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TCRαβ+CD8αα+ intraepithelial lymphocytes (CD8αα+ αβ IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in the near absence of CD8αα+ αβ IELs. BCL6 was expressed by approximately 50% of CD8αα+ αβ IELs and by the majority of thymic PD1+ IELps after agonist selection. Bcl6 deficiency blocked early IELp generation in the thymus, and its expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double-positive thymocytes exhibited increased apoptosis during agonist selection and impaired IELp differentiation and maturation. Together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αβ IELs. Editor's summary: Intraepithelial lymphocytes (IELs) reside within the intestinal epithelium, where they regulate immune tolerance. Unconventional CD8αα+ αβ IELs are selected from thymic IEL precursors (IELps) after strong TCR signaling; however, the transcription factors governing this process of agonist selection are not well defined. Xing et al. found that mice lacking the transcription factor BCL6 in αβ T cells almost did not develop CD8αα+ αβ IELs. Thymic IELps up-regulated BCL6 after TCR stimulation, and BCL6 expression was required for their survival, differentiation, and maturation. These findings identify that BCL6 is required for the development of unconventional CD8αα+ αβ IELs during agonist selection. —Hannah Isles [ABSTRACT FROM AUTHOR]

Objective To evaluate the safety and efficacy of carbon ion and proton therapies for pancreatic cancer (PaC). Methods The databases were electronically searched to collect the studies about the carbon ion and proton therapies for PaC from inception to June 2019. Two reviewers independently screened literature and extracted data. A Meta-analysis was performed by STATA 12.0 and MetaAnalyst Beta 3.13 software. Results A total of 8 studies involving 459 PaC patients were included. The incidence of grade 2, 3 and 5 gastrointestinal (GI) ulcer toxicities in PaC patients treated with carbon ion and proton therapies were 7%, 2% and 0; the incidence of grade 2, 3 and 4 anorexia toxicities were 6%, 3.2% and 0; the 1- and 2-year OS rates were 77% and 45%; the 2-year local control (LC), 1-year freedom from local progression (FFLP) and 1-year local recurrence(LR) rates were 81%, 88% and 15%. The incidence of grade 2, 3, 2-3 GI ulcer toxicities in carbon ion and proton therapies for PaC were 6.8%, 1.5%, 9.2% and 3.5%, 8.3%, 6.1% (P < 0.05); and the 1- and 2-year OS were 77.1%, 44.4% and 77.6%, 49.7% (P > 0.05). Conclusion Carbon ion and proton therapies for PaC are safe and effective; and the security and effectiveness of the two methods are similar.

Objective To evaluate the efficacy and safety of carbon ion and proton therapy for hepatocellular carcinoma (HCC) by Meta-analysis. Methods PubMed, The Cochrane Library, EMBASE, Chinese Journal Full-text, Chinese Biomedical Literature and Wanfang Database were searched to collect relevant clinical studies on carbon ion and proton therapy for HCC. Two reviewers independently screened the literature and extracted data based on inclusion and exclusion criteria. Meta-analysis was carried out by Stata 12.0. Results We included 7 carbon ion and 23 proton therapy studies. According to the combined results, both carbon ion and proton therapies for HCC obtained good local control rate and low adverse reactions, and the incidence of severe adverse reactions was low. Subgroup analysis showed that carbon ion and proton therapies improved the 5-year OS of HCC patients with either favorable or poor prognosis. Conclusion Both carbon ion and proton therapies may be the effective alternative treatment options for HCC with favorable prognosis, and also show better efficacy for HCC patients with poor prognosis.

The bolt is the main connecting part of the RV reducer. Its mechanical properties affect the transmission accuracy of the whole machine. According to the principle of generating the profile of the cycloidal gear. Combining vector method to establish the profile equation of cycloidal wheel after shaping. Apply the principle of deformation coordination. Mechanical analysis of each component of the whole machine. Calculate the force of the bolt in theory; Considering the modification of the cycloidal wheel and the diameter error of the center circle of the pin tooth. Multi-body dynamics analysis in ADAMS. Through simulation analysis,we can know: Different initial mounting angles or different angles of rotation. Different bolts have different trends and different degrees of change. Different angles of rotation. Bolt force is not in the same order. As the angle of rotation of the cycloid increases,the overall force of the bolt increases first and then decreases. As the load increases,the bolt is gradually increased in force. As the load increases,the magnitude of the increase also increases.

Background The high accuracy and high stability of the T0 signal, taking from initial proton target time, are the prerequisite and basis for the efficient operation of the multi-physics spectrometer of Chinese spallation neutron source (CSNS). Purpose This study aims to develop a set of CSNS multi-physical spectrometer T0 trigger monitor system running on the experimental physics and industrial control system (EPICS) platform. Methods First of all, the T0 signal was fed into the T0 fan out device for high precise time stamp marking, and the high-throughput distributed publish-subscribe messaging system Kafka was used to achieve peak-shaving and asynchronous communication of big data traffic. Then, the monitored data was uploaded to the EPICS platform as a process variable (PV), and the Open-Falcon monitoring system and the visualization tool Grafana were used to realize the monitoring and visualization of the data. Results & Conclusions Implemented T0 signal monitoring system can monitor the frequency of the T0 signal of each node and the time delay of T0 in the fan-out and transmission process in real time. so as to ensure the normal operation of the CSNS multi-physics spectrometer.