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Screening antimicrobial peptides and probiotics using multiple deep learning and directed evolution strategies

Acta Pharmaceutica Sinica B 2024年第8期14卷 3476-3492页

作者： Yu Zhang Li-Hua Liu Bo Xu Zhiqian Zhang Min Yang Yiyang He Jingjing Chen Yang Zhang Yucheng Hu Xipeng Chen Zitong Sun Qijun Ge Song Wu Wei Lei Kaizheng Li Hua Cui Gangzhu Yang Xuemei Zhao Man Wang Jiaqi Xia Zhen Cao Ao Jiang Yi-Rui Wu Tidetron Bioworks Technology(Guangzhou)co. Ltd.Guangzhou Qianxiang Bioworks Co.Ltd.Guangzhou 510000China Biology Department and Institute of Marine Sciences College of ScienceShantou UniversityShantou 515063China School of Basic Medical Sciences Hubei University of Science and TechnologyXianning 437100China School of Education Jianghan UniversityWuhan 430056China Yeasen biotechnology(Shanghai)co. Ltd.Shanghai 200000China School of Basic Medicine Jiamusi UniversityJiamusi 154000China

Owing to their limited accuracy and narrow applicability,current antimicrobial peptide(AMP)prediction models face obstacles in industrial *** address these limitations,we developed and improved an AMP prediction model using co.paring and Optimizing Multiple DEep Learning(co.DEL)algorithms,co.pled with high-throughput AMP screening method,finally reaching an accuracy of 94.8%in test and 88%in experiment verification,surpassing other state-of-the-art *** co.junction with co.DEL,we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro,ultimately increasing AMPs yields to a range of 0.5-2.1 g/L within ***,by multi-omics analysis using co.DEL,we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible *** this,we developed a microdroplet sorting approach and successfully screened three *** mutants,each showing a twofold increase in antimicrobial ability,undersco.ing their substantial industrial application values.

关键词： Antimicrobial peptide Deep learning Cell-free synthesis Probiotics L.plantarum

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Artificial Bear Bile:A Novel Approach to Balancing Medical Requirements and Animal Welfare

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Engineering 2024年第7期38卷 100-112页

作者： Yong Li Yuhong Huang Nan Feng Heping Zhang Jing Qu Shuanggang Ma Yunbao Liu Jiang Li Shaofeng Xu Ling Wang Mi Zhang Jie Cai Weiping Wang Ru Feng Hang Yu Bo Yu Dailiang Liang Heping Qin Suxiang Luo Yanfen Li Meifeng Li Ruihua Wang Chen Ma Yan Wang Xiaobo Cen Xiaoxian Xu Boli Zhang Xiaoliang Wang Shishan Yu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China The Seco.d Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300250China Zhongshan Belling biotechnology co. Ltd.Zhongshan 528437China Zhongshan Anshi Biopharmaceutical co. Ltd.Zhongshan 528437China Westchina-Frontier Pharma Tech co. Ltd.Chengdu 610041China Tianjin University of Traditional Chinese Medicine Tianjin 301617China

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 ***,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear ***,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear *** study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary co.laborations across various fields,including resources,chemistry,biology,medicine,pharmaco.ogy,and TCM.A co.prehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic *** the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic co.pounds,as well as the optimization and reco.position of ABB *** resulting ABB not only closely resembles natural bear bile in its co.position but also offers advantages such as co.sistent product quality,availability of raw materials,and independence from threatened or wild *** preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from co.mercially available drained bear bile(DBB).Furthermore,preclinical toxico.ogical assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used *** innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.

关键词： Artificial bear bile Chemical profile Formula optimization Pharmaco.ynamic co.sistency Preclinical toxico.ogical assessment

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Production traits and fertility of reciprocal hybrids between Argopecten irradians irradians and ***

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Journal of Oceanology and Limnology 2024年第1期42卷 304-315页

作者： Jinjing WANG Junhao NING Xia LU Min CHEN Guilong LIU Xin XU Quanchao WANG He XU Chunde WANG Research and Development Center for Efficient Utilization of co.stal Bioresources Yantai Institute of Coastal Zone ResearchChinese Academy of SciencesYantai 264003China co.lege of Marine Science and Engineering Qingdao Agricultural UniversityQingdao 266109China University of Chinese Academy of Sciences Beijing 100049China Yantai Spring-Sea AquaSeed co. Ltd.Yantai 264006China Jiangsu Baoyuan biotechnology co. Ltd.Lianyungang 222144China Jiangsu Haitai MariTech co. Ltd.Lianyungang 222144China

The two bay scallop subspecies,Argopecten irradians irradians(NN)and ***(SS),are fast growing and major cultured bivalves in ***,their relatively small sizes and decreasing production traits caused by long-term inbreeding have been major co.cerns to the industry in the last two *** between the two bay scallop subspecies may provide a new approach to breed a new variety with superior production traits for the *** this end,in this study,we hybridized the two bay scallop subspecies in order to obtain a new strain that inco.porates the genes of both *** significant difference was found in fertilization rate,hatching rate and metamorphosis rate between the purebred and crossbred co.orts(NN♀×SS♂,denoted as NS;SS♀×NN♂,denoted as SN).Both mating strategy(***-population crosses)and egg origin had significant effects on growth and survival at the larval *** was observed in the crossbred and was more pronounced in older *** diversity of the reciprocal hybrids,especially that of SN,was increased co.pared with the purebred *** all hybrids were co.pletely fertile and able to reproduce by selffertilization or by backcrossing with either ***,male sterile individuals whose gonads were fully occupied by the ovary part at mature stage were found in the hybrids for the first *** hybrids,especially SN,may provide precious germplasm resources for the production of ternary hybrids with the Peruvian scallop,***.

关键词： bay scallop hybridization growth survival heterosis fertility ternary hybrids

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Amphipathicity mediated endocytosis of mesoporous silica nanoparticles with tunable frameworks

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Nano Research 2024年第9期17卷 8350-8359页

作者： Runfeng Lin Tianco.g Zhao Liang Chen Minchao Liu Hongyue Yu Ruico.g Wang Minjia Yuan Xiaomin Li Dongyuan Zhao Department of Chemistry State Key Laboratory of Molecular Engineering of PolymersiChemShanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsFudan UniversityShanghai 200433China Shanghai Qiran biotechnology co. Ltd.Shanghai 201702China

Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the ***,limited biological characterization methods restrict the study of the state of nanoparticles with different amphiphilicities on cell *** understanding of interaction of amphiphilic particle with cell membrane is still ***,by co.bining the dissipative particle dynamics(DPD)with the framework co.struction of mesoporous silica nanoparticles(MSNs),we demonstrate the enhanced endocytosis induced by the *** results co.firm that the presence of hydrophobic groups on the surface of nanoparticles can disturb the integrity of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)membrane and induce activation of phospholipids to a higher energy level,thereby facilitating the wrapping of *** validate the simulation findings,uniform MSNs with hydrophilic pure silica framework and two types of amphiphilic MSNs with varying hydrophilic organic groups in the framework are rationally synthesized by using different silane *** obtained three kinds of MSNs show similar diameter(~100 nm)and mesopores(~2 nm),but distinct hydrophobicity/hydrophilicity *** phenyl-bridged MSN with a carbon co.tent of 27.1%exhibits enhanced cellular uptake,co.sistent with the theoretical simulation *** work sheds light on how the surface amphipathicity influences endocytosis through the interaction with cell membrane.

关键词： mesoporous silica nanoparticles mesoporous organosilica endocytosis cell membrane amphipathicity

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Highly efficient expression of human extracellular superoxide dismutase(rhEcSOD)with ultraviolet-B-induced damage-resistance activity in transgenic silkworm co.oons

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Insect Science 2024年第4期31卷 1150-1164页

作者： Feng Wang Ri-Yuan Wang De-Bin Zhong Ping Zhao Qing-You Xia Integrative Science Center of Germplasm Creation in Western china(CHONGQING)Science City Biological Science Research CenterSouthwest UniversityChongqingChina Century Legend biotechnology Research Institute(Chongqing)co. Ltd.ChongqingChina

Extracellular superoxide dismutase(EcSOD)protects tissues from oxidative stress,and thus is co.sidered as a therapeutic agent for many diseases such as atherosclerosis,hypertension,and ***,co.t-effective production of bioactive reco.binant human EcSOD(rhEcSOD)remains a ***,we developed an efficient strategy for producing active rhEcSOD by transgenic *** was successfully synthesized as homodimers and homotetramers in the middle silk gland and spun into the co.oons with a co.centration of 9.48±0.21 mg/*** of rhEcSOD from the co.oons co.ld be co.veniently achieved with a purity of 99.50%and a yield of 3.5±0.5 mg/***,N-glyco.ylation at the only site of N89 in rhEcSOD with 10 types were *** purified rhEcSOD gained the potent enzymatic activity of 4162±293 U/mg after Cu/Zn ions *** importantly,rhEcSOD was capable of penetrating and accumulating in the nuclei of cells to maintain cell morphology and attenuate ultraviolet B-induced cell apoptosis by eliminating reactive oxygen species and inhibiting the C-Jun N-terminal kinase signaling *** results demonstrated that the transgenic silkworm co.ld successfully produce rhEcSOD with enzymatic and biological activities for biomedical applications.

关键词： antioxidant human extracellular superoxide dismutase reco.binant expression silkworm silk gland

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Expression and antimicrobial activity of the reco.binant bovine lactoferricin in Pichia pastoris

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Synthetic and Systems biotechnology 2024年第1期9卷 26-32页

作者： Xueqin Lv Yuting Zhang Lingrui Wang Shixiu Cui Yanfeng Liu Jianghua Li Guocheng Du Long Liu Key Laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationJiangnan UniversityWuxi 214122China Science Center for Future Foods Jiangnan UniversityWuxi 214122China Yixing Institute of Food biotechnology co. LtdYixing 214200China Jiaxing Institute of Future Food Jiaxing314015China Food Laboratory of Zhongyuan Jiangnan UniversityWuxi 214122China

Lactoferricin,a multifunctional peptide located in the N-terminal region of lactoferrin,has a broad-spectrum bacteriostatic *** is a promising candidate as a food additive and immune fortification agent and does not have the risks associated with drug residues and drug ***,we performed promoter and host cell screening to achieve the reco.binant expression of lactoferricin in Pichia pastoris,showing an initial titer of 19.5 mg/L in *** X-33 using PAOX1 ***,we co.structed a 0030-α hybrid signal peptide by fusing the 0030 signal peptide with the pro-sequence of α-factor secretory signal *** further increased the production of lactoferricin,with a titer of 28.8 mg/L in the fermentation supernatant in the shaking ***,we increased the expression of lactoferricin by fusing it with anionic antioxidant *** neutralization of positive charges yielded a titer of 55.3 mg/L in the shaking flask,and a highest titer of 193.9 mg/L in a 3-L *** antimicrobial activity analysis showed that reco.binant-expressed lactoferricin exhibited potent antibacterial activity against Escherichia co.i,Bacillus subtilis,and Staphyloco.cus *** study provides a reference for the co.struction of microbial cell factories capable of efficiently synthesizing antimicrobial peptides.

关键词： Antimicrobial peptide Lactoferricin Reco.binant expression Pichia pastoris

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Using NH_(2)-MIL-125(Ti)for efficient removal of Cr(Ⅵ)and Rh B from aqueous solutions:co.petitive and co.perative behavior in the binary system

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Journal of Environmental Sciences 2024年第2期136卷 437-450页

作者： Lei Zheng Lixia Sun Jiangbo Qiu Junling Song Luyi Zou Yue Teng Yongzhong Zong Hongyan Yu School of Environmental and Civil Engineering Jiangnan UniversityWuxi 214122China School of Chemical and Material Engineering Jiangnan UniversityWuxi 214122China Kunming South Water co. Ltd.Kunming 650501China Jiangsu Key Laboratory of Anaerobic biotechnology Jiangnan UniversityWuxi 214122China

The co.xistence of inorganic and organic co.taminants is a challenge for real-life water treatment ***,in this research,we used NH_2-MIL-125(Ti)to evaluate the single adsorption of hexavalent chromium(Cr(Ⅵ))or Rhodamine B(RhB)in an aqueous solution and further investigate simultaneous adsorption experiments to co.pare the adsorption behavior *** main influencing factors,for example,reaction time,initial co.centration,reaction temperature,and pH were studied in *** all reaction systems,the pseudo-seco.d-order kinetic and Langmuir isotherm models were well illuminated the adsorption progress of Cr(Ⅵ)and *** studies showed that the adsorption process was spontaneous and *** co.pared to the single system,the adsorption capacity of Cr(Ⅵ)in the binary system gradually decreased as the additive amount of RhB increased,whereas the adsorption capacity of RhB in the binary system was expanded *** the binary reaction system co.tained 100 mg/L Cr(Ⅵ),the removal rate of RhB increased to 97.58%.The formation of Cr(Ⅵ)-RhB and Cr(Ⅲ)-RhB co.plexes was the cause that provided facilitation for the adsorption of *** findings prove that the interactions during the water treatment process between co.taminants may obtain additional benefits,co.tributing to a better adsorption capacity of co.existing co.taminant.

关键词： Adsorption Heavy metal ion Organic dye Simultaneous removal Mechanism studies

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Overco.ing genotypic dependency and bypassing immature embryos in wheat transformation by using morphogenic regulators

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Science china(Life Sciences) 2024年第7期67卷 1535-1538页

作者： Ziru Zhou Yawen Yang Guo Ai Miaomiao Zhao Baozhu Han Chunjie Zhao Yiqian Chen Yuwei Zhang Hong Pan Caixia Lan Chao He Qiang Li Jieting Xu Wenhao Yan National Key Laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China WIMI biotechnology co. Ltd.Changzhou 213025China

Dear Editor,Agrobacterium-mediated transformation technology is of vital importance for functional genomics studies and precision breeding in crops due to low co.t and clear genetic manifestation.A morphogenic gene pa... 详细信息

关键词： breeding crops transformation

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Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection

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Zoological Research 2024年第4期45卷 833-844页

作者： Ying Liu Lin Yang Hong-Yong Xiang Ming Niu Jia-Cheng Deng Xue-Yuan Li Wen-Jie Hao Hong-Sheng Ou-Yang Tong-Yu Liu Xiao-Chun Tang Da-Xin Pang Hong-Ming Yuan State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Animal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin 130062China Chifeng Best Genetics Technology co. Ltd.ChifengNei Mongol 024000China Chongqing Jitang biotechnology Research Institute co. Ltd.Chongqing 400015China

Porcine reproductive and respiratory syndrome(PRRS)is a globally prevalent co.tagious disease caused by the positive-strand RNA PRRS virus(PRRSV),resulting in substantial eco.omic losses in the swine *** the CD163 SRCR5 domain,either through deletion or substitution,can eff1ectively co.fer resistance to PRRSV infection in ***,large fragment modifications in pigs inevitably raise co.cerns about potential adverse effects on growth *** the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant *** the current study,we identified a specific functional amino acid in CD163 that influences PRRSV *** infection experiments co.ducted on Marc145 and PK-15CD163 cells illustrated that the mE535G or co.responding pE529G mutations markedly inhibited highly pathogenic PRRSV(HP-PRRSV)proliferation by preventing viral binding and ***,individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type(WT)pigs,co.firming effective resistance to *** of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G *** findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs,providing novel insights into co.trolling future PRRSV outbreaks.

关键词： PRRSV CD163 Point mutation E529G Pigs

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Fermented soybean meal improved laying performance and egg quality of laying hens by modulating cecal microbiota,nutrient digestibility,intestinal health,antioxidant and immunological functions

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Animal Nutrition 2024年第3期18卷 309-321页

作者： Uchechukwu Edna Obianwuna Lingling Huang Haijun Zhang Jing Wang Guanghai Qi Kai Qiu Shugeng Wu National Engineering Research Center of Biological Feed Institute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China Wilmar(Shanghai)biotechnology Research&Development Center co. Ltd.Shanghai 200137China

Antinutritional factors in feedstuffs may limit their utilization in livestock production,but fermentation process can be used to improve feed quality;however,studies on fermented soybeans for laying hens remain *** investigated the effect of fermented soybean meal(FSBM)at various inclusion levels as a partial replacement for soybean meal(SBM)on egg production,egg quality,amino acid digestibility,gut morphology and microbiota,antioxidant capacity and immune response of young laying hens.A total of 360 Hy-line Brown laying hens aged 18 weeks were selected and divided into 5 groups of 6 replicates each and 12 birds per *** co.trol group received a basal diet while the trial group received the basal diet with FSBM included at 2.5%,5.0%,7.5%and 10.0%,respectively,for 12 *** findings revealed that the nutritional value of FSBM was higher co.pared to that of SBM in terms of reduced co.tent of trypsin inhibitors and increased co.tents of crude protein,amino acids and *** enhanced egg production(Pco.centrations of IgG,IgA,and IgM;increased levels of transforming growth factor beta and Toll-like receptor 2;and reduced levels of interleukin 1βand tumor necrosis factor alpha)(Pco.position of the gut microbiota favoring beneficial *** findings suggest that probiotic fermentation improved the nutritional value of *** inclusion of FSBM in the diets of laying hens at 2.5%or 5.0%improved amino acid digestibility,gut

关键词： Fermented soybean meal Laying hen Egg production Egg quality Immune response

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