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BackgroundSystematic reviews and meta-analyses based on observational studies have shown voluntary medical male circumcision (VMMC) may reduce HIV risk among men who have sex with men (MSM). There is a lack of randomized controlled trial (RCT) data assessing the efficacy of VMMC. ObjectiveThe primary objective of this study is to assess the efficacy of VMMC for preventing HIV acquisition among MSM who primarily engage in insertive anal sex. MethodsA multicenter RCT will be conducted among MSM in 8 cities in China. Eligible participants are men aged 18-49 years who self-report ≥2 male sex partners in the past 6 months, predominantly practice insertive anal sex, and are willing to undergo circumcision. Interested men who satisfy inclusion criteria will be tested for HIV 1 month before enrollment and at enrollment, and only those who are HIV negative will be enrolled. At baseline, all enrolled participants will be asked to report sociodemographic characteristics and sexual behaviors; provide a blood sample for HIV, syphilis, and herpes simplex virus type 2 testing; and provide a penile swab for human papillomavirus testing. Participants will be randomly assigned to the intervention or control group. Those in the intervention group will receive VMMC and undergo a web-based weekly follow-up assessment of postsurgery healing for 6 consecutive weeks. All participants will be tested for HIV at 3-, 6-, 9-, and 12-month follow-ups. All participants will also be asked to report sexual behaviors and undergo repeat herpes simplex virus type 2 and human papillomavirus testing at 6- and 12-month follow-ups. The primary end point is HIV seroconversion. Secondary end points are the safety and satisfaction with VMMC and the changes in sexual behaviors after VMMC. The grouped censored data will be analyzed by intention-to-treat approach. ResultsRecruitment for the RCT began in August 2020 and continued through July 2022. Data collection is expected to be completed by July 2023, and full data analysis is going to be completed by September 2023. ConclusionsThis study will be the first RCT to assess the efficacy of VMMC in preventing HIV infection among MSM. Results from this trial will provide preliminary evidence for the potential efficacy of VMMC to reduce incident HIV infection among MSM. Trial RegistrationChinese Clinical Trial Registry ChiCTR2000039436; https://www.chictr.org.cn/showproj.html?proj=63369 International Registered Report Identifier (IRRID)DERR1-10.2196/47160

Triboelectric materials with high charge density are the building-block for the commercial application of triboelectric nanogenerators (TENGs). Unstable dynamic processes influence the change of the charge density on the surface and inside of triboelectric materials. The charge density of triboelectric materials depends on the surface and the internal charge transfer processes. The focus of this review is on recent advances in high charge density triboelectric materials and advances in the fabrication of TENGs. We summarize the existing strategies for achieving high charge density in triboelectric materials as well as their fundamental properties. We then review current optimization methods for regulating dynamic charge transfer processes to increase the output charge density: first, increasing charge injection and limiting charge dissipation to achieve a high average surface charge density, and second, regulating the internal charge transfer process and storing charge in triboelectric materials to increase the output charge density. Finally, we present the challenges and prospects in developing high-performance triboelectric materials.

Soil salinization seriously affects the sustainable development of agricultural production; thus, the timely, efficient, and accurate estimation of soil salt content (SSC) has important research significance. In this study, the feasibility of soil salt content retrieval using machine learning models was explored based on a UAV (unmanned aerial vehicle) multi-spectral remote sensing platform. First, two variable screening methods (Pearson correlation analysis and Grey relational analysis) are used to screen the characteristic importance of 20 commonly used spectral indices. Then, the sensitive spectral variables were divided into a vegetation index group, a salt index group, and a combination variable group, which represent the model. To estimate SSC information for soil depths of 0–20 cm and 20–40 cm, three machine learning regression models were constructed: Support Vector Machine (SVM), Random Forest (RF), and Backpropagation Neural Network (BPNN). Finally, the salt distribution map for a 0–20 cm soil depth was drawn based on the best estimation model. The results of experiments show that GRA is better than PCA in improving the accuracy of the estimation model, and the combination variable group containing soil moisture information performs best. The three machine learning models have achieved good prediction effects to some extent. The accuracy and stability of the model are considered comprehensively, the prediction effect of 0–20 cm is higher than that of 20–40 cm, and the validation set coefficient of determination (R2), Root-Mean-Square-Error (RMSE), and Mean Absolute Error (MAE) of the best inversion model are 0.775, 0.055, and 0.038, and the soil salt spatial map based on the optimal estimation model can reflect the salinization distribution in the study area. Therefore, this study shows that a UAV multi-spectral remote sensing platform combined with machine learning models can better monitor farmland soil salt content.

Medium-sized ring lactams have been found as key structures in various bioactive molecules, and they are of vital importance in natural or pharmaceutical molecule synthesis. In this work 9-membered-ring lactams were synthesized with graphitic carbon nitride (g-C3N4) as photocatalyst, BI-OAc as oxidant under visible light in optimized mild conditions. These reactions exhibit a broad scope of substrates with good to excellent yield (up to 90%). In parallel, an amidyl-radical-involved photocatalytic ring expansion mechanism was proposed. This work paves a new way for the synthesis of medium-sized-ring molecules in a green and economical method.

Abstract Objective Peyronie’s disease (PD) is a fibrotic disorder of the penis, but effective treatments are lacking. Here, we observed the effects of rat-derived bone marrow mesenchymal stem cells (BMSCs) injection in the active phase and chronic phase in a rat model of PD, and the possible mechanism was analysed with fibroblasts derived from rat penile tunica albuginea (TA). Methods Thirty-two male Sprague-Dawley rats were divided into four groups. In sham group, the rats were injected with 50 µL of vehicle. In the PD group, the rats were injected with 50 µg TGF-β1. In the PD + BMSCs early treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 1 day. In the PD + BMSCs late treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 28 days. Twenty-seven days after the last injection, the erectile function of the rats was measured, and then, penile fibrosis was analysed by histology and western blot. In vitro, fibroblasts derived from rat penile TA were used to identify a possible antifibrotic mechanism of BMSCs, and a Smad7 expression vector was used as a positive control. Fibroblasts were pretreated with the Smad7 expression vector or BMSCs for 48 h and then activated with 10 ng/mL TGF-β1 for 24 h. Cells viability was assessed, and Smad7, collagen 3, elastase-2B and osteopontin expression levels were analysed by immunofluorescence and western blot. Furthermore, fibroblasts were transfected with Smad7 siRNA or scramble control to observe whether the effects of BMSCs could be offset. Results Erectile function obviously improved, and fibrosis of penile TA was prevented after BMSCs treatment compared with that in the rats with PD. Furthermore, the effects of BMSCs treatment in the active phase were better than those in the chronic phase. After cocultured with BMSCs, cell viability was not affected, Smad7 expression was upregulated, and collagen 3, elastase-2B and osteopontin levels were decreased in the TGF-β1-treated fibroblasts. After transfection with Smad7 siRNA, the antifibrotic effects of BMSCs were offset. Conclusions The antifibrotic effects of BMSCs treatment in the active phase of the PD rat model were better than those in the chronic phase. A possible mechanism of BMSCs treatment was related to increased Smad7 expression, suggesting a possible effective and safe procedure for the treatment of PD.

Objective: Xueshuantong (lyophilized) for injection (XST) is an effective botanical drug for treating unstable angina pectoris (UAP). However, a meta-analysis of XST combined with conventional treatment (CT) against UAP has not been conducted. Therefore, this study aimed to investigate the effectiveness and safety of XST combined with CT for UAP patients compared to CT alone.Methods: Randomized controlled trials (RCT) of XST in UAP patients were retrieved from the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, VIP, Wanfang, and Chinese Biological Medicine Database databases. A meta-analysis was performed using Revman 5.4 and Stata 16.0, and the quality of the included literature was evaluated based on the Cochrane risk-of-bias 2.0 (RoB2.0) tool. The aggregate 95% confidence intervals (CIs), mean difference (MD), and relative risk (RR) estimates were calculated. A GRADE assessment was performed using GRADEprofiler 3.6, and trial sequent analysis was performed using TSA 0.9.Results: Thirty-four studies involving 3,518 patients were included in the analysis. The combination of CT with XST improved the comprehensive clinical efficacy (RR = 1.22, 95% CI: 1.18–1.26, p < 0.00001) and ECG improvement (RR = 1.24, 95% CI: 1.18–1.31, p < 0.00001). The frequency of angina attacks was lower (MD = −0.73, 95% CI: −0.92 to −0.55, p < 0.00001), and the duration was shorter (MD = −1.08, 95% CI: −1.44 to −0.72, p < 0.00001) in the group that received CT combined with XST compared to the one without XST. Total cholesterol levels (MD = −1.30, 95% CI: −1.83 to −0.78, p < 0.00001) and triglyceride levels (MD = −0.76, 95% CI: −0.93 to −0.59, p < 0.00001) were lower in patients who received CT in combination with XST than those who received CT alone. CT combined with XST reduced whole blood viscosity (MD = −0.72, 95% CI = −0.99 to −0.44, p < 0.00001) and plasma viscosity (MD = −0.24, 95% CI: −0.46 to −0.03, p = 0.03). There was no statistically significant difference in the incidence of cardiovascular events or adverse events among patients treated with the combination of XST and CT compared to CT alone. The GRADE assessment indicated that the composite quality of the evidence was low. The trial sequent analysis showed an adequate sample size and stable findings for the clinical efficacy of CT combined with XST for unstable angina.Conclusion: The present systematic review and meta-analysis conditionally indicate that XST combined with CT improved the clinical outcomes of patients with unstable angina more than CT alone with a better safety profile. However, the results need further validation due to limitations in the quality of the included studies.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022357395.

Soil salinization is a severe soil degradation issue in arid and semiarid regions. The distribution of soil salinization can prove useful in mitigating soil degradation. Remote sensing monitoring technology is available for obtaining the distribution of soil salinization rapidly and nondestructively. In this study, experimental data were collected from seven study areas of the Hetao Irrigation District from July to August in 2021 and 2022. The soil salt content (SSC) was considered at various soil depths, and the crop type and time series were considered as environmental factors. We analyzed the effects of various environmental factors on the sensitivity response of unmanned aerial vehicle (UAV)-derived spectral index variables to the SSC and assessed the accuracy of SSC estimations. The five indices with the highest correlation with the SSC under various environmental factors were the input parameters used in modeling based on three machine learning algorithms. The best model was subsequently used to derive prediction distribution maps of the SSC. The results revealed that the crop type and time series did not affect the relationship strength between the SSC and spectral indices, and that the classification of the crop type and time series can considerably enhance the accuracy of SSC estimation. The mask treatment of the soil pixels can improve the correlation between some spectral indices and the SSC. The accuracies of the ANN and RFR models were higher than SVR accuracy (optimal R2 = 0.52–0.79), and the generalization ability of ANN was superior to that of RFR. In this study, considering environmental factors, a UAV remote sensing estimation and mapping method was proposed. The results of this study provide a reference for the high-precision prediction of soil salinization during the vegetation cover period.

Abstract Learning and studying the structure–activity relationship in the bio‐enzymes is conducive to the design of nanozymes for energy and environmental application. Herein, Fe single‐atom nanozymes (Fe‐SANs) with Fe–N5 site, inspired by the structure of cytochromes P450 (CYPs), are developed and characterized. Similar to the CYPs, the hyperoxide can activate the Fe(III) center of Fe‐SANs to generate Fe(IV)O intermediately, which can transfer oxygen to the substrate with ultrafast speed. Particularly, using the peroxymonosulfate (PMS)‐activated Fe‐SANs to oxidize sulfamethoxazole, a typical antibiotic contaminant, as the model hyperoxides activation reaction, the excellent activity within 284 min−1 g−1(catalyst) mmol−1(PMS) oxidation rate and 91.6% selectivity to the Fe(IV)O intermediate oxidation are demonstrated. More importantly, instead of promoting PMS adsorption, the axial N ligand modulates the electron structure of FeN5 SANs for the lower reaction energy barrier and promotes electron transfer to PMS to produce Fe(IV)O intermediate with high selectivity. The highlight of the axial N coordination in the nanozymes in this work provides deep insight to guide the design and development of nanozymes nearly to the bio‐enzyme with excellent activity and selectivity.

Recent changing patterns of global climate have turned out to be a severe hazard to the horticulture crops production. A wide range of biotic and abiotic stresses often affect plants due to their sessile nature. Horticultural crop losses are mainly caused by abiotic factors such as drought, salt, heat, cold, floods, and ultraviolet radiation. For coping up with these adversities, well-developed mechanisms have been evolved in plants, which play a role in perceiving stress signals and enabling optimal growth responses. Interestingly, the use of phytohormones for suppressing the impact of abiotic stress has gained much attention in recent decades. For circumvention of stress at various levels, including physiological, molecular, as well as biochemical, a sophisticated mechanism is reported to be provided by the phytohormones, thus labeling these phytohormones a significant role in plant growth and development. Phytohormones can improves tolerance against abiotic stresses by increasing seed germination, seedling growth, leaf photosynthesis, root growth, and antioxidant enzymes and reducing the accumulation of reactive oxygen species, malonaldehyde, and electrolyte leakage. Recent discoveries highlight the significant role of a variety of phytohormones including melatonin (MEL), Gamma-aminobutyric acid (GABA), jasmonic acid (JA), salicylic acid (SA), brassinosteroids (BRs), and strigolactones (SLs) in abiotic stress tolerance enhancement of horticultural plants. Thus, current review is aimed to summarize the developmental concepts regarding role of phytohormones in abiotic-stress mitigation, mainly in horticultural crops, along with the description of recent studies which identified the role of different phytohormones in stressed environments. Hence, such a review will help in paving the path for sustainable agriculture growth via involvement of phytohormones in enhancement of abiotic stress tolerance of horticultural crops.

Brown adipocytes contribute to energy balance, and adipocyte development and brown adipocyte thermogenesis are in part regulated by epigenetic modifications. Here the authors report that the histone demethylase Utx maintains brown adipocyte identity via demethylation of PRDM16, which in turn represses myogenic remodelling via DNMT1-mediated Myod1 promoter hypermethylation in mice.

ImportanceProblems with the wellbeing of healthcare workers (HCWs) are widespread and associated with detrimental consequences for the workforce, organizations, and patients.ObjectiveThis study tested the effectiveness of the Web-based Implementation for the Science of Enhancing Resilience (WISER) intervention, a positive psychology program, to improve six dimensions of the wellbeing of HCWs.DesignWe conducted a randomized controlled trial of HCWs between 1 April 2018 and 22 July 2019. Cohort 1 received WISER daily for 10 days. Cohort 2 acted as a waitlist control before receiving WISER.SettingWeb-based intervention for actively employed HCWs across the United States.ParticipantsEligibility criteria included being ≥18 years old and working as a HCW. Each participant was randomized to start the intervention or serve as a waitlist control for 14 days before starting the intervention.InterventionsCohorts received links via 10 texts exposing them to introductory videos and positive psychology exercises (3 good things, cultivating awe, random acts of kindness, cultivating relationships, and gratitude letters).Main outcomes and measuresThe primary outcome was emotional exhaustion; secondary outcomes included depressive symptoms, work-life integration, happiness, emotional thriving, and emotional recovery. All outcomes were assessed at baseline, 1-week post-intervention (primary endpoint), and 1, 6, and 12-month post-intervention. Outcomes were measured using six validated wellbeing instruments, rescaled to 100-point scales for comparison. Six items assessed participants' WISER experience. The analysis employed mixed-effects models.ResultsIn cohorts 1 and 2, 241 and 241 initiated WISER, and 178 (74%) and 186 (77%) completed the 6-month follow-up, respectively. Cohort populations were similar at baseline, mostly female (81; 76%) and nurses (34; 32%) or physicians (22; 23%), with 1–10 years of experience in their current position (54; 52%). Relative to control, WISER significantly improved depressive symptoms [−7.5 (95%CI: −11.0, −4.0), p < 0.001], work-life integration [6.5 (95%CI: 4.1, 8.9), p < 0.001], happiness [5.7 (95%CI: 3.0, 8.4), p < 0.001], emotional thriving [6.4 (95%CI: 2.5, 10.3), p = 0.001], and emotional recovery [5.3 (95%CI: 1.7, 8.9), p = 0.004], but not emotional exhaustion [−3.7 (95%CI: −8.2, 0.8), p = 0.11] at 1 week. Combined cohort results at 1, 6, and 12 months showed that all six wellbeing outcomes were significantly improved relative to baseline (p < 0.05 for all). Favorable impressions of WISER were reported by 87% of participants at the 6-month post-assessment.Conclusion and relevanceWISER improved HCW depressive symptoms, work-life integration, happiness, emotional thriving, and emotional recovery. Improvements in all HCW wellbeing outcomes endured at the 1-, 6-, and 12-month follow-ups. HCW's impressions of WISER were positive.Clinical trials numberhttps://clinicaltrials.gov/ct2/show/, identifier: NCT02603133. Web-based Implementation for the Science of Enhancing Resilience Study (WISER).

The diagnosis related group (DRG) was the most commonly used prospective hospital payment platform in developed countries. One of the major limitations of the DRG system is that the DRG grouping is not sufficiently homogeneous in benchmarking underlying resource needs. We developed a novel hospital payment and management system called Big Data Diagnosis & Intervention Packet (BD-DIP) by applying the similar case mix index (CMI) principles but the grouping is based on unique combination of ICD-10 and ICD-9 v3 codes. The initial prototype of BD-DIP was developed using hospital discharge records in Shanghai and then piloted in Guangzhou, China. The average coefficient of variation of the DB-DIP is about one-third smaller than the US DRG system. Results from the pilot evaluation showed that introduction of the BD-DIP lead to about 5% hospital budget savings and notable improvement in hospital care efficiency, including increased institutional CMI, lower admission rates, smaller variation in hospital charges, and lower patient cost-sharing burdens. The implementation of hospital monitoring tools resulted in identification of potential irregular practices to enable further auditing and investigation. The BD-DIP platform has a number of advantages over DRG-based payment models in terms of more homogeneous resource utilization within groups, design simplicity, dynamic in grouping, and reimbursement value in reflecting real-world treatment pathways and costs, and easy to implement.

BackgroundMyocardial infarction induces elevation of progenitor cells in the circulation, a reparative response inhibited by type-2 diabetes.ObjectivesDetermine if myocardial infarct severity and diabetes interactively influence the migratory activity of CD34+/CXCR4+ progenitor cells and if the migratory test predicts cardiac outcomes.Materials and methodsA longitudinal study was conducted on patients with or without diabetes with a STEMI or NSTEMI. CD34+/CXCR4+ cells were measured in the peripheral blood using flow cytometry, and migratory activity was tested in vitro on cells isolated from samples collected on days 0 and 4 post-infarct. Cardiac function was assessed at three months using cardiac MRI.ResultsOf 1,149 patients screened, 71 (6.3%) were eligible and consented. Fifty had STEMI (16 with diabetes) and 21 NSTEMI (8 with diabetes). The proportion of CD34+/CXCR4+ cells within blood mononuclear cells was 1.96 times higher after STEMI compared with NSTEMI (GMR = 1.96, 95% CI 0.87, 4.37) and 1.55 times higher in patients with diabetes compared to patients without diabetes (GMR = 1.55, 95% CI 0.77, 3.13). In the latter, STEMI was associated with a 2.42-times higher proportion of migrated CD34 + /CXCR4 + cells compared with NSTEMI (GMR = 2.42, 95% CI 0.66, 8.81). In patients with diabetes, the association was the opposite, with a 55% reduction in the proportion of migrated CD34+/CXCR4+ cells. No statistically significant associations were observed between the frequency in peripheral blood or in vitro migration capacity of CD34+/CXCR4+ cells and MRI outcomes.ConclusionWe document the interaction between infarct and diabetes on the migratory activity of CD34+/CXCR4+ cells. The test did not predict functional outcomes in the studied cohort.

In Saudi Arabia, air conditioning is the main consumer of electricity, and increasing its energy efficiency is of great importance for energy conservation and carbon footprint reduction. This study presents the evaluation of a hybrid indirect evaporative cooling-mechanical vapor compression (IEC-MVC) cycle for cooling applications in Saudi Arabia. Most cities in this country are characterized by a high sensible cooling demand, and a few cities near the coasts of the Red sea and the Persian Gulf also need dehumidification. By employing the hybrid system, IEC can undertake about 60% of the cooling load in the summer of arid cities, and energy consumption can be reduced by up to 50%. The contribution of IEC and energy saving are less significant in humid cities because the latent loads have to be handled by MVC. Over the whole year, IEC contributes 50% of the total cooling capacity and reduces energy consumption by 40% in dry cities, while the saving is lower at 15%–25% in humid cities like Mecca and Jeddah. The average water consumption of the IEC is in the range of 4–12 L/hr. The water consumption can be replenished by the condensate collected from the MVC evaporator if the ambient humidity is high. Based on the annual performance, the cost of the IEC-MVC process is calculated, and it is 15%–35% lower than the standalone MVC. The results demonstrate the great potential of the hybrid IEC-MVC cycle in Saudi Arabia.

The quantitative characterization of connectivity of pore geometry and its reconstruction of topological connectivity are two important methods to describe the laws of fluid seepage in porous media.However, the lag of theoretical work severely restricts the emergence of new geometric modeling methods.The tortuosity is one of the key carriers connecting permeability and geometric structure, and its theoretical model has not been broken through.First, combining the Hagen-Poiseuille equation and Darcy formulas, the universal expression of the tortuosity for capillary model and the pore model composed by the particles are derived.Then for the low permeability medium, combined with the formula of capillary pressure, the tortuosity expression correlated to the saturation is obtained.Furthermore, the fractal dimension of tortuosity is introduced to explain the new term of fractal coefficient based on experimental analysis.Considering the bifurcated capillary channel, a bifurcation model was established to analyze the tortuosity characteristics and the geometric relationship between the mother and sub-holes based on the energy optimization criterion was obtained.Taking the salt rock as an example, the applicability and reliability of the theoretical formula of tortuosity are verified, and the research results provide a new idea for calculating the tortuosity of porous media.

Abstract Land-use suitability assessment crucial is for coal mine rehabilitation planning, especially for the coal mines that have undergone varying degrees of mining subsidence. In this study, we present an assessment on the suitability of crop cultivation in the Dawu coal mining district in NW Jiangsu province, Eastern China. Distribution of local land subsidence is delineated with topographic analysis, and the weight-of-evidence (WoE) suitability assessment has encompassed various factors including the conditions of soil (e.g., acidity and porosity), groundwater level, irrigation and drainage, terrain slope, and land pollution. Consequently, the Dawu district is divided into four categories (high, moderate, low, very-low) of agricultural suitability. Collaborating with the local government agencies (e.g., Land and Resources Bureau and Agriculture Bureau), a land-use plan is proposed. In the plan, the highly suitable areas for agriculture (and the surrounding moderately suitable areas) are allocated as farmlands, whilst the other moderately to lowly suitable areas are allocated as ecological zones for restoring the ecosystem and ecological diversity. The barely suitable areas with severe subsidence are allocated as artificial lakes, which also serve as reservoirs for farmland irrigation and drainage. To protect these new farmlands from soil erosion, infrastructure such as embankment and windbreak are also included in our rehabilitation plan. Our study highlights the necessity of forward planning in coal mine rehabilitation.

Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.

In recent years, due to the rapid progress of urbanization, the subway system with the advantages of large transport capacity, punctuality, efficiency, convenience and safety has become one of the main transportation modes in metropolitan areas. With the increase in passenger flow, the comfort of subway passengers has attracted extensive attention from the academic community. In this paper, we begin by analyzing the characteristics of the subway environment and sort out six environmental elements that affect passengers’ comfort, including thermal environment, vibration, noise, lighting, air quality, and air pressure. In addition, the measurement scheme, calculation model, and evaluation method of each element are outlined based on relevant norms and literature. Through reviewing the studies in the past 2 decades, it is found that the in-depth research is still in demand for a comprehensive comfort evaluation model with multi-element coupling. A deep understanding of the subway passengers’ comfort is the basis for the design, development, and operation regulation of the subway environmental control system. Measures to improve comfort, especially the exploitation of energy-saving air conditioning systems, will provide strong support for the sustainable and sound growth of the rail transit industry.

Gastric cancer (GC), a malignant tumor of digestive tract, is characterized by a high death rate. Thus, it is of particular importance to clarify the mechanisms of GC and gain new molecular targets for the sake of preventing and treating GC. It was reported that long non-coding RNAs (IncRNAs) are prognostic factors to cancer. Ferroptosis refers to a process of programmed cell death dependent on iron. This study sets out to investigate the expression and function of ferroptosis-related lncRNA (FRlncRNA) in GC. TCGA datasets offered RNA-seq data for 375 GC patients and clinical data for 443 GC patients. Based on Pearson’s correlation analysis, we studied their expression and identified the FRlncRNAs. Differentially expressed prognosis related to FRlncRNA were determined with the help of the Wilcoxon test and univariate Cox regression analysis. To evaluate the accuracy of the prognostic capacity, researchers used the Kaplan-Meier technique, as well as univariate and multivariate Cox regression and receiver operating characteristic (ROC) curve studies. We also carried out the real-time PCR and CCK8 assays to examine the expression and function of FRlncRNA. In this study, we identified 50 ferroptosis-related DEGs which were involved in tumor progression. In addition, we identified 33 survival-related FRlncRNAs. Among them, lncRNA associated with SART3 regulation of splicing(LASTR) was confirmed to be highly expressed in GC specimens compared to non-tumor specimens in this cohort. Survival assays illuminated that the high LASTR expression predicted a shorter overall survival and progression-free survival of GC patients. Based on multivariate Cox regression analyses, it was confirmed that the GC had a worse chance of surviving the disease overall if their tumors expressed LASTR, which was an independent prognostic indication. Then, Loss-of-function tests showed that knocking down LASTR had a significant effect on reducing the proliferation of GC cells. Finally, we found that the expression of LASTR was negatively associated with CD8 T cells, T cells, Th17 cells, and T helper cells. Overall, our findings identified a novel survival-related FRlncRNA, LASTR which possibly can serve as a novel prognostic biomarker predicting response to cancer immunotherapy and therapeutic target for GC patients.

Background: Mumps is caused by the mumps virus and is characterized by pain and parotid gland swelling. Although its incidence has declined due to vaccines, outbreaks still occur among children. In addition, it can lead to severe complications, so it has a certain perniciousness. Pudilan Xiaoyan oral liquid (PDL), a Chinese patent medicine, commonly treats children with mumps. However, its safety, efficacy, and specific mechanisms lack relevant evaluation and analysis. Therefore, we did a meta-analysis of the randomized controlled trials combined with a network pharmacology analysis to assess the efficacy and safety of PDL in relieving symptoms of mumps in children and investigate its pharmacological mechanisms.Methods: This study systematically searched the China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform, VIP Database, Sinomed, Chinese Medical Journal Full-text Database, PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar for the published randomized controlled trials (date up to 3 March 2022; studies in both English and Chinese) comparing PDL and antiviral drug combination treatment to standalone antiviral drug treatment. The primary outcomes in this study were the effective rate and duration of five characteristic symptoms of children’s mumps. We assessed the pooled data by using a fix-effect or random-effect model. We illustrated an odds ratio (OR) or standardized mean difference (SMD) with a 95% confidence interval (CI) using the Stata 15 software. In network pharmacology, active components of PDL were collected from the traditional Chinese medicine system pharmacology technology platform and the CNKI studies, while mumps’ targets were collected from databases of the Genecards and Online Mendelian Inheritance in Man (OMIM), and then we constructed a “drug-component-target” network and a protein–protein interaction network using Cytoscape 3.9.0 for screening the core components and targets. Next, we ran Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of intersection targets of PDL and mumps. Finally, molecular docking was performed between core components and targets.Results: Of 70 identified studies, 12 were eligible and included in our analysis (N = 1,307 participants). Compared with the antiviral drug treatments, combination treatment using PDL and antiviral drugs provided higher effective rates (OR = 5.94), shorter symptom durations for fever (SMD = −1.05), headache (SMD = −0.69), parotid gland swelling (SMD = −1.30), parotid gland pain (SMD = −2.53), and loss of appetite (SMD = −0.56) with fewer reported side effects. Of the 113 active components of PDL and 57 mumps’ targets, 11 core components like quercetin, isoetin, and seven core targets such as albumin (ALB) and interleukin-6 were obtained. Moreover, the potential pathways identified included cytokine–cytokine receptor interaction and T helper cell 17 (Th17 cell) differentiation. Molecular docking results revealed that most core components and targets could form stable structures. The core components, including isoetin, quercetin, and luteolin, and core targets involving heat shock protein HSP 90-alpha (HSP90AA1), estrogen receptor (ESR1), and ALB showed the best affinities.Conclusion: The combined use of PDL and antiviral drugs could effectively improve the efficacy of mumps among children and rapidly alleviate mumps-related symptoms. This efficacy may be associated with the anti-inflammatory and antiviral mechanisms by which PDL acts using multiple components, multiple targets, and multiple pathways. However, these results should be confirmed by further studies.

Background: Several quantitative systematic reviews of Kanglaite (KLT), an herb preparation used to treat cancer and malignant pleural effusion, have been published in recent years. However, the clinical evidence reported in these studies has not been pursued further and the methodological quality of these meta-analyses remains unknown. Therefore, an overview was designed to map the evidence landscape based on the published meta-analyses on KLT in cancer treatment.Methods: Two bibliographic databases (PubMed and Embase) were searched from inception to 25 November 2021. Two independent reviewers were involved in study selection, data abstraction, and methodological quality assessment using AMSTAR 2. The principal features of publications and the clinical outcomes of efficacy and safety were synthesized narratively, and results of methodological quality were reported as frequencies and percentages with the corresponding 95% confidence intervals. The evidence map was used to visualize the overall quality. Excel 2016 and Stata 17/SE were used for data analysis.Results: Thirteen meta-analyses published in English were included for in-depth analysis. Among them, the year of publication ranged from 2008 to 2021, and the number of included patients ranged from 488 to 2,964. Regarding the cancer type, seven articles focused on non-small cell lung cancer, two on malignant pleural effusion, and four reviews on digestive system malignancies, such as hepatocellular carcinoma and pancreatic cancer. Almost all included meta-analyses reported that KLT as adjunctive therapy could improve various efficacy outcomes (such as disease response rates, quality of life, immune indicators) and reduce the rate of occurrence of adverse reactions, such as nausea and vomiting, leukopenia, and anemia. In terms of their methodological quality, three meta-analyses were of low quality, whereas 10 studies were critically low in quality. The methodological flaws main involved items 2 (“predesigned protocol and registration informatio’’), 3 (“rationale of study design for inclusion”), 4 (“comprehensive search strategy’’), 5 (“literature selection in duplicate’’), 7 (“list of excluded studies with reasons’’), 8 (“adequate information on included studies’’), 10 (“funding support for included primary studies’’), and 12 (“evaluation of the potential impact of risk of bias’’) based on the AMSTAR 2 tool.Conclusion: Current evidence reveals that KLT is effective and safe as an adjunctive treatment for non-small cell lung cancer, malignant pleural effusion, and digestive system malignancies (such as hepatocellular carcinoma). However, the results assessed in this overview should be further verified using well-designed and clearly reported clinical trials and meta-analyses of KLT.

The unique structure and physical properties of perovskite-type catalysts make them highly promising for catalyzing efficient coal combustion. Mesoporous perovskite LaNixFe1−xO3 (x = 0.2, 0.4, 0.6, 0.8) coal combustion catalysts were synthesized using the sol–gel method. The effects of the doping amount of B-site doped nickel on both the crystal structure and catalytic performance were investigated. X-ray diffraction, scanning electron microscopy, and nitrogen adsorption–desorption tests were used to characterize the catalyst samples. Thermogravimetric analysis (TG) and activation energy (Ea) calculations were used to assess the catalyst’s activity for the catalytic combustion of anthracite coal (JF coal, originating from Shanxi, China). Results revealed that nickel doping created lattice distortion and Ni-Fe alloy interactions. The difference in nickel doping significantly affects the morphology and catalytic activity of perovskite. The addition of LaNi0.6Fe0.4O3 (NI6) with a mass fraction of 5% resulted in the highest average burning rate value (va = 4.52%/min) of JF coal among all synthesized catalysts. The Ea of JF coal catalytic combustion, calculated using the Coats–Redfern method and the Doyle method, showed a good agreement with the TG curves. The LaNixFe1-xO3 series catalysts were found to significantly decrease the Ea of JF coal combustion, with a maximum reduction of 42% compared to the case without any catalyst added. Among the synthesized catalysts, NI6 exhibited a favorable catalytic combustion performance and is thus a promising candidate for the clean and efficient utilization of coal resources.

Owing to the similar valence electron structures between the B-N bond and the C-C bond, boron nitride, similar to carbon, can form abundant polymorphs with different frameworks, which possess rich mechanical and electronic properties. Using the hollow, cage-like B16N16 cluster as building blocks, here, we established three new BN polymorphs with low-density porous structures, termed Cub-B16N16, Tet-B16N16, and Ort-B16N16, which have cubic (P4¯3m), tetragonal (P4/nbm), and orthomorphic (Imma) symmetries, respectively. Our density functional theory (DFT) calculations indicated that the existence of porous structure Cub-B16N16, Tet-B16N16, and Ort-B16N16 were not only energetically, dynamically, thermally and mechanically stable, they were even more stable than some known phases, such as sc-B12N12 and Hp-BN. The obtained Pugh’s ratio showed that the Cub-B16N16 and Tet-B16N16 structures were brittle materials, but Ort-B16N16 was ductile. The analysis of ideal strength, Young’s moduli, and shear moduli revealed that the proposed new phases all exhibited sizable mechanical anisotropy. Additionally, the calculation of electronic band structures and density of states showed that they were all semiconducting with a wide, indirect band gap (~3 eV). The results obtained in this work not only identified three stable BN polymorphs, they also highlighted a bottom-up way to obtain the desired materials with the clusters serving as building blocks.

Two-dimensional ferromagnetic (FM) half-metals are highly desirable for the development of multifunctional spintronic nano-devices due to their 100% spin polarization and possible interesting single-spin electronic states. Herein, using first-principles calculations based on density functional theory (DFT) with the Perdew–Burke–Ernzerhof (PBE) functional, we demonstrate that the MnNCl monolayer is a promising FM half-metal for spintronics. Specifically, we systematically investigated its mechanical, magnetic, and electronic properties. The results reveal that the MnNCl monolayer has superb mechanic, dynamic, and thermal (ab initio molecular dynamics (AIMD) simulation at 900 K) stability. More importantly, its intrinsic FM ground state has a large magnetic moment (6.16 μB), a large magnet anisotropy energy (184.5 μeV), an ultra-high Curie temperature (952 K), and a wide direct band gap (3.10 eV) in the spin-down channel. Furthermore, by applying biaxial strain, the MnNCl monolayer can still maintain its half-metallic properties and shows an enhancement of magnetic properties. These findings establish a promising new two-dimensional (2D) magnetic half-metal material, which should expand the library of 2D magnetic materials.

The effects of different pH levels and ionic strength in calcium on the stability and aeration characteristics of dairy emulsions were investigated in this study. The results revealed that the stability and aeration characteristics of the emulsion were enhanced as the pH value increased from 6.5 to 7.0 and were optimal within the pH of 6.8~7.0, while the concentration of free calcium ions (Ca2+) was 2.94~3.22 mM. With the pH subsequently fixed at 6.8 and 7.0, when the addition of CaCl2 was increased to 2.00 mM (free Ca2+ strength > 4.11 mM), stability and aeration characteristics reduced significantly, including the flocculation of fat globules, an increase in particle size, and a decrease in the zeta potential and viscosity of the O/W emulsion, all leading to an increase in interfacial protein mass and decreased overrun and foam firmness. Overall, the results indicated that pH changes and CaCl2 addition significantly influenced the stability and aeration characteristics of dairy emulsions, by influencing free Ca2+ strength, which is an important factor in determining the quality of dairy emulsions.

Community question answering (CQA), with its flexible user interaction characteristics, is gradually becoming a new knowledge-sharing platform that allows people to acquire knowledge and share experiences. The number of questions is rapidly increasing with the open registration of communities and the massive influx of users, which makes it impossible to match many questions to suitable question answering experts (noted as experts) in a timely manner. Therefore, it is of great importance to perform expert recommendation in CQA. Existing expert recommendation algorithms only use data from a single platform, which is not ideal for new CQA platforms with sparse historical interaction and a small number of questions and users. Considering that many mature CQA platforms (source platforms) have rich historical interaction data and a large amount of questions and experts, this paper will fully mine the information and transfer it to new platforms with sparse data (target platform), which can effectively alleviate the data sparsity problem. However, the feature composition of questions and experts in different platforms is inconsistent, so the data from the source platform cannot be directly transferred for training in the target platform. Therefore, this paper proposes feature-alignment-based cross-platform question answering expert recommendation (FA-CPQAER), which can align expert and question features while transferring data. First, we use the rating predictor composed by the BP network for expert recommendation within the domains, and then the feature matching of questions and experts between two domains by similarity calculation is achieved for the purpose of using the information in the source platform to assist expert recommendation in the target platform. Meanwhile, we train a stacked denoising autoencoder (SDAE) in both domains, which can map user and question features to the same dimension and align the data distributions. Extensive experiments are conducted on two real CQA datasets, Toutiao and Zhihu datasets, and the results show that compared to the other advanced expert recommendation algorithms, this paper’s method achieves better results in the evaluation metrics of MAE, RMSE, Accuracy, and Recall, which fully demonstrates the effectiveness of the method in this paper to solve the data sparsity problem in expert recommendation.

Objective To investigate the effect of UBE2W on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. Methods Different interference sequences of UBE2W siRNA(1#, 2# and 3#) were transiently transfected into mouse fibroblast cell line L929.The expression of UBE2W protein was detected by Western blot. The siRNA with the most significant inhibitory effect was selected for transfection in vivo. Ten C57BL / 6 male mice were randomly injected with siRNA (siUbe2w/si-control) via caudal vein and fed with 2.5% DSS to construct two groups of DSS ulcerative colitis models, Ube2w knockdown group and control group with 5 mice in each group. Western blot and RT-qPCR were used to detect the expression of UBE2W in colon tissue of mice. The weights of mice in the two groups were observed, and the severity of colitis was compared by histological score. Results Ube2w siRNA 2# inhibited UBE2W protein expression most significantly in L929 cells. UBE2W mRNA and protein expression in colon tissue of Ube2w knockdown group were lower than those in control group, and weight loss in Ube2w knockdown group was significantly more obvious than that in control group, and the histological score of colitis in knockdown group was 8.60±0.24, which was higher than that in control group (5.20±0.49)(P＜0.05). Conclusions UBE2W is involved in the regulation of inflammatory response and Ube2w knockdown increases the susceptibility to DSS induced ulcerative colitis in mice.

Self-powered sensors can provide energy and environmental data for applications regarding the Internet of Things, big data, and artificial intelligence. Nanogenerators provide excellent material compatibility, which also leads to a rich variety of nanogenerator-based self-powered sensors. This article reviews the development of nanogenerator-based self-powered sensors for the collection of human physiological data and external environmental data. Nanogenerator-based self-powered sensors can be designed to detect physiological data as wearable and implantable devices. Nanogenerator-based self-powered sensors are a solution for collecting data and expanding data dimensions in a future intelligent society. The future key challenges and potential solutions regarding nanogenerator-based self-powered sensors are discussed.

Since 2020, the COVID-19 has accelerated the process of global energy transition. The production and operation of oil and gas companies have been constrained by both climate change and market decline, and the lowcarbon transformation strategy has attracted widespread attention. Based on the analysis of the background of strategic transformation of oil and gas companies, the strategic choice under the vision of carbon neutrality was discussed in detail, which is mainly divided into five aspects: (1) Significantly reduce capital expenditure, investment attitude is more prudent. (2) Large-scale asset impairment operations, the scale of a decade of record high. (3) Focus more on upstream and downstream core assets, and further transform to low carbon terminal. (4) Different types of oil companies have adopted different clean and low-carbon strategies. Among them, European oil companies prefer to develop diversified clean and lowcarbon businesses, American oil companies pay more attention to Carbon Capture and Storage (CCS) and other businesses, and some national oil companies also put forward short and medium term emission reduction targets to follow the trend of energy transition. (5) The heat of oil and gas mergers and acquisitions has slowed down significantly, and low-carbon mergers and acquisitions are favored. Finally, some suggestions were put forward for Chinese oil and gas companies, providing reference for the sustainable development of Chinese oil and gas enterprises.

Abstract Background Systematic lymph node dissection is an important part of radical resection for lung cancer. Insufficient incision of the mediastinal pleura results in a tapered or tunnel-like operation surface, which increases the difficulty of uniportal video-assisted thoracoscopic mediastinal lymph node dissection. The objective of this study was to report our concept of broad exposure and investigate the efficacy and safety of this concept in uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection. Methods We retrospectively analyzed the clinical data of the 204 non-small cell lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery for anatomical lobectomy and systematic lymph node dissection following the concept of broad exposure. SPSS 23.0 software was used for statistical analysis. Results All operations were completed under uniportal video-assisted thoracoscopic surgery following the concept of broad exposure. The median surgery time was 102 (range, 76–285) minutes and the median blood loss was 50 (range, 20–900) milliliters. The median chest tube duration time was 2 (range, 1–6) days, the median postoperative hospital duration time was 5 (range, 4–10) days. The median number of dissected lymph node stations and dissected lymph nodes were 8 (range,6–9) and 15(range,12–19), respectively. The median number of dissected mediastinal lymph nodes stations and dissected mediastinal lymph nodes were 5(range,3–6) and 11(range,10–15), respectively. The up-staging rate of N staging was 6.86%. The postoperative complication rate was 10.29% and there was no perioperative death. Conclusions According to our results, it’s effective and safe to perform uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection following the concept of broad exposure. This new concept not only emphasizes sufficient exposure, but also focuses on protection of important tissues.

The purpose of this study is to assess the feasibility of astaxanthin-rich Oedocladium carolinianum as an immunostimulant in the diet for Trachinotus ovatus. Three experimental diets containing 0% (OC0), 1% (OC1), and 5% (OC5) O. carolinianum powder were formulated for 6-week feeding trials. The results indicated that the OC5 diet boosted the growth performance through decreasing the feed conversion ratio and increasing digestive enzyme activities and intestinal villus length. Meanwhile, fish fed with the OC5 diet promoted antioxidant ability via stimulating the Nrf2-ARE signal pathway and enhancing antioxidant enzyme activities. Furthermore, the OC5 diet exerted hepatoprotective effects by suppressing the lipid deposition and inflammation response and enhancing the transport capacity of cholesterol. Besides, the OC5 diet improved the non-specific immunity by activating the lysozyme and complement system and increasing the nitric oxide content and total nitric oxide synthase activity. Dietary O. carolinianum supplementation promoted the deposition of astaxanthin in the whole body. Therefore, a diet supplemented with 5% O. carolinianum is recommended to boost the growth, antioxidant capacity, immune response, and flesh quality of T. ovatus.

Bulbus Fritillariae (BF) is a kind of herbal medicine widely used in many countries including China, Japan, Korea, and so on. Among the known BF medicinal materials, Bulbus Fritillariae cirrhosae (BF cirrhosae) was reported to have the best curative effect. Due to the limited resources of BF cirrhosae, a lot of adulterants have emerged in the market, impairing the market order, resource development, and above all, clinical efficacy. Here, a novel nucleic acid amplification technique, Recombinase Assisted Loop-mediated isothermal DNA Amplification (RALA), was used to establish a real-time fluorescence isothermal molecular authentication method for five commonly used BF drugs. Moreover, this RALA-based assay can also be developed as a colorimetric detection method for on-site detection. Both real-time fluorescence and visual methods could detect as low as 0.1% genuine targets in the mixed samples. In summary, we report an isothermal detection system for five kinds of BF circulating in the market, providing a new choice for the molecular identification of BF drugs and showing promise in the laboratory testing as well as field identification of other herbal medicines.

Background: Acute bronchitis (AB) is a common disease in pediatrics. Prolonged AB may develop into chronic bronchitis. Bronchitis caused by the influenza virus can lead to severe hypoxia or insufficient ventilation, causing great harm to patients and increasing the burden on children and society. Presently, there is no specific treatment for AB except symptomatic supportive treatment. It is urgent to find an effective treatment for AB. Jinzhen Oral Liquid (JZOL) has been found to have a broad spectrum of anti-inflammatory and antiviral effects in previous clinical and basic studies and has a good effect on AB in children. However, the large-sample, randomized, double-blind, head-to-head, evidence-based studies are lacking. The purpose of this protocol is to evaluate the efficacy, safety, and mechanism of JZOL in the treatment of AB in children.Methods: This is a randomized, double-blind, parallel-controlled multi-center clinical trial. The sample size is 500 participants in the intervention group and the control group respectively, with a total of 1000 participants. They will be recruited by 10 hospitals in China. The Intervention group takes JZOL and Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution (AHCHOS) placebo, while the control group receives AHCHOS and JZOL placebo. The dosage of the two drugs varies according to age and weight. The medication lasts for 7 days. The disappearance time of cough is adopted as the primary outcome. Quality control will be carried out at every stage of data management and processing to ensure that all data are reliable and processed correctly. SAS is used for statistical analysis. Intention-to-treat analysis will be carried out in this trial. All statistical tests are conducted using a two-sided test, and p

Single-photon-based head-mounted microscopy is widely used to record the brain activities of freely-moving animals. However, during data acquisition, the free movement of animals will cause shaking in the field of view, which deteriorates subsequent neural signal analyses. Existing motion correction methods applied to calcium imaging data either focus on offline analyses or lack sufficient accuracy in real-time processing for single-photon data. In this study, we proposed an open-source real-time motion correction (RTMC) plug-in for single-photon calcium imaging data acquisition. The RTMC plug-in is a real-time subpixel registration algorithm that can run GPUs in UCLA Miniscope data acquisition software. When used with the UCLA Miniscope, the RTMC algorithm satisfies real-time processing requirements in terms of speed, memory, and accuracy. We tested the RTMC algorithm by extending a manual neuron labeling function to extract calcium signals in a real experimental setting. The results demonstrated that the neural calcium dynamics and calcium events can be restored with high accuracy from the calcium data that were collected by the UCLA Miniscope system embedded with our RTMC plug-in. Our method could become an essential component in brain science research, where real-time brain activity is needed for closed-loop experiments.

Summary: Background: Atrial fibrillation(AF) has become a significant public health concern in China, with population aging and urbanization. Methods: Data screening was performed for 30,244,930 subjects with medical insurance in the Shanghai Municipal Health Commission database between 2015 and 2020. Patients diagnosed with AF were identified and further assessed for treatment information and clinical outcomes, as well as sex differences and impact of COVID-19 pandemic on AF managment. Findings: AF prevalence was 0.88% in Shanghai, which increased with age and reached 6.70% at subjects 80 years and over. AF was more prevalent in women compared with men (0.89% vs. 0.88%, p

Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: −0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.

Diabetic nephropathy (DN), one of the most detrimental microvascular complications of diabetes, is the leading cause of end-stage renal disease. The pathogenesis of DN is complicated, including hemodynamic changes, inflammatory response, oxidative stress, among others. Recently, many studies have demonstrated that mitophagy, especially PINK1/Parkin-mediated mitophagy, plays an important role in the pathogenesis of DN. Erythropoietin (EPO), a glycoprotein hormone mainly secreted by the kidney, regulates the production of erythrocytes. This research intends to explore the beneficial effects of EPO on DN and investigate related mechanisms. In in vitro experiments, we found that EPO promoted autophagic flux and alleviated mitochondrial dysfunction in terms of mitochondrial fragmentation, elevated mitochondrial ROS as well as the loss of mitochondrial potential, and lowered the apoptosis level in high-glucose-treated mesangial cells. Moreover, EPO increased protein expressions of PINK1 and Parkin, enhanced the co-localization of LC3 with mitochondria, Parkin with mitochondria as well as LC3 with Parkin, and increased the number of GFP-LC3 puncta, resulting in increased level of PINK1/Parkin-mediated mitophagy in mesangial cells. The knockdown of PINK1 abrogated the effect of EPO on mitophagy. In addition, in vivo experiments demonstrated that EPO attenuated renal injury, reduced oxidative stress, and promoted expressions of genes related to PINK1/Parkin-mediated mitophagy in the kidneys of DN mice. In summary, these results suggest that PINK1/Parkin-mediated mitophagy is involved in the development of DN and EPO mitigates DN by restoring PINK1/Parkin-mediated mitophagy.