African Swine Fever Virus MGF-110-9L-deficient Mutant Has Attenuated Virulence in Pigs

African swine fever virus(ASFV) is the etiological agent of African swine fever(ASF), an often lethal disease in domestic and wild pigs. ASF represents a major threat to the swine industry worldwide. Currently, no commercial vaccine is available because of the complexity of ASFV or biosecurity concerns. Live attenuated viruses that are naturally isolated or genetically manipulated have demonstrated reliable protection against homologous ASFV strain challenge. In the present study, a mutant ASFV strain with the deletion of ASFV MGF-110-9 L(ASFV-D9 L) was generated from a highly virulent ASFV CN/GS/2018 parental strain, a genotype II ASFV. Relative to the parental ASFV isolate, deletion of the MGF-110-9 L gene significantly decreased the ability of ASFV-D9 L to replicate in vitro in primary swine macrophage cell cultures. The majority of animals inoculated intramuscularly with a low dose of ASFV-D9 L(10 HAD50) remained clinically normal during the 21-day observational period. Three of five ASFV-D9 L-infected animals displayed low viremia titers and low virus shedding and developed a strong virus-specific antibody response, indicating partial attenuation of the ASFV-D9 L strain in pigs. The findings imply the potential usefulness of the ASFV-D9 L strain for further development of ASF control measures.     

Large-scale pharmacogenomic studies and drug response prediction for personalized cancer medicine

The response rate of most anti-cancer drugs is limited because of the high heterogeneity of cancer and the complex mechanism of drug action. Personalized treatment that stratifies patients into subgroups using molecular biomarkers is promising to improve clinical benefit. With the accumulation of preclinical models and advances in computational approaches of drug response prediction, pharmacogenomics has made great success over the last 20 years and is increasingly used in the clinical practice of personalized cancer medicine. In this article, we first summarize FDA-approved pharmacogenomic biomarkers and large-scale pharmacogenomic studies of preclinical cancer models such as patient-derived cell lines, organoids, and xenografts. Furthermore, we comprehensively review the recent developments of computational methods in drug response prediction, covering network, machine learning, and deep learning technologies and strategies to evaluate immunotherapy response. In the end, we discuss challenges and propose possible solutions for further improvement.     

C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein

Virologica Sinica - The Japanese encephalitis serogroup of the neurogenic Flavivirus has a specific feature that expresses a non-structural protein NS1′ produced through a programmed -1...     

既主内政, 又辖外交——以PHR为中心的基因网络调控植物-菌根真菌的共生

磷是植物生长发育必需的大量矿质营养元素, 但自然界大部分土壤都存在严重缺磷的问题。为了适应这一营养逆境, 植物演化出一系列低磷胁迫应答反应。通过改变基因的转录水平调控低磷胁迫应答反应, 而转录因子PHR1在调控植物对低磷胁迫的转录响应中起关键作用。此外, 大部分陆生植物还能与丛枝菌根真菌建立共生关系, 通过丛枝菌根真菌更有效地从土壤中获取磷元素。最近, 中国科学院分子植物科学卓越创新中心王二涛研究组发现, 以PHR为中心的转录调控网络控制植物-丛枝菌根真菌共生的建立。因此, PHR不但在维持植物细胞自身的磷稳态中发挥作用, 而且参与植物与外界微生物的相互作用, 为植物有效地从环境中获得磷元素提供了另外一条途径。     

胸腹腔镜联合Ivor Lewis食管癌根治术对食管癌患者肺功能、红细胞免疫及应激反应的影响

目的:探讨胸腹腔镜联合Ivor Lewis食管癌根治术对食管癌患者红细胞免疫、肺功能及应激反应的影响。方法:选取2016年5月~2018年6月期间我院收治的食管癌患者150例。根据随机数字表法将患者分为A组(n=75)和B组(n=75),A组予以开胸Ivor Lewis食管癌根治术,B组予以胸腹腔镜联合Ivor Lewis食管癌根治术,比较两组围术期指标、肺功能、红细胞免疫、应激反应及并发症。结果:B组手术时间、住院时间短于A组,术中出血量少于A组(P<0.05);两组清扫淋巴结数目比较无差异(P>0.05)。两组术后1个月第1秒末用力呼气容积(FEV1)、用力呼吸肺活量(FVC)、FEV1/FVC均降低,但B组高于A组(P<0.05)。两组术后3d白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)均升高,但B组低于A组(P<0.05)。两组术后3d红细胞免疫复合物花环率(RBC-ICR)升高,但B组低于A组(P<0.05);红细胞C3b受体花环率(RBC-C3bRR)、肿瘤红细胞花环率(TRR)降低,但B组高于A组(P<0.05)。两组患者术后并发症发生率比较差异无统计学意义(P>0.05)。结论:胸腹腔镜联合Ivor Lewis食管癌根治术治疗食管癌患者,可有效改善围术期各项指标,减轻对机体肺功能、红细胞免疫及应激反应的影响,且不增加并发症发生率。     

黄色肉芽肿性胆囊炎与胆囊癌的临床特征分析及螺旋CT检查的鉴别诊断价值

目的:研究黄色肉芽肿性胆囊炎(XGC)与胆囊癌的临床特征分析及螺旋CT检查的鉴别诊断价值。方法:选取从2018年1月-2020年12月于我院接受腹部螺旋CT检查的41例XGC患者纳入研究,记作XGC组,另取同期医院接受腹部螺旋CT检查的45例胆囊癌患者作为胆囊癌组。分析两组临床特征、螺旋CT检查结果表现,比较两组血清血管内皮生长因子(VEGF)、糖类抗原19-9(CA19-9)水平的差异。并以病理检查为金标准,分析螺旋CT检查用作XGC与胆囊癌鉴别诊断的价值。结果:XGC组患者食欲下降、体重下降人数占比均低于胆囊癌组(均P<0.05);而两组腹痛、黄疸、发热、白细胞(WBC)升高、谷丙转氨酶(ALT)升高、谷草转氨酶(AST)升高、胆囊扩张发生率对比差异无统计学意义(均P>0.05)。XGC组囊壁增厚均匀、壁内有低密度结节人数占比均低于胆囊癌组,而有肿大淋巴结人数占比高于胆囊癌组(均P<0.05)。螺旋CT检查诊断XGC的灵敏度、特异度、准确度分别为95.12(39/41)、95.56%(43/45)、95.35%(82/86)。XGC组患者血清VEGF、CA19-9水平均低于胆囊癌组,差异均有统计学意义(均P<0.05)。结论:XGC患者食欲下降、体重下降发生率低于胆囊癌患者,螺旋CT检查鉴别诊断XGC与胆囊癌的价值较高,值得临床关注。     

LncRNA Kcnq1ot1/miR-214-3p/caspase-1通路调控高糖处理的心脏成纤维细胞焦亡

摘要 目的：探讨长链非编码RNA Kcnq1ot1在高糖处理的心脏成纤维细胞中调控焦亡的作用及具体机制。方法：培养C57BL/6乳鼠原代心脏成纤维细胞,分别用5.5 mM和30 mM葡萄糖培养,用免疫荧光、qRT-PCR和western blot方法检测NLRP3、caspase-1和IL-1β的表达。高糖处理的成纤维细胞抑制Kcnq1ot1,检测caspase-1的表达。生物信息学和荧光素酶报告基因检测验证与Kcnq1ot1和caspase-1存在共同互补结合位点的microRNA。应用qRT-PCR和western blot方法检测高糖诱导的心脏成纤维细胞干扰Kcnq1ot1后miR-214-3p的表达,以及过表达或干扰miR-214-3p后caspase-1的表达水平。高糖诱导的细胞单独干扰Kcnq1ot1或同时抑制Kcnq1ot1和miR-214-3p,检测caspase-1、NLRP3和IL-1?茁的表达水平。结果：高糖诱导的成纤维细胞中焦亡激活,Kcnq1ot1表达明显升高;抑制Kcnq1ot1后caspase-1表达显著下调。生物信息学和荧光素酶报告基因检测发现miR-214-3p与Kcnq1ot1和caspase-1存在共同互补结合位点。高糖诱导的心脏成纤维细胞干扰Kcnq1ot1后miR-214-3p表达升高;过表达 miR-214-3p 后caspase-1表达降低,抑制miR-214-3p后caspase-1表达升高。同时抑制Kcnq1ot1和miR-214-3p可逆转干扰Kcnq1ot1对caspase-1的降低作用。结论：干扰Kcnq1ot1能够通过抑制miR-214-3p/caspase-1信号转导通路,抑制高糖诱导的心脏成纤维细胞焦亡。     

lncRNA CEBPA-AS1靶向miR-455-3p调控胃癌细胞生物学行为的分子机制研究

摘要 目的：探讨lncRNA CEBPA-AS1对胃癌细胞生物学行为的影响及其可能作用机制。方法：qRT-PCR法检测胃癌组织、癌旁组织与正常人胃上皮GES1细胞和人胃癌SNU-1、AGS、HS-746T细胞系中lncRNA CEBPA-AS1、miR-455-3p的表达量。si-NC、si-lncRNA CEBPA-AS1、miR-NC、miR-455-3p mimics、si-lncRNA CEBPA-AS1与anti-miR-NC、si-lncRNA CEBPA-AS1与anti-miR-455-3p分别转染至SNU-1细胞（分别命名为si-NC组、si-lncRNA CEBPA-AS1组、miR-NC组、miR-455-3p组、si-lncRNA CEBPA-AS1+anti-miR-NC组和si-lncRNA CEBPA-AS1+anti-miR-455-3p组）后,MTT实验与平板克隆形成实验分别检测细胞增殖及克隆形成能力,Transwell小室实验检测细胞迁移及侵袭能力,双荧光素酶报告基因实验与qRT-PCR实验验证lncRNA CEBPA-AS1与miR-455-3p的靶向调控关系,Western blot法检测MMP2、MMP9蛋白表达情况。结果：与癌旁组织比较,胃癌组织中lncRNA CEBPA-AS1的表达量显著升高,miR-455-3p的表达量显著降低,差异均有统计学意义（均P＜0.05）。与GES1细胞比较,SNU-1、AGS、HS-746T细胞中lncRNA CEBPA-AS1的表达量显著升高,miR-455-3p的表达量显著降低,其中SNU-1细胞的lncRNA CEBPA-AS1表达量最高,差异均有统计学意义（均P＜0.05）。与si-NC组比较,si-lncRNA CEBPA-AS1组细胞活力降低,细胞克隆形成数、迁移及侵袭细胞数减少,MMP2、MMP9蛋白表达水平降低,差异均有统计学意义（P＜0.05）。与miR-NC组比较,miR-455-3p组细胞活力降低,细胞克隆形成数、迁移及侵袭细胞数减少,MMP2、MMP9蛋白表达水平降低,差异均有统计学意义（P＜0.05）。lncRNA CEBPA-AS1可靶向结合miR-455-3p,并可负调控miR-455-3p的表达。与si-lncRNA CEBPA-AS1+anti-miR-NC组比较,si-lncRNA CEBPA-AS1+anti-miR-455-3p组细胞活力升高,细胞克隆形成数、迁移及侵袭细胞数增多,MMP2、MMP9蛋白表达水平升高,差异均有统计学意义（P＜0.05）。结论：干扰lncRNA CEBPA-AS1表达可通过靶向调控miR-455-3p而抑制胃癌细胞增殖、克隆形成、迁移及侵袭。     

Gut microbiota,inflammation, and molecular signatures of host response to infection

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.     

鳞翅目昆虫抗病毒免疫反应的研究进展

鳞翅目昆虫种类繁多,对农业生产和人类生活产生重大影响,宿主昆虫与病毒相互关系的研究对于利用病毒杀虫剂进行害虫治理和益虫病毒性疾病的预防具有重要意义.因此,鳞翅目昆虫与病毒的互作研究显得尤为重要,宿主昆虫的免疫系统在抗病毒感染过程中发挥着关键作用,对病毒产生不同程度的免疫反应.本文综述了昆虫围食膜和中肠对病毒入侵的防御作用,病毒进入体腔后昆虫所产生的细胞免疫和体液免疫反应,以及RNAi、细胞的自噬与凋亡、Toll、Imd、JAK-STAT和STING信号通路等相关的抗病毒免疫途径,并对昆虫抗病毒免疫研究的制约因素和未来鳞翅目昆虫抗病毒免疫的研究重点进行了讨论,以期为害虫的生物防治和益虫疾病的防控提供理论依据.