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简介：AbstractCell-cell communication is the basis of physiological processes and cell signals. The disease occurs when the cells do not adequately communicate and the messages are blocked. With ligand-receptor interaction databases and single-cell RNA sequencing (scRNA-seq) databases, we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types. This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19. We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes, such as carcinogenesis and SARS-CoV-2 infection.

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简介：Circulatingtumorcells(CTCs)areapopulationoftumorcellsmediatingmetastasis,whichresultsinmostofthecancerrelateddeaths.ThenumberofCTCsintheperipheralbloodofpatientsisrare,andmanyplatformshavebeenlaunchedfordetectionandenrichmentofCTCs.EnumerationofCTCshasalreadybeenusedasaprognosismarkerpredictingthesurvivalrateofcancerpatients.YetCTCsshouldbemorepotential.StudiesonCTCsatsinglecelllevelmayhelprevealingtheunderlyingmechanismoftumorigenesisandmetastasis.Thoughfarfromdeveloped,thisareaofstudyholdsmuchpromiseinprovidingnewclinicalapplicationanddeepunderstandingtowardsmetastasisandcancerdevelopment.

简介：Abstract2019 novel coronavirus disease has resulted in thousands of critically ill patients in China, which is a serious threat to people’s life and health. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported to share the same receptor, angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here, based on the public single-cell RNA-sequencing database, we analyzed the mRNA expression profile of putative receptor ACE2 and AXL receptor tyrosine kinase (AXL) in the early maternal-fetal interface. The result indicates that the ACE2 has very low expression in the different cell types of early maternal-fetal interface, except slightly high in decidual perivascular cells cluster 1 (PV1). Interestingly, we found that the Zika virus (ZIKV) receptor AXL expression is concentrated in perivascular cells and stromal cells, indicating that there are relatively more AXL-expressing cells in the early maternal-fetal interface. This study provides a possible infection route and mechanism for the SARS-CoV-2- or ZIKV-infected mother-to-fetus transmission disease, which could be informative for future therapeutic strategy development.

简介：AbstractThe coronavirus disease 2019 (COVID-19) pandemic has been an unmitigated disaster for society and the economy worldwide. However, much remains unknown about the pathogenesis of, treatment methods for, and preventive measures against COVID-19. Single-cell sequencing is a novel sequencing technology whose use has recently become prevalent in various life-science fields. This high-resolution technology is being used to analyze the COVID-19 pandemic at a single-cell level. In this review, we summarize the application of single-cell sequencing technology to the field of COVID-19-related research, including the biology of severe acute respiratory syndrome coronavirus 2, clinical concerns associated with COVID-19, neutralizing antibody screening, and vaccine development. We also address challenges to, and improvements in, existing single-cell research related to COVID-19.

简介：嗅觉的ensheathing房间(OEC)是有axonal的glial房间的一种唯一的类型支持生长的性质。OEC移植作为axonal损害和demyelinating疾病的有希望的试验性的治疗出现了。然而，OEC的一些基本细胞的性质仍然保持不清楚。在这研究，我们发现不同OEC候补选手人口基于单个孤立的房间的微速摄影的成像展出了不同迁移的性质，可能由于他们的不同细胞骨架组织。而且，OEC潜水艇人口在单个房间的迁居试金显示了不同吸引人的迁移的回答到lysophosphatidic酸(LPA)的一个坡度。最后，我们发现了人口自发地转变了成对方的那个OEC代用品。一起，这些结果示威，第一次到我们的知识，不同OEC潜水艇人口显示不同迁移的性质试管内并且提供新证据当一个单个房间与韧性的功能的显型打字，支持OEC的观点。

简介：AbstractAlthough whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA-seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA-seq data can be used to identify aberrantly spliced genes, detect allele-specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA-seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.

简介：AbstractBackground:Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods:We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results:Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.Conclusion:This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

简介：AbstractTargeted sequencing and whole exome sequencing are the most common approaches used to detect causative variants in Mendelian diseases; however, using DNA-based sequencing techniques, the current molecular diagnostic yield is at best 50%. In recent years, RNA sequencing has been shown to be able to provide a genetic diagnosis in patients whose conditions were previously unable to be identified by DNA analysis. RNA sequencing can reveal expression outliers, aberrant splicing events, allele-specific expression, and new pathogenic variants, and as such can complement and expand on the traditional genomic methods used to diagnose Mendelian diseases. Therefore, RNA sequencing is expected to become a routine method for genetic diagnosis in the future. This article reviews the applications and challenges of RNA sequencing in the genetic diagnosis of Mendelian diseases.

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简介：Asingle-particlemicrobeamfacilityhasbeenconstructedattheLaboratoryofIonBeamBioengineering(LIBB),ChineseAcademyofSciences.Thesystemisdesignedtodeliverthedefinednumberofhydrogenions,coveringarangeofenergyfrom1.0to3.5MeV,intoanareasmallerthanthenucleiofindividuallivingcells.AccuracyoftheparticledetectionsystemandthecelltargetingsysteminthefacilityhasbeenassessedusingCR39(nucleartrackdetector)for2.3MeVprotons.Theresultsdemonstratethattheparticledetectionefficiencyisabove98%,andtheoveralltargetingaccuracyofthemicrobeamislimitedwithin3μmformorethan90%hits.

简介：AbstractBackground:Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression.Methods:Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis.Results:The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05).Conclusion:Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.

简介：AmethodisdescribedwhichpermitstransmissionelectronmicroscopeofsinglecellstreatedwithHpDpluslasermicroirradiation.Thepreselectedsinglecellthatwasirradiatedbylaserunderlightmicroscopeandfollowedfixation,embeddedandsectioningisexaminedunderelectronmicroscope.Theresultsdemonstratedthatatthelightdoseof1.88ml/μm2notonlytheirradiatednucleolusappearedtransparentregion,buttheotherpartssuchasnon-irradiatedmitochondriaincytoplasmcanalsobedamaged.Whenpartialcytoplasmisirradiatedwiththelightdoseof4.50ml/μm2,thedamagesappearinallcytoplasm,butthereislittlechangeinthenucleus.Theexperimentalresultsalsodemonstratethatcytoplasmismoresensitivethannucleus.ItisthemitochondriaincytoplasmthatareverysensitivetoHpDpluslaser.

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简介：Smoothened(SMO)是表明小径的刺猬的一个重要成员。我们为RNA干扰构造了特定的recombinantlentiviral向量，指向SMO基因(NM_005631)观察它在人的雄激素敏感的前列腺癌症房间线的SMO表示，房间增长和房间周期上的效果，LNCaP，并且在雄激素无关的前列腺癌症房间线，PC3。四个siRNA序列被设计并且插入了到lentiviral向量pGCSIL-GFP构造四recombinant向量。有最高的介入效率的向量是有在293T房间包装向量(pHelper1.0和pHelper2.0)为分别地感染LNCaP和PC3房间线由liposome装配lentivirus粒子的co-transfected。SMOmRNA，肿瘤房间增长和房间周期的表示水平被量的实时聚合酶链反应(qRT-PCR)测量，3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)试金和流动cytometry分别地。顺序结果证明recombinantlentiviral向量成功地被构造。pGCSIL-GFP-723有最高的介入效率，在co-transfection，LNCaP和PC3房间与排队以后的命名Lv-SIL-SMO723被感染。与控制组相比，显著地显示出的结果减少了(P<0.05)LNCaP和PC3，S阶段房间的更低的吝啬的百分比和G2/M的更高吝啬的百分比的SMOmRNA表情分阶段执行房间，以及显然减缓增长(P<0.01)在感染的组的LNCaP。然而，PC3的增长没被改变(P>0.05)。在结论，recombinantlentivirus粒子能压制SMO表示，在LNCaP和PC3房间线调整房间周期并且显著地禁止LNCaP房间然而并非PC3房间的增长。

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简介：AbstractSingle-domain antibodies have the characteristics of small molecular weight, strong tissue penetration, and high affinity, and are widely used to construct molecular probes for disease diagnosis and treatment. This article reviews molecular imaging studies including positron emission tomography (PET), single-photon emission computed tomography/computed tomography (CT), PET/CT, and fluorescent imaging of molecular probes composed of single-domain antibodies against eight esophageal squamous cell carcinoma biological targets. These 8 targets are highly expressed on the membrane of esophageal squamous cell carcinoma cells and include epidermal growth factor receptor, human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2, chemokine receptor 4, chemokine receptor 7, and carcinoembryonic antigen. The current problems and solutions are also discussed to provide a reference for future design of molecular imaging probes targeting esophageal squamous cell carcinoma.

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