Single-cell transcriptomics reveal potent extrafollicular B cell response linked with granzyme K+ CD8 T cell activation in lupus kidney.

OBJECTIVES: B and T cells constitute the majority of infiltrating lymphocytes in the kidney and represent the local perpetrators in lupus nephritis (LN), but the underlying pathogenic mechanisms are not well elucidated. The aim of this study is to explore the kidney-specific adaptive immune landscape in patients with active LN at the single-cell level. METHODS: We performed single-cell RNA/B cell receptor (BCR)/T cell receptor (TCR) sequencing analysis on sorting-purified B and T cells from the kidney and paired peripheral blood of patients with active LN, and the periphery of matched controls. Flow cytometry, Assay for Transposase Accessible-sequencing, multiplexed immunohistochemistry and functional studies were performed to validate the transcriptomic results. RESULTS: High infiltrations of intrarenal atypical B cells (ABCs) and antibody-secreting cells (ASCs) were identified in the B cell compartment. The single-cell BCR repertoire analysis revealed strong clonal expansion of intrarenal ASCs dominated by IGHG1 and IGHG3 isotypes, accompanied by lower frequencies of heavy-chain and light-chain somatic mutations, compared with the peripheral ASCs. Notably, a unique expansion of IGHG4-59 and clonal overlap between ABCs and ASCs was found in kidney-specific clonotypes. In the T cell compartment, we identified granzyme K (GZMK)+ CD8 T cells as the dominant kidney-associated T cells which shared inflammation- and stress-related gene pathways with ABCs. Intrarenal GZMK+ CD8 T cells highly expressed IFNG and displayed strong communication with ABCs via the type II interferon (IFN) pathway. Intrarenal GZMK+ CD8 T cells and ABCs were largely co-localised within the tertiary lymphoid structure, and GZMK+ CD8 T cells potentially contributed to the differentiation of ABCs via IFN-γ and interleukin-21. CONCLUSIONS: Our study revealed a potent extrafollicular B cell response linked with overactivation of GZMK+ CD8 T cells in the kidney of patients with LN, which may lead to innovative treatments for LN.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

Interconnected Periodic Macroporous NaNbO3 for High-Efficiency Solar-Driven Photocatalytic Hydrogen Evolution.

Highly ordered periodic macroporous structures have been extensively utilized to significantly enhance the photocatalytic activity. However, constructing 3D interconnected ordered porous ternary nanostructures with highly crystalline frameworks remains a formidable challenge. Here, we introduce the design and fabrication of 3D interconnected periodic macroporous NaNbO3 (PM NaNbO3) to effectively increase the density of surface-active sites and optimize the photogenerated carrier-transfer efficiency. By incorporating Pt as a cocatalyst, PM NaNbO3 exhibits an exceptional photocatalytic hydrogen generation rate of 10.04 mmol h-1 g-1, which is approximately six and five times higher than those of calcined NaNbO3 (C-NaNbO3) and hydrothermal NaNbO3 (H-NaNbO3), respectively. This outstanding performance can be attributed to the synergistic effects arising from its well-interconnected pore architecture, large surface area, enhanced light absorption capability, and improved charge carrier separation and transport efficiency. The findings presented in this study demonstrate an innovative approach toward designing hierarchically periodic macroporous materials for solar-driven hydrogen production.

DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3K-Akt-NF-κB pathway.

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.

Chronic diseases and determinants of community health services utilization among adult residents in southern China: a community-based cross-sectional study.

BACKGROUND: The burden of chronic diseases has become a major public health concern, and high-efficiency use of community health services is essential in combating chronic diseases. This study described the status of chronic diseases in southern China and explored the determinants of health service utilization among adult residents. METHODS: Data were obtained from one part of community survey data from four counties in Ganzhou City, southern China. A multistage, stratified random sampling method was used to conduct a cross-sectional survey between 2018 and 2020. Overall, 7430 valid questionnaires were collected. A lasso-linear regression analysis was performed to explore the determinants of community health service utilization. RESULTS: According to the study, most participants (44.6%) reported having relatively good health, while 42.1% reported having moderate health. Chronic diseases were reported by 66.9% of the respondents. The three most prevalent self-reported chronic diseases were hypertension (22.6%), hyperlipidemia (5.9%), and diabetes (5.9%). Among residents with chronic diseases, 72.1% had one chronic disease, while the rest had multiple. Only 13.9% of residents frequently utilized community health services, while 18.9% never used them. Additionally, among residents who reported having chronic diseases, 14.1% had never attended community health services. Four categories of factors were the key determinants of community health service utilization: (1) personal characteristics, age, and sex; (2) health-related factors, such as family history, self-reported health conditions, and the number of chronic diseases; (3) community health service characteristics, such as satisfaction with and accessibility to community health services; and (4) knowledge of chronic diseases. Specifically, women tend to utilize healthcare services more frequently than men. Additionally, residents who are advanced in age, have a family history of chronic diseases, suffer from multiple chronic conditions, rate their self-reported health condition as poor, have a better knowledge about chronic diseases, have better accessibility to community health services, and have higher the satisfaction with community health services, tend to utilize them more frequently. CONCLUSIONS: Given the limited healthcare resources, the government should promote the effective utilization of community health facilities as a critical community-based strategy to combat the growing threat of chronic diseases in southern China. The priority measures involve enhancing residents' access to and satisfaction with community health services and raising awareness of chronic illnesses among older individuals with poor health status.

Factors Associated with Intention to Use Telerehabilitation for Children with Special Needs: A Cross-Sectional Study.

Background: Children with special health care needs (CSHCN) require long-term and ongoing rehabilitation interventions supporting their development. Telerehabilitation can provide continuous rehabilitation services for CSHCN. However, few studies have explored the intention of CSHCN and their caregivers to use telerehabilitation and its impact on them. Objective: The objective of this study was to identify factors that influence the intention to use telerehabilitation among CSHCN and their caregivers. Methods: This study was a cross-sectional study. Based on the unified theory of acceptance and use of technology, extended with additional predictors (trust and perceived risk [PR]), this study developed a research model and proposed 10 hypotheses. A structured questionnaire was distributed to 176 caregivers. Data were analyzed and research hypotheses were tested using partial least squares structural equation modeling to better understand the factors influencing the use of telerehabilitation. Results: A total of 164 valid questionnaires were collected. CSHCN and their caregivers were overall satisfied with this telerehabilitation medical service. The results of the structural model analysis indicated that social influence (SI), facilitating conditions (FC), and trust had significant effects on behavioral intention (BI) to use telerehabilitation, while the paths between performance expectancy (PE), effort expectancy (EE), and PR and BI were not significant. PE, EE, and SI had a significant effect on trust. Moreover, EE and SI had indirect effects on BI, with trust as the mediator. Conclusions: The results indicated that SI, FC, and trust are significant factors influencing CSHCN and their caregivers' use of telerehabilitation. Trust is also an important mediator for the intention and highly influenced by PE, EE, and SI.

Factors associated with oral health service utilization among young people in southern China.

OBJECTIVES: To identify the patterns and influencing factors of oral health service utilization among college students, and further to provide scientific evidence for policy making on oral health education and behavioral interventions for the college population. METHODS: The study population was college students in Southern China. Totally 678 students participated in the survey. A self-designed questionnaire based on Anderson's model (predisposing factors, enabling factors, need factors) was used to survey college students. Descriptive statistics, χ2 test, and logistic regression were used to analyze influence factors of oral health service utilization among college students. RESULTS: The utilization rate of oral health service in the past 12 months was 30.2%. The primary type of oral health service was treatment (59.6%), and only 12.8% were for prevention. There were 39% of the participants having oral health diseases, of which dental caries (25.7%) and oral bleeding (22.2%) were the main problems. The results from logistic regression analysis revealed that students with better beliefs (OR = 1.84, 95% CI:=1.02-3.43), frequent consumption of sugary drinks (OR = 2.90, 95% CI:=1.90-4.47), teeth brushing frequency > = 2 times per day (OR = 2.09, 95% CI = 1.24-3.61), frequent floss utilization (OR = 2.63, 95% CI = 1.21-5.76), dental caries (OR = 2.07, 95% CI = 1.35-3.17) used oral health services higher, while those lived in rural areas (OR:0.52, 95% CI = 0.34-0.80), and had only a fair concern (OR = 0.48, 95% CI = 0.31-0.74) or no concern (OR = 0.26, 95% CI = 0.08-0.67) on oral health utilized oral health services lower. CONCLUSIONS: Chinese college students demonstrate some knowledge and attitudes towards oral health. However, they tend to neglect oral hygiene and have limited understanding of their own oral issues. Furthermore, the utilization of oral services, such as treatment, remains remarkably low, despite the availability of long-term and favorable health insurance policies. The utilization of oral health services among college students is influenced by various factors, including residing in rural areas, consuming sugary beverages on a daily basis, brushing teeth at least twice a day, and practicing flossing.

KIN17 promotes cell migration and invasion through stimulating the TGF-ß/Smad2 pathway in hepatocellular carcinoma.

KIN17 DNA and RNA binding protein (Kin17) is involved in the regulation of tumorigenesis of diverse human cancers. However, its role in the cancer progression and metastasis in hepatocellular carcinoma (HCC) remains largely unknown. Bioinformatics and immunohistochemistry staining were used to investigate the expression pattern of KIN17 and its prognostic value in HCC patients. The transwell, wound-healing assay was employed to determine the effects of KIN17 on migration and invasion of HCC cells in vitro. The tail veins model was employed to determine the effects of KIN17 on lung metastasis in vivo. The biological mechanisms involved in cell migration and invasion regulated by KIN17 were determined with Western blot analysis method. KIN17 expression was significantly increased in HCC tissues compared with adjacent normal tissues, with particularly higher in portal vein tumor thrombus and intrahepatic metastasis tissues. Patients with higher KIN17 expression experienced poor overall and disease free survival. KIN17 knockdown in HuH7 and HepG2 cells significantly reduced cell migration and invasion abilities, whereas its overexpression promoted migration and invasion in MHCC-97L and HepG2 cells in vitro and in vivo. In HuH7 and HepG2 cells, KIN17 knockdown inhibited the TGF-ß/Smad2 pathway. In contrast, KIN17 overexpression stimulated TGF-ß/Smad2 pathway in MHCC-97L and HepG2 cells, along with the genes involved in the epithelial-mesenchymal transition. These findings suggest that KIN17 promotes migration and invasion in HCC cells by stimulating the TGF-ß/Smad2 pathway. KIN17 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC.

Longitudinal study of patients with antimelanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated interstitial lung disease.

OBJECTIVES: To describe the 8-year longitudinal study and long-term prognosis of a large inception cohort of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) DM-interstitial lung disease (ILD) patients. METHODS: In total, 216 patients diagnosed with MDA5+ DM-ILD were enrolled and followed up to analyse long-term survival rate. Demographic and clinical variables were collected at baseline and each temporal end point. Seventy patients who survived the first year were analysed for the long-term serological and respiratory outcomes. RESULTS: A total of 85 patients (39.3%) died during the follow-up period up to 96 months, with 89% of the deaths occurring in the first year after diagnosis. Long-term outcome was reported in 70 patients. Serological markers including anti-MDA5 antibody showed significant improvement with time. Radiographic findings and pulmonary function also improved notably in the follow-up period, especially in rapidly progressive ILD group, as measured by high-resolution computed tomography imaging scores, the estimated forced vital capacity, estimated diffusing capacity of lung carbon monoxide and dyspnoea scores. Early application of anti-fibrosis therapy helped to improve long-term pulmonary function. CONCLUSIONS: MDA5+ DM-ILD patients had a high mortality rate despite aggressive treatment. Patients who survived the first year usually showed a significant improvement in serological markers and pulmonary function during the long-term follow-up.

Determination of the surface properties and adsorption states of nanoporous materials using the zeta adsorption isotherm.

The adsorption process of porous materials has always been a popular field of research in interfacial physics, and the surface physical parameters of materials can be obtained from their adsorption characteristics, which has a great influence on the performance of materials. Based on the zeta adsorption isotherm, we propose a method based on the zeta adsorption isotherm to predict the entire adsorption process of porous materials and determine material surface properties from the measured isotherm data in the heterogeneity-free range. We applied the zeta constants of the silica adsorption system to the corresponding adsorption isotherm of the porous material. The results showed that the predicted adsorption isotherms are in good agreement with the experimental measurements before pore filling and can effectively identify the pressure ratios at the beginning and end of pore filling. In the region of high-pressure ratios, the Kelvin equation was utilized to calculate the pressure ratio at a contact angle of 0°. The surface parameters of the materials were determined by geometrically calculating the variation of the adsorption amount and the desorption isotherms in the high-pressure ratio range were calculated from these surface parameters. The predicted desorption isotherms can well reflect the adsorption process of silica porous materials in the region of a high-pressure ratio. In addition, for the surface parameters of the materials, the specific surface area calculated from the adsorption and desorption isotherms, respectively, differed by less than 7.9%, and the reliability of the method was verified by comparing the results with those of the argon adsorption systems.

Catatonia in adult anti-NMDAR encephalitis: an observational cohort study.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent autoimmune encephalitis and is closely related to catatonia. This study aimed to investigate the clinical features and disease outcomes of adult catatonic anti-NMDAR encephalitis patients. METHODS: Adult patients diagnosed with anti-NMDAR encephalitis between January 2013 and October 2021 were retrospectively enrolled in this study. According to the Bush Francis Catatonia screening instrument (BFCSI), patients were divided into two groups: those with catatonia and those without catatonia. The modified Rankin scale (mRS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), Neuropsychiatric Inventory (NPI), Patient Health Questionnaire-9 (PHQ-9) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) scores were assessed at follow-up. The Mann-Whitney U test (nonparametric), Student's t test (parametric), and chi-squared test were used to analyse the differences between the two groups. RESULTS: Eighty-four patients were recruited, including twenty-five catatonic patients and fifty-nine noncatatonic patients. Among them, 28 had positive antibody only in cerebrospinal fluid (CSF), 4 had positive antibody only in serum and 52 had positive antibody both in CSF and serum. Catatonic patients experienced more disturbance of consciousness (p = 0.01), aggression (p = 0.046) and affective disorders (p = 0.043) than noncatatonic patients. The mRS scores of the catatonia group assessed at admission (p = 0.045) were worse than those of the non-catatonia group. Catatonic patients were more inclined to develop deep vein thrombosis (p = 0.003), decubitus (p = 0.046), pneumonia (p = 0.025), and to be admitted to the intensive care unit (ICU) (p = 0.011) than noncatatonic patients. All patients in the catatonia group received first-line immunotherapy. At the 24-month follow-up, 2 patients in the catatonia group did not achieve good outcomes. At the last follow-up, the catatonia group had more relapses (p = 0.014) and more neuropsychiatric problems (p = 0.035). CONCLUSIONS: Adult anti-NMDAR encephalitis patients with catatonia present distinct clinical features in disease course and are prone to experience more relapses and long-term neuropsychiatric problems than those without catatonia.

Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice.

The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc- axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms.

GmJAZ3 interacts with GmRR18a and GmMYC2a to regulate seed traits in soybean.

Seed weight is usually associated with seed size and is one of the important agronomic traits that determine yield. Understanding of seed weight control is limited, especially in soybean plants. Here we show that Glycine max JASMONATE-ZIM DOMAIN 3 (GmJAZ3), a gene identified through gene co-expression network analysis, regulates seed-related traits in soybean. Overexpression of GmJAZ3 promotes seed size/weight and other organ sizes in stable transgenic soybean plants likely by increasing cell proliferation. GmJAZ3 interacted with both G. max RESPONSE REGULATOR 18a (GmRR18a) and GmMYC2a to inhibit their transcriptional activation of cytokinin oxidase gene G. max CYTOKININ OXIDASE 3-4 (GmCKX3-4), which usually affects seed traits. Meanwhile, the GmRR18a binds to the promoter of GmMYC2a and activates GmMYC2a gene expression. In GmJAZ3-overexpressing soybean seeds, the protein contents were increased while the fatty acid contents were reduced compared to those in the control seeds, indicating that the GmJAZ3 affects seed size/weight and compositions. Natural variation in JAZ3 promoter region was further analyzed and Hap3 promoter correlates with higher promoter activity, higher gene expression and higher seed weight. The Hap3 promoter may be selected and fixed during soybean domestication. JAZ3 orthologs from other plants/crops may also control seed size and weight. Taken together, our study reveals a novel molecular module GmJAZ3-GmRR18a/GmMYC2a-GmCKXs for seed size and weight control, providing promising targets during soybean molecular breeding for better seed traits.

Proteomic dissimilarities of primary microglia and BV2 cells under stimuli.

Microglia are the static resident cells possessing the phagocytic properties in the central nervous system (CNS). In many relevant studies, the immortalized murine microglial cell line BV2 has been used as a tool in primary microglia (PM) relevant studies. Microglia participate in neuroinflammation by converting into M1- and M2-like phenotypes. In this study, we established M1- and M2-like phenotype response models by exposing PM and BV2 cells to lipopolysaccharides (LPS) and interlukin-4 (IL-4), respectively, and discovered the proteomic differences between the two types of microglia. It turned out that the BV2 cell responses to LPS and IL-4 were narrower and weaker than that of PM. In addition, irradiation, which has been shown to activate microglia and induces neuroinflammation, was also used as a treatment in this study. The results showed that BV2 cells have stronger capacity of DNA damage repair. Besides, irradiation had a negative effect on the regulation of KEGG pathways such as proteasome, ribosome, oxidative phosphorylation and TCA cycle in both cells. Furthermore, the KEGG pathways including cell cycle and DNA replication (significantly downregulated), and antigen processing and presentation and FC γ R mediated phagocytosis (significantly up-regulated) were only found in irradiated PM. These data demonstrate that PM is more fragile to irradiation. Results in this study indicate that BV2 cells only partially model PM, and thus, using BV2 in microglia related studies should be carefully considered.

Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up.

OBJECTIVES: Previous studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of this investigator-initiated study was to compare the efficacy and safety of leflunomide versus azathioprine as maintenance therapy for LN. METHODS: 270 adult patients with biopsy-confirmed active LN from 7 Chinese Rheumatology Centres were enrolled. All patients received induction therapy with 6-9 months of intravenous cyclophosphamide plus glucocorticoids. Patients who achieved complete response (CR) or partial response (PR) were randomised to receive prednisone in combination with leflunomide or azathioprine as maintenance therapy for 36 months. The primary efficacy endpoint was the time to kidney flare. Secondary outcomes included clinical parameters, extrarenal flare and adverse effects. RESULTS: A total of 215 patients were randomly allocated to the leflunomide group (n=108) and azathioprine group (n=107). Kidney flares were observed in 17 (15.7%) leflunomide-treated patients and 19 (17.8%) azathioprine-treated patients. Time to kidney flare did not statistically differ (leflunomide: 16 months vs azathioprine: 14 months, p=0.676). 24-hour proteinuria, serum creatinine, serum albumin, serum C3 and serum C4 improved similarly. Extrarenal flare occurred in two patients from the azathioprine group and one patient from the leflunomide group. The incidence of adverse events was similar in the 2 groups: leflunomide 56.5% and azathioprine 58.9%. CONCLUSIONS: The efficacy and safety profile of leflunomide are non-inferior to azathioprine for maintenance therapy of LN. Leflunomide may provide a new candidate for maintenance therapy in patients with LN. TRIAL REGISTRATION NUMBER: NCT01172002.

Yttrium chloride-induced cytotoxicity and DNA damage response via ROS generation and inhibition of Nrf2/PPARγ pathways in H9c2 cardiomyocytes.

Increasing exploration of rare-earth elements (REEs) has resulted in a high REEs' exposure risk. Owing to their persistence and accumulation of REEs in the environment, their adverse effects have caused widespread concern. However, limited toxicological data are available for the adverse effects of yttrium (Y) and its underlying mechanisms of action. In the present study, H9c2 cardiomyocytes were used in vitro model to investigate the cardiotoxicity of yttrium chloride (YCl3). Results show that YCl3 treatment resulted in reactive oxygen species (ROS) overproduction, decrease in ∆Ψm, and DNA damage. Mechanistically, we detected expression levels of protein in response to cellular DNA damage and antioxidative defense. Results indicated that the phosphorylation of histone H2AX remarkably increased in a dose-dependent manner. At a high YCl3-exposure concentration (120 µM), specific DNA damage sensors ATM/ATR-Chk1/Chk2 were significantly decreased. The protein levels of key antioxidant genes Nrf2/PPARγ/HO-1 were also remarkably inhabited. Additionally, the antioxidant N-acetyl-L-cysteine (NAC) pretreatment promoted the activation of antioxidative defense Nrf2/PPARγ signaling pathways, and prevented the production of cellular ROS, thus protecting the DNA from cleavage. Altogether, our findings suggest that YCl3 can induce DNA damage through causing intracellular ROS overproduction and inhibition of antioxidative defense, leading to cytotoxicity in H9c2 cardiomyocytes.

Relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China.

BACKGROUND: With an increasing incidence of obesity, the relationship between obesity and body image has become a hot research topic worldwide. From high school to university, young people experience changes in their social environment. University students have a high incidence of eating disorders and insufficient physical activity. The purpose of this study was to explore the relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China. METHODS: In total, 1296 university students aged 18-23 years were recruited for this study. The participants completed anthropometric measurements, the Physical Activity Rating scale-3 (PARS-3), and the Chinese-Dutch Eating Behavior Questionnaire (C-DEBQ). The ideal weight and silhouette were reported by university students using a questionnaire. RESULTS: Compared with men, young women had a higher level of body dissatisfaction. For men, body mass index (BMI; ß = 0.76, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.10, P <  0.01) were the significant factors predictive of body dissatisfaction. For women, BMI (ß = 0.57, P <  0.01), muscle mass (ß = 0.12, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.09, P <  0.01) were the significant factors predictive of body dissatisfaction. CONCLUSIONS: University students with high body dissatisfaction had lower physical activity scores and higher restrained eating scores. The data presented here highlight the impact of university students' body dissatisfaction on physical activity deficiency and disordered eating behaviors in China.

Configurations for positive public behaviors in response to the COVID-19 pandemic: a fuzzy set qualitative comparative analysis.

BACKGROUND: The COVID-19 crisis poses considerable threats to public health, and exploring the key configuration conditions of the public behavior response is very important for emergency risk management. OBJECTIVE: This study attempts to reveal differences in the conditional configuration and mechanism of public behavior based on the proposed framework, further make up for the deficiencies of existing research in explaining such issues as "How to promote the public's protective behavior or reduce the public's excessive behavior?" and finally provide new evidence and ideas for the government to improve the emergency management system. METHODS: A total of 735 valid cases were obtained using an online survey and revealed the conditional configuration and mechanism of public behavior differences through a fuzzy set qualitative comparative analysis based on the proposed public behavioral framework. RESULTS: The results show that critical factors including risk communication, trust, risk perception, and negative emotions alone did not constitute a necessary condition for public protective or excessive behavior. The different configurations of influencing factors reveal the complexity of public behavioral risk management, and taking adequate measures to increase public trust and reduce negative public emotions constitute the core path of risk management to enhance positive public behavior. CONCLUSIONS: The configurations of various influencing factors reveal the complexity of public behavioral risk management. For behavioral risk management, governments should focus on adapting to multiple conditions according to their situations and, under the "overall perspective," formulate policies based on local conditions and further form a differentiated risk management path. Practically speaking, for the government, taking adequate measures to increase public trust and reduce negative public emotions is the core path of risk management to enhance positive public behavior.

Mutations in ASH1L confer susceptibility to Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.

Apolipoprotein E genotype predicts subarachnoid extension in spontaneous intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Spontaneous intracerebral haemorrhage (ICH) with subarachnoid extension (SAHE) predicts poor outcomes and haematoma expansion in spontaneous ICH and is also a potential predictor of the severity of vascular amyloid deposition. The biological underpinnings of SAHE remain elusive. A study was conducted to identify risk factors associated with SAHE. METHODS: A retrospective analysis was performed of an ongoing prospective cohort of primary spontaneous supratentorial ICH patients admitted to Tongji Hospital. SAHE was rated on baseline noncontrast computed tomography images by investigators blinded to the clinical data. RESULTS: A total of 189 patients were enrolled. Apolipoprotein E (APOE) ε2 copies (p = 0.020), but not APOE ε4 copies (p > 0.2), were more common in patients with SAHE in univariate analysis. After controlling for confounding factors in multiple logistic regression, lobar haematoma (odds ratio [OR] 14.21, 95% confidence interval [CI] 5.89-34.33; p < 0.001), large haematoma volume (OR 1.04, 95% CI 1.02-1.06; p < 0.001) and APOE ε2 copies (OR 3.07, 95% CI 1.05-8.97; p = 0.041) were three independent predictors of SAHE. For subgroup analysis stratified by location, APOE ε2 showed a possible association with SAHE in lobar ICH (p = 0.026) but not in deep ICH (p > 0.2). No significant association was found between APOE ε4 copies and either lobar (p > 0.2) or deep ICH (p > 0.2). CONCLUSIONS: The APOE ε2 allele predicts SAHE in spontaneous supratentorial ICH. The association may predominantly apply to lobar ICH. Given the established relationship between the APOE ε2 allele and pathological cerebrovascular changes, our findings suggest that SAHE involves genetically driven vessel pathology.