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Su-Hua Yang,1,&ast; Yi-Shan He,2,&ast; Shu-Qin Zheng,3 Xiu-Jun Zhang,3 Hong Dai,1,&ast; Yuan Xue2,3,&ast; 1Department of General Surgery, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Infectious Diseases, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 3Institute of Hepatology, Changzhou Third People’s Hospital, Changzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Dai, Department of General Surgery, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China, Email daihong@njmu.edu.cn Yuan Xue, Institute of Hepatology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, No. 300 Lanling North Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 519 82009059, Email xueyuan@njmu.edu.cnAim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC).Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC.Results: The median follow-up time was 37 months (range: 6– 123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P< 0.01), DC (P< 0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P< 0.01), and HBV DNA positivity (P< 0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, < 0.01, 0.05, and < 0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P< 0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively.Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.Keywords: hepatocellular carcinoma, triglyceride-glucose index, insulin resistance, liver cirrhosis, decompensated cirrhosis

Yi-Sheng He,1,2,&ast; Gui-Hong Wang,3,&ast; Qian Wu,1,2,&ast; Zheng-Dong Wu,1,2 Yue Chen,1,2 Jin-Hui Tao,4 Xin-Yu Fang,1,2 Zhiwei Xu,5 Hai-Feng Pan1,2 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People’s Republic of China; 3Department of Rheumatology, Anqing Hospital Affiliated to Anhui Medical University, Anqing, Anhui, People’s Republic of China; 4Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 5School of Public Health, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia&ast;These authors contributed equally to this workCorrespondence: Zhiwei Xu; Hai-Feng Pan Email xzw1011@gmail.com; panhaifeng1982@sina.comObjective: Gout is a chronic disease caused by the deposition of sodium urate (MSU) crystals. Available data on the association between environmental hazards and gout are scarce. The present study was present to investigate the relationship between short-term exposure to air pollution and hospitalizations for acute gout from 2016 to 2020 in Anqing City, China.Methods: Daily records of hospital admissions for acute gout in Anqing from 1 January 2016 to 31 December 2020 were retrieved from the tertiary first-class hospitals in Anqing. Air pollutants and meteorological data were obtained from the China Environmental Monitoring Station and China Meteorological Data Service Center respectively. We used a time-series analysis to explore the association between air pollution (NO2, O3, and CO) and hospitalizations for acute gout, and conducted stratified analyses by gender, age and season.Results: We observed an association between NO2 and hospitalizations for gout (lag 0, relative risk (RR):1.022, 95% confidence interval (CI):1.004– 1.041). For every 1 mg/m3 increase in CO concentration, hospitalizations for gout increased by 3.9% (lag 11 days, RR=1.039, 95% CI: 1.004– 1.076). Intriguingly, there was a negative association between O3 and hospitalizations for gout (lag0, RR=0.986, 95% CI: 0.976– 0.996). Stratified analyses showed that exposure to high levels of NO2 was considered to be more vulnerable to gout in cold season.Conclusion: Our study showed that short-term exposure to NO2 and CO has a significant effect on hospitalizations for acute gout.Keywords: gout, air pollutants, carbon monoxide, nitrogen dioxide, ozone

Ren-Ren Li,1,* Yu-Sheng He,1,* Meng Liu,1 Zhi-Yu Nie,1 Li-He Huang,2 Zheng Lu,3 Ling-Jing Jin,1 Yun-Xia Li1 1Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People’s Republic of China; 2School of Foreign Languages, Research Center for Ageing, Language and Care, Tongji University, Shanghai 200092, People’s Republic of China; 3Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun-Xia LiDepartment of Neurology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, People’s Republic of ChinaEmail doctorliyunxia@163.comPurpose: This study aimed to characterize white matter lesions (WMLs) and regional cerebral perfusion, and evaluate their correlations with cognitive deficits in Alzheimer’s disease (AD) patients.Patient and methods: One hundred and twenty-eight patients with AD (AD group) and 75 subjects without AD (control group) were recruited. The medical information was collected from each subject. Montreal cognitive assessment (MoCA) was employed for the assessment of cognition. Cranial MRI was performed, and the KIM scoring system was used to evaluate the white matter hyperintensity. The CT perfusion (CTP) imaging was employed to assess the whole cerebral perfusion, and the region of interest (ROI) was selected to determine the blood perfusion at different parts.Results: The education level and MoCA score in AD group were significantly lower than in control group (P

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Emerging research has investigated the potential impact of several modifiable risk factors on the risks of rheumatoid arthritis (RA), but the findings did not yield consistent results. This study aimed to comprehensively explore the genetic causality between modifiable risk factors and the susceptibility of RA risk using the Mendelian randomization (MR) approach., Methods: Genetic instruments for modifiable risk factors were selected from several genome-wide association studies at the genome-wide significance level (p < 5 × 10 -8 ), respectively. Summary-level data for RA were sourced from a comprehensive meta-analysis. The causal estimates linking modifiable risk factors to RA risk were assessed using MR analysis with inverse variance weighting (IVW), MR-Egger, weighted, and weighted median methods., Results: After Bonferroni correction for multiple tests, we found the presence of causality between educational attainment and RA, where there were protective effects of educational attainment (college completion) (odds ratio [OR] = 0.50, 95% CI = 0.36, 0.69, p = 2.87E-05) and educational attainment (years of education) (OR = 0.93, 95% CI = 0.90, 0.96, p = 4.18E-06) on the lower RA risks. Nevertheless, smoking initiation was observed to be associated with increased RA risks (OR = 1.27, 95% CI = 1.09, 1.47, p = .002). Moreover, there was no indication of horizontal pleiotropy of genetic variants during causal inference between modifiable risk factors and RA., Conclusions: Our study reveals the genetic causal impacts of educational attainment and smoking on RA risks, suggesting that the early monitoring and recognition of modifiable risk factors would be beneficial for the preventive counseling/treatment strategies for RA., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Semi-solid lithium-ion batteries (SSLIBs) based on "slurry-like" electrodes hold great promise to enable low-cost and sustainable energy storage. However, the development of the SSLIBs has long been hindered by the lack of high-performance anodes. Here the origin of low initial Coulombic efficiency (iCE, typically <60%) is elucidated in the graphite-based semi-solid anodes (in the non-flowing mode) and develop rational strategies to minimize the irreversible capacity loss. It is discovered that Ketjen black (KB), a nanoscale conductive additive widely used in SSLIB research, induces severe electrolyte decomposition during battery charge due to its large surface area and abundant surface defects. High iCEs up to 92% are achieved for the semi-solid graphite anodes by replacing KB with other low surface-area, low-defect conductive additives. A semi-solid full battery (LiFePO 4 vs graphite, in the non-flowing mode) is further demonstrated with stable cycle performance over 100 cycles at a large areal capacity of 6 mAh cm -2 and a pouch-type semi-solid full cell that remains functional even when it is mechanically abused. This work demystifies the SSLIBs and provides useful physical insights to further improve their performance and durability., (© 2024 Wiley‐VCH GmbH.)

Malignant tumors represent a significant health challenge, critically impacting human well-being. Malignant tumors have become one of the leading causes of death worldwide. According to statistics from the World Health Organization, nearly one-sixth of global deaths in 2020 were caused by malignant tumors. The burden of malignant tumors in our country is also increasing. In recent years, with population aging and changes in lifestyle, the incidence and mortality rates of malignant tumors in China have been steadily rising, malignant tumors have gradually become one of the main causes of death in China. Developing effective diagnostic and treatment methods is of great significance in reducing the burden of malignant tumors in our country. Historically, the focus has been on leveraging the biochemical cues of tumors for both diagnosis and treatment. While valuable, this strategy does not recapitulate the full complexity of tumor diagnosis and management. Recently, the integration of biomechanics and mechanobiology with oncology has highlighted the importance of mechanical cues, which have emerged as new hallmarks of tumors, regulating tumor initiation and development are expected to open potential novel routes for cancer diagnosis and therapeutic interventions. Despite the advances, a thorough literature review suggests a pronounced gap in our understanding of the mechanical properties of tumors. The clinical community has not yet completely recognized the diagnostic and therapeutic relevance of the mechanical cues of tumors. To bridge this knowledge gap, we propose and introduce the paradigm of "Tumor Mechanomedicine". We provide a comprehensive overview of the multi-scale mechanical characteristics of tumors, exploring their influence on tumor biology, from the aspects of tumor biomechanics, tumor mechanobiology, tumor mechanodiagnostics, and tumor mechanotherapeutics. By elucidating the diagnostic and therapeutic potential of these mechanical cues, we aim to furnish the oncology community with fresh insights, paving the way for innovative solutions to persistent clinical conundrums.

Based on a critical examination of type specimens, images of living plants, and the literature has shown Rhododendronoligocarpum to be conspecific with R.leishanicum . Although slight variations in corolla colour exist amongst different populations of R.oligocarpum , it does not serve as a key distinguishing trait. Therefore, we reduced R.oligocarpum to a synonym of R.leishanicum , and recommend placing it in Subsection Maculifera., Competing Interests: The authors have declared that no competing interests exist., (Sheng Chen, Lei Hao, Yi-Hui Deng, Cheng-Hua Yang, Jun-Mei Yuan, Jia-Xin Lou, Yun-Song He, Xiang Chen.)

Introduction: Air pollution is speculated to increase the risk of Coronavirus disease-2019 (COVID-19). Nevertheless, the results remain inconsistent and inconclusive. This study aimed to explore the association between ambient air pollution (AAP) and COVID-19 risks using a meta-analysis with meta-regression modelling., Methods: The inclusion criteria were: original studies quantifying the association using effect sizes and 95 % confidence intervals (CIs); time-series, cohort, ecological or case-crossover peer-reviewed studies in English. Exclusion criteria encompassed non-original studies, animal studies, and data with common errors. PubMed, Web of Science, Embase and Google Scholar electronic databases were systemically searched for eligible literature, up to 31, March 2023. The risk of bias (ROB) was assessed following the Agency for Healthcare Research and Quality parameters. A random-effects model was used to calculate pooled risk ratios (RRs) and their 95 % CIs., Results: A total of 58 studies, between 2020 and 2023, met the inclusion criteria. The global representation was skewed, with major contributions from the USA (24.1 %) and China (22.4 %). The distribution included studies on short-term (43.1 %) and long-term (56.9 %) air pollution exposure. Ecological studies constituted 51.7 %, time-series-27.6 %, cohorts-17.2 %, and case crossover-3.4 %. ROB assessment showed low (86.2 %) and moderate (13.8 %) risk. The COVID-19 incidences increased with a 10 μg/m 3 increase in PM 2.5 [RR = 4.9045; 95 % CI (4.1548-5.7895)], PM 10 [RR = 2.9427: (2.2290-3.8850)], NO 2 [RR = 3.2750: (3.1420-3.4136)], SO 2 [RR = 3.3400: (2.7931-3.9940)], CO [RR = 2.6244: (2.5208-2.7322)] and O 3 [RR = 2.4008: (2.1859-2.6368)] concentrations. A 10 μg/m 3 increase in concentrations of PM 2.5 [RR = 3.0418: (2.7344-3.3838)], PM 10 [RR = 2.6202: (2.1602-3.1781)], NO 2 [RR = 3.2226: (2.1411-4.8504)], CO [RR = 1.8021 (0.8045-4.0370)] and O 3 [RR = 2.3270 (1.5906-3.4045)] was significantly associated with COVID-19 mortality. Stratified analysis showed that study design, exposure period, and country influenced exposure-response associations. Meta-regression model indicated significant predictors for air pollution-COVID-19 incidence associations., Conclusion: The study, while robust, lacks causality demonstration and focuses only on the USA and China, limiting its generalizability. Regardless, the study provides a strong evidence base for air pollution-COVID-19-risks associations, offering valuable insights for intervention measures for COVID-19., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

This study aimed to determine if air pollution affected the risk of periodontitis outpatient visits. We collected the records of 56,456 periodontitis outpatient visits in Hefei, China, from January 1, 2014 to December 31, 2021. The relationship between air pollution and periodontitis outpatient visits was evaluated using distributed lag nonlinear and generalized linear models. Additional analyses were performed, stratifying the data by age, season, and sex. Subgroup analyses showed a significantly higher risk of periodontitis outpatient visits due to NO 2 exposure during the warm season compared with the cold season. Moreover, O 3 exposure was associated with a lower risk of periodontitis outpatient visits in the cold season. The findings suggest that NO 2 exposure is associated with an increased risk of periodontitis outpatient visits, whereas O 3 exposure is associated with a decreased risk of periodontitis outpatient visits. Season is found to be an effect modifier in these associations.

Pyroptosis-mediated neuron death plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). However, the effect of 1,7-diphenyl-4-hepten-3-one (C1), a natural diarylheptanoid, on AD is unclear. Herein, we investigated the therapeutic effect of C1 on APP/PS1 mice and β-amyloid (Aβ)-induced HT22 cells. Our findings showed that C1 attenuated cognitive impairment and mitigated pathological damage in APP/PS1 mice. Furthermore, we found that C1 prevented oxidative stress damage and decreased the levels of pyroptosis-related proteins. In vitro experiments showed that C1 can improve the proliferation of Aβ-induced HT22 cells and decrease the levels of pyroptosis-related proteins in them. When Nrf2 was silenced, the positive effects of C1 in inhibiting pyroptosis were inhibited. Particularly, the production of pyroptosis-associated proteins, including NLRP3, GSDMD, and caspase-1, and the secretion of pro-inflammatory molecules, including IL-1 and IL-18, were increased. Altogether, these findings indicate that C1 can mitigate AD-like pathology via the inhibition of pyroptosis by activating the Nrf2 pathway. We believe that this study can provide alternative strategies for the prevention and treatment of AD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy., Methods: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores., Results: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes., Conclusion: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup., (© 2024. The Author(s).)

Cytidine deaminase defines the properties of cytosine base editors (CBEs) for C-to-T conversion. Replacing the cytidine deaminase rat APOBEC1 (rA1) in CBEs with a human APOBEC3A (hA3A) improves CBE properties. However, the potential CBE application of macaque A3A orthologs remains undetermined. Our current study develops and evaluates engineered CBEs based on Macaca fascicularis A3A (mA3A). Here, we demonstrate that BE4-mA3A and its RNA-editing-derived variants exhibit improved CBE properties, except for DNA off-target activity, compared to BE3-rA1 and BE4-rA1. Unexpectedly, deleting Ser-Val-Arg (SVR) in BE4-mA3A dramatically reduces DNA and RNA off-target activities and improves editing accuracy, with on-target efficiency unaffected. In contrast, a chimeric BE4-hA3A-SVR + shows editing efficiency increased by about 50%, with other properties unaffected. Our findings demonstrate that mA3A-based CBEs could provide prototype options with advantages over rA1- and hA3A-based CBEs for further optimization, highlighting the importance of the SVR motif in defining CBE intrinsic properties., Competing Interests: Declaration of interests C.-Y.R., J.-H.C., and Y.-S.L. have filed patent applications on this work through Jiangnan University., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3'-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The effects of heavy metal exposure on immunological function have sparked widespread concern, but unequivocal evidence on the association between mixed metal exposure and novel systemic inflammatory indexes remains scarce., Objectives: This study aimed to analyze the associations of heavy metals with two novel systemic inflammation indexes and the mediated effects of serum albumin., Methods: Nineteen metals were detected among 4082 U.S. adults based on the NHANES. A linear regression, restricted cubic splines (RCS) regression, weighted quantile sum (WQS), Quantile-based Gcomputation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted to evaluate the associations of single metal and mixed metals with systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) levels, respectively. A series of subgroup analyses were used to identify potentially vulnerable populations. Furthermore, we conducted mediation analyses to investigate the mediated effects of serum albumin on the associations of metals with SII and SIRI., Results: In the single-exposure model, exposure to various metals such as urinary Co, As, and serum Zn, Cu was associated with SII and SIRI (P FDR <0.05). Simultaneously, the above metals were linear positively correlated with SII and SIRI. Mixed-exposure analyses consistently showed that overall mixed urinary metal levels were positively pertinent for SII and SIRI levels, and the metal Co played a significant role in the urinary metal mixtures. Subgroup analyses showed that exposure to urinary Cd in men and elderly people increased SII and SIRI levels. The results of mediation analyses suggested the association of urinary metal mixture with SII and SIRI was mediated by albumin, and the proportion of mediation was 14.45% and 9.49%, respectively., Conclusions: Our findings suggested that metal exposure is strongly associated with the levels of system inflammation indexes and that serum albumin is, in part, a mediator of this association., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to examine rheumatoid arthritis (RA) risk associated with hormonal and reproductive factors in women from the large cohort of the UK Biobank., Methods: Data on hormonal and reproductive factors in women were collected from a prospective cohort of 223 526 UK Biobank participants. The potential relationship between reproductive factors and RA risk was assessed using restricted cubic spline. Hazard ratios (HR) were estimated using Cox proportional hazard regressions., Results: During a median follow-up of 12.39 years, 3313 women with RA were identified. Age at menarche >14 years was associated with a greater RA risk (HR 1.13, 95% CI 1.02 to 1.26) compared with menarche at 13. The multiple adjusted HR for RA in women with menopause at <45 years was 1.46. Reproductive years <33 increased the risk of RA (HR 1.39, 95% CI 1.21 to 1.59). Compared with those with 2 children, women with ≥4 children were associated with a higher risk of RA (HR 1.18, 95% CI 1.04 to 1.34). Women who had a hysterectomy (HR 1.40, 95% CI 1.25 to 1.56) or oophorectomy (HR 1.21, 95% CI 1.08 to 1.35) had a higher risk of RA than those without a hysterectomy or oophorectomy. Both hormone replacement therapy (HRT) use (HR 1.46, 95% CI 1.35 to 1.57) and HRT duration (HR 1.02, 95% CI 1.01 to 1.03) were associated with a higher risk of RA., Conclusions: Some hormonal and reproductive factors were associated with a higher risk of RA. Hormonal and reproductive factors should be considered in risk assessment and formulating management plans in female patients with RA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort., Methods: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence ( net drift , % per year), annual percentage change of prevalence within each age group ( local drift , % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019., Results: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift , higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts., Conclusions: Although a favourable overall temporal trend ( net drift ) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Decrease in estimated glomerular filtration rate (eGFR) during Tenofovir disoproxil fumarate (TDF) treatment remains a concern, and few patients experience partial recovery of eGFR. This study aimed to investigate the risk factors for eGFR recovery in patients with and without hypertriglyceridemia., Methods: A total of 203 patients with chronic HBV infection were prospectively recruited and followed up for three years. Data were collected at baseline, first, second, and third years during TDF treatment., Results: Most patients achieved normal ALT (80.0% vs. 82.5%) and undetectable HBV DNA (95.0% vs. 95.6%) in both groups ( p  > 0.05). For patients with hypertriglyceridemia, eGFR and cholesterol did not change significantly during the 3-year follow-up, while triglyceride (TG) decreased significantly in the first year and persisted at a lower level in the subsequent two years. For patients without hypertriglyceridemia, eGFR declined significantly in the first year of treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG at the four time points. Fifteen (15/183, 8.2%) patients without hypertriglyceridemia experienced eGFR partial recovery in the third year. Univariate and multivariate analyses showed that baseline eGFR <90 mL/(min·1.73 m 2 ) ( p  < 0.01; 95% CI: 0.019-0.284) and age ( p  < 0.01; 95% CI: 0.817-0.960) were independent risk factors for eGFR recovery., Conclusion: eGFR partially recovered in patients without hypertriglyceridemia during TDF treatment, and TG regulation might be a useful strategy to hinder renal function decline, although larger, confirmatory studies are necessary to validate our findings.Key messagesFor patients with normal triglyceride, eGFR declined significantly at the first year of TDF treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG. Baseline eGFR <90 mL/(min·1.73 m 2 ) and age were independent risk factors for eGFR recovery.

Aim: To estimate the age-standardized incidence, prevalence, and mortality rates of autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), asthma, and psoriasis in women of childbearing age from 1990 to 2019, and to further analyze their changing trends, at global, regional, and national levels., Methods: Women of childbearing age was defined as 15-49 years old. The estimates and 95% uncertainty intervals (UIs) for case number of RA, IBD, MS, T1DM, asthma and psoriasis in seven age groups (15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49 years) were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age standardization by direct method was adopted to estimate the age-standardized incidence, prevalence, and mortality rates of these autoimmune diseases in women of childbearing age. Joinpoint regression analysis was utilized to analyze the changing trends of estimated age-standardized incidence, prevalence, and mortality rates from 1990 to 2019 by calculating the average annual percentage change (AAPC) and its 95% confidence intervals (CIs)., Results: In 2019, the estimated global age-standardized incidence, prevalence, and mortality rates of RA in women of childbearing age was 17.13 (95% UI: 12.39 to 22.60), 215.86 (95% UI: 179.04 to 259.70), and 0.06 (95% UI: 0.04 to 0.08); of IBD was 5.85 (95% UI: 4.72 to 7.12), 63.54 (95% UI: 53.50 to 74.37), and 0.11 (95% UI: 0.08 to 0.13); of MS was 1.63 (95% UI: 1.05 to 2.28), 28.74 (95% UI: 23.80 to 34.46), and 0.17 (95% UI: 0.14 to 0.27); of T1DM was 6.22 (95% UI: 2.75 to 11.50), 290.51 (95% UI: 221.39 to 370.19), and 0.63 (95% UI: 0.48 to 0.78); of asthma was 291.14 (95% UI: 157.06 to 468.78), 2796.25 (95%UI: 1987.07 to 3842.97), and 1.42 (95% UI: 1.12 to 1.75), respectively. The estimated global age-standardized incidence and prevalence rates of psoriasis in women of childbearing age was 58.68 (95% UI: 51.04 to 66.85) and 477.20 (95% UI: 440.30 to 515.76). Highest disease burden generally exists in Region of the Americas and European Region. From 1990 to 2019, the estimated global age-standardized incidence and prevalence rates of RA (AAPC: 0.18, 95% CI: 0.11 to 0.24; AAPC: 0.24, 95% CI: 0.18 to 0.30) and T1DM (AAPC: 1.47, 95% CI: 1.40 to 1.54; AAPC: 0.83, 95% CI: 0.79 to 0.88) in women of childbearing age showed significantly increasing trends whereas those of IBD (AAPC: -0.76, 95% CI: -0.80 to -0.73; AAPC: -0.65, 95% CI: -0.70 to -0.60), MS (AAPC: -0.20, 95% CI: -0.23 to -0.16; AAPC: -0.25, 95% CI: -0.26 to -0.23), asthma (AAPC: -0.53, 95% CI: -0.60 to -0.47; AAPC: -0.74, 95% CI: -0.81 to -0.68), and psoriasis (AAPC: -0.83, 95% CI: -0.85 to -0.82; AAPC: -0.99, 95% CI: -1.02 to -0.96) showed significantly decreasing trends. Favorably, the estimated global age-standardized mortality rate of RA (AAPC: -1.32, 95% CI: -1.63 to -1.01), IBD (AAPC: -0.95, 95% CI: -1.06 to -0.84), MS (AAPC: -0.96, 95% CI: -1.12 to -0.80), T1DM (AAPC: -1.05, 95% CI: -1.21 to -0.89), and asthma (AAPC: -2.27, 95% CI: -2.34 to -2.19) in women of childbearing age all declined. The changing trends of estimated age-standardized incidence, prevalence, and mortality rates varied significantly across 204 countries and territories., Conclusions: Our study provides an accurate estimation on the age-standardization of disease indicators of autoimmune diseases in women of childbearing age. There are remarkable disparities in the incidence, prevalence, and mortality burden related to autoimmune diseases in women of childbearing age, as well as their changing trends across the world, suggesting that each individual government should establish flexible health policies and make reasonable source allocation to address different needs for autoimmune diseases in this population., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

The LiNi 0.8 Mn 0.1 Co 0.1 O 2 (NMC811) cathode material has been of significant consideration owing to its high energy density for Li-ion batteries. However, the poor cycling stability in a carbonate electrolyte limits its further development. In this work, we report the excellent electrochemical performance of the NMC811 cathode using a rational electrolyte based on organic ionic plastic crystal N -ethyl- N -methyl pyrrolidinium bis(fluorosulfonyl)imide C 2 mpyr[FSI], with the addition of (1:1 mol) LiFSI salt. This plastic crystal electrolyte (PC) is a thick viscous liquid with an ionic conductivity of 2.3 × 10 -3 S cm -1 and a high Li + transference number of 0.4 at ambient temperature. The NMC811@PC cathode delivers a discharge capacity of 188 mA h g -1 at a rate of 0.2 C with a capacity retention of 94.5% after 200 cycles, much higher than that of using a carbonate electrolyte (54.3%). Moreover, the NMC811@PC cathode also exhibits a superior high-rate capability with a discharge capacity of 111.0 mA h g -1 at the 10 C rate. The significantly improved cycle performance of the NMC811@PC cathode can be attributed to the high Li + conductivity of the PC electrolyte, the stable Li + conductive CEI film, and the maintaining of particle integrity during long-term cycling. The admirable electrochemical performance of the NMC811|C 2 mpyr[FSI]:[LiFSI] system exhibits a promising application of the plastic crystal electrolyte for high voltage layered oxide cathode materials in advanced lithium-ion batteries.

We report a chiral phosphoric acid catalyzed apparent hydrolytic ring-opening reaction of racemic aziridines in a regiodivergent parallel kinetic resolution manner. Harnessing the acyloxy-assisted strategy, the highly stereocontrolled nucleophilic ring-opening of aziridines with water is achieved. Different kinds of aziridines are applicable in the process, giving a variety of enantioenriched aromatic or aliphatic amino alcohols with up to 99% yields and up to >99.5 : 0.5 enantiomeric ratio. Preliminary mechanistic study as well as product elaborations were inducted as well., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Osteoarthritis (OA) is a threat to public health issue with high morbidity and disability worldwide. However, unequivocal evidence on the link between air pollution and OA remains little, especially in multi-study sites. This study aimed to explore the relationship between short-term exposure to main air pollutants and the risk of OA outpatient visits in multi-study sites. A multi-city time-series analysis was performed in Anhui Province, Central-Eastern China from January 1, 2015, to December 31, 2020. We used a two-stage analysis to assess the association between air pollution and daily OA outpatient visits. City-specific associations were estimated with a distributed lag nonlinear model and then pooled by random-effects or fixed-effects meta-analysis. Stratified analysis was conducted by gender, age, and season. Additionally, the disease burden of OA attributable to air pollutant exposure was calculated. A total of 35,700 OA outpatients were included during the study period. The pooled exposure-response curves showed that PM 2.5 and PM 10 concentrations below the reference values could increase the risk of OA outpatient visits. Concretely, per 10 ug/m 3 increase in PM 2.5 concentration was linked to an elevated risk of OA outpatient visits at lag 2 and lag 3 days, where the effect reached its highest value on lag 2 day (RR: 1.023, 95%CI: 1.005-1.041). We observed that a 10 μg/m 3 increase in PM 10 was positively correlated with OA outpatient visits (lag2 day, RR: 1.011, 95%CI: 1.001-1.025). Nevertheless, no statistical significance was discovered in gaseous pollutants (including SO 2 , O 3 , and CO). Additionally, a significant difference was found between cold and warm seasons, but not between different genders or age groups. This study reveals that particulate matter is an important factor for the onset of OA in Anhui Province, China. However, there is no evidence of a relationship of gaseous pollutants with OA in this area., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To explore the microanatomy and functional MRI(fMRI) of arcuate fasciculus(AF) and superior longitudinal fasciculus(SLF),and to analyze their functions. Methods: Ten normal adult cadaveric head specimens (20 cerebral hemispheres) were fixed with 10% methanal at the Translational Research Institute for Neurological Disorders of the Wannan Medical Collegefrom February to December 2022.The Klingler fiber dissection technique was utilized to perform white matter fiber dissection,with a magnification ranging from 6 to 40.The study focused on the microanatomical structures of the AF and SLF,aiming to explore their relationships with deep brain fibers.Furthermore, six healthy adult volunteers who underwent fMRI of the brain were included.The collected diffusion tensor imaging (DTI) data were processed and integrated with the microanatomical findings for a comprehensive analysis. Results: After removing the gray matter of the cerebral cortex,the superficial U fibers were exposed.The long association fibers that beneath the U fibers were the AF and SLF,which were the main long association fibers in the superficial layers of the brain.The AF could be divided into dorsal and ventral parts,while the SLF could be divided into Ⅰ,Ⅱ,and Ⅲ.SLF Ⅰ lied within the upper bank of the cingulate sulcus,travels medial to the callosal sulcus.The SLF Ⅱ,Ⅲ,and the AF were located on the lateral surface of the brain.By removing the gray matter of the insular cortex and the extreme capsule,exposing the external capsule and claustrum.Subsequently,the AF and SLF Ⅱ,Ⅲ were dissected,revealing the corona radiata and sagittal stratum,along with other deep brain fibers.During the dissection,it was observed that there was a close connection between the AF,SLF Ⅱ,and the deep brain fibers.Furthermore,in the regions above the lateral fissure of the cerebral hemisphere,there was no direct connection of long association fibers between the gray matter cortex and the deep U fibers in the coronal plane.These findings were further supported by DTI studies. Conclusions: The AF and SLF are the major long association fibers that located in the superficial layers of the brain,and closely connect to the gray matter cortex and U fibers,even closely relate with deep brain fibers.In the regions above the lateral fissure of the hemisphere,only the AF and SLF Ⅱ and Ⅲ serve as superficial long association fibers in the anterior-posterior direction.These fibers are likely involved in the transmission of brain functional information between the top and bottom gray matter cortex in the coronal plane above the lateral fissure.

The electronic properties, in particular, the occupation number of 5f electrons and the valence state of U ions in uranium sesquinitride (U 2 N 3 ) are studied by using density functional theory (DFT) calculations merged with dynamical mean-field theory (DMFT). The results demonstrate that j=5/2 and j=7/2 manifolds are in the weakly correlated metallic and weakly correlated insulating regimes, respectively. The quasi-particle weights indicate that LS coupling scheme is more feasible for 5f electrons, which are not in the orbital-selective localized state. The weighted summation of the occupation probabilities of 5f n (n=0,1,2,3,4) atomic configurations suggests that 5f electrons have the inter-configuration fluctuation, or the mixed-valence state for U ions, together with an average occupation number of 5f electrons n 5f ∼2.234, which is in good agreement with the electron localization function (ELF) and occupation analysis based on other DFT-based calculations. The 5f n -mixing-driven inter-configuration fluctuation might originate from the dual nature of 5f electrons, and the flexible electronic configuration of U ions. Finally, the so-called quasiparticle band structure is also discussed., (© 2023 Wiley-VCH GmbH.)

With the deepening of research on the correlation between meteorological factors and autoimmune diseases, the relationship between climate change and dermatomyositis (DM) has come to our attention. This study aimed to explore the short-term correlation between meteorological factors and DM outpatient visits. Daily records of hospital outpatient visits for DM, air pollutants, and meteorological factor data in Hefei from January 1, 2018 to December 31, 2021 were obtained. The mean temperature (MT), relative humidity (RH), diurnal temperature range (DTR), and temperature change between neighboring days (TCN) were used to quantify environmental temperature and humidity and their variations. And we performed a time series analysis using a generalized linear model (GLM) in combination with a distributed lag nonlinear model (DLNM). Furthermore, gender and age were further stratified for the analysis. The sensitivity analysis was also performed. A total of 4028 DM outpatient visits were recorded during this period. There were statistically significant associations of low temperature (5th, 1.5 °C), low RH (1st, 48.6%), high RH (99th, 99%), high DTR (75th, 12.6°c), and low TCN (10th, -2.7 °C) that were associated with risk of DM outpatient visits, with lag days of 30, 16, 16, 10, and 14, respectively. Moreover, women were more susceptible to high RH exposure and low TCN exposure, while the elderly were more susceptible to low temperature. This study concluded that exposure to low temperature, extreme RH, and temperature changes (especially high DTR and low TCN) was associated with an increased risk of DM outpatient visits., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, a growing number of studies have found that air pollution plays critical roles in the onset and development of autoimmune diseases, but few studies have shown an association between air pollutants and dermatomyositis (DM). We sought to investigate the relationship between short-term exposure to air pollution and outpatient visits for DM and to quantify the burden of DM due to exposure to air pollutants in Hefei, China. Daily records of hospital outpatient visits for DM, air pollutants and meteorological factors data in Hefei from January 1, 2018 to December 31, 2021 were obtained. We used a distributed lag non-linear model (DLNM) in conjunction with a generalized linear model (GLM) to explore the association between air pollution and outpatient visits for DM, and conducted stratified analyses by gender, age and season. Moreover, we used attributable fraction (AF) and attributable number (AN) to reflect the burden of disease. A total of 4028 DM clinic visits were recorded during this period. High concentration nitrogen dioxide (NO 2 ) exposure was associated with increased risk of DM outpatient visits (relative risk (RR) 1.063, 95% confidence interval (CI) 1.015-1.114, lag 0-5). Intriguingly, exposure to high concentration ozone (O 3 ) was associated with reduced risk of outpatient visits for DM (RR 0.974, 95% CI 0. 0.954-0.993, lag 0-6). The results of stratified analyses showed that the cold season (vs. warm season) were more susceptible to outpatient visits for DM associated with NO 2 and O 3 exposure. In addition, we observed that an increased risk of DM outpatient visits was attributable to high concentration NO 2 exposure, while high concentration O 3 exposure was associated with a decreased risk of DM outpatient visits. This study provided a scientific basis for the etiology research and health protection of DM., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Evidence suggests a possible association between ambient air pollutants and oral diseases. Nevertheless, information regarding the relationship between air pollutants and pulpitis is scarce and inconclusive. In view of this, the present study aimed to investigate the relationship between short-term exposure to air pollution and outpatient visits for pulpitis. Daily data on outpatient visits for pulpitis, air pollutants, and meteorological data in Hefei, China, was collected from January 1, 2015 to December 31, 2021. The association between exposure to air pollutants and pulpitis outpatient visits was evaluated using distributed lag non-linear model (DLNM) and a generalized linear model (GLM). Furthermore, stratified analyses were performed by gender, age and season. A total of 93,324 records of outpatient visits for pulpitis were included in this study. The results showed that exposure to NO 2 , PM 2.5 , and CO were positively correlated with an increased risk of pulpitis outpatient visits. Each 10 μg/m 3 increase in NO 2 and PM 2.5 concentration, at lag 0-2 day, was associated with a 2.4% (relative risk (RR) = 1.024, 95% confidence interval (CI): 1.014-1.035) and 0.5% (RR = 1.005, 95% CI: 1.000-1.010) increase in pulpitis outpatient visits, respectively. With a 1 mg/m 3 increase in CO concentration, the risk of pulpitis outpatient visits increased by 9.1% (RR = 1.091, 95% CI: 1.031-1.154, lag 0-1 day). Intriguingly, exposure to O 3 was associated with a decreased risk of pulpitis outpatient visits (RR = 0.990, 95% CI: 0.984-0.995, lag 0-5 day). Subgroup analysis revealed that in the warm season, exposure to PM 2.5 , O 3 , and CO was related with a significantly higher outpatient risk of pulpitis than in the cold season. Additionally, the influence of PM 2.5 and CO exposure at age < 65 years was significantly stronger than at age ≥ 65 years. In conclusion, exposure to ambient NO 2 , PM 2.5 , and CO is associated with an increase in pulpitis outpatient visits in Hefei, China. Conversely, exposure to O 3 reduces the risk of outpatient visits for pulpitis. Age and season are effect modifiers of these associations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: With the increase in macrolide-resistant M. pneumoniae infections, off-label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric patients with severe refractory M. pneumoniae pneumonia (SRMPP)., Methods: We retrospectively reviewed the medical records of children with SRMPP between January 2017 and November 2020 at Beijing Children's Hospital. They were divided into the moxifloxacin group and azithromycin group according to whether or not moxifloxacin was used. The clinical symptoms, radiographs of both knees, and cardiac ultrasounds of the children were collected after drug withdrawal for at least 1 year. A multidisciplinary team reviewed all adverse events and determined their relationship with moxifloxacin., Results: A total of 52 children with SRMPP were included in this study (31 in the moxifloxacin group and 21 in the azithromycin group). In the moxifloxacin group, four patients had arthralgia, one had joint effusion, and seven had heart valve regurgitation. In the azithromycin group, three patients had arthralgia, one had claudication, and one had heart valve regurgitation; no obvious knee abnormalities were observed in the radiographs. No statistically significant differences in clinical symptoms or imaging findings were found between the groups. As for the adverse events, 11 patients in moxifloxacin group were deemed to be doubtfully related and one possibly related to moxifloxacin; in the azithromycin group, four patients were regarded to be doubtfully related to azithromycin and one not related., Conclusion: Moxifloxacin was well tolerated and safe for treating SRMPP in children., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor ( Vldlr ) in retinal neovascularization and hypoxia-induced factor 1 alpha ( Hif1a ). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development., 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 © 2023 Pan, He, Lu, Pan, Wei, Jin, Wang and Chen.)

Aim: To describe burden, and to explore cross-country inequalities across sociodemographic development levels for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis (PS)., Methods: The estimates and their 95% uncertainty interval (UI) for disability-adjusted life-years (DALYs) of RA, IBD, MS and PS were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age-standardized DALYs rate (ASDR) across 204 countries, as well as age and sex distribution of global DALYs rate of these four ADs were illustrated. Slope index of inequality and concentration index, which are two standard metrics of absolute and relative gradient inequality recommended by World Health Organization (WHO), were utilized to quantify the distributive inequalities in the burden of ADs., Results: In 2019, the ASDR of RA, IBD, MS and PS varied remarkably across 204 countries, with different age and sex distribution of global DALYs rate. The slope index of inequality changed from 26.7 (95% CI: 20.7 to 32.8) in 1990 to 40.3 (95% CI: 31.9 to 48.7) in 2019 for RA, from 17.1 (95% CI: 12.4 to 21.7) in 1990 to 25.2 (95% CI: 20.1 to 30.2) in 2019 for IBD, from 19.3 (95% CI: 15.2 to 23.4) in 1990 to 28.9 (95% CI: 24.2 to 33.5) in 2019 for MS, from 42.3 (95% CI: 33.1 to 51.6) in 1990 to 40.2 (95% CI: 32.5 to 48.0) in 2019 for PS. Moreover, the concentration index showed 20.4 (95% CI: 18.9 to 22.0) in 1990 and 18.2 (95% CI: 16.7 to 19.6) in 2019 for RA, 25.0 (95% CI: 23.0 to 27.1) in 1990 and 33.5 (95% CI: 31.6 to 35.5) in 2019 for IBD, 46.7 (95% CI: 44.0 to 49.3) in 1990 and 41.8 (95% CI: 39.6 to 44.1) in 2019 for MS, 31.7 (95% CI: 29.0 to 34.4) in 1990 and 32.6 (95% CI: 29.9 to 35.2) in 2019 for PS., Conclusions: There is a strong heterogeneity in ASDR across all countries, as well as in age and sex distribution of global DALYs rate for four ADs including RA, IBD, MS and PS. Countries with higher sociodemographic development levels shouldered disproportionately higher burden of ADs, and the magnitude of this sociodemographic development level-related inequalities exacerbated over time., Competing Interests: Declaration of Competing Interest This statement is to certify 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 © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to construct a competent model that can effectively predict the prognosis of patients with gastric carcinoid (GC) or neuroendocrine carcinoma (NEC)., Patients and Methods: Data of patients with GC or NEC were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. Univariable and multivariable Cox analysis was used to determine the independent factors for patients with GC or NEC. Nomograms were established based on the independent factors and the results were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA)., Results: A total of 214 patients with GC and 65 patients with gastric NEC were extracted from the SEER database. Independent prognostic factors for patients with GC were M stage, gender, age, and chemotherapy. Independent prognostic factors for patients with gastric NEC included age, M stage, and chemotherapy. ROC curves, calibration curves, and DCA confirmed that the nomograms can precisely predict the prognosis of patients with GC and NEC., Conclusions: The nomograms can effectively predict survival in patients with GC or NEC, which may assist the clinician in their decision-making and quantitatively judge the prognosis of individual patients.

Na 4 MnV(PO 4 ) 3 /C (NMVP) has been considered an attractive cathode for sodium-ion batteries with higher working voltage and lower cost than Na 3 V 2 (PO 4 ) 3 /C. However, the poor intrinsic electronic conductivity and Jahn-Teller distortion caused by Mn 3+ inhibit its practical application. In this work, the remarkable effects of Zr-substitution on prompting electronic and Na-ion conductivity and also structural stabilization are reported. The optimized Na 3.9 Mn 0.95 Zr 0.05 V(PO 4 ) 3 /C sample shows ultrafast charge-discharge capability with discharge capacities of 108.8, 103.1, 99.1, and 88.0 mAh g -1 at 0.2, 1, 20, and 50 C, respectively, which is the best result for cation substituted NMVP samples reported so far. This sample also shows excellent cycling stability with a capacity retention of 81.2% at 1 C after 500 cycles. XRD analyses confirm the introduction of Zr into the lattice structure which expands the lattice volume and facilitates the Na + diffusion. First-principle calculation indicates that Zr modification reduces the band gap energy and leads to increased electronic conductivity. In situ XRD analyses confirm the same structure evolution mechanism of the Zr-modified sample as pristine NMVP, however the strong ZrO bond obviously stabilizes the structure framework that ensures long-term cycling stability., (© 2023 Wiley-VCH GmbH.)

Background: The evolution of insect resistance to pesticides poses a continuing threat to sustainable pest management. While much is known about the molecular mechanisms that confer resistance in model insects and few agricultural pests, far less is known about fruit pests. Field-evolved resistance to synthetic insecticides such as lambda-cyhalothrin has been widely documented in Cydia pomonella, a major invasive pest of pome fruit worldwide, and the increased production of cytochrome P450 monooxygenases (P450s) has been linked to resistance in field-evolved resistant populations. However, the underlying molecular mechanisms of P450-mediated insecticide resistance remain largely unknown., Results: Here we found that functional redundancy and preference of metabolism by P450s genes in the CYP9A subfamily confer resistance to lambda-cyhalothrin in Cydia pomonella. A total of four CYP9A genes, including CYP9A61, CYP9A120, CYP9A121, and CYP9A122, were identified from Cydia pomonella. Among these, CYP9A120, CYP9A121, and CYP9A122 were predominantly expressed in the midgut of larvae. The expression levels of these P450 genes were significantly induced by a lethal dose that would kill 10% (LD 10 ) of lambda-cyhalothrin and were overexpressed in a field-evolved lambda-cyhalothrin resistant population. Knockdown of CYP9A120 and CYP9A121 by RNA-mediated interference (RNAi) increased the susceptibility of larvae to lambda-cyhalothrin. In vitro assays demonstrated that recombinant P450s expressed in Sf9 cells can metabolize lambda-cyhalothrin, but with functional redundancy and divergence through regioselectivity of metabolism. CYP9A121 preferred to convert lambda-cyhalothrin to 2'-hydroxy-lambda-cyhalothrin, whereas CYP9A122 only generated 4'-hydroxy metabolite of lambda-cyhalothrin. Although possesses a relatively low metabolic capability, CYP9A120 balanced catalytic competence to generate both 2'- and 4'-metabolites., Conclusion: Collectively, these results reveal that metabolic functional redundancy of three members of the CYP9A subfamily leads to P450-mediated lambda-cyhalothrin resistance in Cydia pomonella, thus representing a potential adaptive evolutionary strategy during its worldwide expansion. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Objective: Emerging evidence has highlighted the possible links of environmental pollution with several cardiovascular diseases (CVDs). The current study aimed to explore the impact of short-term air pollution exposure on CHD hospitalization in Hefei., Methods: Data about the daily number of CHD admissions (from 2014 to 2021) were retrieved from the First Affiliated Hospital of Anhui Medical University. Air pollutants and meteorological data were obtained from the China Environmental Monitoring Station and the China Meteorological Data Service Center, respectively. The correlation between air pollution and CHD hospitalization was assessed using distributed lag non-linear model (DLNM) and Poisson generalized linear regression., Results: In the single-pollutant model, NO 2 , O 3 , and CO strongly correlated with CHD hospitalization rate. Specifically, exposure to NO 2 (lag0, relative risk [RR]: 1.013, 95%CI: 1.002-1.024, per 10 μg/m 3 increase) and CO (lag13, RR: 1.035, 95%CI: 1.001-1.071, per 1 μg/m 3 increase) revealed a positive correlation with an increased rate of CHD hospitalization. Interestingly, O 3 had a protective association with hospitalization of CHD (lag0, RR: 0.993, 95%CI: 0.988-0.999, per 10 μg/m 3 increase). Similar results, to those of the single-pollutant model, were revealed following verification using two-pollutant models. Subgroup analyses indicated that young people, women, and people in hot seasons were more susceptible to NO 2 exposure, while the elderly, women, and people in cold seasons were more susceptible to O 3 . Furthermore, the elderly were more susceptible to CO exposure., Conclusion: Overall, exposure to NO 2 and CO increases the rate of CHD hospitalization, but exposure to O 3 shows a protective association with the rate of CHD hospitalization. Therefore, early preventive measures against air pollutants should be applied to protect vulnerable patients with CHD., 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 © 2023 Feng, Lang, Chen, Harry Asena, Fang, Zhang, Jiang, Fang, Chen, He, Wang and Pan.)

Objective: This study aims to explore the association between early administration of vasopressors and in-hospital mortality in acute pancreatitis (AP) patients admitted to the ICU., Patients and Methods: The MIMIC-IV database was used to identify AP patients who had and had not received vasopressors. Univariate and multivariate logistic regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were used for statistical analysis., Results: A total of 894 AP patients admitted to the ICU were included in the study. Among them, AP patients who received vasopressors were associated with an increased risk of in-hospital mortality in the unadjusted model (OR: 7.77, 95% CI 4.92-12.61, p<0.001), multivariable-adjusted model (OR: 2.51,95% CI 1.1-5.76, p<0.05), PSM model (OR: 2.58, 95% CI 1.03-6.85, p<0.05) and IPTW model (OR: 1.82, 95% CI 1.06-3.15, p<0.05) compared with patients who did not receive vasopressors. In the subgroup analysis, age (≥ 65 years old: OR: 2.5, 95% CI 0.82-7.91; <65 years old: OR: 4.63, 95% CI 0.84-26.41), male (OR: 1.19, 95% CI 0.35-4.03), ethnicity (white: OR: 2.49, 95% CI 0.81-7.62; non-white: OR: 4.28, 95% CI 0.85-23.7), usage of norepinephrine (OR: 2.29, 95% CI 0.91-5.78), and single-use of vasopressor (OR: 1.48, 95% CI 0.43-4.95) were not associated with in-hospital mortality in patients with AP, whereas vasopressin (OR: 4.27, 95% CI 1.24-15.13; p<0.05) and phenylephrine usage (OR: 4.75, 95% CI 1.66-13.95; p<0.05), combined vasopressor usage (OR: 4.41, 95% CI 1.55-12.96; p<0.01), and female usage (OR: 7.89, 95% CI 2.03-34.2; p<0.01) were associated with in-hospital mortality., Conclusions: Early vasopressor use is significantly associated with increased in-hospital mortality among critically ill AP patients. This association might be greater in females, vasopressin, phenylephrine, and combined vasopressor users. Our results may benefit clinicians as they can guide the rational use of vasopressors in critically ill AP patients admitted to the ICU.

For the upsurge of high breakdown strength ([Formula: see text]), efficiency ([Formula: see text]), and discharge energy density ([Formula: see text]) of next-generation dielectrics, nanocomposites are the most promising candidates. However, the skillful regulation and application of nano-dielectrics have not been realized so far, because the mechanism of enhanced properties is still not explicitly apprehended. Here, we show that the electric field cavity array in the outer interface of nanosieve-substrate could modulate the potential distribution array and promote the flow of free charges to the hole, which works together with the intrinsic defect traps of active Co 3 O 4 surface to trap and absorb high-energy carriers. The electric field and potential array could be regulated by the size and distribution of mesoporous in 2-dimensional nano-sieves. The poly(vinylidene fluoride-co-hexafluoropropylene)-based nanocomposites film exhibits an [Formula: see text] of 803 MV m -1 with up to 80% enhancement, accompanied by high [Formula: see text] = 41.6 J cm -3 and [Formula: see text]≈ 90%, outperforming the state-of-art nano-dielectrics. These findings enable deeper construction of nano-dielectrics and provide a different way to illustrate the intricate modification mechanism from macro to micro., (© 2022. The Author(s).)

A micro-cubic Prussian blue (PB) with less coordinated water is first developed by electron exchange between graphene oxide and PB. The obtained reduced graphene oxide-PB composite exhibited increased redox reactions of the Fe sites and delivered ultrahigh specific capacity of 163.3 mA h g -1 (30 mA g -1 ) as well as excellent cycle stability as a cathode in sodium-ion batteries.

Background: Correlation between Triglyceride (TG) and estimated glomerular filtration rate (eGFR) remains largely unknown in overweight and non-overweight patients., Aim: To investigated the dynamic changes of eGFR and lipid profiles during 3-year tenofovir disoproxil fumarate (TDF) treatment in patients with chronic hepatitis B (CHB) and overweight., Methods: A total of 202 CHB patients who received TDF treatment at the Third People's Hospital of Changzhou (Changzhou, China) and Nanjing Drum Tower Hospital (Nanjing, China) between January 2016 and May 2018 were retrospectively enrolled. According to the body mass index (BMI) at the initiation of TDF treatment, CHB patients were divided into overweight (BMI ≥ 25 kg/m 2 ) and non-overweight (BMI < 25 kg/m 2 ) groups. Logistic regression was applied for the analysis of risk factors for eGFR < 90 mL/(min·1.73 m 2 )., Results: There is no significant difference in hepatitis B virus DNA (HBV DNA) negativity and hepatitis Be antigen (HBeAg) loss between patients with overweight and non-overweight (both P > 0.05). More patients in non-overweight group achieved alanine aminotransferase normalization compared with those in overweight group ( χ 2 = 11.036, P < 0.01). In non-overweight patients, the eGFR significantly declined in the 1 st year ( P < 0.01), then remained at a relatively lower level. TG significantly declined in the 2 nd year ( P = 0.02) and increased in the 3 rd year. Moreover, TG was negatively correlated with GFR at the four-time points ( P = 0.002, 0.030, 0.007, 0.008, respectively). In overweight patients, eGFR and TG remained relatively stable during the 3-year treatment, and eGFR showed no significant relationship with TG. Moreover, multivariate analysis showed that age [ P < 0.01, 95%CI (0.97-1.005)] and baseline eGFR [ P < 0.01, 95%CI (5.056-33.668)] were independent risk factors for eGFR < 90 mL/(min·1.73 m 2 ) at the 3 rd year., Conclusion: Dynamic changes in renal function were conversely related to TG during TDF treatment in patients with CHB and normal BMI, but not with overweight., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Emerging evidence showed that air pollutants are associated with development and recurrence of autoimmune disorders, but there is scarce evidence regarding the relationship between air pollutants and Sjogren's syndrome (SS). We sought to investigate whether air pollutants affect the risk of outpatient visits for SS and to quantify the burden of SS visits attributable to air pollution exposure in Hefei, China., Methods: Daily data on outpatient visits for SS, air pollutants and meteorological data in Hefei, China, from January 1, 2015 to December 31, 2020 were obtained. A distributed lag non-linear model in conjunction with a generalized linear model were employed to assess the relationship between air pollution and SS outpatient visits. Stratified analyses were further performed by gender, age and season. Attributable fraction (AF) and attributable number (AN) were used to reflect disease burden., Results: There were 4501 records of outpatient visits for SS. Exposure to PM 2.5 was associated with increased risk of SS outpatient visits (relative risk (RR) = 1.218, 95% confidence interval (CI): 1.017-1.458, lag 0-14 day). An increase of 24 μg/m 3 (interquartile range) in NO 2 concentration was associated with 26.3% increase in the risk of SS outpatient visits (RR = 1.263, 95%CI: 1.105-1.445, lag 0-10 day). In contrast, exposure to O 3 was associated with decreased risk of SS outpatient visits (RR = 0.692, 95%CI: 0.510-0.939, per 63 μg/m 3 in O 3 exposure, lag 0-27 day). Stratified analyses showed that females (vs. males) was more vulnerable to SS outpatient visits associated with NO 2 and O 3 exposure. SS patients aged ≥65 years (vs. aged <65 years) were susceptible to PM 2.5 exposure. Exposure to PM 2.5 or NO 2 in the cold season was associated with higher risk of SS outpatient visits than that in the warm season. In addition, the AN (232, 95%CI: 119, 324) and AF (5.16%, 95%CI: 2.55%, 7.21%) of NO 2 exposure were higher than those of PM 2.5 exposure., Conclusion: PM 2.5 and NO 2 exposure are associated with increased risk of SS outpatient visits, while O 3 exposure appears to be associated with decreased risk of SS outpatient visits. The effect of air pollutants exposure on risk of SS outpatients can be modified by age, gender and season. The burden of SS outpatient visits attributable to NO 2 exposure is higher than those attributable to PM 2.5 exposure., 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 © 2022 Elsevier Inc. All rights reserved.)

Gout is a chronic disease with inflammatory arthritis caused by monosodium urate (MSU) crystals deposition, an elevated serum urate level (hyperuricaemia) is the critical factor leading to MSU crystals deposition and promoting the progression of gout. The onset and development of gout is generally the result of multiple factors, such as diet, heredity and environmental factors. Although genetics and diet are thought to play as major factors, a growing body of research evidence has highlighted that environmental factors also play a significant role in the onset and exacerbation of gout. Recent studies have shown that air pollutants such as particulate matter, sulfur dioxide (SO 2 ) and carbon monoxide (CO) may increase the risk of hospitalizations for gout, and that the changes in temperature and humidity may affect uric acid (UA) levels. There is also seasonal trend in gout. It has been demonstrated that environmental factors may induce or accelerate the production and release of pro-inflammatory mediators, causing an unbalance oxidative stress and systemic inflammation, and then participating in the overall process or a certain link of gout. Moreover, several environmental factors have shown the ability to induce the production urate and regulate the innate immune pathways, involving in the pathogenesis of gout. Nevertheless, the role of environmental factors in the etiology of gout remains unclear. In this review, we summarized the recent literatures and aimed to discuss the relationship between environmental factors (such as microclimate, season, ambient/indoor air pollution and extreme weather) and gout. We further discussed the inflammatory mechanisms of environmental factors and gout and the comprehensive effects of environmental factors on gout. We also made a prospect of the management and treatment of gout, with special consideration to environmental factors associated with gout., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Emerging evidence witnesses the association of air pollution exposure with sleep disorders or the risk of obstructive sleep apnea (OSA); however, the results are not consistent. OSA patients with or without a low arousal threshold (LAT) have different pathology and therapeutic schemes. No study has evaluated the potential diverse effects of air pollution on the phenotypes of OSA. The current study aimed to evaluate the associations of short-term and long-term exposure to air pollution with sleep-disordered measures and OSA phenotypes. This cross-sectional study consisted of 4634 participants from a sleep center in Taipei from January 2015 to April 2019. The personal exposure to ambient PM 2.5 and NO 2 was assessed by a spatial-temporal model. Overnight polysomnography was used to measure the sleep parameters. According to a developed clinical tool, we defined the low arousal threshold (LAT) and identified the OSA patients with or without LAT. We applied a generalized linear model and multinomial logistic regression model to estimate the change of sleep measures and risk of the OSA phenotypes, respectively, associated with an interquartile range (IQR) increment of personal pollution exposure after adjusting for the essential confounders. In the single-pollutant model, we observed the associations of NO 2 with sleep-disordered measures by decreasing the total sleep time, sleep efficiency, extending the time of wake after sleep onset, and the association of NO 2 with the increased risk of LAT OSA by around 15%. The two-pollutant model with both long-term and short-term exposures confirmed the most robust associations of long-term NO 2 exposure with sleep measures. An IQR increment of NO 2 averaged over the past year (6.0 ppb) decreased 3.32 min of total sleep time and 0.85% of sleep efficiency. Mitigating exposure to air pollution may improve sleep quality and reduce the risk of LAT OSA., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Meteorological variables are regarded as risk factors for inflammatory diseases, but their associations with uveitis, one of the leading causes accounting for blindness worldwide with an estimated prevalence of 38-714 cases/100,000 person-years, have not been thoroughly investigated. The present study explored the short-term association between meteorological variables and hospital admissions for uveitis in Hefei City, China. Daily data on uveitis hospital admissions and meteorological variables including mean temperature (MT) (°C), diurnal temperature range (DTR) (°C), and relative humidity (RH) (%), from 2014 to 2020, were collected. A time-series study using generalized linear model combined with distributed lag non-linear model was applied. Totally, 1911 admissions for uveitis including 894 first admissions and 1017 readmissions were reported during the study period. The associations of high percentile of MT (75th, 24.5℃) and low percentile of DTR (25th, 5.4℃) with uveitis admissions were observed to be statistically significant from lag9 (RR = 1.041, 95%CI: 1.002-1.081) to lag11 (RR = 1.053, 95%CI: 1.003-1.104) and lag4 (RR = 1.053, 95%CI: 1.019-1.088) to lag5 (RR = 1.052, 95%CI: 1.020-1.085), respectively. Moreover, a significant association between low percentile of RH (1th, 44%) and uveitis admissions appeared at lag0-8 (RR = 1.869, 95%CI: 1.017-3.434) and lasted until lag0-13 (RR = 2.539, 95%CI: 1.102-5.850) in the cumulative lag structure. Subgroup analyses indicated that males and the young seemed to be more sensitive to high MT exposure, while females appeared to be more vulnerable to low DTR exposure. Interestingly, both the young and the elderly are susceptible to low DTR and low RH exposure. Furthermore, high MT and low DTR exposure were associated with increased risk of first admission for uveitis. In summary, exposure to high-value of MT and low-value of DTR and RH may increase the hospital admissions for uveitis, especially for the status of first admission., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Winner-loser effects influence subsequent agonistic interactions between conspecifics. Previous winning experiences could strengthen future aggression and increase the chance of winning the next agonistic interaction, while previous losing experiences could have the opposite effect. Although the role of A-to-I RNA editing has been recently implicated in chronic social defeat stress and aggressive behavior, it remains to be further elucidated in chronic social conflicts in agonistic interactions, especially in the repeated aggression (winners) and repeated defeat (losers) resulted from these conflicts. In the current study, transcriptome-wide A-to-I RNA editing in the dorsal striatum was investigated in a mouse model of chronic social conflicts, and compared between mice repeatedly winning and losing daily agonistic interactions. Our analysis identified 622 A-to-I RNA editing sites in the mouse dorsal striatum, with 23 to be differentially edited in 22 genes, most of which had been previously associated with neurological, psychiatric, or immune disorders. Among these differential RNA editing (DRE) sites four missense variants were observed in neuroligin 2 ( Nlgn2 ), Cdc42 guanine nucleotide exchange factor 9 (Arhgef9) BLCAP apoptosis inducing factor ( Blcap ), and cytoplasmic FMR1 interacting protein 2 ( Cyfip2 ), as well as two noncoding RNA sites in small nucleolar RNA host gene 11 ( Snhg11 ) and the maternally expressed 3 ( Meg3 ) gene. Moreover, significant changes were observed in gene functions and pathways enriched by genes with A-to-I RNA editing in losers and especially winners compared to controls. Our results demonstrate that repeated winning and losing experiences in chronic social conflicts are linked to A-to-I RNA editing pattern difference, underlining its role in the molecular mechanism of agonistic interactions between conspecifics., 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 © 2022 Ru, Kong, Ren, He, Xia, Li, Liang, Feng, Wei and Chen.)

Objectives: To study the effect of parent-child cooperative music therapy on the core symptoms of children with autism spectrum disorder (ASD) and their mothers., Methods: In this prospective study, 112 children with ASD and their mothers were divided into a music therapy group and an applied behavior analysis (ABA) group using a random number table ( n =56 each). The children in the ABA group were treated with ABA, and those in the music therapy group were given parent-child cooperative music therapy in addition to the ABA treatment. The duration of intervention was 8 weeks for both groups. Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), Parenting Stress Index-Short form (PSI-SF), Family APGAR Index, and Herth Hope Index (HHI) were used to evaluate the core symptoms of children with ASD and the parenting stress, family APGAR index, and hope level of mothers before and after intervention., Results: A total of 100 child-mother dyads completed the whole study, with 50 child-mother dyads in each group. After intervention, the children in the music therapy group had significantly lower total score of ABC scale and scores of sensation, social interaction, and somatic movement, as well as a significantly lower total score of CARS than those in the ABA group ( P <0.05). After intervention, compared with the mothers in the ABA group, the mothers in the music therapy group had significantly higher total score of PSI-SF and score of parent-child dysfunctional interaction, significantly higher total score of HHI and scores of each dimension, and significantly higher total score of APGAR and scores of cooperation and intimacy ( P <0.05)., Conclusions: Parent-child cooperative music therapy combined with ABA can alleviate the core symptoms of children with ASD, reduce the parenting stress of their mothers, and improve family APGAR index and hope level.

This study explored the phytoestrogen-like effect of Siwu Decoction(SWD) and the estrogen receptor(ER)-mediated molecular mechanism based on network pharmacology and in vivo experiment. The active components and targets of SWD were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and related targets of &quot;estrogen&quot; from GeneCards and Online Mendelian Inheritance in Man(OMIM). Cytoscape and STRING were employed to construct the protein-protein interaction(PPI) network and &quot;chemical component-target-disease&quot; network and core targets were identified, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets by R software. For the in vivo experiment, the 22-day-old SD female rats were treated(ig) with SWD for 4 days. Via hematoxylin-eosin(HE) staining, the morphological changes of rat uterus were observed. Reverse transcriptase-polymerase chain reaction(RT-PCR) was performed to detect mRNA expression of ER subtypes, estrogen-related targets, and the main regulatory factors in the estrogen signaling pathway. The results indicated 74 targets of SWD exerted phytoestrogen-like effect. KEGG pathway enrichment result suggested that estrogen signaling pathway was closely related to the phytoestrogen-like effect of SWD. Rats in SWD group demonstrated significantly thickened endometrium and significantly decreased expression of ERα, ERβ, and G protein-coupled estrogen receptor(GPER) mRNA in ovarian tissue. In addition, significant lowering of ERα and ERβ mRNA expression and significant rise of GPER mRNA expression in uterine tissue were observed in the SWD group. The expression of mitogen-activated protein kinase(MAPK) p38, MEK1/2 and extracellular signal-regulated kinase(ERK)1/2 mRNA was significantly low while that of epidermal growth factor receptor(EGFR) mRNA was significantly high in both ovarian and uterine tissues of SWD group compared with those in the control group. In conclusion, the phytoestrogen-like effect of SWD is closely related to the estrogen signaling pathway. The result lays a basis for revealing molecular mechanism of SWD in the treatment of gynecological diseases.

Recent studies suggest that RNA editing is associated with impaired brain function and neurological and psychiatric disorders. However, the role of A-to-I RNA editing during sepsis-associated encephalopathy (SAE) remains unclear. In this study, we analyzed adenosine-to-inosine (A-to-I) RNA editing in postmortem brain tissues from septic patients and controls. A total of 3024 high-confidence A-to-I RNA editing sites were identified. In sepsis, there were fewer A-to-I RNA editing genes and editing sites than in controls. Among all A-to-I RNA editing sites, 42 genes showed significantly differential RNA editing, with 23 downregulated and 19 upregulated in sepsis compared to controls. Notably, more than 50% of these genes were highly expressed in the brain and potentially related to neurological diseases. Notably, cis-regulatory analysis showed that the level of RNA editing in six differentially edited genes was significantly correlated with the gene expression, including HAUS augmin-like complex subunit 2 ( HAUS2 ), protein phosphatase 3 catalytic subunit beta ( PPP3CB ), hook microtubule tethering protein 3 ( HOOK3 ), CUB and Sushi multiple domains 1 ( CSMD1 ), methyltransferase-like 7A ( METTL7A ), and kinesin light chain 2 ( KLC2 ). Furthermore, enrichment analysis showed that fewer gene functions and KEGG pathways were enriched by edited genes in sepsis compared to controls. These results revealed alteration of A-to-I RNA editing in the human brain associated with sepsis, thus providing an important basis for understanding its role in neuropathology in SAE., 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 © 2022 Zhang, Pan, Wei, Ren, Ru, Xia, He, Lin and Chen.)