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FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

Signal Transduction and Targeted Therapy 2024年第5期9卷 2260-2274页

作者： Hao Meng Zhiying liao Yanting Ji Dong Wang Yang Han Chaolin Huang Xujuan Hu Jingyi Chen Hengrui Zhang Zonghong Li Changliang Wang Hui Sun Jiaqi Sun Lihua Chen Jiaxiang Yin Jincun Zhao tao Xu Huisheng Liu School of Biomedical Engineering Guangzhou Medical UniversityGuangzhou 511495 GuangdongChina Guangzhou National Laboratory Guangzhou 510320 GuangdongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Center for Translational Medicine Wuhan Jinyintan HospitalWuhan 430023 HubeiChina School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou 510006 GuangdongChina

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

关键词： ACE2 FGF7 islet

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Base editor-mediated large-scale screening of functional mutations in bacteria for industrial phenotypes

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Science China(Life Sciences) 2024年第5期67卷 1051-1060页

作者： Yaomeng Yuan Xihao liao Shuang Li Xin-Hui Xing Chong Zhang MOE Key Laboratory for Industrial Biocatalysis Institute of Biochemical EngineeringDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 440300China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China

Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.

关键词： base editor high-throughput large-scale screening Escherichia coli functional mutation

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Effects of fracture evolution and non-Darcy flow on the thermal performance of enhanced geothermal system in 3D complex fractured rock

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International Journal of Mining Science and Technology 2024年第4期34卷 443-459页

作者： Yachen Xie Jianxing liao Pengfei Zhao Kaiwen Xia Cunbao Li Department of Civil and Mineral Engineering University of TorontoToronto M5S1A4Canada College of Water Resources and Hydropower Sichuan UniversityChengdu 610225China State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsWuhan 430071China College of Civil Engineering Guizhou UniversityGuiyang 550025China Institute of Geosafety School of Engineering and TechnologyChina University of GeosciencesBeijing 100083China State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground Engineering Shenzhen UniversityShenzhen 518060China

In fractured geothermal reservoirs,the fracture networks and internal fluid flow behaviors can significantly impact the thermal performance.In this study,we proposed a non-Darcy rough discrete fracture network(NR-DFN)model that can simultaneously consider the fracture evolution and non-Darcy flow dynamics in studying the thermo-hydro-mechanical(THM)coupling processes for heat extraction in geothermal reservoir.We further employed the model on the Habanero enhanced geothermal systems(EGS)project located in Australia.First,our findings illustrate a clear spatial-temporal variation in the thermal stress and pressure perturbations,as well as uneven spatial distribution of shear failure in 3D fracture networks.Activated shear failure is mainly concentrated in the first fracture cluster.Secondly,channeling flow have also been observed in DFNs during heat extraction and are further intensified by the expansion of fractures driven by thermal stresses.Moreover,the combined effect of non-Darcy flow and fracture evolution triggers a rapid decline in the resulting heat rate and temperature.The NR-DFN model framework and the Habanero EGS's results illustrate the importance of both fracture evolution and non-Darcy flow on the efficiency of EGS production and have the potential to promote the development of more sustainable and efficient EGS operations for stakeholders.

关键词： Coupled THM model Non-Darcy flow Deformable DFN Enhanced geothermal systems

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Ignition processes and characteristics of charring conductive polymers with a cavity geometry in precombustion chamber for applications in micro/nano satellite hybrid rocket motors

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Defence Technology（防务技术） 2024年第2期32卷 55-66页

作者： Zhiyuan Zhang Hanyu Deng Wenhe liao Bin Yu Zai Yu Nanjing University of Science and Technology Nanjing 210094China

The arc ignition system based on charring polymers has advantages of simple structure,low ignition power consumption and multiple ignitions,which bringing it broadly application prospect in hybrid propulsion system of micro/nano satellite.However,charring polymers alone need a relatively high input voltage to achieve pyrolysis and ignition,which increases the burden and cost of the power system of micro/nano satellite in practical application.Adding conductive substance into charring polymers can effectively decrease the conducting voltage which can realize low voltage and low power consumption repeated ignition of arc ignition system.In this paper,a charring conductive polymer ignition grain with a cavity geometry in precombustion chamber,which is composed of PLA and multiwall carbon nanotubes(MWCNT)was proposed.The detailed ignition processes were analyzed and two different ignition mechanisms in the cavity of charring conductive polymers were revealed.The ignition characteristics of charring conductive polymers were also investigated at different input voltages,ignition grain structures,ignition locations and injection schemes in a visual ignition combustor.The results demonstrated that the ignition delay and external energy required for ignition were inversely correlated with the voltages applied to ignition grain.Moreover,the incremental depth of cavity shortened the ignition delay and external energy required for ignition while accelerated the propagation of flame.As the depth of cavity increased from 2 to 6 mm(at 50 V),the time of flame propagating out of ignition grain changed from 235.6 to 108 ms,and values of mean ignition delay time and mean external energy required for ignition decreased from 462.8 to 320 ms and 16.2 to 10.75 J,respectively.The rear side of the cavity was the ideal ignition position which had a shorter ignition delay and a faster flame propagation speed in comparison to other ignition positions.Compared to direct injection scheme,swirling injection provided a more favorable flow field

关键词： Micro/nano satellite hybrid propulsion Arc ignition Charring conductive polymer Ignition mechanism Ignition characteristic Repeated ignition

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Ferrihydrite transformation impacted by coprecipitation of lignin:Inhibition or facilitation?

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Journal of Environmental Sciences 2024年第5期139卷 23-33页

作者： Lin Liu Zhihui Yang Weichun Yang Wen Jiang Qi liao Mengying Si Feiping Zhao School of Metallurgy and Environment Central South UniversityChangsha 410083China Chinese National Engineering Research Center for Control&Treatment of Heavy Metal Pollution(CNERC-CTHMP) Changsha 410083China

Lignin is a common soil organic matter that is present in soils,but its effect on the transformation of ferrihydrite(Fh)remains unclear.Organic matter is generally assumed to inhibit Fh transformation.However,lignin can reduce Fh to Fe(Ⅱ),in which Fe(Ⅱ)-catalyzed Fh transformation occurs.Herein,the effects of lignin on Fh transformation were investigated at 75℃ as a function of the lignin/Fh mass ratio(0-0.2),pH(4-8)and aging time(0-96 hr).The results of Fh-lignin samples(mass ratios=0.1)aged at different pH values showed that for Fh-lignin the time of Fh transformation into secondary crystalline minerals was significantly shortened at pH 6 when compared with pure Fh,and the Fe(Ⅱ)-accelerated transformation of Fh was strongly dependent on pH.Under pH 6,at low lignin/Fh mass ratios(0.05-0.1),the time of secondary mineral formation decreased with increasing lignin content.For high lignosulfonate-content material(lignin:Fh=0.2),Fh did not transform into secondary minerals,indicating that lignin content plays a major role in Fh transformation.In addition,lignin affected the pathway of Fh transformation by inhibiting goethite formation and facilitating hematite formation.The effect of coprecipitation of lignin on Fh transformation should be useful in understanding the complex iron and carbon cycles in a soil environment.

关键词： Ferrihydrite transformation Lignin Hematite Goethite Fe(Ⅱ)-catalyzed Reactive Fe(Ⅲ)species

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Probiotic cocktails accelerate baicalin metabolism in the ileum to modulate intestinal health in broiler chickens

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Journal of Animal Science and Biotechnology 2024年第2期15卷 779-794页

作者： Mingkun Gao Chaoyong liao Jianyang Fu Zhonghua Ning Zengpeng Lv Yuming Guo State Key Laboratory of Animal Nutrition and Feeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China National Engineering Laboratory for Animal Breeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

Background Baicalin and probiotic cocktails are promising feed additives with broad application prospects.While probiotic cocktails are known to enhance intestinal health,the potential synergistic impact of combining baicalin with probiotic cocktails on the gut health of broiler chickens remains largely unexplored.Therefore,this study aims to investigate the influence of the combined administration of baicalin and probiotic cocktails on the composition of ileal and cecal microbiota in broiler chickens to elucidate the underlying mechanisms responsible for the healthpromoting effects.Results A total of 3201-day-old male Arbor Acres broilers were divided into 4 groups,each with 8 replicates of 10 chicks per replicate.Over a period of 42 d,the birds were fed a basal diet or the same diet supplemented with 37.5 g/t baicalin(BC),1,000 g/t probiotic cocktails(PC),or a combination of both BC(37.5 g/t)and PC(1,000 g/t).The results demonstrated that BC+PC exhibited positive synergistic effects,enhancing intestinal morphology,immune function,and barrier function.This was evidenced by increased VH/CD ratio,sIgA levels,and upregulated expression of occludin and claudin-1(P<0.05).16S rRNA analysis indicated that PC potentiated the effects of BC,particularly in the ileum,where BC+PC significantly increased theα-diversity of the ileal microbiota,altered itsβ-diversity,and increased the relative abundance of Flavonifractor(P<0.05),a flavonoid-metabolizing bacterium.Furthermore,Flavonifractor positively correlated with chicken ileum crypt depth(P<0.05).While BC+PC had a limited effect on cecal microbiota structure,the PC group had a very similar microbial composition to BC+PC,suggesting that the effect of PC at the distal end of the gut overshadowed those of BC.Conclusions We demonstrated the synergistic enhancement of gut health regulation in broiler chickens by combining baicalin and probiotic cocktails.Probiotic cocktails enhanced the effects of baicalin and accelerated its metabolism in the ileum,thereby influencing the ileal

关键词： Baicalin Gut health Ileal microbiota Probiotic cocktails Synergistic effects

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Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng liao Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer therapy.This pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal cells.Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical studies.However,to date,the clinical success of drugs targeting the innate immune pathway remains limited.Interestingly,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression.The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation.In this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell types.We propose that within the TME,the innate immune pathway exhibits multidimensional diversity.This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks.The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways.Refining our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

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Regulation of rhizosphere microenvironment by rice husk ash for reducing the accumulation of cadmium and arsenic in rice

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Journal of Environmental Sciences 2024年第2期136卷 1-10页

作者： Yi Jiang Ya Liu Xuantao Yi Peng Zeng Bohan liao Hang Zhou Jiaofeng Gu College of Environmental Science and Engineering Central South University of Forestry and TechnologyChangsha 410004China Hunan Engineering Laboratory for Control of Rice Quality and Safety Changsha 410004China

It is important to reduce Cd and As content in brown rice in contaminated paddy soils.We conducted research on the effects of rice husk ash (RHA) on the Cd and As in the rhizosphere microenvironment (soil,porewater,and iron plaque) and measured the Cd,As,and Si content in rice plants.The main elements in RHA were Si (29.64%) and O (69.17%),which had the maximum adsorption capacity for Cd was 42.49 mg/kg and for As was 18.62 mg/kg.Soil pH and available Si content increased,while soil available Cd and As decreased following application of 0.5%–2%RHA.RHA promote the transformation of Cd to insoluble fraction,while As was transformed from a poorly soluble form to a more active one.RHA reduced Cd content and increased Si content in porewater,and reduced As only at the later rice growth stages.RHA increased the amount of iron plaque,thereby decreasing the Cd content in iron plaque,while increased the As content in it.Cd and inorganic As content in brown rice were decreased,to 0.31 mg/kg and 0.18 mg/kg,respectively.The decrease of Cd in brown rice was due to the decrease of Cd mobility in soil,thereby reducing root accumulation,while the decrease of As in brown rice was affected by the transport from roots to stems.Therefore,RHA can be considered as a safe and efficient in-situ remediation amendment for Cd and As co-contaminated paddy soil.

关键词： Rice husk ash(rha) Cadmium Arsenic Silicon Rice Soil

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Agricultural Investment Project Decisions Based on an Interactive Preference Disaggregation Model Considering Inconsistency

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 3125-3146页

作者： Xingli Wu Huchang liao Shuxian Sun Zhengjun Wan Business School Sichuan UniversityChengdu610064China National Institute of Measurement and Testing Technology Chengdu610021China

Agricultural investment project selection is a complex multi-criteria decision-making problem,as agricultural projects are easily influenced by various risk factors,and the evaluation information provided by decisionmakers usually involves uncertainty and inconsistency.Existing literature primarily employed direct preference elicitation methods to address such issues,necessitating a great cognitive effort on the part of decision-makers during evaluation,specifically,determining the weights of criteria.In this study,we propose an indirect preference elicitation method,known as a preference disaggregation method,to learn decision-maker preference models fromdecision examples.To enhance evaluation ease,decision-makers merely need to compare pairs of alternatives with which they are familiar,also known as reference alternatives.Probabilistic linguistic preference relations are employed to account for the presence of incomplete and uncertain information in such pairwise comparisons.To address the inconsistency among a group of decision-makers,we develop a pair of 0-1mixed integer programming models that consider both the semantics of linguistic terms and the belief degrees of decision-makers.Finally,we conduct a case study and comparative analysis.Results reveal the effectiveness of the proposed model in solving agricultural investment project selection problems with uncertain and inconsistent decision information.

关键词： Multiple criteria analysis preference disaggregation inconsistency probability linguistic preference relation investment project selection

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Development of Mixed Insulation Oil as Alternative Liquid Dielectric:A Review

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 1242-1258页

作者： Jian Hao Jingwen Zhang Wenyu Ye Ruijing liao Lijun Yang State Key Laboratory of Power Transmission Equipment Technology School of Electrical EngineeringChongqing UniversityChongqing 400044China IEEE CSEE

Use of traditional mineral oil(MO)as a liquid insulation in transformers has spanned more than 130 years.However,MO has poor heat resistance,a low ignition point,and is a non-renewable resource,which does not meet development requirements for high-performance and environmentally friendly insulation oil.Consequently,researchers have explored alternatives such as natural ester(NE)and synthetic ester(SE)oils,as well as mixed insulation oils.Mixed insulating oil is a blend of diverse insulating oil types,with optimal performance achieved by adjusting proportions of base oils.This article summarizes the innovative achievements and development of mixed insulation oil in terms of development of mixed ratio,basic physical chemical properties,electrical properties,thermal stability,and application including operation and maintenance technology.Through these efforts,this article aims to provide recommendations for future development of mixed insulating oils to advance liquid dielectric research based on enhancement mechanisms.

关键词： Environmentally friendly insulation oil ester oils high-performance mineral oil mixed insulation oils

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