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In vivo evaluation of guide-free Cas9-induced safety risks in a pig model

Signal Transduction and Targeted Therapy 2024年第8期9卷 3493-3506页

作者： Weikai Ge Shixue Gou Xiaozhu Zhao Qin Jin Zhenpeng Zhuang Yu Zhao Yanhui Liang Zhen Ouyang Xiaoyi Liul Fangbing Chen Hui Shi Haizhao Yan Han Wu Liangxue Lai Kepin Wang China-New Zealand Joint Laboratory on Biomedicine and Health CAS Key Laboratory of Regenerative BiologyGuangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineJoint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Sanya institute of Swine resource Hainan Provincial Research Center of Laboratory AnimalsSanya 572000China Guangdong Provincial Key Laboratory of Large Animal models for Biomedicine Wuyi UniversityJiangmen 529020China Guangzhou National Laboratory Guangzhou 510005China SUniversity of Chinese Academy of Sciences 100049 BeijingChina research Unit of Generation of Large Animal Disease Models Chinese Academy of Medical Sciences(2019RU015)Guangzhou 510530China

The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene ***,there are concerns about the safety of this system,specifically related to the use of guide-free *** studies have shown that guidefree Cas9 can induce genomic instability in ***,the in vivo safety risks associated with guide-free Cas9 have not been evaluated,which is necessary for the development of gene therapy in clinical *** this study,we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in *** findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in *** severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 ***,prolonged expression of Cas9 in pigs led to abnormal phenotypes,including a significant decrease in body weight,which may be attributable to genomic damage-induced nutritional absorption and metabolic ***,we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression,raising the risk of tumor *** in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene *** research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRiSPR/Cas9 system in clinical practice.

关键词： CRISPR/Cas9 vivo alone

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Developing fertility control for rodents: a framework for researchers and practitioners

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Integrative Zoology 2024年第1期19卷 87-107页

作者： Giovanna MASSEI Jens JACOB Lyn A.HINDS Botstiber institute for Wildlife Fertility Control Department of Environment and GeographyUniversity of YorkHeslingtonYorkUK Rodent research Institute for Epidemiology and Pathogen DiagnosticsJulius Kühn–Institute(JKI)Federal Research Institute for Cultivated PlantsMünsterGermany CSIRO Health and Biosecurity CanberraACTAustralia

Fertility control is often heralded as a humane and effective technique for management of overabundant wildlife,including *** intention is to reduce the use of lethal and inhumane methods,increase farm productivity and food security as well as reduce disease transmission,particularly of *** developed a framework to guide researchers and stakeholders planning to assess the effectiveness of a potential contraceptive agent for a particular *** guidelines describe the overarching research questions which must be sequentially addressed to ensure adequate data are collected so that a contraceptive can be registered for use in broad-scale rodent *** framework indicates that studies should be undertaken iteratively and,at times,in parallel,with initial research being conducted on(1)laboratory-based captive assessments of contraceptive effects in individuals;(2)simulation of contraceptive delivery using bait markers and/or surgical sterilization of different proportions of afield-based or enclosure population to determine how population dynamics are affected;(3)development of mathematical models which predict the outcomes of different fertility control scenarios;and(4)implementation of large-scale,replicated trials to validate contraceptive efficacy under various management-scalefield *** some circumstances,fertility control may be most effective when integrated with other methods(*** culling).Assessment of non-target effects,direct and indirect,and the environmental fate of the contraceptive must also be *** fertility control for a species is a resource-intensive commitment but will likely be less costly than the ongoing environmental and economic impacts by rodents and rodenticides in many contexts.

关键词： captive studies field applications modeling oral contraceptive delivery population management rodents

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Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential

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Zoological research 2024年第5期45卷 1001-1012页

作者： Li-Na Cha Juan Yang Jin-Ai Gao Xin Lu Xiao-Long Chang Rebecca Caroline Thuku Qi Liu Qiu-Min Lu Dong-Sheng Li Ren Lai Ming-Qian Fang Engineering Laboratory of Peptides of Chinese Academy of Sciences Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Center for Non-Human PrimatesNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Key Laboratory of Genetic Evolution&Animal ModelsSino-African Joint Research Centerand New Cornerstone Science LaboratoryKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650201China School of Molecular Medicine Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China First Affiliated Hospital of Kunming Medical University KunmingYunnan 650032China

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic *** contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionally with the coagulation and inflammation cascades,providing a novel target for therapeutic drug development in ischemic *** this study,we identified a bat-derived oligopeptide from Myotis myotis(Borkhausen,1797),designated LE6(Leu-Ser-Glu-Glu-Pro-Glu,702 Da),with considerable potential in stroke therapy due to its effects on the contact kinin ***,LE6 demonstrated significant inhibitory effects on PK and FXIIa,with inhibition constants of 43.97μmol/L and 6.37μmol/L,*** vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin *** murine models,LE6 effectively inhibited carrageenan-induced mouse tail thrombosis,FeCl3-induced carotid artery thrombosis,and photochemically induced intracerebral ***,LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion ***,the low toxicity,hemolytic activity,and bleeding risk of LE6,along with its synthetic simplicity,underscore its clinical *** conclusion,as an inhibitor of FXIIa and PK,LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

关键词： PK FXIIa Anti-thromboinflammation Ischemic stroke therapies Oligopeptide

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Brain Mechanisms Underlying Panic Attack and Panic Disorder

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Neuroscience Bulletin 2024年第6期40卷 795-814页

作者： Xuyan Guan Peng Cao Tsinghua institute of Multidisciplinary Biomedical research Tsinghua UniversityBeijing102206China National institute of Biological Sciences(NIBS) Beijing102206China

Panic disorder is a psychiatric disorder characterized by recurrent panic attacks,with a prevalence of~4%in the general population,causing heavy personal and socioeconomic *** similarities of animal defense responses to clinical panic attack symptoms in humans make it possible to translate neuroanatomical pathways identified in animal studies to panic disorder in ***,in this review we first present a basic overview of panic disorder in humans including the main subtypes,models commonly used to trigger panic attacks,related hypotheses,the neurotransmitter systems that may be involved,and the current clinical treatments to give the reader a comprehensive understanding of panic *** animal section introduces the models that trigger panic-like behavior in animals and the brain regions that may be involved,providing insights for future elucidation of the neural circuit mechanisms behind panic attacks.

关键词： Panic disorder Panic attack Defense responses Animal studies Humans

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Credible and Facile Fluorometric Detection of Soybean Trypsin Inhibitor Activity with a Water-Soluble Poly(diphenylacetylene) Derivative

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Transactions of Tianjin University 2024年第4期30卷 305-313页

作者： Jiao Tang Xiao Tang Jiaxiang Tang Wei Qi Qianwei Pan Jinhong Zeng Housheng Xia Jianping Zhou Zhongyi Sheng Junfeng Niu Zhejiang Tiantai Xianghe Industrial Co. Ltd.Taizhou 317200China Zhejiang Xianghe Track Fastener research institute Taizhou 317200China Shaoxing institute for Food and Drug Control Shaoxing 312000China Key Laboratory of Chemical and Biological Processing Technology for farm Products of Zhejiang Province School of Biological and Chemical EngineeringZhejiang University of Science and TechnologyHangzhou 310023China

Herein,a novel method for fl uorometric detection of soybean trypsin inhibitor(SBTI)activity based on a water-soluble poly(diphenylacetylene)derivative was *** quenching of the polymer via p-nitroaniline,produced from the trypsin-catalyzed decomposition of N-benzoyl-DL-arginine-4-nitroanilide hydrochloride(L-BAPA),was well described using the Stern-Volmer *** activity was quantitatively assessed based on changes in the fl uorescence intensity of the *** strategy has several advantages,such as high sensitivity and ease of ***,its applicability to other biochemical analyses is promising.

关键词： Fluorometric detection Soybean trypsin inhibitor Inhibition activity Fluorescence quenching

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Evaluation of Soil Fertility Quality and Environmental Driving Factors in Different Soil Types of Artificial Forests

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Meteorological and Environmental research 2024年第2期15卷 64-70页

作者： Songyu YU Zhenhui LIAO Mingwu YANG Ronghui HU Yuanyuan SHI Junyu ZHAO Guangxi Zhuang Autonomous Region State-owned Sanmenjiang Forest farm Liuzhou 545006China Guangxi Zhuang Autonomous Region State-owned Huangmian Forest farm Luzhai 545618China Guangxi Forestry research institute Nanning 530002China

The aim was to clarify the environmental driving factors of soil fertility indicators in artificial forests of Guangxi and comprehensively evaluate the soil fertility *** collecting data on the current status of soil in artificial forests,the spatial distribution of major soil fertility indicators was analyzed,and the distribution map of the fertility index of artificial forests in the entire region and the comprehensive fertility index of artificial forests of different soil types were *** correspondence analysis method was used to analyze soil fertility indicators and environmental factors,and the environmental driving factors of soil fertility indicators for artificial forests of the main soil types in Guangxi were *** results showed that over 90%of the soil fertility index of artificial forests in the entire region was between 0.20 and *** order of soil fertility index of different soil types of artificial forests from high to low was yellow brown soil>yellow red soil>yellow soil>red soil>limestone soil>latosolic red soil>*** artificial forests of latosolic red soil,the correlation between soil alkaline nitrogen and organic matter,annual average temperature was high,while the correlation between soil available phosphorus and organic matter,pH was high,and the correlation between soil available potassium and environmental factors such as slope,altitude,rainfall,accumulated temperature,and slope aspect was *** artificial forests of red soil,the correlation between soil alkaline nitrogen and slope,altitude was high,while the correlation between soil available phosphorus and accumulated temperature,rainfall was high,and the correlation between soil available potassium and pH was *** artificial forests of limestone soil,there was a high correlation between soil alkaline nitrogen and slope,organic matter,a high correlation between soil available phosphorus and accumulated temperature,rainfall,and a high correlation bet

关键词： Soil fertility index GIS Forest soil Canonical correspondence analysis

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Amorphous BaTiO_(3) Electron Transport Layer for Thermal Equilibrium-Governed γ-CsPbl_(3) Perovskite Solar Cell with High Power Conversion Efficiency of 19.96%

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Energy & Environmental Materials 2024年第3期7卷 291-302页

作者： Changhyun Lee Chanyong Lee Kyungjin Chae Taemin Kim Seaeun Park Yohan Ko Yongseok Jun Department of Energy Environment Policy and Technology Graduate School of Energy and Environment(KU-KIST Green School)Korea UniversitySeoul 02841Republic of Korea Nano Electronic Materials and Components research Center Gumi Electronics and Information Technology Research Institute(GERI)Gumi 39171Republic of Korea Energy Materials research Center Clean Energy Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea

Compared to organic-inorganic hybrid perovskites,the cesium-based allinorganic lead halide perovskite(CsPbI_(3))is a promising light absorber for perovskite solar cells owing to its higher resistance to thermal ***,additional research is required to reduce the nonradiative recombination to realize the full potential of CsPbI_(3).Here,the diffusion of Cs ions participating in ion exchange is proposed to be an important factor responsible for the bulk defects inγ-CsPbI_(3)*** based on first-principles density functional theory reveal that the[PbI_(6)]^(4-)octahedral tilt modifies the perovskite crystallographic properties inγ-CsPbI_(3),leading to alterations in its bandgap and crystal *** addition,by substituting amorphous barium titanium oxide(a-BaTiO_(3))for TiO_(2)as the electron transport layer,interfacial defects caused by imperfect energy levels between the electron transport layer and perovskite are ***-resolution transmission electron microscopy and electron energy loss spectroscopy demonstrate that a-BaTiO_(3)forms entirely as a single phase,as opposed to Ba-doped TiO_(2)hybrid nanoclusters or separate domains of TiO_(2)and BaTiO_(3)***,inorganic perovskite solar cells based on the a-BaTiO_(3)electron transport layer achieved a power conversion efficiency of 19.96%.

关键词： amorphous BaTiO_(3) electron transport layer moisture γ-CsPbI_(3)

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Livelihood Vulnerability and Adaptation for Households Engaged in Forestry in Ecological Restoration Areas of the Chinese Loess Plateau

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Chinese Geographical Science 2024年第5期34卷 849-868页

作者： YANG Qingqing CHEN Yang LI Xiaomin YANG Jie GAO Yanhui Northwest Land and Resources research Center Global Regional and Urban Research InstituteShaanxi Normal UniversityXi’an 710119China School of Geographical Science and Tourism Shaanxi Normal UniversityXi’an 710119China School of Tourism and research institute of Human Geography Xi’an International Studies UniversityXi’an 710128China

Chinese Loess Plateau has achieved a win-win situation concerning ecological restoration and socio-economic ***,synergistic development may not be realized at the local *** areas undergoing ecological restoration,livelihood vulner-ability may be more pronounced due to the inflexibility,policy protection,and susceptibility to climate and market changes in forestry *** this issue has attracted academic interest,empirical studies are relatively *** study,centered on Jiaxian County,Shaanxi Province of China explored the households’livelihood vulnerability and coping strategies and group heterogeneity con-cerned with livelihood structures or forestry resources through field investigation,comprehensive index assessment,and nonparametric *** showed that:1)the percentage of households with high livelihood vulnerability indicator(LVI)(>0.491)reached 46.34%.2)Eight groups in livelihood structures formed by forestry,traditional agriculture,and non-farm activities were significantly different in LVI,land resources(LR),social networks(SN),livelihood strategies(LS),housing characteristics(HC),and socio-demo-graphic profile(SDP).3)The livelihood vulnerability of the groups with highly engaged/reliance on jujube(Ziziphus jujuba)forest demonstrated more prominent livelihood vulnerability due to the increased precipitation and cold market,where the low-engaged with reliance type were significantly more vulnerable in LVI,SDP,LR,and HC.4)The threshold of behavioral triggers widely varied,and farmers dependent on forestry livelihoods showed negative coping ***,the cutting behavior was strongly associated with lagged years and government subsidies,guidance,and high returns of ***,the findings can provide guidance on the dir-ection of livelihood vulnerability mitigation and adaptive government management in ecologically restored *** issue of farmers’livelihood sustainability in the context of ecologi

关键词： livelihood vulnerability forestry coping behaviors climate change market change Jiaxian County

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Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

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Journal of Animal Science and Biotechnology 2024年第1期15卷 313-328页

作者： Dirkjan Schokker Soumya K.Kar Els Willems Alex Bossers Ruud A.Dekker Alfons J.M.Jansman Wageningen Bioveterinary research LelystadThe Netherlands Wageningen Livestock research Wageningen University&ResearchWageningenThe Netherlands Royal Agrifirm Group ApeldoornThe Netherlands institute for Risk Assessment Sciences Utrecht UniversityUtrechtThe Netherlands

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning *** study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were *** study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression *** Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals *** the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal *** genes are involved in biological processes related to immunity and inflammatory *** example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum *** the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O con

关键词： Immune system Intestinal functionality Microbiota Piglets Zinc oxide

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Effects of the concentration and nature of total dissolved solids in drinking water on feed intake, nutrient digestion, energy balance,methane emission, ruminal fermentation, and blood constituents in different breeds of young goats and hair sheep

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Animal Nutrition 2024年第1期16卷 84-95页

作者： Amlan Kumar Patra Luana Paula dos Santos Ribeiro Hirut Yirga Adekayode O.Sonibare Ahmed R.Askar Ali H.Hussein Ryszard Puchala Arthur Louis Goetsch American institute for Goat research Langston University Animal and Poultry Nutrition Department Desert Research Center Agriculture Food and Natural ResourcesEastern New Mexico University

Understanding how different livestock species and breeds respond to consumption of brackish water could improve usage of this ***,Angora,Boer,and Spanish goat doelings and Dorper,Katahdin,and *** ewe lambs (6 animals per animal type[AT];initial age=296±2.1 days)consuming water with varying concentrations of minerals of a natural brackish water source (BR) and sodium chloride (NaCl;SL) were used to determine effects on water and feed intake,nutrient digestion,heat energy,methane emission,ruminal fluid conditions,and blood constituent *** were 6 simultaneous 6 (water treatments[WT])×6 (AT) Latin squares with 3-wk *** WT were fresh (FR),BR alone (100-BR),a similar total dissolved solids (TDS) concentration as 100-BR via NaCl addition to FR (100-SL),BR with concentrations of all minerals increased by approximately 50%(150-BR),a similar TDS level as 150-BR by NaCl addition to FR (150-SL),and a similar 150 TDS level achieved by addition of a 1:1 mixture of BR minerals and NaCl to 100-BR (150-BR/SL).Concentrations (mg/kg) in BR were 4928 TDS,85.9 bicarbonate,224.9 calcium,1175 chloride,60.5 magnesium,4.59 potassium,1387sodium,1962 sulfate,and 8.3 boron,and TDS in other WT were 209,5684,7508,8309,and 7319 mg/kg for FR,100-SL,150-BR,150-SL,and 150-BR/SL,*** were very few significant effects of WT or AT×WT interactions,although AT had numerous *** intake was affected by AT (P=0.02)and WT (P=0.04),with greater water intake for 150-SL than for FR,100-BR,100-SL,and *** matter intake among AT was lowest (P<0.05) for *** of organic matter and neutral detergent fiber and heat energy differed among AT (P<0.05),but nitrogen digestion and ruminal methane emission were similar among *** aldosterone concentration was higher (P<0.05) for FR than for other *** conclusion,all AT seemed resilient to these WT regardless of mineral source and concentrations,with TDS less than 8300 mg/kg,which did

关键词： Goats Hair sheep Nutrient utilization Ruminal fermentation Salinity Water quality

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