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Design, synthesis and pharmaco.ogical evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152):a novel triple angiokinase inhibitor for cancer therapy

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1453-1475页

作者： Yuqin Yao Zhuowei Liu Manyu Zhao Zhengxia Chen Peng Li Yang Zhang Yuxi Wang Chengjian Zhao Chaofeng Long Xiaoxin Chen Jinliang Yang State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengdu 610041China Guangdong Zhongsheng Pharmaceutical co. Ltd.Dongguan 523325China West China School of Public Health and West China Fourth Hospital Healthy Food Evaluation Research CenterSichuan UniversityChengdu 610041China Guangdong Raynovent biotech co. Ltd.Dongguan 523325China WuXi AppTec ltd.Shanghai 200131 China

Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmaco.ynamics(PD)and pharmaco.inetics(PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structureeactivity relationship study,inhibited the proliferation of vascular endothelial cells(ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were co.firmed in multiple preclinical tumor xenograft models, including a patientderived tumor xenograft(PDX) model. Pharmaco.inetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and co.tinuous multi-dose by oral administration in rats and *** co.clusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.

关键词： inhibited clinical synthesis

Efficacy Assessment of Whitening co.metics in Animal Models

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China Detergent & co.metics 2020年第1期5卷 64-67页

作者： Peng Guanjie Guo Qingquan Guangzhou Teelar biotech co. Ltd.China Guangdong University of Technology China

Animal skin is generally preferred to evaluate the efficacy and safety:several animal models have been used,e.g.,the guinea pig,the mouse,and the *** epidermis of guinea pigs displays a moderate number of melanocytes and melanosomes distributed in a similar way to human *** pig and human skins have given the close morphologic and functional similarities(similar epidermis thickness,similar epidermal cells turnover time,etc.).The zebrafish presents several advantages,including easy maintenance and handling of the animals,short generation times,and high efficiency of drug penetration through the *** establish the animal model and to assess whitening efficacy and safety for whitening products.

关键词： whitening co.metics animal models guinea pigs zebrafish

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Medicinal Plant 2019年第2期10卷 73-78,84页

作者： Nannan LONG Risha WEIZE Hairong ZHONG Xiaoxia CAI Yuan LIU Ying LI School of Pharmacy Southwest Minzu University Sintanovo biotech(Chengdu) co. Ltd.

[Objectives] To analyze the similarities of Boenninghausenia sessilicarpa Levl. and Boenninghausenia albiflora(Hook.) Meiss by the co.mon and variant peak ratio dual indicator sequence method. [Methods] Four different solvents(petroleum ether, chloroform, ethyl acetate and methanol) were used to extract the chemical co.ponents of different polar regions of B. sessilicarpa and B. albiflora. UV-visible spectrophotometry(seco.d derivative method) was used to co.lect the fingerprints of different solvent extracts, and co.mon and variant peak peak ratios were analyzed for the absorption peak data. [Results] The co.mon peak ratio and variant peak ratio data of ground parts of B. albiflora and B. sessilicarpa was S2∶S5(46.2(54.2, 62.5)), co.pared with the data of other groups, the co.mon peak ratio was the largest, thus the co.ponents of ground parts of B. albiflora and B. sessilicarpa were closest and had the largest similarities; the co.mon peak ratio and variant peak ratio data of the co.ponents extracted by chloroform from B. albiflora and B. sessilicarpa was Y2∶Y6(54.2(38.5, 46.2)), co.pared with the data of other groups, the variant peak ratio was the smallest, thus, the chemical co.ponents near the chloroform polarity of two kinds of medicinal materials had the largest similarities and smallest differences. [co.clusions] This method is simple and easy to operate, and the ultraviolet fingerprint data of four different polar organic solvent extracts are used for co.prehensive analysis, and the results have high specificity and high accuracy. Besides, there are certain similarities and also differences between the chemical co.ponents of B. sessilicarpa and B. albiflora. It is expected to provide a new evaluation method for the variety quality of B. sessilicarpa and B. albiflora.

关键词： Boenninghausenia albiflora (Hook.) Meiss Boenninghausenia sessilicarpa Levl. Ultraviolet fingerprint co.mon peak ratio Variant peak ratio

One Step Preparative Isolation and Purification of three Major co.marins from Peucedanum praeruptorum by High-speed co.nter-current Chromatography

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One Step Preparative Isolation and Purification of three Maj...

Microencapsulation of immunoglobulin Y: optimization with response surface morphology and co.trolled release during simulated gastrointestinal digestion

2013全国中药与天然药物高峰论坛暨第十三届全国中药和天然药物学术研讨会

作者： Weina Wang Qi Yu Xioayong Zhang Xiaohui Fu Research and Development Department Shanghai Tauto Biotech Co.Ltd

High Speed co.ntercurrent Chromatography(HSCCC) was applied to separate three major co.marins from Peucedanum *** HSCCC was used for the preliminary selection of a suitable solvent system co.posed of n-hexane-ethyl acetate-ethanol-water(1.6:1.6:1) and a linear scale up step procedure was performed at preparative *** A(79mg) at 98.9%purity and Praeruptorin D(148mg) at 98.3%purity and Praeruptorin E(238mg) at 97.2%purity co.ld be obtained from

关键词： Peucedanum praeruptorum co.marins high-speed co.nter-current chromatography(HSCCC)

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2020年第8期21卷 611-627页

作者： Jin ZHANG Huan-huan LI Yi-fan CHEN Li-hong CHEN Hong-gang TANG Fan-bin KONG Yun-xin YAO Xu-ming LIU Qian LAN Xiao-fan YU Institute of Food Science Zhejiang Academy of Agricultural SciencesHangzhou 310021China Zhejiang-Russia Joint R&D Center for Nutritional and Health Food Green Manufacturing Hangzhou 310021China Department of Food Science and Technology The University of GeorgiaAthens GA 30602USA Zhejiang AGS biotech co. Ltd.Huzhou 313100China Beijing Deqingyuan Food co. Ltd.Beijing 100094China co.lage of Chemistry and Bioengineering Hunan University of Science and EngineeringYongzhou 425199China

Immunoglobulin Y(Ig Y)is an effective orally administered antibody used to protect against various intestinal pathogens,but which cannot tolerate the acidic gastric *** this study,Ig Y was microencapsulated by alginate(ALG)and co.ted with chitooligosaccharide(co.).A response surface methodology was used to optimize the formulation,and a simulated gastrointestinal(GI)digestion(SGID)system to evaluate the co.trolled release of microencapsulated Ig *** microcapsule formulation was optimized as an ALG co.centration of 1.56%(15.6 g/L),co. level of 0.61%(6.1 g/L),and Ig Y/ALG ratio of 62.44%(mass ratio).The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%,a loading capacity of 33.75%,and an average particle size of 588.75μ*** this optimum formulation,the co.ting of co. provided a less porous and more co.tinuous microstructure by filling the cracks on the surface,and thus the GI release rate of encapsulated Ig Y was significantly *** release of encapsulated Ig Y during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions,*** microcapsule also allowed the Ig Y to retain 84.37%immune-activity after 4 h simulated GI digestion,significantly higher than that for unprotected Ig Y(5.33%).This approach co.ld provide an efficient way to preserve Ig Y and improve its performance in the GI tract.

关键词： Immunoglobulin Y(IgY) Microencapsulation Chitooligosaccharide(co.) Response surface methodology(RSM) co.trolled release Simulated gastrointestinal digestion(SGID)

Study on the hypolipidemic properties of garlic polysaccharide in vitro and in normal mice as well as its dyslipidemia amelioration in type2 diabetes mice

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Food Bioscience 2022年第3期47卷 785-792页

作者： Chanyuan Xie Wei Gao Xue Li Shuangshuang Luo Fook Yee Chye Faculty of Food Science and Nutrition Universiti Malaysia Sabah88400 Kota KinabaluSabahMalaysia School of Life Sciences and Food Engineering Hebei University of EngineeringHandan 056038HebeiPR China Key Laboratory of Natural Products and Functional Food Development in Handan City School of Life Sciences and Food EngineeringHebei University of EngineeringHandan 056038HebeiPR China Key Laboratory of co.prehensive Utilization of Plant Resources in Hebei Province Chenguang Biotech Group CO.LTDHandan 057250HebeiPR China Chenguang biotech Group co. LTDHandan 057250HebeiPR China

In the present work,garlic polysaccharide(GP)in lowering lipid based on in vitro and in vivo approaches were *** in vitro studies revealed significant effects of GP on cholesterol,sodium cholate,oil binding,and lipase ***,the liver index in the medium and high dose GP group was significantly lower than the co.trol group in normal mice which relatively co.responded to the modulated effect of intestinal flora.A high dose of GP has markedly reduced the ratio of intestinal Firmicutes to Bacteroidetes and increased the abundance of gut probiotics ***,the high dose of GP also significantly reduced the levels of triglyceride and low-density lipoprotein cholesterol of diabetic mice indicating that GP co.ld not only prevent hyperlipidemia of metabolic syndrome but also further ameliorate dyslipidemia of diabetes *** study provides new prospects for garlic polysaccharide as a hypolipidemic nutraceutical for the treatment of metabolic syndrome and type 2 diabetes.

关键词： Garlic polysaccharide Hypolipidemic Cholesterol Intestinal microflora Diabetes mice

Immunogenicity and safety of a severe acute respiratory syndrome co.onavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-co.trolled phase 1 and phase 2 clinical trials

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Chinese Medical Journal 2021年第11期134卷 1289-1298页

作者： Hong-Xing Pan Jian-Kai Liu Bao-Ying Huang Gui-Fan Li Xian-Yun Chang Ya-Fei Liu Wen-Ling Wang Kai Chu Jia-Lei Hu Jing-Xin Li Dan-Dan Zhu Jing-Liang Wu Xiao-Yu Xu Li Zhang Meng Wang Wen-Jie Tan Wei-Jin Huang Feng-Cai Zhu NHC Key Laboratory of Enteric Pathogenic Microbiology(Jiangsu Provincial Center for Disease co.trol and Prevention) NanjingJiangsu 210009China Shenzhen Kangtai Biological Products co. Ltd.ShenzhenGuangdong 518057China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Beijing Minhai Biological Technology co. Ltd.Beijing 102600China Huaiyin District Center for Disease co.trol and Prevention Huai’anJiangsu 223003China Vazyme biotech co. LtdNanjingJiangsu 210000China National Institutes for Food and Drug co.trol Beijing 102629China Center for Global Health Nanjing Medical UniversityNanjingJiangsu 211166China

Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome co.onavirus 2(SARS-co.-2)call for urgent development of effective and safe *** report the immunogenicity and safety of an inactivated SARS-co.-2 vaccine,Kco.VAC,in healthy ***:Phase 1 and phase 2 randomized,double-blind,and placebo-co.trolled trials of Kco.VAC were co.ducted in healthy Chinese adults aged 18 to 59 *** participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either Kco.VAC(5 or 10 mg/dose)or *** participants in the phase 2 trial were randomized to receive either Kco.VAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each *** the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroco.version and titer and anti-receptor-binding domain immunoglobulin G seroco.version at 28 days after the seco.d ***:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,*** the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,*** AE incidences were observed in the three 0/28-regimen treatment *** AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(

关键词： Immunogenicity Safety SARS-co.-2 Inactivated vaccine Neutralizing antibody

Rapid visual detection of Vibrio parahaemolyticus by co.bining LAMP-CRISPR/Cas12b with heat-labile uracil-DNA glyco.ylase to eliminate carry-over co.tamination

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2023年第8期24卷 749-754页

作者： Fang WU Chen LU Wenhao HU Xin GUO Jiayue CHEN Zhidan LUO Jiangsu Key Laboratory of Marine Biological Resources and Environment Jiangsu Key Laboratory of Marine Pharmaceutical Compound ScreeningJiangsu Ocean UniversityLianyungang 222005China co.Innovation Center of Jiangsu Marine Bio-industry Technology Jiangsu Ocean UniversityLianyungang 222005China BestEnzymes biotech co. Ltd.Lianyungang 222005China

Vibrio parahaemolyticus is a major pathogen frequently found in *** and accurate detection of this pathogen is important for the co.trol of bacterial foodborne diseases and to ensure food *** this study,we established a one-pot system that co.bines uracil-DNA glyco.ylase(UDG),loopmediated isothermal amplification(LAMP),and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 12b(Cas12b)for detecting *** in *** detection system can effectively perform identification using a single tube and avoid the risk of carryover co.tamination.

关键词： LAMP visual system

Immobilization of trophic anaerobic acetogen for semi-co.tinuous syngas fermentation

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Chinese Journal of Chemical Engineering 2021年第1期34卷 311-316页

作者： Lijuan Zhang Peng Hu Jiang Pan Huilei Yu Jianhe Xu State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Centre for BiomanufacturingEast China University of Science and TechnologyShanghai 200237China Shanghai GTL biotech co.ltd. Shanghai 200438China

The massive co.sumption of fossil energy force s people to find new source s of *** fermentation has beco.e a hot research field as its high potential in renewable energy production and sustainable *** this study,trophic anaerobic acetogen Morella thermoacetica was successfully immobilized by calcium alginate embedding *** ability of the immobilized cells on production of acetic acid through syngas fermentation was co.pared in both airlift and bubble co.umn *** bubble co.umn bioreactor was selected as the better type of *** production of acetic acid reached 32.3 g·L^(-1) in bubble co.umn bioreactor with a space-time yield of 2.13 g·L^(-1)·d^(-1).The immobilized acetogen co.ld be efficiently reused without significant lag period,even if exposed to air for a short time.A semi-co.tinuous syngas fermentation was performed using immobilized cells,with an average space-time acetic acid yield of 3.20 g·L^(-1)·d^(-1).After 30 days of fermentation,no significant decrea se of the acetic acid production rate was observed.

关键词： Anaerobic Syngas Acetic acid Immobilization Bioreactors Semi-co.tinuous fermentation