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Increasing isobutanol yield by double-gene deletion of PDC6 and LPD1 in Saccharomyces cerevisiae

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Chinese Journal of Chemical Engineering 2016年第8期24卷 1074-1079页

作者： Aili Zhang Yang Li Yuhan Gao Hongxing Jin School of Chemical Engineering and Technology Hebei University of Technology

As a new biofuel, isobutanol has received more attentions in recent years. Because of its high tolerance to higher alcohols, Saccharomyces cerevisiae has potential advantages as a platform microbe to produce isobutanol. In this study, we investigated integration effects of enhancing valine biosynthesis by overexpression of ILV2 and BAT2 with eliminating ethanol formation by deletion of PDC6 and decreasing acetyl-Co A biosynthesis by deletion of LPD1 on isobutanol titers. Our results showed that deletion of LPD1 in strains overexpressing BAT2 and ILV2 increased isobutanol titer by 5.3-fold compared with control strain. Additional deletion of PDC6 in lpd1Δ strains carrying overexpressed BAT2 and ILV2 further increased isobutanol titer by 1.5 fold. Overexpression of BAT2 and ILV2 in lpd1Δ strains and pdc6Δ strains decreased ethanol titers. Glycerol titers of the engineered strains did not have greater changes than that of control strain, while their acetic acid titers were higher, perhaps due to the imbalance of cofactors in isobutanol synthesis. Our researches suggest that double-gene deletion of PDC6 and LPD1 in strains overexpressing BAT2 and ILV2 could increase isobutanol production dramatically than single-gene deletion of PDC6 or LPD1. This study reveals the integration effects of overexpression of ILV2/BAT2 and double-gene deletion of LPD1 and PDC6 on isobutanol production, and helps understanding future developments of engineered strains for producing isobutanol.

关键词： Saccharomyces cerevisiae Isobutanol Ethanol Pyruvate decarboxylase

Regioselective electrochemical radical cascade cyclization of internal alkynes to selenated and trifluoromethylated dihydropyran

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Science China Chemistry 2023年第11期66卷 3178-3185页

作者： Mingming Yu Tiantian Huang Lin Zhang Muhammad Shabbir Yuhan Gao Yi-Hung Chen Hong Yi Aiwen Lei The Institute for Advanced Studies(IAS) Wuhan UniversityWuhan 430072China National Research Center for Carbohydrate Synthesis Jiangxi Normal UniversityNanchang 330022China

Dihydropyran(DHP)compounds are not only found in natural products and bioactive molecules,but also serve as important precursors in organic synthesis.Nonetheless,traditional methods for the construction of such compounds are usually limited to disubstituted DHPs.To address this synthetic challenge,reported here is an efficient electrochemical strategy toward the selenated and trifluoromethylated DHP compounds.The reaction proceeded smoothly under mild electrolysis conditions.The broad substrate scope(>50 examples)and scalable synthesis demonstrated the complexity-building potential of the strategy.Initial mechanistic studies reveal that cyclization may involve a radical process.This protocol may promote the further development of diversified synthesis of multi-substituted dihydropyran.

关键词： electrochemical organic synthesis dihydropyran cascade cyclization selenylation trifluoromethylation

Ungulate bocaparvovirus 4 and rodent bocavirus are different genotypes of the same species of virus

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Virologica Sinica 2022年第2期37卷 215-222页

作者： Wenqiao He Yuhan Gao Yuqi Wen Xuemei Ke Zejin Ou Jiaqi Fu Mingji Cheng Yun Mo Qing Chen Department of Epidemiology School of Public HealthGuangdong Provincial Key Laboratory of Tropical Disease ResearchSouthern Medical UniversityGuangzhou510515China Xiamen Center for Disease Control and Prevention Xiamen361000China

Bocaviruses are associated with many human infectious diseases, such as respiratory tract infections, gastroenteritis, and hepatitis. Rats are known to be reservoirs of bocaviruses, including rodent bocavirus and rat bocavirus.Recently, ungulate bocaparvovirus 4, a known porcine bocavirus, has also been found in rats. Thus, investigating bocaviruses in rats is important for determining the origin of the viruses and preventing and controlling their transmission. To the best of our knowledge, no study to date has investigated bocaviruses in the livers of rats. In this report, a total of 624 rats were trapped in southern China between 2014 and 2017. Liver and serum samples from rats were tested for the prevalence of bocaviruses using PCR. Sequences related to ungulate bocaparvovirus 4and rodent bocavirus were detected in both liver and serum samples. Interestingly, the prevalence of ungulate bocaparvovirus 4(reference strain: KJ622366.1) was higher than that of rodent bocavirus(reference strain:KY927868.1) in both liver(2.24% and 0.64%, respectively) and serum samples(2.19% and 0.44%, respectively).The NS1 regions of ungulate bocaparvovirus 4 and rodent bocavirus related sequences displayed over 84% and88% identity at the nucleic acid and amino acid levels, respectively. Furthermore, these sequences had similar genomic structure, genomic features, and codon usage bias, and shared a common ancestor. These viruses also displayed greater adaptability to rats than pigs. Our results suggested that ungulate bocaparvovirus 4 and rodent bocavirus may originate from rats and may be different genotypes of the same bocavirus species.

关键词： Ungulate bocaparvovirus 4 Rodent bocavirus(RoBoV) Genome Rats

Understanding the mechanistic regulation of ferroptosis in cancer:the gene matters

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Journal of Genetics and Genomics 2022年第10期49卷 913-926页

作者： Min gao Kexin Fan yuhan Chen Guangjian Zhang Jing Chen Yilei Zhang The Institute of Molecular and Translational Medicine Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesXi'an Jiaotong University Health Science CenterXi'anShaanxi 710061China Department of Thoracic Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi 710061China Department of Obstetrics Xi'an New Chang'an Maternity HospitalXi'anShaanxi 710001China Shaanxi Stem Cell Engineering Application Research Center Shaanxi Jiuzhou Biomedical Science and Technology GroupXi'anShaanxi 710065China

Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases,such as tumor suppression.Though initially being found from anticancer drug screening and considered not essential as apoptosis for growth and development,numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes,including several tumor suppressors and oncogenes.In this review,we introduce the basic concepts of ferroptosis,characterized by the features of non-apoptotic,iron-dependent,and overwhelmed accumulation of lipid peroxides,and the underlying regulated circuits are considered to be pro-ferroptotic pathways.Then,we discuss several established lipid peroxidation defending systems within cells,including SLC7A11/GPX4,FSP1/CoQ,GCH1/BH4,and mitochondria DHODH/CoQ,all of which serve as anti-ferroptotic pathways to prevent ferroptosis.Moreover,we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways.The regulation of proand anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a contextdependent manner,highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy.

关键词： Ferroptosis Ferroptotic pathways Genetic regulation Tumor suppression Cancer therapy

Dynamics of a family of rational maps concerning renormalization transformation

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Frontiers of Mathematics in China 2020年第4期15卷 807-833页

作者： yuhan ZHANG Junyang gao Jianyong QIAO Qinghua WANG School of Science China University of Mining and TechnologyBeijing 100083China School of Science Beijing University of Posts and TelecommunicationsBeijing 100876China

Considering a family of rational maps Tnλconcerning renormalization transform ation,we give a perfect description about the dynamical properties of Tnλand the topological properties of the Fatou components F(Tnλ).F... 详细信息

关键词： Completely invariant domain quasi-circle Hausdorff dimension renormalization transformation

Modelling and validation of flash flood inundation in drylands

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Journal of Geographical Sciences 2024年第1期34卷 185-200页

作者： gao Dan YIN Jie WANG Dandan YANG yuhan LU Yi CHEN Ruishan School of Geographic Sciences East China Normal UniversityShanghai 200241China Key Laboratory of Geographic Information Science of Ministry of Education East China Normal UniversityShanghai 200241China National Disaster Reduction Center of China Ministry of Emergency Management of People's Republic of ChinaBeijing 100124China School of Design Shanghai Jiao Tong UniversityShanghai 200240China

In the context of climate change and human activities,flood disasters in arid mountainous areas have become increasingly frequent,and seriously threatened the safety of people's lives and property.Rapid and accurate flash flood inundation modelling is an essential foundational research area,which can aid in the reduction of casualties and the minimization of disaster losses;however,this modelling is also very difficult,and models need to be urgently developed to address flash flood forecasting and warnings.The objective of this study is to construct a numerical modelling method for flash floods in drylands.Based on a 2D high-resolution flood numerical model(Flood Map-Hydro Inundation2D),we hindcasted the dynamic process of flash flooding and show the spatio-temporal characteristics of flash flood inundation for the“8·18”flash flood disaster that occurred in Datong county,Qinghai province.The results showed that the model output effectively agreed with the observed inundation after the event in terms of both spatial extent and temporal process.Extensive flooding mainly occurred between 00:00 and 01:00 on August 18,2022.Qingshan,Hejiazhuang and Longwo villages were affected most heavily.We further conducted model sensitivity analysis and found that the model was highly sensitive to both roughness and hydraulic conductivity in drylands,and the effect of hydraulic conductivity was more pronounced.Our study confirmed the good performance of our model for the simulation of flash flooding in arid areas and provides a potential method for flash flood assessment and management in arid areas.

关键词： flash flood numerical modelling arid areas Datong county Flood Map-Hydro Inundation2D

Two-Stage Edge-Side Fault Diagnosis Method Based on Double Knowledge Distillation

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Computers, Materials & Continua 2023年第9期76卷 3623-3651页

作者： Yang Yang yuhan Long Yijing Lin Zhipeng gao Lanlan Rui Peng Yu State Key Laboratory ofNetworking and Switching Technology Beijing University of Posts and TelecommunicationsBeijing100876China School of Computer Science and Engineering Nanyang Technological University639798Singapore Science and Technology on Communication Networks Laboratory The 54th Research Institute of China Electronics Technology Group CorporationShijiazhuang050051China

With the rapid development of the Internet of Things(IoT),the automation of edge-side equipment has emerged as a significant trend.The existing fault diagnosismethods have the characteristics of heavy computing and storage load,and most of them have computational redundancy,which is not suitable for deployment on edge devices with limited resources and capabilities.This paper proposes a novel two-stage edge-side fault diagnosis method based on double knowledge distillation.First,we offer a clustering-based self-knowledge distillation approach(Cluster KD),which takes the mean value of the sample diagnosis results,clusters them,and takes the clustering results as the terms of the loss function.It utilizes the correlations between faults of the same type to improve the accuracy of the teacher model,especially for fault categories with high similarity.Then,the double knowledge distillation framework uses ordinary knowledge distillation to build a lightweightmodel for edge-side deployment.We propose a two-stage edge-side fault diagnosismethod(TSM)that separates fault detection and fault diagnosis into different stages:in the first stage,a fault detection model based on a denoising auto-encoder(DAE)is adopted to achieve fast fault responses;in the second stage,a diverse convolutionmodel with variance weighting(DCMVW)is used to diagnose faults in detail,extracting features frommicro andmacro perspectives.Through comparison experiments conducted on two fault datasets,it is proven that the proposed method has high accuracy,low delays,and small computation,which is suitable for intelligent edge-side fault diagnosis.In addition,experiments show that our approach has a smooth training process and good balance.

关键词： Fault diagnosis knowledge distillation edge-side lightweight model high similarity

High-Speed Trains Automatic Operation with Protection Constraints: A Resilient Nonlinear Gain-based Feedback Control Approach

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IEEE/CAA Journal of Automatica Sinica 2019年第4期6卷 992-999页

作者： Shigen gao yuhan Hou Hairong Dong Sebastian Stichel Bin Ning IEEE the State Key Laboratory of Rail Traffic Control and Safety Beijing Jiaotong UniversityBeijing 100044China the Division of Rail Vehicles KTH Royal Inititute of Technology

This paper addresses the control design for automatic train operation of high-speed trains with protection constraints.A new resilient nonlinear gain-based feedback control approach is proposed,which is capable of guaranteeing,under some proper non-restrictive initial conditions,the protection constraints control raised by the distance-to-go(moving authority)curve and automatic train protection in practice.A new hyperbolic tangent function-based model is presented to mimic the whole operation process of high-speed trains.The proposed feedback control methods are easily implementable and computationally inexpensive because the presence of only two feedback gains guarantee satisfactory tracking performance and closed-loop stability,no adaptations of unknown parameters,function approximation of unknown nonlinearities,and attenuation of external disturbances in the proposed control strategies.Finally,rigorous proofs and comparative simulation results are given to demonstrate the effectiveness of the proposed approaches.

关键词： Automatic train operation high-speed train nonlinear gain feedback protection constraint resilient control

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylationmediated mitophagy

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Acta Pharmaceutica Sinica B 2022年第2期12卷 838-852页

作者： Xin Sun yuhan Shu Guiqin Ye Caixia Wu Mengting Xu Ruilan gao Dongsheng Huang Jianbin Zhang Department of Oncology Cancer Center of Zhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou 310014China Clinical Research Institute Zhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou 310014China Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province Hangzhou Medical CollegeHangzhou 310014China College of Biomedical Engineering&Instrument Science Zhejiang UniversityHangzhou 310028China Department of Hematology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China

Parkin,an E3 ubiquitin ligase,plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy.Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level,but the underlying mechanism is poorly understood.Here,our study demonstrated that inhibition of histone deacetylase(HDAC)by treatment of HDACis activates mitophagy through mediating Parkin acetylation,leading to inhibition of cervical cancer cell proliferation.Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer,indicating the low acetylation level of Parkin.Using mass spectrometry,Parkin is identified to interact with two upstream molecules,acetylase acetyl-Co A acetyltransferase 1(ACAT1)and deacetylase HDAC2.Under treatment of suberoylanilide hydroxamic acid(SAHA),Parkin is acetylated at lysine residues 129,220 and 349,located in different domains of Parkin protein.In in vitro experiments,combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1(PINK1)and the function of Parkin in mitophagy induction and tumor suppression.In tumor xenografts,the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA.Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis,which offers a new mitophagy modulation strategy for cancer therapy.

关键词： Parkin Mitophagy ACAT1 HDAC2 Acetylation Ubiquitination Tumor suppression Cervical cancer