TNFAIP8 protein functions as a tumor suppressor in inflammation-associated colorectal tumorigenesis

Tumor necrosis factor-α-induced protein 8 (TNFAIP8 or TIPE) is a member of the TNFAIP8 family. While TIPE was broadly considered to be pro-cancerous, its precise roles in carcinogenesis especially those of the intestinal tract are not clear. Here, we show that genetic deletion of TIPE in mice exacerbated chemical-induced colitis and colitis-associated colon cancer. Loss of TIPE exacerbated inflammatory responses and inflammation-associated dysbiosis, leading to the activation of NF-κB and STAT3, and it also accelerated dysplasia, DNA damage and proliferation of intestinal epithelial cells. We further show that colon microbiota were essential for increased tumor growth and progression in Tipe^−/− mice. The tumor suppressive function of TIPE originated primarily from the non-hematopoietic compartment. Importantly, TIPE was downregulated in human colorectal cancers, and patients with low levels of Tipe mRNA were associated with reduced survival. These results indicate that TIPE serves as an important modulator of colitis and colitis-associated colon cancer.Subject terms: Cancer microenvironment, Chronic inflammation     

管氏肿腿蜂密度对其寄生及繁衍能力的影响

本研究以管氏肿腿蜂Sclerodermus guani雌成蜂为研究对象,拟探明寄生蜂密度对其寄生及繁衍能力的影响,为该寄生蜂行为生物学研究提供科学依据。本研究以松墨天牛Monochamus alternatus幼虫(0.350～0.450 g)为寄主,设置8种不同雌蜂密度(1～8头/寄主),对比分析不同雌蜂密度下,管氏肿腿蜂的寄生行为和效能,以及雌蜂生殖力和子代适合度变化。结果表明,随雌蜂密度增加,管氏肿腿蜂蛰刺发生前历时、寄主麻痹历时及产卵前历时均缩短。基于Hassell-Varley数据模型分析(E=0.9023×P^-0.9378),雌蜂的寻找效应随自身密度增加而逐渐变小,雌蜂间的干扰降低了寄生效能。雌蜂生殖力随其密度增加而降低,单雌平均产卵量及产雌量明显下降,雌蜂密度为1头/寄主时,单雌产卵量分别是4头/寄主和8头/寄主处理下的1.4倍和2.4倍。子代适合度也随雌蜂密度增加而变化,子代发育历期明显缩短,低龄幼虫存活率和单雌体重均下降。雌蜂密度为1头/寄主时,其子代发育历期最长,平均为26.7 d, 8头/寄主时最短,平均为24.0 d。雌蜂密度为1头/寄主时...     

Epac‐2 ameliorates spontaneous colitis in Il‐10 −/− mice by protecting the intestinal barrier and suppressing NF‐κB/MAPK signalling

Intestinal barrier dysfunction and intestinal inflammation interact in the progression of Crohn''s disease (CD). A recent study indicated that Epac‐2 protected the intestinal barrier and had anti‐inflammatory effects. The present study examined the function of Epac‐2 in CD‐like colitis. Interleukin‐10 gene knockout (Il‐10 ^−/−) mice exhibit significant spontaneous enteritis and were used as the CD model. These mice were treated with Epac‐2 agonists (Me‐cAMP) or Epac‐2 antagonists (HJC‐0350) or were fed normally (control), and colitis and intestinal barrier structure and function were compared. A Caco‐2 and RAW 264.7 cell co‐culture system were used to analyse the effects of Epac‐2 on the cross‐talk between intestinal epithelial cells and inflammatory cells. Epac‐2 activation significantly ameliorated colitis in mice, which was indicated by reductions in the colitis inflammation score, the expression of inflammatory factors and intestinal permeability. Epac‐2 activation also decreased Caco‐2 cell permeability in an LPS‐induced cell co‐culture system. Epac‐2 activation significantly suppressed nuclear factor (NF)‐κB/mitogen‐activated protein kinase (MAPK) signalling in vivo and in vitro. Epac‐2 may be a therapeutic target for CD based on its anti‐inflammatory functions and protective effects on the intestinal barrier.     

三只羊岩溶峰丛洼地桃树优质高产栽培技术研究

在广西三只羊岩溶峰丛洼地进行幼龄期桃树作物套种、施肥以及疏果等栽培技术的对比试验。结果表明,套种黄豆能明显促进桃树基茎和主枝直径的增长,套种玉米则抑制桃树基茎和主枝直径的增长;混施猪粪水和磷肥的桃树其果实品质明显优于混施羊粪和磷肥以及牛粪和磷肥的桃树的果实;同时,中等疏果强度,即保留枝条上桃果间距14~18cm,可获最大种植效益,桃果重量增加50.3%,桃树的产值提高52.9%。     

褪黑素对盐胁迫下普通菜豆芽期核酸修复的调控机制

普通菜豆(Phaseolus vulgaris)是重要的食用豆作物,然而其极易受盐胁迫危害,导致产量下降。褪黑素能提高植物耐盐能力。为探明外源褪黑素调控普通菜豆耐盐能力的机制,以普通菜豆品种奶花芸豆(GZ-YD014)为实验材料,设置水(W,对照)、盐胁迫(S)和盐胁迫+100μmol·L^–1褪黑素(M+S) 3个处理。结果发现,盐胁迫抑制了普通菜豆胚根的生长,使其长度、表面积、体积以及直径显著降低,外源褪黑素可缓解盐胁迫对普通菜豆胚根生长的抑制。外施褪黑素显著降低盐胁迫下活性氧积累和丙二醛(MDA)含量,提高保护酶(过氧化物酶、超氧化物歧化酶、过氧化氢酶以及抗坏血酸过氧化物酶)活性,增加渗透调节物质(可溶性糖和可溶性蛋白)以及生长素(IAA)、赤霉素(GA)和玉米素(ZT)的含量,降低脱落酸(ABA)含量。通过转录组分析挖掘出217个差异表达基因(DEGs),DEGs在GO富集中显著(P-value<0.05)富集到核酸相关条目上,在KEGG富集中显著(P-value<0.05)富集到核酸损伤修复(包括碱基切除修复、错配修复以及核苷酸切除修复)通路。...     

NKG2D discriminates diverse ligands through selectively mechano‐regulated ligand conformational changes

Stimulatory immune receptor NKG2D binds diverse ligands to elicit differential anti‐tumor and anti‐virus immune responses. Two conflicting degeneracy recognition models based on static crystal structures and in‐solution binding affinities have been considered for almost two decades. Whether and how NKG2D recognizes and discriminates diverse ligands still remain unclear. Using live‐cell‐based single‐molecule biomechanical assay, we characterized the in situ binding kinetics of NKG2D interacting with different ligands in the absence or presence of mechanical force. We found that mechanical force application selectively prolonged NKG2D interaction lifetimes with the ligands MICA and MICB, but not with ULBPs, and that force‐strengthened binding is much more pronounced for MICA than for other ligands. We also integrated steered molecular dynamics simulations and mutagenesis to reveal force‐induced rotational conformational changes of MICA, involving formation of additional hydrogen bonds on its binding interface with NKG2D, impeding MICA dissociation under force. We further provided a kinetic triggering model to reveal that force‐dependent affinity determines NKG2D ligand discrimination and its downstream NK cell activation. Together, our results demonstrate that NKG2D has a discrimination power to recognize different ligands, which depends on selective mechanical force‐induced ligand conformational changes.     

Spatiotemporal cytokinin response imaging and ISOPENTENYLTRANSFERASE 3 function in Medicago nodule development

Most legumes can establish a symbiotic association with soil rhizobia that trigger the development of root nodules. These nodules host the rhizobia and allow them to fix nitrogen efficiently. The perception of bacterial lipo-chitooligosaccharides (LCOs) in the epidermis initiates a signaling cascade that allows rhizobial intracellular infection in the root and de-differentiation and activation of cell division that gives rise to the nodule. Thus, nodule organogenesis and rhizobial infection need to be coupled in space and time for successful nodulation. The plant hormone cytokinin (CK) contributes to the coordination of this process, acting as an essential positive regulator of nodule organogenesis. However, the temporal regulation of tissue-specific CK signaling and biosynthesis in response to LCOs or Sinorhizobium meliloti inoculation in Medicago truncatula remains poorly understood. In this study, using a fluorescence-based CK sensor (pTCSn::nls:tGFP), we performed a high-resolution tissue-specific temporal characterization of the sequential activation of CK response during root infection and nodule development in M. truncatula after inoculation with S. meliloti. Loss-of-function mutants of the CK-biosynthetic gene ISOPENTENYLTRANSFERASE 3 (IPT3) showed impairment of nodulation, suggesting that IPT3 is required for nodule development in M. truncatula. Simultaneous live imaging of pIPT3::nls:tdTOMATO and the CK sensor showed that IPT3 induction in the pericycle at the base of nodule primordium contributes to CK biosynthesis, which in turn promotes expression of positive regulators of nodule organogenesis in M. truncatula.

Precise spatial and temporal characterization of cytokinin (CK) responses reveals the function of the CK biosynthesis gene ISOPENTENYLTRANSFERASE 3 during nodule development in Medicago truncatula.     

Roles of mesenchymal stem cells and exosomes in interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder pain/discomfort, urgency, urinary frequency, pelvic pain and nocturia. Although the pathophysiology of IC/BPS is not fully understood, the hypothesis suggests that mast cell activation, glycosaminoglycan (GAG) layer defects, urothelium permeability disruption, inflammation, autoimmune disorder and infection are potential mechanisms. Mesenchymal stem cells (MSCs) have been proven to protect against tissue injury in IC/BPS by migrating into bladders, differentiating into key bladder cells, inhibiting mast cell accumulation and cellular apoptosis, inhibiting inflammation and oxidative stress, alleviating collagen fibre accumulation and enhancing tissue regeneration in bladder tissues. In addition, MSCs can protect against tissue injury in IC/BPS by secreting various soluble factors, including exosomes and other soluble factors, with antiapoptotic, anti‐inflammatory, angiogenic and immunomodulatory properties in a cell‐to‐cell independent manner. In this review, we comprehensively summarized the current potential pathophysiological mechanisms and standard treatments of IC/BPS, and we discussed the potential mechanisms and therapeutic effects of MSCs and MSC‐derived exosomes in alleviating tissue injury in IC/BPS models.