2018-2019年中国流行性腮腺炎流行特征和病毒基因特征分析

阐明中国(未包括香港、澳门特别行政区和台湾地区,下同)2018-2019年流行性腮腺炎(流腮)流行特征和病毒基因特征。对2018-2019年中国流腮流行病学和病毒学监测数据进行描述流行病学和分子流行病学分析。2018-2019年中国流腮年报告发病率分别为18.65/10万和21.48/10万,15岁以下儿童和青少年是我国流腮的高发人群,分别占总病例数的85.30%和82.56%。流腮的流行具有明显的季节性特征。全国各省、自治区、直辖市份均有流腮病例报告,西部和中部地区发病率高于东部地区。2018-2019年共获得160条腮腺炎病毒(Mumps virus,MuV)SH基因序列,其中150条(93.75%)序列鉴定为F基因型MuV,在我国11个省份检测到;10条(6.25%)序列为G基因型MuV,2019年在广东、湖北和新疆3个省份检测到。和我国既往流行MuV代表株相比,2018-2019年流行的F基因型MuV代表株序列在基因亲缘性关系树上相对集中。现阶段我国流腮的流行病学特征未发生明显改变,仍呈现病毒自然流行模式;F基因型作为优势流行基因型,在我国大部分地区持续流行,但毒株的遗传多态性有所降低,这可能和我国实施1剂次腮腺炎疫苗常规免疫策略有关。G基因型MuV主要在我国局部地区流行,但流行范围在逐渐扩大。建议进一步加强两剂次腮腺炎疫苗接种工作,降低我国腮腺炎易感人群。同时持续性开展MuV流行学和病毒学监测工作,为鉴别病毒的来源,确定病毒传播途径和评估腮腺炎疫苗免疫策略奠定重要的基础。     

Genetic Analysis of Human Adenovirus Type 7 Strains Circulating in Different Parts of China

To investigate the molecular epidemiology and genetic variation of human adenovirus type 7(HAdV-7) in children with acute respiratory infections(ARI) in China. HAdV-7-positive respiratory samples collected from children with ARI in Beijing, Shijiazhuang, Wenzhou and Guangzhou from 2014–2018 were selected for gene amplification and sequence analysis. Fifty-seven HAdV-7 clinical strains with hexon, penton base and fiber gene sequences were obtained. Meanwhile17 strains were selected randomly from different cities for whole genome sequencing. Phylogenetic and variation analyses were performed based on the obtained sequences, HAdV-7 prototype strain Gomen(AY594255), vaccine strains(AY495969 and AY594256) and representative sequences of strains. The phylogenetic trees constructed based on whole genome sequences, major capsid protein genes(hexon, penton base and fiber) and the early genes(E1, E2, E3 and E4) were not completely consistent. The HAdV-7 strains obtained in this study always clustered with most of the circulating strains worldwide from the 1980 s to the present. Compared with the HAdV-7 prototype strain Gomen(AY594255), some amino acid mutations in loop1 and loop2 of hexon and the RGD loop region of the penton base gene were observed. Recombination analysis showed that partial regions of 55 k Da protein and 100 kDa hexon-assembly associated protein genes among all HAdV-7 strains in this study were from HAdV-16 and HAdV-3, respectively. Our study demonstrated the molecular evolution characteristics of HAdV-7 strains circulating in China and provided basic reference data for the prevention, control and vaccine development of HAdV-7.     

Diversity,structure and function of the coiled‐coil domains of plant NLR immune receptors

Plant nucleotide‐binding, leucine‐rich repeat receptors (NLRs) perceive pathogen avirulence effectors and activate defense responses. Nucleotide‐binding, leucine‐rich repeat receptors are classified into coiled‐coil (CC)‐containing and Toll/interleukin‐1 receptor (TIR)‐containing NLRs. Recent advances suggest that NLR CC domains often function in signaling activation, especially for induction of cell death. In this review, we outline our current understanding of NLR CC domains, including their diversity/classification and structure, their roles in cell death induction, disease resistance, and interaction with other proteins. Furthermore, we provide possible directions for future work.     

肺结节病合并Alternaria alternata所致皮肤链格孢病1例

患者,女,61岁,确诊肺结节病、口服糖皮质激素7月,双手背及腕部红色斑块3个月。组织病理示表皮轻度棘层增厚,真皮浅、中层中性粒细胞、淋巴、组织细胞、浆细胞、多核巨细胞混合性浸润,可见散在双轮廓厚壁酵母样结构。六铵银染色见不规则肿胀菌丝及酵母样厚壁孢子。真菌培养见棕/灰褐色菌落,镜下见棕色分隔孢子。ITS区序列分析鉴定为Alternaria alternate。口服伊曲康唑胶囊200 mg/d,联合外用硝酸舍他康唑乳膏2次/d,连续用药4个月后皮损完全消退,随访半年,未见复发。     

Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Gene therapy has become the most effective treatment for monogenic diseases. Congenital LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin gene. Ob/ob mouse is a monogenic obesity model, which carries a homozygous point mutation of C to T in Exon 2 of the Leptin gene. Here, we attempted to edit the mutated Leptin gene in ob/ob mice preadipocytes and inguinal adipose tissues using CRISPR/Cas9 to correct the C to T mutation and restore the production of LEPTIN protein by adipocytes. The edited preadipocytes exhibit a correction of 5.5% of Leptin alleles and produce normal LEPTIN protein when differentiated into mature adipocytes. The ob/ob mice display correction of 1.67% of Leptin alleles, which is sufficient to restore the production and physiological functions of LEPTIN protein, such as suppressing appetite and alleviating insulin resistance. Our study suggests CRISPR/Cas9-mediated in situ genome editing as a feasible therapeutic strategy for human monogenic diseases, and paves the way for further research on efficient delivery system in potential future clinical application.     

Experimental warming shifts coupling of carbon and nitrogen cycles in an alpine meadow

增温对高寒草甸生态系统碳氮循环耦合关系的影响 陆地生态系统碳吸收受土壤氮素可用性的调节。然而,全球变化背景下的不同生态系统组分的碳氮比及其所反映的碳氮循环耦合关系尚不十分清楚。本文运用数据同化的方法,将一个高寒草甸增温试验的14组数据同化到草地生态系统模型中,从而评估了增温如何影响陆地生态系统的碳氮循环耦合关系。研究结果表明,增温提高了土壤氮素的有效性,降低了土壤活性碳库的碳氮比,导致植物对土壤氮的吸收增加。但是由于植物叶片吸收的碳比吸收的氮增加更多,使得叶片中碳氮比增加,而根部的碳输入增加则低于氮的增加,导致根部的碳氮比减少。同时,增温降低了凋落物碳氮比,可能是在土壤高氮有效性的条件下,凋落物氮的固定得到增强;而且增温加速了凋落物的分解。同时增温还增加了慢速土壤有机质的碳氮比,使得该土壤碳库的碳固存潜力增大。由于大多数模型在不同的环境中通常使用相对固定的碳氮比,本研究所发现的气候变暖条件下碳氮比的差异变化可为模型参数化提供一个有效的参考,有利于模型对未来气候变化背景下生态系统碳氮耦合关系响应的预测。     

Human bone marrow mesenchymal stem cell-derived extracellular vesicles impede the progression of cervical cancer via the miR-144-3p/CEP55 pathway

Cervical cancer is the most common gynaecological malignancy, with a high incidence rate and mortality rate in middle-aged women. Human bone marrow mesenchymal stem cells (hBMSCs) have been implicated in the initiation and subsequent development of cancer, along with the involvement of extracellular vesicles (EVs) mediating intracellular communication by delivering microRNAs (miRNAs or miRs). This study is aimed at investigating the physiological mechanisms by which EVs-encapsulated miR-144-3p derived from hBMSCs might mediate the progression of cervical cancer. The expression profiles of centrosomal protein, 55 Kd (CEP55) and miR-144-3p in cervical cancer cell lines and tissues, were quantified by RT-qPCR and Western blot analysis. The binding affinity between miR-144-3p and CEP55 was identified using in silico analysis and luciferase activity determination. Cervical cancer cells were co-cultured with EVs derived from hBMSCs that were treated with either miR-144-3p mimic or miR-144-3p inhibitor. Cervical cancer cell proliferation, invasion, migration and apoptosis were detected in vitro. The effects of hBMSCs-miR-144-3p on tumour growth were also investigated in vivo. miR-144-3p was down-regulated, whereas CEP55 was up-regulated in cervical cancer cell lines and tissues. CEP55 was targeted by miR-144-3p, which suppressed cervical cancer cell proliferation, invasion and migration and promoted apoptosis via CEP55. Furthermore, similar results were obtained by hBMSCs-derived EVs carrying miR-144-3p. In vivo assays confirmed the tumour-suppressive effects of miR-144-3p in hBMSCs-derived EVs on cervical cancer. Collectively, hBMSCs-derived EVs-loaded miR-144-3p impedes the development and progression of cervical cancer through target inhibition of CEP55, therefore providing us with a potential therapeutic target for treating cervical cancer.     

Identification of five small heat shock protein genes in Spodoptera frugiperda and expression analysis in response to different environmental stressors

Spodoptera frugiperda (J. E. Smith) is a highly adaptable polyphagous migratory pest in tropical and subtropical regions. Small heat shock proteins (sHsps) are molecular chaperones that play important roles in the adaptation to various environment stressors. The present study aimed to clarify the response mechanisms of S. frugiperda to various environmental stressors. We obtained five S. furcifera sHsp genes (SfsHsp21.3, SfsHsp20, SfsHsp20.1, SfsHsp19.3, and SfsHsp29) via cloning. The putative proteins encoded by these genes contained a typical α-crystallin domain. The expression patterns of these genes during different developmental stages, in various tissues of male and female adults, as well as in response to extreme temperatures and UV-A stress were studied via real-time quantitative polymerase chain reaction. The results showed that the expression levels of all five SfsHsp genes differed among the developmental stages as well as among the different tissues of male and female adults. The expression levels of most SfsHsp genes under extreme temperatures and UV-A-induced stress were significantly upregulated in both male and female adults. In contrast, those of SfsHsp20.1 and SfsHsp19.3 were significantly downregulated under cold stress in male adults. Therefore, the different SfsHsp genes of S. frugiperda play unique regulatory roles during development as well as in response to various environmental stressors.