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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

《医学前沿（英文）》 doi: 10.1007/s11684-023-1017-7

摘要： The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS3) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

关键词： single-cell RNA-seq     glioma     radial glia     primitive oligodendrocyte precursor cell     immune escape    

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Distinct mononuclear diploid cardiac subpopulation with minimal cell–cell communications persists in

《医学前沿（英文）》   页码 939-956 doi: 10.1007/s11684-023-0987-9

摘要： A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM–fibroblast (FB) communications and one maintaining MNDCM status with least CM–FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell–cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell–cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.

关键词： mononuclear diploid cardiomyocytes     cell–cell communication     cardiac fibroblast     single-cell RNA sequencing     cardiac regeneration    

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PathogenTrack and Yeskit: tools for identifying intracellular pathogens from single-cell RNA-sequencing

《医学前沿（英文）》 2022年 第16卷 第2期   页码 251-262 doi: 10.1007/s11684-021-0915-9

摘要： Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.

关键词： scRNA-seq     intracellular pathogen     microbe     COVID-19     SARS-CoV-2    

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Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies:a single-institution study of 225 cases

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 468-477 doi: 10.1007/s11684-015-0419-6

摘要：

Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow (BM) infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders (T-LPD, all with BM infiltration) and 196 cases of T-/natural-killer-cell lymphoma (T/NKCL, 56 with BM infiltration and 140 without BM infiltration). The estimated 5-year overall survival (OS) rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum β-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration (P = 0.0264 and P<0.0001, respectively). Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies.

关键词： mature T-cell lymphoid malignancies     clonal T-cell population     bone marrow infiltration     prognostic factors    

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Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed

Ying Huo, Peng Yuan, Qingyuan Qin, Zhiqiang Yan, Liying Yan, Ping Liu, Rong Li, Jie Yan, Jie Qiao

《医学前沿（英文）》 2021年 第15卷 第1期   页码 144-154 doi: 10.1007/s11684-020-0792-7

摘要： Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30–32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1, 2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.

关键词： human metaphase II oocyte     vitrification     cryostorage duration     single-cell RNA-Seq     lncRNA    

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A cytoprotective graphene oxide-polyelectrolytes nanoshell for single-cell encapsulation

Luanying He, Yulin Chang, Junhao Zhu, Ying Bi, Wenlin An, Yiyang Dong, Jia-Hui Liu, Shihui Wang

《化学科学与工程前沿（英文）》 2021年 第15卷 第2期   页码 410-420 doi: 10.1007/s11705-020-1950-9

摘要： Graphene oxide (GO) has been increasingly utilized in the fields of food, biomedicine, environment and other fields because of its benign biocompatible. We encapsulated two kinds of GO with different sizes on yeast cells with the assistance of polyelectrolytes poly (styrene sulfonic acid) sodium salt (PSS) and polyglutamic acid (PGA) (termed as Y@GO). The result does not show a significant difference between the properties of the two types of Y@GO (namely Y@GO1 and Y@GO2). The encapsulation layers are optimized as Yeast/PGA/PSS/PGA/GO/PGA/PSS based on the morphology, dispersity, colony-forming unit, and zeta potential. The encapsulation of GO increases the roughness of the yeast. It is proved that the Y@GO increases the survival time and enhance the activity of yeast cells. The GO shell improves the resistance of yeast cells against pH and salt stresses and extends the storage time of yeast cells.

关键词： GO     yeast     polyelectrolyte     cytoprotection     nanomaterials    

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intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem celltransplantation for adult patients with lymphoid malignancies: a prospective single-arm phase II study

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿（英文）》 2021年 第15卷 第1期   页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要： Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide     allogeneic hematopoietic stem cell transplantation     lymphoid malignancies    

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Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different

Xin Zou, Ke Chen, Jiawei Zou, Peiyi Han, Jie Hao, Zeguang Han

《医学前沿（英文）》   页码 185-192 doi: 10.1007/s11684-020-0754-0

摘要：

It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV and originated from Wuhan (China), invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

关键词： 2019-nCoV     ACE2     single-cell RNA-seq    

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锌空燃料电池电站

朱梅,徐献芝,苏润

《中国工程科学》 2004年 第6卷 第12期   页码 62-64

摘要：

燃料电池发电技术已经受到人们越来越多的重视。介绍了利用锌空气燃料电池技术建设电站，利用分体式电极技术制造世界上最大的单电池，该电站采用独特的分离循环技术，可以提高电站总体效率。给出建设电站的相关参数。

关键词： 燃料电池     锌空气燃料电池     分体式电极     单电池     分离循环技术    

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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer     cancer screening     single cell     molecular alterations     precancerous lesion     therapy resistance    

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基于集成液体交换的微流控芯片的完整单细胞动态变形测量 Article

Xu Du, Di Chang, Shingo Kaneko, Hisataka Maruyama, Hirotaka Sugiura, Masaru Tsujii, Nobuyuki Uozumi, Fumihito Arai

《工程（英文）》 2023年 第24卷 第5期   页码 94-101 doi: 10.1016/j.eng.2022.08.020

摘要：

本文报道了采用一种集成了力感应和液体交换功能的微流控芯片来测量单细胞力学性能的方法。使用光学镊子操纵和定位在推力探针和力传感器探针之间的单个细胞。这两个芯片上的探针被设计用来捕获和使细胞变形。通过移动由外力驱动的推力探针，而使单个细胞变形。层流在探针之间形成液-液界面以改变细胞外环境。通过控制注入压力来改变界面的位置。通过调整两个正压力和一个负压力来平衡流动的扩散和扰动。在微流控芯片中测定了不同渗透浓度环境下的单个集胞藻（Synechocystis）菌株PCC 6803 的力学性能。在0.3~0.7 s 内实现液体交换过程，同时也显示了单个细胞的动态变形。可以在30 s 内收集不同渗透浓度下两个杨氏模量值的测量结果以及单个细胞在渗透压冲击下的动态响应。研究了野生型（WT）和突变型集胞藻细胞的动态变形，揭示了机械敏感（MS）通道的功能机制。该系统提供了一种监测单个完整细胞响应快速外部渗透变化的实时力学动力学的新方法；因此，该系统为准确描述细胞中MS通道的生理功能提供了新的机会。

关键词： 微流控芯片     力学性能     动态变形     单细胞     液体交换    

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中国城市化进程中的粮食安全与风/煤制天然气单细胞蛋白的研究

曹 晨,余 波,顾为东

《中国工程科学》 2015年 第17卷 第3期   页码 107-112

摘要：

据预测2030年我国人口将会达到峰值14.5亿，城市化率达到70 %，届时城市人口新增3亿，总数将超过10亿。随着总人口的持续增加以及城市人口的迅速膨胀，我国未来将会面临严峻的粮食不足问题，尤其以蛋白质为代表的营养物质将会出现严重短缺。本文针对这一问题，提出了以风力发电为能源，以煤制天然气为原料的单细胞蛋白制备新思路，新途径。此方法通过煤制天然气生产单细胞蛋白，既解决了传统煤炭利用中碳排放高、环境负荷大等缺点，实现了煤炭的升级、绿色利用，又解决了利用石油、工农业废弃物生产单细胞蛋白所产生的食品安全性等问题。另外，此方法可实现大规模工业化生产，为解决我国未来蛋白质不足提供一条绿色、高效、切实可行的新途径。

关键词： 城镇化；粮食安全；非并网发电；煤制天然气；单细胞蛋白    

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微生物组分析技术的发展趋势：从单细胞功能成像到菌群大数据

徐健, 马波, 苏晓泉, 黄适, 徐欣, 周学东, 黄巍, Rob Knight

《工程（英文）》 2017年 第3卷 第1期   页码 66-70 doi: 10.1016/J.ENG.2017.01.020

摘要：

方法学创新一直是微生物组学研究的核心驱动力。我们认为在未来五到十年，微生物组的方法学体系在研究理念与技术平台方面将发生三大变革：①从监测菌群“结构”变化向监测菌群“功能/状态”变化的变革；②从细胞“群体”分析精度向细胞“个体”分析精度的转变；③从“数据分析”向“数据科学”的跨越。在这里我们针对实现上述三大方法学变革需要克服的关键科学或技术挑战，重点介绍了部分中国微生物组分析方法学研究团队及其国际合作伙伴的最新工作进展。我们相信中国微生物组计划应把握住当前这一重要机遇，通过在微生物组分析方法学前沿开展富有雄心、远见、创意与竞争力的交叉合作研究，为国际微生物组计划贡献一系列“中国制造”的新方法、新工具和新仪器。

关键词： 微生物组     方法学创新     单细胞分析     大数据     中国微生物组计划    

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SOFC单电池测试方法

屠恒勇

《中国工程科学》 2013年 第15卷 第2期   页码 33-38

摘要：

固体氧化物燃料电池（SOFC）性能的测试结果能揭示材料和制备方法及其性能之间的复杂关系，确定燃料电池内部损耗的各种来源，并指导有关材料和制备技术的研发。在SOFC进入商业化发展的前期，测试方法的标准化有助于建立基础研究和开发研究间的有效和可靠联系，实现各研究机构所得测试结果的可比性，从而推动基础研究成果转化为现实的生产力。本文综述了国际上有关单电池标准测试系统的建立和步骤的制定以及测试结果报告的标准化，指出了在我国建立完善的SOFC发电技术标准体系的重要性和迫切性。

关键词： 固体氧化物燃料电池     性能测试     测试步骤     标准化    

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基于元胞自动机的电阻存储器多比特固定型故障诊断 Research Article

Sutapa SARKAR1, Biplab Kumar SIKDAR2, Mousumi SAHA3

《信息与电子工程前沿（英文）》 2022年 第23卷 第7期   页码 1110-1126 doi: 10.1631/FITEE.2100255

摘要： 本文提出一种用于可变电阻式存储器（ReRAM）、基于组的动态固定型故障诊断方案。传统的静态随机存取存储器、动态随机存取存储器、NAND和NOR闪存受可扩展性、功率、封装密度等限制。可变电阻式存储器这类下一代存储器被认为具有多种优势，如高封装密度、非易失性、可扩展性和低功耗，但单元可靠性一直是个问题。不可靠的内存操作是由于大量使用写入或内存密集型工作负载而导致的永久性固定型故障。越来越多的固定型故障也限制了芯片寿命。因此，本文提出一种基于元胞自动机（CA）的动态消除固定型故障设计，以解决不可靠的电池功能和不稳定的电池寿命问题。引入可扩展的块级故障诊断和恢复方案，以确保在出现多比特固定型故障情形下仍可读取数据。该方案是一种新颖方法，因其目标是消除一般故障条件下对固定型故障的数量和性质的限制。所提方案基于Wolfram零边界和周期性边界CA理论。引入多种特殊类别CA——单长循环单吸引子元胞自动机（SACA）、单长循环双吸引子元胞自动机（TACA）和单长循环多吸引子元胞自动机（MACA）——以实现完全容错。目标微架构单元设计具有最佳空间开销。

关键词： 电阻存储器；电池可靠性；块级故障诊断；单长循环单吸引子元胞自动机；单长循环双吸引子元胞自动机；单长循环多吸引子元胞自动机    

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标题 作者 时间 类型 操作

Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

期刊论文

Distinct mononuclear diploid cardiac subpopulation with minimal cell–cell communications persists in

期刊论文

PathogenTrack and Yeskit: tools for identifying intracellular pathogens from single-cell RNA-sequencing

期刊论文

Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies:a single-institution study of 225 cases

null

期刊论文

Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed

Ying Huo, Peng Yuan, Qingyuan Qin, Zhiqiang Yan, Liying Yan, Ping Liu, Rong Li, Jie Yan, Jie Qiao

期刊论文

A cytoprotective graphene oxide-polyelectrolytes nanoshell for single-cell encapsulation

Luanying He, Yulin Chang, Junhao Zhu, Ying Bi, Wenlin An, Yiyang Dong, Jia-Hui Liu, Shihui Wang

期刊论文

intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem celltransplantation for adult patients with lymphoid malignancies: a prospective single-arm phase II study

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

期刊论文

Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different

Xin Zou, Ke Chen, Jiawei Zou, Peiyi Han, Jie Hao, Zeguang Han

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