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A novel shark VNAR antibody-based immunotoxin targeting TROP-2 for cancer therapy

Acta Pharmaceutica Sinica B 2024年第11期14卷 4806-4818页

作者： Xiaozhi Xi Yanqing Wang Guiqi An Shitao Feng Qiumei Zhu Zhongqiu Wu Jin Chen Zhicheng Zuo Qiang Wang Ming-Wei Wang Yuchao Gu College of marine Science and Biological engineering Qingdao University of Science and TechnologyQingdao 266042China Laboratory for marine Drugs and Bioproducts of Qingdao marine Science and technology center School of Medicine and PharmacyOcean University of ChinaQingdao 266003China Oncology Department Shandong Second Provincial General HospitalJinan 250022China College of Chemistry and Chemical engineering Shanghai University of Engineering ScienceShanghai 201620China research center for Deepse1 2ioresources(Sanya)Hainan 572025China

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

关键词： Shark VNAR Immunotoxins TROP-2Epitope identification Anti-tumor Pseudomonas exotoxin A Nanobody Breast cancer

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Inhibition of citral nanoemulsion to growth,spoilage ability and Al-2/luxS quorum sensing system of Shewanella putrefaciens CN-32:a study on bacteriostasis from in vitro culture and gene expression analysis

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food Quality and Safety 2022年第3期6卷 435-445页

作者： Zhiheng Hu Yaoxian Chin Jiayin Huang Jiaying Zhou Gaoshang Li Yaqin Hu Chunhong Yuan Jianchu Chen College of Biosystems engineering and food Science National-Local Joint Engineering Laboratory of Intelligent Food Technology and EquipmentZhejiang Key Laboratory for Agro-Food ProcessingIntegrated Research Base of Southern Fruit and Vegetable Preservation TechnologyFuli Institute of Food ScienceZhejiang UniversityHangzhouChina College of food Science and engineering Hainan Tropical Ocean UniversityYazhou Bay Innovation InstituteMarine Food Engineering Technology Research Center of Hainan ProvinceCollaborative Innovation Center of Marine Food Deep ProcessingSanyaChina Department of food Production and Environmental Management Faculty of AgricultureIwate UniversityUeda4-3-5MoriokaJapan

Objectives:The bacteriostatic effects of a citral nanoemulsion against Shewanella putrefaciens CN-32(SHP CN-32)were investigated using in vitro culture and gene expression analysis,forbuilding a potential application in spoilage microorganism control and aquatic products quality *** and Methods:SHP CN-32 was treated by prepared citral nanoemulsion when the minimal inhibitory concentration(MIC)was *** growth curve,membrane integrity,scanning electron microscope(SEM)observation,biofilm formation and quorum sensing(QS)signaling molecule Al-2 content were evaluated in different MIC treatment groups(0 to 1.00 MIC).The gene expression status of SHP CN-32 in O and 0.50 MIC groups were compared using transcriptome sequencing and quantitative polymerase chain reaction(PCR).Results:The in vitro culture revealed that the citral nanoemulsion could inhibit the growth of SHP CN-32 with MIC of approximately 200μg/*** of membrane *** and biofilm formation suggested significant biological structure damage in bacteria after ***,the Qs signaling molecule Al-2 content showed a decline with increasing treatment *** sequencing and quantitative PCR revealed that the majority genes related diversified functional metabolic pathways of SHP CN-32 were downregulated at varying ***:A significant bacteriostasis of citral nanoemulsion against SHP CN-32 was verified via the results of growth inhibition,structural destruction,signal molecular decrease and gene expression downregulation of *** synergies significantly affect the characteristic expression of SHP CN-32,revealing the application potential as bacteriostat,QS inhibitor and preservative in aquatic products.

关键词： Shewanella putrefaciens citral quorum sensing system gene expression analysis

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engineering a fumaric acid-responsive two-component biosensor for dynamic range improvement in Escherichia coli

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Systems Microbiology and Biomanufacturing 2022年第3期2卷 533-541页

作者： Huiqin Yang Xiaoyan Yang Yanbo Lu Quanxian Shu Shenghu Zhou Yu Deng National engineering research center of Cereal Fermentation and food Biomanufacturing Jiangnan University1800 Lihu RoadWuxi 214122JiangsuChina Jiangsu provincial research center for Bioactive Product Processing technology Jiangnan University1800 Lihu RoadWuxi 214122JiangsuChina shandong provincial Key Laboratory of Fat and Oil Deep-Processing Shandong Bohi Industry Co.LtdNo.333Binhe RoadBoxing Industrial ParkBinzhou 256599ShandongChina

Due to the selective permeability of the cytomembrane,high-yield fumaric acid strains form a steep difference between intra-and extracellular *** biosensors cannot detect the real concentration change of extracellular fumaric *** overcome this limitation,a two-component biosensor(TCB)that could respond to extracellular fumaric acid was designed based on the DcuS-DcuR two-component *** two-component system consists of a histidine kinase(SK)and response *** is a transmembrane histidine kinase sensor that can detect concentration changes in extracellular *** improve the dynamic range of the constructed fumaric acid TCB,we optimized the expression ratio and expression intensity of dcuS and *** found that the optimum expression ratio of dcuS:dcuR was 46:*** this ratio,the higher was the expression level,the greater the dynamic *** addition,we modified the ATP-binding site on the DcuS,and the final dynamic range of the TCB reached ***,the obtained fumaric acid-responsive TCB with a high dynamic range is reported for the first time,providing a synthetic biology tool for high-throughput screening and dynamic metabolic regulation of fumaric acid cell factories.

关键词： Biosensor Fumaric acid Histidine kinase Response regulator Two-component system

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A new chloro-azaphilone derivative with pro-angiogenesis activity from the hadal trench-derived fungus Chaetomium globosum YP-106

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Journal of Oceanology and Limnology 2023年第3期41卷 1145-1151页

作者： Yaqin FAN Chunjiao JIANG Peihai LI Cong WANG Hao CHEN MNR Key Laboratory of marine Eco-Environmental Science and technology First Institute of OceanographyMinistry of Natural ResourcesQingdao 266061China shandong provincial Key Laboratory of Applied Mycology School of Life SciencesQingdao Agricultural UniversityQingdao 266109China engineering research center of Zebrafish Models for Human Diseases and Drug Screening of shandong Province Shandong Provincial Engineering Laboratory for Biological Testing TechnologyKey Laboratory for Biosensor of Shandong ProvinceBiology InstituteQilu University of Technology(Shandong Academy of Sciences)Jinan 250103China Key Laboratory of Chemistry and engineering of Forest Producer State Ethnic Affairs CommissionGuangxi Key Laboratory of Chemistry and Engineering of Forest ProductsGuangxi Collaborative Innovation Center for Chemistry and Engineering of Forest ProductsSchool of Chemistry and Chemical EngineeringGuangxi Minzu UniversityNanning 53006China

A new chloro-azaphilone derivative chaetoviridin L(1)along with four known analogues,namely,chaetomugilin A(2),chaetoviridin E(3),chaetomugilin O(4),and chaephilone D(5),is isolated and identified from the culture extract of Chaetomium globosum YP-106,a deep-sea derived fungus obtained from the hadal zone seawater collected in the Yap *** structures were determined based on detailed interpretation of nuclear magnetic resonance(NMR)spectroscopic,mass spectrometry(MS)data analysis and comparison with the reported *** absolute configuration of the new compound was established by quantum chemical calculations of electronic circular dichroism(ECD).All the isolated compounds were evaluated for pro-angiogenesis activity using zebra fish *** 1,2,and 5significantly promoted the angiogenesis in a dose-dependent manner and thus,these compounds might be used as promising molecules for the treatment of cardiovascular disease.

关键词： marine natural products marine-Keyword:marine nabta globosum pro-angjogo nesis activity

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Effects of spray adjuvants and operation modes on droplet deposition and elm aphid control using an unmanned aerial vehicle

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International Journal of Agricultural and Biological engineering 2023年第2期16卷 1-9页

作者： Zechen Dou Zhihao Fang Xiaoqiang Han Muhammad Zeeshan Yapeng Liu Yubin Lan College of Agriculture/Key Laboratory of Oasis Agricultural Pest Management and Plant Protection Resources Utilization Shihezi UniversityShihezi 832003XinjiangChina College of Agricultural engineering and food Science Shandong University of TechnologyZibo 255049ShandongChina shandong provincial engineering technology research center for Agricultural Aviation Intelligent Equipment Zibo 255049ShandongChina College of Electronics engineering(College of Artificial Intelligence) South China Agricultural UniversityGuangzhou 510642China

A conventional spraying mode and a fully autonomous fruit tree operation mode using a model DJ T30 unmanned aerial vehicle(UAV)were used to control aphids control on elm trees and to clarify the distribution of droplets in elm trees sprayed by a *** effects of six aviation spray adjuvants on elm canopy droplet deposition and aphid control were *** software was used to analyze and measure the droplet density and deposition of water sensitive paper in two modes;this was done to calculate the droplet uniformity,depositional penetration,and droplet penetration,and to verify the aphid control *** results showed that the droplet density increased by 79.7%-100.7% in the upper canopy and 0-394.1%in the lower canopy without adjuvants in the fully autonomous fruit tree operation *** upper canopy deposits increased by 65.7%-179.3%,and the lower canopy increased by 0-152.8%.When adjuvants were added,the droplet density in the upper canopy increased by 49.7-56.1%using Jiexiaofeng(JXF),and the lower canopy increased by 138.2%-177.8% using JXF,45.8%-141.3%using Beidatong(BDT),45.5%-92.9% using Gongbei(GB),0-93.5% using Maisi(MS),and 0-95.2%using Manniu(MN).The deposits of the upper canopy increased by 888.1-1154.2% using JXF,0-1298.3% using MN,0-343.9%using BDT,0-422.5% using GB,0-580.3% using *** lower canopy increased by 746.4%-1426.0%using JXF,226.2%-231.0% using BDT,435.8%-644.0% using GB,255.0%-322.4%using MS,and 249.3%-360.0%using *** JXF was added,the droplet uniformity,droplet penetration and depositional penetration were better than when using other *** effects of JXF,BDT and GB in controlling aphids was significantly better than other adjuvants(p<0.05).The following control effects were observed;94.1% with JXF,93.1% with BDT,and 93.3% with GB after 3 d of application,and 97.9% with JXF,95.6% with BDT,and 97.1% with GB after 7 d of *** the same time,the application of the fully autonomous fruit tree operation mode a

关键词： adjuvants UAV operation mode droplet deposition aphid

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Deciphering the cellular heterogeneity of the insect brainwith single-cell RNA sequencing

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Insect Science 2024年第2期31卷 314-327页

作者： Xiaofei Wang Yifan Zhai Hao Zheng Institute of Plant Protection Shandong Academy of Agricultural SciencesJinanChina College of food Science and Nutritional En-gineering China Agricultural UniversityBeijingChina Key Laboratory of Natural Enemies Insects Ministry of Agriculture and RuralAffairsJinanChina shandong provincial engineering technology research center on Biocontrol of Crops Diseases and In-sectPests JinanChina

Insects show highly complicated adaptive and sophisticated behaviors, includ-ing spatial orientation skills, learning ability, and social interaction. These behaviors arecontrolled by the insect brain, the central part of the nervous system. The tiny insect brainconsists of millions of highly differentiated and interconnected cells forming a complexnetwork. Decades of research has gone into an understanding of which parts of the insectbrain possess particular behaviors, but exactly how they modulate these functional conse-quences needs to be clarified. Detailed description of the brain and behavior is required todecipher the complexity of cell types, as well as their connectivity and function. Single-cell RNA-sequencing (scRNA-seq) has emerged recently as a breakthrough technologyto understand the transcriptome at cellular resolution. With scRNA-seq, it is possible touncover the cellular heterogeneity of brain cells and elucidate their specific functions andstate. In this review, we first review the basic structure of insect brains and the links toinsect behaviors mainly focusing on learning and memory. Then the scRNA applicationson insect brains are introduced by representative studies. Single-cell RNA-seq has allowedresearchers to classify cell subpopulations within different insect brain regions, pinpointsingle-cell developmental trajectories, and identify gene regulatory networks. These devel-opments empower the advances in neuroscience and shed light on the intricate problemsin understanding insect brain functions and behaviors.

关键词： behavior brain cell type insect single-cell RNA sequencing

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Acetylcholinesterase inhibitors and antioxidants mining from marine fungi:bioassays,bioactivity coupled LC-MS/MS analyses and molecular networking

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marine Life Science & technology 2020年第4期2卷 386-397页

作者： Yingying Nie Wencong Yang Yayue Liu Jingming Yang Xiaoling Lei William HGerwick Yi Zhang center for marine Drugs research and Development Shenzhen Institute of Guangdong Ocean UniversityShenzhen 518000China College of food Science and technology Key Laboratory of Guangdong Province Aquatic Products Processing and SafetyGuangdong Province Engineering Laboratory for Marine Biological ProductsGuangdong Provincial Engineering Technology Research Center of Marine FoodKey Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education InstitutionZhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain HealthResearch Institute for Marine Drugs and NutritionGuangdong Ocean UniversityZhanjiang 52408&China center for marine Biotechnology and Biomedicine Scripps Institution of OceanographyUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Collaborative Innovation center of Seafood Deep Processing Dalian Polytechnic UniversityDalian 116034China

marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's *** this paper,the combined bioassay model of acetylcholinesterase(AChE)inhibition,1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging,and Artemi ci larval lethality was used to evaluate the activity and toxicity of 35 n narine fun gal strains from seas around *** bioactive constitue nfs were revealed by thin layer chromatography(TLC)autography,bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking(GNPS).The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound,'tacrine;for which the ratio was 89.8%at 200 pig/*** strains displayed both AChE inhibition(inhibition ratios>20%at 200 pg/ml)and DPPH scavenging activity(scavenging ratios>30%at 200 pg/ml)together with low Artemia larval toxicity(lethal rates<12%).TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents,includi ng strains Talaromyces sp.C2\-\,Aspergillus ter re us C23-3,Trichoderma harzianum DLEN2008005,and Penicillium corylophilum *** the most potent sample F-l 1-1-b(derived from Aspergillus tern us C23-3),five AChE inhibitors and seven antioxida nts were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS,and LC-MS/MS coupled with DPPH ***,with the aid of GNPS,the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D,arisugacin A and an unknown compound 4,and the seven antioxidants were assigned as butyrolactone *** E,a phenolic derivative and possibly unknown compounds 8-10 and 12.

关键词： Acetylcholinesterase inhibition Antioxida marine fungi LC-MS/MS Molecular networking

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Ferulic acid alleviates the reduction of beef myofibrillar protein digestibility mediated by protein oxidation: Insight from peptide release

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food Science and Human Wellness 2024年

作者： Yantao Yin Yongcun Lu Naiyong Xiao Shucheng Liu Wangang Zhang College of food Science and technology， Guangdong Ocean University， Guangdong provincial Key Laboratory of Aquatic Product Processing and Safety， Guangdong provincial engineering Laboratory for marine Biological Products， Guangdong provincial engineering technology research center of Seafood Key Laboratory of Meat Processing and Quality Control， College of food Science and technology， Nanjing Agricultural University

This study investigated the protective effect of ferulic acid (FA) on the digestibility of oxidized beef myofibrillar protein (MP). MP were treated with varying concentrations of FA (20， 40， and 80 μmol/g protein) and then exposed to oxidation. The results showed that FA inhibited carbonyl in a dose-dependent manner (P < 0.05). Fluorescence spectroscopy and molecular docking studies revealed FA was bonded to MP via hydrophobic interactions and hydrogen bonds. SDS-PAGE and TEM analysis indicated that FA mitigated the aggregation of oxidized MP. Peptidomic analysis showed FA protected 34.24% peptides recover from oxidation loss， and theses recovered peptide were mainly distributed in hydrophobic regions and lysine sites. In vitro digestion showed FA remarkably improved digestibility of oxidized MP (P < 0.05)， with 80 μmol/g protein FA mitigating 67.85% loss in digestibility. Overall， FA effectively preserved the release of peptides by inhibiting hydrophobic aggregation and oxidation of lysine residues， thereby alleviating the decrease in digestibility of oxidized MP.

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Nutritional properties of Europen eel(Anguilla anguilla)bone peptide-calcium and its apoptosis effect on Caco-2 cells

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food Science and Human Wellness 2022年第6期11卷 1482-1490页

作者： Hui Teng Yuewei Qian Xiaoyun Fan Hui Cao Yuting Tian Lei Chen Guangdong provincial Key Laboratory of Aquatic Product Processing and Safety Guangdong Province Engineering Laboratory for Marine Biological ProductsGuangdong Provincial Engineering Technology Research Center of SeafoodKey Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education InstitutionCollege of Food Science and TechnologyGuangdong Ocean UniversityZhanjiang 524088China College of food Science Fujian Agriculture and Forestry UniversityFuzhou 350002China

The present study aimed at making a rational usage for European eel bone by-products by preparing Europen eel bone peptide chelated calcium(EBPC-Ca).Nutritional properties and bioactivity of EBPC-Ca were *** showed that nutritional properties of calcium ions will cause intra-and inter-molecular folding and aggregation of peptide to uniformly form EBPC-Ca *** chelated compound of EBPC and calcium ion triggered a strong apoptosis in heterogeneous human epithelial colorectal adenocarcinoma(Caco-2)in concentration-and time-dependent *** blot analysis revealed that the EBPC-Ca induced apoptosis may be the result of a blocked autophagy flux through mitochondrial-dependent ***,the increase in FGF-23 protein expression inhibited the absorption of calcium ions and alleviated cell *** was also found that the cell apoptosis occurs with significant increases in the levels of reactive oxygen species(ROS)and Ca^(2+)in the cells,indicating the anti-tumor potential of EBPC-Ca may involve multiple channels.

关键词： Europen eel bone Peptide Calcium Nutritional properties Caco-2 Apoptosis

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Characterization of acid-and pepsin-soluble collagens from spines and skulls of skipjack tuna(Katsuwonus pelamis)

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Chinese Journal of Natural Medicines 2014年第9期12卷 712-720页

作者： YU Di CHI Chang-Feng WANG Bin DING Guo-Fang LI Zhong-Rui Zhejiang provincial engineering technology research center of marine Biomedical Products School of Food and PharmacyZhejiang Ocean University

Acid-soluble collagen(ASC) and pepsin-soluble collagen(PSC) from the spine(ASC-SP and PSC-SP) and skull(ASC-SK and PSC-SK) of the skipjack tuna, Katsuwonus pelamis, were successfully isolated and characterized. The yields of ASC-SP, PSC-SP, ASC-SK and PSC-SK were(2.47 ± 0.39)%,(5.62 ± 0.82)%,(3.57 ± 0.40)%, and(6.71 ± 0.81)%, respectively, on the basis of dry weight. The four collagens contained Gly(330.2-339.1 residues/1 000 residues) as the major amino acid, and their imino acid contents were between 168.8 and 178.2 residues/1 000 residues. Amino acid composition, SDS-PAGE, and FTIR investigations confirmed that ASC-SP and ASC-SK were mainly composed of type I collagen, and had higher contents of high-molecular weight cross-links than those of PSC-SK and PSC-SP. The FTIR investigation also certified all the collagens had triple helical structure. The denaturation temperatures of ASC-SK, PSC-SK, ASC-SP, and PSC-SP were 17.8, 16.6, 17.6, and 16.5 °C, respectively. All isolated collagens were soluble at acidic pH(1-5) and lost their solubilities when the NaCl concentration was above 2%(W/V). The isolated collagens from the spines and skulls of skipjack tuna could serve as an alternative source of collagens for further application in food, cosmetic, biomedical, and pharmaceutical industries.

关键词： solubility imino viscosity residues collagen helical amide biomedical chains pharmaceutical

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