Immunopeptidome mining reveals a novel ERS-induced target in T1D.

Autoreactive CD8+ T cells play a key role in type 1 diabetes (T1D), but the antigen spectrum that activates autoreactive CD8+ T cells remains unclear. Endoplasmic reticulum stress (ERS) has been implicated in ß-cell autoantigen generation. Here, we analyzed the major histocompatibility complex class I (MHC-I)-associated immunopeptidome (MIP) of islet ß-cells under steady and ERS conditions and found that ERS reshaped the MIP of ß-cells and promoted the MHC-I presentation of a panel of conventional self-peptides. Among them, OTUB258-66 showed immunodominance, and the corresponding autoreactive CD8+ T cells were diabetogenic in nonobese diabetic (NOD) mice. High glucose intake upregulated pancreatic OTUB2 expression and amplified the OTUB258-66-specific CD8+ T-cell response in NOD mice. Repeated OTUB258-66 administration significantly reduced the incidence of T1D in NOD mice. Interestingly, peripheral blood mononuclear cells (PBMCs) from patients with T1D, but not from healthy controls, showed a positive IFN-γ response to human OTUB2 peptides. This study provides not only a new explanation for the role of ERS in promoting ß-cell-targeted autoimmunity but also a potential target for the prevention and treatment of T1D. The data are available via ProteomeXchange with the identifier PXD041227.

Clinical application of a free flap supplied by the osteocutaneous branch of the anterior interosseous artery.

OBJECTIVES: To explore the clinical application and efficacy of transplantation of free composite flaps supplied by radial osteocutaneous branch of the dorsal branch of the anterior interosseous artery for reconstructing bone and skin defects in the hand. MATERIAL AND METHODS: Anatomically, the radial osteocutaneous branch of the dorsal branch of the anterior interosseous artery has constant collateral anastomoses which can provide a large dorsoradial flap from the dorsum of the forearm. This flap was used for reconstruction in five cases of cutaneous and phalangeal defects. RESULTS: Reconstruction was successful in all five cases, with consolidated phalanx and good cosmetic results. All donor sites could be closed directly. CONCLUSION: Reconstruction with dorsoradial forearm flaps is a reliable procedure which causes minimal trauma. Thus, it is an ideal approach for repairing cutaneous and phalangeal defects.

Physiological responses of low- and high-cadmium accumulating Robinia pseudoacacia-rhizobium symbioses to cadmium stress.

The role of rhizobia in alleviating cadmium (Cd) stress in woody legumes is still unclear. Therefore, two types of black locust (Robinia pseudoacacia L.) with high and low Cd accumulation abilities were selected from 11 genotypes in China, and the effects of rhizobium (Mesorhizobium huakuii GP1T11) inoculation on the growth, CO2 and H2O gas exchange parameters, Cd accumulation, and the absorption of mineral elements of the high (SX) and low Cd-accumulator (HB) were compared. The results showed that rhizobium-inoculation significantly increased biomass, shoot Cd contents, Cd accumulation, root-to-shoot translocation factor (TF) and the absorption and accumulation of mineral elements in both SX and HB. Rhizobium-inoculation increased chlorophyll a and carotenoid contents, and the intercellular carbon dioxide concentrations in HB plants. Under Cd exposure, the high-accumulator SX exhibited a significant decrease in photosynthetic CO2 fixation (Pn) and an enhanced accumulation of Cd in leaves, but coped with Cd exposure by increasing chlorophyll synthesis, regulating stomatal aperture (Gs), controlling transpiration (Tr), and increasing the absorption and accumulation of mineral elements. In contrast, the low-accumulator HB was more sensitive to Cd exposure despite preferential accumulation of Cd in roots, with decreased chlorophyll and carotenoid contents, but significantly increased root biomass. Compared to the low-accumulator HB, non-inoculated Cd-exposed SX plants had higher chlorophyll contents, and rhizobium-inoculated Cd-exposed SX plants had higher Pn, Tr, and Gs as well as higher levels of P, K, Fe, Ca, Zn, and Cu. In conclusion, the high- and low-Cd-accumulator exhibited different physiological responses to Cd exposure. Overall, rhizobium-inoculation of black locust promoted the growth and heavy metal absorption, providing an effective strategy for the phytoremediation of heavy metal-contaminated soils by this woody legume.

Sub-Second Long Lifetime Triplet Exciton Reservoir for Highly Efficient and Stable Organic Light-Emitting Diode.

In organic light-emitting diode (OLED), achieving high efficiency requires effective triplet exciton confinement by carrier-transporting materials, which typically have higher triplet energy (ET) than the emitter, leading to poor stability. Here, an electron-transporting material (ETM), whose ET is 0.32 eV lower than that of the emitter is reported. In devices, it surprisingly exhibits strong confinement effect and generates excellent efficiency. Additionally, the device operational lifetime is 4.9 times longer than the device with a standard ETM, 1,3,5-tri(1-phenyl-1H-benzo[d]imidazol-2-yl) phenyl (whose ET 0.36 eV is higher than the emitter). This anomalous finding is ascribed to the exceptionally long triplet state lifetime (≈0.2 s) of the ETM. It is named as long-lifetime triplet exciton reservoir effect. The systematic analysis reveals that the long triplet lifetime of ETM can compensate the requirement for high ET with the help of endothermic energy transfer. Such combination of low ET and long lifetime provides equivalent exciton confinement effect and high molecular stability simultaneously. It offers a novel molecular design paradigm for breaking the dilemma between high efficiency and prolonged operational lifetime in OLEDs.

Direct Hot-Electron Transfer at the Au Nanoparticle/Monolayer Transition-Metal Dichalcogenide Interface Observed with Ultrahigh Spatiotemporal Resolution.

Plasmon-induced hot-electron transfer at the metallic nanoparticle/semiconductor interface is the basis of plasmon-enhanced photocatalysis and energy harvesting. However, limited by the nanoscale size of hot spots and femtosecond time scale of hot-electron transfer, direct observation is still challenging. Herein, by using spatiotemporal-resolved photoemission electron microscopy with a two-color pump-probe beamline, we directly observed such a process with a concise system, the Au nanoparticle/monolayer transition-metal dichalcogenide (TMD) interface. The ultrafast hot-electron transfer from Au nanoparticles to monolayer TMDs and the plasmon-enhanced transfer process were directly measured and verified through an in situ comparison with the Au film/TMD interface and free TMDs. The lifetime at the Au nanoparticle/MoSe2 interface decreased from 410 to 42 fs, while the photoemission intensities exhibited a 27-fold increase compared to free MoSe2. We also measured the evolution of hot electrons in the energy distributions, indicating the hot-electron injection and decay happened in an ultrafast time scale of ∼50 fs without observable electron cooling.

Direct Repair of ruptured nerve stump to middle trunk for restoration of extrinsic finger extension in total brachial plexus injuries.

BACKGROUND: Attempts to restore independent hand function in total brachial plexus injuries (TBPI) have often failed due to the inconsistent results of fingers extension reconstruction. An innovative technique is described to achieve this by direct neurorrhaphy of residual (ruptured) roots with the middle trunk. METHODS: Direct coaptation of the ruptured roots to the middle trunk and, simultaneously, transferring the anterior division of the middle trunk to the posterior division of lower trunk was performed in 64 patients of TBPI. The return of extension of the elbow, wrist and fingers were monitored. RESULTS: The excellent and good muscle strength of finger extension was noted in 45.3% cases. The patients were divided into group A (>32 years) and group B (≤32 years) according to ROC curve analysis. The difference of excellent and good rates of finger and wrist extension muscle strengths between the two groups was statistically significant (χ 2=4.635, P=0.031 χ 2=6.615, P=0.010). CONCLUSIONS: Direct neurorrhaphy of ruptured nerve root stumps with the middle trunk could achieve satisfactory results for finger extension in TBPI for patients ≤32 years old. Long nerve defects (4-6.5 cm) could be overcome by freeing the nerve and adducting the arm against the trunk.

Non-targeted metabolomics study for discovery of hepatocellular carcinoma serum diagnostic biomarker.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Due to the asymptomatic features of HCC at early stages, patients are often diagnosed at advanced stages and missed effective treatment. Thus, there is an urgent need to identify sensitive and specific biomarkers for HCC early diagnosis. In the present study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was used to profile serum metabolites from HCC patients, liver cirrhosis (LC) patients, and normal controls (NC). Univariate and multivariate statistical analyses were performed to obtain the metabolomic differences of the three groups and select significantly changed metabolites that can be used as diagnostic biomarkers. In total, 757 differential metabolites were quantified among the three groups, and pathway enrichment analysis of these metabolites indicated that glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism were the most altered pathways involved in HCC development. Receiver operating characteristic (ROC) curve analysis was performed to select and evaluate the diagnostic biomarker performance. Seven metabolites were identified as potential biomarkers that can differentiate HCC from LC and NC, and LC from NC with the good diagnostic performance of area under the curve (AUC) from 0.890 to 0.990. In summary, our findings provide highly effective biomarker candidates to differentiate HCC from LC and NC, LC, and NC, which shed insight into HCC pathological mechanisms and will be helpful in better understanding and managing HCC.

Mixed reality in primary retroperitoneal tumour surgery: Evaluation of preoperative and intraoperative application value.

OBJECTIVE: To evaluate the feasibility and application value of mixed reality technology (MR) in Primary retroperitoneal tumour (PRT) surgery. METHODS: From 276 patients who underwent PRT resection at the First Affiliated Hospital of Xi'an Jiaotong University, we screened 46 patients who underwent MR-assisted retroperitoneal tumour resection and 46 patients who underwent tumour resection without MR assistance. The intraoperative and postoperative recovery of the patients in both groups were compared, and the reliability and validity of the application of MR were further examined using the Likert scale. RESULTS: There was a significant difference in the mean intraoperative bleeding volume between the two groups, but it was reduced in the MR group. The results of the Likert scale showed higher scores in the MR group than non-MR group. CONCLUSIONS: MR can be used to assist PRT resection and has great potential to improve the rate of complete retroperitoneal tumour resection.

Separating Crystal Growth from Nucleation Enables the In Situ Controllable Synthesis of Nanocrystals for Efficient Perovskite Light-Emitting Diodes.

Colloidal perovskite nanocrystals (PNCs) display bright luminescence for light-emitting diode (LED) applications; however, they require post-synthesis ligand exchange that may cause surface degradation and defect formation. In situ-formed PNCs achieve improved surface passivation using a straightforward synthetic approach, but their LED performance at the green wavelength is not yet comparable with that of colloidal PNC devices. Here, it is found that the limitations of in situ-formed PNCs stem from uncontrolled formation kinetics: conventional surface ligands confine perovskite nuclei but fail to delay crystal growth. A bifunctional carboxylic-acid-containing ammonium hydrobromide ligand that separates crystal growth from nucleation is introduced, leading to the formation of quantum-confined PNC solids exhibiting a narrow size distribution. Controlled crystallization is further coupled with defect passivation using deprotonated phosphinates, enabling improvements in photoluminescence quantum yield to near unity. Green LEDs are fabricated with a maximum current efficiency of 109 cd A-1 and an average external quantum efficiency of 22.5% across 25 devices, exceeding the performance of their colloidal PNC-based counterparts. A 45.6 h operating half-time is further documented for an unencapsulated device in N2 with an initial brightness of 100 cd m-2 .

Fabrication of Textured Ni-Coated Carbon Tubes for a Flexible Strain Sensor: Effect of the Device Elastic Modulus on Sensor Performance.

The exploration of flexible resistive sensors with excellent performance remains a challenge. In this paper, a nickel-coated carbon tube with a textured structure was prepared as a conductive sensitive material and inserted into the poly(dimethylsiloxane) (PDMS) polymer; interestingly, the sensor performance was controlled by the elastic modulus of the matrix resin. The results show that Pd2+ may be adsorbed by the active groups on the surface of a plant fiber as a catalytic center for the reduction of Ni2+. After 300 °C annealing, the inner plant fiber would be carbonized and attached to the outside of the nickel tube; to be precise, the textured Ni-encapsulated C tube was fabricated successfully. It is worth noting that the C tube serves as a layer of support for the external Ni coating, providing sufficient mechanical strength. In addition, resistance sensors with different properties were prepared by controlling the elasticity modulus of the PDMS polymer by introducing different contents of curing agents. The limit uniaxial tensile strain was enhanced from 42 to 49% and sensitivity reduced from 0.2 to 2.0% with the elasticity modulus of the matrix resin increasing from 0.32 to 2.2 MPa. As expected, the sensor is obviously appropriate for the detection of elbow joints, human speaking, and human joints with the reduction of the elasticity modulus of the matrix resin. To be precise, the optimal elastic modulus of the sensor matrix resin would facilitate the improvement of its sensitivity to monitor different human behaviors.

Active fluorescent modulation for low-noise super-resolution microscopy.

Extracting the position of individual molecular probes with high precision is the basis and core of super-resolution microscopy. However, with the expectation of low-light conditions in life science research, the signal-to-noise ratio (SNR) decreases and signal extraction faces a great challenge. Here, based on temporally modulating the fluorescence emission at certain periodical patterns, we achieved super-resolution imaging with high sensitivity by largely suppressing the background noise. We propose simple bright-dim (BD) fluorescent modulation and delicate control by phase-modulated excitation. We demonstrate that the strategy can effectively enhance signal extraction in both sparsely and densely labeled biological samples, and thus improve the efficiency and precision of super-resolution imaging. This active modulation technique is generally applicable to various fluorescent labels, super-resolution techniques, and advanced algorithms, allowing a wide range of bioimaging applications.

On-chip integrated exceptional surface microlaser.

The on-chip integrated visible microlaser is a core unit of high-speed visible-light communication with huge bandwidth resources, which needs robustness against fabrication errors, compressible linewidth, reducible threshold, and in-plane emission. However, until now, it has been a great challenge to meet these requirements simultaneously. Here, we report a scalable strategy to realize a robust on-chip integrated visible microlaser with further improved lasing performances enabled by the increased orders (n) of exceptional surfaces, and experimentally verify the strategy by demonstrating the performances of a second-order exceptional surface-tailored microlaser. We further prove the potential application of the strategy by discussing an exceptional surface-tailored topological microlaser with unique performances. This work lays a foundation for further development of on-chip integrated high-speed visible-light communication and processing systems, provides a platform for the fundamental study of non-Hermitian photonics, and proposes a feasible method of joint research for non-Hermitian photonics with nonlinear optics and topological photonics.

Differentially-expressed genes related to glutathione metabolism and heavy metal transport reveals an adaptive, genotype-specific mechanism to Hg2+ exposure in rice (Oryza sativa L.).

Rice consumption is an essential cause of mercury (Hg) exposure for humans in Asia. However, the mechanism of Hg transport and accumulation in rice plants (Oryza sativa L.) remains unclear. Here, rice genotypes with contrasting Hg uptake and translocation abilities, i.e. H655 (high Hg-accumulator) and H767 (low Hg-accumulator), were selected from 261 genotypes. Through comparative physiological and transcriptome analyses, we investigated the processes responsible for the relationship between Hg accumulation, transport and tolerance. The results showed significant stimulation of antioxidative metabolism, particularly glutathione (GSH) accumulation, and up-regulated expression of regulatory genes of glutathione metabolism for H655, but not for H767. In addition, up-regulated expression of GSH S-transferase (GST) and OsPCS1 in H655 that catalyzes the binding of Hg and GSH, enhances the Hg detoxification capacity, while high-level expression of YSL2 in H655 enhances the transport ability for Hg. Conclusively, Hg accumulation in rice is a consequence of enhanced expression of genes related to Hg binding with GSH and Hg transport. With these results, the present study contributes to the selection of rice genotypes with limited Hg accumulation and to the mitigation of Hg migration in food chains thereby enhancing nutritional safety of Hg-polluted rice fields.

Lead accumulation and biochemical responses in Rhus chinensis Mill to the addition of organic acids in lead contaminated soils.

Adding organic acid is an effective approach to assist phytoremediation. The effects of organic acids on phytoremediation efficiency are unknown in Rhus chinensis. This study aimed to evaluate the effect of citric acid (CA) and oxalic acid (OA) on the lead phytoremediation potential of R. chinensis with significantly inhibited growth in Pb-contaminated soil. The experimental pot culture study evaluated the long-term physiological response and metal accumulation patterns of R. chinensis grown in varying Pb-treated soil, and examined the effects of 0.5 and 1.0 mmol L-1 CA and OA on the growth, oxidative stress, antioxidant system, and Pb subcellular distribution of R. chinensis grown in pots with 1000 mg kg-1 Pb. Compared with the control, the biomass, leaf area, root morphological parameters, and chlorophyll concentration of R. chinensis decreased, whereas the carotenoid, malondialdehyde, H2O2, and O2˙- concentrations, and superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activity increased under Pb stress. A copious amount of Pb was taken up and mainly stored in the cell walls of the roots. The application of CA and OA increased plant growth. The highest shoots and roots biomass increase recorded was 44.4 and 61.2% in 1.0 mmol L-1 OA and 0.5 mmol L-1 CA treatment, respectively. The presence of CA and OA increased SOD, POD, and CAT activities and decreased the H2O2, O2˙- and malondialdehyde content. A concentration of 0.5 mmol L-1 CA significantly increased the Pb concentration in the organs. The other organic acid treatments changed root Pb concentrations slightly while increasing shoot Pb concentrations. The translocation factor values from organic acid treatments were increased by 38.8-134.1%. Our results confirmed that organic acid could alleviate the toxicity of stunted R. chinensis and improve phytoremediation efficiency.

A variety test platform for the standardization and data quality improvement of crop variety tests.

Variety testing is an indispensable and essential step in the process of creating new improved varieties from breeding to adoption. The performance of the varieties can be compared and evaluated based on multi-trait data from multi-location variety tests in multiple years. Although high-throughput phenotypic platforms have been used for observing some specific traits, manual phenotyping is still widely used. The efficient management of large amounts of data is still a significant problem for crop variety testing. This study reports a variety test platform (VTP) that was created to manage the whole workflow for the standardization and data quality improvement of crop variety testing. Through the VTP, the phenotype data of varieties can be integrated and reused based on standardized data elements and datasets. Moreover, the information support and automated functions for the whole testing workflow help users conduct tests efficiently through a series of functions such as test design, data acquisition and processing, and statistical analyses. The VTP has been applied to regional variety tests covering more than seven thousand locations across the whole country, and then a standardized and authoritative phenotypic database covering five crops has been generated. In addition, the VTP can be deployed on either privately or publicly available high-performance computing nodes so that test management and data analysis can be conveniently done using a web-based interface or mobile application. In this way, the system can provide variety test management services to more small and medium-sized breeding organizations, and ensures the mutual independence and security of test data. The application of VTP shows that the platform can make variety testing more efficient and can be used to generate a reliable database suitable for meta-analysis in multi-omics breeding and variety development projects.

Various mobile genetic elements carrying optrA in Enterococcus faecium and Enterococcus faecalis isolates from swine within the same farm.

OBJECTIVES: In this study, the distribution of the oxazolidinone/phenicol resistance gene optrA and the mobile genetic elements involved in its dissemination were analysed among enterococcal isolates from a farrow-to-finish swine farm. METHODS: Enterococcus faecium and Enterococcus faecalis isolates were obtained from all pig production stages in the farm. The optrA-carrying E. faecium and E. faecalis isolates were subjected to PFGE and antimicrobial susceptibility testing. Complete sequences of the genetically unrelated optrA-carrying E. faecium and E. faecalis isolates were determined using Illumina HiSeq and MinION platforms. RESULTS: The optrA gene was present in 12.2% (23/188) of the E. faecium and E. faecalis isolates, most of which originated from nursery and finishing stages. The 23 optrA-positive Enterococcus isolates represented 15 PFGE types. WGS of representative isolates of the 15 PFGE types showed that optrA was carried by diverse genetic elements either located in the chromosomal DNA or on plasmids. A novel optrA-bearing genetic element was identified on two distinct multi-resistance plasmids from E. faecium. Two new hybrid plasmids carrying several resistance genes were found in two E. faecalis isolates. pC25-1-like plasmids and chromosomally integrated Tn6674 and Tn6823-like transposons were prevalent in the remaining Enterococcus isolates. CONCLUSIONS: The gene optrA was found in genetically unrelated E. faecium and E. faecalis isolates from the same farm. Analysis of the genetic contexts of optrA suggested that horizontal transfer including different plasmids and transposons played a key role in the dissemination of optrA in this farm.

Outcome of Nerve Grafting for Radiation-Induced Brachial Plexopathy.

BACKGROUND: There is no consensus on the optimal treatment for radiation-induced brachial plexopathy (RIBP). OBJECTIVE: To present our experience of using nerve resection and autografting as a treatment strategy for this challenging condition. METHODS: From September 2014 to January 2020, 8 patients with RIBP were treated with segmental nerve resection and autografting, with or without other supplementary procedures. All patients underwent sural nerve grafting to the musculocutaneous nerve. All were female with a mean age of 53 (range 38-64) years. Seven were on the left, and 1 was on the right. The mean follow-up duration was 33 (range 17-72) months. RESULTS: By the final review, 7 of 8 patients regained at least antigravity elbow flexion. Four patients reached Medical Research Council (MRC) grade 4, 3 MRC grade 3, and MRC grade 2 recovery in the biceps. The mean Visual Analog Score for pain improved from 2.6 preoperatively to 0.6 postoperatively ( P = .042). CONCLUSION: Nerve resection and autografting may restore satisfactory elbow flexion in patients with RIBP.

Enhancing Weak-Signal Extraction for Single-Molecule Localization Microscopy.

Single-molecule localization microscopy (SMLM) has been widely used in biological imaging due to its ultrahigh spatial resolution. However, due to the strategy of reducing photodamage to living cells, the fluorescence signals of emitters are usually weak and the detector noises become non-negligible, which leads to localization misalignments and signal losses, thus deteriorating the imaging capability of SMLM. Here, we propose an active modulation method to control the fluorescence of the probe emitters. It actually marks the emitters with artificial blinking character, which directly distinguishes weak signals from multiple detector noises. We demonstrated from simulations and experiments that this method improves the signal-to-noise ratio by about 10 dB over the non-modulated method and boosts the sensitivity of single-molecule localization down to -4 dB, which significantly reduces localization misalignments and signal losses in SMLM. This signal-noise decoupling strategy is generally applicable to the super-resolution system with versatile labeled probes to improve their imaging capability. We also showed its application to the densely labeled sample, showing its flexibility in super-resolution nanoscopy.

Proteomic identification of MHC class I-associated peptidome derived from non-obese diabetic mouse thymus and pancreas.

The peptides repertoire presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC I-associated peptidome (MIP), which regulates thymus development, peripheral survival and function during lifetime of CD8+ T cells. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic ß cells destruction mediated primarily by autoreactive CD8+ T cells. Non-obese diabetic (NOD) mouse is an important animal model of T1D. Here, we deeply analyzed the MIP derived from NOD mice thymus and pancreas, and demonstrated that the thymus MIP source proteins partially shared with the MIP source proteins derived from NOD mice pancreas and ß cell line. One H-2Kd restricted peptide SLC35B126-34 which was shared by MIP derived from both NOD mice pancreatic tissues and islet ß-cell line, but absent in MIP from NOD thymus tissues, showed ability to stimulate IFN-γ secretion and proliferation of NOD mice splenic CD8+ T cells. The global view of the MHC I-associated self-peptides repertoire in the thymus and pancreas of NOD mice may serve as a biological reference to identify potential autoantigens targeted by autoreactive CD8+ T cells in T1D. Data are available via ProteomeXchange with identifier PXD031966. SIGNIFICANCE: The peptides repertoire presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC I-associated peptidome (MIP). The MIP presented by thymic antigen presenting cells (APCs) is crucial for shaping CD8+ T cell repertoire and self-tolerance, while the MIP presented by peripheral tissues and organs is not only involved in maintaining periphery CD8+ T cell survival and homeostasis, but also mediates immune surveillance and autoimmune responses of CD8+ T cells under pathological conditions. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the destruction of pancreatic ß cells, mediated primarily by autoreactive CD8+ T cells. Non-obese diabetic (NOD) mouse is one of important animal models of spontaneous autoimmune diabetes that shares several key features with human T1D. The global view of the MHC I-associated self-peptides repertoire in the thymus and pancreas of NOD mice may serve as a good biological reference to identify potential autoantigens targeted by autoreactive CD8+ T cells in T1D. It has great significance for further clarifying the immune recognition and effect mechanism of autoreactive CD8+ T cells in the pathogenesis of T1D, and then developing antigen-specific immune intervention strategies.