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Islet transplantation is a promising therapy for diabetes treatment. However, the molecular underpinnings governing the immune response, particularly T-cell dynamics in syngeneic and allogeneic transplant settings, remain poorly understood. Understanding these T cell dynamics is crucial for enhancing graft acceptance and managing diabetes treatment more effectively. This study aimed to elucidate the molecular mechanisms, gene expression differences, biological pathway alterations, and intercellular communication patterns among T-cell subpopulations after syngeneic and allogeneic islet transplantation. Using single-cell RNA sequencing, we analyzed cellular heterogeneity and gene expression profiles using the Seurat package for quality control and dimensionality reduction through t-SNE. Differentially expressed genes (DEGs) were analyzed among different T cell subtypes. GSEA was conducted utilizing the HALLMARK gene sets from MSigDB, while CellChat was used to infer and visualize cell-cell communication networks. Our findings revealed genetic variations within T-cell subpopulations between syngeneic and allogeneic islet transplants. We identified significant DEGs across these conditions, highlighting molecular discrepancies that may underpin rejection or other immune responses. GSEA indicated activation of the interferon-alpha response in memory T cells and suppression in CD4+ helper and γδ T cells, whereas TNFα signaling via NFκB was particularly active in regulatory T cells, γδ T cells, proliferating T cells, and activated CD8+ T cells. CellChat analysis revealed complex communication patterns within T-cell subsets, notably between proliferating T cells and activated CD8+ T cells. In conclusion, our study provides a comprehensive molecular landscape of T-cell diversity in islet transplantation. The insights into specific gene upregulation in xenotransplants suggest potential targets for improving graft tolerance. The differential pathway activation across T-cell subsets underscores their distinct roles in immune responses posttransplantation.

Abstract Blockchain and blockchain‐based decentralised applications have been attracting increasing attention recently. In public blockchain systems, users usually connect to third‐party peers or run a peer to join the P2P blockchain network. However, connecting to unreliable blockchain peers will lead to resource waste and even loss of cryptocurrencies by repeated transactions. In order to select reliable blockchain peers, it is urgently needed to evaluate and predict their reliability of them. Faced with this problem, we propose hybrid blockchain reliability prediction (H‐BRP), a Hybrid Blockchain Reliability Prediction model, to extract the blockchain reliability factors and then make the personalised prediction for each user. Comprehensive experiments conducted on 100 blockchain requesters and 200 blockchain peers demonstrate the effectiveness of the proposed H‐BRP model. Further, the implementation and dataset of 2,000,000 test cases are released.

Blockchain-based decentralized applications (DApp) draw more attention with the increasing development and wide application of blockchain technologies. A wealth of funds are invested into the crowd-funding of various types of DApp. As reported in August 2022, there are more than 5,000 DApps with more than 1.67 million daily Unique Active Wallets (users). However, the definition, architectures, and classifications of the DApps are still not cleared up till now. This survey aims to provide a comprehensive overview of DApps for further research. First, the definitions and typical architectures of DApps are presented. Then we collect 3,118 popular DApps and categorize them into different types, and summarize their typical advantages and challenges. Finally, we provide an overview of the recent research problems of DApps from the perspectives of economics, security, and performance and then figure out promising research opportunities in the future.

CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency caused T cell-dependent wasting disease driven by chronic gut immune dysregulation. CD5 inhibition also exacerbated acute experimental colitis. Mechanistically, loss of CD5 increased phospho-Stat3 levels, leading to elevated IL-17A secretion. Our data reveal a new facet of CD5 function in shaping the T cell cytokine profile.

Tree is an essential factor affecting airflow and pollutant diffusion in the urban street canyon. The wind environment in the urban street canyon will be effectively improved by expounding the mechanism and implementing greening measures. Moreover, it will help decrease the pollutant concentration around the street canyon. This paper reviews the airflow and pollutant diffusion numerical simulation in the street canyon under the tree influence. Firstly, the numerical mathematical model used for pollutant diffusion and airflow in urban street canyons under the influence of trees is summarized. The representation of trees’ numerical mathematical model in the simulation domain is mainly proposed. Secondly, the wind environment and pollutant distribution factors influencing urban street canyons are elaborated and analyzed, including tree characteristics, layout, street canyon shape, and thermal. Furthermore, current research progress and deficiencies are discussed. Finally, the future research direction of wind environment and pollutant distribution simulation in urban streets under the influence of trees is pointed out.

Abstract Background This study aimed to determine the effect of PKM2 knockout in STZ induced type 1 diabetes mellitus (T1D) mouse models and to explore the possible mechanism. Method PKM2fl/fl C57BL/6 mouse was backcrossed with Ins‐1cre C57BL/6 mouse to generate β‐cell‐specific PKM2 knockout mouse after tamoxifen administration. The expression level of PKM2 in pancreas tissues was detected by quantitative reverse‐transcription polymerase chain reaction and western blot analysis. The blood glucose levels in STZ induced T1D mouse models were measured to validate the establishment of T1D models. The pathological changes of T1D mouse were examined by hematoxylin and eosin. The oxidative stress (OS) and inflammatory response in T1D mouse were determined by measuring the expression levels of malondialdehyde, superoxide dismutase, and 8‐OHdG in pancreatic tissues and the serum levels of interleukin‐6 and tumor necrosis factor‐α. The ability to catabolize glucose was assessed through intraperitoneal glucose tolerance test and insulin tolerance test. Results β‐cell‐specific PKM2 knockout was successfully achieved in PKM2fl/flcre+ mouse. T1D mouse with PKM2 knockdown had decreased blood glucose level and suppressed cell apoptosis. PKM2 knockout in T1D mouse attenuated β cell injury. OS and inflammatory response in T1D mouse with PKM2 knockout were also suppressed compared with T1D mouse without PKM2 knockout. Conclusion PKM2 knockout in T1D mouse can attenuate OS and inflammatory response as well as decrease blood glucose level, suggesting the potential of PKM2 as a drug target for T1D treatment.

Summary: Background: we demonstrated that disulfide-bond A oxidoreductase-like protein (DsbA-L) was involved in the progression of renal fibrosis. However, the precise function of DsbA-L in acute kidney injury (AKI), and the mechanisms involved, have yet to be elucidated. Methods: We illustrate the DsbA-L interacted with VDAC1 by co-IP (co-immunoprecipitation) in vitro and vivo, and found the interaction parts of them by mutation experiment. The above findings were verified by co-localization of them. In addition, we constructed the two model of PT-DsbA-L and VDAC1 KO mice to verify the function of DsbA-L and VDAC1 in models of VAN, CLP and I/R-induced AKI. Findings: The PT-DsbA-L-KO mice showed amelioration of I/R, VAN-, and CLP-induced AKI progression via the downregulation of VDAC1. Finally, we confirmed these changes in signal molecules by examining in HK-2 cells and kidney biopsies taken from patients with ischemic or acute interstitial nephritis (AIN)-induced AKI. Mechanistically, DsbA-L interacted with amino acids 9–13 and 22–27 of VDAC1 in the mitochondria of BUMPT cells to induce renal cell apoptosis and mitochondrial injury. Interpretation: This work suggested that DsbA-L, located in the proximal tubular cells, drives the progression of AKI, by directly upregulating the levels of VDAC1.Running Title: The role of DsbA-L in AKI Funding: National Natural Science Foundation of China, a grant from Key Project of Hunan provincial science and technology innovation, Department of Science and Technology of Hunan Province project of International Cooperation and Exchanges, Changsha Science and Technology Bureau project, Natural Science Foundation of Hunan Province, Fundamental Research Funds for the Central Universities of Central South University, Hunan Provincial Innovation Foundation For Postgraduate China Hunan Provincial Science and Technology Department.

CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency caused T celldependent wasting disease driven by chronic gut immune dysregulation. CD5 inhibition also exacerbated acute experimental colitis. Mechanistically, loss of CD5 increased phospho-Stat3 levels, leading to elevated IL-17A secretion. Our data reveal a new facet of CD5 function in shaping the T cell cytokine profile. [ABSTRACT FROM AUTHOR]