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Synthetic Gene Circuit-Based Assay with Multilevel Switch Enables Background-Free and Absolute Quantification of Circulating Tumor DNA

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Research 2023年第4期6卷 821-832页

作者： Chao zhang Zedong Li Jie Liu Chang Liu haoqing zhang Won Gu Lee Chunyan Yao Hui Guo Feng Xu The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and TechnologyXi’an Jiaotong UniversityXi’an 710049P.R.China Bioinspired Engineering and Biomechanics Center(BEBC) Xi'an Jiaotong UniversityXi’an 710049P.R.China TFX GroupXi'an Jiaotong University Institute of Life Health Xi'an 710049P.R.China Department of Mechanical Engineering Kyung Hee UniversityYongin 17104Republic of Korea Department of Transfusion Medicine Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038P.R.China Department of Medical Oncology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061P.R.China

Circulating tumor DNA(ctDNA)detection has found widespread applications in tumor diagnostics and treatment,where the key is to obtain accurate quantification of ctDNA.However,this remains challenging due to the issue of background noise associated with existing assays.In this work,we developed a synthetic gene circuit-based assay with multilevel switch(termed CATCH)for background-free and absolute quantification of ctDNA.The multilevel switch combining a small transcription activating RNA and a toehold switch was designed to simultaneously regulate transcription and translation processes in gene circuit to eliminate background noise.Moreover,such a multilevel switch-based gene circuit was integrated with a Cas9 nickase H840A(Cas9n)recognizer and a molecular beacon reporter to form CATCH for ctDNA detection.The CATCH can be implemented in one-pot reaction at 35°C with virtually no background noise,and achieve robust absolute quantification of ctDNA when integrated with a digital chip(i.e.,digital CATCH).Finally,we validated the clinical capability of CATCH by detecting drug-resistant ctDNA mutations from the plasma of 76 non-small cell lung cancer(NSCLC)patients,showing satisfying clinical sensitivity and specificity.We envision that the simple and robust CATCH would be a powerful tool for next-generation ctDNA detection.

关键词： Circulating specificity absolute

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川西鲜水河、安宁河和龙门山断裂带地热水的水文地球化学特征及成因模式的讨论

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中国地质 2024年第1期51卷 341-359页

作者：吕国森章旭张云辉 SAFONOVA Inna 黄豪擎余中友代倩西南交通大学地球科学与环境工程学院四川成都611756 四川省华地建设工程有限责任公司四川成都610081 成都水文地质工程地质中心四川成都610081 自然资源部地质灾害风险防控工程技术创新中心四川成都611730 中国地质调查局军民融合地质调查中心四川成都610036

[研究目的]研究川西鲜水河断裂带、安宁河断裂带和龙门山断裂带地热水的水化学特征及成因模式,可为川西地热水资源的合理开发利用提供重要参考依据。[研究方法]本文运用水文地球化学、热储温度计算、氢氧同位素等方法分析了分布在3条断... 详细信息

[研究目的]研究川西鲜水河断裂带、安宁河断裂带和龙门山断裂带地热水的水化学特征及成因模式,可为川西地热水资源的合理开发利用提供重要参考依据。[研究方法]本文运用水文地球化学、热储温度计算、氢氧同位素等方法分析了分布在3条断裂带上的48处典型温泉(地热井)的水化学组分、水化学过程、热储温度和深度、热水补给来源等特征,并探讨了其形成模式。[研究结果]结果显示:(1)鲜水河断裂带热水水化学类型以HCO_(3)-Na型为主;龙门山断裂带主要为SO_(4)-Na和Cl-Na型;安宁河断裂带包括HCO_(3)·Cl-Na、HCO_(3)·SO_(4)-Ca·Mg和Cl·SO_(4)-Na型等。(2)3条断裂带地热水组分主要受硅酸盐矿物溶解和离子交换作用控制。(3)鲜水河断裂带热储温度为129.6~210.6℃,深度为2532~4184 m,冷水混入比为66%~82%;安宁河断裂带热储温度为81~121.9℃,深度为2155~3519 m,冷水混入比为52%~95%;龙门山断裂带热储温度为108.2~153℃,深度为3573~5654 m,冷水混入比为68%~89%。(4)3条断裂带的地热水接受大气降雨补给,补给高程分别为鲜水河断裂带2493~5034 m、安宁河断裂带3235~3839 m和龙门山断裂带1628~4574 m。(5)鲜水河断裂带地热水的“δ^(18)O漂移”程度强于安宁河断裂带,龙门山断裂带部分地热水出现“δ^(18)O漂移”和“负向漂移”特征。[结论]基于本次研究得到的3条断裂带地热水成因模式,鲜水河断裂带地热水的开发潜力优于安宁河断裂带、龙门山断裂带,是四川省中高温地热资源开发利用的优势靶区。

关键词：断裂带地热水水文地球化学热储补给来源形成模式地热地质调查工程龙门山四川西部

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郴州地区罕见地中海贫血基因突变及血液学特征的分析

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中华医学遗传学杂志 2024年第6期41卷 708-714页

作者：李彩云张健曹颖丽张昊晴黄东群谭菊芳侯帅雷冬竹郴州市第一人民医院中心医院郴州423000 南华大学衡阳医学院衡阳421001

目的:探讨湖南省郴州地区人群地中海贫血罕见突变类型的分布及血液学特点,为地贫的遗传咨询及有效防控提供依据。方法:以2015年1月至2021年12月郴州市第一人民医院收集的37370例样本作为研究对象,对其进行血常规和血红蛋白电泳筛查,采... 详细信息

目的:探讨湖南省郴州地区人群地中海贫血罕见突变类型的分布及血液学特点,为地贫的遗传咨询及有效防控提供依据。方法:以2015年1月至2021年12月郴州市第一人民医院收集的37370例样本作为研究对象,对其进行血常规和血红蛋白电泳筛查,采用高通量测序技术进行地贫基因检测,探讨罕见地贫突变的分布及血液学特点。结果:共检出基因突变8355例,其中罕见型突变185例,共涉及27种突变类型。罕见型α-地贫--THAI和CD31(AGG>AAG)具有典型的小细胞低色素特征,而SEA-HPFH、CD14(CTG>-TG)、CD37(TGG>TAG)、-90(C>T)、Codon 15(G>A)、IVS-Ⅰ-128(T>G)、CD 86(GCC>GC-)及ChineseGγ+(Aγδβ)0均具有典型的小细胞低色素及HbA2或HbF升高的β-地贫血液学特征。β-珠蛋白基因的-50(G>A)杂合子大多平均红细胞体积、平均红细胞血红蛋白含量正常或轻微下降,而HbA 2不高。结论:郴州地区地中海贫血变异类型多样。上述结果可为制定地中海贫血的防控方案和开展优生优育提供数据支撑。

关键词：地中海贫血基因检测罕见突变血液学特征

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Optimal Scheduling for Flexible Regional Integrated Energy Systemwith Soft Open Point

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Computer Modeling in Engineering & Sciences 2022年第5期131卷 1101-1123页

作者： Wen Xu Dongdong Ren Biyi Yi haoqing Zhen Youbing zhang Xuesong zhang Zhejiang Huayun Electric Power Engineering Design&Consulting Co. Ltd.Hangzhou310026China College of Information Engineering Zhejiang University of TechnologyHangzhou310023China Electric Power Research Institute of State Grid Zhejiang Electric Power Company Hangzhou310014China

The Regional Integrated Energy System(RIES)has brought new modes of development,utilization,conversion,storage of energy.The introduction of Soft Open Point(SOP)and the application of Power to Gas(P2G)technology will greatly deepen the coupling of the electricity-gas integrated energy system,improve the flexibility and safety of the operation of the power system,and bring a deal of benefits to the power system.On this background,an optimal dispatch model of RIES combined cold,heat,gas and electricity with SOP is proposed.Firstly,RIES architecture with SOP and P2G is designed and its mathematical model also is built.Secondly,on the basis of considering the optimal scheduling of combined cold,heat,gas and electricity,the optimal scheduling model for RIES was established.After that,the original model is transformed into a mixed-integer second-order cone programming model by using linearization and second-order cone relaxation techniques,and the CPLEX solver is invoked to solve the optimization problem.Finally,the modified IEEE 33-bus systemis used to analyze the benefits of SOP,P2G technology and lithium bromide absorption chillers in reducing systemnetwork loss and cost,as well as improving the system’s ability to absorb wind and solar and operating safety.

关键词： Regional integrated energy system power to gas soft open point wind and photovoltaic power permeation lithium bromide chiller operating cost

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小麦根内细菌群落与黄花叶病发生的关联机制

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植物病理学报 2024年第2期54卷 398-409页

作者：张锐彬秦方锦张昊青吴传发祝贞科葛体达羊健陈剑平李科林中南林业科技大学环境科学与工程学院长沙410004 宁波市农业技术推广总站宁波315211 宁波大学植物病毒学研究所省部共建农产品质量安全危害因子与风险防控国家重点实验室农业部/浙江省植保生物技术重点实验室宁波315211

植物根系微生物组在宿主生长发育、养分吸收以及病害抵御等方面发挥重要作用。为探究小麦根系微生物组变化与黄花叶病发生的关联机制,进而寻求小麦黄花叶病的生物防治方法,本研究采集了健康(H)、中度发病(M)和重度发病(S)小麦根系样品,... 详细信息

植物根系微生物组在宿主生长发育、养分吸收以及病害抵御等方面发挥重要作用。为探究小麦根系微生物组变化与黄花叶病发生的关联机制,进而寻求小麦黄花叶病的生物防治方法,本研究采集了健康(H)、中度发病(M)和重度发病(S)小麦根系样品,研究了不同发病程度下小麦根内细菌群落结构及其环境驱动机制。结果表明:随着发病程度的增加,小麦根内细菌群落丰富度呈下降趋势。细菌群落结构在不同发病程度之间显著分异,且与根际土壤养分含量变化有关。其中短小杆菌属(Curtobacterium)、根瘤菌属(Rhizobium)、中慢生根瘤菌属(Mesorhizobium)、鞘氨醇单胞菌属(Sphingomonas)、人藤黄色杆菌属(Luteibacter)在发病小麦根内富集,其相对丰度与根际土壤中硝态氮(NO-3-N)、有效磷(AP)、有机碳(SOC)、全磷(TP)、全钾(TK)、植物体内碳(PC)含量呈显著正相关,与根际土壤中铵态氮(NH+4-N)、镁(Mg)含量呈显著负相关。泛菌属(Pantoea)在健康小麦根内富集,其相对丰度与植物体内氮(PN)含量呈显著正相关。以上结果表明,小麦根内细菌群落结构变化与小麦黄花叶病的发生及根际土壤养分含量增加有关。

关键词：小麦黄花叶病根内细菌微生物多样性高通量测序

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基于热电制冷的微流体线性降温特性研究

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制冷学报 2024年第1期45卷 55-62页

作者：王好卿孙东方高才程文龙周培唐景春朱俊叶韩雪张梦飞合肥工业大学汽车与交通工程学院合肥230009 中国科学技术大学工程科学学院合肥230026

目前,微流体的精确线性降温是微流控技术在医学和生命科学等领域发展应用过程中面临的难题。为实现微流控芯片目标区域的线性降温,本文设计了基于热电制冷的微流体芯片温度调控系统,通过数值模拟和实验测试,实现了电流、制冷量及微流体... 详细信息

目前,微流体的精确线性降温是微流控技术在医学和生命科学等领域发展应用过程中面临的难题。为实现微流控芯片目标区域的线性降温,本文设计了基于热电制冷的微流体芯片温度调控系统,通过数值模拟和实验测试,实现了电流、制冷量及微流体温度之间的线性耦合响应。结果表明:常规恒定电流驱动热电制冷器时,微流体样品池降温过程线性度仅为0.598,采用单一函数非稳态电流可显著提升微流体降温的线性度,但在不同时间段仍存在冷量盈余与缺口,无法满足线性降温的精度要求。因此,将多种电流波形耦合获得了实现热电冷却微流体线性降温的非稳态过渡电流机制,最终实现了微流体在-19~26℃与24~42℃/min之间的线性降温,线性度在0.9981以上,并通过实验验证了热电冷却微流体线性降温机制的准确性。

关键词：热电制冷微流控线性降温降温速率非稳态电流

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A methodology for regulating fuel stratification and improving fuel economy of GCI mode via double main-injection strategy

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Frontiers in Energy 2023年第5期17卷 678-691页

作者： haoqing WU Yaoyuan zhang Shijie MI Wenbin ZHAO Zhuoyao HE Yong QIAN Xingcai LU Key Laboratory for Power Machinery and Engineering of the Ministry of Education Shanghai Jiao Tong UniversityShanghai 200240China

Gasoline compression ignition(GCI)combustion faces problems such as high maximum pressure rise rate(MPRR)and combustion deterioration at high loads.This paper aims to improve the engine performance of the GCI mode by regulating concentration stratification and promoting fuel-gas mixing by utilizing the double main-injection(DMI)strategy.Two direct injectors simultaneously injected gasoline with an octane number of 82.7 to investigate the energy ratio between the two main-injection and exhaust gas recirculation(EGR)on combustion and emissions.High-load experiments were conducted using the DMI strategy and compared with the single main-injection(SMI)strategy and conventional diesel combustion.The results indicate that the DMI strategy have a great potential to reduce the MPRR and improve the fuel economy of the GCI mode.At a 10 bar indicated mean effective pressure,increasing the main-injection-2 ratio(Rm-2)shortens the injection duration and increases the mean mixing time.Optimized Rm-2 could moderate the trade-off between the MPRR and the indicated specific fuel consumption with both reductions.An appropriate EGR should be adopted considering combustion and emissions.The DMI strategy achieves a highly efficient and stable combustion at high loads,with an indicated thermal efficiency(ITE)greater than 48%,CO and THC emissions at low levels,and MPRR within a reasonable range.Compared with the SMI strategy,the maximum improvement of the ITE is 1.5%,and the maximum reduction of MPRR is 1.5 bar/°CA.

关键词： gasoline compression ignition injection strategy fuel stratification high efficiency high load

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Supporting and retaining competent primary care workforce in low-resource settings:lessons learned from a prospective cohort study

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Family Medicine and Community Health 2023年第4期11卷 13-35页

作者： Mingyue Li haoqing Tang Huixian Zheng Yiran Tian Xiaoran Cheng Haozhe Cheng Xiaotian zhang Dan Hu Xiaoyun Liu School of Public Health Peking UniversityBeijingChina China Center for Health Development Studies Peking UniversityBeijingChina School of Health Policy and Management Nanjing Medical UniversityNanjingJiangsuChina

Objective Assess whether local health facilities can adequately support the performance of general practitioners(GPs)trained by China’s national compulsory services programme(CSP).Design Prospective cohort study.Setting Health facilities in middle and western rural areas in China,2015–2022.Participants Cohorts of CSP graduates from 2015 to 2019 in four major medical universities.Main outcomes Job performance measured by a 12-item Job Performance Scale;productivity measured by outpatient volume per day;turnover measured by ever changing jobs within the past year.Results 91.2%,92.0%and 90.5%GPs working in township health centres reported inadequate medication,equipment and external assistance from higher level hospitals,while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%.The top three tests reported as lacking were blood gases(67.7%),microbiology(61.6%)and cancer biomarkers(49.7%);the top three lacked procedures were CT scan(64.8%),MRI scan(58.1%)and ambulatory BP monitoring(55.8%);and the top three lacked drugs were drugs for cardiovascular diseases(23.3%),systematic hormonal preparations(17.7%)and traditional Chinese medicines(13.0%).Multivariable analysis showed that facility support was positively associated with job performance—adequate medication increased job performance by 2.2 points(95%CI 0.7to 3.8),and adequate external assistance increased job performance by 3.3 points(95%CI 1.8to 4.8).Facility support was also positively associated with productivity—adequate medication increased outpatients seen per day by 20%(95%CI 0.1to 0.3),and adequate equipment increased outpatients seen per day by 12%(95%CI 0.0to 0.2).Facility support did not have significant impact on turnover,but GPs who changed jobs in the past year were 1.9–2.3 times more likely to report adequate facility support.Conclusion GPs in township health centres experienced a high prevalence of shortage in facility support.The identification of a positive association between facility support and perfo

关键词： retaining adequate facility

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人工智能在超声专科医师规范化培训中的作用

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中国继续医学教育 2024年第10期16卷 153-157页

作者：贾彩霞吴蓉胡浩清金利芳张璐妮上海市第一人民医院超声科上海200080 上海市嘉定区中医医院功能科上海201899

专科医师规范化培训是在住院医师培训的基础上,培养高水平专科医师的重要手段。超声医学涉及全身各个系统,课程复杂,超声新技术发展迅速,而传统培养模式下超声人才培养周期长,不利于超声医生临床业务水平和科研能力的深入发展,迫切需要... 详细信息

专科医师规范化培训是在住院医师培训的基础上,培养高水平专科医师的重要手段。超声医学涉及全身各个系统,课程复杂,超声新技术发展迅速,而传统培养模式下超声人才培养周期长,不利于超声医生临床业务水平和科研能力的深入发展,迫切需要新理论、新方法引入超声专科医师规范化培训。人工智能(artificialintelligence,AI)的快速发展对医学教育产生了深刻影响,为人才的个性化教育提供了有效的途径。文章从超声专科医师规范化培训的现状及存在的问题和意义,以及AI在超声专科医师规范化培训中的作用和面临的机遇与挑战等几个方面,探讨AI如何应用于超声专科医师规范化培训,以期为建立全面、系统的基础理论和专业技能培训方案提供新的方法,为完善超声高质量专业人才的培养提供依据。

关键词：人工智能超声医学专科医师规范化培训医学教育实践技能教育模式

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Development and application of a GIS-based artificial neural network system for water quality prediction: a case study at the Lake Champlain area

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Journal of Oceanology and Limnology 2020年第6期38卷 1835-1845页

作者： LU Fang zhang haoqing LIU Wenquan Shandong Provincial Key Laboratory of Marine Environment and Geological Engineering Ocean University of ChinaQingdao 266100China Laboratory for Marine Geology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266000China Key Laboratory of Marine Environment and Ecology Ministry of EducationQingdao 266100China Key Laboratory of Marine Sedimentology and Environmental Geology First Institute of OceanographyMinistry of Natural Resources(MNR)Qingdao 266061China

Artificial Neural Network(ANN)models have been extensively applied in the prediction of water resource variables,and Geographical Information System(GIS)includes powerful functions to visualize spatial data.In order to provide an efficient tool for environmental assessment and management that combines the advantages of these two modules,a GIS-based ANN water quality prediction system was developed in the present study.The ANN module and ArcGIS Engine module,along with a dynamic database,were imbedded in the system,which integrates water quality prediction via the ANN model and spatial presentation of the model results.The structure of the ANN model could be modified through the graphical user interface to optimize the model performance.The developed system was applied to a real case study for the prediction of the total phosphorus concentration in the Lake Champlain area.The prediction results were verified with the monitoring data,and the performance of the developed model was further evaluated through graphical techniques and quantitative statistical methods.Overall,the developed system provided satisfactory prediction results,and spatial distribution maps of the predicted results were obtained,which coincided with the monitored values.The developed GIS-based ANN water quality prediction system could serve as an efficient tool for engineers and decision makers.

关键词： water quality prediction Geographical Information System(GIS) artificial neural network integration system development

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