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Establishing cell suitability for high-level production of licorice triterpenoids in yeast

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4134-4148页

作者： Wentao Sun Shengtong Wan Chuyan Liu Ruwen wang Haocheng Zhang Lei Qin Runming wang Bo Lv chun Li Department of Chemical Engineering Tsinghua UniversityBeijing 100084China Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information TechnologyInstitute of Biochemical EngineeringSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China The University of Chicago ChicagoIL 60637USA Key Lab for Industrial Biocatalysis Ministry of EducationTsinghua UniversityBeijing 100084China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China

Yeast has been an indispensable host for synthesizing complex plant-derived naturalcompounds, yet the yields remained largely constrained. This limitation mainly arises from overlookingthe importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein,beyond conventional enzyme engineering, we dissected metabolic suitability with a framework forsimultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenoustriterpenoids. We further developed phospholipid microenvironment engineering strategies, dramaticallyimproving yeast’s suitability for the high performance of endoplasmic reticulum (ER)-localized, ratelimitingplant P450s. Combining metabolic and microenvironment suitability by manipulating only threegenes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)andGPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rarelicorice triterpenoids derived from consecutive oxidation of b-amyrin by two P450 enzymes afterfermentation optimization. This production holds substantial commercial value, highlighting the criticalrole of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatileframework applicable to various plant natural product biosynthetic pathways.

关键词： Cell suitability Phospholipid microenvironment Cytochrome P450 Triterpenoids Saccharomyces cerevisiae

Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity:Insight from recent research

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World Journal of Diabetes 2024年第4期15卷 586-590页

作者： Hui-Hong Tang Dong wang Cheng-chun Tang Department of Cardiology Zhongda HospitalSoutheast UniversityNanjing 210009Jiangsu ProvinceChina School of Medicine Southeast UniversityNanjing 210009Jiangsu ProvinceChina

Obesity is a prevalent cause of diabetes mellitus(DM)and is a serious danger to human *** 2 DM(T2DM)mostly occurs along with *** obesity-induced DM is caused by an excessive long-term diet and surplus *** surgery can improve the symptoms of T2DM in some obese *** different types of bariatric surgery may have different *** are some models built by researchers to discuss the surgical procedures’effects on me-tabolism in diabetes animal models and diabetes *** is high time to conclude all this effects and recommend procedures that can better improve metabolism.

关键词： Bariatric surgery Obesity Diabetes Animal models Diabetes patients

Achieving strength-ductility synergy in novel paramagnetic Fe-based medium-entropy alloys through deep cryogenic deformation

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Rare Metals 2024年第9期43卷 4493-4507页

作者： Hu-Wen Ma Yan-chun Zhao Li Feng Tian-Zeng Liu Zhi-Qi Yu Bo Jin wang-chun Duan Peter K.Liaw Dong Ma State Key Laboratory of Advanced Processing and Recycling of Non-Ferrous Metals Lanzhou University of TechnologyLanzhou 730050China Wenzhou Pump and Valve Engineering Research Institute Lanzhou University of TechnologyWenzhou 325105China Iron and Steel Research Institute Jiuquan Iron and Steel CorporationJiayuguan 735100China Lanzhou Resources and Environment Voc-Tech University Lanzhou 730123China Department of Materials Science and Engineering The University of TennesseeKnoxvilleTN 37996-2200USA Neutron Science Center Songshan Lake Materials LaboratoryDongguan 523808China

Cryogenic pre-deformation treatment has been widely used to effectively improve the comprehensive mechanical properties of steels and novel ***,the dislocation evolution and phase transformation induced by different degrees of deep cryogenic deformation are not yet fully *** this study,the effects of multiple cryogenic pre-treatments on the mechanical properties and deformation mechanisms of a paramagnetic Fe_(63.3)Mn_(14-)Si_(9.1)Cr_(9.8)C_(3.8)medium-entropy alloy(MEA)were investigated,leading to the discovery of a pretreated MEA that exhibits exceptional mechanical properties,including a fracture strength of 3.0 GPa,plastic strain of 26.1%and work-hardening index of *** addition,X-ray diffraction(XRD)and transmission electron microscopy(TEM)analyses revealed that multiple cryogenic pre-deformation treatments significantly increased the dislocation density of the MEA(from 9×10^(15)to 4×10^(16)m^(-2)after three pretreatments),along with a transition in the dislocation type from predominantly edge dislocations to mixed dislocations(including screw-and edge-type dislocations).Notably,this pretreated MEA retained its paramagnetic properties(μ_(r)<1.0200)even after *** calculations showed that cryogenic pretreatment can significantly reduce the stacking fault energy of the MEA by a factor of approximately four(i.e.,from 9.7 to2.6 m J·m^(-2)),thereby activating the synergistic effects of transformation-induced plasticity,twinning-induced plasticity and dislocation strengthening *** synergistic effects lead to simultaneous strength and ductility enhancement of the MEA.

关键词： Deep cryogenic transformation Iron-based medium-entropy alloys Dislocation evolution Phase transformation Stacking fault energy

Development and validation of an immunogenic cell death-related prognostic model, and landscape of the tumor immune microenvironment in glioblastoma

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Genes & Diseases 2024年第3期11卷 72-74页

作者： sha Yang Mei Deng Yunbiao Xiong Bing Xiong Junwu Fu Jia wang Jiqin Zhang Guoqiang Han Jian Liu Ying Tan Guizhou University Medical College GuiyangGuizhou 550025China Department of Neurosurgery Guizhou Provincial People's HospitalGuiyangGuizhou 550002China Department of Anesthesiology Guizhou Provincial People's HospitalGuiyangGuizhou 550002China Department of Neurosurgery Chongqing Emergency Medical CenterChongqing400000China

The important role of immunogenic cell death(ICD)in many tumors is increasingly being ***,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well *** obtained GBM samples from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases,as well as the immunotherapy cohort from the IMvigor210 *** used unsupervised clustering to obtain two ICDrelated clusters,corresponding to the ICD-low and ICD-high subtypes respectively,and the tumor immune microenvironment and prognosis of the two subtypes were significantly different.

关键词： immune Cancer prognosis

Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

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Neural Regeneration Research 2024年第7期19卷 1568-1574页

作者： Qi Gu Weiping sha Qun Huang Jin wang Yi Zhu Tianli Xu Zhenhua Xu Qiancheng Zhu Jianfei Ge Shoujin Tian Xiaolong Lin Department of Orthopaedic Surgery Zhangjiagang Hospital Affiliated to Soochow UniversitySuzhouJiangsu ProvinceChina Orthopedics Laboratory The First People’s Hospital of Zhangjiagang CitySuzhouJiangsu ProvinceChina Department of Anesthesiology Zhangjiagang Hospital Affiliated to Soochow UniversitySuzhouJiangsu ProvinceChina

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord *** growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species *** relationship between heme oxygenase-1and ferroptosis remains controve *** this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord *** addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord *** r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme ***,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd *** findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

关键词： ferroptosis fibroblast growth factor 21 functional recovery heme oxygenase-1 lipid peroxidation neuron reactive oxygen species spinal cord injury

NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

General and specialized metabolites in peanut roots regulate arbuscular mycorrhizal symbiosis

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Journal of Integrative Agriculture 2024年第8期23卷 2618-2632页

作者： Li Cui Jianguo wang Zhaohui Tang Zheng Zhang sha Yang Feng Guo Xinguo Li Jingjing Meng Jialei Zhang Yakov Kuzyakov Shubo Wan Institute of Crop Germplasm Resources Shandong Academy of Agricultural Sciences/Scientific Observing and Experimental Station of Crop Cultivation in East ChinaMinistry of Agriculture and Rural AffairsJinan 250100China shandong Academy of Agricultural Sciences Jinan 250100China Department of Soil Science of Temperate Ecosystems Department of Agricultural Soil ScienceUniversity of GöttingenGöttingen 37077Germany Peoples Friendship University of Russia(RUDN University) Miklukho-Maklaya StMoscow 117198Russia Institute of Environmental Sciences Kazan Federal University420049 KazanRussia

Arbuscular mycorrhizae(AM)fungi form symbiotic associations with plant roots,providing nutritional benefits and promoting plant growth and defenses against various *** changes in the roots during AM fungal colonization are key to understanding the development and maintenance of these ***,we investigated metabolic changes in the roots of peanut(Arachis hypogaea L.)plants during the colonization and development of AM symbiosis,and compared them to uncolonized *** primary changes during the initial stage of AM colonization were in the contents and compositions of phenylpropanoid and flavonoid *** compounds function in signaling pathways that regulate recognition,interactions,and pre-colonization between roots and AM *** compounds decreased by 25%when the symbiosis was fully established compared to the initial colonization *** AM symbiosis was established,general metabolism strongly shifted toward the formation of lipids,amino acids,carboxylic acids,and *** compounds increased by 8.5%from the pre-symbiotic stage to well-established ***-phosphatidylcholines,which are signaling compounds,were only present in AM roots,and decreased in content after the symbiosis was *** the initial stage of AM establishment,the content of salicylic acid increased two-fold,whereas jasmonic acid and abscisic acid decreased compared to uncolonized *** jasmonic acid content decreased in roots after the symbiosis was well *** symbiosis was associated with high levels of calcium,magnesium,and D-(+)-mannose,which stimulated seedling ***,specific metabolites that favor the establishment of AM symbiosis were common in the roots,primarily during early colonization,whereas general metabolism was strongly altered when AM symbiosis was *** conclusion,specialized metabolites function as signaling compounds to establish AM *** compounds are no longe

关键词： Arachis hypogaea L. arbuscular mycorrhizae fungi metabolites symbiotic association

Design parameter optimization method for a prestressed steel structure driven by multi-factor coupling

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Frontiers of Structural and Civil Engineering 2024年第7期18卷 1066-1083页

作者： Guo-Liang SHI Zhan-Sheng LIU De-chun LU Qing-Wen ZHANG Majid DEZHKAM Ze-Qiang wang Faculty of Architecture Civil and Transportation EngineeringBeijing University of TechnologyBeijing 100124China The Key Laboratory of Urban Security and Disaster Engineering of the Ministry of Education Beijing University of TechnologyBeijing 100124China Beijing Building Construction Research Institute Co. Ltd.Beijing 100039China

To achieve efficient structural design,it is crucial to reduce the cost of materials while ensuring structural *** study proposes an optimization method for design parameters(DPs)in a prestressed steel structure driven by multi-factor *** accomplish this,a numerical proxy model of prestressed steel structures is established with integration of DPs and mechanical parameters(MPs).A data association-parameter analysis-optimization selection system is established.A correlation between DPs and MPs is established using a back propagation(BP)neural *** correlation provides samples for parameter analysis and optimization *** are used to characterize the safety of the *** on the safety grade analysis,the key DPs that affect the mechanical properties of the structure are obtained.A mapping function is created to match the MPs and the key *** optimal structural DPs are obtained by setting structural materials as the optimization objective and safety energy as the constraint *** theoretical model is applied to an 80-m-span gymnasium and verified with a scale test physical *** MPs obtained using the proposed method are in good agreement with the experimental *** with the traditional design method,the design cycle can be shortened by more than 90%.Driven by the optimal selection method,a saving of more than 20% can be achieved through reduction of structural material ***,the cross-sectional dimensions of radial cables have a substantial influence on vertical *** initial tension and cross-sectional size of the upper radial cable exhibit the most pronounced impact on the stress distribution in that *** initial tension and cross-sectional size of the lower radial cable hold the greatest sway over the stress distribution in that cable.

关键词： structure design association relationship performance analysis optimum selection experimental verification

In-situ SEM characterization of fracture mechanism of TiB/Ti-2Al-6Sn titanium matrix composites after electroshocking treatment

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Rare Metals 2024年第6期43卷 2805-2818页

作者： Ya-Ya Wu Jian Zhou Guo-Lei Han Yan Wen Zhou wang Li-Qiang wang Wei-Jie Lv Le-chun Xie Lin Hua Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan 430070China Hubei Collaborative Innovation Center for Automotive Components Technology Wuhan 430070China Faculty of Materials and Manufacturing Beijing University of TechnologyBeijing 100124China State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China

In this article,in-situ scanning electron microscope characterization of the tensile properties of TiB/Ti-2Al-6Sn titanium matrix composite(TMC)was conducted before and after electroshocking treatment(EST).After EST,the tensile strength increased by 113.2 *** effect of EST on the tensile strength and fracture behavior of TiB was investigated using in-situ characterization of the fracture morphology and crack propagation path of the matrix and *** EST,TiB fracture introduced cracks that extended into the matrix,resulting in material *** EST,the refined TiB improved the bearing capacity of the matrix,thereby improving TMC ***,after EST,the cracks were introduced into the matrix,and resulting the fracture of matrix *** an increase in the external load,cracks in the matrix were observed to propagate to TiB,and the refined TiB was fractured,detached,and pulled out,resulting in the formation of *** the propagation path of the main crack after EST showed that the deflection angle of the main crack *** micro structure of the fracture surface indicated that the fracture of the matrix was plastic,whereas that of TiB was *** EST,the size and area of the dimples increased,confirming the increase in *** results revealed that the comprehensive mechanical properties of TiB/Ti-2Al-6Sn improved after ***,EST is an efficient method for tailoring the micro structures and mechanical properties of TMCs.

关键词： TiB/Ti-2Al-6Sn In-situ microstructure characterization Tensile properties Reinforcement Electroshocking treatment(EST)