Immunotherapy following transplantation has long been a central focus in both anti-rejection strategies and the induction of immune tolerance. Regulatory B cells (Bregs) can directly suppress the immune system via the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Additionally, Bregs exert indirect immunosuppressive effects through the secretion of cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and granzyme B (GrB), among which IL-10 plays a particularly critical role. This review summarizes recent progress in the classification, functional characteristics, and activation mechanisms of Bregs, as well as their potential applications in transplantation immunotherapy, aiming to provide a theoretical foundation for Breg-targeted strategies in transplant immune modulation.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Immunotherapy following transplantation has long been a central focus in both anti-rejection strategies and the induction of immune tolerance. Regulatory B cells (Bregs) can directly suppress the immune system via the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Additionally, Bregs exert indirect immunosuppressive effects through the secretion of cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and granzyme B (GrB), among which IL-10 plays a particularly critical role. This review summarizes recent progress in the classification, functional characteristics, and activation mechanisms of Bregs, as well as their potential applications in transplantation immunotherapy, aiming to provide a theoretical foundation for Breg-targeted strategies in transplant immune modulation.

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Objective To discuss the clinical application of coronary CT angiography(CCTA)-derived fractional flow reserve(CT-FFR)in evaluating the risk stratification of the coronary artery stenosis and atherosclerotic plaque quantitative parameters.Methods A total of 122 patients,who received CCTA examination at the Xuzhou Municipal Central Hospital of China,were enrolled in this study.The patients were divided into non-ischemia group(CT-FFR＞0.8,n=66)and ischemia group(CT-FFR0.8,n=56).The characteristics of atherosclerotic plaque were compared between the two groups.Logistic regression analysis was used to analyze the correlation between plaque characteristics and ischemic lesions.Results There were 218 vessels having a CT-FFR＞0.8 and 174 vessels having a CT-FFR ≤0.8.Statistically significant differences in the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％existed between the two groups(all P＜0.05).Logistic regression analysis indicated that the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％were the risk factors for myocardial ischemia.Conclusion CT-FFR can be used for the risk stratification of coronary stenosis and atherosclerotic plaque characteristics,which can evaluate the local myocardial blood supply condition from the anatomical stenosis and functional level so as to optimize the diagnosis and treatment measures.

Liver cancer ranks as the sixth most common cancer globally,with hepatocellular carcinoma(HCC)accounting for approximately 75％-85％of cases.Most patients present with moderately advanced disease,while those with advanced HCC face limited and ineffective treatment options.Despite diagnostic efforts,no ideal tumor marker exists to date,highlighting the urgent clinical need for improved early detection of HCC.A key research objective is the development of assays that target specific pathways involved in HCC progression.This review explores the pathological origin and development of HCC,providing insights into the mechanistic rationale,clinical statistics,and the advantages and limitations of commonly used diagnostic tumor markers.Additionally,it discusses the potential of emerging biomarkers for early diagnosis and offers a brief overview of relevant assay methodologies.This review aims to summarize existing markers and investigate new ones,providing a basis for subsequent research.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

Objective:To investigate the effects of 30% ethanol elution fraction of Artemisia absinthium extract with macroporous resin (AAEM-30%) on the dendritic cell (DC) and immunity of mice. Methods:AAEM-30% was obtained from the alcoholic extracts of A. absinthium by AB-8 macroporous resin, and its polysaccharide, flavonoid, and terpenoid contents were determined. The expressions of AAEM-30% on DC surface molecular cluster of differentiation (CD) 40, CD80 and CD86 were detected in vitro by flow cytometry, and the expressions of DC cytokines IL-6 and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The effect of AAEM-30% on the immune function of ICR mice was measured in vivo with different doses (50 and 100 mg/kg) and different administration methods (subcutaneous injection, intraperitoneal injection, and gavage). Results:The contents of polysaccharides, flavonoids, and terpenoids in AAEM-30% were 24.30%, 22.50% and 28.19%, respectively. AAEM-30% significantly enhanced the expression of CD40, and CD86 and the secretion of IL-6 and TNF-α (all P<0.001). Compared with the control group, no statistically significant differences were found in the body mass of mice compared with the three administration methods (all P>0.05). The thymus index in the 50 and 100 mg/kg AAEM-30% intraperitoneal injection groups and the spleen index in the 50 mg/kg AAEM-30% gavage group were increased (all P<0.05). CD19 + cells increased in the 100 mg/kg AAEM-30% intraperitoneal injection group ( P<0.01) and in the 50 mg/kg AAEM-30% gavage group ( P<0.05). The CD11b + and CD11c + counts increased in the 100 mg/kg AAEM-30% gavage group ( P<0.05). The number of CD4 + and CD8 + T lymphocytes was increased by both gavage and intraperitoneal administration (all P<0.05). Conclusions:AAEM-30% can promote the maturation of DC and enhanced the immunity of mice without obvious side effects.