PD-L1 on ex-vivo Expanded Toll-like-receptor-Bregs Prevents Allograft Rejection by Breg Viability Promotion, CD4T Effector Cell Suppression, and Tregs Induction.

Achieving immune tolerance is a key goal in organ transplantation, as it eliminates the need for long-term immunosuppression. Regulatory B cells (Bregs) present a promising strategy for inducing tolerance. Our previous findings demonstrate that the adoptive transfer of ex vivo-expanded murine splenic B regulatory cells, referred to as TLR-Bregs (TLR9/TLR4 stimulation), induces tolerance to allografts.

Implantable and Biodegradable Smart Textiles for Continuous Limb and Gastrointestinal Motility Monitoring.

The thriving of internet of things and mobile healthcare requires a myriad of sensing devices for continuous implantable and wearable monitoring over extended periods. However, lack of biocompatibility and degradability has become a bottleneck for rehabilitation and close-loop diagnosis and therapy as well as in-vivo biomonitoring platforms. Herein, an implantable and biodegradable smart textile (IBST) composed of natural loofah sponge is reported, carbon ink, and silver nanoparticles.

The generation and evaluation of TKO/hCD55/hTM/hEPCR gene-modified pigs for clinical organ xenotransplantation.

Introduction: Genetically edited pigs, modified using CRISPR-Cas9 technology, hold promise as potential sources for xenotransplantation. However, the optimal combination of genetic modifications and their expression levels for initial clinical trials remains unclear. This study investigates the generation of TKO/hCD55/hTM/hEPCR (6GE) pigs and evaluates their compatibility with human immune and coagulation systems.

Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE.

Objectives: SLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire's role in SLE has garnered significant interest due to its potential in both diagnostics and therapeutics. Our study aimed to delineate the variances in the TCRβ repertoire between patients with SLE and healthy individuals, correlating these differences with the severity and subtypes of SLE.

Graft-derived cell free DNA: used for assessment of early graft status and its implications for long-term kidney function.

Background: The long-term graft survival is closely related to its early status, yet the indices for assessing the early graft status are complex and lack quantitative values. The aim of this study is to investigate the potential of GcfDNA as a comprehensive, non-invasive, convenient, and quantifiable indicator for evaluating early graft status.

Methods: In this study, 138 recipients who underwent primary kidney transplantation were enrolled.

Sweet taste receptors play roles in artificial sweetener-induced enhanced urine output in mice.

Sweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear.

Sucralose regulates postprandial blood glucose in mice through intestinal sweet taste receptors Tas1r2/Tas1r3.

Background: Non-nutritive sweeteners (such as sucralose) bind to sweet receptors Tas1r2/Tas1r3 on intestinal endocrine L cells after diets to upregulate blood glucose. However, the mechanism by which sucralose regulates postprandial blood glucose (PBG) has not been clarified to date. We hypothesized that the gut sweet taste receptor was one of the targets for sucralose to regulate PBG.

Meeting report: Xenotransplantation Development Conference in Neijiang, China.

A conference on progress in the development of xenotransplantation in China was held in Neijiang, Sichuan, in May 2023, and was attended by approximately 100 established researchers and trainees. Progress in xenotransplantation research was reviewed by both Chinese and foreign experts. The topics discussed ranged from genetic engineering of pigs and the results of pig-to-nonhuman primate organ transplantation to the requirements for designated pathogen-free (DPF) pig facilities and regulation of xenotransplantation.

Bonding Behavior of Cement Mortar Retrofitting for Adobe Masonry Wallette with Groove, Wire Mesh, Shear Dowel, and Sticky Rice Paste.

Damaged adobe masonry is essential to retrofit not only for continued use by less developed populations but also for historical preservation and vernacular landmark maintenance. Coating mortar on adobe can greatly improve the static load-carrying capacity of adobe masonry Wallette. Four retrofitting methods are carried out to enhance the cooperation of mortar and adobe; these four methods focus on the factors of roughness, shear dowel, and mesh size and a novel biological and traditional Chinese binder, sticky rice pulp.

Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets.

Objective: Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application.

In vivo induction of regulatory T cells by anti-CD45RB antibody causes transferable tolerance to discordant human xenogenic islets.

Background: The treatment of diabetes by islet cell transplantation has become an accepted therapy, with transplantation of xenogeneic islet cells an attractive alternative to the problem. Previous studies in mice have demonstrated that anti-CD45RB induce immune tolerance in human pancreatic islet cells. The current study was to define the mechanism of action of anti-CD45RB induced nonspecific immune tolerance to heteroantigens.

Current status of xenotransplantation research and the strategies for preventing xenograft rejection.

Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas.

Anti-rheumatic drug-induced hepatitis B virus reactivation and preventive strategies for hepatocellular carcinoma.

To date, an estimated 300 million people worldwide have been infected with chronic hepatitis B virus (HBV). Although anti-HBV therapies have improved the long-term survival profile of chronic carriers, viral reactivation still poses a significant challenge for preventing HBV-related hepatitis, hepatocellular carcinoma (HCC), and death. Immuno-modulating drugs, which are widely applied in managing rheumatic conditions, are commonly associated with HBV reactivation (HBVr) as a result of drug-induced immune suppression.

International Human Xenotransplantation Inventory: A 10-year Follow-up.

Background: Following the recommendations by a panel of experts gathered by the World Health Organization in 2005, an inventory was established to collect practices of human xenotransplantation worldwide ( www.humanxenotransplant.org ).

Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans.

Genetic variants in the asialoglycoprotein receptor 1 (ASGR1) are associated with a reduced risk of cardiovascular disease (CVD) in humans. However, the underlying molecular mechanism remains elusive. Given the cardiovascular similarities between pigs and humans, we generated ASGR1-deficient pigs using the CRISPR/Cas9 system.

Modifying strategies for SDF-1/CXCR4 interaction during mesenchymal stem cell transplantation.

Mesenchymal stem cell (MSC) transplantation is regarded as a promising candidate for the treatment of ischaemic heart disease. The major hurdles for successful clinical translation of MSC therapy are poor survival, retention, and engraftment in the infarcted heart. Stromal cell-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) constitutes one of the most efficient chemokine/chemokine receptor pairs regarding cell homing.

Properties of regulatory B cells regulating B cell targets.

Regulatory B cells (Bregs) have shown promise as anti-rejection therapy applied to organ transplantation. However, less is known about their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naïve B cells, stimulated by TLR ligand agonists, converted into B cells with regulatory properties (Bregs-TLR) that prevented allograft rejection.

An Unbiased Machine Learning Exploration Reveals Gene Sets Predictive of Allograft Tolerance After Kidney Transplantation.

Efforts at finding potential biomarkers of tolerance after kidney transplantation have been hindered by limited sample size, as well as the complicated mechanisms underlying tolerance and the potential risk of rejection after immunosuppressant withdrawal. In this work, three different publicly available genome-wide expression data sets of peripheral blood lymphocyte (PBL) from 63 tolerant patients were used to compare 14 different machine learning models for their ability to predict spontaneous kidney graft tolerance. We found that the Best Subset Selection (BSS) regression approach was the most powerful with a sensitivity of 91.

TGF-β-secreting regulatory B cells: unsung players in immune regulation.

Regulatory B cells contribute to the regulation of immune responses in cancer, autoimmune disorders, allergic conditions and inflammatory diseases. Although most studies focus on regulatory B lymphocytes expressing interleukin-10, there is growing evidence that B cells producing transforming growth factor β (TGF-β) can also regulate T-cell immunity in inflammatory diseases and promote the emergence of regulatory T cells that contribute to the induction and maintenance of natural and induced immune tolerance. Most research on TGF-β regulatory B cells has been conducted in models of allergy, cancer and autoimmune diseases, but there has, as yet, been limited scrutiny of their role in the transplant setting.

Bactericidal/Permeability-Increasing Protein Improves Cognitive Impairment in Diabetic Mice Blockade of the LPS-LBP-TLR4 Signaling Pathway.

Emerging evidence suggests that the bactericidal/permeability-increasing protein (BPI) is involved in the process of cognitive impairment in diabetes. However, its underlying mechanism remains elusive. In this study, we found that BPI affects cognitive impairment due to diabetes through the lipopolysaccharide (LPS)-lipopolysacharide-binding protein (LBP)-toll-like receptor 4 (TLR4) signaling pathway.

A novel prevascularized tissue-engineered chamber as a site for allogeneic and xenogeneic islet transplantation to establish a bioartificial pancreas.

Although sites for clinical or experimental islet transplantation are well established, pancreatic islet survival and function in these locations remain unsatisfactory. A possible factor that might account for this outcome is local hypoxia caused by the limited blood supply. Here, we modified a prevascularized tissue-engineered chamber (TEC) that facilitated the viability and function of the seeded islets in vivo by providing a microvascular network prior to transplantation.

Epidemiological and clinical based study on four passages of COVID-19 patients: intervention at asymptomatic period contributes to early recovery.

Background: With the worldwide spread of the 2019 novel coronavirus, scarce knowledge is available on the clinical features of more than two passages of patients. Further, in China, early intervention policy has been enacted since February. Whether early intervention contributes to swift recovery is still unknown.