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Modelling-based evaluation of the effect of quarantine control by the Chinese government in the coronavirus disease 2019 outbreak [article]

Xinkai Zhou, Zhigui Wu, Ranran Yu, Shanni Cao, Wen Fang, Zhen Jiang, Fang Yuan, Cao Yan, Dijun Chen
2020 medRxiv   pre-print
The novel coronavirus disease 2019 (COVID-19) epidemic, which was first identified in Wuhan, China in December 2019 has rapidly spread all over China and across the world. By the end of February 2020, the epidemic outside Hubei province in China has been well controlled, yet the next wave of transmission in other countries may have just begun. A retrospective modeling of the transmission dynamics would provide insights into the epidemiological characteristics of the disease and evaluation of
more » ... effectiveness of the strict measures that have been taken by central and local governments of China. Using a refined susceptible-exposed-infectious-removed (SEIR) transmission model and a new strategy of model fitting, we were able to estimate model parameters in a dynamic manner. The resulting parameter estimation can well reflect the prevention policy scenarios. Our simulation results with different degrees of government control suggest that the strictly enforced quarantine and travel ban have significantly decreased the otherwise uncontrollable spread of the disease. Our results suggest similar measures should be considered by other countries that are of high risk of COVID-19 outbreak.
doi:10.1101/2020.03.03.20030445 fatcat:nya6knjbire7tki4a2g3kc6nkq

H2A.Z Nucleosome Positioning Has No Impact on Genetic Variation in Drosophila Genome

Yitao Tang, Shan Dong, Xinkai Cao, Qing Zhou, Guitao Ding, Cizhong Jiang, Huaijun Zhou
2013 PLoS ONE  
Nucleosome occupancy results in complex sequence variation rate heterogeneity by either increasing mutation rate or inhibiting DNA repair in yeast, fish, and human. H2A.Z nucleosome is extensively involved in gene transcription activation and regulation. To test whether H2A.Z nucleosome has the similar impact on sequence variability in the Drosophila genome, we profiled the H2A.Z nucleosome occupancy and sequence variation rate at gene ends and splicing sites. Consistent with previous studies,
more » ... 2A.Z nucleosome positioning helps to demarcate the borders of exons. Nucleosome occupancy is anticorrelated with sequence divergence rate in the regions flanking transcription start sites and splicing sites. However, there is no rate heterogeneity between the linker DNA and H2A.Z nucleosomal DNA regardless of nucleosome occupancy, fuzziness, positioning in promoter, coding, and intergenic regions, young or old genes. But the rate at intergenic nucleosomes and the flanking linker regions is higher than that at the genic counterparts. Further analyses found that the high sequence divergence rate in the promoter regions that are usually nucleosome depleted regions may be likely resulted from the high mutation rate in the enriched tandem repeats. Interestingly, within nucleosomes spanning splicing sites, sequence variability of nucleosomal DNA significantly increases from the end within exons to the other end protruding into introns. The relaxed functional constraint in introns contributes to the high rate of nucleosomal DNA residing in introns while the strict functional constraint in exons maintains the low rate of nucleosomal DNA residing in exons. Taken together, H2A.Z nucleosome occupancy has no effect on sequence variability of Drosophila genome, which is likely determined by local sequence composition and the concomitant selection pressure.
doi:10.1371/journal.pone.0058295 pmid:23472174 pmcid:PMC3589275 fatcat:kry6nu6dyzd4dfbb6p5lw6sulm

MOSFET'S 1/f Noise's Equivalent Capacity Model and the Switching Time Analysis

Xinkai Fang, Lijun Cao
2013 Journal of Engineering Science and Technology Review  
Lijun Cao, Shandong university (weihai), E-mail address: ISSN: 1791-2377 © 2013 Kavala Institute of Technology. All rights reserved.  ... 
doi:10.25103/jestr.062.10 fatcat:sl3s5hzxprht5i3g7mzrxl2s7y

The characteristics of ctDNA reveal the high complexity in matching the corresponding tumor tissues

Nong Yang, Yi Li, Zhidong Liu, Hao Qin, Duanming Du, Xinkai Cao, Xiaoqing Cao, Jun Li, Dongge Li, Bo Jiang, Lincan Duan, Haiyan Yang (+8 others)
2018 BMC Cancer  
Next-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues. Methods: We recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our
more » ... ethod and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR). Results: Considering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93. 6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA. Conclusions: In late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.
doi:10.1186/s12885-018-4199-7 pmid:29566644 pmcid:PMC5865353 fatcat:g5rrvkj6ong2bai4csasonsyra

Nucleosome eviction along with H3K9ac deposition enhances Sox2 binding during human neuroectodermal commitment

Yanhua Du, Zhenping Liu, Xinkai Cao, Xiaolong Chen, Zhenyu Chen, Xiaobai Zhang, Xiaoqing Zhang, Cizhong Jiang
2017 Cell Death and Differentiation  
Neuroectoderm is an important neural precursor. However, chromatin remodeling and its epigenetic regulatory roles during the differentiation of human neuroectodermal cells (hNECs) from human embryonic stem cells (hESCs) remain largely unexplored. Here, we obtained hNECs through directed differentiation from hESCs, and determined chromatin states in the two cell types. Upon differentiation, H2A.Z-mediated nucleosome depletion leads to an open chromatin structure in promoters and upregulates
more » ... ssion of neuroectodermal genes. Increase in H3K9ac signals and decrease in H3K27me3 signals in promoters result in an active chromatin state and activate neuroectodermal genes. Conversely, decrease in H3K9ac signals and increase in H3K27me3 signals in promoters repress pluripotency genes. Moreover, H3K9ac signals facilitate the pluripotency factor Sox2 binding to target sites unique to hNECs. Knockdown of the acetyltransferase Kat2b erases H3K9ac signals, disrupts Sox2 binding, and fails the differentiation. Our results demonstrate a hierarchy of epigenetic regulation of gene expression during the differentiation of hNECs from hESCs through chromatin remodeling.
doi:10.1038/cdd.2017.62 pmid:28475175 pmcid:PMC5442478 fatcat:opybi2q67rhszfmhp3wgkn3yri

Salt-Templated Nanoarchitectonics of CoSe2-NC Nanosheets as an Efficient Bifunctional Oxygen Electrocatalyst for Water Splitting

Hong Cao, Hailong Li, Linhao Liu, Kangning Xue, Xinkai Niu, Juan Hou, Long Chen
2022 International Journal of Molecular Sciences  
Recently, the extensive research of efficient bifunctional electrocatalysts (oxygen evolution reaction (OER) and hydrogen evolution reaction (HER)) on water splitting has drawn increasing attention. Herein, a salt-template strategy is prepared to synthesize nitrogen-doped carbon nanosheets encapsulated with dispersed CoSe2 nanoparticles (CoSe2-NC NSs), while the thickness of CoSe2-NC NSs is only about 3.6 nm. Profiting from the ultrathin morphology, large surface area, and promising electrical
more » ... onductivity, the CoSe2-NC NSs exhibited excellent electrocatalytic of 10 mA·cm−2 current density at small overpotentials of 247 mV for OER and 75 mV for HER. Not only does the nitrogen-doped carbon matrix effectively avoid self-aggregation of CoSe2 nanoparticles, but it also prevents the corrosion of CoSe2 from electrolytes and shows favorable durability after long-term stability tests. Furthermore, an overall water-splitting system delivers a current density of 10 mA·cm−2 at a voltage of 1.54 V with resultants being both the cathode and anode catalyst in alkaline solutions. This work provides a new way to synthesize efficient and nonprecious bifunctional electrocatalysts for water splitting.
doi:10.3390/ijms23095239 pmid:35563630 pmcid:PMC9099664 fatcat:5wvhdaqhpvgohcn3galim5zyd4

Modelling-based evaluation of the effect of quarantine control by the Chinese government in the coronavirus disease 2019 outbreak

Xinkai Zhou, Zhigui Wu, Ranran Yu, Shanni Cao, Wen Fang, Zhen Jiang, Fang Yuan, Chao Yan, Dijun Chen
2020 Science China Life Sciences  
doi:10.1007/s11427-020-1717-9 pmid:32394245 pmcid:PMC7212835 fatcat:n3w2thn3rrcw5m7p4fkh22poq4

MicroRNA-449 and MicroRNA-34b/c Function Redundantly in Murine Testes by Targeting E2F Transcription Factor-Retinoblastoma Protein (E2F-pRb) Pathway

Jianqiang Bao, Ding Li, Li Wang, Jingwen Wu, Yanqin Hu, Zhugang Wang, Yan Chen, Xinkai Cao, Cizhong Jiang, Wei Yan, Chen Xu
2012 Journal of Biological Chemistry  
MicroRNAs (miRNAs) are post-transcriptional regulators involved in the regulation of gene expression. Results: miR-449 and miR-34b/c function redundantly in male germ cells. Conclusion: CREM-SOX5-mediated miR-449 expression regulates male germ cell development by targeting the E2F-pRb pathway. Significance: Upstream regulators of miR-449 expression and a redundant role between miR-449 and miR-34b/c in the control of male germ cell development were revealed.
doi:10.1074/jbc.m111.328054 pmid:22570483 pmcid:PMC3381132 fatcat:gtkbkugab5gw3nas626u3e5x6y

High performance of targeted next generation sequencing on variance detection in clinical tumor specimens in comparison with current conventional methods

Dan Su, Dadong Zhang, Kaiyan Chen, Jing Lu, Junzhou Wu, Xinkai Cao, Lisha Ying, Qihuang Jin, Yizhou Ye, Zhenghua Xie, Lei Xiong, Weimin Mao (+1 others)
2017 Journal of Experimental & Clinical Cancer Research  
Next generation sequencing (NGS) is being increasingly applied for assisting cancer molecular diagnosis. However, it is still needed to validate NGS accuracy on detection of DNA alternations based on a large number of clinical samples, especially for DNA rearrangements and copy number variations (CNVs). This study is to set up basic parameters of targeted NGS for clinical diagnosis and to understand advantage of targeted NGS in comparison with the conventional methods of molecular diagnosis.
more » ... hods: Genomic DNA from 1000 Genomes Project and DNA from cancer cell lines have been used to establish the basic parameters for targeted NGS. The following confirmation was conducted by clinical samples. The multiple variants tested by amplification-refractory mutation system (ARMS), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were evaluated by targeted NGS to determine the sensitivity. Furthermore, the multiple variants detected by targeted NGS were confirmed by current conventional methods to elucidate the specificity. Results: At sequencing depth of 500×, the maximal sensitivities on detecting single nucletic variances (SNVs) and small insertions/deletions (Indels) can reach 99% and 98.7% respectively, and in 20% of cancer cells, CNV detection can reach to the maximal level. The following confirmation of the sensitivity and specificity was conducted by a large cohort of clinical samples. For SNV and indel detection in clinical samples, targeted NGS can identify all hotspot mutations with 100% sensitivity and specificity. On ALK fusion detection, about 86% IHC-identified cases could be identified by targeted NGS and all ALK fusion detected by targeted NGS were confirmed by IHC. For HER2-amplification, 14 HER2amplification cases identified by target NGS were all confirmed by FISH and about 93.3% of Her-2 IHC (3+) cases were identified by targeted NGS. Finally, the targeted NGS platform developed here has accurately detected EGFR hotspot mutations in 215 NSCLC patients.
doi:10.1186/s13046-017-0591-4 pmid:28882180 pmcid:PMC5590190 fatcat:qiwxa42cffabjlkkhyinheyynm

Transcription factor ISL1 is essential for pacemaker development and function

Xingqun Liang, Qingquan Zhang, Paola Cattaneo, Shaowei Zhuang, Xiaohui Gong, Nathanael J. Spann, Cizhong Jiang, Xinkai Cao, Xiaodong Zhao, Xiaoli Zhang, Lei Bu, Gang Wang (+12 others)
2015 Journal of Clinical Investigation  
The sinoatrial node (SAN) maintains a rhythmic heartbeat; therefore, a better understanding of factors that drive SAN development and function is crucial to generation of potential therapies, such as biological pacemakers, for sinus arrhythmias. Here, we determined that the LIM homeodomain transcription factor ISL1 plays a key role in survival, proliferation, and function of pacemaker cells throughout development. Analysis of several Isl1 mutant mouse lines, including animals harboring an
more » ... ecific Isl1 deletion, revealed that ISL1 within SAN is a requirement for early embryonic viability. RNA-sequencing (RNA-seq) analyses of FACS-purified cells from ISL1-deficient SANs revealed that a number of genes critical for SAN function, including those encoding transcription factors and ion channels, were downstream of ISL1. Chromatin immunoprecipitation assays performed with anti-ISL1 antibodies and chromatin extracts from FACS-purified SAN cells demonstrated that ISL1 directly binds genomic regions within several genes required for normal pacemaker function, including subunits of the L-type calcium channel, Ank2, and Tbx3. Other genes implicated in abnormal heart rhythm in humans were also direct ISL1 targets. Together, our results demonstrate that ISL1 regulates approximately one-third of SAN-specific genes, indicate that a combination of ISL1 and other SAN transcription factors could be utilized to generate pacemaker cells, and suggest ISL1 mutations may underlie sick sinus syndrome.
doi:10.1172/jci68257 pmid:26193633 pmcid:PMC4563735 fatcat:taqrccyfwbgoxfpib4loz5nawm

Bile cell‑free DNA as a novel and powerful liquid biopsy for detecting somatic variants in biliary tract cancer

Ningjia Shen, Dadong Zhang, Lei Yin, Yinghe Qiu, Jian Liu, Wenlong Yu, Xiaohui Fu, Bin Zhu, Xiaoya Xu, Anqi Duan, Zishuo Chen, Xiang Wang (+12 others)
2019 Oncology Reports  
Tissue sampling of biliary tract carcinomas (BTCs) for molecular characterization is challenging. The aim of this study was to investigate the possibility of identifying individual actionable mutations derived from bile cell‑free DNA (cfDNA) using targeted deep sequencing. Ten BTC patients, four with gallbladder carcinomas and six with cholangiocarcinomas, were enrolled in the present study. Using targeted deep sequencing with a panel of 150 tumor‑related genes, paired bile cfDNA and tumor DNA
more » ... ere analyzed for mutational variants individually and then compared. The present study, to the best of our knowledge, is the first to reveal that bile cfDNA is predominantly comprised of long DNA fragments, which is not the case for plasma cfDNA. Herein, paired bile cfDNA and tumors from ten BTC patients were examined using targeted deep sequencing. When comparing bile cfDNA and tumor DNA for single nucleotide variation (SNV)/insertion and deletion (Indel), the results using targeted deep sequencing revealed high sensitivity (94.7%) and specificity (99.9%). Additionally, the sensitivity of detecting a copy number variation (CNV) was 75.0%, with a specificity of 98.9%. When comparing two bile extraction methods, including percutaneous transhepatic cholangial drainage and operation, no significant difference in SNV/Indel or CNV detection sensitivity was noted. Moreover, when examining the tumor stage and incidence site, AJCC stage II and the distal bile duct both had significantly decreased CNV detection sensitivities. The present study revealed that targeted deep sequencing can reliably detect mutational variants within bile cfDNA obtained from BTC patients. These preliminary results may shed light on bile cfDNA as a promising liquid biopsy for BTC patients.
doi:10.3892/or.2019.7177 pmid:31173267 pmcid:PMC6610033 fatcat:yqskdkto7rdhphjs2uuo4akl5q

Evaluation of ecosystem service of straw return to soil in a wheat field of China

Siyuan Cui, 1. Jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou 225009, Jiangsu, China, Guangqiao Cao, Xinkai Zhu, 2. Key Laboratory of Modern Agricultural Equipment, Ministry of Agriculture, Nanjing Institute of Agricultural Mechanization, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China, 3. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, Jiangsu, China
2021 International Journal of Agricultural and Biological Engineering  
Cao et al.  ...  Consistent with the results of Cao et al.  ... 
doi:10.25165/j.ijabe.20211401.5698 fatcat:cscfdhtvjjd6xdaauorimadnpa

Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non–Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel

Zhijie Wang, Jianchun Duan, Shangli Cai, Miao Han, Hua Dong, Jun Zhao, Bo Zhu, Shuhang Wang, Minglei Zhuo, Jianguo Sun, Qiming Wang, Hua Bai (+18 others)
2019 JAMA Oncology  
Tumor mutational burden (TMB), as measured by whole-exome sequencing (WES) or a cancer gene panel (CGP), is associated with immunotherapy responses. However, whether TMB estimated by circulating tumor DNA in blood (bTMB) is associated with clinical outcomes of immunotherapy remains to be explored. To explore the optimal gene panel size and algorithm to design a CGP for TMB estimation, evaluate the panel reliability, and further validate the feasibility of bTMB as a clinical actionable biomarker
more » ... for immunotherapy. In this cohort study, a CGP named NCC-GP150 was designed and virtually validated using The Cancer Genome Atlas database. The correlation between bTMB estimated by NCC-GP150 and tissue TMB (tTMB) measured by WES was evaluated in matched blood and tissue samples from 48 patients with advanced NSCLC. An independent cohort of 50 patients with advanced NSCLC was used to identify the utility of bTMB estimated by NCC-GP150 in distinguishing patients who would benefit from anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) therapy. The study was performed from July 19, 2016, to April 20, 2018. Assessment of the Spearman correlation coefficient between bTMB estimated by NCC-GP150 and tTMB calculated by WES. Evaluation of the association of bTMB level with progression-free survival and response to anti-PD-1 and anti-PD-L1 therapy. This study used 2 independent cohorts of patients with NSCLC (cohort 1: 48 patients; mean [SD] age, 60 [13] years; 15 [31.2%] female; cohort 2: 50 patients; mean [SD] age, 58 [8] years; 15 [30.0%] female). A CGP, including 150 genes, demonstrated stable correlations with WES for TMB estimation (median r2 = 0.91; interquartile range, 0.89-0.92), especially when synonymous mutations were included (median r2 = 0.92; interquartile range, 0.91-0.93), whereas TMB estimated by the NCC-GP150 panel found higher correlations with TMB estimated by WES than most of the randomly sampled 150-gene panels. Blood TMB estimated by NCC-GP150 correlated well with the matched tTMB calculated by WES (Spearman correlation = 0.62). In the anti-PD-1 and anti-PD-L1 treatment cohort, a bTMB of 6 or higher was associated with superior progression-free survival (hazard ratio, 0.39; 95% CI, 0.18-0.84; log-rank P = .01) and objective response rates (bTMB ≥6: 39.3%; 95% CI, 23.9%-56.5%; bTMB <6: 9.1%; 95% CI, 1.6%-25.9%; P = .02). The findings suggest that established NCC-GP150 with an optimized gene panel size and algorithm is feasible for bTMB estimation, which may serve as a potential biomarker of clinical benefit in patients with NSCLC treated with anti-PD-1 and anti-PD-L1 agents.
doi:10.1001/jamaoncol.2018.7098 pmid:30816954 pmcid:PMC6512308 fatcat:zycml3k6kzaajfveaqqyucwkcu

IEEE/ASME Transactions on Mechatronics

2021 IEEE/ASME transactions on mechatronics  
TECHNICAL EDITORS alMa y. alanis University of Guadalajara, Mexico PinHas bEn-Tzvi Virginia Tech, USA giovanni bErsElli University of Genova, Italy zHuMing bi Purdue University, USA DongPu cao  ...  University of Waterloo, Canada giusEPPE carbonE University of Calabria, Italy jEn-yuan (jaMEs) cHang National Tsing Hua University, Taiwan DongMEi cHEn University of Texas at Austin, USA XinKai  ... 
doi:10.1109/tmech.2021.3086658 fatcat:cl2j522r6jgs5js2kvotjfcq5a

IEEE/ASME Transactions on Mechatronics

2021 IEEE/ASME transactions on mechatronics  
TECHNICAL EDITORS alMa y. alanis University of Guadalajara, Mexico PinHas bEn-Tzvi Virginia Tech, USA giovanni bErsElli University of Genova, Italy zHuMing bi Purdue University, USA DongPu cao  ...  University of Waterloo, Canada giusEPPE carbonE University of Calabria, Italy jEn-yuan (jaMEs) cHang National Tsing Hua University, Taiwan DongMEi cHEn University of Texas at Austin, USA XinKai  ... 
doi:10.1109/tmech.2021.3056303 fatcat:c37dy242pnep3c76jl343muhj4
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