肝细胞癌远处转移相关DNA拷贝数变异的全基因组分析

目的探讨与肝细胞癌(HCC)远处转移相关的DNA拷贝数变异(copy number alteration,CNA)分子标志。方法采用高分辨率Agilent 244K微阵列比较基因组杂交(aCGH)方法检测63例HCC样本基因组DNA的CNA特征。以Log-rank检验、Kaplan-Meier生存分析以及Cox风险比例模型,分析各DNA片段CNA与HCC远处转移的相关性。结果染色体片段12p12.2-13.31丢失是HCC患者远处转移的显著危险因素(P<0.01,Log-rank检验)。与非丢失者相比,12p12.2-13.31丢失HCC患者的远处转移风险比(hazard ratio,HR)为22.98(95%CI=4.29～123.22,P<0.01)。多变量Cox回归分析显示,12p12.2-13.31丢失是HCC远处转移的独立预测因素(HR=7.94,95%CI=1.14～55.61,P<0.05)。结论染色体片段12p12.2-13.31丢失增加HCC远处转移风险,可作为预测HCC远处转移的一个分子标志。

Trace metal elements: a bridge between host and intestinal microorganisms

Trace metal elements, such as iron, copper, manganese, and zinc, are essential nutrients for biological processes. Although their intake demand is low, they play a crucial role in cell homeostasis as the cofactors of various enzymes. Symbiotic intestinal microorganisms compete with their host for the use of trace metal elements. Moreover, the metabolic processes of trace metal elements in the host and microorganisms affect the organism's health. Supplementation or the lack of trace metal elements in the host can change the intestinal microbial community structure and function. Functional changes in symbiotic microorganisms can affect the host's metabolism of trace metal elements. In this review, we discuss the absorption and transport processes of trace metal elements in the host and symbiotic microorganisms and the effects of dynamic changes in the levels of trace metal elements on the intestinal microbial community structure. We also highlight the participation of trace metal elements as enzyme cofactors in the host immune process. Our findings indicate that the host uses metal nutrition immunity or metal poisoning to resist pathogens and improve immunity.

Targeting small GTPases:emerging grasps on previously untamable targets.pioneered by KRAS

Small GTPases including Ras,Rho,Rab,Arf,and Ran are omnipresent molecular switches in regulating key cellular functions.Their dysregulation is a therapeutic target for tumors,neurodegeneration,cardiomyopathies,and infection.However,small GTPases have been historically recognized as“undruggable”.Targeting KRAS,one of the most frequently mutated oncogenes,has only come into reality in the last decade due to the development of breakthrough strategies such as fragment-based screening,covalent ligands,macromolecule inhibitors,and PROTACs.Two KRAS^(G12C)covalent inhibitors have obtained accelerated approval for treating KRAS^(G12C)mutant lung cancer,and allele-specific hotspot mutations on G12D/S/R have been demonstrated as viable targets.New methods of targeting KRAS are quickly evolving,including transcription,immunogenic neoepitopes,and combinatory targeting with immunotherapy.Nevertheless,the vast majority of small GTPases and hotspot mutations remain elusive,and clinical resistance to G12C inhibitors poses new challenges.In this article,we summarize diversified biological functions,shared structural properties,and complex regulatory mechanisms of small GTPases and their relationships with human diseases.Furthermore,we review the status of drug discovery for targeting small GTPases and the most recent strategic progress focused on targeting KRAS.The discovery of new regulatory mechanisms and development of targeting approaches will together promote drug discovery for small GTPases.

一株耐盐日本曲霉的筛选及其溶磷促生作用

【目的】从内蒙古种植葵花的盐碱地中筛选高效溶磷真菌,为盐碱地增产节肥开发生物肥料提供溶磷菌种资源。【方法】利用ITS r DNA序列鉴定菌株、固体培养基测定耐盐性,液体摇床培养与盆栽试验结合分析菌株溶磷能力,盆栽和田间试验明确菌株M1促进作物生长和增产作用;LC-MS技术测定菌株M1在液体培养基中分泌有机酸和植物激素含量,明确菌株M1的溶磷和促生机理。【结果】溶磷菌株M1鉴定为日本曲霉(Aspergillus japonicus)。液体培养基接种菌株M1培养6 d,以Ca_3(PO_4)_2为磷源时上清液有效磷达1020.89 mg/L,溶解率为63.30%;以AlPO_4为磷源时有效磷达995.69 mg/L,溶解率为48.59%;以贵州开阳磷矿粉、江苏锦屏磷矿粉、云南晋宁磷矿粉、河北钒山磷矿粉和云南昆阳磷矿粉为磷源接种菌株M1,从晋宁磷矿粉释放的有效磷浓度最高,达到363.64 mg/L。菌株M1可耐受10%NaCl。将M1制备的菌剂分别接种于施用Ca_3(PO_4)_2、AlPO_4和开阳磷矿粉3种磷源的4种盆栽试验土壤包括北京石灰性潮土、安徽黏性潮土、安徽水稻土和山东沿海盐潮土。结果显示,菌株M1对玉米植株促生效果显著,玉米植株鲜重比对照提高2.14%–90.91%、干重增加22.15%–268.28%;土壤有效磷提高21.81–24.27 mg/kg。菌株M1与4种土壤的适配性均高于对照菌株DSM 821。田间小区花生产量结果显示,接种溶磷菌剂M1增产效果最好,花生果实产量达4.46 t/hm^2,比不接种菌剂的对照处理增加0.81 t/hm^2,增产22.19%。菌株M1在含有磷酸三钙、磷酸铝和开阳磷矿粉3种难溶磷培养液中经过6 d培养,均产生7种有机酸,其中草酸和柠檬酸含量最高,分别为616.16 mg/L和413.69 mg/L;培养液均能检测到吲哚乙酸(IAA)和玉米素,IAA含量为15.45–77.58 mg/L,玉米素浓度为0.06–0.11 mg/L。【结论】获得了一株高效溶解多种难溶磷的日本曲霉菌M1,它能显著增加土壤有效磷、促进玉米生长和花生增产,与4种典型土壤适配性好,具有良好的农业应用前景。

一株高效拮抗向日葵菌核菌的细菌菌株YC16的筛选及其作用效果研究

[目的]筛选高效拮抗向日葵菌核菌的细菌菌株,为开发防治菌核菌病害、提高向日葵产量的生物菌剂提供菌种资源。[方法]以羧甲基纤维素钠(CMC)、小麦秸秆纤维素为唯一碳源的无机盐培养基,分离高效降解纤维素的细菌菌株;采用纤维素降解菌与菌核菌的平板对峙方法,进一步筛选拮抗菌核菌的菌株;利用16S rDNA序列鉴定菌株、PDYA平板对峙实验检验上述所选拮抗菌株的抑菌谱;采用离体向日葵新鲜叶片、草炭土基质盆栽实验,观察拮抗菌菌株抑制菌核菌生长的能力;温室盆栽和田间试验条件下,研究其防治向日葵菌核菌病害、促进生长和提高产量的效果。[结果]筛选了一株高效抑制菌核菌的细菌YC16,经过16S rDNA序列分析,鉴定为解淀粉芽孢杆菌。YC16菌株能够抑制8种病原真菌生长,包括齐整小核菌、腐皮镰孢菌、尖孢镰刀菌、稻梨孢、辣椒疫霉、镰刀菌、尖镰孢黄瓜专化型和向日葵菌核菌;抑制菌核菌感染叶片,抑制率达到了80.42%;抑制盆栽基质中菌核菌的菌丝生长,基质表面菌丝密度比对照减少了50%以上。盆栽接种YC16的向日葵生物量比对照提高54.9%,田间向日葵接种YC16菌剂对菌核菌引发的盘腐病防治效果达39%-100%,产量提高24.4%-30.2%。[结论]YC16生物菌剂施用于土壤,能够有效防治向日葵的茎腐病和盘腐病,展现了防治向日葵菌核病和提高产量的双重效果,是一株具有良好应用前景的高效菌种资源。

Potential role of Lactobacillus plantarum in colitis induced by dextran sulfate sodium through altering gut microbiota and host metabolism in murine model

Inflammatory bowel disease(IBD) is a chronic lifelong disease characterized by inflammation of the gastrointestinal tract.Although more and more treatment options serve IBD, there is still no cure. It is important to find an effective treatment for IBD.This study aims to investigate whether Lactobacillus plantarum(L. plantarum) could alleviate colitis induced by dextran sulfate sodium(DSS). Following the DSS challenge, L. plantarum on DSS-mediated inflammatory colon lesions in mice, and L.plantarum therapy heightened the relative abundance of the colon-resident Actinobacteria. Analysis of serum metabolomics also indicated that the content of MG(18:4(6 Z, 9 Z, 12 Z, 15 Z)/0:0/0:0) was increased in response to L. plantarum therapy, and this was also the case for indolepyruvate and 1-hydroxyibuprofen. However, 13-oxooctadecadienoic acid(13-oxo ODE) and indolylacryloylglycine content fell following the DSS challenge. Based on these results, the study elucidates the mitigatory effects of L. plantarum in colitis, which depend on its regulation of the colonic microbial community and its modification of serum metabolites. The results revealed that L. plantarum mitigated inflammatory colon lesions, reprogrammed the microbial community and altered the level of serum metabolites in a murine model challenged with DSS. The study may present a potential therapeutic strategy for colitis.

丹酚酸B通过介导SIRT3/FOXO1信号通路减轻非酒精性脂肪肝的氧化应激反应

丹酚酸B(Salvianolic acid B,Sal B)是一种多酚类抗氧化剂,已被证明在多种疾病中具有抗脂质积累、抗炎和清除氧自由基的活性。我们旨在研究Sal B是否可以改善非酒精性脂肪性肝病(Non-alcoholic fatty liver disease,NAFLD)的疾病进展并探索其可能的机制。通过油酸诱导HepG2细胞建立NAFLD模型组细胞,Sal B干预模型细胞建立治疗组细胞,进行生化分析及油红O染色检测各组细胞内脂质含量,通过免疫荧光及流式细胞仪检测细胞内活性氧(reactive oxygen species,ROS)含量;试剂盒及酶标仪定量细胞内脂氧化物丙二醛(Malonydialdehyde,MDA)的含量;通过蛋白质印迹分析、RT-qPCR和免疫沉淀(Immunoprecipitation,IP)检测参与氧化应激的信号通路蛋白,包括SIRT3、SOD2和FOXO1通路蛋白。研究发现,油酸(Oleic acid,OA)可以诱导细胞内脂质、过氧化物及脂氧化物的积累,降低SIRT3的表达,并促进FOXO1乙酰化。然而Sal B治疗后显著扭转了这些趋势。进一步通过转染SIRT3质粒及SIRT3 siRNA发现,SIRT3质粒转染后降低了乙酰化FOXO1的表达,并显著增强了Sal B诱导的SIRT3含量和对FOXO1去乙酰化的调节。SIRT3 siRNA转染后,Sal B诱导的乙酰化FOXO1下调被阻断,表明Sal B对细胞保护作用是通过SIRT3介导FOXO1去乙酰化所致。SIRT3/FOXO1通路是控制NAFLD氧化应激的关键治疗靶点,Sal B通过SIRT3介导FOXO1去乙酰化能减轻OA诱导的肝脂肪变性和氧化应激反应,对NAFLD细胞有保护作用。

Role of dietary amino acids and microbial metabolites in the regulation of pig intestinal health

With the rapid development of sequencing technology,research on pigs has focused on intestinal microbes.Accumulating evidence suggests that the metabolites of intestinal microbes are the key medium for interactions between microbes and the host.Amino acid metabolism is involved in the growth and immune processes of pigs.The gut microbes of pigs are heavily involved in the metabolism of amino acids in their hosts.Here,we review the latest relevant literature.Research findings show that microbial metabolites,such as indoles,short-chain fatty acids,and ammonia,play a key role in gut health.Moreover,we summarize the effects of amino acids on the structure of the gut microbial community and the metabolism of amino acids by pig gut microbes.Evidence shows that microbial amino acid metabolites act as signal molecules in the intestine and play an important role in the intestinal health of pigs.