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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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spp., foodborne pathogens threatening neonates and infants

Qiming CHEN, Yang ZHU, Zhen QIN, Yongjun QIU, Liming ZHAO

《农业科学与工程前沿（英文）》 2018年 第5卷 第3期   页码 330-339 doi: 10.15302/J-FASE-2018208

摘要：

Cronobacter spp. (formerly Enterobacter sakazakii) are special foodborne pathogens. Cronobacter infection can cause necrotizing enterocolitis, sepsis and meningitis in all age groups, especially neonates and infants, with a high fatality of up to 80%, although the infection is rare. Outbreaks of Cronobacter infection are epidemiologically proven to be associated with contaminated powdered infant formula (PIF). Cronobacter spp. can resist dry environments and survive for a long period in food with low water activity. Therefore, Cronobacter spp. have become serious pathogens of neonates and infants, as well as in the dairy industry. In this review, we present the taxonomy, pathogenesis, resistance, detection and control of Cronobacter spp.

关键词： Cronobacter spp.     desiccation resistance     pathogen control     pathogen detection     powdered infant formula    

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基于细胞内应变评估的卵母细胞去核方法及其在机器人化克隆中的应用 Article

孙明竹, 刘曜玮, 崔茂盛, 赵启立, 赵相飞, 张艺荻, 黄晶晶, 卢桂章, 赵新

《工程（英文）》 2023年 第24卷 第5期   页码 73-83 doi: 10.1016/j.eng.2022.04.016

摘要：

自1996 年第一只克隆羊诞生，克隆技术由于在动物育种方面的巨大潜力而得到了很大关注。体细胞核移植技术是动物克隆的核心，其操作过程非常复杂，不可避免地造成细胞内损伤。通常来说，只有不到1%的重构胚胎能够发育成克隆动物，克隆的低成功率是制约其广泛应用的主要原因之一。为此，本文提
出了一种基于细胞内应变评估的卵母细胞去核方法，以减少体细胞核移植中的潜在细胞内损伤，从而提高克隆成功率。首先，根据细胞内速度场计算细胞内应变，进而将内应变作为评价标准来改进去核操作；在此基础上，开发了一套机器人批量体细胞核移植系统，用于实现机器人化克隆。实验结果表明，本文方法将体细胞核移植后的胚胎囊胚率从10.0%提高到20.8%，并成功获得17 头克隆小猪。这是世界上首批由机器人完成克隆操作获得的克隆动物。对比手动核移植操作，本文将克隆成功率从平均0.73%提升到了2.50%，大幅提升了克隆效率。与此同时，基于细胞内应变的去核方法有望应用于其他生物操作，并建立一种通用的减少细胞内损伤的细胞操作规范。

关键词： 卵母细胞去核     机器人化克隆     细胞内应变     细胞内损伤     光流法    

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Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

《农业科学与工程前沿（英文）》 2016年 第3卷 第2期   页码 102-112 doi: 10.15302/J-FASE-2016100

摘要： Plants are frequently affected by pathogen infections. To effectively defend against such infections, two major modes of innate immunity have evolved in plants; pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity. Although the molecular components as well as the corresponding pathways involved in these two processes have been identified, many aspects of the molecular mechanisms of the plant immune system remain elusive. Recently, the rapid development of omics techniques (e.g., genomics, proteomics and transcriptomics) has provided a great opportunity to explore plant–pathogen interactions from a systems perspective and studies on protein–protein interactions (PPIs) between plants and pathogens have been carried out and characterized at the network level. In this review, we introduce experimental and computational identification methods of PPIs, popular PPI network analysis approaches, and existing bioinformatics resources/tools related to PPIs. Then, we focus on reviewing the progress in genome-wide PPI networks related to plant–pathogen interactions, including pathogen-centric PPI networks, plant-centric PPI networks and interspecies PPI networks between plants and pathogens. We anticipate genome-wide PPI network analysis will provide a clearer understanding of plant–pathogen interactions and will offer some new opportunities for crop protection and improvement.

关键词： plant–pathogen interactions     systems biology     omics     plant immunity     protein–protein interaction     network    

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Resveratrol reduces intracellular reactive oxygen species levels by inducing autophagy through the AMPK-mTOR

Jun Song, Yeping Huang, Wenjian Zheng, Jing Yan, Min Cheng, Ruxing Zhao, Li Chen, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2018年 第12卷 第6期   页码 697-706 doi: 10.1007/s11684-018-0655-7

摘要：

Oxidative stress induced by free fatty acid aggravates endothelial injury, which leads to diabetic cardiovascular complications. Reduction of intracellular oxidative stress may attenuate these pathogenic processes. The dietary polyphenol resveratrol reportedly exerts potential protective effects against endothelial injury. This study determined whether resveratrol can reduce the palmitic acid (PA)-induced generation of reactive oxygen species (ROS) and further explored the underlying molecular mechanisms. We found that resveratrol significantly reduced the PA-induced endothelial ROS levels in human aortic endothelial cells. Resveratrol also induced endothelial cell autophagy, which mediated the effect of resveratrol on ROS reduction. Resveratrol stimulated autophagy via the AMP-activated protein kinase (AMPK)-mTOR pathway. Taken together, these data suggest that resveratrol prevents PA-induced intracellular ROS by autophagy regulation via the AMPK-mTOR pathway. Thus, the induction of autophagy by resveratrol may provide a novel therapeutic candidate for cardioprotection in metabolic syndrome.

关键词： resveratrol     reactive oxygen species     AMPK     mTOR     autophagy    

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Intracellular trehalose improves the survival of human red blood cells by freeze-drying

HE Hui, LIU Baolin, HUA Zezhao, LI Chuan, WU Zhengzheng

《能源前沿（英文）》 2007年 第1卷 第1期   页码 120-124 doi: 10.1007/s11708-007-0014-x

摘要： Freeze-drying of human red blood cells has a potential important application for blood transfusion. The aim of this study was to investigate the effects of intracellular trehalose on the survival of red blood cells after freeze-drying and rehydration. Fresh red blood cells were incubated in trehalose solutions of various concentrations at 37vH for 7 h following freeze-drying. Polyvinylpyrrolidone, Trehalose, sodium citrate, and human serum albumin were used as extracellular protective agents for the freeze-drying of red blood cells. The results indicated that the intracellular trehalose concentration was increased with increasing concentration of extracellular trehalose solution, and the maximum concentration of intracellular trehalose reached 35 mmol/L. The viability of freeze-dried red blood cells increased with the increment of intracellular trehalose concentration.
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Locally enhanced electric field treatment (LEEFT) for water disinfection

Jianfeng Zhou, Ting Wang, Cecilia Yu, Xing Xie

《环境科学与工程前沿（英文）》 2020年 第14卷 第5期 doi: 10.1007/s11783-020-1253-x

摘要： • Nanowire-assisted LEEFT is applied for water disinfection with low voltages. • LEEFT inactivates bacteria by disrupting cell membrane through electroporation. • Multiple electrodes and device configurations have been developed for LEEFT. • The LEEFT is low-cost, highly efficient, and produces no DBPs. • The LEEFT can potentially be applicable for water disinfection at all scales. Water disinfection is a critical step in water and wastewater treatment. The most widely used chlorination suffers from the formation of carcinogenic disinfection by-products (DBPs) while alternative methods (e.g., UV, O3, and membrane filtration) are limited by microbial regrowth, no residual disinfectant, and high operation cost. Here, a nanowire-enabled disinfection method, locally enhanced electric field treatment (LEEFT), is introduced with advantages of no chemical addition, no DBP formation, low energy consumption, and efficient microbial inactivation. Attributed to the lightning rod effect, the electric field near the tip area of the nanowires on the electrode is significantly enhanced to inactivate microbes, even though a small external voltage (usually<5 V) is applied. In this review, after emphasizing the significance of water disinfection, the theory of the LEEFT is explained. Subsequently, the recent development of the LEEFT technology on electrode materials and device configurations are summarized. The disinfection performance is analyzed, with respect to the operating parameters, universality against different microorganisms, electrode durability, and energy consumption. The studies on the inactivation mechanisms during the LEEFT are also reviewed. Lastly, the challenges and future research of LEEFT disinfection are discussed.

关键词： Water treatment     Nanotechnology     Pathogen inactivation     Electroporation     Nanowire     Chemical-free    

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Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 387-411 doi: 10.1007/s11684-018-0646-8

摘要：

Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

关键词： TGF-β     EMT     lung cancer     pancreatic cancer     latent form     immune function     GARP    

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Clinical manifestations and pathogen characteristics in children admitted for suspected COVID-19

Xiaofang Cai, Hanlan Jiang, Simin Zhang, Shengying Xia, Wenhui Du, Yaoling Ma, Tao Yu, Wenbin Li

《医学前沿（英文）》 2020年 第14卷 第6期   页码 776-785 doi: 10.1007/s11684-020-0820-7

摘要： Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread around the world. However, approaches to distinguish COVID-19 from pneumonia caused by other pathogens have not yet been reported. We retrospectively analyzed the clinical data of 97 children with probable COVID-19. A total of 13 (13.4%) patients were confirmed positive for SARS-CoV-2 infection by nucleic acid RT-PCR testing, and 41 (42.3%) patients were found to be infected with other pathogens. Notably, no pathogen was detected in 43 (44.3%) patients. Among all patients, 25 (25.8%) had familial cluster exposure history, and 52 (53.6%) had one or more coexisting conditions. Fifteen (15.5%) patients were admitted or transferred to the PICU. In the 11 confirmed COVID-19 cases, 5 (45.5%) and 7 (63.6%) were positive for IgM and IgG against SARS-CoV-2, respectively. In 22 patients with suspected COVID-19, 1 (4.5%) was positive for IgG but negative for IgM. The most frequently detected pathogen was (29, 29.9%). One patient with confirmed COVID 19 died. Our results strongly indicated that the detection of asymptomatic COVID 19 or coexisting conditions must be strengthened in pediatric patients. These cases may be difficult to diagnose as COVID-19 unless etiologic analysis is conducted. A serologic test can be a useful adjunctive diagnostic tool in cases where SARS-CoV-2 infection is highly suspected but the nucleic acid test is negative.

关键词： coronavirus disease 2019     pediatrics     emergency     retrospective investigation     severe acute respiratory syndrome coronavirus 2    

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Composition, dispersion, and health risks of bioaerosols in wastewater treatment plants: A review

Yunping Han, Lin Li, Ying Wang, Jiawei Ma, Pengyu Li, Chao Han, Junxin Liu

《环境科学与工程前沿（英文）》 2021年 第15卷 第3期 doi: 10.1007/s11783-020-1330-1

摘要： Abstract • Bioaerosols are produced in the process of wastewater biological treatment. • The concentration of bioaerosol indoor is higher than outdoor. • Bioaerosols contain large amounts of potentially pathogenic biomass and chemicals. • Inhalation is the main route of exposure of bioaerosol. • Both the workers and the surrounding residents will be affected by the bioaerosol. Bioaerosols are defined as airborne particles (0.05–100 mm in size) of biological origin. They are considered potentially harmful to human health as they can contain pathogens such as bacteria, fungi, and viruses. This review summarizes the most recent research on the health risks of bioaerosols emitted from wastewater treatment plants (WWTPs) in order to improve the control of such bioaerosols. The concentration and size distribution of WWTP bioaerosols; their major emission sources, composition, and health risks; and considerations for future research are discussed. The major themes and findings in the literature are as follows: the major emission sources of WWTP bioaerosols include screen rooms, sludge-dewatering rooms, and aeration tanks; the bioaerosol concentrations in screen and sludge-dewatering rooms are higher than those outdoors. WWTP bioaerosols contain a variety of potentially pathogenic bacteria, fungi, antibiotic resistance genes, viruses, endotoxins, and toxic metal(loid)s. These potentially pathogenic substances spread with the bioaerosols, thereby posing health risks to workers and residents in and around the WWTP. Inhalation has been identified as the main exposure route, and children are at a higher risk of this than adults. Future studies should identify emerging contaminants, establish health risk assessments, and develop prevention and control systems.

关键词： Wastewater treatment plant     Bioaerosols     Pathogen     Dispersion     Risk assessment    

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Pathogen evolution, prevention/control strategy and clinical features of COVID-19: experiences from China

《医学前沿（英文）》 doi: 10.1007/s11684-023-1043-5

摘要： Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported at the end of 2019 as a worldwide health concern causing a pandemic of unusual viral pneumonia and many other organ damages, which was defined by the World Health Organization as coronavirus disease 2019 (COVID-19). The pandemic is considered a significant threat to global public health till now. In this review, we have summarized the lessons learnt during the emergence and spread of SARS-CoV-2, including its prototype and variants. The overall clinical features of variants of concern (VOC), heterogeneity in the clinical manifestations, radiology and pathology of COVID-19 patients are also discussed, along with advances in therapeutic agents.

关键词： coronavirus disease 2019     SARS-CoV-2     epidemiology     clinical features    

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Effect of the ultraviolet/chlorine process on microbial community structure, typical pathogens, and antibiotic resistance genes in reclaimed water

《环境科学与工程前沿（英文）》 2022年 第16卷 第8期 doi: 10.1007/s11783-022-1521-z

摘要：

• UV/chlorine can effectively remove VBNC pathogens, ARGs and MGEs in reclaimed water.

关键词： UV/chlorine process     Pathogen     Antibiotic resistance genes     High-throughput qPCR     Reclaimed water    

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海水养殖细菌性病害检测方法研究进展

肖婧凡,王玥,张元兴,雷霁霖

《中国工程科学》 2014年 第16卷 第9期   页码 10-15

摘要：

随着我国水产养殖业的不断发展，各种病害问题日益突出。细菌性病害在所有病害中占到相当大的比例，因此其检测方法的开发在水产养殖病害发现、防治、无公害水产品生产及卫生质量检验中均具有重要意义。本文对近年来国内外主要海水养殖细菌性病害检测方法的研究情况进行综述，介绍了主要细菌性病害的各种检测方法的原理、应用及其研究进展，为我国今后建立水产养殖细菌性病害检测方法标准及推动相应检测产品的商品化提供参考。

关键词： 水产养殖     细菌性病害     检测方法    

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用于精准和响应性治疗胞质耐药菌的刚性药物递送系统 Article

曲少奇, 黄晓勇, 宋祥彬, 吴逸璠, 马晓溦, 沈建忠, 朱奎

《工程（英文）》 2022年 第15卷 第8期   页码 57-66 doi: 10.1016/j.eng.2021.12.021

摘要：

随着细菌耐药性的快速出现和广泛传播，导致抗菌药物对致命性细菌病原体的疗效逐渐降低。目前新型抗菌药物的发现和开发进展十分缓慢，因此迫切需要新的治疗策略来对抗多重耐药（multidrug-resistant, MDR）细菌，尤其是宿主细胞中的病原菌。功能性纳米颗粒作为细胞内药物递送系统具有良好发展潜力，主要优点为高生物相容性和可调节的表面修饰。基于纳米颗粒刚性可增强细胞摄取，制备了涂有细菌响应性磷脂的刚性功能化纳米颗粒（rigidity-functionalized nanoparticles, RFN）以促进内吞作用，从而增加细胞内抗菌药物累积。以耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus, MRSA）和致病性蜡样芽孢杆菌为模型，RFN在4 h 内清除了99%的MDR细菌，证明了其精准递送和高抗菌疗效。另外，通过改变表面的磷脂成分来调节静电效应，实现了RFN精准靶向溶酶体和重新编程其在细胞内分布。最后，RFN在由MRSA引起的伤口感染和菌血症动物模型中显示出高疗效。综上所述，本研究提供了一个易于调控的刚性递送系统，该系统具有响应释放特性，并且通过抗菌药物胞内重分布提升抗菌疗效，为未来针对胞质细菌感染的精准治疗提供新思路。

关键词： 抗菌药物     细菌     介孔二氧化硅     磷脂     刚性    

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标题 作者 时间 类型 操作

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

期刊论文

spp., foodborne pathogens threatening neonates and infants

Qiming CHEN, Yang ZHU, Zhen QIN, Yongjun QIU, Liming ZHAO

期刊论文

基于细胞内应变评估的卵母细胞去核方法及其在机器人化克隆中的应用

孙明竹, 刘曜玮, 崔茂盛, 赵启立, 赵相飞, 张艺荻, 黄晶晶, 卢桂章, 赵新

期刊论文

Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

期刊论文

Resveratrol reduces intracellular reactive oxygen species levels by inducing autophagy through the AMPK-mTOR

Jun Song, Yeping Huang, Wenjian Zheng, Jing Yan, Min Cheng, Ruxing Zhao, Li Chen, Cheng Hu, Weiping Jia

期刊论文

Intracellular trehalose improves the survival of human red blood cells by freeze-drying

HE Hui, LIU Baolin, HUA Zezhao, LI Chuan, WU Zhengzheng

期刊论文

Locally enhanced electric field treatment (LEEFT) for water disinfection

Jianfeng Zhou, Ting Wang, Cecilia Yu, Xing Xie

期刊论文

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

期刊论文

Clinical manifestations and pathogen characteristics in children admitted for suspected COVID-19

Xiaofang Cai, Hanlan Jiang, Simin Zhang, Shengying Xia, Wenhui Du, Yaoling Ma, Tao Yu, Wenbin Li

期刊论文

Composition, dispersion, and health risks of bioaerosols in wastewater treatment plants: A review

Yunping Han, Lin Li, Ying Wang, Jiawei Ma, Pengyu Li, Chao Han, Junxin Liu

期刊论文

Pathogen evolution, prevention/control strategy and clinical features of COVID-19: experiences from China

期刊论文

孙钰：Robotic Intracellular Manipulation and Measurement（2019年8月25日）

孙钰(院士)

2021年01月20日

会议视频

Effect of the ultraviolet/chlorine process on microbial community structure, typical pathogens, and antibiotic resistance genes in reclaimed water

期刊论文

海水养殖细菌性病害检测方法研究进展

肖婧凡,王玥,张元兴,雷霁霖

期刊论文

用于精准和响应性治疗胞质耐药菌的刚性药物递送系统

曲少奇, 黄晓勇, 宋祥彬, 吴逸璠, 马晓溦, 沈建忠, 朱奎

期刊论文