Sinensetin ameliorates high glucose-induced diabetic nephropathy via enhancing autophagy in vitro and in vivo

Diabetic nephropathy (DN) affects around 40% of people with diabetes, the final outcome of which is end-stage renal disease. The deficiency of autophagy and excessive oxidative stress have been found to participate in the pathogenesis of DN. Sinensetin (SIN) has been proven to have strong antioxidant capability. However, the effect of SIN on DN has not been studied. We examined the effect of SIN on cell viability and autophagy in the podocyte cell line, MPC5 cells, treated with high glucose (HG). For in vivo studies, DN mice models were established by intraperitoneal injected with streptozotocin (40 mg/kg) for 5 consecutive days and fed with a 60% high-fat diet, and SIN was given (10, 20, and 40 mg/kg) for 8 weeks via intraperitoneal injection. The results showed that SIN could protect MPC5 cells against HG-induced damage and significantly improve the renal function of DN mice. Moreover, SIN remarkably restored the autophagy activity of MPC5 cells which was inhibited under HG conditions. Consistent with this, SIN efficiently improved autophagy in the kidney tissue of DN mice. In brief, our findings demonstrated the protective effect of SIN on DN via restoring the autophagic function, which might provide a basis for drug development.     

Metabolic alterations in patients with Helicobacter pylori-related gastritis: The H. pylori-gut microbiota-metabolism axis in progression of the chronic inflammation in the gastric mucosa

Purpose

To characterize the serum metabolism in patients with Helicobacter pylori-positive and H. pylori-negative gastritis.

Methods

Clinical data and serum gastric function parameters, PGI (pepsinogen I), PGII, PGR (PGI/II), and G-17 (gastrin-17) of 117 patients with chronic gastritis were collected, including 57 H. pylori positive and 60 H. pylori negative subjects. Twenty cases in each group were randomly selected to collect intestinal mucosa specimens and serum samples. The gut microbiota profiles were generated by 16S rRNA gene sequencing, and the serum metabolites were analyzed by a targeted metabolomics approach based on liquid chromatography–mass spectrometry (LC–MS) technology.

Results

Altered expression of 20 metabolites, including isovaleric acid, was detected in patients with HPAG. Some taxa of Bacteroides, Fusobacterium, and Prevotella in the gut microbiota showed significant correlations with differentially expressed metabolites between H. pylori positive and H. pylori negative individuals. As a result, an H. pylori-gut microbiota-metabolism (HGM) axis was proposed.

Conclusion

Helicobacter pylori infection may influence the progression of mucosal diseases and the emergence of other complications in the host by altering the gut microbiota, and thus affecting the host serum metabolism.     

缺铁胁迫对梨叶片中GA信号转导相关基因的影响

以不同程度缺铁的‘砀山酥梨’组培苗为实验材料,应用ELISA法测定叶片中内源GA含量,并依据NCBI上GA氧化酶GA2ox同源基因的保守序列,采用RACE技术克隆其基因全长,从梨基因组数据库中比对获得GA受体GID1的4个等位基因和DELLA蛋白的4个等位基因,通过实时RT-PCR分析GA2ox基因和GID1的4个等位基因和DELLA蛋白的4个等位基因的相对表达量,以探讨缺铁对梨叶片GA含量及其信号转导相关基因表达的影响。结果表明:(1)梨叶片中GA含量随着其缺铁程度的加重而增加。(2)克隆出梨叶片中GA2ox基因,其cDNA全长为1 014bp(GenBank登录号为KJ008976)。(3)GA2ox基因的表达量并未随梨缺铁程度增加而上升;GA受体GID1的4个等位基因相对表达量均随梨缺铁程度的加重而增加,其相对表达量与GA含量呈正相关关系;在DELLA蛋白的4个等位基因中,仅DELLA1相对表达量随着梨缺铁程度的加重而逐渐增加,说明DELLA1对缺铁胁迫最敏感。推测梨缺铁诱导了GA合成,但并没有促进活性GA向无活性GA转化。     

基于宏基因组技术解析南极不同纬度地区土壤抗生素抗性基因的分布与迁移

[目的] 南极洲不同地区环境极端多样,且受人类活动影响不一。本研究旨在探究南极不同纬度地区土壤抗生素抗性基因（ARGs）的分布特征与迁移机制。[方法] 下载南极不同纬度地区及加拿大阿尔伯特地区养殖场附近土壤宏基因组数据集,利用MetaWRAP进行组装,使用CARD、PlasFlow和ICEberg数据库对ARGs与可移动遗传元件（MGEs）进行注释。[结果] 在南极不同纬度地区土壤中,优势菌门为变形菌门、放线菌门、拟杆菌门和厚壁菌门。共注释出25类406种ARGs,以多重耐药类、四环素类及氨基糖苷类抗生素抗性基因为主。NMDS分析结果表明,南极不同纬度地区与养殖场附近土壤中ARGs的分布特征显著不同（ANISOM,P=0.001）。南极高纬度地区ARGs占总基因数的比例为0.28%,显著低于低纬度地区（1.93%,P<0.01）。不同抗生素类型的ARGs呈现不同的区域分布模式,其中硝基咪唑类、氨基糖苷类、糖肽类与大环内酯类ARGs主要分布在南极高纬度地区,四环素类与磺胺类ARGs主要分布在南极低纬度地区（P<0.05）。南极土壤中ARGs的迁移研究表明,质粒携带的ARGs占检测到的ARGs的17%。同时,共发现163个整合与接合元件（ICEs）可携带多抗耐药类、肽类和四环素类等14类ARGs。这些携带ARGs的ICEs主要分布于α-、β-与γ-变形菌纲中。[结论] 南极高纬度与南极低纬度地区土壤中ARGs的分布存在差异性,质粒与ICEs共同介导ARGs的迁移。本研究为进一步了解抗生素时代之前的原始抗性组提供数据基础。     

一株抗蓝舌病病毒8型VP2蛋白单克隆抗体识别的线性抗原表位的鉴定

为研究本实验室制备的一株抗蓝舌病病毒8型(BTV-8)VP2蛋白的单克隆抗体(MAb)3G11识别的B细胞抗原表位,利用噬菌体肽库展示技术对3G11识别的抗原表位进行筛选并鉴定。经过4轮淘选后挑取蓝斑测序,测序结果经分析后获得KLLAT序列,与BTV-8 VP2蛋白氨基酸序列比对后获得共同的短肽序列为283LL284;合成4种短肽序列:KLLAA、KALAT、KLAAT和KLLAT,与3G11细胞上清和腹水分别进行间接ELISA鉴定,结果表明,短肽KLLAA和KLLAT与3G11细胞上清及腹水具有较强的结合能力;与24种BTV标准阳性血清反应结果表明,这两种短肽都可与BTV-8阳性血清发生特异性反应;序列分析结果可见,该表位的氨基酸序列283LL284在不同来源的BTV-8毒株间保守,确定283LL284为MAb3G11识别抗原表位的关键氨基酸。本研究为建立8型BTV特异性的免疫学检测方法和相关病毒蛋白的功能研究奠定了基础。     

SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition

Thyroid cancer (TC) is one of the most common malignancies involving the head and neck, and its incidences are increasing every year. Small G protein signaling modulators 2 (SGSM2) belongs to a newly identified protein group that contributes to numerous cancer progression. However, its role in TC remains unknown. The aim of this study was to explore the functions and underlying molecular mechanism of SGSM2 in the progression of thyroid tumorigenesis. Here, we demonstrated that SGSM2 expression was markedly decreased in TC, and that lower SGSM2 expression was potentially related to worse patient prognosis. Meanwhile, the SGSM2 levels were not directly correlated with BRAF or RAS mutations in TC. Based on our functional analysis, ectopic SGSM2 expression strongly prevented cell proliferation, migration, invasion, and tumorigenic activity in TC cells that harbored wild type RAS. Mechanistically, we demonstrated that SGSM2 interacted with Small G protein Ras-associated protein 1(RAP1) and augmented its activity. Activated RAP1 then competitively suppressed RAS activation and thereby downregulated output of MAPK/ERK and PI3K/Akt networks, which are primary contributors of TC. In summary, the present study reports a tumor suppressive role of SGSM2 in TC. Moreover, we revealed the underlying molecular mechanism, thus providing a potential therapeutic target for TCs that harbor wild type RAS.Subject terms: Prognostic markers, Tumour biomarkers, Thyroid cancer

A schematic model of SGSM2 suppressing the progression of RAS^WT thyroid cancer.     

Three-dimensional domain swapping as a mechanism to lock the active conformation in a super-active octamer of SARS-CoV main protease

Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses. The main protease (M^pro) of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing. M^pro is initially produced as part of viral polyproteins and it is matured by autocleavage. Here, we report that, with the addition of an N-terminal extension peptide, M^pro can form a domain-swapped dimer. After complete removal of the extension peptide from the dimer, the mature M^pro self-assembles into a novel super-active octamer (AO-M^pro). The crystal structure of AO-M^pro adopts a novel fold with four domain-swapped dimers packing into four active units with nearly identical conformation to that of the previously reported M^pro active dimer, and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains. Compared with the previously well characterized form of M^pro, in equilibrium between inactive monomer and active dimer, the stable AO-M^pro exhibits much higher proteolytic activity at low concentration. As all eight active sites are bound with inhibitors, the polyvalent nature of the interaction between AO-M^pro and its polyprotein substrates with multiple cleavage sites, would make AO-M^pro functionally much more superior than the M^pro active dimer for polyprotein processing. Thus, during the initial period of SARS-CoV infection, this novel active form AO-M^pro should play a major role in cleaving polyproteins as the protein level is extremely low. The discovery of AO-M^pro provides new insights about the functional mechanism of M^pro and its maturation process.     

柴达木盆地荒漠植物功能性状及其对环境因子的响应

植物功能性状是植物适应环境的外在表达,反映了植物在不同环境中的生存策略,探究干旱区荒漠植物功能性状及其与环境之间的关系,有助于理解植物适应极端干旱环境的生态对策,为保护荒漠地区生态系统提供理论依据。以柴达木盆地为研究区,选取8个植物功能性状指标,包含4种植物生活型,10种荒漠植物,探究荒漠植物功能性状的基本特征及其对环境因子的响应。研究表明：柴达木盆地植物叶片碳含量(LCC)、叶片氮含量(LNC)、叶片磷含量(LPC)、叶片C∶N、叶片N∶P、叶片稳定碳同位素(Leafδ¹³C)、叶片干物质含量(LDMC)和植株高度(Height)的变化范围分别为272.07—466.00mg/g、12.40—44.50mg/g、0.51—2.07mg/g、8.62—29.74、11.37—39.29、-27.38‰—-14.80‰、100—480mg/g、3.00—264.22cm。不同生活型间LNC、LPC、叶片N∶P和LDMC差异不显著,LCC、叶片C∶N、叶片δ¹³C和植株高度存在显著差异。LNC、LPC和叶片N∶P与全球、中国和青藏高原相比不存在显...