytic degradation performance of dyes (Methylene blue, Rhodamine B, Methyl orange, Orange II, Methyl green) and antibiotics (Norfloxacin, Bisphenol A, Tetracycline) over a wide pH range of 3-11 and under different coexisting anion conditions (Cl - , HCO 3 - , NO 3 - , HA), suggesting the excellent adaptability for practical usage. This study could potentially lead to novel perspectives on the remediation of water areas such as groundwater and deep-water areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke., Methods: This study was divided into two parts. The first part of the experiment：SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectively；HE staining was used to observe the cortical pathological changes；immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experiment：The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot., Results: In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased ( P <0.01)；the volume of cerebral infarction in the model group was significantly increased ( P <0.01)；the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increased；the cerebral microvascular density was significantly increased ( P <0.01)；the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased ( P <0.01, P <0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated ( P <0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated ( P <0.01, P <0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased ( P <0.01), the volume of cerebral infarction was significantly decreased ( P <0.01)；the degree of brain edema and neuronal necrosis were alleviated；the cerebral microvascular density was significantly increased ( P <0.01)；the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased ( P <0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased ( P <0.01, P <0.05), while the mRNA and protein expression of ADAMTS1 were decreased ( P <0.05, P <0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased( P <0.05), while the mRNA and protein expression of ADAMTS1 were increased ( P <0.01, P <0.05)., Conclusions: Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

Aspergillus niger (A. niger) spores can induce numerous health problems. Once the airflow-imposed drag force on an A. niger spore exceeds its binding force with the colony, the spore is detached. Turbulent flow may considerably increase the spore detachment. No method is currently available for prediction of the drag force on a spore and its detachment in turbulent flows. This investigation measured the turbulent velocities and detachment of A. niger colonies in a wind tunnel. Computational fluid dynamics (CFD) was employed to model an A. niger unit subjected to turbulent flow blowing. The top 1 % quantile instantaneous velocity of the turbulent flow was specified as the steady entry flow boundary condition for solving the peak velocity distribution and the peak drag forces onto spores. The predicted spore detachment ratios were compared with the measurement data for model validation. The results revealed that the spore detachment ratios with a turbulence intensity of 17 % to 20 % can be twice to triple the ratio with a turbulence intensity of approximately 1 %, when the average velocity for blowing remains the same. The proposed CFD model can accurately predict the detachment ratios of the A. niger spores. ENVIRONMENTAL IMPLICATION: Some people are sensitive to the Aspergillus niger (A. niger) spores, and excessive exposure can cause nasal congestion, skin tingling, coughing, and even asthma. Turbulent flow can considerably increase the spore detachment, due to the increased airflow-imposed drag force on the spores during turbulence. This investigation developed a numerical model to solve for the peak velocity distribution and the peak drag forces onto spores in turbulent flows to predict the spore detachment. With the numerical tool, the airborne fungal spore concentrations would be predictable, which paves a way for intelligent and precise control of fungal aerosol pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aphids are sap-feeding plant pests that depend on their symbiotic relationships with the primary endosymbiont Buchnera aphidicola to adapt to impoverished diets. However, how the host plant affects the aphid primary symbiont and aphid adaptation to host plant transfer are poorly known. In this study, aphid symbiont screening and genotype identification were used to establish 2 aphid strains (Rhopalosiphum maidis [Rm] and Rhopalosiphum padi [Rp] strains) containing only Buchnera without any secondary symbionts for both wheat aphid species (R. maidis and R. padi). Aphid fitness and Buchnera titers were unstable on some of these host plants after transferring to novel host plants (G1-G5), which were influenced by host plant species and generations; however, they stabilized after prolonged feeding on the same plants for 10 generations. The electropenetrography (EPG) records showed that the allocation of aphid feeding time was significantly distinct in the 6 host plants; aphids had more intracellular punctures and spent more nonprobing time on green bristlegrass which was not conducive to its growth compared with other plants. The content of soluble sugar, soluble protein, and amino acid in the leaves of the 6 host plants were also clearly separated. The correlation coefficient analysis showed that the nutrient contents of host plants had significant correlations with aphid feeding behaviors, fitness, and Buchnera titers. In the meantime, aphid fitness, and Buchnera titers were also affected by aphid feeding behaviors. Also, Buchnera titers of aphid natural populations on 6 host plants showed a visible difference. Our study deepened our understanding of the interaction among aphids, endosymbionts, and host plants, indicating that the host plant nutrient content is a predominant factor affecting aphid adaptation to their diet, initially affecting aphid feeding behaviors, and further affecting aphid fitness and Buchnera titers, which would further contribute to exploiting new available strategies for aphid control., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E 2 ) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E 2 , there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: To investigate the effect of increased cardiac output induced by dobutamine on cerebral blood flow (CBF) in healthy volunteers using magnetic resonance 3D-pseudo-continuous arterial spin labeling technology. Methods: A prospective study was conducted on 48 healthy volunteers recruited by handy sampling from June 2021 to January 2022. Physiological parameters before (at rest state) and after (under stress state) dobutamine-induced increase in cardiac output were analyzed. Quantitative CBF maps were generated by using arterial spin labeling difference imaging and proton density weighted reference image processing, and CBF changes under the rest and stress states were compared. Multivariable logistic regression model was used to analyze factors associated with reduced CBF. Results: A total of 48 subjects were included, with an age [ M ( Q 1 , Q 3 )] of 25.0 (24.0, 28.0) years, including 43 men and 5 women. Compared with the rest state, the CBF in the anterior cerebral artery [(36.2±6.9) vs (34.5±6.5) ml·(100 g) -1 ·min -1 , P =0.006] and the middle cerebral artery perfusion area [(35.8±6.5) vs (34.1±6.4) ml·(100 g) -1 ·min -1 , P =0.006] decreased under the stress state, however there was no statistically significant change in CBF in the posterior cerebral artery and the vertebral-basilar artery perfusion area (all P >0.05). Logistic regression analysis showed that the decrease in CBF in the anterior cerebral artery and middle cerebral artery supply regions during the stress state were correlated with an increase in diastolic blood pressure [ OR (95% CI ): 0.887 (0.796-0.989) and 0.895 (0.805-0.994), both P <0.05]. Conclusions: Dobutamine-induced increase in cardiac output leads to a decrease in CBF in anterior cerebral circulation but has no effect on posterior circulation. The increase in diastolic blood pressure is associated with decreased CBF under the stress state. Changes in CBF should be considered in the context of increased cardiac output.

Family with sequence similarity 135 member B (FAM135B) is a novel driver gene in esophageal squamous cell carcinoma (ESCC). However, little is known regarding its biological functions and mechanisms in ESCC. Here, we identified that the high expression of FAM135B was associated with lymph node metastasis and infiltrating development of ESCC. Elevated FAM135B expression promoted ESCC migration and invasion in vitro and lung metastasis in vivo. Furthermore, epithelial-mesenchymal transition (EMT)-related pathways were enriched in ESCC samples with high levels of FAM135B and FAM135B positively regulated EMT markers. Mechanistically, we observed that FAM135B interacted with the intermediate domain of TRAF2 and NCK-interacting kinase (TNIK), activating the Wnt/β-catenin signaling pathway. The facilitation of TNIK on ESCC migration and invasion was reversed by FAM135B siRNA. In addition, the N6-methyladenosine (m6A) modification positively regulated FAM135B expression, with methyltransferase like 3 (METTL3) acting as its substantial m6A writer. The pro-EMT effects of METTL3 overexpression were reversed by silencing FAM135B. Collectively, these findings illustrate the critical role of ABCDE in ESCC progression and provide new insights into the upstream and downstream mechanisms of FAM135B. NEW & NOTEWORTHY This study reveals for the first time that the novel cancer-related gene, FAM135B, promotes ESCC metastasis both in vitro and in vivo. Besides, we substantiate FAM135B's action on the β-catenin pathway through interacting with TNIK, thereby elucidating the promotional effect of FAM135B on ESCC EMT. Furthermore, we provide initial evidence demonstrating that METTL3-mediated m6A modification upregulates the expression of FAM135B in ESCC cells.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×10 4  Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Harmine is present in a variety of medicinal plants, and its effects on colon cancer cells remain unclear. Here, we found that harmine exhibited significant inhibitory effects on the proliferation of colon cancer cells by inhibiting the phosphorylation levels of the FAK/AKT and ERK1/2/CREB. Furthermore, harmine also inhibited the migration of colon cancer cells and suppressed the expression levels of MMP-2, MMP-9, and VEGF. Additionally, harmine-induced apoptosis in colon cancer cells by regulating the expression of Bcl-2 and Bax. In conclusion, our findings suggest that harmine exerts a significant inhibitory effect on the development of colon cancer cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8 + T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8 + T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC., (© 2024. The Author(s).)

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: To evaluate the effect of stent implantation for vertebrobasilar artery stenosis，by using 3D arterial spin labeling (3D ASL) technique., Methods: A retrospective analysis was conducted on the clinical and 3D ASL data of 48 patients who underwent vertebral-basilar artery stenting. Post-labeling delay times (PLD) of 1.5 s and 2.5 s were chosen, and the average regional cerebral blood flow (rCBF) values were measured in nine brain regions of the posterior circulation: bilateral thalamus, bilateral occipital lobes, bilateral cerebellar hemispheres, midbrain, pons, and medulla. The 48 patients were divided into two groups based on the presence or absence of acute ischemic stroke in the posterior cerebral circulation region detected by diffusion-weighted imaging (DWI). The preoperative and postoperative rCBF results were statistically analyzed., Results: In the infarct group, there were significant increases in rCBF values of all nine brain regions at both PLD = 1.5 s and 2.5 s postoperatively compared to preoperatively. At PLD = 1.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were found in the right thalamus, left cerebellum, midbrain, and pons regions (P < 0.05). At PLD = 2.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were observed in the left occipital lobe, right cerebellum, midbrain, and pons regions (P < 0.05). When analyzing the rCBF values of the brain regions with recent infarcts in the infarct group, there was a significant increase in postoperative rCBF values compared to preoperative values (P < 0.05). After excluding the data from brain regions with recent infarcts, the CBF values in the remaining brain regions were also increased postoperatively, and some brain regions showed statistically significant differences in rCBF values between the preoperative and postoperative periods (P < 0.05). In the non-infarct group, there were no statistically significant differences in the preoperative and postoperative rCBF values in all brain regions at both PLD = 1.5 s and 2.5 s (P > 0.05)., Conclusion: The application of 3D ASL technology shows significant value in assessing the surgical efficacy of vertebral-basilar artery stenting, especially in patients with acute posterior circulation infarction., (Copyright © 2024. Published by Elsevier Inc.)

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L 3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC 50 value of 7.1 μM. Molecular docking demonstrated that 17 could bond with AChE well (-8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H 2 O 2 -induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 μM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate whether the child-centered treatment significantly increased satisfaction as revealed by CBCL scores and decreased duration of nasal endoscopy., Methods: A total of 206 pediatric patients were selected as study participants. Using a random number table, the participants were divided into the control group and the treatment group, with 103 cases in each group. The control group received routine nursing care, whereas the treatment group received child-centered health education nursing intervention. The differences between the two groups were observed in four aspects: examination compliance, child behavior checklist (CBCL) scores, the satisfaction level of the patient's family with the nurses in the endoscopy room, and the average duration of the nasal endoscopy., Results: Subsequent to the implementation of the intervention, it was observed that within the treatment group, the level of compliance among pediatric patients undergoing nasal endoscopy exhibited a statistically significant increase when compared to the control group; the CBCL scores of both groups were lower than those before nursing care, and those of the treatment group were statistically significantly lower than those of the control group; the satisfaction rate of the patient's family in two groups was 74 % and 90 %, respectively. The average duration of nasal endoscopy was statistically significantly lower in the treatment group than that in the control group., Conclusions: The implementation of a child-centered health education nursing intervention for pediatric patients undergoing nasal endoscopy has been shown to effectively mitigate instances of crying and screaming, enhance patient compliance, reduce examination duration, and elevate the overall satisfaction levels among their respective families., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA. Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings. Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023-1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013-1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18-1.49, p -value <0.001). Conclusion: Our findings underscore the clinical importance of screening for ILD in RA patients and suggest that effective management of RA could significantly benefit ILD patients. The potential applicability of novel RA treatments to ILD warrants further exploration. Additionally, racial disparities in the manifestation of these diseases should not be overlooked, as they may offer new perspectives for targeted therapies in diverse populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhang, Guo, Qiao, Song, Zhang, Zhang and Zhang.)

Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.

Background and Purpose: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC)., Methods: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated., Results: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively., Conclusions: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group., (© 2024. The Author(s).)

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress., (© 2024 John Wiley & Sons Ltd.)

Preservation and restoration of hand function after burn injuries are challenging yet imperative. This study aimed to assess the curative effect of a composite skin graft over an acellular dermal matrix (ADM) and a thick split-thickness skin graft (STSG) for treating deep burns on the hand. Patients who met the inclusion criteria at the First Affiliated Hospital of Wenzhou Medical University between September 2011 and January 2020 were retrospectively identified from the operative register. We investigated patient characteristics, time from operation to the start of active motion exercise, take rates of skin graft 7 days post-surgery, donor site recovery, complications and days to complete healing. Patients were followed up for 12 months to evaluate scar quality using the Vancouver Scar Scale (VSS) and hand function through total active motion (TAM) and the Jebsen-Taylor Hand Function Test (JTHFT). A total of 38 patients (52 hands) who received thin STSG on top of the ADM or thick STSG were included. The location of the donor sites was significantly different between Group A (thick STSG) and Group B (thin STSG + ADM) (p = 0.03). There were no statistical differences in age, gender, underlying disease, cause of burn, burn area, dominant hand, patients with two hands operated on and time from burn to surgery between the two groups (p > 0.05). The time from operation to the start of active motion exercise, take rates of skin graft 7 days post-surgery and days to complete healing were not significantly different between Group A and Group B (p > 0.05). The rate of donor sites requiring skin grafting was lower in Group B than in Group A (22.2% vs. 100%, p < 0.001). There were no statistically significant differences in complications between the groups (p = 0.12). Moreover, 12 months postoperatively, the pliability subscore in the VSS was significantly lower in Group A than in Group B (p = 0.01). However, there were no statistically significant differences in vascularity (p = 0.42), pigmentation (p = 0.31) and height subscores (p = 0.13). The TAM and JTHFT results revealed no statistically significant differences between the two groups (p = 0.22 and 0.06, respectively). The ADM combined with thin STSG is a valuable approach for treating deep and extensive hand burns with low donor site morbidity. It has a good appearance and function in patients with hand burns, especially in patients with limited donor sites., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)