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Multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants

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Science China(Life Sciences) 2024年第1期67卷 83-95页

作者： Guangshan Xie Lin Zhu Siwen Liu Cun Li Xin Diao Yanhao Zhang Xiuli Su Yuanyuan Song Guodong Cao Li Zhong Pui Wang Xiaojuan Liu Bobo Wing-yee Mok Shusheng Zhang Dong-Yan Jin jie Zhou Honglin Chen Zongwei Cai State Key Laboratory of Environmental and Biological Analysis Hong Kong Baptist UniversityHong Kong SARChina State Key Laboratory for Emerging Infectious Diseases and Department of MicrobiologyLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina College of Chemistry Zhengzhou UniversityZhengzhou 450001China School of Biomedical Sciences The University of Hong KongHong Kong SARChina HKBU Shenzhen Institute of Research and Continuing Education Shenzhen 518000China

SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and *** high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide *** markers for evaluating the pathogenicity of new variants are therefore *** comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels,six key molecules on the polyamine biosynthesis pathway including putrescine,SAM,dc-SAM,ODC1,SAMS,and SAMDC were found to be differentially upregulated and associated with pathogenicity of *** validate our discovery,human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 *** ODC1 as a proof-ofconcept,differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system(RAS)and positively associated with ACE2 *** experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern(VOCs)and was found to be correlated with each VOCs’pathogenic ***,the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid *** work,therefore,presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.

关键词： SARS-CoV-2 multi-omics attenuated variant predictive pathogenic marker polyamine biosynthesis

Identification of Persister Drug Combination Clinafloxacin+Cefuroxime+Gentamicin That Eradicates Persistent Pseudomonas aeruginosa Infection in a Murine Cystic Fibrosis Model

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Infectious Microbes & Diseases 2023年第1期5卷 21-28页

作者： Yuting Yuan Rebecca yee Naina Gour Xinzhong Dong jie Feng Wanliang Shi Ying Zhang Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public HealthBaltimoreMarylandUSA The Solomon H.Snyder Department of Neuroscience and the Center for Sensory Biology Johns Hopkins University School of MedicineBaltimoreMarylandUSA State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhouZhejiangChina Jinan Microecological Biomedicine Shandong Laboratory JinanShandongChina

Pseudomonas aeruginosa can cause persistent infections,such as biofilm infections,in cystic fibrosis patients,which are difficult to cure due to non-growing persister bacteria that are not effectively killed by the current *** antibiotic activity against growing *** is well documented,their activity against non-growing stationary phase cultures is less ***,we evaluated six major classes of antibiotics,including cell wall and cell membrane inhibitors,protein synthesis inhibitors,DNA synthesis inhibitors,RNA synthesis inhibitors,sulfa drugs and nitrofurantoin,for their activity against growing and non-growing *** foundthat cell wall and cell membrane inhibitors(cefuroxime and colistin),DNA synthesis inhibitors(clinafloxacin)and sulfa drugs(sulfamethoxazole)had good activity against stationary-phase bacteria,while protein synthesis inhibitors(gentamicin),RNA synthesis inhibitor(rifampin)and nitrofurantoin showed relatively poor *** was the only drug able to completely eradicate stationary-phase bacteria within four *** cefuroxime+gentamicin+clinafloxacin combination was able to kill all bacteria from a biofilm within two days,whereas the clinically used drug combination cefuroxime+gentamicin/colistin only partially killed the *** amurine persistent cystic fibrosis lung infectionmodel,only the cefuroxime+gentamicin+clinafloxacin drug combination eradicated all bacteria from the lungs,whereas clinafloxacin alone,cefuroxime+clinafloxacin or the currently recommended drug combination cefuroxime+gentamicin failed to do *** complete eradication is a property of the clinafloxacin combination,as the otherwise identical levofloxacin combination did not clear the bacterial loads from the *** findings offer new therapeutic options for more effective treatment of persistent *** infections,with possible implications for treating other persistent infections.

关键词： Pseudomonas aeruginosa persisters stationary-phase bacteria biofilm clinafloxacin cystic fibrosis

A novel chemotherapy strategy for advanced hepatocellular carcinoma: a multicenter retrospective study

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Chinese Medical Journal 2022年第19期135卷 2338-2343页

作者： Juxian Sun Chang Liu jie Shi Nanya Wang Dafeng Jiang Feifei Mao Jingwen Gu Liping Zhou Li Shen Wan yee Lau Shuqun Cheng Department of Hepatic Surgery VI Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200433China Department of Integrative Oncology Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200433China Department of Outpatient Department Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200433China Department of Oncology First Hospital of Jlin UniversityChangchunJlin 1300China Department of Oncology Zhejiang Sian International Hospital JiaxingZhejang 314000China Tongji University Cancer Center Shanghai Tenth People's HospitaSchool of MedicineTongji UniversitShanghai 200040China Faculty of Medicine The Chinese University of Hong KongPrince of Wales HospitalShatinNew TerritoriesHong Kong SAR 999077China.

Background:Chemotherapy is a common treatment for advanced hepatocellular carcinoma,but the effect is not *** study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid(ATRA)to infusional fluorouracil,leucovorin,and oxaliplatin(FOLFOX4)for advanced hepatocellular carcinoma(HCC).Methods:We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital,First Hospital of Jilin University,and Zhejiang Sian International Hospital and retrospectively compared for overall *** Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age,sex,and disease ***:From July 2013 to July 2018,111 patients with HCC were included in this *** median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group(P<0.001).The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group(3.6 monthsvs.1.8 months,P<0.001).Hazard ratios for overall survival and disease progression were 0.465(95%confidence interval:0.298–0.726;P=0.001)and 0.474(0.314–0.717;P<0.001)after adjusting for potential confounders,***:ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.

关键词： Hepatocellular carcinoma ATRA plus FOLFOX4 Overall survival All-trans-retinoic acid Fluorouracil Leucovorin Oxaliplatin

Combined FOLFOX4 with all-trans retinoic acid versus FOLFOX4 with placebo in treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a randomized, double-blind comparative study

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5096-5105页

作者： Juxian Sun Feifei Mao Chang Liu Fan Zhang Dafeng Jiang Weixing Guo Lei Huo Liping Zhou Wan yee Lau jie Shi Shuqun Cheng Department of Hepatic Surgery VI Third Affliated Hospital of Naval Medical UniversityShanghaiChina Tongji University Cancer Center Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghaiChina Department of General Surgery Fujian Cancer HospitalFujan Medical UniversityFuzhouChina Department of Oncology Zhejiang Sian International HospitalJiaxingChina Department of Radiology Third Affliated Hospital of Naval Medical UniversityShanghaiChina Faculty of Medicine The Chinese University of Hong KongPrince of Wales HospitalShatinNew TerritoriesHong Kong SARChina

The majority of hepatocellular carcinoma(HCC)cases are diagnosed at an advanced ***,there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis(EHM).Systemic chemotherapy,such as FOLFOX4(infusions of fluorouracil,leucovorin,and oxaliplatin),has been reported for treating advanced HCC with EHM,but its effectiveness is very poor.

关键词： FOLFOX4 metastasis chemotherapy

hale gas reservoir modeling and production evaluation considering complex gas transport mechanisms and dispersed distribution of kerogen

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Petroleum Science 2021年第1期18卷 195-218页

作者： jie Zeng Jishan Liu Wai Li yee-Kwong Leong Derek Elsworth Jianchun Guo School of Engineering The University of Western Australia35 Stirling HighwayPerthWA 6009Australia Department of Energy and Mineral Engineering G3 Center and Energy InstituteThe Pennsylvania State UniversityUniversity ParkPA 16802USA State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Southwest Petroleum UniversityChengdu 610500China

Stimulated shale reservoirs consist of kerogen,inorganic matter,secondary and hydraulic *** dispersed distribution of kerogen within matrices and complex gas flow mechanisms make production evaluation *** we establish an analytical method that addresses kerogen-inorganic matter gas transfer,dispersed kerogen distribution,and complex gas flow mechanisms to facilitate evaluating gas *** matrix element is defined as a kerogen core with an exterior inorganic *** most previous models,we merely use boundary conditions to describe kerogen-inorganic matter gas transfer without the instantaneous kerogen gas source *** is closer to real inter-porosity flow conditions between kerogen and inorganic *** diffusion,surface diffusion,adsorption/desorption,and slip corrected flow are involved in matrix gas ***-fracture coupling is realized by using a seven-region linear flow *** model is verified against a published model and field *** reveal that inorganic matrices serve as a major gas source especially at early *** provides limited contributions to production even under a pseudo-steady *** properties’influence starts from the late matrix-fracture inter-porosity flow regime,while inorganic matter properties control almost all flow regimes except the early-mid time fracture linear flow *** contribution of different linear flow regions is also documented.

关键词： Analytical solution Shale gas reservoir Well performance Kerogen and inorganic matter

Dominance of Brassica and No Effects of Raphanus in Mature Seed Production in Intergeneric Hybrid between Brassica rapa ssp. Pekinensis and Raphanus

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American Journal of Plant Sciences 2022年第3期13卷 416-432页

作者： Soo-Seong Lee Cho yee Son eunsil Kim Hosub Shin Jeong eun Park Seung Hwa Yu Jin Hoe Huh BioBreeding Institute Anseong Gyeonggi South Korea Department of Agriculture Forestry and Bioresources College of Agriculture & Life Science Seoul National University Seoul South Korea

We succeeded in producing mature seed from a line of Brassica rapa ssp. pekinensis that had been hybridized with Raphanus sativus var. major. Our focus was on dominance of B. rapa ssp. pekinensis;radish (R. sativus var. major) had no influence. Marker tests for similarity showed that the original CR291M-64 x HwiM-2 hybrid was an inbred CR291M-64, rather than a genuine cross;this appears to have resulted from weak self-incompatibility in this strain. The plants from the mature seed bloomed with reddish flowers differently shown up to present. The intergeneric hybrid between Brassica inbred and Raphanus hybrid was very weak in strength compared to the Brassica inbred which was self-pollinated even though the cause of the weak was not identified. The hybrids between Brassica hybrid, dominant and elite recessive, and Raphanus can be developed in large quantities using mature hybrid seed without resorting to ovule culture techniques.

关键词： Intergeneric Hybrid Brassica Dominance No Raphanus Effect Mature Seed

Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 487-495页

作者： Hao Xing Yi-jie Zheng Jun Han Han Zhang Zhen-Li Li Wan-yee Lau Feng Shen Tian Yang Department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital Naval Medical University Medical Scientific Affairs Abbott Diagnostics Faculty of Medicine The Chinese University of Hong Kong

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

关键词： Hepatocellular carcinoma Meta-analyses Protein induced by vitamin K absence or antagonist-Ⅱ Alpha-fetoprotein

Portal vein tumor thrombus is a bottleneck in the treatment of hepatocellular carcinoma

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Cancer Biology & Medicine 2016年第4期13卷 452-458页

作者： Ju-Xian Sun jie Shi Nan Li Wei-Xing Guo Meng-Chao Wu Wan-yee Lau Shu-Qun Cheng Department of Hepatic Surgery VI Eastern Hepatobiliary Surgical Hospital Faculty of Medicine Chinese University of Hong Kong

The effect of portal vein tumor thrombus(PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: "hepatocellular carcinoma" AND "portal vein tumor thrombus." Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy(RT), transhepatic arterial chemoembolization(TACE), transarterial radioembolization(TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT,TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.

关键词：门静脉肝癌治疗 MEDLINE 临床试验随机对照试验识别机制计算机检索

Typing of biliary tumor thrombus influences the prognoses of patients with hepatocellular carcinoma

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Cancer Biology & Medicine 2021年第3期18卷 808-815页

作者： Juxian Sun Jiayi Wu Chang Liu jie Shi Yonggang Wei Jianyin Zhou Zhibo Zhang Wan yee Lau Maolin Yan Shuqun Cheng Department of Hepatic SurgeryⅥ The Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200433China Shengli Clinical Medical College Fujian Medical UniversityFuzhou 350001China Department of Hepatobiliary Surgery Fujian Provincial HospitalFuzhou 350001China Department of Hepatobiliary Surgery West China HospitalSichuan UniversityChengdu 610041China Department of Hepatobiliary Surgery Zhongshan HospitalXiamen UniversityXiamen 361004China Department of Hepatobiliary Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350002China Faculty of Medicine The Chinese University of Hong KongHong Kong 999077China

Objective:To establish a new classification of biliary tumor thrombus(BTT).Methods:Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging *** and multivariate analyses were used to determine factors affecting the overall survival(OS)to form the basis of our new classification for ***:All 6 international staging systems showed overlapping survival *** followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of *** on these data,a new BTT classification was defined as:TypeⅠ:intrahepatic BTT;and TypeⅡ:extrahepatic BTT involving a common bile duct or common hepatic ***Ⅰwas further subdivided into type Ia:BTT involving a second-order intrahepatic duct or above,and type Ib:BTT involving a first-order intrahepatic ***Ⅱwas further subdivided into typeⅡa and typeⅡb using a cut-off total bilirubin(TB)>300μmol/*** numbers(percentages)of patients with typesⅠandⅡBTT were 69(34.2%)and 133(65.8%),*** median OS of typeⅠpatients was significantly higher than that of typeⅡpatients(37.5 months vs.23.2 months;P=0.002).Using subgroup analyses,OS outcomes were significantly different between the subgroups of typeⅡb and type IIa,although there was no significant difference between the type Ia and type Ib subgroups(P=0.07).Conclusions:A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.

关键词： Hepatocellular carcinoma biliary tumor thrombus staging system surgery prognosis