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Abstract Purpose Steatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF). Materials and methods The UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman. Results One hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF. Conclusion UDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach. Critical relevance statement UDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting). Trial registration The research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 ( http://www.chictr.org.cn/ ). The registration number is ChiCTR 2300076457. Key Points There is a lack of non-invasive quantitative measurement options for hepatic steatosis. UDFF demonstrated excellent reproducibility in measuring hepatic steatosis. S8, end-expiratory, supine, and fasting may be the more stable measuring condition. Training could improve the operators’ measurement stability. Variable measurement state affects the repeatability of the UDFF values (Cov). Graphical Abstract

Abstract Background At present, unequal allocation of medical resources represents a major problem for medical service management in China and many other countries. Equity of intensive care unit (ICU) bed allocation is essential for timely and equitable access to medical care for critically ill patients. This study analysed the equity of ICU bed allocation in 31 provincial regions in China, and the associated factors, to provide a theoretical basis for improvement in the allocation of ICU beds. Methods The equity of ICU bed allocation was investigated in 31 provincial regions in China in 2021. The Gini coefficient combined with Lorenz curves were used to analyse the current status of ICU bed allocation by both population and service area. The spatial heterogeneity and aggregation of ICU bed density were analysed using the Global Moran’s index. The spatial distribution pattern was visualized via LISA maps using the Local Moran’s index. Three grey correlation models were constructed to assess the key factors influencing ICU bed density. Finally, robustness analysis was performed to test the reliability of the results. Results The allocation of ICU beds in China was highly inequitable by service area (Gini = 0.68) and showed better balance by population distribution (Gini = 0.14). The distribution of ICU beds by service area was highly spatially clustered (Global Moran’s I = 0.22). The bed utilization rate exhibited the strongest association with ICU bed density by population. Registered nurses per 10,000 square kilometres was the strongest factor affecting ICU bed density by service area. Conclusions The allocation of ICU beds by population is better than by service area; the allocation by service area is less equitable in China. These findings emphasise the need to implement better measures to reduce ICU bed equity differences between regions and balance and coordinate medical resources. Service area size, bed utilization, the number of registered nurses and other key factors should be considered when performing regional health planning for ICU bed supply. This will increase the equitable access to critical medical services for all populations.

Abstract Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide.

Abstract Background The aim of this study was to investigate the clinical features of Nocardia infections, antibiotic resistance profile, choice of antibiotics and treatment outcome, among others. In addition, the study compared the clinical and microbiological characteristics of nocardiosis in bronchiectasis patients and non-bronchiectasis patients. Methods Detailed clinical data were collected from the medical records of 71 non-duplicate nocardiosis patients from 2017 to 2023 at a tertiary hospital in Zhengzhou, China. Nocardia isolates were identified to the species level using MALDI-TOF MS and 16S rRNA PCR sequencing. Clinical data were collected from medical records, and drug susceptibility was determined using the broth microdilution method. Results Of the 71 cases of nocardiosis, 70 (98.6%) were diagnosed as pulmonary infections with common underlying diseases including bronchiectasis, tuberculosis, diabetes mellitus and chronic obstructive pulmonary disease (COPD). Thirteen different strains were found in 71 isolates, the most common of which were N. farcinica (26.8%) and N. cyriacigeorgica (18.3%). All Nocardia strains were 100% susceptible to both TMP-SMX and linezolid, and different Nocardia species showed different patterns of drug susceptibility in vitro. Pulmonary nocardiosis is prone to comorbidities such as bronchiectasis, diabetes mellitus, COPD, etc., and Nocardia is also frequently accompanied by co-infection of the body with pathogens such as Mycobacterium and Aspergillus spp. Sixty-one patients underwent a detailed treatment regimen, of whom 32 (52.5%) received single or multi-drug therapy based on TMP-SMX. Bronchiectasis was associated with a higher frequency of Nocardia infections, and there were significant differences between the bronchiectasis and non-bronchiectasis groups in terms of age distribution, clinical characteristics, identification of Nocardia species, and antibiotic susceptibility (P

Introduction and Objectives: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. Materials and Methods: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. Results: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). Conclusions: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.

Abstract Landslides, recognized as a significant global natural disaster, necessitate an exploration of the impact of various resolution types in sampling strategies on Landslide Susceptibility Mapping (LSM) results. This study focuses on the segment from Zigui to Badong within the Three Gorges Reservoir Area, utilizing two resolution types: sampling resolution and spatial resolution, The Support Vector Machine (SVM) is employed to obtain LSM results, which are then analyzed using Receiver Operating Characteristic (ROC) curve, specific category accuracy and statistical methods. Artificial Neural Network (ANN) and Convolutional Neural Network (CNN) were used to verify the reliability of the results. Additionally, five common machine learning models, including Logistic Regression (LR), are used to conduct experiments on four sampling resolutions (10 m,30 m,50 m and 70 m) to further investigate the effect of sampling resolution on LSM results. These are evaluated using a comprehensive quantitative method. The results reveal that increasing spatial resolution improves the prediction accuracy, while increasing sampling resolution produces a contrary effect. Furthermore, the impact of spatial resolution on LSM results is more pronounced than that of sampling resolution. Finally, Fanjiaping landslide and Huangtupo landslide are selected as references for comparative analysis, with the results aligning with engineering reality.

ObjectiveThe aberrant mobilization and activation of various T lymphocyte subpopulations play a pivotal role in the pathogenesis of diabetic kidney disease (DKD), yet the regulatory mechanisms underlying these processes remain poorly understood. Our study is premised on the hypothesis that the dysregulation of immune checkpoint molecules on T lymphocytes disrupts kidney homeostasis, instigates pathological inflammation, and promotes DKD progression.MethodsA total of 360 adult patients with DKD were recruited for this study. The expression of immune checkpoint molecules on T lymphocytes was assessed by flow cytometry for peripheral blood and immunofluorescence staining for kidney tissue. Single-cell sequencing (scRNA-seq) data from the kidneys of DKD mouse model were analyzed.ResultsPatients with DKD exhibited a reduction in the proportion of CD3+TIM-3+ T cells in circulation concurrent with the emergence of significant albuminuria and hematuria (p=0.008 and 0.02, respectively). Conversely, the incidence of infection during DKD progression correlated with an elevation of peripheral CD3+TIM-3+ T cells (p=0.01). Both univariate and multivariate logistic regression analysis revealed a significant inverse relationship between the proportion of peripheral CD3+TIM-3+ T cells and severe interstitial mononuclear infiltration (OR: 0.193, 95%CI: 0.040,0.926, p=0.04). Immunofluorescence assays demonstrated an increase of CD3+, TIM-3+ and CD3+TIM-3+ interstitial mononuclear cells in the kidneys of DKD patients as compared to patients diagnosed with minimal change disease (p=0.03, 0.02 and 0.002, respectively). ScRNA-seq analysis revealed decreased gene expression of TIM3 on T lymphocytes in DKD compared to control. And one of TIM-3's main ligands, Galectin-9 on immune cells showed a decreasing trend in gene expression as kidney damage worsened.ConclusionOur study underscores the potential protective role of TIM-3 on T lymphocytes in attenuating the progression of DKD and suggests that monitoring circulating CD3+TIM3+ T cells may serve as a viable strategy for identifying DKD patients at heightened risk of disease progression.

BackgroundThe objective of this study is to study the adverse effects of coal mining environment on workers to discover early effective biomarkers.MethodsThe molecular epidemiological study was conducted with 502 in-service workers, who were divided into miner and auxiliary. We measured the individual levels of dust exposure for participants. Clinical examinations were conducted by qualified doctors. Peripheral blood was collected to measure biochemistry, hemogram, and karyocyte apoptosis.ResultsAll workers were healthy who have not found with any diseases that can be diagnosed medically in the physical examination and showed no difference in dust exposure level, age, height, weight, and body mass index between groups. The working years of miners were lower than that of auxiliaries (p

Objective: The regional inequality of emergency medicine beds distribution has a great impact on population health as well as the accessibility of emergency services. This study aimed to explore the regional inequality of emergency medicine bed distribution and its influencing factors.Methods: The Gini coefficient and health resource agglomeration were used to analyze the regional inequality of emergency medicine beds distribution by area from 2012 to 2021 in China. Grey correlation models were used to explore the factors influencing the regional inequality of emergency medicine beds distribution.Results: From 2012 to 2021, Gini coefficients of emergency medicine beds distribution by geographic in China showed a worsening trend, rising from 0.6229 to 0.6636. The average HRAD index was 3.43 in the east and 0.44 in the west. Population structure factors have the greatest influence on the regional inequality of emergency medicine beds distribution.Conclusion: Health resources allocation strategy only according to population size should be changed. In formulating policies for emergency medicine beds allocation should take into account population structure, financial structure of expenditure, the inequality of geographical distribution and so on.

Objective: To establish a Bama minipigs model with Non-Alcoholic Fatty Liver (NAFL) induced by a high-fat diet and investigate the application of attenuation coefficient (ATT) and ultrasound-derived fat fraction (UDFF) in the diagnosis of NAFL. Methods: Six-month-old male Bama minipigs were randomly divided into normal control and high-fat groups (n = 3 pigs per group), and fed with a control diet and high-fat diet for 32 weeks. Weight and body length were measured every four weeks, followed by quantitative ultrasound imaging (ATT and UDFF), blood biochemical markers, and liver biopsies on the same day. Using the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) as a reference, we analyzed the correlation between ATT, UDFF, and their score results. Results: Compared with the normal control group, the body weight, body mass index (BMI), and serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the High-fat group were significantly different at Week 12 (P

Abstract Objectives This study aimed to analyze the possible causes of changes in cardiac function and investigate the feasibility of clinical assessment of gastrointestinal cancer in patients with or without acute kidney injury (AKI) assessed using a non-invasive impedance cardiography (ICG, Bioz. Cardio Dynamics, USA) to identify independent risk factors. Methods Patients admitted to the Fourth Hospital of Hebei Medical University, China, between May 1, 2019, and February 15, 2022, were included in this study. A total of 51 patients with gastrointestinal cancer (31 men and 20 women, mean age 61.1 ± 10.9 years) with or without AKI were evaluated for ICG. A total of 19 patients underwent ultrasound cardiography (UCG) and ICG evaluations. Result There was a significant positive correlation between cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI), and ejection fraction (EF) measured using UCG and ICG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001), CIICG and CIUCG (r = 0.718, P = 0.001), SVICG and SVUCG (r = 0.837, P

Background: Rituximab (RTX) is a monoclonal antibody that selectively targets CD20 and is frequently used in the treatment of membranous nephropathy (MN). Analysis of the therapeutic efficacy and safety of RTX in treating MN in practice and a comparative pharmacoeconomic analysis of the RTX and traditional tacrolimus (TAC) regimens can provide valuable insights to aid decision-making by the government and relevant medical insurance departments.Methods: We conducted a statistical analysis of medical records from patients diagnosed with MN who underwent RTX treatment between 1 January 2019 and 1 January 2023. The TAC data were obtained from the clinical literature. The efficacy rates and incidence of adverse effects (AEs) were calculated to compare the efficacy and safety of RTX and TAC. Based on the patient’s disease status, we developed a Markov model to compare the total cost, remission rate, and incremental cost-effectiveness ratio (ICER) of the two regimens. Both univariate and probability sensitivity analyses were performed to validate the stability of the developed model.Results: The RTX group enrolled 53 patients with MN, and the 12-month overall efficacy rate was not significantly different from that of the TAC group with 35 patients (86.79% vs. 71.4%, p = 0.0131); however, the relapse rate was significantly lower in the RTX group (3.77% vs. 22.8%, p = 0.016). The RTX group demonstrated no severe AEs (SAEs), while the TAC group demonstrated six cases of SAEs, including 4 cases of severe pneumonia, 1 case of lung abscess and 1 case of interstitial lung disease, accounting for 7.89% of traditional tacrolimus-treated patients. The baseline analysis results revealed that over a 5-year post-treatment period, RTX increased quality-adjusted life years (QALYs) by 0.058 and costs by ¥7,341. Assuming three times the 2022 domestic gross domestic product as the willingness-to-pay (WTP) threshold per QALY, the ICER of RTX compared to TAC was ¥124,631.14/QALY, which is less than the WTP threshold of ¥257,094/QALY, indicating that RTX treatment is approximately two times more cost-effective compared to TAC.Conclusion: The current analysis indicates that despite the expensive unit price of RTX, it remains a cost-effective treatment option for MN compared to TAC.

Structural health monitoring and damage identification aim to detect the internal damage and evaluate the health conditions of the practical engineering structure, which has been the most popular research field for several decades. The sensitivity-based method incorporated with the regularization techniques is the classical and useful approach, and it can obtain accurate damage detection results. However, with the development of civil engineering structures, this classical method faces two problems: one is it is only applied to simple structures rather than full-scale structures, and second is the iterative calculation efficiency is lower. Therefore, aiming at these drawbacks, the two improvement strategies have been introduced to the original method for its enhancement in the application potential and computational efficiency. The proposed method has been verified based on two examples, i.e., a numerical steel truss with 144 elements and a full-scale experimental steel truss with 160 elements. The results prove that the proposed method has better efficiency and good application potential in the practical full-scale engineering structure.

With increasing anthropogenic activities, freshwater ecosystems around the world are becoming increasingly affected by various pressures, including eutrophication, overfishing, and irrational stocking, which may have a negative impact on the food web structure. Despite the extensive research and proposed management measures for eutrophic lakes, there are only few analysis on long-term monitoring data regarding fishery resources. Additionally, there is a lack of evaluation and prediction of the effectiveness of current fish management policies. To remedy this, we analyzed long-term monitoring data from Lake Taihu, China, a severely eutrophicated lake with a skewed fish size structure exhibiting dominance of small individuals. We first constructed 14 Ecopath models to investigate how trophic interactions and biomass fluxes changed from 2007 to 2020. Subsequently, the Ecosim model was used to predict how the biomass of fish and the ecosystem network respond to the initiated 10-years fishing ban. Our results demonstrate long-term changes in fish biomass and ecosystem stability. The analyses revealed that 1) the biomass development in different feeding types of fish is controlled by human activities (mainly catches and stocking) and trophic interactions and 2) the rate of decline in ecosystem network stability slows down during the fishing ban. The primary focus of this study was to fill the gap in long-term serial studies of fish monitoring data and ecosystem stability in the lake and, for the first time, to predict the outcome of the fishing ban from an ecosystem perspective using the Ecosim model. Overall, our results emphasize the importance of rational stocking and fishing policies and provide a better understanding of the changes in the ecological dynamics in Lake Taihu of relevance for the management and restoration of the lake.

In monomictic lakes, the potential intensification of hypolimnetic deoxygenation due to human activities and climate change threatens lake ecosystems and water quality. Understanding the trends and mechanisms of hypolimnetic deoxygenation would allow for the adaptive management of monomictic lakes. This study investigated the trends and drivers of hypolimnetic deoxygenation in Lake Fuxian (a monomictic lake in south-western China) over the past 150 years using paleolimnological evidence and historical records. Analysis of enrichment factors for molybdenum (Mo), uranium (U), and vanadium (V), and ratios of U/thorium (Th), pristane (Pr)/phytane (Ph), and total organic carbon (TOC)/total phosphorus (TP) in a dated sediment core indicated that the extent of hypolimnetic deoxygenation was relatively low before 1994 and increased substantially thereafter. Nutrient monitoring records and sediment n-alkane proxies indicated notable eutrophication of the lake since 1986 and a greater degree of human disturbance in the catchment between 1951 and 1967. Due to their asynchronous occurrence, eutrophication and catchment disturbance could not be the major drivers of hypolimnetic deoxygenation. Interestingly, climate records indicated that the local ambient temperature exhibited similar trends to that of hypolimnetic deoxygenation, including markedly higher temperatures after 1994. This implies that prolonged water column stratification due to climate warming could have promoted hypolimnetic deoxygenation by limiting oxygen exchange between the upper and lower water columns. In comparing the results with those of Lake Erhai, another monomictic lake with contrasting morphology and hydrology characteristics, we found that the low surface area/depth ratio and long water residence time in Lake Fuxian enable dissolved oxygen of the lake hypolimnion vulnerable to temperature over the lake.

Abstract Biomanipulation has been widely used in the ecological restoration of eutrophic lakes for decades. However, biomanipulation is prone to failure if external nutrient loads are not reduced. In order to explore the importance of filter‐feeding fish and bivalves on algal control, an outdoor mesocosm experiment was conducted using different nutrient concentrations. Four treatments simulating daily loads of nutrients in Lake Taihu were studied: current, two times, and three times average daily loads of nutrients with both fish (Aristichthys nobilis) and Asian clam (Corbicula fluminea) and as a control current daily loads without fish or bivalves. Results showed that stocking of filter‐feeding fish and bivalves (80 g m−3 bighead carp; 200 g cm−2 clams) at two times daily nutrient loads could effectively control water column Chl a concentrations and phytoplankton biomass. At higher nutrient concentrations (TN ≥ 260 μg L−1 d−1; TP ≥ 10 μg L−1 d−1), top‐down control of filter‐feeding fish and bivalves was less effective and bottom‐up effects resulted in significant increases of Chl a concentration. Thus, as phytoplankton biomass in freshwater ecosystems is determined by both the top‐down effects of predators and the bottom‐up effects of nutrients, external loadings should be controlled when filter‐feeding fish and bivalves are used for algal control to ensure the efficacy of biomanipulation.

ABSTRACT: Objectives: This study investigated the prevalence and significant clinical outcomes of pre-extensively drug-resistant plus additional drug-resistant tuberculosis (pre-XDR-plus) in Henan Provincial Chest Hospital between 2017 and 2021. Methods: We analysed and summarized the drug sensitivity test (DST) results of clinical Mycobacterium tuberculosis (MTB) strains in TB patients seeking care in the Tuberculosis Clinical Medical Research Centre of Henan Province between 2017 and 2021. Medical records of pre-extensively drug-resistant plus additional drug-resistant TB patients were statistically analysed, including demographic characteristics, regimens, and outcomes. Results: Of the 3689 Mycobacterium tuberculosis strains, 639 (17.32%), 353 (9.56%), and 109 (2.95%), multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (pre-XDR), and pre-XDR-plus, respectively. The proportion of MDR decreased from 19.1% in 2017 to 17.5% in 2021 (χ2 = 0.686, P = 0.407), the proportion of pre-XDR from 11.4% in 2017 to 9.0% in 2021 (χ2 = 2.39, P = 0.122), and pre-XDR-plus from 4.7% in 2017 to 1.8% in 2020, with the declining trend was significant (χ2 = 9.348, P = 0.002). The most commonly used anti-TB drugs were pyrazinamide (PZA, 37/46, 80.43%) and cycloserine (CS, 32/46, 69.57%), followed by linezolid (LZD, 25/46, 54.35%), protionamide (TH, 25/46, 54.35%), and para-aminosalicylic acid (PAS, 23/46, 50.00%). Patients receiving the LZD regimen were 5 times more likely to have a favourable outcome than those not receiving LZD (OR = 6.421, 95% CI 2.101–19.625, P = 0.001). Patients receiving a regimen containing CS were 4 times more likely to have a favourable outcome compared to those not taking CS (OR = 5.444, 95% CI 1.650–17.926, P = 0.005). Conclusions: Our data suggest that the population of pre-XDR-plus had significantly decreased over the past five years in the Henan Provincial Chest Hospital. The COVID-19 and flood disaster affect TB patients’ selection of medical services. In addition, the pre-XDR-plus patients whose regimens contain LZD or CS were more likely to have favourable outcomes.

Abstract Background The orchid growth and development often associate with microbes. However, the interaction between plant performance and microbial communities within and surrounding plants is less understood. Dendrobium catenatum, which used to be an endangered orchid species, has become a billion dollar industry in China. Simulated natural cultivation modes, such as living tree epiphytic (LT) and cliff epiphytic (CE) cultivations, improve the production or quality of D. catenatum and contribute to the development of D. catenatum industry. In a previous study, morphological characteristics, anatomical structure, and main bioactive components (polysaccharides and ethanol-soluble extractives) of D. catenatum grown under LT and CE significantly differed from a facility cultivation mode, pot (PO) cultivation, were observed. Whether cultivation mode affects bacterial and fungal communities of D. catenatum, thereby affecting the chemical quality of this plant, need to be explored. Results Both three plant organs (leaf, stem, and root) and cultivating substrates obtained under three cultivation modes: living tree epiphytic (LT), cliff epiphytic (CE), and pot (PO) cultivation were examined by adopting high-throughput sequencing methods. Subsequently, bacterial and fungal correlations with D. catenatum main chemical components, stem polysaccharides and ethanol-soluble extractives and leaf phenols and flavonoids, were elucidated. The results showed that microbial communities of the plants and substrates are both influenced by the cultivation mode. However, the plants and their cultivating substrates exhibited different patterns of bacterial and fungal composition, with clearly distinguished dominant bacterial groups, but shared dominance among fungal groups. Bacteria and fungi differed in abundance, diversity, and community structure, depending on the cultivation environment and plant organ. Both bacterial and fungal communities were affected by cultivation mode and plant organ. In both plants and substrates, PO bacterial and fungal community structure differed significantly from those of LT and CE modes. Bacterial and fungal community structure differed significantly between roots and the other two plant organs examined (stems and leaves). Several bacteria and fungi were positively correlated with main chemical components in D. catenatum. Conclusions The findings indicate that microbial communities of the plants and substrates were both influenced by the cultivation mode and plant organ, and some of them were positively correlated with main chemical components in D. catenatum. The research would enhance our understanding of interactions between Dendrobium and the microbial environment, and to provide a theoretical basis for the development of improved D. catenatum cultivation methods.

AbstractAquaculture in lakes is an important human activity that could accelerate eutrophication. Its impacts on aquatic ecosystems have attracted extensive attention. This study was carried out in Gaoyou Lake, China. We investigated environmental variables and phytoplankton in areas with different aquaculture intensities over four seasons. Marked differences in diversity, biomass and phytoplankton community structure were observed across areas. The 59 phytoplankton taxa identified could be divided into 20 functional groups (PFGs), of which groups B, D, E, J, MP, P, S1, W1 and Y were dominant PFGs in different areas. Total phosphorus (TP), ratio of nitrogen and phosphorus (TN/TP) and chemical oxygen demand (CODMn) were important driving factors for spatial differences in phytoplankton functional groups. Aquaculture altered the phytoplankton community structure, leading to a significant increase in phytoplankton biomass and diversity, especially cyanobacterial biomass. However, phytoplankton biomass and diversity could be significantly reduced and restored to natural levels after the cessation of aquaculture. This study clarified the effects of aquaculture activity on the phytoplankton community, thereby providing fundamental information for better understanding the impacts of aquaculture on lake eutrophication.

Abstract Germline PALB2 pathogenic variants are associated with an increased lifetime risk for breast, pancreatic, and ovarian cancer. However, the interpretation of the pathogenicity of numerous PALB2 missense variants of uncertain significance (VUSs) identified in germline genetic testing remains a challenge. Here we selected ten potentially pathogenic PALB2 VUSs identified in 2279 Chinese patients with breast cancer and evaluated their impacts on PALB2 function by systematic functional assays. We showed that three PALB2 VUSs p.K16M [c.47 A > T], p.L24F [c.72 G > C], and p.L35F [c.103 C > T] in the coiled-coil domain impaired PALB2-mediated homologous recombination. The p.L24F and p.L35F variants partially disrupted BRCA1-PALB2 interactions, reduced RAD51 foci formation in response to DNA damage, abrogated ionizing radiation-induced G2/M checkpoint maintenance, and conferred increased sensitivity to olaparib and cisplatin. The p.K16M variant presented mild effects on BRCA1-PALB2 interactions and RAD51 foci formation. Altogether, we identify two novel PALB2 VUSs, p.L24F and p.L35F, that compromise PALB2 function and may increase cancer risk. These two variants display marked olaparib and cisplatin sensitivity and may help predict response to targeted therapy in the clinical treatment of patients with these variants.

Benzotriazole ultraviolet stabilizers (BUVSs) are emerging pollutants that are widely detected in aquatic ecosystems. While structure-dependent effects of BUVSs are reported, the relationship between biotransformation and toxicity outcomes remains unclear. In this study, zebrafish embryos were exposed to two common BUVSs (UV-234 and UV-326) at 1, 10, and 100 µg/L for up to 7 days. Comparison of their uptake and biotransformation revealed that the bioaccumulation capacity of UV-234 was higher than that of UV-326, while UV-326 was more extensively biotransformed with additional conjugation reactions. However, UV-326 showed low metabolism due to inhibited phase II enzymes, which may result in the comparable internal concentrations of both BUVSs in larval zebrafish. Both BUVSs induced oxidative stress while decreased MDA, suggesting the disturbance of lipid metabolism. The subsequent metabolomic profiling revealed that UV-234 and UV-326 exerted different effects on arachidonic acid, lipid, and energy metabolism. However, both BUVSs negatively impacted the cyclic guanosine monophosphate / protein kinase G pathway. This converged metabolic change resulted in comparable toxicity of UV-234 and UV-326, which was confirmed by the induction of downstream apoptosis, neuroinflammation, and abnormal locomotion behavior. These data have important implications for understanding the metabolism, disposition, and toxicology of BUVSs in aquatic organisms.

COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.

Abstract Background To examine the correlation between the occurrence of adenomyosis and the outcome of vaginal repair of cesarean section scar defects (CSDs). Methods A total of 278 women with CSD were enrolled in this retrospective observational cohort study at the Shanghai First Maternity & Infant Hospital between January 2013 and August 2017. Patients were divided into two groups according to preoperative magnetic resonance imaging (MRI) findings: the adenomyosis group and the non-adenomyosis group. They all underwent vaginal excision and suturing of CSDs and were required to undergo examinations 3 and 6 months after surgery. Preoperative and postoperative clinical information was collected. Optimal healing was defined as a duration of menstruation of no more than 7 days and a thickness of the residual myometrium (TRM) of no less than 5.8 mm after vaginal repair. Results Before vaginal repair, for patients in the adenomyosis group, the mean duration of menstruation was longer and TRM was significantly thinner than those in patients in the non-adenomyosis group (p

The design and fabrication of nanomaterials with controllable morphology and size is of critical importance to achieve excellent catalytic performance in heterogeneous catalysis. In this work, cobalt oxide (Co3O4) nanostructures with different morphologies (nanoplates, microflowers, nanorods and nanocubes) were successfully constructed in order to establish the morphology–property–performance relationship of the catalysts. The morphology and structure of the nanostructured Co3O4 were characterized by various techniques, and the catalytic performance of the as-prepared nanostructures was studied by monitoring the reduction of p-nitrophenol to p-aminophenol in the presence of excess NaBH4. The catalytic performance was found to be strongly dependent on their morphologies. The experimental results show that the pseudo-first-order reaction rate constants for Co3O4 nanostructures with various shapes are, respectively, 1.49 min−1 (nanoplates), 1.40 min−1 (microflowers), 0.78 min−1 (nanorods) and 0.23 min−1 (nanocubes). The Co3O4 nanoplates exhibited the highest catalytic activity among the four nanostructures, due to their largest specific surface area, relatively high total pore volume, best redox properties and abundance of defect sites. The established correlation between morphology, property and catalytic performance in this work will offer valuable insight into the design and application of nanostructured Co3O4 as a potential non-noble metal catalyst for p-nitrophenol reduction.

As urbanization progresses, large cities continue to attract population, causing depopulation and regional development imbalances, especially in remote rural areas facing sustainability challenges. This study aims to explore local resource potential and assess critical factors for regional revitalization, offering design strategies to promote local sustainability. The study is based on the UN Sustainable Development Goals (SDGs) and assesses the status of regional development through field research. The Delphi method was employed to interview experts and build a multi-tiered sustainable development evaluation indicator framework (Level 1: B1–B3, Level 2: C1–C8, Level 3: D1–D16), covering economic, social, and environmental dimensions. The weights of the indicators were determined through the analytic hierarchy process (AHP), and the fuzzy comprehensive evaluation (FCE) method was applied to comprehensively assess the sustainable development status of Qianfeng Community. The research findings revealed that due to population outflow and a lack of participation in co-building channels, the region scored lowest in “local employment & entrepreneurship (D2)”, “innovation & entrepreneurship culture (D10)”, and “endogenous development (D16)”. Consequently, the study proposes the establishment of a regional revitalization co-creation platform based on “life projects” as part of a sustainable design strategy. These research results provide valuable case studies and strategic references for future regional revitalization and sustainable design initiatives.

Chinese government proposed the “Double Carbon Target” (DCT) in 2020 to deal with the increasing global warming crisis. In this regard, the study identifies temporal and spatial evolution characteristics of environmental efficiency through the DEA-SBM model and further explores the impact of DCT on the environmental efficiency of coal cities using scenario analysis method. Empirical results show that: 1) Both economic efficiency and environmental efficiency of China’s coal cities are first rising and then falling during the period 2003–2022, and the gap between coal cities and non-coal cities was very small before 2011, but it begins to be enlarged after 2011. The main reason is environmental regulation has exerted a significant impact on coal cities; 2) the difference in environmental efficiency among coal cities is huge due to their policies for supporting renewable energy. Some cities have broken carbon lock-in by the favorite policy for renewable energy, while others have been trapped into path dependence on the coal-related industry; 3) generally, the more amount of emission reduction required, the lower the environmental efficiency of coal cities in the carbon neutralization scenario. Furthermore, some cities rich of renewable energy resources, such as Erdos, and Xuzhou, still have better environmental performance under different carbon neutralization scenarios, while others will encounter many transformation barriers and even may cause a social crisis. Therefore, it is suggested that some coal cities in northwest China can vigorously develop solar energy to improve environmental efficiency.

Background: Type 1 diabetes mellitus (T1DM) is one of the most common endocrine and metabolic diseases in children. Pancreatic β cells are thought to be critical cells involved in the progression of T1DM, and their injury would directly lead to impaired insulin secretion.Purpose: To investigate the protective effects of allicin on pancreatic β cell injury and elucidate the underlying mechanism.Methods: The streptozotocin (STZ)-induced mouse T1DM model in vivo and STZ-induced pancreatic β cell Min6 model in vitro were used to explore the effects of allicin on T1DM. The experiments include fasting blood glucose test, oral glucose tolerance detection, HE staining, immunohistochemistry, immunofluorescence, TUNEL staining, western blot, real-time quantitative PCR (RT-qPCR), and flow cytometry.Results: Allicin could significantly decrease blood glucose level, improve islet structure and insulin expression, and inhibit apoptosis to reduce STZ-induced pancreatic β cell injury and loss through activating AMPK/mTOR mediated autophagy pathway.Conclusion: Allicin treatment significantly reduced STZ-induced T1DM progression, suggesting that allicin may be a potential therapy option for T1DM patients.

Abstract Objectives Conventional glucocorticoid (GC) treatment poses significant risks for opportunistic infections due to its suppressive impact on CD4+ T cells. This study aimed to explore the mechanisms by which GCs modulate the functionality of CD4+ T cells during infection. Methods We consistently measured FOXP3, inflammatory cytokines and phospho‐S6 ribosomal protein levels in CD4+ T cells from patients undergoing conventional GC treatment. Using Foxp3EGFP animals, we investigated the dynamic activation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and its correlation with the immunoregulatory function of CD4+ T cells under the influence of GCs. Results GCs dynamically altered the expression pattern of FOXP3 in CD4+ T cells, promoting their acquisition of an active T regulatory (Treg) cell phenotype upon stimulation. Mechanistically, GCs undermined the kinetics of the mTORC1 pathway, which was closely correlated with phenotype conversion and functional properties of CD4+ T cells. Dynamic activation of the mTORC1 signaling modified the GC‐dampened immunoregulatory capacity of CD4+ T cells by phenotypically and functionally bolstering the FOXP3+ Treg cells. Interventions targeting the mTORC1 pathway effectively modulated the GC‐dampened immunoregulatory capacity of CD4+ T cells. Conclusion These findings highlight a novel mTORC1‐mediated mechanism underlying CD4+ T cell immunity in the context of conventional GC treatment.

Sertraline (SER) is one of the most commonly detected antidepressants in the aquatic environment that can negatively affect aquatic organisms at low concentrations. Despite some knowledge on its acute toxicity to fish, the effects of chronic SER exposure remain poorly understood along with any underlying mechanisms of SER-induced toxicity. To address this knowledge gap, the effects of chronic exposure to three SER concentrations from low to high were investigated in zebrafish. Juvenile zebrafish were exposed to three concentrations of 1, 10, or 100 μg/L of SER for 28 d, after which indicators of oxidative stress and neurotoxicity in the brain were measured. Superoxide dismutase (SOD) activity was significantly enhanced by SER at 1 up to 100 μg/L, and catalase (CAT) activity was significantly induced by SER at 1 or 10 μg/L. The activity of acetylcholinesterase (AChE) was significantly induced by 10 and 100 μg/L of SER, and the serotonin (5-HT) level was significantly increased by all three concentrations of SER. To ascertain mechanisms of SER-induced toxicity, transcriptomics was conducted in the brain of zebrafish following 100 μg/L SER exposure. The molecular signaling pathways connected with circadian system and the immune system were significantly altered in the zebrafish brain. Based on transcriptomic data, the expression levels of six circadian clock genes were measured, and three genes were significantly altered in relative abundance in fish from all experimental treatments with SER, including cryptochrome circadian regulator 2 (cry2), period circadian clock 2 (per2), and period circadian clock 3 (per3). We hypothesize that the circadian system may be related to SER-induced neurotoxicity and oxidative stress in the central nervous system. This study reveals potential mechanisms and key events (i.e., oxidative stress and neurotoxicity) associated with SER-induced toxicity, and improves understanding of the molecular and biochemical pathways putatively perturbed by SER.

The slender structure is prone to be affected by horizontal force; therefore, the seismic performance needs to be considered carefully. Meanwhile, due to the low cost and good performance on the seismic resistance of the Tuned liquid dampers (TLDs) system, it has been widely used for vibration control. Regarding the abovementioned background, in this study, we conduct the experiment to investigate the seismic performance of the slender structure with the integral water tank, and two designed parameters (the placement location and the water level of the water tank) are studied. The experimental phenomenon and the structural accelerations are recorded to be analyzed further and discussed, then a useful design guide for an integral water tank is summarized. Finally, some practical and helpful advice and conclusions are put forward for the design of the water tank that is used for the purpose of seismic resistance in the slender structure. Our research can fill the blank in the research on the integral water tank of TLDs system, which also has good potential to achieve the enhancement of slender structure seismic performance.

PurposePostmastectomy radiotherapy (PMRT) after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial clinical stage cT1-2N+, especially for those who achieved ypT1-2N0, is still controversial. This study was to evaluate the survival prognosis of cT1-2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1-2N+ stage, receiving NAC with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was disease-free survival (DFS), and secondary endpoint was overall survival (OS). Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1-2N+ patients achieved ypT0-2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0-2N+). The 5-year DFS of ypT0-2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0-2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0-2N0 non-PMRT subgroup and cT1-2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0-2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn effective response to NAC (ypT0-2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1-2N+ breast cancer patients with ypT0-2N0 after NAC.

Green (technical) innovation is expected to be an effective tool for addressing environmental crises. However, the effect of environmental regulations on green innovation may depend on the type of environmental regulation. To that end, this study utilizes panel data covering 30 Chinese provinces to explore the mechanism underlying the relationship between these two variables in light of the heterogeneity in environmental regulations and pollutants. The direct effects of three types of environmental regulations and four pollutants are verified, as are the thresholds in the effects of environmental regulations on green innovation. The results show that 1) both market-incentive and public participation-based environmental regulations have positive effects on green innovation, while command-and-control regulations do not. Unlike the effects of the market-incentive tool, which has a single threshold, the effect of public participation-based environmental regulations has two thresholds, which indicates that there is too little public participation for such regulations to be effective and too much for them to be sensitive to environmental protection. 2) Three of the four pollutants (industrial wastewater, waste gas, and carbon emissions) have a significantly positive impact on green innovation only when they exceed the first threshold value, whereas an increase in industrial solid waste has little effect on green innovation until it exceeds the second threshold value. 3) In the eastern region, all three kinds of environmental regulations play significant roles in promoting green innovation, and their effects are greater than those in the western region. However, the effect of environmental regulations in the central region is not different from that in the western region.

Abstract Nano‐based immunotherapy of therapeutic biomolecules is attractive but tremendously hampered by the poor delivery efficiency. This study reports a novel delivery system of fluorinated‐coordinative‐epigallocatechin gallate (EGCG), referring as FEGCG/Zn, through the integration of fluorination and zinc ions (Zn2+) into EGCG. The robust therapeutics of FEGCG/Zn are measured in terms of the regulating effect on programmed cell death ligand 1 (PD‐L1), the effective delivery of diverse biomolecules, and the hitchhiking ability using living cells. Taking small interfering RNA of PD‐L1 (siPD‐L1) and erythrocytes as an example, the fabricated biomimetic system achieves excellent siPD‐L1 delivery and further improves siPD‐L1 accumulation in tumors. Finally, the combination of FEGCG/Zn and siPD‐L1 promotes antitumor immunotherapy through alleviation of T cells exhaustion by regulating PD‐L1 expression in tumor cells. The results demonstrate that FEGCG/Zn substantially regulates PD‐L1 expression and improves immune‐biomolecule delivery by forming biomimetic nanoassemblies, offering a versatile platform for cancer immunotherapy.

Objective: Circulating tumor cells (CTCs) play a critical role in cancer metastasis, but their prevalence and significance remain unclear. This study attempted to track the epithelial-mesenchymal transition (EMT) status of CTCs in breast cancer patients and investigate their clinical relevance. Methods: In this study, the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT status in breast cancer. A total of 89 breast cancer patients were recruited, including stage 0–III (n = 60) and late stage (n = 29) cases. Results: Using the negFACS-IF:E/M platform, it was found that in human epidermal growth factor receptor 2 (HER2)+ patients, mesenchymal CTCs usually exhibited a high percentage of HER2+ cells. Stage IV breast cancer patients had considerably more CTCs than stage 0–III patients. Among stage 0–III breast cancers, the HER2 subtype included a significantly higher percentage of mesenchymal and biphenotypic (epithelial and mesenchymal) CTCs than the luminal A or B subtypes. Among stage IV patients, CTCs were predominantly epithelial in cases with local recurrence and were more mesenchymal in cases with distant metastasis. By applying a support vector machine (SVM) algorithm, the EMT status of CTCs could distinguish between breast cancer cases with metastasis/local recurrence and those without recurrence. Conclusions: The negFACS-IF:E/M platform provides a flexible and generally acceptable method for the highly sensitive and specific detection of CTCs and their EMT traits in breast cancer. This study demonstrated that the EMT status of CTCs had high clinical relevance in breast cancer, especially in predicting the distant metastasis or local recurrence of breast cancer.

Tracking moving objects in a city, such as suspicious vehicles or persons, is important for public safety management. Traditionally, target tracking is assisted by the pre-deployed stationary surveillance cameras, which are with insufficient coverage. In this work, we propose a different approach called Co-Tracking, a real-time target tracking system that leverages both citizens' mobile phones and stationary surveillance cameras to track moving objects collaboratively. Two key techniques are focused. Firstly, in order to accurately assign tracking tasks, we propose the Middle Query Location Prediction (MQLP) algorithm for predicting the target's location. Secondly, in order to efficiently utilizes these human/machine resources, we propose a heuristic algorithm, namely S-Maximum, to optimize the task allocation, including maximizing the number of completed tracking tasks and minimizing the number of mobile phones. Experimental results show that the proposed Co-Tracking system can effectively track moving objects with low incentive costs.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM develops and is sustained by inflammation and immunosuppression from the tumor microenvironment (TME). This study sought to identify a reliable TME-related biomarker that could provide survival prediction and new insight into therapy for UM patients. Based on clinical characteristics and the RNA-seq transcriptome data of 80 samples from The Cancer Genome Atlas (TCGA) database, PRRX1 as a TME- and prognosis-related gene was identified using the ESTIMATE algorithm and the LASSO–Cox regression model. A prognostic model based on PRRX1 was constructed and validated with a Gene Expression Omnibus (GEO) dataset of 63 samples. High PRRX1 expression was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Comprehensive results of the prognostic analysis showed that PRRX1 was an independent and reliable predictor of UM. Then the results of immunological characteristics demonstrated that higher expression of PRRX1 was accompanied by higher expression of immune checkpoint genes, lower tumor mutation burden (TMB), and greater tumor cell infiltration into the TME. Gene set enrichment analysis (GSEA) showed that high PRRX1 expression correlated with angiogenesis, epithelial–mesenchymal transition (EMT), and inflammation. Furthermore, downregulation of PRRX1 weakened the process of EMT, reduced cell invasion and migration of human UM cell line MuM-2B in vitro. Taken together, these findings indicated that increased PRRX1 expression is independently a prognostic factor of poorer OS and MFS in patients with UM, and that PRRX1 promotes malignant progression of UM by facilitating EMT, suggesting that PRRX1 may be a potential target for UM therapy.

T cell immunoglobulin domain and mucin domain 3 (TIM3) was initially identified as an inhibitory molecule on IFNγ-producing T cells. Further research discovered the broad expression of TIM3 on different immune cells binding to multiple ligands. Apart from its suppressive effects on the Th1 cells, recent compelling experiments highlighted the indispensable role of TIM3 in the myeloid cell-mediated inflammatory response, supporting that TIM3 exerts pleiotropic effects on both adaptive and innate immune cells in a context-dependent manner. A large number of studies have been conducted on TIM3 biology in the disease settings of infection, cancer, and autoimmunity. However, there is a lack of clinical evidence to closely evaluate the role of T cell-expressing TIM3 in the pathogenesis of chronic kidney disease (CKD). Here, we reported an intriguing case of Mycobacterium tuberculosis (Mtb) infection that was characterized by persistent overexpression of TIM3 on circulating T cells and ongoing kidney tubulointerstitial inflammation for a period of 12 months. In this case, multiple histopathological biopsies revealed a massive accumulation of recruited T cells and macrophages in the enlarged kidney and liver. After standard anti-Mtb treatment, repeated renal biopsy identified a dramatic remission of the infiltrated immune cells in the tubulointerstitial compartment. This is the first clinical report to reveal a time-course expression of TIM3 on the T cells, which is pathologically associated with the progression of severe kidney inflammation in a non-autoimmunity setting. Based on this case, we summarize the recent findings on TIM3 biology and propose a novel model of CKD progression due to the aberrant crosstalk among immune cells.

Graphene can effectively improve the mechanical and electrical properties of cement-based materials due to its excellent tensile strength, thermal conductivity and electrical conductivity. In this paper, the effects of freeze–thaw on the conductivity and sensing properties of graphene-based cement materials were investigated. After the preparation of graphene-based cement materials, they were subjected to different times of freeze–thaw action. The experiments were designed to analyze the influence of freeze–thaw on the electrical conductivity, humidity sensitivity, thermosensitivity and pressure sensitivity of graphene-based cement composites. The results show that the influence of freeze–thaw on the electrical conductivity of graphene is mainly manifested in the influence on the resistivity and the extension of the polarization time, and the influence on the percolation transition zone is small. After freeze–thaw, the polarization time of the specimen decreases with the increase of the relative water content. The temperature has a great influence on the polarization effect of graphene-based cement composites and the composites with graphene content of the zone B still show satisfactory pressure-sensitive property after freeze–thaw.

A facile and one-step route has been employed for the synthesis of highly uniform CoOOH nanorings assembled on the surface of reduced graphene oxide (CoOOH/rGO nanocomposite). The physicochemical properties of the obtained CoOOH/rGO nanocomposite were characterized using X-ray diffraction pattern (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 physical adsorption (BET) and X-ray photoelectron spectroscopy (XPS). The TEM and SEM results confirmed that CoOOH nanorings (edge length ∼ 95 nm) were uniformly decorated on reduced graphene oxide nanosheets using the simple precipitation–oxidation–reduction method. When used as a catalyst for the reduction of p-nitrophenol to p-aminophenol in the presence of excess NaBH4, the resulting CoOOH/rGO nanocomposite exhibited good activity and stability. When the initial concentration of p-nitrophenol was 1.25 × 10−4 mol·L−1, p-nitrophenol could be fully reduced within 3.25 min at room temperature. The apparent rate constant was estimated to be 1.77 min−1, which is higher than that of pure CoOOH nanorings. Moreover, p-nitrophenol could still be completely reduced within 6 min in the fifth successive cycle. The superior catalytic performance of the nanocomposite is attributed to the synergistic effect between the highly dispersed CoOOH nanorings and the unique surface properties of the reduced graphene oxide nanosheets, which greatly increased the concentration of p-nitrophenol near CoOOH nanorings on reduced graphene oxide surface and improved the local electron density at the interface.

Abstract Cellular senescence is a persistently hypoproliferative state with diverse stressors in a specific aging microenvironment. Senescent cells have a double‐edged sword effect: they can be physiologically beneficial for tissue repair, organ growth, and body homeostasis, and they can be pathologically harmful in age‐related diseases. Among the hallmarks of senescence, the SASP, especially SASP‐related extracellular vesicle (EV) signalling, plays the leading role in aging transmission via paracrine and endocrine mechanisms. EVs are successful in intercellular and interorgan communication in the aging microenvironment and age‐related diseases. They have detrimental effects on downstream targets at the levels of immunity, inflammation, gene expression, and metabolism. Furthermore, EVs obtained from different donors are also promising materials and tools for antiaging treatments and are used for regeneration and rejuvenation in cell‐free systems. Here, we describe the characteristics of cellular senescence and the aging microenvironment, concentrating on the production and function of EVs in age‐related diseases, and provide new ideas for antiaging therapy with EVs.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and in other parts of the world and exhibits a poor prognosis. Growth inhibitor 5 (ING5) is a new member of the growth inhibitor (ING) protein family and is involved in many important cellular functions, such as the cell cycle, apoptosis, and chromatin remodeling. As a newly discovered tumor suppressor, ING5 has been shown to inhibit lung cancer proliferation and distant metastasis through the AKT pathway. In lung cancer tumors, ING5 can attenuate the ability of cancer cells to invade normal tumor-adjacent tissues. However, ING5 has rarely been studied in ESCC. Here, we found that in ESCC EC-109 cancer cells, ING5 overexpression inhibited cell proliferation and tumor invasion, whereas, in ESCC TE-1 cancer cells, ING5 knockdown promoted cell invasion. In a nude mouse xenograft model, ING5 overexpression inhibited tumor growth and the invasion ability of ESCC cells. Further studies revealed that ING5 overexpression inhibited IL-6/CXCL12 expression at both the mRNA and protein levels as well as morphological changes. We found for the first time that ING5 inhibits ESCC cell migration and invasion by downregulating the IL-6/CXCL12 signaling pathway.

Trophoblast cells synthesize and secrete prostaglandins (PGs), which are essential for ruminants in early gestation to recognize pregnancy. Hormones in the intrauterine environment play an important role in regulating PGs synthesis during implantation, but the underlying mechanism remains unclear. In this study, co-treatment of sheep trophoblast cells (STCs) with progesterone (P4), estradiol (E2), and interferon-tau (IFN-τ) increased the ratio of prostaglandin E2 (PGE2) to prostaglandin F2α (PGF2α) and upregulated peroxisome proliferator-activated receptor γ (PPARγ) expression, while inhibiting the mechanistic target of rapamycin (mTOR) pathway and activating cellular autophagy. Under hormone treatment, inhibition of PPARγ activity decreased the ratio of PGE2/PGF2α and cellular activity, while activating expression of the mTOR downstream marker—the phosphorylation of p70S6K (p-p70S6K). We also found that the PPARγ/mTOR pathway played an important role in regulating trophoblast cell function. Inhibition of the mTOR pathway by rapamycin increased the ratio of PGE2/PGF2α and decreased the expression of apoptosis-related proteins after inhibiting PPARγ activity. In conclusion, our findings provide new insights into the molecular mechanism of prostaglandin regulation of trophoblast cells in sheep during early pregnancy, indicating that the PPARγ/mTOR pathway plays an important role in PGs secretion and cell viability.

Recently, the light-type pier can be easily observed in urban elevated roads and bridge structures. This type of pier is broadly used in the field of structural engineering. The Thin-Walled Steel-Reinforced Concrete Pier (TSRCP), as the typical pier of the light-type piers, shows a better mechanical performance than the conventional reinforced concrete pier due to the enhancement of the H-shape steel. In terms of the TSRCP, the designed parameters, including the depth–width ratio (DWR) and axial compression ratio (ACR), have been determined in this study as the concerned variables. Then, a low cyclic loading experiment is conducted based on the three test specimens to investigate the effects of the concerned variables on the failure of the specimens. Meanwhile, some comparative studies are carried out based on the failure processes and modes, critical loading values (cracking, yielding and ultimate state), strain and ductility. The obtained experimental results demonstrate that all specimens illustrate a bending failure mode under the vertical and horizontal low cyclic loadings. Furthermore, for the concerned variables, the increasing DWR will reduce the ultimate bearing capacity of the TSRCP but enhance the plastic deformation. For the ACR, the decrease positively affects the cracking load, further improving the ultimate bearing capacity; however, the deformation capacity will be restrained. Finally, Abaqus is adopted to model the failure processes of three specimens; the comparative study has been conducted based on the simulated and experimental results. After that, the effects of the concerned variables on the failure performances are discussed. Meanwhile, the horizontal ultimate bearing capacity calculated equation for the TSRCP was deduced and validated based on the experimental and simulated data; the verification proves that the proposed equation can obtain a good result. In this study, the complex calculated process of the original equation can be simplified, which not only provides a convenient and useful way to design and manufacture this type of component but can serve as a guideline for validating the practical engineering applications.

Farming operation and amino acid profiles of pond-reared Chinese mitten crabs, Eriocheir sinensis (Milne Edwards, 1853), collected from different areas in Jiangsu Province, China were investigated and compared with the aim to elucidate how farming practices affected the nutritional values of three edible tissues (muscle, hepatopancreas and gonad) of crab. The crab pond aquaculture practices including snail input, macrophytes coverage, total commercial feed, the ratio of trash fish to total feed, were much higher in Gaochun and Jintan than that in other sites (having larger pond size), which leads to higher average individual body weight and commercial yields. Further, the mean body weight, muscle weight, carapace length and width, and the ratio of gonad to hepatopancreas were significantly higher in Jintan, Suzhou and Gaochun areas than in other regions. Amino acid assessment showed that all crabs collected delivered high-quality protein (Amino acid score >1 except Valine), the main amino acids being glutamic acid, aspartic acid, and alanine. Significant differences in amino acid profiles were observed between sites, tissues and sexes. Muscles were rich in total amino acids, essential amino acids, and delicious amino acids, followed by gonads and hepatopancreas. The contents of essential amino acids in crab muscles from Gaochun, Jintan, Suzhou and Guannan were significantly higher than those from Suqian, Sihong and Xinghua. All the amino acids except Serine and Glycine were significantly higher in gonads from males than from females. The redundancy analysis revealed that the snail input, trash fish ratio to the total feed, macrophytes coverage and total trash fish supply explained 84.3% of the variation in the amino acid content and structure in crabs from Gaochun, Jintan and Suzhou. Overall, our results show that mitten crabs collected in Jiangsu province had good nutritional quality suitable for human dietary needs, and that farming practices, especially degree of fish-source protein feeding, influence the amino acids composition of crabs.

Gitelman Syndrome (GS) is an inherited autosome recessive disorder syndrome, which can be caused by the gene mutations of solute carrier family 12 member 3 gene (SLC12A3). In present study, the urine cells (UCs) of a 7-year-old male GS patient with the homozygote SLC12A3 gene mutation p.T60M (c.179C > T) were reprogrammed into induced pluripotent stem cells (iPSCs) named WMUi021-A through the commercial Sendai virus reprogramming kit. The pluripotent markers OCT4 and SOX2 can be expressed positively in WMUi021-A, which can be differentiated into three germ layers in vitro as well as maintain a stable karyotype (46, XY).

Noonan Syndrome (NS) is an inherited autosome dominant disorder syndrome, which can be caused by the mutations of serine/threonine kinase rapidly accelerated fibrosarcoma 1 (RAF1) gene. Here, an induced pluripotent stem cell (iPSC) line named WMUi022-A derived from urine cells (UCs) of a 9-year-old male NS patient with the heterozygote RAF1 gene mutation p.S257L (c.770C > T) was established through the commercial Sendai virus reprogramming kit. The pluripotent markers like OCT4 and SOX2 can be expressed positively in WMUi022-A, which can be induced into three germ layers in vitro as well as maintain a normal karyotype (46, XY).

Lowe Syndrome (LS) is a rare X-linked multisystemic disorder syndrome, which can be caused by the gene mutations of OCRL. In present study, the urine cells (UCs) derived from a 12-year-old male LS patient with the hemizygote OCRL gene mutation p.M876N (c.2626dupA) were reprogrammed into induced pluripotent stem cells (iPSCs) named WMUi031-A through the commercial Sendai virus reprogramming kit. The pluripotent markers OCT4 and SOX2 can be expressed positively in WMUi031-A, which can be differentiated into three germ layers in vitro as well as maintain a stable karyotype (46, XY).

Bartter Syndrome (BS) is a group of rare inherited autosome-recessive disease, which can be caused by the gene mutations of sodium–potassium-chloride cotransporter gene (SLC12A1). Here, the urine cells (UCs) derived from a 4-year-old female BS patient with the homozygote SLC12A1 gene mutation p.A244D (c.731C>A) were reprogramming into induced pluripotent stem cells (iPSCs) named WMUi019-A using a commercial Sendai virus reprogramming kit. The pluripotent stem cell markers like OCT4 and SSEA4 can be positively expressed in this iPSC line, which can also be induced to differentiate into three germ layers in vitro and maintain a stable karyotype (46, XY).

Antley-Bixler syndrome (ABS) is a rare inherited autosome recessive malformation syndrome, which can be caused by the gene mutations of cytochrome P450 oxidoreductase (POR). In this study, the urine cells (UCs) derived from a 5-year-old female ABS patient with the homozygote POR gene mutation p.R457H (c.1825C>G) were reprogramming into induced pluripotent stem cells (iPSCs) named WMUi018-A using a commercial Sendai virus reprogramming kit. The pluripotent markers of stem cells like OCT4 and SOX2 can be positively expressed in this iPSC line, which can be induced to differentiate into three germ layers in vitro and maintain a stable karyotype (46, XX).

The mutations of polyglutamine binding protein 1 gene (PQBP1) can lead to the rare inherited X-linked Renpenning syndrome (X-RSY). Here, an induced pluripotent stem cell (iPSC) line WMUi017-A was generated through reprogramming the urine cells of a 5-year-old male X-RSY patient with the hemizygous PQBP1 gene mutation p.P609A (c.1825C>G) using the commercial Sendai virus reprogramming system. The established iPSCs can stably express pluripotent stem cell markers OCT4 and NANOG, and can be induced into three germ layers and maintain a normal karyotype (46, XY) in vitro.