Increased TCR signaling in regulatory T cells is disengaged from TCR affinity.

Foxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, TCR affinity and specificities that support Treg function, and how these compare to autoimmune T cells remain unresolved. In this study, we used antigen agnostic and epitope-focused analyses to compare TCR repertoires of regulatory and effector T cells that spontaneously infiltrate pancreatic islets of non-obese diabetic mice.

Antibody-Mediated Targeting of a Hybrid Insulin Peptide Toward Neonatal Thymic Langerin-Positive Cells Enhances T-Cell Central Tolerance and Delays Autoimmune Diabetes.

Thymic presentation of self-antigens is critical for establishing a functional yet self-tolerant T-cell population. Hybrid peptides formed through transpeptidation within pancreatic β-cell lysosomes have been proposed as a new class of autoantigens in type 1 diabetes (T1D). While the production of hybrid peptides in the thymus has not been explored, due to the nature of their generation, it is thought to be highly unlikely.

Background-free room temperature phosphorescence and digital image colorimetry detection of melamine by carbon nitride quantum dots in cellulose matrix with smartphone-based portable device.

Carbon nitride quantum dots (CNQDs) were embedded in the sodium carboxymethyl cellulose (CMC) matrix to form CNQDs-CMC film to explore the room temperature phosphorescence (RTP) of CNQDs, which suppress the non-radiative relaxation process due to the internal hydrogen bonding interactions between CMC and CNQDs. Then, a simple, inexpensive, background-free miniature device integrating with CNQDs-CMC film and smartphone was fabricated for rapid and quantitative detection of melamine (MEL). In the present of MEL, the yellow RTP color of the CNQDs-CMC film was quenched and photographed by the smartphone.

A dormant T-cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type 1 diabetes.

The contribution of low-affinity T cells to autoimmunity in the context of polyclonal T-cell responses is understudied due to the limitations in their capture by tetrameric reagents and low level of activation in response to antigenic stimulation. As a result, low-affinity T cells are often disregarded as nonantigen-specific cells irrelevant to the immune response. Our study aimed to assess how the level of self-antigen reactivity shapes T-cell lineage and effector responses in the context of spontaneous tissue-specific autoimmunity observed in NOD mice.

T-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope.

Accumulating evidence supports a critical role for posttranslationally modified (PTM) islet neoantigens in type 1 diabetes. However, our understanding regarding thymic development and peripheral activation of PTM autoantigen-reactive T cells is still limited. Using HLA-DR4 humanized mice, we observed that deamidation of GAD65115-127 generates a more immunogenic epitope that recruits T cells with promiscuous recognition of both the deamidated and native epitopes and reduced frequency of regulatory T cells.

A Colorimetric Assay for the Detection of Glucose and HO Based on Cu-Ag/g-CN/ZIF Hybrids with Superior Peroxidase Mimetic Activity.

In this work, we report the synthesis of Cu-Ag bimetallic nanopartiles and g-CN nanosheets decorated on zeolitic imidazolate framework-8 (ZIF-8) to form a Cu-Ag/g-CN/ZIF hybrid. The hybrid was synthesized and characterized by Transmission electron microscopy (TEM), Fourier transformed infrared (FTIR), the X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The Cu-Ag/g-CN/ZIF hybrid has intrinsic peroxidaselike catalytic activity towards the oxidation of TMB in the presence of HO.

A dual-modal fluorometric and colorimetric nanoprobe based on graphitic carbon nitrite quantum dots and Fe (II)-bathophenanthroline complex for detection of nitrite in sausage and water.

A fluorometric and colorimetric dual-mode sensing platform based on graphitic carbon nitrite quantum dots (g-CNQDs) and Fe (II)-bathophenanthroline complex (BPS-Fe) was designed to the sensitive detection of nitrite (NO) in sausage and water. In this system, the fluorescence of g-CNQDs was quenched by BPS-Fe complex due to the inner filter effect (IFE). When NO was present, Fe was oxidized by nitrite to form BPS-Fe complex with BPS, leading to the recovery of the fluorescence from g-CNQDs.

Generation of T Cell Receptor Retrogenic Mice.

The ability to express and study a single T cell receptor (TCR) in vivo is an important aspect of both basic and translational immunological research. Traditionally, this was achieved by using TCR transgenic mice. In the past decade, a more efficient approach for single TCR expression was developed.

Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis.

Decoding the molecular composition of individual Ngn3 + endocrine progenitors (EPs) during pancreatic morphogenesis could provide insight into the mechanisms regulating hormonal cell fate. Here, we identify population markers and extensive cellular diversity including four EP subtypes reflecting EP maturation using high-resolution single-cell RNA-sequencing of the e14.5 and e16.

Alleviation of high-fat diet-induced atherosclerosis and glucose intolerance by a novel GLP-1 fusion protein in ApoE(-/-) mice.

We have previously constructed an engineered anti-diabetic fusion protein using glucagon-like peptide-1 and the globular domain of adiponectin. Herein, we evaluated the therapeutic effects of this fusion protein (GAD) on high-fat diet (HFD)-fed ApoE(-/-) mice. The lipid-lowering effect of GAD was determined in C57BL/6 mice using a lipid tolerance test.

Linker engineering for fusion protein construction: Improvement and characterization of a GLP-1 fusion protein.

Protein engineering has been successfully applied in protein drug discovery. Using this technology, we previously have constructed a fusion protein by linking the globular domain of adiponectin to the C-terminus of a glucagon-like peptide-1 (GLP-1) analog. Herein, to further improve its bioactivity, we reconstructed this fusion protein by introducing linker peptides of different length and flexibility.

Optimized soluble expression and purification of an aggregation-prone protein by fusion tag systems and on-column cleavage in Escherichia coli.

Previously we constructed a fusion protein based on GLP-1 and globular adiponectin but unfortunately its yield was low because it was mainly expressed as inclusion bodies. Herein to optimize the soluble expression of this fusion protein we tried several fusion tag systems. Fusion tags, including GST-, Trx- and MBP-tag, greatly improved the soluble expression of the fusion protein.