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Enhanced catalytic efficiency and substrate specificity of Streptomyces griseus trypsin by evolution‑guided mutagenesis

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Systems Microbiology and Biomanufacturing 2023年第2期3卷 287-297页

作者： Jingcheng Shi Chaofan duan Bo Pang Yang Wang Guocheng du Zhen Kang The Science Center for Future Foods Jiangnan UniversityWuxi 214122China The Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan University1800 Lihu RoadWuxi 214122JiangsuChina The Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

Streptomyces griseus trypsin(SGT)is a bacteria-sourced trypsin that could be potentially applied to industrial insulin ***,SGT produced by microbial hosts displayed low catalytic efficiency and undesired preference to lysine *** this study,by engineering theαsignal peptide in Pichia pastoris,we increased the SGT amidase activity to 67.91 U mL^(−1)in shake flask ***,we engineered SGT by evolution-guided mutagenesis and obtained three variants A45S,V177I and E180M with increased catalytic *** this basis,we performed iterative combinatorial mutagenesis and constructed a mutant A45S/V177I/E180M which the amidase activity reached 98 U mL^(−1)in shake flasks and 2506 U mL^(−1)in 3-L fed-batch ***,single mutation T190 to S190 increased the substrate catalytic preference of R to K and the R/K value was improved to 7.5,which was 2 times better than the animal-sourced trypsin.

关键词： Trypsin Enzyme engineering Pichia pastoris Streptomyces griseus

Targeting cancer stem cells in drug discovery: Current state and future perspectives

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World Journal of Stem Cells 2019年第7期11卷 398-420页

作者： Fang-Yu du Qi-Fan Zhou Wen-Jiao Sun Guo-Liang Chen Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical University

In recent decades,cancer stem cells(CSCs)have been increasingly identified in many ***-related signaling pathways and their functions provide new strategies for treating *** aberrant activation of related signaling pathways(e.g.,Wnt,Notch,and Hedgehog pathways)has been linked to multiple types of malignant tumors,which makes these pathways attractive targets for cancer *** display many characteristic features,such as self-renewal,differentiation,high tumorigenicity,and drug ***,there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication,survival,and *** crosstalk occurs among different signaling pathways and potentially leads to compensatory ***,multitarget inhibitors will be one of the main methods to overcome the drug resistance of *** small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials,and some inhibitors,such as vismodegib,sonidegib,and glasdegib,have been *** cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo *** signal transducers and activators of transcription 3(STAT3)inhibitor BBI608 is being evaluated in a phase III trial for a variety of *** derivatives of BBI608 are the main focus of STAT3 inhibitor development,which is another strategy for CSC *** addition to the potential pharmacological inhibitors targeting CSCrelated signaling pathways,other methods of targeting CSCs are available,such as nano-drug delivery systems,mitochondrion targeting,autophagy,hyperthermia,immunotherapy,and CSC microenvironment *** addition,we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.

关键词： Cancer stem cells Cancer stem cell-related signaling pathways Nano-drug delivery system Immunotherapy Mitochondrion Cancer stem cell

The efficacy and safety of besifloxacin for acute bacterial conjunctivitis: a Meta-analysis

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International Journal of Ophthalmology(English edition) 2019年第6期12卷 1027-1036页

作者： Jun-Jie Wang Xin-Yi Gao Hong-Zhuo Li Shan-Shuang du Changzhi Medical College Changzhi 046000Shanxi ProvinceChina Shaanxi Ophthalmic Medical Center Xi’an No.4 HospitalAffiliated Guangren HospitalSchool of MedicineXi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Heping Hospital Affiliated to Changzhi Medical College Changzhi 046000Shanxi ProvinceChina

AIM: To evaluate the relative efficacy and safety of besifloxacin for treatment of acute bacterial ***: A comprehensive search in PubMed, EMBASE Web of Science, Cochrane Central Database and CNKI was undertaken for randomized controlled trials(RCTs) comparing besifloxacin with other treatments or placebo. The primary outcome measures were clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, and bacterial eradication rates of different kinds of pathogens. Safety outcomes were the number of adverse effects(AEs). The final search was performed on August ***: Eight RCTs were included. Five studies compared the efficacy and safety of besifloxacin with placebo, 2 studies compared besifloxacin with moxifloxacin, and 1 study compared besifloxacin with gatifloxacin. A total of 3105 patients met the inclusion criteria. Besifloxacin presented higher efficacy and safety than did placebo in clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, bacterial eradication rates of different kinds of pathogens and the number of AEs. There was no significant difference between besifloxacin and moxifloxacin or gatifloxacin in the comparison items mentioned ***: Besifloxacin is highly effective and safe for treatment of acute bacterial conjunctivitis. Further comparative trials regarding the effect of besifloxacin for treatment of acute bacterial conjunctivitis will aid in treatment decisions.

关键词： besifloxacin acute bacterial conjunctivitis Meta-analysis randomized controlled trials

Machine learning-based detection of cervical spondylotic myelopathy using multiple gait parameters

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Biomimetic Intelligence & Robotics 2023年第2期3卷 30-40页

作者： Xinyu Ji Wei Zeng Qihang Dai Yuyan Zhang Shaoyi du Bing Ji School of Control Science and Engineering Shandong UniversityJinan 250061China School of Physics and Electromechanical Engineering Longyan UniversityLongyan 364012China Institute of Artificial Intelligence and Robotics Xi’an Jiaotong UniversityXi’an 710049China

Cervical spondylotic myelopathy(CSM)is the main cause of adult spinal cord dysfunction,mostly appearing in middle-aged and elderly ***,the diagnosis of this condition depends mainly on the available imaging tools such as X-ray,computed tomography and magnetic resonance imaging(MRI),of which MRI is the gold standard for clinical ***,MRI data cannot clearly demonstrate the dynamic characteristics of CSM,and the overall process is far from ***,this study proposes a new method using multiple gait parameters and shallow classifiers to dynamically detect the occurrence of *** the present study,45 patients with CSM and 45 age-matched asymptomatic healthy controls(HCs)were recruited,and a three-dimensional(3D)motion capture system was utilized to capture the locomotion ***,63 spatiotemporal,kinematic,and nonlinear parameters were extracted,including lower limb joint angles in the sagittal,coronal,and transverse ***,the Shapley Additive exPlanations(SHAP)value was utilized for feature selection and reduction of the dimensionality of features,and five traditional shallow classifiers,including support vector machine(SVM),logistic regression(LR),k-nearest neighbor(KNN),decision tree(DT),and random forest(RF),were used to classify gait patterns between CSM patients and *** the basis of the 10-fold cross-validation method,the highest average accuracy was achieved by SVM(95.56%).Our results demonstrated that the proposed method could effectively detect CSM and thus serve as an automated auxiliary tool for the clinical diagnosis of CSM.

关键词： Cervical spondylotic myelopathy Gait analysis Machine learning Shapley Additive exPlanations

Experimental study on the working performance of different milling tools for multistage fracturing ball seats

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Petroleum Science 2020年第6期17卷 1699-1716页

作者： Jia-Qi Che Han-Xiang Wang Yan-Wen Zhang Ming-Chao du Shao-Hua Ma College of Mechanical and Electronic Engineering China University of Petroleum(East China)Qingdao 266580ShandongPeople’s Republic of China

To achieve the secondary production in multistage fracturing wells of tight oil,milling tools are usually used to remove the multistage fracturing ball seats to achieve production with a large diameter in *** this paper,first of all,the working mechanism of milling tools for multistage fracturing ball seats was studied and a mechanical analysis model of single abrasive grain was ***,an experimental system for milling tools was developed,and the experimental tests of the flat,the blade,and the slope milling tool were conducted in ***,the morphology of chips and the surface morphology of the workpiece after the experiment were ***,the working performance of milling tools was evaluated from the perspectives of working safety,working efficiency,and wear resistance of the milling *** results show that the torque of the milling tool increases nonlinearly with the increase in the cutting depth of the abrasive grain and increases linearly with the increase in the cutting ***,the chips are irregular particles and the size is mainly from 10 to 50μ***,the chips should be pumped up with a small pump pressure and a large *** this,the cutting depths of the abrasive grains are from 216.20 to 635.47μm and the bottom surface of the milling tool should be eccentric to avoid the zero point of cutting ***,the torque of the slope milling tool is 23.8%larger than that of the flat milling tool,which is also 30.4%smaller than that of the blade milling *** with the flat milling tool,the working efficiency of the blade milling tool improves by 79.9%and the slope milling tool improves by 111.1%.Also,the wear resistance of the blade milling tool decreases by 102.7%,while the slope milling tool declines by 32.6%when compared with the flat milling ***,the slope milling tool has the characteristics of moderate torque,stable working conditions,the highest working efficiency,and fine wear resistan

关键词： Multistage fracturing ball seat Milling tool Working performance Tight oil Experimental system Single abrasive grain

Wearable Fiber‑Based Supercapacitors Enabled by Additive‑Free Aqueous MXene Inks for Self‑Powering Healthcare Sensors

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Advanced Fiber Materials 2022年第6期4卷 1535-1544页

作者： Junlin Ma Zewei Cui Yuhang du Jianxin Zhang Changkai Sun Chengyi Hou Nan Zhu Zhang Dayu School of Chemistry Dalian University of TechnologyDalian 116024LiaoningChina State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai 201620People’s Republic of China Research&Educational Center for the Control Engineering of Translational Precision Medicine(R‑ECCE‑TPM) School of Biomedical EngineeringDalian University of TechnologyDalian 116024LiaoningChina

Wearable fiber-based electronics have found diverse applications including energy storage,healthcare or thermal management,*** particular,additive-free aqueous inks play significant roles in fabrication of wearable fiber-based devices,owning to their nontoxic nature and ease of ***,wearable carbon fiber-based asymmetric supercapacitors(WASSC)are developed based on additive-free aqueous MXene inks,for self-powering healthcare *** sediments of MXene without further modification are used as ***,combined with additive-free aqueous MXene/polyaniline(MP)inks,WASSC,with a wide voltage window and high capacitance is developed for practical energy ***,WASSC has been successfully utilized to power wearable pressure sensors that could monitor motions and pulse *** wearable self-powered monitoring system on can accurately monitor the human motions,pronunciation,swallow or wrist pulse,without using the rigid *** advantage realizes a great potential in simple and cost effective monitoring of human health and ***,self-powered system enables waste recycling of MXene and provides an effective approach for designing wearable and fiber-based self-powered sensors.

关键词： Wearable electronics Additive-free aqueous inks Fiber-based supercapacitors MXene Self-powered sensor

Construction of citrus gene coexpression networks from microarray data using random matrix theory

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Horticulture Research 2015年第1期2卷 193-200页

作者： Dongliang du Nidhi Rawat Zhanao Deng Fred G.Gmitter Jr. Citrus Research and Education Center Institute of Food and Agricultural SciencesUniversity of FloridaLake AlfredFL 33850USA Gulf Coast Research and Education Center Institute of Food and Agricultural SciencesUniversity of FloridaWimaumaFL 33598USA

After the sequencing of citrus genomes,gene function annotation is becoming a new *** coexpression analysis can be employed for function annotation using publicly available microarray data *** this study,230 sweet orange(Citrus sinensis)microarrays were used to construct seven coexpression networks,including one condition-independent and six condition-dependent(Citrus canker,Huanglongbing,leaves,flavedo,albedo,and flesh)*** total,these networks contain 37633 edges among 6256 nodes(genes),which accounts for 52.11%measurable genes of the citrus ***,these networks were partitioned into functional modules using the Markov Cluster *** enriched Gene Ontology biological process terms and KEGG pathway terms were detected for 343 and 60 modules,***,independent verification of these networks was performed using another expression data of 371 *** study provides new targets for further functional analyses in citrus.

关键词： measurable orange partitioned

A Multi-Wavelength Study of the 3B/X1.2 Flare Observed on 2003 October 26

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Chinese Journal of Astronomy and Astrophysics 2005年第6期5卷 645-664页

作者： Hui Li Jian-Ping Li Cheng Fang Brigitte Schmieder Arkadiusz Berlicki Qiu-Sheng du Purple Mountain Observatory Chinese Academy of Sciences Nanjing 210008 Department of Astronomy Nanjing University Nanjing 210093 Observatoire de Paris Section de Meudon LESIA i~-9-2195 Meudon Principal CedexFrance Institute of Theoretical Astrophysics University of Oslo Blindern N-0315 Oslo Norway Astronomical Institute of the Wroctaw University ul.Kopernika 11 51-622 Wroctaw Poland

We report results from a multi-wavelength study of the 3B/X1.2 tworibbon disk flare （S15E44）, which was well observed by both ground-based and space-borne instruments. Two pairs of conjugate kernels - K1 and K4, and K2 and K3 - in the Ha images are identified. These kernels are linked by two different systems of EUV loops. K1 and K4 correspond to the two 17 GHz and 34 GHz microwave sources observed by the Nobeyama Radioheliograph （NoRH）, while K2 and K3 have no corresponding microwave sources. Optical spectroscopic observations suggest that all the four kernels are possible precipitating sites of non-thermal electrons. Thus the energy of electron deposited in K2 and K3 should be less than 100keV. Two-dimensional distributions of the full widths at half maximum （FWHM） of the Ha profiles and the line-of-sight （LOS） velocities derived from the Ca n 8542 A profiles indicate that the largest FWHM and LOS velocity tends to be located near the outer edges of Hα kernels, which is consistent with the scenario of current two-ribbon flare models and previous results. When non-thermal electron bombardment is present, the observed Hα and Ca II 8542 A profiles are similar to previous observational and theoretical results, while the He I 10830 A profiles are different from the theoretical ones. This puts some constraints on future theoretical calculation of the He I 10830 A line.

关键词： Sun flares - Sun X-rays - line profiles

MHC polymorphism and disease-resistance to Edwardsiella tarda in six turbot(Scophthalmus maximus) families

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Chinese Science Bulletin 2012年第25期57卷 3262-3269页

作者： du Min CHEN SongLin LIU YanHong NIU BaoZhen YANG JingFeng ZHANG Bo Key Laboratory for Sustainable Utilization of Marine Fisheries Resources Ministry of AgricultureYellow Sea Fisheries Research InstituteChinese Academy of Fishery SciencesQingdao 266071China College of Life Sicence and Technology Honghe UniversityMengzi 661100China College of Aqua-Life Science and Technology Shanghai Ocean UniversityShanghai 200090China

This study examined genetic variation in the major histocompatibility complex(MHC) Class II B gene in turbot(Scophthalmus maximus) by virulent bacterial pathogen *** hundred fry from each of six families were infected with Edwardsiella tarda by intraperitoneal *** mortality ranged from 28.0% to 83.3%.Complete exon 2 and intron 1 sequences of MHC Class II B genes were amplified from five survivor and five non-survivor individuals per family using the clone-sequence ***-seven sequences from 60 individuals revealed 37 different alleles,25 of which were unique to this *** 25 unique alleles belonged to 16 major allele *** alleles were used to examine the association between alleles and resistance/susceptibility to *** alleles were present in an individual,suggesting a minimum of three loci or copies of the turbot MHC Class II B *** rate of non-synonymous substitution(d N) was 2.30 and 1.58 times higher than synonymous substitution(d S) in the peptide-binding regions(PBR) and non-PBR in whole families,respectively,which suggested balancing selection on exon 2 of the MHC Class II B gene in *** allele,Scma-DBB1*02,was significantly more prevalent in survivor stock than in non-survivor stock(P=0.001).Therefore,this allele might be associated with resistance to bacteria.A second allele,Scma-DBB1*10,was significantly more prevalent in non-survivor stock(P=0.021),and is likely associated with susceptibility to bacteria.

关键词：迟钝爱德华氏菌基因多态性大菱鲆 MHC 家庭鱼苗主要组织相容性复合体抗病性