Search

Abstract Background Drug addiction is a significant public health concern, and aggression is common among people with drug addiction. Despite mounting evidence showing that the Dark Triad is a risk factor for aggression, the mediating and moderating mechanisms underlying this relationship are less known. This study tested the mediation effect of self-control in the association between the Dark Triad and aggression and whether this mediation was moderated by physical exercise. Methods A cross-sectional study was conducted in two compulsory drug rehabilitation centers in Nanning, China. A convenience sample of 564 drug abstainers completed a questionnaire to assess their Dark Triad, self-control, aggression, and physical exercise levels. Mediation and moderation analyses were carried out in SPSS macro-PROCESS. Results Self-control partially mediated the positive association between the Dark Triad and aggression. Physical exercise moderated the indirect effect of the Dark Triad on aggression via self-control, with the effect decreasing with the increase in physical exercise levels. Conclusions This study offers fresh insights into the underlying mediating and moderating mechanisms between the Dark Triad and aggression. The findings provide important practical implications for future intervention and prevention programs to address aggression among drug abstainers, which may be realized through strengthening self-control and physical exercise.

Abstract Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Abstract Neuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-β, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduces multiple endpoints of renal injury and fibrosis. We find that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreases cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we find that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease.

Abstract Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.

BackgroundPrevious studies have found an association between basal metabolic rate (BMR) and various malignant neoplasms, including bone tumors. BMR is also associated with bone mineral density, but the causality between BMR and benign neoplasms of bone and articular cartilage remains uncertain.DesignSingle nucleotide polymorphisms (SNPs) associated with BMR (p < 5 × 10-8) were used as instrumental variables for Mendelian randomization analysis of neoplasm risk. The inverse variance weighted (IVW) method was the primary approach, with the weighted median and MR-Egger regression serving as supplements.ResultsIn this MR analysis, the IVW method supported a causal relationship between BMR and benign neoplasms of bone and articular cartilage (OR = 1.417; 95% CI, 1.039 to 1.930; p = 0.027). No evidence of heterogeneity or pleiotropy in the selected SNPs was found in our study. Thus, based on these results, we discovered a possible causal relationship between BMR and benign neoplasms of bone and articular cartilage.ConclusionsIn this MR study, evidence suggested a genetic correlation between genetically predicted BMR and the risk of neoplasms in bone and articular cartilage.

Summary: Oxygen therapy is widely used in clinical practice; however, prolonged hyperoxia exposure may result in hyperoxic acute lung injury (HALI). In this study, we investigated the role of FAM134B in hyperoxia-induced apoptosis, cell proliferation, and epithelial-to-mesenchymal transition (EMT) using RLE-6TN cells and rat lungs. We also studied the effect of CeO2-NPs on RLE-6TN cells and lungs following hyperoxia exposure. FAM134B was inhibited in RLE-6TN cells and rat lungs following hyperoxia exposure. Overexpressing FAM134B promoted cell proliferation, and reduced EMT and apoptosis following hyperoxia exposure. FAM134B activation increased ER-phagy, decreased apoptosis, improved lung structure damage, and decreased collagen fiber deposition to limit lung injury. These effects could be reversed by PI3K/AKT pathway inhibitor LY294002. Additionally, CeO2-NPs protected RLE-6TN cells and lung damage following hyperoxia exposure by ameliorating impaired ER-phagy. Therefore, FAM134B restoration is a potential therapeutic target for the HALI. Moreover, CeO2-NPs can be used for the treatment of HALI.

Abstract This study aims to explore the relationship between traffic flow states and crash type/severity in the scenarios of normal crashes, primary crashes, and secondary crashes using the association rules mining approach. The crash data and real‐time traffic data were collected from the I‐880 freeway for five years in California, USA. The secondary crashes were identified using a speed contour plot approach. Traffic flow states were identified by the three‐phase flow theory. The results showed that the free flow is associated with the proportion of the sideswipe normal crash, the hit object primary crash, and the injury primary crash. The synchronized flow, the wide moving jams, and the transitional state from synchronized flow to wide moving jams are associated with the proportion of the rear‐end secondary crash. The transitional state from synchronized flow to free flow is associated with the proportion of the rear‐end primary crash and the property damage only primary crash. In addition, the unsafe speed behaviour can increase the proportion of the rear‐end normal, primary, and secondary crashes. The unsafe lane change behaviour can increase the proportion of the sideswipe normal, primary, and secondary crashes. These results have the potential to reduce the secondary crash probability.

Abstract This study aimed to investigate the relationship between the utilization of household water treatment devices (UHWTD) and both overall and cause-specific mortality, addressing the lack of comprehensive prospective research in this area. The study was a population-based prospective cohort study using data from the US National Health and Nutrition Examination Survey (NHANES 1999–2010). Among the 30,322 participants included in the study, the group without UHWTD (No UHWTD) was younger but reported worse baseline health compared to the UHWTD group. During an average follow-up period of 14.3 years, 6811 participants died. After adjusting for age, sex, and other covariates, No UHWTD was significantly associated with a higher risk of overall (adjusted hazard ratio [aHR]: 1.221, 95% Confidence Interval [CI]: 1.147–1.300), heart (aHR: 1.405, 95% CI: 1.241–1.589), cancer (aHR: 1.176, 95% CI: 1.003–1.379), Alzheimer’s disease (aHR: 1.404, 95% CI: 1.027–1.919), and nephrosis (aHR: 1.613, 95% CI: 1.026–2.537) mortality compared to UHWTD. Moreover, those main association almost remained after further adjustment for water source. Additionally, we observed a lower detection rate of bromoform, chloroform, bromodichloromethane, and dibromochloromethane in tap water when household water treatment devices was used compared to No UHWTD. The utilization of household water treatment devices in this prospective cohort was associated with modest reductions in the risk of overall, heart, cancer, Alzheimer’s disease, and nephrosis mortality. These findings suggest that the use of household water treatment devices may have the potential to influence health outcomes and extend life expectancy.

Abstract Compound droughts with low soil moisture (SM) and high vapor pressure deficit (VPD) pose significant threats to terrestrial carbon sink and agricultural production. However, the frequency and intensity of compound droughts and their adverse impacts on the carbon cycle remain highly uncertain. Here, we define and identify vegetation compound droughts (VCDs) when low SM and high VPD severely limit and adversely affect vegetation carbon uptake. We find frequent and severe VCDs and their considerable adverse impacts on carbon uptake in mid- and low-latitude regions, particularly in drylands. Risks of VCDs have been greatly underestimated as the widely adopted quantile-based approach identifies only 11% of VCDs and 26% of global GPP anomalies due to VCDs. The frequency and intensity of VCDs and their adverse impacts on carbon uptake are projected to increase further, irrespective of whether the CO2 fertilization effect on vegetation growth and photosynthesis is considered or not. These findings improve our understanding of current and future risks of VCDs and underline the importance of adaptation measures to cope with the adverse impacts of ever-increasing compound droughts.

Background Serum fibrinogen/albumin ratio (FAR) is a new inflammatory marker related to a variety of diseases, and it has been shown to be associated with stroke. This study is to investigate the relationship between serum FAR and early neurological deterioration (END) in patients with recent small subcortical infarction (RSSI).Patients and methods Consecutive RSSI patients admitted to the First Affiliated Hospital of Zhengzhou University from June 2015 to June 2022 were enrolled. The National Institute of Health Stroke Scale (NIHSS) was utilized to evaluate the severity of the patients at admission and within seven days post-admission. END was defined as an increase of ≥2 points in NIHSS score from admission or ≥1 point in the motor item of the score within seven days post-admission. Multivariate logistic regression analysis was employed to identify risk factors for END. The correlation between FAR and END was investigated using restricted cubic spline (RCS) analysis. Subgroup analysis was used to assess stability across different populations.Results A total of 766 RSSI patients were included in the analysis, with 538 males (70.24%). END occurred in 115 (15.01%) patients. Multivariate logistic regression analysis revealed that FAR (OR = 1.016, 95%CI: 1.005–1.028), PAD (OR = 1.805, 95%CI: 1.161–2.807) and age (OR = 1.028, 95%CI: 1.009–1.048) were associated with END in RSSI patients. RCS analysis indicated a linear correlation between FAR and END (p for nonlinear = .128). Subgroup analysis indicated association between FAR and END in male (OR = 1.02, 95%CI: 1.00–1.03), patients aged ≤65 years (OR = 1.02, 95%CI: 1.00–1.03) and patients without smoking history (OR = 1.02, 95%CI: 1.00–1.03).Conclusions Elevated FAR levels were associated with the occurrence of END within seven days after admission in RSSI patients, especially in men, age ≤65 years, or patients without smoking history.

Abstract Resistance and resilience are widely used to characterize ecosystem drought stability. Tradeoff between resistance and resilience have been reported, but its long‐term trends remain uncertain at global scale. Based on remotely sensed vegetation indices, we assessed the spatiotemporal dynamics of drought resistance and resilience. Result revealed that there was a significant decline in the tradeoff between resistance and resilience, corresponding to a substantial increase in the proportion of areas with high resistance‐high resilience or low resistance‐low resilience. In the South Sahel, South Africa and Central China, the increased precipitation and vegetation coverage contribute to enhanced drought stability constructed by resistance and resilience; while rising temperature, decreased water availability and deforestation lead to declined stability in northeastern North America, South America and the Congo region. Increases in the areas with low resistance‐low resilience resulting from declining tradeoffs warn of increased regional ecosystem vulnerability.

BackgroundWhile text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. ObjectiveThis study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. MethodsFrom December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of

Cerebrovascular diseases, including ischemic strokes, hemorrhagic strokes, and vascular malformations, are major causes of morbidity and mortality worldwide. The advancements in neuroimaging techniques have revolutionized the field of cerebrovascular disease diagnosis and assessment. This comprehensive review aims to provide a detailed analysis of the novel imaging methods used in the diagnosis and assessment of cerebrovascular diseases. We discuss the applications of various imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and angiography, highlighting their strengths and limitations. Furthermore, we delve into the emerging imaging techniques, including perfusion imaging, diffusion tensor imaging (DTI), and molecular imaging, exploring their potential contributions to the field. Understanding these novel imaging methods is necessary for accurate diagnosis, effective treatment planning, and monitoring the progression of cerebrovascular diseases.

Purpose: To explore the association between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation and nystagmus. Design: Retrospective cohort study. Methods: A retrospective review was conducted for 3408 patients with amblyopia who had not yet started amblyopia treatment utilizing a large amblyopia patient database maintained at Zhongshan Ophthalmic Centre. Six amblyogenic factor subtypes were identified: anisometropia, isoametropia, strabismus, anisometropia and strabismus, monocular visual deprivation, and binocular visual deprivation amblyopia. Monocular best corrected visual acuity (BCVA), the contrast sensitivity function (CSF), fixation, and stereopsis were compared between the subtypes before and after propensity score matching (PSM) for age and sex. Results: The two deprivation groups had poorer BCVA and CSF than the other groups. There were no systematic differences in CSF between the non-deprivation groups. Nystagmus was more common in the bilateral amblyopia groups compared to the monocular amblyopia groups. Eccentric fixation was uncommon with the exception of the anisometropia and strabismus group which had an eccentric fixation rate of 20%. Distance stereoacuity measured without monocular cues was absent for almost all patients. The results were consistent when analyzed using PSM. Conclusion: Visual deprivation causes more severe amblyopia than other amblyogenic factors. For non-deprivation amblyopia subtypes, individual differences such as variation in the severity of the amblyogenic factor might be more important in determining pre-treatment vision than whether amblyopia was caused by refractive error, strabismus or both.

Abstract To explore the associations between high uterine artery pulsatility index (UtA-PI) values and congenital heart disease (CHD) risk and whether they differed between singleton and multiple pregnancies. This hospital-based cohort study involving 52,047 pregnant women who underwent prenatal examinations from 2012 to 2016. Infants born to the included pregnant women were followed until 42 days after birth to identify those with CHDs. Generalized estimating equations were used to estimate the associations of high right UtA-PI (> 95th percentile) values with maternal preeclampsia and fetal CHDs. Logistic regression analyses were conducted using path analysis models to quantify the effect of high right UtA-PI values on fetal CHD risk. A total of 42,552 women and 43,470 infants (147 with CHDs) were included. Preeclampsia risk was associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 3.01; 95% CI 2.57–3.52). CHD risk was marginally associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 2.26, 95% CI 1.03–4.95). Considering only two factors, 96.0% of the fetal CHD risk was mediated by preeclampsia in singleton-pregnant women, while 93.8% of the risk was related to a high right UtA-PI in multiple-pregnant women. A high right UtA-PI was marginally associated with an increased fetal CHD risk in singleton-pregnant women and might play an important role in multiple-pregnant women. Further studies are warranted to confirm these findings given the high loss to follow-up rate.

Abstract Background No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. Methods RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. Results Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p

Abstract Facing the dual threats of climate and socioeconomic changes, how Tibet can seize the opportunity for ecological restoration to enhance environmental quality while improving the relationship between humans and nature is of great significance for regional sustainable development. Situated in an ecologically vulnerable area, the cognitive structure of Tibetan residents regarding resources and policies is a crucial reference for evaluating whether environmental governance is sustainable. We aimed to detect what impact ecological restoration in Tibet had on the cognitive structures of stakeholders. We distributed questionnaires to Tibetan residents, distinguished experimental groups (EG, n = 325) and control groups (CG, n = 165) by the implementation of ecological restoration projects or not, used a network approach to construct indicators of overall connectivity and evenness for assessing the cognitive structure and explored the influencing factors on cognitive structures. We found that interviewees in areas where ecological restoration was implemented had more positive perceptions of the importance of ecosystem services, the relationship between ecological conservation and well‐being, attitudes towards ecological restoration, and the impact of governance measures. The overall connectivity and evenness of the EG were significantly higher than those of the CG. It showed an increase in positive stakeholder perceptions about policy and nature and a greater emphasis on the balance between environmental protection and productive life. The implementation of ecological restoration enhanced the connection between local people and the environment. Elevation and annual precipitation were the geographic influencing factors that dominated overall connectivity. Based on the cognitive structure of Tibetan residents, the implementation of ecological restoration enhanced connections in social‐ecological systems elements, played a positive role in the human–nature relationship and promoted collective governance of common pool resources. Safeguarding and improving residents' livelihoods and enhancing the regional low‐connectivity cognitive structure under different geographical contexts are important for future governance. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Grassland provides multiple ecosystem services and plays a key role in preventing desert encroachment and maintaining oasis stability. In China, the area of cropland in oases has expanded significantly in recent decades, which results in a rapid increase in agricultural water demand and encroachment on grassland subsistence space. However, our knowledge about how the expansion of cropland affects oasis grasslands remains limited. We used machine learning, temporal segmentation of spectral trajectories, and maximum covariance analysis to generate an annual oasis grassland aboveground biomass (AGB) data set at 30‐m resolution from 1989 to 2021 based on multiple remotely sensed and ground observation data sets, and investigated the dynamics of grassland AGB under cropland expansion in oases. We found that overall oasis grassland AGB increased significantly (0.3 gm−2 yr−1, P

Exploring the antecedents that affect the team innovation performance can better promote the organization to research the potential factors to enhance the organizational innovation competitiveness. Drawing upon information processing theory, we develop a moderated mediation model to examine the relationship between team pro-social rule breaking and team innovation performance. A three-wave field study is constructed from two large manufacturing enterprises from 82 team leaders and their 382 subordinates in Shanghai, China. The results reveal that team pro-social rule breaking is positively related to team innovation performance through team reflexivity. In addition, the relationship between team pro-social rule breaking and team innovation performance via team reflexivity is positive only when team learning orientation is high. The implications, limitations, and future research directions of these findings are discussed.

Abstract Although biomass‐derived carbon (biochar) has been widely used in the energy field, the relation between the carbonization condition and the physical/chemical property of the product remains elusive. Here, we revealed the carbonization condition's effect on the morphology, surface property, and electrochemical performance of the obtained carbon. An open slit pore structure with shower‐puff‐like nanoparticles can be obtained by finely tuning the carbonization temperature, and its unique pore structure and surface properties enable the Li–O2 battery with cycling longevity (221 cycles with 99.8% Coulombic efficiency at 0.2 mA cm−2 and controlled discharge–charge depths of 500 mAh g−1) and high capacity (16,334 mAh g−1 at 0.02 mA cm−2). This work provides a greater understanding of the mechanism of the biochar carbonization procedure under various pyrolysis conditions, paving the way for future study of energy storage devices.

Abstract Glioblastoma (GBM) is notorious for malignant neovascularization that contributes to undesirable outcome. However, its mechanisms remain unclear. This study aimed to identify prognostic angiogenesis‐related genes and the potential regulatory mechanisms in GBM. RNA‐sequencing data of 173 GBM patients were obtained from the Cancer Genome Atlas (TCGA) database for screening differentially expressed genes (DEGs), differentially transcription factors (DETFs), and reverse phase protein array (RPPA) chips. Differentially expressed genes from angiogenesis‐related gene set were extracted for univariate Cox regression analysis to identify prognostic differentially expressed angiogenesis‐related genes (PDEARGs). A risk predicting model was constructed based on 9 PDEARGs, namely MARK1, ITGA5, NMD3, HEY1, COL6A1, DKK3, SERPINA5, NRP1, PLK2, ANXA1, SLIT2, and PDPN. Glioblastoma patients were stratified into high‐risk and low‐risk groups according to their risk scores. GSEA and GSVA were applied to explore the possible underlying GBM angiogenesis‐related pathways. CIBERSORT was employed to identify immune infiltrates in GBM. The Pearson's correlation analysis was performed to evaluate the correlations among DETFs, PDEARGs, immune cells/functions, RPPA chips, and pathways. A regulatory network centered by three PDEARGs (ANXA1, COL6A1, and PDPN) was constructed to show the potential regulatory mechanisms. External cohort of 95 GBM patients by immunohistochemistry (IHC) assay demonstrated that ANXA1, COL6A1, and PDPN were significantly upregulated in tumor tissues of high‐risk GBM patients. Single‐cell RNA sequencing also validated malignant cells expressed high levels of the ANXA1, COL6A1, PDPN, and key DETF (WWTR1). Our PDEARG‐based risk prediction model and regulatory network identified prognostic biomarkers and provided valuable insight into future studies on angiogenesis in GBM.

Abstract Hypophosphatasia (HPP) is a metabolic bone disease that manifests as developmental abnormalities in bone and dental tissues. HPP patients exhibit hypo-mineralization and osteopenia due to the deficiency or malfunction of tissue non-specific alkaline phosphatase (TNAP), which catalyzes the hydrolysis of phosphate-containing molecules outside the cells, promoting the deposition of hydroxyapatite in the extracellular matrix. Despite the identification of hundreds of pathogenic TNAP mutations, the detailed molecular pathology of HPP remains unclear. Here, to address this issue, we determine the crystal structures of human TNAP at near-atomic resolution and map the major pathogenic mutations onto the structure. Our study reveals an unexpected octameric architecture for TNAP, which is generated by the tetramerization of dimeric TNAPs, potentially stabilizing the TNAPs in the extracellular environments. Moreover, we use cryo-electron microscopy to demonstrate that the TNAP agonist antibody (JTALP001) forms a stable complex with TNAP by binding to the octameric interface. The administration of JTALP001 enhances osteoblast mineralization and promoted recombinant TNAP-rescued mineralization in TNAP knockout osteoblasts. Our findings elucidate the structural pathology of HPP and highlight the therapeutic potential of the TNAP agonist antibody for osteoblast-associated bone disorders.

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein–protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.

Introduction Perceived risk of COVID-19 infection is associated with smoking behaviors, but the change in smoking across different settings are uncertain. We examined the associations of perceived increased susceptibility to COVID-19 due to smoking with change in smoking at home and on the streets. Methods We analyzed data of 1120 current cigarette smokers aged ≥15 years from a population-based telephone survey in Hong Kong. Perceived increased susceptibility to COVID-19 due to smoking, change in smoking, intention to quit, and tobacco dependence were measured. We used Poisson regression with robust variance to estimate adjusted risk ratio (ARR) for associations, adjusting for sociodemographic characteristics, intention to quit, and time to first cigarette after waking. Results More current smokers reduced smoking on the streets (46.1%; 95% CI: 42.8–50.0) than at home (8.7%; 95% CI: 7.0–10.8). Perceived increased susceptibility to COVID-19 due to smoking was associated with smoking reduction at home (ARR=3.29; 95% CI: 1.80–6.00, p

Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100β, albumin, MMP-9, MMP-2, MMP-12, IL-1β, TNF-α, IL-6, IFN-γ, TGF-β, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed.

BackgroundLupus nephritis (LN) is a common and severe glomerulonephritis that often occurs as an organ manifestation of systemic lupus erythematosus (SLE). However, the complex pathological mechanisms associated with LN have hindered the progress of targeted therapies.MethodsWe analyzed glomerular tissues from 133 patients with LN and 51 normal controls using data obtained from the GEO database. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key gene modules. The least absolute shrinkage and selection operator (LASSO) and random forest were used to identify hub genes. We also analyzed immune cell infiltration using CIBERSORT. Additionally, we investigated the relationships between hub genes and clinicopathological features, as well as examined the distribution and expression of hub genes in the kidney.ResultsA total of 270 DEGs were identified in LN. Using weighted gene co-expression network analysis (WGCNA), we clustered these DEGs into 14 modules. Among them, the turquoise module displayed a significant correlation with LN (cor=0.88, p

IntroductionFrailty can lead to a decrease in the patient's resistance to interference such as injury and disease, and cause a series of complications. An increasing number of studies have found that pre-operative frailty exacerbates the occurrence of adverse events after carotid artery revascularization, but an integrated quantitative analysis is currently lacking. Therefore, we conducted a meta-analysis to evaluate the impact of pre-operative frailty on patients undergoing carotid artery revascularization.MethodAccording to the PRISMA guidelines, we systematically searched for relevant studies on Medline, Embase, Ovid, CINAHL, Web Of Science, and Cochrane Library from establishment until June 2023. Summarize the risk of adverse outcome events through OR and 95% CI.ResultsA total of 16 cohort studies were included, including 1692338 patients. Among patients who underwent carotid artery revascularization surgery, the prevalence of pre-operative frailty was 36% (95% CI = 0.18–0.53, P

Unraveling the complexity of the 17 interacting sustainable development goals (SDGs) is crucial for their achievement. Empirically revealing the dimensions of the SDGs helps generalize the dominant features of SDGs and better understand their drivers. Here, using a database of 166 countries’ progress toward achieving each individual SDG, we found that about 70% of the variability of national SDG performance can be captured by three dimensions: socioeconomic development at the expense of resource and climate, the environment, and development at the expense of equality. Moreover, these dimensions are mainly affected by the economy; as gross domestic product (GDP) per capita increases, the first dimension increases monotonically, the environment dimension decreases and then increases, and the inequality dimension increases and then decreases. Our findings indicate a dim prospect of eventually achieving all SDGs because of the conflicts between economic growth and resource and climate goals under the current development paradigm, highlighting the importance of sustainable transformation.

Abstract Background Spinal cord injury (SCI) causes nearly all patients to suffer from protracted disabilities. An emerging therapeutic strategy involving the recruitment of endogenous neural stem cells (NSCs) has been developed. However, endogenous NSCs in the adult spinal cord differentiate into mostly astrocytes after traumatic injury, forming glial scars, which is a major cause of regeneration failure in SCI. Thus, understanding which factors drive the activation and differentiation of endogenous NSCs after SCI is critical for developing therapeutic drugs. Methods The infiltration, state, and location of CD8+ T cells in spinal cord after traumatic injury were analyzed by flow cytometry and immunofluorescence (IF) staining. The Basso Mouse Scale (BMS) scores and rotarod testing were used for motor behavioral analysis. NSCs were co-cultured with CD8+ T cells. EdU assay was used to detect proliferative cells. Western blotting was used to analyze the expression levels of STAT1, p-STAT1, and p27. ChIP-seq and ChIP-qRT-PCR analyses were used to detect the downstream of STAT1. Nestin-CreERT2::Ai9 transgenic mice were used to genetic lineage tracing of Nestin+ NSCs after SCI in vivo. Results A prolonged increase of activated CD8+ T cells occurs in the injured spinal cords. The behavioral analysis demonstrated that the administration of an anti-CD8 antibody promotes the recovery of locomotor function. Then, we discovered that CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1 pathway in vitro. ChIP-seq and ChIP-qRT-PCR analysis revealed that STAT1 could directly bind to the promoters of astrocyte marker genes GFAP and Aldh1l1. Genetic lineage tracing of Nestin+ NSCs demonstrated that most NSCs differentiated into astrocytes following SCI. Depleting CD8+ T cells reduced the differentiation of NSCs into astrocytes and instead promoted the differentiation of NSCs into oligodendrocytes. Conclusion In conclusion, CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1-GFAP/Aldhl1l axis. Our study identifies INF-γ as a critical mediator of CD8+ T-cell-NSC cross talk and a potential node for therapeutic intervention in SCI.

ObjectiveMultiple myeloma (MM) is a highly characteristic tumor that is influenced by numerous factors that determine its prognosis. Studies indicate that the presence of circulating plasma cells (cPCs) is a detrimental factor that significantly impacts the prognosis of patients with MM.MethodsThis study retrospectively analyzed the prognostic value of cPCs quantified by 10-color flow cytometry in 145 newly diagnosed MM (NDMM) cases in the First Affiliated Hospital of Soochow University from November 2018 to February 2021. The study was approved by the Ethics Committee of the hospital (2021 No. 93).ResultsOf the 145 patients, 99 (68.2%) were detected cPCs. Through receiver operating characteristics (ROC) analysis, an optimal threshold of 0.165% was identified as a predictor for overall survival (OS). The median progression-free survival (PFS) was 33 months in patients with cPCs ≥0.165%, whereas those with cPCs

Abstract The rational design of large‐area exposure, nonagglomeration, and long‐range dispersion of metal nanoparticles (NPs) in the catalysts is critical for the development of energy storage and conversion systems. Little attention has been focused on modulating and developing catalyst interface contact engineering between a carbon substrate and dispersed metal. Here, a highly dispersed ultrafine ruthenium (Ru) NP strategy by double spatial confinement is proposed, that is, incorporating directed growth of metal–organic framework crystals into a bacterial cellulose templating substrate to integrate their respective merits as an excellent electrocatalytic cathode catalyst for a quasi‐solid‐state Li–O2 battery. The porous carbon matrix with highly dispersed ultrafine Ru NPs is well designed and used as cathode catalysts in a Li–O2 battery, demonstrating a high discharge areal capacity of 6.82 mAh cm–2 at 0.02 mA cm–2, a high‐rate capability of 4.93 mAh cm–2 at 0.2 mA cm–2, and stable discharge/charge cycling for up to 500 cycles (2000 h) with low overpotentials of ~1.4 V. This fundamental understanding of the structure–performance relationship demonstrates a new and promising approach to optimize highly efficient cathode catalysts for solid‐state Li–O2 batteries.

BackgroundSome eating habits may be related to the development of gastrointestinal diseases, obesity, and related metabolic dysfunctions. Because of long working hours, and shift schedules, physicians are more likely to form such eating habits and have a high risk of developing these diseases.ObjectivesWe aimed to investigate the association between physicians’ eating habits and their health perception and diseases.MethodsBetween 24 June and 5 August 2020, we performed convenience sampling of in-service physicians in hospitals in mainland China. A questionnaire was administered to collect data pertaining to basic sociodemographic characteristics, eating habits, health-related information such as body mass index classification, and prevalence of common diseases. The associations among eating habits and perceived suboptimal health status, micronutrient deficiency-related diseases, obesity, and related metabolic diseases were analysed.ResultsThe prevalence of unhealthy eating habits was high: more eating out-of-home (53.4% in hospital canteens, 23.0% in restaurants and takeaways), fewer meals at home, irregular meals (30.5%), and eating too fast (the duration

Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases.

Objectives Amblyopia is the most common cause of unilateral visual impairment in children and requires long-term treatment. This study aimed to quantify the impact of pandemic control measures on amblyopia management.Design and setting This was a retrospective cohort study of data from a large amblyopia management database at a major tertiary eye care centre in China.Participants Outpatients with amblyopia who visited the hospital from 1 June 2019, through 28 February 2022.Primary and secondary outcome measures The primary outcome was the number of first and follow-up in-person visits to the hospital for amblyopia treatment. Secondary outcomes included the time interval between consecutive visits and improvement of vision (visual acuity, contrast sensitivity and stereopsis). Patient records were grouped into prepandemic and during pandemic periods.Results A total of 10 060 face-to-face visits for 5361 patients (median age 6.7 years, IQR 5.4, 8.9) that spanned two lockdown periods were included in the analysis, of which 28% were follow-up visits. Pandemic control measures caused a sharp decline in the number of outpatient visits (3% and 30% of prepandemic levels in the months directly after the start of the first (2020) and second (2021) periods of pandemic control measures, respectively). However, these drops were followed by pronounced rebounds in visits that exceeded prepandemic levels by 51.1% and 108.5%, respectively. The interval between consecutive visits increased significantly during the pandemic from a median (IQR) of 120 (112, 127) days in 2019 to 197 (179, 224) in 2020 (p

IntroductionSaccharomyces boulardii (S. boulardii) has shown clinical beneficial effect in inflammatory bowel diseases recently. However, the underlying mechanisms remain incompletely understood. The aim of present study was to tested whether S. boulardii targets gut microbiota to protect against the development of experimental colitis in mice.MethodsFemale C57BL/6 mice were gavaged with S. boulardii for 3 weeks before being challenged with dextran sulphate sodium to induce ulcerative colitis. Bodyweight, diarrhea severity, intestinal permeability, colonic histopathology, colonic inflammatory status, and epithelial cell death of mice were examined. The fecal microbiota and its metabolomic profiles were detected by 16S rDNA sequencing and UPLC-MS, respectively.Results and DiscussionSupplementation with S. boulardii significantly prevented weight loss and colon shortening, lowered colonic inflammation, ameliorated epithelial injury, and enhanced the intestinal barrier integrity in colitis mice. By inhibiting the abundance of pathogenic bacteria and increasing the probiotics abundance, S. boulardii improved the microbial diversity and restored the microbiota dysbiosis. Moreover, it also modulated microbial metabolome and altered the relative contents of metabolites involving amino acids, lipids, energy and vitamin metabolisms. These yeast-driven shifts in gut flora and metabolites are were associated with each other and with the inflammation profile in colitis. Collectively, S. boulardii exerts protective effects on colitis in mice by reshaping gut microbiome and its metabolic profile, indicating it as a promising therapeutic avenue.

The current price guided demand response mechanism is difficult to accurately achieve the expected load reduction goal for the grid company, while the direct control demand response mechanism cannot meet the requirements of users for autonomous power consumption. Therefore, it is necessary to formulate an incentive compatible demand response mechanism to take the needs of demand-side users and the grid company into account. Based on the current bidding demand response program, a two-stage transaction mechanism of demand response quota based on blockchain is proposed in this work. Firstly, a two-stage transaction mechanism for demand response quota considering day-ahead bidding transaction and intra-day double auction transaction is designed. Then, the smart contract is introduced to realize the proposed blockchain-based two-stage transaction mechanism of demand response quota, and all the smart contract functions involved in each business link are customized. Finally, the effectiveness of the proposed transaction mechanism of demand response quota is illustrated by the simulation results on the platform of Remix IDE.

Abstract Aims Previous prediction studies for 30 day readmission in patients with heart failure were built mainly based on electronic medical records and rarely involved patient‐reported outcomes. This study aims to develop and validate a nomogram including patient‐reported outcomes to predict the possibility of 30 day all‐cause readmission in older patients with heart failure and to explore the value of patient‐reported outcomes in prediction model. Methods and results This was a prospective cohort study. The nomogram was developed and internally validated by Logistic regression analysis based on 381 patients in training group from March to December 2019. The nomogram was externally validated based on 170 patients from July to October 2020. Receiver operating characteristic curves, calibration plots and decision‐curve analysis were used to evaluate the performance of the nomogram. A total of 381 patients' complete data were analysed in the training group and 170 patients were enrolled in the external validation group. In the training group, 14.4% (n = 55) patients were readmitted to hospitals within 30 days of discharge and 15.9% (n = 27) patients were readmitted in the external validation group. The nomogram included six factors: history of surgery, changing the type of medicine by oneself, information acquisition ability, subjective support, depression level, quality of life, all of which were significantly associated with 30 day readmission in older patients with heart failure. The areas under the receiver operating characteristic curves of nomogram were 0.949 (95% CI: 0.925, 0.973, sensitivity: 0.873, specificity: 0.883) and 0.804 (95% CI: 0.691, 0.917, sensitivity: 0.778, specificity: 0.832) respectively in the training and external validation groups, which indicated that the nomogram had better discrimination ability. The calibration plots demonstrated favourable coordination between predictive probability of 30 day readmission and observed probability. Decision‐curve analysis showed that the net benefit of the nomogram was better between threshold probabilities of 0–85%. Conclusions A novel and easy‐to‐use nomogram is constructed and demonstrated which emphasizes the important role of patient‐reported outcomes in predicting studies. The performance of the nomogram drops in the external validation cohort and the nomogram must be validated in a wide prospective cohort of HF patients before its clinical relevance can be demonstrated. All these findings in this study can assist professionals in identifying the needs of HF patients so as to reduce 30 day readmission.

Background/purpose: Glide path management (GPM) is a consequential clinical step that serves to influence predictably successful root canal therapy. However, the effect of GPM on the shaping ability of single-file system remains controversial. This study compared the performance of rotary single-file One Curve (OC) and reciprocating single-file Reciproc Blue (RCB) in combination with/without different glide path techniques: no glide path preparation (NG), PathFile (PF), ProGlider (PG) and WaveOne Gold Glider (WOGG), respectively. Materials and methods: 80 simulated curved canals (n = 10 canals/per group) were instrumented to an apical size of 0.25 mm using OC and RCB in combination with/without different glide path techniques, respectively. The amount of resin removal, canal transportation, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis of the data was performed by using Kruskal–Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: Post–glide path analysis found that WOGG and PG produced less canal transportation and curvature straightening than PF (P

Abstract Background Retroperitoneal fibrosis is a rare disease characterized by chronic nonspecific inflammation, which leads to clinical compression manifestations of retroperitoneal organs especially ureter. Approximately 70 percent of retroperitoneal fibrosis cases are idiopathic which has no clear etiology. This study reported a rare case of a 48-year-old woman presented with idiopathic retroperitoneal fibrosis and endometrial cancer. Case presentation A 48-year-old woman presented with irregular vaginal bleeding without abdominal pain, bloating or discomfort. The patient was diagnosed iRPF after splenectomy 13 years ago. Then she took prednisone for 2 years and took tamoxifen for about 11 years. She stopped taking the medication from October 2019 to May 2020 and then started taking tamoxifen again until November 2020. Two weeks after she stopped taking tamoxifen, she presented with irregular vaginal bleeding. Gynecological ultrasound revealed a thick endometrium with uneven echo enhancement and blood flow signals. Then diagnostic curettage was performed with pathological examination showed endometroid carcinoma. Later, the patient was admitted to Peking University Third Hospital for surgery. Preoperative imaging examinations, including CT, MRI, and PET/CT, all showed pelvic enlarged lymph nodes and they were highly suspected to have lymph node metastasis. The patient underwent laparoscopic surgical staging and enlarged lymph nodes in the pelvic and aortic regions were removed. Finally, the pathology confirmed that endometrioid adenocarcinoma and fibrosis, but there was no tumor infiltration in these enlarged lymph nodes. The patient is now in good condition. Conclusion This case report stressed the difficulty to distinguish between lymph node metastasis and inflammatory hyperplasia by common imaging methods. Due to increased surgical difficulty among retroperitoneal patients, lymphadenectomy should be carefully evaluated to avoid additional surgical complications and over-treatment.

Monocular perceptual learning has shown promising performance in restoring visual function in amblyopes beyond the critical period in the laboratory. However, the treatment outcome is variable and indeterminate in actual clinical and neuroscientific practice. We aimed to explore the efficacy of monocular perceptual learning in the clinical setting. By combining continuous monitoring of perceptual learning and clinical measurements, we evaluated the efficacy and characteristics of visual acuity and contrast sensitivity function improvement and further explored the individualized effect after perceptual learning. Amblyopes (average age:17 ± 7 years old) were trained in a monocular two-alternative forced choice identification task at the 50% contrast threshold of the amblyopic eye for 10–15 days. We found that monocular perceptual learning improves both visual acuity and contrast sensitivity function in amblyopia. The broader activation of spatial contrast sensitivity, with a significant improvement in lower spatial frequencies, contributed to improving visual acuity. Visual acuity changes in the early stage can predict the endpoint treatment outcomes. Our results confirm the efficacy of monocular perceptual learning and suggest potential predictors of training outcomes to assist in the future management of clinical intervention and vision neuroscience research in amblyopia beyond the critical period of visual plasticity.

Non-alcoholic fatty liver disease (NAFLD) is a global public health issue, of which the prevalence is about 25% worldwide. The incidence of NAFLD is increasing in patients with obesity, type 2 diabetes (T2DM) and the metabolic syndrome. The crosstalk between gut microbiota and metabolism-related diseases has been raised great concern. Patients with NAPLD were observed with disruption of gut microbiota. Several researches showed that gut microbiota was the determination in the progression of NAFLD by the experiments using fecal microbiota transplants. The application of probiotics, as one of the most important strategies for the regulation of gut microbiota disorder, have been explored whether it is beneficial to gut-related diseases of intestine-distal organs. Some probiotics were showed to improve the liver parameters and phenotype in patients with NAFLD. The oral intake of them might become the effective management for the prevention and treatment of NAFLD. In this review, we summarized the human clinical trials focusing on the effects of probiotics on NAFLD to give some evidential reference for the administration of NAFLD.

IntroductionBoth perceived benefits and harms of COVID-19 have been reported, but whether they affect confidence in coping with the pandemic and mental health remains uncertain.ObjectiveTo examine the association of perceived benefits and harms of COVID-19 with confidence in coping with the pandemic and mental health symptoms.MethodsA population-based survey was conducted on 7,535 Hong Kong adults from 22 February to 23 March 2021, when the 4th wave of COVID-19 was under control. Information on sociodemographic characteristics, perceived benefits (10 options) and harms (12 options) of COVID-19, confidence in coping with the pandemic (range 0–10), loneliness (range 0–4), anxiety (General Anxiety Disorders-2, range 0–6) and depression (Patient Health Questionnaire-2, range 0–6) was collected. Latent profile analysis was used to identify the combined patterns of perceived benefits and harms of COVID-19. The associations of combined patterns with confidence in coping with COVID-19, loneliness, anxiety, and depression were examined using linear regression (β coefficient) adjusting for sociodemographic characteristics.ResultsThe combined patterns of perceived benefits and harms were classified into benefit (n = 4,338, 59.3%), harm (n = 995, 14.0%), and ambivalent (n = 2,202, 26.7%) groups. Compared with the ambivalent group, the benefit group had a significantly higher level of confidence (adjusted β 0.46, 95% CI 0.33 to 0.58), and lower levels of loneliness (−0.35, −0.40 to-0.29), anxiety (−0.67, 0.76 to-0.59), and depression (−0.65, −0.73 to-0.57). The harm group had a significantly lower level of confidence (−0.35, −0.53 to-0.16), and higher levels of loneliness (0.38, 0.30 to 0.45), anxiety (0.84, 0.73 to 0.96), and depression (0.95, 0.84 to 1.07).ConclusionPerceived greater benefit from COVID-19 was associated with better mental health and stronger confidence in coping with the pandemic.

Background: Mutations in the collagen components of the glomerular basement membrane (GBM) often lead to hereditary glomerulonephritis. Previous studies have identified that autosomal dominant mutations of Col4A3, Col4A4 or Col4A5 are associated with thin basement membrane nephropathy (TBMN), Alport syndrome and other hereditary kidney diseases. However, the genetic mutations underlying other glomerulonephritis types have not been elucidated.Methods: In this study, we investigated a Chinese family with hereditary nephritis using the methods of genetic sequencing and renal biopsy. Genomic DNA was extracted from peripheral blood of the proband and her sister, and subsequently was performed genetic sequencing. They were found to have the similar mutation sites. Other family members were then validated using Sanger sequencing. The proband and her sister underwent renal puncture biopsies, and experienced pathologists performed PAS, Masson, immunofluorescence, and immunoelectron microscopic staining of the kidney tissue sections.Results: Through genetic sequencing analysis, we detected a novel heterozygous frameshift mutation c.1826delC in the COL4A4 (NM_000092.4) gene coding region, and 1 hybrid missense variation c.86G>A (p. R29Q) was also detected in the TNXB (NM_019105.6) gene coding region in several members of this Chinese family. Interestingly, we found that the same mutations caused different clinical features and distinct pathological changes in individual family members, which confirmed that pathological and genetic testing are crucial for the diagnosis and treatment of hereditary kidney diseases.Conclusion: In this study, we found a novel heterozygous mutation in Col4A4 and co-mutations of the TNXB gene in this Chinese family. Our study indicated that the same Col4A4 mutated variants produced different pathological and clinical changes in different family members. This discovery may provide novel insights into the study of hereditary kidney disease. In addition, new genetic biology techniques and renal biopsy of individual family members are essential.

Chlamydia psittaci is the pathogen of psittacosis and infects a wide range of birds and even humans. Human infection occurs most commonly in those with a history of contact with birds or poultry. We describe a case of psittacosis in a human immunodeficiency virus infected patient in Zhejiang Province for the first time. C. psittaci infection was confirmed by nested polymerase chain reaction (PCR) and Real-Time PCR. Phylogenetic analysis revealed that the sequences from the patient’s samples clustered with genotype A in the same branch. Our study highlights the possibility of diagnosing psittacosis in patients with a chronic disease such as HIV-infected patients, and should increase awareness and surveillance of psittacosis in China.

The spread of antibiotic resistance genes (ARGs) in the environment exacerbates the contamination of these genes; therefore, the role plants play in the transmission of resistance genes in the food chain requires further research. Giant pandas consume different bamboo parts at different times, which provides the possibility of investigating how a single food source can affect the variation in the spread of ARGs. In this study, metagenomic analysis and the Comprehensive Antibiotic Resistance Database (CARD) database were used to annotate ARGs and the differences in gut microbiota ARGs during the consumption of bamboo shoots, leaves, and culms by captive giant pandas. These ARGs were then compared to investigate the impact of bamboo part consumption on the spread of ARGs. The results showed that the number of ARGs in the gut microbiota of the subjects was highest during the consumption of bamboo leaves, while the variety of ARGs was highest during the consumption of shoots. Escherichia coli, which poses a higher risk of ARG dissemination, was significantly higher in the leaf group, while Klebsiella, Enterobacter, and Raoultella were significantly higher in the shoot group. The ARG risk brought by bamboo shoots and leaves may originate from soil and environmental pollution. It is recommended to handle the feces of giant pandas properly and regularly monitor the antimicrobial and virulence genes in their gut microbiota to mitigate the threat of antibiotic resistance.

Abstract Background Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China. Methods We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock. Results Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I2 = 99.2%; p

Abstract Whether metabolites derived from injured renal tubular epithelial cells (TECs) participate in renal fibrosis is poorly explored. After TEC injury, various metabolites are released and among the most potent is adenosine triphosphate (ATP), which is released via ATP-permeable channels. In these hemichannels, connexin 43 (Cx43) is the most common member. However, its role in renal interstitial fibrosis (RIF) has not been fully examined. We analyzed renal samples from patients with obstructive nephropathy and mice with unilateral ureteral obstruction (UUO). Cx43-KSP mice were generated to deplete Cx43 in TECs. Through transcriptomics, metabolomics, and single-cell sequencing multi-omics analysis, the relationship among tubular Cx43, ATP, and macrophages in renal fibrosis was explored. The expression of Cx43 in TECs was upregulated in both patients and mice with obstructive nephropathy. Knockdown of Cx43 in TECs or using Cx43-specific inhibitors reduced UUO-induced inflammation and fibrosis in mice. Single-cell RNA sequencing showed that ATP specific receptors, including P2rx4 and P2rx7, were distributed mainly on macrophages. We found that P2rx4- or P2rx7-positive macrophages underwent pyroptosis after UUO, and in vitro ATP directly induced pyroptosis by macrophages. The administration of P2 receptor or P2X7 receptor blockers to UUO mice inhibited macrophage pyroptosis and demonstrated a similar degree of renoprotection as Cx43 genetic depletion. Further, we found that GAP 26 (a Cx43 hemichannel inhibitor) and A-839977 (an inhibitor of the pyroptosis receptor) alleviated UUO-induced fibrosis, while BzATP (the agonist of pyroptosis receptor) exacerbated fibrosis. Single-cell sequencing demonstrated that the pyroptotic macrophages upregulated the release of CXCL10, which activated intrarenal fibroblasts. Cx43 mediates the release of ATP from TECs during renal injury, inducing peritubular macrophage pyroptosis, which subsequently leads to the release of CXCL10 and activation of intrarenal fibroblasts and acceleration of renal fibrosis.

Abstract Background Carbon dot has been widely used in biomedical field as a kind of nanomaterial with low toxicity and high biocompatibility. CDs has demonstrated its unique advantages in assisted drug delivery, target diagnosis and targeted therapy with its small size and spontaneous fluorescence. However, the potential biosafety of CDs cannot be evaluated. Therefore, we focused on the study of liver, the target organ involved in CDs metabolism, to evaluate the risk of CDs in vitro. Methods and results Liver macrophage KUP5 cells and normal liver cells AML12 cells were incubated in CDs at the same concentration for 24 h to compare the different effects under the same exposure conditions. The study found that both liver cell models showed ATP metabolism disorder, membrane damage, autophagosome formation and lysosome damage, but the difference was that, KUP5 cells exhibited more serious damage than AML12 cells, suggesting that immunogenic cell type is particularly sensitive to CDs. The underlying mechanism of CDs-induced death of the two hepatocyte types were also assessed. In KUP5 cells, death was caused by inhibition of autophagic flux caused by autophagosome accumulation, this process that was reversed when autophagosome accumulation was prevented by 3-MA. AML12 cells had no such response, suggesting that the accumulation of autophagosomes caused by CDs may be specific to macrophages. Conclusion Activation of the TFEB-lysosome pathway is important in regulating autophagy and apoptosis. The dual regulation of ERK and mTOR phosphorylation upstream of TFEB influences the death outcome of AML12 cells. These findings provide a new understanding of how CDs impact different liver cells and contribute to a more complete toxicological safety evaluation of CDs.

The aim of this in vitro study was to evaluate the effect of three final irrigants, namely QMix, MTAD and EDTA, combined with three irrigation techniques, namely conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI) and photon-induced photoacoustic streaming (PIPS), on smear layer removal, dentin mineral content and microhardness in oval-shaped canals. 130 decoronated premolars with single, oval root canals were equally divided into1 blank control group and 12 treatment groups (n=10) according to the final irrigation protocols. Roots in treatment groups were instrumented with ProTaper Gold to size F4 and subjected to final irrigation. Smear layer removal was assessed by using a four-level scoring system under an environmental scanning electron microscope. Energy dispersive X-ray spectroscopy was performed to measure the dentin mineral content. Dentin microhardness was measured by Knoop microhardness testing. Statistical analysis of the data was performed by using Kruskal-Wallis test, followed by Dunn’s post hoc test with Bonferroni correction. PUI- and PIPS-activated QMix and EDTA removed smear layer more effectively than MTAD groups (p