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Although most [CD8.sup.+] T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self- peptides. Recognition and elimination of pathogenic target cells that express these Qa-1- self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses., Introduction The immune system has evolved complex mechanisms that allow efficient destruction of microbial pathogens while sparing the host's own tissues. Maintenance of this balance depends, in part, on regulatory [...]

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1‐/‐ mice. Further, we show that A1‐reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV‐infected IFNAR1‐/‐ mice also induced neuronal cell death through the activation of A1‐reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach. [ABSTRACT FROM AUTHOR]

The exponential development in quantum phenomena is directly correlated with the decreasing size of nano‐semiconductor transistors. Consequently, the use of a quantum structure that deviates from traditional transistor types becomes imperative. Electrostatically defined nanoscale devices within 2D semiconductor heterostructures serve as foundational elements for diverse quantum electrical circuits. Van der Waals heterostructures, distinguished by atomically flat interfaces and inherent 2D characteristics, offer advantages such as large‐scale uniformity, flexibility, and portability over conventional bulk semiconductor heterostructures. Herein, the intricate electronic behavior of a MoS2/WSe2 encapsulated heterostructure governed by split‐gate and middle‐gate configurations is investigated, revealing a distinctive step‐like current profile at a low temperature of 77 K. The observed four regimes in the current highlight the impact of quantum confinement induced by reduced lateral dimensions, coupled with precise electrostatic confinement controlled by gate voltages. The temperature dependence of the phenomena emphasizes the role of thermal effects on carrier scattering mechanisms. In addition, the pinch‐off characteristics with different temperatures, middle‐gate voltages, and drain biases are explored. This study contributes to a deeper understanding of electrostatic effects in 2D transition metal dichalcogenide heterostructures and holds promise for the development of advanced electronic devices with tailored confinement for enhanced functionalities. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusions This study aimed to screen oral squamous cell carcinoma (OSCC) diagnostic and prognostic candidates and investigate the potential functions and mechanisms of candidates in the chemoresistance of OSCC cell lines.Differential expression profiling of lncRNA was performed in a large cohort of OSCC patients from the Cancer Genome Atlas database to identify OSCC diagnostic and prognostic candidates. Taxol resistance in OSCC cell lines was analyzed using MTT assay. OSCC cell lines transfected with EIF3J‐DT pcDNA or siRNA were used to determine its regulatory effects on apoptosis, cell cycle distribution and autophagy using flow cytometry and western blot.We identified EIF3J‐DT as a candidate for OSCC diagnosis and prognosis. The expression level of EIF3J‐DT in OSCC cell lines correlates with taxol resistance. EIF3J‐DT silencing attenuated taxol resistance, and EIF3J‐DT overexpression enhanced taxol resistance in OSCC cell lines. Silencing of EIF3J‐DT reduced taxol resistance by inducing apoptosis, cell cycle arrest, and ATG14‐mediated autophagy inhibition in OSCC cell lines.We found that EIF3J‐DT induced chemoresistance by regulating apoptosis, cell cycle, and autophagy in OSCC cell lines, which EIF3J‐DT might provide a novel therapeutic approach for OSCC as well as a diagnostic and prognostic factor. [ABSTRACT FROM AUTHOR]

BackgroundMetabolic syndrome (MS) is known to increase the risk of various cardiometabolic diseases and in-sulin resistance (IR) has known to have central role in the development of MS. Many surrogate indices of IR have been proposed and the detection of MS might be a suitable model for assessing the accuracy of surrogate indices. The aims of our study are to invest the most appropriate index by assessment of the diagnostic capacity of IR among each surrogate index and identifying cut-off values for discriminating uncomplicated MS in Korean adults.MethodsA cross-sectional study was performed, assessing 294 Korean adults, 85 of whom were diagnosed with uncomplicated MS. The sensitivities and specificities of five surrogate IR indices were compared to discriminate MS from healthy subjects; these included fasting serum insulin, homeostasis model assessment-insulin resistance index, quantitative insulin sensitivity check index, McAuley index, and Disse index. Correlations between each index value were assessed using Pearson's and Spearman's correlation methods.ResultsThe McAuley index showed the highest area under the curve (0.85), specificity (86.12%), accuracy (82.31%), positive predictive value (68.13%), and negative predictive value (88.67%) to distinguish MS, with a cut-off point of 5.3 defined. Correlation coefficients of the five indices showed that the McAuley index had the strongest correlation with IR.ConclusionThe McAuley index showed the best accuracy in the detection of MS as a surrogate marker of IR. To establish more effective and accurate standards of measuring IR, comprehensive and multi-scaled studies are required.