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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.

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration‐resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron‐dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate‐specific membrane antigen (PSMA)‐targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane‐coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M‐gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA‐specific, CRPC‐targeting platform for ferroptosis induction with increased efficacy and safety. [ABSTRACT FROM AUTHOR]

Selective producing ethanol from CO2 electroreduction is highly demanded, yet the competing ethylene generation route is commonly more thermodynamically preferred. Herein, we reported an efficient CO2‐to‐ethanol conversion (53.5 % faradaic efficiency at −0.75 V versus reversible hydrogen electrode (vs. RHE)) over an oxide‐derived nanocubic catalyst featured with abundant "embossment‐like" structured grain‐boundaries. The catalyst also attains a 23.2 % energy efficiency to ethanol within a flow cell reactor. In situ spectroscopy and electrochemical analysis identified that these dualphase Cu(I) and Cu(0) sites stabilized by grain‐boundaries are very robust over the operating potential window, which maintains a high concentration of co‐adsorbed *CO and hydroxyl (*OH) species. Theoretical calculations revealed that the presence of *OHad not only promote the easier dimerization of *CO to form *OCCO (ΔG~0.20 eV) at low overpotentials but also preferentially favor the key *CHCOH intermediate hydrogenation to *CHCHOH (ethanol pathway) while suppressing its dehydration to *CCH (ethylene pathway), which is believed to determine the remarkable ethanol selectivity. Such imperative intermediates associated with the bifurcation pathway were directly distinguished by isotope labelling in situ infrared spectroscopy. Our work promotes the understanding of bifurcating mechanism of CO2ER‐to‐hydrocarbons more deeply, providing a feasible strategy for the design of efficient ethanol‐targeted catalysts. [ABSTRACT FROM AUTHOR]

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Purpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear. Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results. Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell–cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor–ligand pair. Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD. [ABSTRACT FROM AUTHOR]