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Abstract Background Frailty and its components are proposed to associate with kidney function, but little attention is paid to the significance of changes in their status on rapid loss of kidney function. This study aimed to investigate the association between changes in frailty and its components status with rapid loss of renal function. Methods This study used data from China Health and Retirement Longitudinal Study (CHARLS). Frailty status was measured using the Fried frailty phenotype (FP) scale, including five components: slowness, weakness, exhaustion, inactivity, and shrinking. Frailty status was further classified into three levels: robust (0 component), prefrail (1–2 components) and frail (3–5 components). Changes in frailty status were assessed by frailty status at baseline and 4- year follow-up. Rapid loss of kidney function was defined as a rate of estimate glomerular filtration rate(eGFR) decline ≥ 4 ml/min per 1.73 m2per year. Logistic regression models were performed to assess the association between changes in frailty status and its components status with rapid eGFR decline. Results A total of 2705 participants were included with 316 (11.68%) participants categorized as rapid eGFR decline during the 4-year follow-up. Compared with baseline prefrail participants who progressed to frail, prefrail participants who maintained prefrail or recovered to robust status had decreased risks of rapid eGFR decline (stable prefrail status, OR = 0.608, 95% CI: 0.396–0.953; recover to robust, OR = 0.476, 95% CI: 0.266–0.846). In contrast, among baseline robust or frail participants, we did not find changes in frailty status significantly affect the risks of rapid loss of kidney function. Moreover, participants who experienced incident weakness showed the significant relationship with an increased risk of rapid eGFR decline (OR = 1.531, 95% CI: 1.051–2.198) compared to stable non-weakness participants. Other changes of frailty components status did not significantly affect the risks of rapid eGFR decline. Conclusions The progression of frailty status increases the risks of rapid eGFR decline among prefrail populations. Preventing weakness, may benefit kidney function.

Abstract Background For youths, abnormalities in ambulatory blood pressure (ABP) patterns are known to be associated with increased cardiovascular disease risk and potential target organ damage. Body composition, including indicators such as lean mass index (LMI), fat mass index (FMI), and visceral fat level (VFL), plays a significant role in blood pressure (BP) regulation. However, little is known about the association between these body composition indicators and ABP. Therefore, the present study examined the association between these body composition indicators and BP among Chinese youths. Methods A total of 477 college students aged 17 to 28 years old (mean ± Standard deviation = 18.96 ± 1.21) from a university in Changsha, Hunan Province, China, were included in this study. Body composition indicators were measured with a bioelectrical impedance body composition analyzer, and 24-hour ambulatory blood pressure monitoring (ABPM) was conducted. Multivariable logistic regression was performed to assess the relationship between body composition indicators and abnormal ABP. Results The prevalence of abnormal BP, including 24-hour BP, daytime BP, nighttime BP, and clinic BP, were 4.8%, 4.2%, 8.6%, and 10.9%, respectively. After adjusting for potential covariates, LMI [abnormal 24-hour BP (OR = 1.85, 95%CI:1.31, 2.62), abnormal daytime BP (OR = 1.76, 95%CI:1.21, 2.58), abnormal nighttime BP (OR = 1.64, 95%CI:1.25, 2.14), abnormal clinic BP (OR = 1.84, 95%CI:1.38, 2.45)], FMI [abnormal 24-hour BP (OR = 1.20, 95%CI:1.02, 1.41), abnormal daytime BP (OR = 1.30, 95%CI:1.07, 1.57), abnormal nighttime BP (OR = 1.24, 95%CI:1.10, 1.39), abnormal clinic BP (OR = 1.42, 95%CI:1.22, 1.65)], and VFL [abnormal 24-hour BP (OR = 1.22, 95%CI:1.06, 1.39), abnormal daytime BP (OR = 1.29, 95%CI:1.10, 1.51), abnormal nighttime BP (OR = 1.24, 95%CI:1.12, 1.39), abnormal clinic BP (OR = 1.38, 95%CI:1.21, 1.57)] are positively linked to abnormal BP. Additionally, there were significant sex differences in the association between body composition and abnormal BP. Conclusions Our findings suggested maintaining an individual’s appropriate muscle mass and fat mass and focusing on the different relations of males’ and females’ body composition is crucial for the achievement of appropriate BP profiles.

Abstract Objective Develop a practical scoring system based on radiomics and imaging features, for predicting the malignant potential of incidental indeterminate small solid pulmonary nodules (IISSPNs) smaller than 20 mm. Methods A total of 360 patients with malignant IISSPNs (n = 213) and benign IISSPNs (n = 147) confirmed after surgery were retrospectively analyzed. The whole cohort was randomly divided into training and validation groups at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used to debase the dimensions of radiomics features. Multivariate logistic analysis was performed to establish models. The receiver operating characteristic (ROC) curve, area under the curve (AUC), 95% confidence interval (CI), sensitivity and specificity of each model were recorded. Scoring system based on odds ratio was developed. Results Three radiomics features were selected for further model establishment. After multivariate logistic analysis, the combined model including Mean, age, emphysema, lobulated and size, reached highest AUC of 0.877 (95%CI: 0.830–0.915), accuracy rate of 83.3%, sensitivity of 85.3% and specificity of 80.2% in the training group, followed by radiomics model (AUC: 0.804) and imaging model (AUC: 0.773). A scoring system with a cutoff value greater than 4 points was developed. If the score was larger than 8 points, the possibility of diagnosing malignant IISSPNs could reach at least 92.7%. Conclusion The combined model demonstrated good diagnostic performance in predicting the malignant potential of IISSPNs. A perfect accuracy rate of 100% can be achieved with a score exceeding 12 points in the user-friendly scoring system.

Abstract Background The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. Methods The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. Results The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value 1.2 or

High frequency words, which are key to a text, must be mastered to achieve minimum levels of reading proficiency. However, knowledge about the frequency of items in a language is very limited. Given this consideration, WordSift (www.wordsift.org), a word cloud tool based on high frequency and key words can assist English as a Foreign Language learners of intermediate level who have difficulty in reading the text due to limited vocabulary knowledge and all of its distinctive features can be applied in varied stages of reading instruction.

When exposed to moderate to high temperatures, nanomaterials typically suffer from severe grain coarsening, which has long been a major concern that prevents their wider applications. Here, we proposed an effective strategy to inhibit grain coarsening by constructing grain boundary (GB) complexions with multiple codoped dopants, which hindered coarsening from both energetic and kinetic perspectives. To demonstrate the feasibility of this strategy, multiple selected dopants were doped into a ZrO2–SiO2 nanocrystalline glass ceramic (NCGC) to form GB complexions. The results showed that NCGC was predominantly composed of ZrO2 nanocrystallites (NCs) distributed in an amorphous SiO2 matrix. Ultrathin layers of GB complexions (~2.5 nm) were formed between adjacent ZrO2 NCs, and they were crystalline superstructures with co-segregated dopants. In addition, a small amount of quartz solid solution was formed, and it adhered to the periphery of ZrO2 NCs and bridged the adjacent NCs, acting as a “bridging phase”. The GB complexions and the “bridging phase” synergistically enhanced the coarsening resistance of ZrO2 NCs up to 1000 °C. These findings are important for understanding GB complexions and are expected to provide new insights into the design of nanomaterials with excellent thermodynamic stability.

Abstract Objective Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Compared with fixed offshore wind turbines, the vibration problem of floating offshore wind turbines is particularly prominent, and further reduction of the vibration of floating offshore wind turbines has become an engineering challenge. In order to solve this problem, a novel vibration suppression device, inerter-based absorber (IBA) is introduced, and the vibration control of semi-submersible offshore wind turbines is studied. A comprehensive optimization method, namely the structure-immittance approach, is utilized to design the IBA in a systematic way. In order to search for the optimum vibration suppression performance, a simplified dynamic model of the semi-submersible offshore wind turbine, and the IBA dynamic equations are established using D’Alembert’s principle. Simultaneous suppression of the vibration response of the floating platform and tower of a semi-submersible offshore wind turbine is realized using the dual IBA control strategy. Furthermore, by implementing the optimum IBA in the OpenFAST software, the vibration suppression benefits of the dual IBA compared with the dual tuned mass damper (TMD) are verified under the coupling effects of wind and waves. The results show that the vibration control performance of the dual IBA control strategy is significantly better than that of the single one, and that of the dual IBA is better than that of the dual TMD. In addition, under the condition of achieving the same suppression performance as the TMD, IBA installed at the nacelle and the platform can respectively decrease the required absorber mass by 23.9% and 32.2%, which can greatly reduce the manufacture cost of the device.

Abstract Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

AIM: To develop a classifier for traditional Chinese medicine (TCM) syndrome differentiation of diabetic retinopathy (DR), using optimized machine learning algorithms, which can provide the basis for TCM objective and intelligent syndrome differentiation. METHODS: Collated data on real-world DR cases were collected. A variety of machine learning methods were used to construct TCM syndrome classification model, and the best performance was selected as the basic model. Genetic Algorithm (GA) was used for feature selection to obtain the optimal feature combination. Harris Hawk Optimization (HHO) was used for parameter optimization, and a classification model based on feature selection and parameter optimization was constructed. The performance of the model was compared with other optimization algorithms. The models were evaluated with accuracy, precision, recall, and F1 score as indicators. RESULTS: Data on 970 cases that met screening requirements were collected. Support Vector Machine (SVM) was the best basic classification model. The accuracy rate of the model was 82.05%, the precision rate was 82.34%, the recall rate was 81.81%, and the F1 value was 81.76%. After GA screening, the optimal feature combination contained 37 feature values, which was consistent with TCM clinical practice. The model based on optimal combination and SVM (GA_SVM) had an accuracy improvement of 1.92% compared to the basic classifier. SVM model based on HHO and GA optimization (HHO_GA_SVM) had the best performance and convergence speed compared with other optimization algorithms. Compared with the basic classification model, the accuracy was improved by 3.51%. CONCLUSION: HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR. It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.

Abstract Background Balance plays a crucial role in the daily activities of older adults. Aquatic-based exercises (AE) are widely conducted as an alternative to land-based exercises (LE). Previous studies have compared AE and LE as effective ways to improve balance and have yielded inconsistent results. Therefore, this review aimed to compare the effects of AE and LE on balance function in older adults. Methods Electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched. Randomized controlled trials published from January 2003 to June 2023 were included following predetermined criteria. Data extraction was carried out by two independent reviewers. Data synthesis was conducted using RevMan 5.3 software. The fixed-effect model or random-effect model was chosen based on the results of the heterogeneity test. Meta-analysis for the effect sizes of balance outcomes was calculated as standardized mean difference (SMD) with 95% confidence intervals (CI). The quality of the included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. This review was registered at PROSPERO CRD42023429557. Results A total of 29 studies involving 1486 older adults (with an average age of 66.2 years) were included. Meta-analysis results indicated that AE could improve balance ability based on two tests: the Berg balance scale (BBS: SMD = 1.13, 95% CI 0.25 to 2.00, p = 0.01, I2 = 94%) and the 30-s chair stand test (30 CST: SMD = 2.02, 95% CI 0.50 to 3.54, p = 0.009, I2 = 96%). However, there were no significant differences between the AE group and the LE group in terms of the 6-min walking test (6 MWT: SMD = 0.13, 95% CI -0.16 to 0.43, p = 0.38, I2 = 62%) and time up to go test (TUGT: SMD = 0.44, 95% CI -0.44 to 0.91, p = 0.07, I2 = 85%). Older adults with different health conditions have different gains in different balance measurements after AE intervention and LE intervention. Conclusions Although this was influenced by participant health status, transfer effects, sample size, and other factors, AE offers better benefits than LE for improving balance function in older adults.

Abstract In this study, a newly developed composite of biochar-poly(m-phenylenediamine) (BC-PmPD) exhibiting a distinct skeletal structure was synthesized for the purpose of extracting Cr(VI) from aqueous solutions. BC was employed as a supportive carrier onto which PmPD nanoparticles were uniformly affixed through in-situ polymerization and oxidation synthesis, both within and outside the layered configuration of BC. The structural stability and morphologies of BC-PmPD were assessed utilizing Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, thermogravimetric analysis, analysis of specific surface area and pore size, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction. In comparison to other modified BCs reported, BC-PmPD exhibited the highest Cr(VI) removal rate. Specifically, at 303 K, BC-PmPD achieved a maximum Cr(VI) removal capacity of 775 mg g−1, surpassing the capabilities of unmodified BC and PmPD by 10.4 and 2.13 times, respectively. Analyses involving XPS, FTIR, and density functional theory calculation confirmed that proton transfer happened between protonated amine (−NH2) functional group within the structure of BC-PmPD and HCrO4 − before the formation of hydrogen bond. Subsequently, environmentally persistent free radicals facilitated the reduction of the adsorbed Cr(VI). Quantification of the functional groups indicated that the amino group was responsible for 93.0% of the Cr(VI) adsorption in BC-PmPD. BC-PmPD displayed potent adsorption and reduction capabilities, alongside notable stability, repeatability, and promising potential for application in the remediation for high concentrations of Cr(VI) in electroplating wastewater scenarios. Graphical Abstract

Abstract Radiomics uses automated algorithms to extract high‐order features from images, which can contribute to clinical decisions such as therapeutic efficacy evaluation. We assessed the value of a dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI)‐based radiomics model for predicting pathological complete response (pCR) after a second cycle of neoadjuvant chemotherapy (NAC) in patients with mass breast cancer. We retrospectively analyzed data from 149 patients with mass breast cancer who underwent NAC between January 2017 and December 2022. Using DCE‐MRI, before NAC and after a second cycle of NAC, the least absolute shrinkage and selection operator and logistic regression (LR) algorithms were applied for feature selection and radiomics modeling. We found significant differences in two clinical imaging features (molecular subtypes, background parenchymal enhancement changes) and two radiomics features. Clinical and radiomics features were employed to build clinical, radiomics, and combined models to predict pCR. The LR model that combined clinical and radiomics features had an area under the curve of 0.811, higher than that for the imaging or radiomics model. Our findings suggest that a combined model based on imaging and radiomics features can improve early prediction of NAC efficacy for patients with mass breast cancer.

IntroductionWhile lymph node metastasis (LNM) plays a critical role in determining treatment options for endometrial cancer (EC) patients, the existing preoperative methods for evaluating the lymph node state are not always satisfactory. This study aimed to develop and validate a nomogram based on intra- and peritumoral radiomics features and multiparameter magnetic resonance imaging (MRI) features to preoperatively predict LNM in EC patients.MethodsThree hundred and seventy-four women with histologically confirmed EC were divided into training (n = 220), test (n = 94), and independent validation (n = 60) cohorts. Radiomic features were extracted from intra- and peritumoral regions via axial T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) mapping. A radiomics model (annotated as the Radscore) was established using the selected features from different regions. The clinical parameters were statistically analyzed. A nomogram was developed by combining the Radscore and the most predictive clinical parameters. Decision curve analysis (DCA) and the net reclassification index (NRI) were used to assess the clinical benefit of using the nomogram.ResultsNine radiomics features were ultimately selected from the intra- and peritumoral regions via ADC mapping and T2WI. The nomogram combining the Radscore, serum CA125 level, and tumor area ratio achieved the highest AUCs in the training, test and independent validation sets (nomogram vs. Radscore vs. clinical model: 0.878 vs. 0.850 vs. 0.674 (training), 0.877 vs. 0.838 vs. 0.668 (test), and 0.864 vs. 0.836 vs. 0.618 (independent validation)). The DCA and NRI results revealed the nomogram had greater diagnostic performance and net clinical benefits than the Radscore alone.ConclusionThe combined intra- and peritumoral region multiparameter MRI radiomics nomogram showed good diagnostic performance and could be used to preoperatively predict LNM in patients with EC.

Abstract Realizing room-temperature magnetic skyrmions in two-dimensional van der Waals ferromagnets offers unparalleled prospects for future spintronic applications. However, due to the intrinsic spin fluctuations that suppress atomic long-range magnetic order and the inherent inversion crystal symmetry that excludes the presence of the Dzyaloshinskii-Moriya interaction, achieving room-temperature skyrmions in 2D magnets remains a formidable challenge. In this study, we target room-temperature 2D magnet Fe3GaTe2 and unveil that the introduction of iron-deficient into this compound enables spatial inversion symmetry breaking, thus inducing a significant Dzyaloshinskii-Moriya interaction that brings about room-temperature Néel-type skyrmions with unprecedentedly small size. To further enhance the practical applications of this finding, we employ a homemade in-situ optical Lorentz transmission electron microscopy to demonstrate ultrafast writing of skyrmions in Fe3-x GaTe2 using a single femtosecond laser pulse. Our results manifest the Fe3-x GaTe2 as a promising building block for realizing skyrmion-based magneto-optical functionalities.

Abstract Background The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. Methods A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions. Results There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. Conclusions The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

ABSTRACTWater pollutions can severely affect water environment, causing water quality degradation and threatening aquatic wildlife. Deemed as guideline for maximum environmental impact assessment, water pollution peak concentration (WPPC) has been intensively studied to organize effective countermeasures. In this study, a back propagation artificial neural network (BPANN) coupled with genetic algorithm (GA) was constructed to predict peak concentrations. Compared with BPANN, multiple linear regressions model (MLRM) and step-wise multiple linear regressions model (SMLRM), GA-BPANN model showed superior accuracy in both simulating and predicting peak concentrations (R2 = 0.93 and 0.67 0.69 respectively). In 12 peak concentration cases, GA-BPANN model’s mean absolute relative error (MARE) ranges from 0.0 to 0.58, averaged at 0.09, significantly lower than BPANN, MLRM and SMLRM (MARE = 0.29, 0.45 and 0.48). Further analysis revealed that GA-BPANN model can be used as an effective and efficient tool for water quality simulation and early warning prediction.

BackgroundIn China, bacillary dysentery (BD) is the third most frequently reported infectious disease, with the greatest annual incidence rate of 38.03 cases per 10,000 person-years. It is well acknowledged that temperature is associated with BD and the previous studies of temperature-BD association in different provinces of China present a considerable heterogeneity, which may lead to an inaccurate estimation for a region-specific association and incorrect attributable burdens. Meanwhile, the common methods for multi-city studies, such as stratified strategy and meta-analysis, have their own limitations in handling the heterogeneity. Therefore, it is necessary to adopt an appropriate method considering the spatial autocorrelation to accurately characterize the spatial distribution of temperature-BD association and obtain its attributable burden in 31 provinces of China.MethodsA novel three-stage strategy was adopted. In the first stage, we used the generalized additive model (GAM) model to independently estimate the province-specific association between monthly average temperature (MAT) and BD. In the second stage, the Leroux-prior-based conditional autoregression (LCAR) was used to spatially smooth the association and characterize its spatial distribution. In the third stage, we calculate the attribute BD cases based on a more accurate estimation of association.ResultsThe smoothed association curves generally show a higher relative risk with a higher MAT, but some of them have an inverted “V” shape. Meanwhile, the spatial distribution of association indicates that western provinces have a higher relative risk of MAT than eastern provinces with 0.695 and 0.645 on average, respectively. The maximum and minimum total attributable number of cases are 224,257 in Beijing and 88,906 in Hainan, respectively. The average values of each province in the eastern, western, and central areas are approximately 40,991, 42,025, and 26,947, respectively.ConclusionBased on the LCAR-based three-stage strategy, we can obtain a more accurate spatial distribution of temperature-BD association and attributable BD cases. Furthermore, the results can help relevant institutions to prevent and control the epidemic of BD efficiently.

The natural product Desmosdumotin D (hereafter referred to as Des-D), isolated from the plant Desmos dumosus, showed potent anti-HIV activity. However, the subsequent pharmacological activity and clinical studies are limited due to the low content of Des-D in the plant. Therefore, the total synthesis path of Des-D was optimized in this paper, and the total yield was increased from 4.4% to 11.9%. Additionally, twelve analogues were obtained following the synthesis route of Des-D. The anti-HIV activity evaluation results in vitro showed that Des-D had the highest activity, with an IC50 value of 13.6 μM, and compounds 17 and 11 had the lowest anti-HIV activity, with IC50 values of 101.3 μM and 161.0 μM, respectively. Through the molecular docking of compounds Des-D and 17 with HIV-IN, the results show that phenolic hydroxyl groups and two benzene rings interact with HIV-IN and are possible pharmacodynamic groups.

Abstract Rich in renewable resources, extensive acreage, and bioenergy expertise, Brazil, however, has no established strategies for sustainable aviation fuels, particularly e-kerosene. We extend the lens from the often-studied economic feasibility of individual e-kerosene supply chains to a system-wide perspective. Employing energy system analyses, we examine the integration of e-kerosene production into Brazil’s national energy supplies. We introduce PyPSA-Brazil, an open-source energy system optimisation model grounded in public data. This model integrates e-kerosene production and offers granular spatial resolution, enabling federal-level informed decisions on infrastructure locations and enhancing transparency in Brazilian energy supply scenarios. Our findings indicate that incorporating e-kerosene production can bolster system efficiency as Brazil targets a carbon-neutral electricity supply by 2050. The share of e-kerosene in meeting kerosene demand fluctuates between 2.7 and 51.1%, with production costs varying from 113.3 to 227.3 €/MWh. These costs are influenced by factors such as biokerosene costs, carbon pricing, and export aspirations. Our findings are relevant for Brazilian policymakers championing aviation sustainability and offer a framework for other countries envisioning carbon-neutral e-kerosene production and export.

Assessing the functional traits and ecological stoichiometric characteristics of dominant species across different life forms within plant communities in karst environments and investigating the inherent connection between them can provide insights into how species adjust their functional attributes in response to habitat heterogeneity. This approach offers a more comprehensive understanding of ecosystem processes and functions in contrast to examination of the taxonomic diversity of species. This study examines the relationship between the functional characteristics of dominant species in plant communities of various life forms in karst environments, focusing on deciduous leaf–soil ecological stoichiometry. The investigation relies on community science surveys, as well as the determination and calculation of plant functional traits and ecological stoichiometries, in plant communities of various life forms in Guizhou (a province of China). The findings of our study revealed considerable variability in the functional trait characteristics of dominant species across different plant-community life forms. Specifically, strong positive correlations were observed among plant height (PLH), leaf area (LA), leaf dry matter content (LDMC), and specific leaf area (SLA) in the dominant species. Additionally, our results indicated no significant differences in leaf ecological stoichiometry among different life forms. However, we did observe significant differences and strong positive correlations between soil N:P, withered material C:N, and apomictic C:P. Furthermore, our study found that plant height (PLH), leaf area (LA), and specific leaf area (SLA) were particularly sensitive to the ecological stoichiometry of soil and apomixis. The results of our study suggest that the functional traits of diverse plant-community life forms in karst regions are capable of adapting to environmental changes through various expressions and survival strategies. The development of various plant-community life forms in karst areas is particularly vulnerable to phosphorus limitation, and the potential for litter decomposition and soil nutrient mineralization is comparatively weaker. The functional traits of various plant-community life forms in karst regions exhibit greater sensitivity to both the soil’s C:N ratio and the C:N ratio of apomictic material. Habitat variations may influence the ecological stoichiometric characteristics of the plant leaf–apomictic soil continuum.

Ferroptosis, a distinct form of cell death, is characterized by the iron-mediated oxidation of lipids and is finely controlled by multiple cellular metabolic pathways. These pathways encompass redox balance, iron regulation, mitochondrial function, as well as amino acid, lipid, and sugar metabolism. Additionally, various disease-related signaling pathways also play a role in the regulation of ferroptosis. In recent years, with the introduction of the concept of ferroptosis and the deepening of research on its mechanism, ferroptosis is closely related to various biological conditions of eye diseases, including eye organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanism of ferroptosis, and its latest research progress in ophthalmic diseases and reviews the research on ferroptosis in ocular diseases within the framework of metabolism, active oxygen biology, and iron biology. Key regulators and mechanisms of ferroptosis in ocular diseases introduce important concepts and major open questions in the field of ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs will be made in the regulation mechanism of ferroptosis and the use of ferroptosis to promote the treatment of eye diseases. At the same time, natural compounds may be the direction of new drug development for the potential treatment of ferroptosis in the future. Open up a new way for clinical ophthalmologists to research and prevent diseases.

Folate receptor autoantibody (FRAA) has caught increasing attention since its discovery in biological fluids of patients with autism spectrum disorder (ASD), but quantification and understanding of its function are still in their infancy. In this study, we aimed to quantify serum binding-FRAA and explore its relation with serum folate, vitamin B12 (VB12) and ferritin. We quantitated serum binding-FRAA in 132 ASD children and 132 typically-developing (TD) children, as well as serum levels of folate, VB12 and ferritin. The results showed that serum binding-FRAA in the ASD group was significantly lower than that in the TD group (p 0.05). However, there was significant difference in boys between these two groups, not girls. Additionally, the combination of nitrite and binding-FRAA showed potential diagnostic value in patients with ASD (AUC > 0.7). Moreover, in the ASD group, the level of folate was consistent with that of binding-FRAA, whereas in the TD group, the binding-FRAA level was high when the folate level was low. Altogether, these differences revealed that the low serum FRAA in autistic children was mediated by multiple factors, which deserves more comprehensive investigation with larger population and mechanistic studies.

Abstract Background Insulin resistance (IR) had been reported to be associated with age; however, few studies have explored the association between IR and biological age (BA). The HOMA-IR value is a useful indicator of the extent of IR. This cross-sectional study is to explore the relationship between HOMA-IR and BA/advanced aging in the US population. Methods This study is a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) data. The survey comprised 12,266 people from the NHANES, and their full HOMA-IR data as well as BA data were extracted. Four multiple linear regressions were performed to analyze the association between HOMA-IR and BA, and four multiple logistic regression models were performed to analyze the association between HOMA-IR and advanced aging. In addition, trend tests and stratified analysis were performed and smoothed fitted curves were plotted to test the robustness of the results. Results HOMA-IR was positively correlated with BA [β: 0.51 (0.39, 0.63)], and it was the same to advanced aging [OR: 1.05 (1.02, 1.07)], and both showed a monotonically increasing trend. The trend tests showed that the results were stable (all P for trend

Objective: To explore whether Lycium barbarum polysaccharide (LBP) can reduce the apoptosis of retinal photoreceptor cells in retinitis pigmentosa (RP) mice by inhibiting nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling pathway. Methods: (i) In vitro experiments, mouse retinal ganglion cells (661W cells) were divided into normal, model, LBP low-dose (LBP-L, 40 mg/L), LBP middle-dose (LBP-M, 80 mg/L), LBP high-dose (LBP-H, 160 mg/L), and positive drug control (NLRP3 inhibitor, 160 mg/L) groups. And the 661W cells were exposed to varying concentrations of H2O2 ranging from 50 to 400 μmol/L to determine the optimal concentration for inducing apoptosis (200 μmol/L). Then the cell viability was assessed using Cell Counting Kit-8 (CCK-8), while the apoptosis rate was detected by flow cytometry; the expression of NLRP3 was detected by immunofluorescence; and the expression of apoptosis markers was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). (ii) In vivo assays were carried out with the use of C57/BL6 and Rd10 mice. The animal experimental groups were divided into normal, model, LBP-L, LBP-M, LBP-H, and NLRP3 inhibitor groups, in which the normal group was C57/BL6 mice and the other groups were Rd10 mice. Ten mice were included in each group, and the corresponding drugs were administered intragastrically for a duration of four weeks. NF-κB/NLRP3 pathway and the expression of apoptosis markers were observed by electroretinogram, histopathological examination, and WB to assess the effects of LBP on retinal photoreceptor cell apoptosis. Results: (i) In vitro experiments, compared with the normal group, the apoptosis rate of 661W cells in model group was significantly increased (P < 0.01), and the expression levels of key proteins of NF-κB/NLRP pathway, such as NLRP3, NF-κB, p-NF-κB, and pro-apoptotic protein caspase-3, were up-regulated (P < 0.01). The rate of Bax/Bcl-2 was increased (P < 0.01), and the concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly increased (P < 0.01). Compared with the model group, high dose of LBP decreased the apoptosis rate of 661W cells (P < 0.01), and down-regulated the expression levels of the key proteins of NF-κB/NLRP3 pathway, including NF-κB, NLRP3, p-NF-κB, and caspase-3 (P < 0.01). The rate of Bax/Bcl-2 was decreased (P < 0.01), and the concentrations of IL-1β and TNF-α were decreased (P < 0.01). (ii) In vivo experiments, high dose of LBP significantly increased morphological changes in the outer nuclear layer (ONL) thickness of Rd10 mice, as well as functional changes in the amplitudes of the a-wave and b-wave (P < 0.01), which also down-regulated the expression levels of NF-κB (P < 0.05), NLRP3, p-NF-κB, and caspase-3 (P < 0.01), reduced the Bax/Bcl-2 rate (P < 0.01), and decreased the concentrations of IL-1β (P < 0.01) and TNF-α (P < 0.05). Conclusion: LBP could improve both retinal morphology and function, providing protection to photoreceptors from apoptosis through the inhibition of the NF-κB/NLRP3 pathway.

Abstract The use of marine microalgae in industrial systems is attractive for converting CO2 into value-added products using saline water and sunlight. The plant nature and demonstrated industrial potential facilitate Chlorella spp. as excellent model organisms for both basic research and commercial application. However, the transformation method has not been developed in marine Chlorella spp., thus genetic engineering is hindered in exploiting the industrial potentialities of these strains. In this study, we provided a transformation protocol for the marine Chlorella strain MEM25, which showed robust characteristics, including high production of proteins and polyunsaturated fatty acids in multiple cultivation systems over various spatial–temporal scales. We showed that transformants could be obtained in a dramatically time-saving manner (comparable to Saccharomyces cerevisiae) with four functional proteins expressed properly. The transgenes are integrated into the genome and can be successfully inherited for more than two years. The development of a marine Chlorella transformation method, in combination with the complete genome, will greatly facilitate more comprehensive mechanism studies and provide possibilities to use this species as chassis for synthetic biology to produce value-added compounds with mutual advantage in neutralization of CO2 in commercial scales.

A positioning grid is a key clamping structure for fixing the transverse and axial positions of fuel assemblies in nuclear reactors, and it is generally prepared by the transverse stamping of a Zr-4 sheet. However, the texture formed in the processing process of Zr-4 sheets can affect formability, resulting in cracking in the stamping process. Therefore, the relationship between the formability of Zr-4 sheets and the normal Kearns factor (Fn) of basal texture was studied in this paper. The results showed that the Zr-4 sheet with an Fn equaling 0.720, prepared by an isobaric reduction rolling process, would crack in the stamping process. To avoid the cracking during stamping, the formability improvement of Zr-4 sheets based on texture optimization was discussed. By using the finite element model (FEM) and a visco plastic self-consistent (VPSC) model coupled simulation, the relationship between the initial textures and formabilities of Zr-4 sheet is established. It is found that the hardening exponents (n) decreased with increasing Fns in VPSC simulations. Meanwhile, as the Fn increases, cracks are prone to occur at the bottom corner of the stamped sheet in finite element simulation. Given the results from FEM and VPSC simulations, it is proposed that the Fn should be controlled to be less than 0.7 for preventing cracks in the sheet during stamping. Additionally, a new rolling process named non-isobaric reduction rolling was designed in which the Fn of the Zr-4 sheet is successfully reduced to 0.690. The stamping results indicate that the sheet is free of cracks under an Fn of 0.690. Therefore, texture optimization with the proposed rolling process can improve the formability of Zr-4 sheets, which effectively solves the cracking problem of Zr-4 sheets.

Lonicerae japonicae Flos (LJF) is a natural plant containing abundant antioxidant ingredients. In order to extract more antioxidants from LJF, in this study, a novel strategy was proposed for optimizing the extraction factor level by response surface methodology with a tailored deep eutectic solvent (DES) as the extraction solvent and antioxidant ability as the evaluation index. After optimizing the composition of DES and the extraction condition, the extracts obtained by our proposed method yielded better antioxidant ability (229.1–249.1 μmol TE/g DW) and higher antioxidant contents (34.2–36.5 mg GAE/g DW for total phenolics and 119.6–123.0 mg RE/g DW for total flavonoids) from LJF in 5 min without organic solvent consumption that were significantly superior to the Chinese Pharmacopoeia extraction method. The K-T solvation parameter and a scanning electron microscope were adopted to explore the extraction mechanism, and the results showed that the polarity and damage effect on plant cells of DES were crucial for the extraction of antioxidants. In addition, after combining the HPLC fingerprint and partial least squares model, chlorogenic acid, rutin, and 3,5-O-Dicaffeoylquinic acid were screened as the antioxidant Q-markers of LJF. This work demonstrates that an optimization strategy based on antioxidant ability and tailored DES has the potential to extract more antioxidants from natural plants.

In the future, high-speed vehicles will develop towards the integration of aviation and aerospace technologies, such as longer range and faster speed, and constantly break through the boundary of flight speed and cruising space. With the continuous increase of flight speed, the thermal load is becoming more and more severe. Meanwhile, the requirements of multi-function integrated design of thermal protection structures and strong constraints on structural quality have put forward new requirements and challenges for thermal protection. In response to these, new features and needs of thermal protection are emerged, and the demand for thermal protection has undergone significant changes. There are obvious gaps in existing technologies, design methods, and recognition of relevant scientific issues, so revolutionary technologies are urgently needed. Therefore, the concept of new thermal barrier was proposed in this paper. It analysed the research status of long time heating, non-ablative heat protection and refined thermal environment prediction, pointed out the specific connotation and important development direction of new thermal barrier, reviewed the new direction and new methods being explored in thermal protection technology, including low ablative/non-ablative technology, system genome material design method, channel-based innovative thermal protection technology, etc. It is believed that solving the new thermal barrier is a scientific and technological problem to break through the limit of existing thermal protection technology, and it is necessary to break through the bottleneck problem of thermal protection of high-speed aircraft with multi-approach combination, multi-method synthesis and multidiscipline crossing. It explores innovative solutions to the problem of new thermal barrier from the aspects of refined thermal environment prediction and control, multi-scale performance prediction of thermal protection materials, new design approach of thermal protection materials, innovative thermal structure, etc. The progress of related research was summarized.

Abstract Objectives This study aimed to investigate the incidence, consequences, and predictors of serious chemotherapy‐induced thrombocytopenia (CIT) in nasopharyngeal carcinoma (NPC). Materials and Methods We retrospectively reviewed the clinical records of patients with NPC between 2013 and 2015. Multivariate Cox proportional hazards regression model and propensity score matching were used to estimate the effect of serious CIT on overall survival. Univariate and multivariate logistic regression analyses were applied to identify the predictors of serious CIT. Results and Conclusion The incidence of serious CIT was 5.21% in patients with NPC. Patients who experienced serious thrombocytopenia had a worse long‐term prognosis, while the difference in short‐term survival rate was slight. Chemotherapy regimens of gemcitabine and platinum, 5‐fluorouracil and platinum, taxane and platinum, serum potassium ion concentration, serum lactate dehydrogenase levels, platelet count, red blood cell count, and estimated glomerular filtration rate were predictors of serious CIT.

Abstract Background Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. Methods The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P

Abstract Background To develop and validate a predictive nomogram for tumor residue 3–6 months after treatment based on postradiotherapy plasma Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II–IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods In this retrospective study, 1050 eligible patients with stage II–IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3–6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314). Results Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.

Summary: Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95–428.68 h]) than that of Placebo (271.33 h [IQR 219.00–529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07–1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

Chinese herbs and their purified components in aquafeeds have been proved effective to combat stress in aquatic animals to combat toxic environmental stress. Lycium barbarum poly-saccharides (LBP) is an active antioxidant, anti-inflammatory and antitoxic purified herbal agent. The objective of this paper was to evaluate the effect of 0.1–2.0% LBP on the hepatopancreas of Chinese mitten crab (Eriocheir sinensis) challenged with 2 mg/kg T-2 toxin orally for 5 weeks. The results showed that feeding LBP significantly restored the hepatopancreas index (HI), gonadsomatic index (GSI) reduced by T-2 toxin. Moreover, H&E sections indicated that LBP dose-dependently restored the disrupted microstructure of the hepatopancreas. In antioxidative capacity, significant increases in malondialdehyde (MDA) reduction and elevated glutathione (GSH) content, gluta-thione reductase (GPx) activity were seen in the 0.5% LBP group. In addition, reactive oxygen species (ROS) and apoptosis rate of hepatopancreas showed the anti-apoptotic effect of LBP doses, plus qPCR assay of 10 apoptosis-related genes to support them. The mRNA abundance of three pro-inflammatory genes was significantly reduced by LBP, corroborating its anti-inflammatory efficacy. In brief, feed supplementation with LBP alleviated the oxidative stress-apoptosis-inflammation induced by co-feeding T-2 toxin in E. sinensis, maintained the structural and functional integrity of the hepatopancreas, prevented degenerative atrophy.

Summary: It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p

Objective: To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases.Methods: Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software.Results: A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren’s syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], p = 0.003), ACR50 (RR 1.80 [1.43, 2.26], p < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], p = 0.001), DAS28 (WMD −1.11 [−1.69, −0.52], p = 0.0002), reduce ESR (WMD −11.05 [−14.58, −7.51], p < 0.00001), CRP (SMD −1.52 [−2.02, −1.02], p < 0.00001), RF (SMD −1.65 [−2.48, −0.82], p < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], p < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD −1.62 [−2.20, −1.05], p < 0.00001), BASFI score (WMD −1.07 [−1.39, −0.75], p < 0.00001), VAS (WMD −2.01 [−2.83, −1.19], p < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD −1.71 [−2.44, −0.98], p < 0.00001; IGU only group: WMD −2.10 [−2.40, −1.81], p < 0.00001) and ESSDAI score (IGU + other therapy group: WMD −1.62 [−2.30, −0.94], p < 0.00001; IGU only group: WMD −1.51 [−1.65, −1.37], p < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer’s test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], p < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], p = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], p = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function.Conclusion: Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia.Systematic Review Registration: (CRD42021289489).

Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease characterized by itching. The gut microbiome can help maintain skin immune homeostasis by regulating innate and adaptive immunity. Here, we report a case of AD in a 15-year-old adolescent boy who benefited from washed microbiota transplantation (WMT). WMT was performed for three courses, with each course lasting for three consecutive days and an interval of one month between two courses. Clinical assessments were conducted at each WMT course, and skin, blood, and stool samples were collected for microbial analysis. After three months of WMT treatment, the boy’s itchiness was effectively controlled: his skin showed noticeable improvement, with reduced Staphylococcus aureus in the skin lesions. The scores of SCORAD (SCORing Atopic Dermatitis), EASI (Eczema Area and Severity Index), NRS (Numerical Rating Scale), and DLQI (Dermatology Life Quality Index) significantly decreased compared to the baseline. Serum levels of eosinophil ratio, tumor necrotic factor-α, and interleukin-6 also reduced to the normal levels. There was a significant decrease in S. aureus in the skin lesions. Additionally, the intestinal flora became more diverse, and the abundance of Bifidobacterium species, significantly increased after WMT. No adverse events were reported during the treatment and the 1-year follow-up period. This case report provides direct clinical evidence for WMT as a novel promising treatment strategy for AD, and preliminary experimental data suggests the existence of an intestinal-skin axis in terms of the gut microbiota and the skin immune homeostasis.

Aim of the study: To assess the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and to explore the mechanisms by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP. Methods: Hydrogen peroxide(H2O2) was used to induce oxidative stress in 661 W cells, which were then examined using flow cytometry and enzyme linked immunosorbent assay (ELISA). Changes in mitochondria were observed by using an electron microscope to characterize the ferroptosis of the cells. The protective effect of FSE on the retina function and structure of rd10 mice was evaluated using histopathological examination, fundus photographs, and electroretinography (ERG). Protein expression levels of Tumor Protein p53 (P53), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione peroxidase 4 (GPX4), Arachidonate-12-Lipoxygenase (ALOX12), and Dipeptidyl peptidase 4 (DPP4) were evaluated by Western blot assays in Vivo and in Vitro. Results: H2O2-induced 661 W cells increased oxidative stress products and P53 and ALOX12, decreasing the expression of SLC7A11, GPX4, and DPP4. GPX4 activator does not reduce reactive oxygen species (ROS) generation and has little effect on ferroptosis. Fer-1 and FSE attenuate ROS generation and inhibit ferroptosis of photoreceptors in RP via inhibited P53 expression and increased SLC7A11 and GPX4 expression. Conclusion: FSE may be available in clinical therapeutics to alleviating RP and the mechanism by which inhibits ferroptosis of photoreceptors following oxidative stress via the P53/ SLC7A11 pathway.

Abstract Background Endometriosis is a crippling, ongoing, chronic inflammatory condition. The management of these patients has been impacted by the current COVID-19 pandemic, which is still controversial. This study compared the clinical therapy outcomes and psychological scores between before and during- the epidemic. Method The data of patients who were diagnosed with endometriosis in the Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital from January 2018 to December 2022 were collected. The patients were divided into pre- and intra-COVID groups. The treatment results and psychological status of the two groups were compared. Results A total of 1022 patients with endometriosis were enrolled, with a mean age of 33.16 ± 9.81 years and a BMI of 23.90 ± 3.04 kg/m2, of which 434 cases (434/1022, 42.5%) were in the pre-COVID group and 588 cases (588/1022, 57.5%) in the intra-COVID group. Both groups were well balanced for age, BMI, history of abdominopelvic surgery, family relationships, education level, and duration between initial diagnosis and admission. Compared to the Pre-COVID group, the intra-COVID group had a higher proportion of patients with chronic pelvic pain (297/434, 68.4% vs. 447/588, 76.0%, p = 0.007) and dysmenorrhea (249/434, 62.8% vs. 402/588, 70.0%, p

From the perspective of institutional change of IPO regulation, this paper discusses the relationship between IPO pricing regulation and audit fees in China. This paper finds that the audit fees of IPO companies are higher in the stage of pricing regulation in comparison to the stage of pricing marketization. We also find auditors charge higher audit fees for the private companies than state-owned companies during the IPO pricing regulation period. Furthermore in regions with tighten legislation, IPO audit fees are higher in the IPO pricing regulation period.

Abstract Improvements in modelling energy systems of populous emerging economies are highly decisive for a successful global energy transition. The models used–increasingly open source–still need more appropriate open data. As an illustrative example, we take the Brazilian energy system, which has great potential for renewable energy resources but still relies heavily on fossil fuels. We provide a comprehensive open dataset for scenario analyses, which can be directly used with the popular open energy system model PyPSA and other modelling frameworks. It includes three categories: (1) time series data of variable renewable potentials, electricity load profiles, inflows for the hydropower plants, and cross-border electricity exchanges; (2) geospatial data on the administrative division of the Brazilian federal states; (3) tabular data, which contains power plant data with installed and planned generation capacities, aggregated grid network topology, biomass thermal plant potential, as well as scenarios of energy demand. Our dataset could enable further global or country-specific energy system studies based on open data relevant to decarbonizing Brazil’s energy system.

Considering the increased risk of urban flooding and drought due to global climate change and rapid urbanization, the imperative for more accurate methods for streamflow forecasting has intensified. This study introduces a pioneering approach leveraging the available network of real-time monitoring stations and advanced machine learning algorithms that can accurately simulate spatial–temporal problems. The Spatio-Temporal Attention Gated Recurrent Unit (STA-GRU) model is renowned for its computational efficacy in forecasting streamflow events with a forecast horizon of 7 days. The novel integration of the groundwater level, precipitation, and river discharge as predictive variables offers a holistic view of the hydrological cycle, enhancing the model’s accuracy. Our findings reveal that for a 7-day forecasting period, the STA-GRU model demonstrates superior performance, with a notable improvement in mean absolute percentage error (MAPE) values and R-square (R2) alongside reductions in the root mean squared error (RMSE) and mean absolute error (MAE) metrics, underscoring the model’s generalizability and reliability. Comparative analysis with seven conventional deep learning models, including the Long Short-Term Memory (LSTM), the Convolutional Neural Network LSTM (CNNLSTM), the Convolutional LSTM (ConvLSTM), the Spatio-Temporal Attention LSTM (STA-LSTM), the Gated Recurrent Unit (GRU), the Convolutional Neural Network GRU (CNNGRU), and the STA-GRU, confirms the superior predictive power of the STA-LSTM and STA-GRU models when faced with long-term prediction. This research marks a significant shift towards an integrated network of real-time monitoring stations with advanced deep-learning algorithms for streamflow forecasting, emphasizing the importance of spatially and temporally encompassing streamflow variability within an urban watershed’s stream network.