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Recent Advances in the Development of Indolizine Scaffolds:Synthetic Methodology and Mechanistic Insights

Chinese Journal of Chemistry 2025年第3期43卷 315-348页

作者： Jiuzhong Huang Chunsheng Li Xiaoning Li Guangyu Li Ziyi Yang Yinke Yu Yanping Xie Hao Huang Fuchao Yu Zhihua He First Affiliated Hospital Gannan Medical UniversityGanzhouJiangxi341000 China Jiangxi Province Key Laboratory of Pharmacology of Traditional Chinese Medicine School of PharmacyGannan Medical UniversityGanzhouJiangxi341000 China School of Chemistry and Chemical Engineering Zhaoqing UniversityZhaoqingGuangdong526060 China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunmingYunnan650500 China

Indolizine is a nitrogen-containing heterocycle with strong aromaticity,possessing a delocalized 10π-electron *** on the indolizine scaffolds,numerous molecules with biological activity and organic functional materials have been *** 2016,over 110 papers have been published on the synthesis of indolizine scaffolds,but the reviews on synthesizing indolizine scaffolds have been incomplete and not ***,from the perspective of the structure of indolizine with the combination of pyrrole and pyridine ring,we focus on the construction of indolizine scaffolds through the diversity of starting substrates,including pyridine derivatives(N1-substituted pyridinium salt derivatives,C2-substituted pyridine derivatives,N1-and C2-free substituted pyridine derivatives),pyrrole derivatives and unoriginal ring ***,the corresponding reaction mechanisms of synthetic methodologies are also ***,this review not only paves the way for indolizine synthesis but also provides insight into exploring new reaction modes for constructing nitrogen-containing heterocycles.

关键词： Indolizine scaffolds Synthetic methodology Mechanistic insights Pyridine derivatives Pyrrole derivatives Unoriginal ring substrates

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Engineered AAV13 variants with enhanced transduction and confined spread

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Zoological Research 2024年第4期45卷 781-790页

作者： Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for Biomedicine Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality Control Technology for Virus-Based Therapeutics Guangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of Sciences Beijing 100049China Zhongnan Hospital Wuhan UniversityWuhanHubei 430072China Brain Case Biotechnology Co. Ltd.ShenzhenGuangdong 518107China College of Life Sciences Wuhan UniversityWuhanHubei 430072China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the context of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关键词： Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency

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Modulating carrier density of the(Ag)_(x)(MoO_(3))_(y)system to enhance SERS:Localized surface plasmon resonance contribution

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Journal of Materiomics 2023年第2期9卷 387-394页

作者： Lin Zhu Zhu Mao Peng Li Menglei Xu Zhen Meng Lei Chen Bing Zhao Stake Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchun130012China School of Chemistry and Life Science Advanced Institute of Materials ScienceChangchun University of Technology Changchun130012China Key Laboratory of Functional Materials Physics and Chemistry of the Ministry of Education Jilin Normal UniversityChangchun130103China

Semiconductors typically exhibit long-wavelength LSPR absorption in the infrared region due to lower carrier *** the carrier density of semiconductors and blue-shifting their LSPR absorption to the visible and near-infrared region has always been a great ***,we discussed how the controllable carrier of(Ag)x(MoO_(3))y composite influences the LSPR based on SERS test and UVeViseNIR absorption *** were surprised to find that the LSPR absorption wavelength can be easily tuned from 950 to 735 nm by changing the sputtering power of MoO_(3)of the(Ag)x(MoO_(3))_(y)*** shows that LSPR can be precisely adjusted by increasing the semiconductor content and even the carrier *** addition,the carrier density was measured by Hall effect to investigate the SERS intensity change caused by electromagnetic(EM)enhancement,and obtain the relationship between the *** findings of this work provide an idea for tunable LSPR and the research of EM contributions to SERS.

关键词： Carrier density Localized surface plasmon resonance Semiconductor Electromagnetic Surface-enhanced Raman scattering

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Engineered nanoplatform mediated gas therapy enhanced ferroptosis for tumor therapy in vivo

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Bioactive Materials 2025年第2期44卷 488-500页

作者： Kun Xu Ke Li Ye He Yulan Mao Xuan Li Liangshuai Zhang Meijun Tan Yulu Yang Zhong Luo Peng Liu Kaiyong Cai Key Laboratory of Biorheological Science and Technology Ministry of Education College of BioengineeredChongqing University Chongqing400044PR China Thomas Lord Department of Mechanical Engineered and Materials Science Duke UniversityDurhamNC27708USA Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies School of Materials and EnergySouthwest UniversityChongqing400715PR China School of Life Science Chongqing UniversityChongqing400044PR China

The high glutathione(GSH)environment poses a significant challenge for inducing ferroptosis in tumor cells,necessitating the development of nanoplatforms that can deplete intracellular *** this study,we developed an engineered nanoplatform(MIL-100@Era/L-Arg-HA)that enhances ferroptosis through gas ***,we confirmed that the Fe element in the nanoplatform undergoes valence changes under the influence of high GSH and H_(2)O_(2)in tumor ***,L-Arg generates NO gas in the presence of intracellular H_(2)O_(2),which reacts with ***,Erastin depletes GSH by inhibiting the cystine/glutamate antiporter system,reducing cystine uptake and impairing GPX4,while also increasing intracellular H_(2)O_(2)levels by activating NOX4 protein *** these combined GSH-depletion mechanisms,we demonstrated that MIL-100@Era/L-Arg-HA effectively depletes GSH levels,disrupts GPX4 function,and increases intracellular lipid ROS levels in ***,this nanoplatform significantly inhibited tumor cell growth and extended the survival time of tumor-bearing mice in *** engineered nanoplatform,which enhances ferroptosis through gas therapy,shows significant promise for ferroptosis-based cancer therapy and offers potential strategies for clinical tumor treatment.

关键词： Gas therapy Ferroptosis GSH NO

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HBXIP blocks myosin-ⅡA assembly by phosphorylating and interacting with NMHC-ⅡA in breast cancer metastasis

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1053-1070页

作者： Lu Zhang Xiaolei Zhou Bowen Liu Xuhe Shi Xianmeng Li Feifei Xu Xueli Fu Xue Wang Kai Ye Tianzhi Jin Huimin Sun Qianqian Li Weiying Zhang Lihong Ye State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein SciencesDepartment of Biochemistry and Molecular BiologyCollege of Life SciencesNankai UniversityTianjin 300071China College of Food Science&Biology Hebei University of Science and TechnologyShijiazhuang 050091China Henan Key Laboratory of Immunology and Targeted Drugs School of Laboratory MedicineXinxiang Medical UniversityXinxiang 453003China

Tumor metastasis depends on the dynamic balance of the actomyosin *** a key component of actomyosin filaments,non-muscle myosin-ⅡA disassembly contributes to tumor cell spreading and ***,its regulatory mechanism in tumor migration and invasion is poorly ***,we found that oncoprotein hepatitis B X-interacting protein(HBXIP) blocked the myosin-ⅡA assemble state promoting breast cancer cell ***,mass spectrometry analysis,co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain(ACD) of non-muscle heavy chain myosin-ⅡA(NMHC-ⅡA).The interaction was enhanced by NMHC-ⅡA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβⅡ.Moreover,HBXIP induced the transcription of PRKCB,encoding PKCβⅡ,by coactivating Sp1,and triggered PKCβⅡ kinase ***,RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate(BZF) suppressed breast cancer metastasis via inhibiting PKCβⅡ-mediated NMHC-ⅡA phosphorylation in vitro and in *** reveal a novel mechanism by which HBXIP promotes myosin-ⅡA disassembly via interacting and phosphorylating NMHC-ⅡA,and BZF can serve as an effective anti-metastatic drug in breast cancer.

关键词： Breast cancer metastasis Actomyosin cytoskeleton HBXIP Myosin-IIA NMHC-IIA Phosphorylation PKCβII Bezafibrate

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The future and technique challenges of high-speed ground effect vehicle enrolled in maritime transportation

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Aerospace Traffic and Safety 2024年第1期1卷 43-54页

作者： Jianhong Sun Chenlu Wang Daren Zheng Zhi Sun Hao Liu Zhuoran Sheng Shengrun Zhang Weidong Zhao Key Laboratory of Aircraft Environment Control and Life Support MIITNanjing 210016China Key Laboratory of Civil Aviation Emergency Science&Technology CAACNanjing 211106China

This paper presents a high-speed ground effect vehicle(HS-GEV)used specifically for maritime *** the limitations of current vessels,including various types of watercraft and high-speed boats,in fulfilling of needs in different maritime transportation scenarios,the HS-GEV emerges as a promising solution to address unmet *** efficiently accomplish maritime transportation missions with quickness and safety,several critical features are emphasized,including short take-off on water,flight maneuverability and flight *** key techniques required to achieve these features,as well as recent progress highlights,are *** and promoting these crucial techniques is also suggested as a future step to improve HS-GEV *** its predominant features,the HS-GEV holds immense application value in enhancing a high-speed maritime transportation system that aligns with the evolving needs of the real world.

关键词： HS-GEV Maritime Transportation Drag Reduction Combined Power Wing-in-Ground(WIG)Effect Ground Effect Vehicle(GEV)

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PERFORMANCE ANALYSIS AND IMPROVEMENT OF TURBINE-POWERED AIR CYCLE SYSTEM

PERFORMANCE ANALYSIS AND IMPROVEMENT OF TURBINE-POWERED AIR ...

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2024 CSAA/IET International Conference on Aircraft Utility Systems, AUS 2024

作者： Li, Kaining Wu, Yan Lu, Qihang Zhang, Dalin Key Laboratory of Aircraft Environment Control and Life Support Ministry of Industry and Information Technology Nanjing University of Aeronautics and Astronautics Nanjing China Nanjing Engineering Institute of Aircraft Systems Nanjing China

In order to reduce the engine bleed air consumption of fighter jet environmental control systems with high-power electronic equipment compartments, a comparative analysis was conducted on the typical turbine-powered closed cycle systems TP-ACS/HPWS and PTMS-ACS/HPWS. On this basis, improvements were made to PTMS-ACS/HPWS, and the TP-CACS architecture was proposed. The influence of flight conditions, electronic cabin heat load, and other parameters on the engine bleed air consumption of the three systems was analysed through modelling and calculation. The calculation results show that by adjusting the operating pressure and flight altitude, PTMS-ACS/HPWS generally consumes less engine bleed air than TP-ACS/HPWS, and its operation adjustment is more convenient;on this basis, a turbine-powered closed air cycle system TP-CACS with independent regulation of cabin air supply is proposed, and under different electronic cabin thermal loads and flight conditions, the TP-CACS engine has the lowest bleed airflow consumption and the best performance;one of the development directions for future environmental control systems is to combine closed loop systems with independent cabin air supply. © The Institution of Engineering & technology 2024.

关键词： CLOSED AIR CYCLE SYSTEM ELECTRONIC EQUIPMENT COOLING PERFORMANCE ANALYSIS POWER TURBINE

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CRISPR-mediated editing of BnaNRAMP1 homologous copies creates a low Cd-accumulation oilseed rape germplasm with unaffected yield

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Journal of Integrative Agriculture 2025年第5期24卷 1704-1717页

作者： Ying Zhang Rui Wang Tianshun Luo Jingyan Fu Meng Yin Maolin Wang Yun Zhao Key Laboratory for Bio-Resources and Eco-Environment College of Life SciencesSichuan UniversityChengdu 610065China Science and Technology Innovation Center of Sichuan Modern Seed Industry Group Chengdu 611100China

Brassica napus,one of the most important oil crops cultivated globally,is severely impacted by prolonged soil contamination with cadmium(Cd),resulting in decreased yields and poor seed *** crop exhibits a high adsorption capacity for Cd,making creating seed resources with low Cd accumulation an essential strategy to alleviate this *** address this issue,we genetically edited BnaNRAMP1 in *** by targeting three different exon regions,resulting in new germplasm resources with significant differences in Cd accumulation capacity and unaffected *** these,the mutant K140-22,specifically targeting the 7th exon,is distinguished by its substantially reduced Cd ***,enzyme assays of the antioxidant defense system in both roots and shoots of K140-22 revealed its enhanced antioxidant activity,which contributes to elucidating the molecular mechanisms of plant tolerance to heavy metal ***,this mutant also maintained equivalent agronomic traits and seed quality,which highlights its potential as a germplasm resource for rapeseed breeding for low Cd accumulation and elevating rapeseed economic value in Cd-contaminated soil.

关键词： Brassica napus Cd accumulation BnaNRAMP1-edited lines gene editing

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Transcriptome analysis shows that Glomus versiforme decrease the accumulation and toxicity of cadmium in Ipomoea aquatic Forsk

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Environmental science and Pollution Research 2024年第30期31卷 43023-43036页

作者： Xu, Pei-Xuan Li, Ren-Jie Zhu, Qi-Ying Jing, Yuan-Xiao Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization Key Laboratory of Ecology and Environmental Science in Guangdong Higher Education College of Life Sciences South China Normal University Guangzhou510631 China

So far, the physiological and molecular mechanisms of the impact of arbuscular mycorrhizal fungus (AMF) on Cd absorption, transport and detoxification in Ipomoea aquatica (water spinach) are still unclear. In the present study, a pot experiment was performed to investigate the impact of AMF-Glomus versiforme (Gv) on the photosynthetic characteristics, Cd uptake, antioxidative system and transcriptome in water spinach in the soils supplemented with 5 mg Cd kg−1. Gv inoculation improved significantly the photosynthetic characteristics and growth of water spinach. Furthermore, Gv colonization significantly promoted the activities of catalase (CAT), peroxidase (POD) and glutathione reductase (GR), contents of glutathione (GSH) and ascorbic acid (AsA), and the total antioxidant capacity (TCA), but decreased malondialdehyde (MDA) content in water spinach. In addition, Gv inoculation significantly increased pH in rhizosphere soils and decreased the Cd concentrations and uptakes in water spinach. Importantly, 2670 differentially expressed genes (DEGs) were screened in water spinach root colonized with Gv in 5 mg Cd kg−1 soil, of which 2008 DEGs were upregulated and 662 DEGs were downregulated. Especially, the expression levels of POD, CAT, GR, dehydroascorbate reductase 2 (DHAR2), glutathione S-transferase U8 (GSTU8) and glutathione synthetase (GSHS) and cytochrome P450 (Cyt P450) genes were significantly up-regulated in water spinach inoculated with Gv. Meanwhile, the plant cadmium resistance protein 2 (PCR2), metal tolerance protein 4 (MTP4), ATP-binding cassette transporter C family member (ABCC), ABC-yeast cadmium factor 1 (ABC-YCF1) and metallothionein (MT) genes were also up-regulated in mycorrhizal water spinach. Our results firstly elucidated the mechanism by which AMF reduced the uptake and phytotoxicity of Cd in water spinach through a transcriptome analysis. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

关键词： Detoxification

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Role of c-Jun NH_(2)-terminal kinase-mediated mitogen-activated protein kinase pathway in response to pesticides in Apis cerana cerana

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Insect science 2023年第1期30卷 47-64页

作者： Xiao-Jing Niu Li-Jun Wang Hui Meng Hong-Fang Wang Bao-Hua Xu Chen Wang State Key Laboratory of Crop Biology College of Life SciencesShandong Agricultural UniversityTaianShandong ProvinceChina College of Animal Science and Technology Shandong Agricultural UniversityTaianShandong ProvinceChina

The mitogen-activated protein kinase(MAPK)cascade pathway plays an important role in regulating stress *** function of the c-Jun NH_(2)-terminal kinase(JNK),a component of the MAPK cascade pathway,in Apis cerana cerana(Acc)remains ***,JNK was isolated and identified from *** analyses revealed there is a typical serine/threonine protein kinase catalytic domain in the AccJNK *** expression profile analysis showed that AccJNK was significantly induced by pesticide *** further explore the functional mechanisms of AccJNK,a yeast 2-hybrid screen was performed,activator protein-1(AP-1)was screened as the interaction partner of AccJNK,and the interaction relationship was further verified by pull-down *** real-time polymerase chain reaction showed the expression pattern of AccAP-I was similar to that of *** a knockdown of AccJNK or AccAP-I by RNA interference,the survival rate of Acc after pesticide treatments ***,the expression levels of antioxidant-related genes and the activities of antioxidant enzymes increased,suggesting that the knockdown of AccJNK or AccAP-I increased the antioxidant capacity of *** study revealed that the JNK-mediated MAPK pathway responds to pesticide stress by altering the antioxidant capacity of Acc.

关键词： Apis cerana cerana MAPK cascade oxidative stress pesticide stress RNA interference

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