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Abstract Triplostegia glandulifera Wall (T. glandulifera) is an ethnomedicine commonly used by ethnic minorities in Yunnan, China, to treat kidney disease. However, there are few reports on the renoprotective effects of this substance, and the active ingredients remain unclear. In this study, we extracted the polysaccharide fractions TGB and TGC using the water extraction-alcohol precipitation method and determined their molecular weight (Mw) and monosaccharide composition. The study investigated the protective effects of TGB and TGC fractions against diabetic nephropathy (DN) using an in vitro high glucose-induced HRMCs model and an in vivo STZ-induced diabetic mouse model. HPLC analysis revealed that TGB contained D-galacturonic acid, D-glucose, D-galactose, and D-arabinose, and had a lower Mw than TGC. In vitro, TGB showed concentration-dependent antioxidant activity and effectively reduced abnormal proliferation and while attenuating oxidative stress in HRMCs. In mice with diabetes, TGB corrected the dysregulation of glucose-lipid metabolism and alleviated oxidative stress in the kidneys. Additionally, it improved renal function and reduced renal tissue damage. The study suggests that the low Mw polysaccharides (TGB) have better activity against DN through the antioxidative stress mechanism. Graphical Abstract

Summary: T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor γ t (RORγt) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORγt impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium. This indicates distinct RORγt roles in central nervous system pathogenesis versus gut-associated protective Th17 responses. Mechanically, RORγt/Runx1-dependent upregulation of galectin-3 (Lgals3) and chemokine receptor Ccr6 in CD4+ T cells is essential for EAE development but not for bacterial clearance. Moreover, Lgals3 is selectively required for recruiting macrophages to produce interleukin (IL)-1β, which in turn promotes Ccr6 expression on CD4+ T cells during EAE pathogenesis. Our findings highlight different RORγt-regulated Th17 pathways in autoimmunity and anti-bacterial immunity, with implications for therapies targeting Th17-mediated autoimmunity while preserving effective anti-bacterial responses.

ObjectiveCiprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures.MethodsThis phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18–65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at −8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain.ResultsA total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, −4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p

Abstract Background The overexpression of ALOX5AP has been observed in many types of cancer and has been identified as an oncogene. However, its role in acute myeloid leukemia (AML) has not been extensively studied. This study aimed to identify the expression and methylation patterns of ALOX5AP in bone marrow (BM) samples of AML patients, and further explore its clinical significance. Methods Eighty-two de novo AML patients and 20 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the alteration of ALOX5AP. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of ALOX5AP expression to discriminate AML. The prognostic value of ALOX5AP was identified by the Kaplan–Meier method and log-rank test. It was further validated in four independent cohorts (n = 1186). Significantly different genes associated with ALOX5AP expression were subsequently compared by LinkedOmics, and Metascape database. Results The level of ALOX5AP expression was significantly increased in bone marrow cells of AML patients compared with healthy donors (P

The Lobster Eye Imager for Astronomy (LEIA) is the pathfinder of the wide-field X-ray telescope used in the Einstein Probe mission. In this study, we present an image of the Virgo Cluster taken by LEIA in the 0.5–4.5 keV band with an exposure time of ∼17.3 ks in the central region. This extended emission is generally consistent with the results obtained by ROSAT. However, the field is affected by bright point sources due to the instrument’s Point Spread Function (PSF) effect. Through fitting of the LEIA spectrum of the Virgo Cluster, we obtained a temperature of 2.1−0.1+0.3 keV, which is consistent with the XMM-Newton results (∼2.3 keV). Above 1.6 keV, the spectrum is dominated by the X-ray background. In summary, this study validates LEIA’s extended source imaging and spectral resolution capabilities for the first time.

Henosepilachna vigintioctomaculata is distributed in several Asian countries. The larvae and adults often cause substantial economic losses to Solanaceae crops such as potato, tomato, eggplant, and Chinese boxthorn. Even though a chromosome-level genome has been documented, the expression profiles of genes involved in development are not determined. In this study, we constructed embryonic, larval, pupal, and adult transcriptomes, generated a comprehensive RNA-sequencing dataset including ~52 Gb of clean data, and identified 602,773,686 cleaned reads and 33,269 unigenes. A total of 18,192 unigenes were successfully annotated against NCBI nonredundant protein sequences, Swissprot, Eukaryotic Orthologous Groups, Gene Ontology (GO), or Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. There were 3580, 2040, 5160, 2496, 3008, and 3895 differentially expressed genes (DEGs) between adult/egg, egg/larval, larval/pupal, adult/pupal, egg/pupal, and adult/larval samples, respectively. GO and KEGG analyses of the DEGs highlighted several critical pathways associated with specific developing stages. This is the first comprehensive transcriptomic dataset encompassing all developmental stages in H. vigintioctomaculata. Our data may facilitate the exploitation of gene targets for pest control and can serve as a valuable gene resource for future molecular investigations.

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence Mycobacterium tuberculosis (Mtb) burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose Mtb-HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD). Firstly, our investigation unveils that Mtb infection triggers severe pulmonary pathology in males, marked by shifts in metabolic signaling involving heightened lipid hydrolysis and proinflammatory signaling driven by IL-6 and localized pro-inflammatory CD8+ cells. This stands in stark contrast to females on a control regular diet (RD). Secondly, our findings indicate that both fat loss and fat gain in males lead to significantly elevated (1.6-fold (p ≤ 0.01) and 1.7-fold (p ≤ 0.001), respectively) Mtb burden in the lungs compared to females during Mtb infection (where fat loss and gain did not alter Mtb load in the lungs). This upsurge is associated with impaired lung lipid metabolism and intensified mitochondrial oxidative phosphorylation-regulated activity in lung CD8+ cells during Mtb infection. Additionally, our research brings to light that females exhibit a more robust systemic IFNγ (p ≤ 0.001) response than males during Mtb infection. This heightened response may either prevent active disease or contribute to latency in females during Mtb infection. In summary, our comprehensive analysis of the interplay between body fat changes and sex bias in Mtb infection reveals that alterations in body fat critically impact pulmonary pathology in males. Specifically, these changes significantly reduce the levels of pulmonary CD8+ T-cells and increase the Mtb burden in the lungs compared to females. The reduction in CD8+ cells in males is linked to an increase in mitochondrial oxidative phosphorylation and a decrease in TNFα, which are essential for CD8+ cell activation.

Objectives: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. Methods: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. Results: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of

Brain cancer: opportunities to block “super-enhanced” tumor growth “Superenhancer” regions within the genome help coordinate the malignant growth of brain tumors, and could offer a target for the development of therapies and prognostic biomarkers. These regions contain a dense accumulation of gene regulatory sequences, which operate in collaboration to establish cellular identity. A review by Jian Qu and colleagues at Central South University, Changsha, China, shows how these regulatory sequences get hijacked in various brain cancers and can facilitate tumor cell proliferation and invasion. Many tumor cells acquire mutations that lead to the formation of superenhancers that are absent in healthy cells. However, this process also offers therapeutic opportunities, and researchers have identified numerous drug candidates that can potentially block tumorigenesis by selectively interfering with superenhancer function. Superenhancer activity could also provide a potentially useful clinical signature for assessing tumor aggressiveness.

Massive low-grade thermal energy and water vapor are stored in the hot and humid airflow of mines, typically resulting in a poor underground working environment and posing threats to worker safety and health. The direct discharge of exhausted ventilation air causes an enormous waste of resources as well as pollution problems to the surrounding environment. Therefore, the extraction and utilization of mine ventilation heat and humidity have become some of the most important ways to solve thermal damage problems in deep mines, thereby boosting their low-carbon transformation development. Affected by the changes in the surface atmospheric and downhole heat and humidity sources, the hot and humid airflow parameters in mines change with time. Real-time determination of the hot and humid airflow characteristics in mines is key to extracting low-grade thermal energy from the underground environment efficiently. In this paper, the distribution law and variation characteristics of key heat and humidity joints are determined based on the real-time calculation of the hot and humid air network. A calculation model of condensation heat and humidity extraction is established, and the technology of low-grade condensation waste heat extraction from heat and humidity airflow is also developed, which, in composition, forms a low-grade heat in situ utilization system combined with refrigeration and dehumidification. Furthermore, the centralized and distributed thermal and humidity extraction and resource utilization methods of coal mine ventilation are put forward. The effects of heat extraction and water recovery are also analyzed using examples. The results show that around 224 t of moisture is wasted every day in ventilation air emission, whose recycling has economic benefits. Thousands of kilowatts of thermal energy are stored in the ventilation air emission, which can be used as direct heat energy or converted electricity. An approximately linear relationship is revealed between the temperature decrease and theoretical moisture recovery from ventilation air emission, providing a rapid way for engineering estimation. The analysis of the heat recovery shows that heat extraction is favored by high initial temperature and humidity due to high values and efficiencies. The application of heat–moisture recovery in underground nodes can effectively moderate the in situ working environment and simultaneously recover some energy as a supply to running costs. This work provides significant construction ideas and a theoretical basis for the extraction and utilization of low-level thermal energy and heat damage control in mines.

Acute myeloid leukaemia (AML) is maintained by self-renewing leukemic stem cells. Here the authors show that Heat Shock Transcription Factor 1 (HSF1) is specifically required for the maintenance of AML stem cells, while sparing steady-state and stressed haematopoiesis and that pharmacologically targeting HSF1 may have broad anti-leukemic effects.

Introduction: In the past decade, super-enhancer (SE) has become a research hotspot with increasing attention on cancer occurrence, development, and prognosis. To illustrate the hotspots of SE in cancer research and its evolutionary tendency, bibliometric analysis was carried out for this topic.Methods: Literature published before Dec 31, 2022, in WOSCC, was systematically classified, and Citespace, bibliometric.com/app, and GraphPad Prism analyzed the data.Results: After screening out inappropriate documents and duplicate data, 911 publications were selected for further bibliometric analysis. The top five research areas were Oncology (257, 28.211%), Cell Biology (210, 23.052%), Biochemistry Molecular Biology (209, 22.942%), Science Technology Other Topics (138, 15.148%), and Genetics Heredity (132, 14.490%). The United States of America (United States) has the highest number of documents (462, 50.71%), followed by China (303, 33.26%). Among the most productive institutions, four of which are from the United States and one from Singapore, the National University of Singapore. Harvard Medical School (7.68%) has the highest percentage of articles. Young, Richard A, with 32 publications, ranks first in the number of articles. The top three authors came from Whitehead Institute for Biomedical Research as a research team. More than two-thirds of the research are supported by the National Institutes of Health of the United States (337, 37.654%) and the United States Department of Health Human Services (337, 37.654%). And “super enhancer” (525), “cell identity” (258), “expression” (223), “cancer” (205), and “transcription factor” (193) account for the top 5 occurrence keywords.Discussion: Since 2013, SE and cancer related publications have shown a rapid growth trend. The United States continues to play a leading role in this field, as the top literature numbers, affiliations, funding agencies, and authors were all from the United States, followed by China and European countries. A high degree of active cooperation is evident among a multitude of countries. The role of SEs in cell identity, gene transcription, expression, and inhibition, as well as the relationship between SEs and TFs, and the selective inhibition of SEs, have received much attention, suggesting that they are hot issues for research.

Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%–65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes.Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC.Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research.Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.

CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity.

Abstract Background Gene expression analysis can provide useful information for analyzing complex biological mechanisms. However, many reported findings are unrepeatable due to small sample sizes relative to a large number of genes and the low signal-to-noise ratios of most gene expression datasets. Results Meta-analysis of multi-data sets is an efficient method for tackling the above problem. To improve the performance of meta-analysis, we propose a novel meta-analysis framework. It consists of two parts: (1) a novel data augmentation strategy. Various cross-platform normalization methods exist, which can preserve original biological information of gene expression datasets from different angles and add different “perturbations” to the dataset. Using such perturbation, we provide a feasible means for gene expression data augmentation; (2) elastic data shared lasso (DSL- $${{\varvec{L}}}_{\mathbf{2}}$$ L 2 ). The DSL- $${\mathbf{L}}_{\mathbf{2}}$$ L 2 method spans the continuum between individual models for each dataset and one model for all datasets. It also overcomes the shortcomings of the data shared lasso method when dealing with highly correlated features. Comprehensive simulation experiment results show that the proposed method has high prediction and gene selection performance. We then apply the proposed method to non-small cell lung cancer (NSCLC) blood gene expression data in order to identify key tumor-related genes. The outcomes of our experiment indicate that the method could be used for identifying a set of robust disease-related gene signatures that may be used for NSCLC early diagnosis or prognosis or even targeting. Conclusion We propose a novel and effective meta-analysis method for biological research, extrapolating and integrating information from multiple gene expression datasets.

Abstract Objective To evaluate the value of ultrasound-based radiomics in the preoperative prediction of type I and type II epithelial ovarian cancer. Methods A total of 154 patients with epithelial ovarian cancer were enrolled retrospectively. There were 102 unilateral lesions and 52 bilateral lesions among a total of 206 lesions. The data for the 206 lesions were randomly divided into a training set (53 type I + 71 type II) and a test set (36 type I + 46 type II) by random sampling. ITK-SNAP software was used to manually outline the boundary of the tumor, that is, the region of interest, and 4976 features were extracted. The quantitative expression values of the radiomics features were normalized by the Z-score method, and the 7 features with the most differences were screened by using the Lasso regression tenfold cross-validation method. The radiomics model was established by logistic regression. The training set was used to construct the model, and the test set was used to evaluate the predictive efficiency of the model. On the basis of multifactor logistic regression analysis, combined with the radiomics score of each patient, a comprehensive prediction model was established, the nomogram was drawn, and the prediction effect was evaluated by analyzing the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. Results The AUCs of the training set and test set in the radiomics model and comprehensive model were 0.817 and 0.731 and 0.982 and 0.886, respectively. The calibration curve showed that the two models were in good agreement. The clinical decision curve showed that both methods had good clinical practicability. Conclusion The radiomics model based on ultrasound images has a good predictive effect for the preoperative differential diagnosis of type I and type II epithelial ovarian cancer. The comprehensive model has higher prediction efficiency.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life.Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1β, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated.Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21–3.01), significantly higher than in the MTX group 2.06 (1.81–2.32), p < 0.0001), and the median (IQR) β-CTX in the JBQG group was 0.4 (0.32–0.43), significantly lower than in the MTX group 0.55 (0.47–0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1–3), a decrease from 3 (2–4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1–2), a decrease from 2 (1–2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8–16), significantly lower than in the MTX group 26 (16–30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12–20), with a significant difference compared to the MTX group 19 (13–25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10–18), with a significant difference compared to the MTX group 16 (11–22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05).Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.