A novel immunogenic cell death-related gene risk signature can identify biomarkers of gliomas and predict the immunotherapeutic response.

Immunogenic cell death (ICD) is a type of cell death that plays a pivotal role in immunity. Recent studies have identified the critical role of ICD in glioma treatment. This study aimed to use ICD-associated differentially expressed genes (ICD-DEGs) to predict survival of glioma patients. We investigated the relationship between clinical prognosis and the date-to-clinical prognosis of 1,721 glioma patients by examining the expression, methylation, and mutation status of ICD-related genes (IRGs) in these patients. Our prediction of survival in glioma patients was based on three risk genes, and we explored the association between these genes and clinical outcomes. Additionally, IRG expression was used to stratify glioma patients. We further examined the relationship among the three subgroups in terms of immune microenvironment heterogeneity and immunotherapy response. In addition, this study also included analyses of histograms and sensitivity to antitumor drugs. The expression of these genes was externally validated by RT-qPCR, Western blot (WB), and immunohistochemistry (IHC) in glioma and normal brain tissue. Our findings reveal that most IRGs are overexpressed in glioma tumor tissues, and this high expression was confirmed through histological validation. We successfully developed predictive models for three prognostic genes associated with ICD. These models not only predict survival in glioma but also correlate with the tumor's immune microenvironment. Finally, using consensus clustering, we identified three ICD-associated subtypes. Notably, patients with the C3 subtype showed high levels of immune cell infiltration, whereas those with the C1 subtype exhibited lower levels of immune cell infiltration. We successfully developed an innovative IRG-based systematic approach for evaluating glioma patients. This stratification in experimental studies opens new avenues for prognosis and assessing immunotherapy responses in glioma patients. Our study demonstrates the effectiveness of this approach in treating glioma, potentially paving the way for more promising and effective therapeutic strategies in the future.

Bifunctional Iminophosphorane Catalyzed Amide Enolization for Enantioselective Cyclohexadienone Desymmetrization.

The organocatalytic enolization of 2-arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5-cyclohexadienones, yielding 3D fused N-heterocycles, is described. The transformation represents the first strong activating group-free activation of carboxamides via α-C-H deprotonation in a metal-free, catalytic, and enantioselective reaction, and is achieved by employing a bifunctional iminophosphorane (BIMP) superbase.

Effect of exoskeleton robot-assisted training on gait function in chronic stroke survivors: a systematic review of randomised controlled trials.

OBJECTIVES: Numbers of research have reported the usage of robot-assisted gait training for walking restoration post-stroke. However, no consistent conclusion has been reached yet about the efficacy of exoskeleton robot-assisted training (ERAT) on gait function of stroke survivors, especially during the chronic period. We conducted a systematic review to investigate the efficacy of ERAT on gait function for chronic stroke survivors. DESIGN: This review followed the Participant, Intervention, Comparison and Outcome principle. DATA SOURCES: PubMed, Cochrane Library, Web of Science, Embase and Cumulative Index to Nursing and Allied Health Literature databases were systematically searched until December 2022. ELIGIBILITY CRITERIA: Only randomised controlled trials (RCTs) were included and these RCTs took patients who had a chronic stroke as participants, exoskeleton robot-assisted gait training as intervention, regular rehabilitation therapy as comparison and gait-related functional assessments as outcomes. DATA EXTRACTION AND SYNTHESIS: Data extraction and synthesis used the reporting checklist for systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The risk of bias and methodological quality of included studies were evaluated by two independent investigators under the guidance of Cochrane risk of bias. RESULTS: Out of 278 studies, a total of 10 studies (n=323, mean age 57.6 years, 63.2% males) were identified in this systematic review. According to the Cochrane risk of bias, the quality of these studies was assessed as low risk. Six studies reported favourable effects of ERAT on gait function involving gait performance, balance function and physical endurance, and the ERAT group was significantly superior when compared with the control group. In contrast, the other four trials showed equal or negative effects of ERAT considering different study designs. All the included studies did not claim any serious adverse events. CONCLUSION: ERAT could be an efficient intervention to improve gait function for individuals who had a chronic stroke. However, more rigorously designed trials are required to draw more solid evidence. PROSPERO REGISTRATION NUMBER: CRD42023410796.

Exosomal PD-L1 derived from head and neck squamous cell carcinoma promotes immune evasion by activating the positive feedback loop of activated regulatory T cell-M2 macrophage.

The positive feedback loop of activated regulatory T cells (aTregs) and M2 macrophages (M2) play a vital role in promoting the tumor immunosuppressive microenvironment of head and neck squamous cell carcinoma (HNSCC). However, the key factors regulating the positive feedback loop remain unclear. Herein, we investigated the effect of PD-L1 carried on exosomes derived from tumor cells (TEXs) on the aTreg-M2 positive feedback loop, as well as their role in mediating immunosuppression. In our study, TEXs with or without PD-L1 (TEX-PD-L1 or TEX-PD-L1KO) were treated with CD4+CD25- T cells and M0 macrophages, and the effect on the differentiation of aTregs, M2 and the aTreg-M2 positive feedback loop was assessed. TEXs carried more PD-L1 than tumor cells and not only promoted the differentiation of aTregs and M2, but also, most importantly, enhanced the positive feedback loop of aTreg-M2, which inhibited the proliferation of CD4+CD25- T cells and in turn led to tumor immune escape. Moreover, in vivo study showed that TEX-PD-L1KO could inhibit tumor growth and significantly improve the antitumor efficacy in both the peripheral and tumor microenvironments. Collectively this study revealed the role and mechanism of TEX-PD-L1 in negative immune regulation, and targeting TEX-PD-L1 may be a new idea and strategy for immunotherapy of HNSCC.

Hydrochemical characterization and quality assessment of groundwater in the hilly area of the Taihang Mountains in Henan Province, China.

This study evaluated the quality of groundwater and its suitability for drinking and irrigation in the hilly area of the Taihang Mountains in Henan Province, China. Groundwater samples were collected from 43 unconfined and 20 confined wells and analyzed. The pollution index of groundwater (PIG) was estimated based on the physicochemical parameters, and seven indices, including the sodium adsorption ratio (SAR), sodium percentage (%Na), residual sodium carbonate (RSC), permeability index (PI), magnesium ratio (MR), Kelley's ratio (KR), and corrosivity ratio (CR), were calculated to qualify the groundwater within the research area for irrigation activities. Multivariate statistical techniques were performed to better understand the hydrochemical processes. Chemical analysis showed that the dominant cation and anion were Ca2+ and HCO3-, respectively, and the principal hydrochemical facies was Ca-Mg-HCO3. In terms of pH, total dissolved solids, Na+, Cl-, F-, and SO42-, most samples were well within the limits prescribed by Chinese standards for drinking water quality, but more than half of the unconfined samples exceeded the specified limits for total hardness and nitrate. The PIG values suggested the pollution level was insignificant for all confined water samples and 72.09% of unconfined water samples, but the PIG distribution map showed that the water in the south central part of the study area had low to moderate pollution. According to the computed values of SAR, %Na, RSC, PI, KR, and MR and the results of a salinity diagram, the results further indicated that most of the studied samples were appropriate for irrigation usage. Only the CR values rendered 41.86% of the unconfined samples and 20% of the confined samples unfit for irrigation. Hence, proper measures are needed to resolve the corrosivity problem. Factor analysis resulted in the extraction of 3 factors that explained 81% of the data variability, and the extracted factors pointed towards geogenic factors governing the groundwater quality.

The effectiveness of low intensity exercise and blood flow restriction without exercise on exercise induced muscle damage: A systematic review.

OBJECTIVE: To investigate the evidence and provide clinical recommendations for low intensity exercises(LIE) and blood flow restriction(BFR) without exercise on reducing the effects of exercise induced muscle damage(EIMD). METHOD: PubMed, Embase, Web of science, and PEDro(Physiotherapy Evidence Database) were searched up to December 2019 for studies that included LIE or BFR without exercise and their effect on EIMD. RESULTS: Out of 3192 studies, 23 were included with 17 on LIE and 6 on BFR without exercise. 11 studies demonstrated positive effects for LIE on EIMD, with two level 2 and nine level 3 studies. Two level 2 and two level 3 studies found benefits for BFR without exercise on reducing the negative effects of EIMD, while two level 2 studies found did not find benefits for BFR without exercise. CONCLUSION: Moderate to low levels of evidence supported LIE, particularly in the form of protective low load eccentric exercise, in reducing the negative effects of EIMD. Conflicting moderate to low levels of evidence was found regarding BFR without exercise. There does seem to be potential benefit for BFR without exercise in untrained individuals. Clinicians can provide clinical recommendations as LIE and BFR without exercise reducing EIMD.

A billion cups: The diversity, traditional uses, safety issues and potential of Chinese herbal teas.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal teas have long been consumed by Chinese people for preventive and/or therapeutic healthcare. Although herbal teas are widely consumed by many cultural groups in different regions of China, no thorough review has been undertaken to assess the diversity of the country's herbal tea usage. This literature review, complemented by a quantitative survey in an important tea market in Kunming, begins to fill this knowledge gap. AIMS OF THE STUDY: The study aims to summarize the current knowledge of plant species used as herbal teas by different cultural groups in different regions of China, with a focus on the teas' perceived traditional healthcare functions, related phytochemical/pharmaceutical research, and safety issues. MATERIALS AND METHODS: The study involved a comprehensive literature review and a market survey. The literature review was based on published ethnobotanical studies of herbal teas in China. We searched the Web of Science™, ELSEVIER, the China National Knowledge Infrastructure (CNKI) and the China Science and Technology Journal Database to locate relevant studies (including journal articles, Masters/PhD dissertations and books) that were published before March 2017. A species list was compiled based on the review and supplemented with information retrieved from the Scifinder database (https://scifinder.cas.org) and the Chinese Pharmacopoeia (2010). A Use Value Index was employed for ranking the most cited species. Based on the 29 most cited species, we discussed the current research status in relation to healthcare benefits and safety concerns of herbal teas in China. To better understand the current status of the herbal tea market in China, we also surveyed 136 tea vendors at the Xiongda Tea Market in Kunming. Information gathered from the survey included the species sold, the sale prices and the form of the herbal tea product. RESULTS: The literature identified 759 plant species used as herbal tea in China and the market survey identified an additional 23 species. Most of the species used were from the Leguminosae, Compositae and Lamiaceae families. Twenty two provinces and fourteen ethnic minority groups have records on the consumption of herbal teas. Southern China uses up to 82% of the total species, and 211 out of 759 species are used by minority groups. Thirty categories of traditional healthcare functions are linked with herbal teas, with clearing away heat, relieving toxicity and suppressing cough being the most important functions. There is phytochemical/pharmaceutical evidence to support the claimed healthcare benefits of some Chinese herbal teas. Although Chinese herbal teas are generally safe to consume, overdoses of some herbal teas and some unapproved mixtures of species may cause health risks. Based on our market survey, the prices of most herbal teas range between 100 and 200 RMB (US$15-30) per kg. CONCLUSIONS: A rich array of herbal tea species with various traditional healthcare functions have long been used in China, and as such there is a huge market potential for Chinese herbal teas. More pharmaceutical/phytochemical research is needed to assess a wide range of perceived healthcare benefits of Chinese herbal teas. Our research highlights the need to study herbal teas through an ethnopharmacological perspective and by employing a holistic approach, which requires greater consideration of traditional knowledge in the pharmacological research design. Product safety and sustainability issues should also be considered, so the traditional applications of herbal teas can be transformed to efficient health boosting functional products.

Enantioselective bifunctional iminophosphorane catalyzed sulfa-Michael addition of alkyl thiols to unactivated ß-substituted-α,ß-unsaturated esters.

The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated ß-substituted-α,ß-unsaturated esters catalyzed by a bifunctional iminophosphorane (BIMP) organocatalyst is described. The low acidity of the alkyl thiol pro-nucleophiles is overcome by the high Brønsted basicity of the catalyst and the chiral scaffold/thiourea hydrogen-bond donor moiety provides the required enantiofacial discrimination in the addition step. The reaction is broad in scope with respect to the alkyl thiol and ß-substituent of the α,ß-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivity (up to 97 : 3 er) and can operate down to 1 mol% catalyst loading.