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Background Oxidative stress and energy metabolism are important factors that affect sperm quality in male individuals. However, the majority of available studies are based on animal models, and evidence from human studies is still inadequate. Besides, most previous studies have paid more attention to the effects of oxidative stress and energy metabolism on sperm concentration and motility, with a little focus on their impact on sperm motility velocity and trajectory and other specific objective indicators evaluating the state of male infertility. Objective To investigate the effects of biological indicators related to oxidative stress and energy metabolism on sperm concentration, motility, movement velocity and trajectory in male adults, thus to provide epidemiological evidence for precise intervention of male reproductive health problems. Methods One hundred and nine volunteers were recruited as subjects from the Center of Reproductive Medicine in Xijing Hospital, Air Force Medical University from June to December 2021. Their semen samples were collected. The computer-assisted sperm analysis system was applied to detect sperm concentration parameters (sperm concentration, linear motion sperm concentration), sperm motility〔total sperm motility, progressive motility (PR), non-progressive motility (NP) 〕, sperm motility velocity parameters〔curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP) 〕 and sperm motility trajectory parameters 〔mean amplitude of lateral head displacement (ALH), mean beat-cross frequency (BCF), mean angular displacement (MAD), linearity coefficient (LIN), wobble coefficient (WOB), straightness coefficient (STR) 〕. Besides that, the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in semen samples were measured as oxidative stress markers, and the level of sperm adenosine triphosphate (ATP) was measured to assess the level of energy metabolism. General linear model (GLM) was used to evaluate the correlation of MDA and GSH and ATP with sperm quality parameters. Results A total of 67 sperm samples were used to examine oxidative stress level, and 42 sperm samples were employed to assess the level of energy metabolism. The analysis using the GLM demonstrated that in terms of oxidative stress level, MDA level was negatively correlated with linear motion sperm concentration, total sperm motility, PR, NP, VCL, VSL, VAP, ALH, BCF, MAD, LIN, WOB, and STR (P

Chimeric antigen receptor T cell (CAR-T) is a kind of adoptive cell immunotherapy, in which T cells are genetically modified to exert targeted killing effect on tumors. CAR-T cell therapy has shown remarkable antitumor efficacy for the treatment of tumors, especially for hematological malignancies, but is less effective in solid tumors. Single-target CAR-T is prone to off-target effect during application, and there is a risk of relapse or more refractory treatment. The development of double-target or multi-target CAR-T is expected to extend the antigen coverage of target cells, effectively avoids antigen escape and prevents tumor recurrence, and prolongs the survival time of patients. This article reviews the advances of multi-target chimeric antigen receptor T cell, and discusses the prospect of its development.

Background: Immune checkpoint blockade (ICB) therapy can be effective against clear cell renal cell carcinoma (ccRCC), but many patients show no benefit. Tumor-derived pericytes (TDPs) may promote tumor progression by influencing T cells and are an immunotherapy target; however, they may comprise functionally distinct subtypes. We aimed to identify markers of tumor-promoting TDPs and develop TDP-targeting strategies to enhance ICB therapy effectiveness against ccRCC. Methods: We analyzed the relationship between endosialin (EN) expression and cytotoxic T-lymphocyte (CTL) infiltration in ccRCC tumor samples using flow cytometry and in a ccRCC-bearing mice inhibited for EN via knockout or antibody-mediated blockade. The function of ENhigh TDPs in CTL infiltration and tumor progression was analyzed using RNA-sequencing (RNA-seq) data from ccRCC tissue-derived TDPs and single-cell RNA-seq (scRNA-seq) data from an online database. The role of EN in TDP proliferation and migration and in CTL infiltration was examined in vitro. Finally, we examined the anti-tumor effect of combined anti-EN and anti-programmed death 1 (PD-1) antibodies in ccRCC-bearing mice. Results: High EN expression was associated with low CTL infiltration in ccRCC tissues, and inhibition of EN significantly increased CTL infiltration in ccRCC-bearing mice. RNA-seq and scRNA-seq analyses indicated that high EN expression represented the TDP activation state. EN promoted TDP proliferation and migration and impeded CTL infiltration in vitro. Finally, combined treatment with anti-EN and anti-PD-1 antibodies synergistically enhanced anti-tumor efficacy. Conclusion: ENhigh TDPs are in an activated state and inhibit CTL infiltration into ccRCC tissues. Combined treatment with anti-EN and anti-PD-1 antibodies may improve ICB therapy effectiveness against ccRCC. [ABSTRACT FROM AUTHOR]