Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

Acute graft-versus-host disease(a GVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor(G-CSF) has been demonstrated to relieve the a GVHD reaction.However, the role of G-CSF-primed donor Tcells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c) and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model, especially in the lung and gut. Moreover, we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator(ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD, especially for its precise regulation in GVHD target organs.     

聚多巴胺的表面修饰功能在组织工程的应用进展*

聚多巴胺作为贻贝的仿生材料,可由多巴胺在碱性环境中自发形成。由于其较好的黏附特性以及组织相容性,在生命科学等领域有着广泛的应用。将聚多巴胺对材料进行表面修饰,既可以保护材料免受强氧化剂、酸碱等外界的侵蚀,也可以通过表面改性赋予材料新的功能,使其在各领域发挥更好的作用。对聚多巴胺的制备原理、生物性能,以及近年来在组织工程领域(骨组织、软骨组织、硬脑膜组织、血管组织、耳组织)的运用进行综述,以期为后续聚多巴胺作为组织工程黏附材料的研究提供参考。     

蛹虫草原基分化的差异蛋白质组学研究

蛹虫草子实体形成及发育的蛋白分子机制尚不清楚,本研究引入SWATH非标记定量蛋白质组学技术,对蛹虫草Cordyceps militaris 905菌株的菌丝体（mycelium,My）、原基（primordium,Po）、生长期子实体（developmental fruiting body,DF）和成熟期子实体（mature fruiting body,MF）进行了比较蛋白质组学分析。经搜库比对,从蛹虫草的My、Po、DF和MF中依次鉴定蛋白1 136个、1 090个、1 018个和997个（global FDR 1%）,经维恩分析后获得C. militaris 905蛹虫草表达蛋白1 578个。在此基础上,SWATH非标记技术定量蛋白1 109个。本研究获得了蛹虫草Po期与My期、DF期与Po期、MF期与DF期的差异表达蛋白,依次为115个、352个和104个,并对菌丝体分化形成原基的差异表达蛋白进行了重点解析。GO注释结果表明,Po期与My期差异表达蛋白以有机含氮类化合物代谢为主,其中AMP（活性成分虫草素合成的中间产物）从头生物合成途径富集最为显著。约1/5的差异表达蛋白参与氧化还原反应,还原酶活性的蛋白在原基中几乎都上调表达,而氧化功能的蛋白受到抑制,表明蛹虫草原基分化可能受到氧化应激的诱导。蛋白互作网络分析结果进一步表明,氧化还原反应与核苷类物质代谢相关联,可能通过影响AMP从头生物合成途径来调控虫草素的生物合成。对蛹虫草子实体系统的蛋白质组学研究和解析有利于揭示子实体形成的蛋白分子机制,为蛹虫草的基础和栽培研究提供了理论支撑。     

The novel peptide NbPPI1 identified from Nicotiana benthamiana triggers immune responses and enhances resistance against Phytophthora pathogens

In plants, recognition of small secreted peptides, such as damage/danger‐associated molecular patterns (DAMPs), regulates diverse processes, including stress and immune responses. Here, we identified an SGPS (Ser‐Gly‐Pro‐Ser) motif‐containing peptide, Nicotiana tabacum NtPROPPI, and its two homologs in Nicotiana benthamiana, NbPROPPI1 and NbPROPPI2. Phytophthora parasitica infection and salicylic acid (SA) treatment induced NbPROPPI1/2 expression. Moreover, SignalP predicted that the 89‐amino acid NtPROPPI includes a 24‐amino acid N‐terminal signal peptide and NbPROPPI1/2‐GFP fusion proteins were mainly localized to the periplasm. Transient expression of NbPROPPI1/2 inhibited P. parasitica colonization, and NbPROPPI1/2 knockdown rendered plants more susceptible to P. parasitica. An eight‐amino‐acid segment in the NbPROPPI1 C‐terminus was essential for its immune function and a synthetic 20‐residue peptide, NbPPI1, derived from the C‐terminus of NbPROPPI1 provoked significant immune responses in N. benthamiana. These responses led to enhanced accumulation of reactive oxygen species, activation of mitogen‐activated protein kinases, and up‐regulation of the defense genes Flg22‐induced receptor‐like kinase (FRK) and WRKY DNA‐binding protein 33 (WRKY33). The NbPPI1‐induced defense responses require Brassinosteroid insensitive 1‐associated receptor kinase 1 (BAK1). These results suggest that NbPPI1 functions as a DAMP in N. benthamiana; this novel DAMP provides a potentially useful target for improving plant resistance to Pytophthora pathogens.     

Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes

Neurodevelopmental disorders(NDDs) are a set of complex disorders characterized by diverse and cooccurring clinical symptoms. The genetic contribution in patients with NDDs remains largely unknown.Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations(DNMs) in 86 genes and 2,385 rare inherited mutations(RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes. Furthermore, the DNMs of16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as background. We prioritize 26 novel candidate genes. Notably, six of these genes d ITSN1, UBR3, CADM1,RYR3, FLNA, and PLXNA3 d preferably contribute to autism spectrum disorders(ASDs), as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse model. Importantly, these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated networks. Together, our study expands the genetic spectrum of Chinese NDDs,further facilitating both basic and translational research.     

W86F/W86A突变对细菌视紫红质光循环影响的差异性分析

细菌视紫红质(bacteriorhodopsin,bR)是一种光驱受体蛋白,每个活性单元由3个单体组成,每个单体由一分子视蛋白和一分子的视黄醛发色团共价结合而成,其功能为从胞内向胞外定向传输质子,利用形成的质子浓度梯度将光能转化为化学能.光照后视黄醛发色团构型发生all-trans向13-cis转变,蛋白的构象也随之发生了一系列具有稳定中间态的变化并驱动质子的定向传递.为探讨bR视黄醛键合区保守性氨基酸色氨酸86 (Tryptop-han86,w86)对其光循环中间态和质子泵功能的影响,本研究采用定点突变技术将W86突变为侧链大小不同的F86和A86,通过原位紫外-可见光吸收光谱、闪光光解光谱、pH滴定、固体核磁共振等技术手段,探究W86F和W86A突变对bR光循环及质子泵功能影响差异性的分子机制.结果 表明,W86F和W86A突变均造成了bR暗适应状态下视黄醛顺反异构平衡向顺式构型占优的方向移动,且W86F突变可造成反式构型的完全消失.此外,无论是W86F还是W86A突变都造成了蛋白光循环中间态的减弱且衰减延长,以及质子泵功能减弱,但影响机制各有所不同,这可能与这两个突变对视黄醛多烯链上电子云的分布以及周围残基造成的扰动程度不同有关.     

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou,China

Science China Life Sciences - Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been...     

Understanding the “SMART” features of hematopoietic stem cells and beyond

Science China Life Sciences - Since the huge success of bone marrow transplantation technology in clinical practice, hematopoietic stem cells (HSCs) have become the gold standard for defining the...     

Re-detectable positive SARS-CoV-2 RNA tests in patients who recovered from COVID-19 with intestinal infection

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a novel coronavirus that causes Coronavirus Disease 2019(COVID-19)(Yang and Wang,2020),has spread to more than 200 countries and infected more than 9,000,000 people as of Jun 2020.Tens of thousands of patients with COVID-19 have recovered and been discharged from hospital.However,there are reports of recovered patients who subsequently tested positive for SARSCoV-2 after discharge(re-detectable positive,RP)(An et al.,2020;Lan et al.,2020),and this has led to increasing focus on the mechanism(s)underlying RP.