Quan Zhuang

Organ transplantation is an indispensable therapeutic approach for patients experiencing end-stage organ failure. Despite ongoing advancements and refineme

Lysine acetyltransferase 2A (KAT2A) has been reported to modulate gene expression through acetylation on specific histone lysines. Previous research has shown that continuous inflammation promotes lupus nephritis renal damage. Our previous study has shown that KAT2A to exerts its pro-inflammatory role on this process by regulating the cyclic GMP-AMP synthase (cGAS) in immune cells. However, the underlying mechanism that KAT2A regulates cGAS expression and activation is still obscure and worth to be elucidated. Immunofluorescence was conducted to localize KAT2A primarily in the renal tubular interstitial regions of lupus nephritis (LN) tissues. Dual luciferase reporter assays and ChIP-qPCR were performed to investigate KAT2A's regulatory effects on the cGAS promoter. Additionally, we assessed the acetylation of specific lysine residues (K171, K279, and K439) on the cGAS peptide by CoIP and western blot and evaluated their impact on cGAS function. ChIP-seq was also used to localize KAT2A on severl other genes besides cGAS. Our in vitro studies demonstrated that KAT2A negatively regulates the cGAS promoter within a specific region and acetylates the K279 residue on cGAS peptide, which in turn negatively affects cGAS function. However, in vivo studies using the MRL/lpr lupus mouse model revealed that the KAT2A inhibitor MB-3 had a protective effect, significantly improving proteinuria and survival time. Given the differences between in vitro and in vivo environments, it is possible that KAT2A regulates additional molecules and signaling pathways besides cGAS. ChIP-seq analysis suggested that KAT2A may also bind to the promoter of three prime repair exonuclease 2 (TREX2), which could indirectly enhance cGAS expression. In summary, our research indicates that KAT2A negatively regulates cGAS expression and function at both transcriptional and post-translational levels in vitro. However, KAT2A exhibits a pro-inflammatory effect in a lupus mouse model, possibly due to its regulation of molecules other than cGAS. KEY MESSAGES: Lysine acetyltransferase 2A (KAT2A) negatively affects cGAS expression and function in vitro; KAT2A negatively regulates the cGAS promoter within a specific region and acetylates the K279 residue on cGAS peptide; ChIP-seq analysis suggested that KAT2A may also bind to the promoter of three prime repair exonuclease 2 (TREX2); KAT2A inhibitor MB-3 had a protective effect in MRL/lpr lupus mouse model, significantly improving proteinuria and survival time.

This study examines the extensive incidence of microplastics (MPs) within freshwater and Marine ecosystems, characterizing their distribution, composition, and potential health implications for immunosuppressed populations. Utilizing an extensive dataset curated through collaboration with global stakeholders, we systematically analyzed microplastic concentrations and types in various aquatic environments, correlating findings with prevailing environmental parameters such as temperature and turbidity. Our results indicate a pronounced presence of MPs in both Fresh water and Marine Water, with distinct variations. Freshwater ecosystems predominantly exhibited microplastics originating from urban wastewater and recreational activities, demonstrating higher concentrations of fragments and fibers indicative of local anthropogenic influences. In contrast, Marine environments showcased a more diverse spectrum of microplastic morphologies, including debris from larger plastic aggregates and microbeads, facilitated by extensive oceanic dispersal mechanisms. The analysis revealed significant bioaccumulation potential of these contaminants within aquatic organisms, raising concerns regarding food chain transfer and subsequent exposure risks to humans, particularly immunocompromised individuals. Pathological assessments suggest that MPs may exacerbate pre-existing health vulnerabilities by serving as vectors for harmful substances, including endocrine-disrupting chemicals, thus posing increased risks of impaired immune responsiveness and chronic inflammatory conditions. Given these findings, our research underscores the urgency for more rigorous monitoring protocols and public health strategies aimed at mitigating microplastic pollution and protecting at-risk populations. Thus, this investigation not only contributes to the growing body of knowledge regarding microplastic dynamics in aquatic ecosystems but also emphasizes the critical necessity for a multidisciplinary approach to address the intricate relationship between environmental contaminants and human health outcomes.

Organ transplantation is an indispensable therapeutic approach for patients experiencing end-stage organ failure. Despite ongoing advancements and refinements in immunosuppressive therapies aimed at mitigating graft rejection and enhancing graft longevity, environmental influences including particulate matter 2.5 (PM2.5) have emerged as significant determinants of post-transplant health. PM2.5, a prevalent environmental contaminant, is particularly concerning due to its widespread presence and detrimental biological effects. Notably, the living environment of transplant recipients further exacerbates the complexity of post-transplant outcomes. Evaluating findings from recent investigations, this review delves into the influence of PM2.5 exposure on the immune system. The findings identify its capacity to provoke systemic inflammation, disrupt cytokine profiles, and compromise immune tolerance mechanisms. Such immune dysfunction poses direct risks to graft integrity, with potential implications for both graft health and the prospects of achieving long-term graft survival in affected patients.

Kidney transplantation constitutes a pivotal intervention for patients experiencing end-stage renal disease (ESRD), offering significant enhancements in quality of life and longevity relative to dialysis. However, the residual prevalence of erectile dysfunction (ED) in male recipients, affecting approximately 20-50%, signals a pressing concern in post-transplant health management. This review investigates the intricate interplay between hormonal fluctuations, specifically testosterone and thyroid hormones, and the psychosocial dynamics encompassing anxiety, depression, and overall quality of life in this demographic. It explores the multifaceted etiologies of ED, encompassing neurovascular, hormonal, and psychological dimensions that converge post-transplant. Further, the review critically examines current therapeutic strategies, emphasizing an integrated, multidisciplinary approach that simultaneously addresses hormonal disruptions, psychosocial factors, and metabolic disturbances. The primary objective is to bridge the existing knowledge gap regarding the pre- and post-transplant experiences of ED among male patients, thereby informing clinical practices aimed at optimizing sexual health outcomes and enhancing the overall well-being of kidney transplant recipients. Through rigorous evaluation of contemporary studies, this work underscores the necessity for comprehensive interventions that prioritize both physiological and psychological health in addressing ED within this vulnerable population.

Antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and destruction of small blood vessels. AAV could be fatal if left untreated. Prompt diagnosis and treatment are crucial to protect AAV‐related organs and tissue. Plasmapheresis, a therapeutic intervention aimed at removing harmful substances from the blood, devotes benefits to AAV treatment. However, the specific immune mechanism underlying its effectiveness remains unclear. In our research, we used single‐cell RNA sequencing (scRNA‐seq) to study the variation of peripheral blood mononuclear cells (PBMCs) before and after plasmapheresis in AAV patients. From this work, we explored a novel method for monocyte classification. In addition, flow cytometry was used to detect the relationship between the monocyte clusters and AAV activity under the new monocyte clustering method. Our scRNA‐seq results revealed significant changes in monocyte clusters following treatment, which could be classified into three clusters (CD14+ monocytes, FCGR1A+ monocytes, and FCGR3A+ monocytes). In addition, our flow cytometry results showed that FCGR3A+ (CD16+) monocytes were positively correlated with AAV activity, whereas FCGR1A+ (CD16‐CD64+) monocytes were negatively correlated with AAV activity. This may be related to the different biological effects of CD16 and CD64 on monocytes after interacting with the Fc region of ANCAs. In conclusion, our research sheds light on the immune landscape of AAV before and after plasmapheresis, identifying specific monocyte clusters linked to disease activity. These findings offer insights for novel monitoring methods and therapeutic targets in AAV.