Progress in mechanism-based diagnosis and treatment of tuberculosis comorbid with tumor

Tuberculosis (TB) and tumor, with similarities in immune response and pathogenesis, are diseases that are prone to produce autoimmune stress response to the host immune system. With a symbiotic relationship between the two, TB can facilitate the occurrence and development of tumors, while tumor causes TB reactivation. In this review, we systematically sorted out the incidence trends and influencing factors of TB and tumor, focusing on the potential pathogenesis of TB and tumor, to provide a pathway for the co-pathogenesis of TB comorbid with tumor (TCWT). Based on this, we summarized the latest progress in the diagnosis and treatment of TCWT, and provided ideas for further exploration of clinical trials and new drug development of TCWT

Systematic Assessment of the Effect of Internal Library in Targeted Analysis of SWATH-MS.

Targeted analysis of sequential window acquisition of all theoretical mass spectra (SWATH-MS) requires the spectral library, which can be generated by shotgun mass spectrometry (MS) or by the pseudo-spectra files directly obtained from SWATH-MS data. The external library generated by shotgun MS is employed in most SWATH-MS research. However, performance of the internal library, which is constructed by pseudo-spectra files, in the targeted analysis of SWATH-MS has not been systemically evaluated. Here, we show that up to 40% of the peptides detected by the internal library were not overlapped with those detected by the external library for most SWATH-MS data sets. However, the internal library did not identify extra phosphopeptides compared with the external library for phosphoproteomic SWATH-MS data. Therefore, the internal library should be incorporated into the external library for targeted analysis of nonphosphoproteomic SWATH-MS, given that it can significantly increase the number of peptides of SWATH-MS without requiring additional instrument measurement time

RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome

韩家淮教授课题组的这项研究揭示了活性氧簇（ROS）通过直接特异地氧化受体相互作用丝氨酸/苏氨酸激酶1（RIP1）上的三个关键的半胱氨酸，进而特异地增强RIP1在S161上的自磷酸化，从而促进坏死小体的形成和程序性细胞坏死的发生。证实了RIP1的激酶活性在程序性细胞坏死中的主要功能是自磷酸化S161，且S161就是人们长期寻找的RIP1上与坏死相关的功能性磷酸化位点。坏死小体的形成是程序性细胞坏死发生的必要复合物，而S161的磷酸化是RIP1有效募集RIP3形成有功能的坏死小体所必需的。由于ROS的产生依赖于坏死小体里的RIP3的功能，因此ROS介导了程序性坏死通路里的正反馈调控。研究阐明了ROS促进程序性细胞坏死的分子机制，回答了领域内长期存在的两个科学问题，对全面解析程序性坏死机制并协助疾病治疗具有重要意义。 张荧荧和苏晟为该论文的共同第一作者。该项研究得到了973计划和国家自然科学基金委员会重点和重大研究计划项目的经费支持。【Abstract】Necroptosis is a type of programmed cell death with great significance in many pathological processes. Tumour necrosis factor-a(TNF), a proinflammatory cytokine, is a prototypic trigger of necroptosis. It is known that mitochondrial reactive oxygen species (ROS) promote necroptosis, and that kinase activity of receptor interacting protein 1 (RIP1) is required for TNF-induced necroptosis. However, how ROS function and what RIP1 phosphorylates to promote necroptosis are largely unknown. Here we show that three crucial cysteines in RIP1 are required for sensing ROS, and ROS subsequently activates RIP1 autophosphorylation on serine residue 161 (S161). The major function of RIP1 kinase activity in TNF-induced necroptosis is to autophosphorylate S161. This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis. Since ROS induction is known to require necrosomal RIP3, ROS therefore function in a positive feedback circuit that ensures effective induction of necroptosis.This work was supported by the National Natural Science Foundation of China (91029304, 31420103910, 31330047 and 81630042), the National Basic Research Program of China (973 Program; 2015CB553800, 2013CB944903, 2014CB541804), the 111 Project (B12001), the National Science Foundation of China for Fostering Talents in Basic Research (J1310027)

Group-DIA: analyzing multiple data-independent acquisition mass spectrometry data files

Discovery proteomics has limited quantification capabilities because of stochastic precursor-ion selection. Several data-independent acquisition (DIA) methods have been proposed to overcome this limitation1, 2, 3, 4, including the sequential-window acquisition of all theoretical mass spectra (SWATH-MS)4.the National Science Foundation (NSF) of China (grants 91429301 and 31221065), 973 Program 2015CB553800, National Major Project 2013ZX10002-002, 111 Project B12001, funding from Xiamen City (grant 3502Z20130027) and the NSF of China for Fostering Talents in Basic Research (grant J1310027)

Ppm1b negatively regulates necroptosis through dephosphorylating ​Rip3

该研究论文发现蛋白磷酸酶Ppm1b 通过去磷酸化RIP3负调控程序性细胞坏死（necroptosis），阐明了RIP3磷酸化状态的精确调控对于细胞和机体在生理和病理状态下的存活至关重要。The auto-phosphorylation of murine ​receptor-interacting protein 3 (​Rip3) on Thr 231 and Ser 232 in the necrosome is required to trigger necroptosis. However, how ​Rip3 phosphorylation is regulated is still largely unknown. Here we identified ​protein phosphatase 1B (​Ppm1b) as a ​Rip3 phosphatase and found that ​Ppm1b restricts necroptosis in two settings: spontaneous necroptosis caused by ​Rip3 auto-phosphorylation in resting cells, and ​tumour necrosis factor-α (​TNF)-induced necroptosis in cultured cells. We revealed that ​Ppm1b selectively suppresses necroptosis through the dephosphorylation of ​Rip3, which then prevents the recruitment of ​mixed lineage kinase domain-like protein (​Mlkl) to the necrosome. We further showed that ​Ppm1b deficiency (​Ppm1bd/d) in mice enhanced ​TNF-induced death in a ​Rip3-dependent manner, and the role of ​Ppm1b in inhibiting necroptosis was evidenced by elevated ​Rip3 phosphorylation and tissue damage in the caecum of ​TNF-treated ​Ppm1bd/d mice. These data indicate that ​Ppm1b negatively regulates necroptosis through dephosphorylating ​Rip3 in vitro and in vivo

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure