DLGCN:基于图卷积网络的药物-lncRNA[]关联预测

为实现高通量识别新的药物-长链非编码RNA(Long non-coding RNA, lncRNA)关联,本文提出了一种基于图卷积网络模型来识别潜在药物-lncRNA关联的方法DLGCN(Drug-LncRNA graph convolution network)。首先,基于药物的结构信息和lncRNA的序列信息分别构建了药物-药物和lncRNA-lncRNA相似性网络,并整合实验证实的药物-lncRNA关联构建了药物-lncRNA异质性网络。然后,将注意力机制和图卷积运算应用于该网络中,学习药物和lncRNA的低维特征,基于整合的低维特征预测新的药物-lncRNA关联。通过效能评估,DLGCN的受试者工作特性曲线下面积(Area under receiver operating characteristic, AUROC)达到0.843 1,优于经典的机器学习方法和常见的深度学习方法。此外,DLGCN预测到姜黄素能够调控lncRNA MALAT1的表达,已被最近的研究证实。DLGCN能够有效预测药物-lncRNA关联,为肿瘤治疗新靶点的识别和抗癌药物的筛选提供了重要参考。     

5份粳型亲籼种质的生物学特性及育种利用

本研究以5份自主选育的粳型亲籼种质明恢413、明恢1616、明恢1707、明恢512和明恢509为研究材料,通过对其生物学特性和育种利用进行研究和评价,以期为今后开展粳型亲籼种质资源的选育和籼粳亚种间杂种优势的利用提供理论参考。生物学特性研究结果表明:5份粳型亲籼种质的播始历期偏长,株高适中,直立穗型,穗子小,着粒密,单株有效穗数多,结实率均在75%以上,千粒重中等。程式指数判定表明,明恢413、明恢1616、明恢1707、明恢512的籼粳属性为偏粳;明恢509的籼粳属性为粳。5份粳型亲籼种质均具有良好的亲籼性,与籼型两系不育系测交F1的结实率均在75%以上,最高可达89.80%;同时能够恢复野败型、印水型、K型等籼型三系不育系,测交F1的结实率均在80%以上,其恢复谱广、恢复力强。光合特性分析表明,其剑叶在生育后期能够保持较高的光合速率,利于籽粒的充实饱满。5份粳型亲籼种质的杂种优势表现:除播始历期、株高和千粒重外,在穗长、单株有效穗数、每穗总粒数、结实率、一次枝梗数和二次枝梗数等性状上均表现出明显的竞争优势。其中,穗长、一次枝梗数、二次枝梗数和每穗总粒数所表现出的竞争优势均超过10...     

Genetic validation of Aspergillus fumigatus phosphoglucomutase as a viable therapeutic target in invasive aspergillosis

Aspergillus fumigatus is the causative agent of invasive aspergillosis, an infection with mortality rates of up to 50%. The glucan-rich cell wall of A. fumigatus is a protective structure that is absent from human cells and is a potential target for antifungal treatments. Glucan is synthesized from the donor uridine diphosphate glucose, with the conversion of glucose-6-phosphate to glucose-1-phosphate by the enzyme phosphoglucomutase (PGM) representing a key step in its biosynthesis. Here, we explore the possibility of selectively targeting A. fumigatus PGM (AfPGM) as an antifungal treatment strategy. Using a promoter replacement strategy, we constructed a conditional pgm mutant and revealed that pgm is required for A. fumigatus growth and cell wall integrity. In addition, using a fragment screen, we identified the thiol-reactive compound isothiazolone fragment of PGM as targeting a cysteine residue not conserved in the human ortholog. Furthermore, through scaffold exploration, we synthesized a para-aryl derivative (ISFP10) and demonstrated that it inhibits AfPGM with an IC₅₀ of 2 μM and exhibits 50-fold selectivity over the human enzyme. Taken together, our data provide genetic validation of PGM as a therapeutic target and suggest new avenues for inhibiting AfPGM using covalent inhibitors that could serve as tools for chemical validation.     

超抗原SEA增强小鼠对HBV DNA 疫苗的免疫反应

观察超抗原SEA(D227A)的真核表达载体(pmSEA),对HBVDNA疫苗诱导Balbc小鼠(H2d)免疫应答的调节作用。肌内注射空载体pcDNA3、HBVDNA疫苗加pmSEA佐剂(pHBVS2S+pmSEA)或不加佐剂(pHBVS2S);ELISA法测定血清抗HBs;ELISPOT检测分泌IFNγ的脾淋巴细胞;4h51Cr释放法检测小鼠脾细胞CTL活性。HBVDNA佐剂组免疫小鼠抗HBsAg抗体滴度明显高于不加佐剂组,其IgG1IgG2a的比例不同于多肽免疫组,二者分别为0.282与10。HBVDNA佐剂组均能增强IgG1和IgG2a的产生,是不加佐剂组的1.36、1.73倍。佐剂组小鼠脾淋巴细胞IFNγ的分泌量是不加佐剂组2～3倍。CTL细胞杀伤活性(E:T=100)佐剂组与不加佐剂组分别为:69.77%±7.5%、42.81%±7.7%,差异显著(P<0.05)。HBVDNA疫苗具有较强的免疫原性,能够诱导机体产生特异性的抗体及CTL反应;pmSEA佐剂能够提高小鼠对DNA疫苗的免疫应答,有望成为DNA疫苗的免疫佐剂。     

冀西北坝上半干旱区南瓜油葵间作的水分效应

针对冀西北高原水源匮乏、利用低效问题,于2009-2010年在农业部张北农业资源与生态环境重点野外观测试验站通过南瓜//油葵不同间作群体结构试验,探讨了该区南瓜水分高效的种植方式。试验设南瓜单作（Sp）,南瓜行间作1行油葵（IC1）,南瓜行间作2行油葵（IC2）和油葵单作（So）4个处理。结果表明,南瓜行间种植两行油葵（IC2）在南瓜生长中后期出现了油葵与南瓜争夺水分的现象,而南瓜行间种植一行油葵（IC1）无此现象。各处理间水量平衡各分量有较大的差异,在整个生育时期降雨量为201.6mm的情况下,渗漏量占的比重非常小,并且土壤蓄水量变化均为负值,绝大部分水分都是以气态水蒸散掉,但不同间作方式蒸散失水量不同,其中IC1较So、Sp和IC2分别少散失土壤水分36.33%、19.00%和34.87%。得益于油葵的偏利效应使南瓜经济产量下降30.00% ~71.42%,而间种油葵单株产量相对单作田提高190.71%~ 241.26%,虽其土地当量比LER和水分当量比WER分别达1.08~1.22和1.07~1.26,但IC1复合群体的经济效益只能与南瓜单作田持平,其他处理明显低于单作南瓜。在冀西北高原雨养背景下,稀植高效的南瓜单作生产能够实现对区域水资源的高效利用。     

高效液相色谱测定发酵液中1，3－二羟基丙酮（DHA）方法的建立

摘要：本文建立了简单且准确的测定1,3-二羟基丙酮（DHA）的高效液相色谱（HPLC）方法。以Alltima C18（5μm,250×4.6mm）为分离柱,5％甲醇水溶液（0.05％H3PO4调pH至3.0）,流速为1mL/min,用紫外检测器在200nm处检测DHA。结果测得DHA标准样品的保留时间为6.2min,并测得DHA的线性范围为0.1～10.0 g/L。用HPLC法测得以甘油为底物发酵产DHA发酵液中DHA含量为6.2 g/L。并证明高效液相色谱法可有效应用于产DHA发酵过程中产物的检测。     

力学环境对软骨基质代谢的影响

正常关节软骨所受压力是由动态压力与静态压力交替完成。压力引起软骨一系列生理变化包括细胞及细胞外基质成分变形、组织内液体流动、水流电位和生理生化变化。这些变化直接调控细胞外基质代谢。体外构建有良好功能的组织工程化软骨是目前软骨病变、缺损理想的修复方法。研究力学环境对软骨基质代谢的影响,对构建组织工程化软骨有深远意义。     

科尔沁沙地湖泊消涨对气候变化的响应

湖泊是受气候变化影响显著的地理单元之一,不同地区湖泊消涨与气候变化关系的分析是理解陆地水文过程对未来气候变化响应的关键之一。对干旱、半干旱地区而言,湖泊消涨对气候变化的响应是干旱区生态保护和未来可持续发展的重要指征。气候变化对湖泊的影响研究在不同的区域已有较多的研究,但是针对湖泊群且基于湖泊大小分级和不同降水强度的对应研究还很鲜见。有鉴于此,作者在RS和GIS技术支持下,采用湖泊大小和降水强度分级的方法,分析了科尔沁沙地湖泊群消涨与气候变化的关系。在1971-2010年间,年均气温波动升高和降水量波动减少是该区域的主要气候变化特点。从5年移动平均分析来看,1990年是气温变化的转折点,1991-2010年的平均气温7.36（?0.55）℃,高于全球同期平均增温0.52℃。在1975-2009年间,科尔沁沙地湖泊面积和数量的变化趋势呈抛物线型减少,在1995年湖泊面积与数量最高。进入21世纪,湖泊面积萎缩、数量减少呈明显的加快趋势。到2009年,面积>0.05km2湖泊数量仅为81个,不足高峰期（1995年）的11%;湖泊总面积为4375.0hm2,不到1995年的26%。本研究表明,湖泊消涨主要受到年降水量波动影响,与年内降水分布格局无关,气温变化的影响不显著。     

Protein kinase C delta null mice exhibit structural alterations in articular surface,intra-articular and subchondral compartments

IntroductionStructural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta (PKC-δ) plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known.MethodsHistological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone–cartilage interface in PKC-δ knockout (KO) mice. The morphology and organization of chondrocytes were studied using confocal microscopy. Glycosaminoglycan content was studied by micromass culture of chondrocytes of PKC-δ KO mice.ResultsWe uncovered atypical structural demarcation between articular cartilage and subchondral bone of PKC-δ KO mice. Histology analyses revealed a thickening of the articular cartilage and calcified bone–cartilage interface, and decreased safranin O staining accompanied by an increase in the number of hypertrophic chondrocytes in the articular cartilage of PKC-δ KO mice. Interestingly, loss of demarcation between articular cartilage and bone was concomitant with irregular chondrocyte morphology and arrangement. Consistently, in vivo calcein labeling assay showed an increased intensity of calcein labeling in the interface of the growth plate and metaphysis in PKC-δ KO mice. Furthermore, in vitro culture of chondrocyte micromass showed a decreased alcian blue staining of chondrocyte micromass in the PKC-δ KO mice, indicative of a reduced level of glycosaminoglycan production.ConclusionsOur data imply a role for PKC-δ in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction.

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