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In situ autophagy regulation in synergy with phototherapy for breast cancer treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2317-2332页

作者： Huijuan zhang Xiangyang Xuan Yaping Wang Zijun Qi kexuan Cao Yingmei Tian Chaoqun Wang Junbiao Chang Zhenzhong zhang Lin Hou School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases Zhengzhou 450001China Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou 450001China School of Chemistry and Molecular Engineering Zhengzhou UniversityZhengzhou 450001China

Autophagy is an important factor in reducing the efficacy of tumor phototherapy(including PTT and PDT).Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/*** project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor *** achieve this goal,we first synthesized TRANSFERRIN(Tf)biomimetic mineralized nano-tellurium(Tf-Te)as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te *** autophagy inhibitor hydroxychloroquine(HCQ)and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/*** entering breast cancer cells through the“self-guidance system”,Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation,to efficiently induce PTT/PDT ***,the disulfide bond broke down in response to GSH,and the nanoparticles disintegrated to release Fe2+and HCQ at fixed *** simultaneously induce lysosomal alkalinization and increased osmotic pressure,effectively inhibit autophagy,and synergistically enhance the therapeutic effect of *** vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6%on 4T1 tumor-bearing *** multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

关键词： Autophagy Tumor phototherapy Synergistic sensitization HCQ TRANSFERRIN Disulfide bond reconstruction GSH Biomimetic mineralized nano-tellurium

The transcription factors TLR1 and TLR2 negatively regulate trichome density and artemisinin levels in Artemisia annua

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Journal of Integrative Plant Biology 2022年第6期64卷 1212-1228页

作者： Zongyou Lv JinXing Li Shi Qiu Fei Qi Hang Su Qitao Bu Rui Jiang kexuan Tang Lei zhang Wansheng Chen Research and Development Center of Chinese Medicine Resources and Biotechnology Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pharmacy Changzheng HospitalSecond Military Medical UniversityShanghai 200003China Department of Pharmaceutical Botany School of PharmacySecond Military Medical UniversityShanghai 200433China Joint International Research Laboratory of Metabolic&Developmental Sciences Key Laboratory of Urban Agriculture(South)Ministry of AgriculturePlant Biotechnology Research CenterFudan‐SJTU‐Nottingham Plant Biotechnology R&D CenterShanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Subtropical Silviculture Zhejiang A&F UniversityHangzhou 311300China

The important antimalarial drug artemisinin is biosynthesized and stored in Artemisia annua glandular trichomes and the artemisinin content correlates with trichome density;however,the factors affecting trichome development are largely ***,we demonstrate that the *** R2R3 MYB transcription factor TrichomeLess Regulator 1(TLR1)negatively regulates trichome *** ***,TLR1 overexpression lines had 44.7%–64.0%lower trichome density and 11.5%–49.4%lower artemisinin contents and TLR1-RNAi lines had 33%–93.3%higher trichome density and 32.2%–84.0%higher artemisinin contents compared with non-transgenic ***1 also negatively regulates the expression of anthocyanin biosynthetic pathway genes in *** heterologously expressed in Arabidopsis thaliana,TLR1 interacts with GLABROUS3a,positive regulator of trichome development,and represses trichome *** two-hybrid and pull-down assays indicated that TLR1 interacts with the WUSCHEL homeobox(WOX)protein AaWOX1,which interacts with the LEAFY-like transcription factor ***2 overexpression in Arabidopsis and *** showed that TLR2 reduces trichome development by reducing gibberellin ***,artemisinin contents were 19%–43%lower in TLR2-overexpressing *** plants compared to *** data indicate that TLR1 and TLR2 negatively regulate trichome density by lowering gibberellin levels and may enable approaches to enhance artemisinin yields.

关键词： artemisinin Artemisia annua L. LFY MYB transcription factor trichome WOX

Nature-inspired materials and designs for flexible lithium-ion batteries

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Carbon Energy 2022年第5期4卷 878-900页

作者： Heng Li Huibo Wang Dan Chan Zhu Xu kexuan Wang Mingzheng Ge Yanyan zhang Shi Chen Yuxin Tang State Key Laboratory of High-Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghaiChina Institute of Applied Physics and Materials Engineering University of MacaoMacao SARChina College of Chemical Engineering Fuzhou UniversityFuzhouChina School of Textile and Clothing Nantong UniversityNantongChina

Flexible lithium-ion batteries(FLBs)are of critical importance to the seamless power supply of flexible and wearable electronic ***,the simultaneous acquirements of mechanical deformability and high energy density remain a major challenge for *** billions of years of evolutions,many plants and animals have developed unique compositional and structural characteristics,which enable them to have both high mechanical deformability and robustness to cope with the complex and stressful *** by nature,many new materials and designs emerge recently to achieve mechanically flexible and high storage capacity of lithiumion batteries at the same ***,we summarize these novel FLBs inspired by natural and biological materials and *** first give a brief introduction to the fundamentals and challenges of ***,we highlight the latest achievements based on nature inspiration,including fiber-shaped FLBs,origami and kirigami-derived FLBs,and the nature-inspired structural designs in ***,we discuss the current status,remaining challenges,and future opportunities for the development of *** concise yet focused review highlights current inspirations in FLBs and wishes to broaden our view of FLB materials and designs,which can be directly“borrowed”from nature.

关键词： bioinspired materials flexibility lithium-ion batteries structural design

Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1500-1513页

作者： Guoping Shu Yueli Tang Mingyuan Yuan Ning Wei Fangyuan zhang Chunxian Yang Xiaozhong Lan Min Chen kexuan Tang Lien Xiang Zhihua Liao Key Laboratory of Eco-environments in Three Gorges Reservoir Region(Ministry of Education) Chongqing Engineering Research Centre for Sweet PotatoSWU-TAAHC Medicinal Plant Joint R&D CentreSchool of Life SciencesSouthwest UniversityChongqing 400715China TAAHC-SWU Medicinal Plant Joint R&D Centre Xizang Agricultural and Husbandry CollegeNyingchi 860000China College of Pharmaceutical Sciences Southwest UniversityChongqing 400715China College of Environmental Science and Engineering China West Normal UniversityNanchong 637009China

Artemisia annua is the main natural source of artemisinin *** ***,extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid(ABA)treatment can increase artemisinin ***-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis ***,we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1,which AabZIP1 does not directly ***,it was found that AabZIP1 up-regulates AaMYC2expression through direct binding to its promoter,and that AaMYC2 binds to the promoter of AaALDH1to activate its *** addition,AabZIP1 directly transactivates wax biosynthesis genes AaCER1and *** biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression,whereas they were significantly decreased in RNAi-AabZIP1 ***,we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis,which may have general *** have also identified AabZIP1 as a promising candidate gene for the development of *** plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

关键词： Artemisia annua AabZIP1 AaMYC2 Artemisinin biosynthesis Drought tolerance Wax biosynthesis

Realizing the highly reversible Zn^(2+)and Na^(+) dual ions storage in high-crystallinity nickel hexacyanoferrate microcubes for aqueous zinc-ion batteries

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Journal of Materials Science & Technology 2023年第33期164卷 102-110页

作者： kexuan Wang Zhu Xu Heng Li Huibo Wang Mingzheng Ge Jilei Liu Shengwen Li Zekun Hu Mengyu Zhu Yanyan zhang Yuxin Tang Shi Chen Institute of Applied Physics and Materials Engineering University of MacaoMacao SAR 999078China State Key Laboratory of High-Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050China College of Materials Science and Engineering Hunan Joint International Laboratory of Advanced Materials and Technology of Clean EnergyHunan Province Key Laboratory for Advanced Carbon Materials and Applied TechnologyHunan UniversityChangsha 410082China College of Chemical Engineering Fuzhou UniversityFuzhou 350116China

Prussian blue analogues(PBAs)with the 3D open framework are regarded as promising cathode candidates for aqueous Zinc ion batteries(ZIBs).Among various PBAs,nickel hexacyanoferrate(NiHCF)has attracted considerable attention because of its high operating voltage and economic ***,the cyclability of NiHCF is unsatisfactory due to poor structural stability during Zn^(2+) ions insertion/***,the ion storage mechanism of NiHCF in aqueous electrolytes has not been fully revealed ***,high-crystallinity NiHCF(HC-NiHCF)microcubes with improved structural stability and larger crystal plane spacing are *** the first time,highly reversible Zn2+ions and Na+ions co-insertion/extraction are achieved for the HC-NiHCF microcubes in mixed aqueous electrolyte,as evidenced by various observations including two separated discharge plateaus and sequential changes of Na 1s and Zn 2p signals in ex-situ X-ray photoelectron spectroscopy(XPS).As a result,a high specific capacity of 73.9 mAh g^(−1) is obtained for the HC-NiHCF microcubes at 0.1 A g−1,combined with enhanced cycle stability(75%vs.16.4%)over 1000 cycles at 2 A g^(−1).The reversible Zn^(2+) ions and Na+ions co-insertion in HC-NiHCF microcubes reveals a new ion storage mechanism of Ni-based PBAs in aqueous electrolytes.

关键词： Aqueous zinc-ion batteries Prussian blue analogues Ion storage mechanism Dual ions storage High crystallinity

The AaBBX21–AaHY5 module mediates light-regulated artemisinin biosynthesis in Artemisia annua L.

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Journal of Integrative Plant Biology 2024年第8期66卷 1735-1751页

作者： Weizhi He Hang Liu zhangkuanyu Wu Qing Miao Xinyi Hu Xin Yan Hangyu Wen Yaojie zhang Xueqing Fu Li Ren kexuan Tang Ling Li Frontiers Science Center for Transformative Molecules Joint International ResearchLaboratory of Metabolic and Developmental SciencesKey Laboratory of Urban Agriculture(South)Ministry of AgriculturePlant Biotechnology Research CenterFudan-SJTU-Nottingham Plant Biotechnology R&D CenterSchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Institute for Agri-Food Standards and Testing Technology Shanghai Academy of Agricultural SciencesShanghai 201403China

The sesquiterpene lactone artemisinin is an important anti-malarial component produced by the glandular secretory trichomes of sweet wormwood(Artemisia annua L.).Light was previously shown to promote artemisinin production,but the underlying regulatory mechanism remains *** this study,we demonstrate that ELONGATED HYPOCOTYL5(HY5),a central transcription factor in the light signaling pathway,cannot promote artemisinin biosynthesis on its own,as the binding of AaHY5 to the promoters of artemisinin biosynthetic genes failed to activate their *** analysis and yeast two-hybrid screening revealed the B-box transcription factor AaBBX21 as a potential interactor with ***21 showed a trichome-specific expression ***,the AaBBX21–AaHY5 complex cooperatively activated transcription from the promoters of the downstream genes AaGSW1,AaMYB108,and AaORA,encoding positive regulators of artemisinin ***,AaHY5 and AaBBX21 physically interacted with the *** E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1(COP1).In the dark,AaCOP1 decreased the accumulation of AaHY5 and AaBBX21 and repressed the activation of genes downstream of the AaHY5–AaBBX21 complex,explaining the enhanced production of artemisinin upon light *** study provides insights into the central regulatory mechanism by which light governs terpenoid biosynthesis in the plant kingdom.

关键词： AaBBX21 AaHY5 AaCOP1 Artemisia annua L. artemisinin biosynthesis light

AaWRKY17, a positive regulator of artemisinin biosynthesis, is involved in resistance to Pseudomonas syringae in Artemisia annua

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Horticulture Research 2021年第1期8卷 2926-2936页

作者： Tiantian Chen Yongpeng Li Lihui Xie Xiaolong Hao Hang Liu Wei Qin Chen Wang Xin Yan Kuanyu Wu-zhang Xinghao Yao Bowen Peng Yaojie zhang Xueqing Fu Ling Li kexuan Tang Joint International Research Laboratory of Metabolic and Developmental Sciences Frontiers Science Center for Transformative MoleculesPlant Biotechnology Research CenterFudan-SJTU-Nottingham Plant Biotechnology R&D CenterSchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Laboratory of Medicinal Plant Biotechnology College of PharmacyZhejiang Chinese Medical UniversityHangzhou 310053China

Artemisia annua,a traditional Chinese medicinal plant,remains the only plant source for artemisinin production,yet few genes have been identified to be involved in both the response to biotic stresses,such as pathogens,and artemisinin ***,we isolated and identified the WRKY transcription factor(TF)AaWRKY17,which could significantly increase the artemisinin content and resistance to Pseudomonas syringae in *** one-hybrid(Y1H),dual-luciferase(dual-LUC),and electrophoretic mobility shift assay(EMSA)results showed that AaWRKY17 directly bound to the W-box motifs in the promoter region of the artemisinin biosynthetic pathway gene amorpha-4,11-diene synthase(ADS)and promoted its ***-time quantitative PCR(RT-qPCR)analysis revealed that the transcript levels of two defense marker genes,Pathogenesis-Related 5(PR5)and NDR1/HIN1-LIKE 10(NHL10),were greatly increased in AaWRKY17-overexpressing transgenic *** ***,overexpression of AaWRKY17 in *** resulted in decreased susceptibility to *** results indicated that AaWRKY17 acted as a positive regulator in response to *** ***,our findings demonstrated that the novel WRKY transcription factor AaWRKY17 could potentially be used in transgenic breeding to improve the content of artemisinin and pathogen tolerance in ***.

关键词： expression AaW resistance

Two-photon 3D printed spring-based Fabry-Pérot cavity resonator for acoustic wave detection and imaging

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Photonics Research 2023年第5期11卷 780-786页

作者： HEMING WEI zhangLI WU kexuan SUN HAIYAN zhang CHEN WANG KEMIN WANG TIAN YANG FUFEI PANG XIAOBEI zhang TINGYUN WANG SRIDHAR KRISHNASWAMY Key Laboratory of Specialty Fiber Optics and Optical Access Networks Joint International Research Laboratory of Specialty Fiber Optics and Advanced CommunicationShanghai UniversityShanghai 200444China School of Mechatronic Engineering and Automation Shanghai UniversityShanghai 200444China State Key Laboratory of Advanced Optical Communication Systems and Networks Key Laboratory for Thin Film and Microfabrication of the Ministry of EducationSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Center for Smart Structures and Materials Northwestern UniversityEvanstonIllinois 60208USA

Optical fiber microresonators have attracted considerable interest for acoustic detection because of their compact size and high optical ***,we have proposed,designed,and fabricated a spring-based Fabry-Pérot cavity microresonator for highly sensitive acoustic *** observed two resonator vibration modes:one relating to the spring vibration state and the other determined by the point-clamped circular plate vibration *** found that the vibration modes can be coupled and optimized by changing the structure *** proposed resonator is directly 3D printed on an optical fiber tip through two-photon polymerization and is used for acoustic detection and *** experiments show that the device exhibits a high sensitivity and low noise equivalent acoustic signal level of 2.39 mPa∕Hz^(1∕2)at 75 kHz that can detect weak acoustic waves,which can be used for underwater object *** results demonstrate that the proposed work has great potential in acoustic detection and biomedical imaging applications.

关键词： resonator fiber cavity

The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis

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Molecular Plant 2018年第6期11卷 776-788页

作者： Qian Shen Lida zhang Zhihua Liao Shengyue Wang Tingxiang Yan Pu Shi Meng Liu Xueqing Fu Qifang Pan Yuliang Wang Zongyou Lv Xu Lu Fangyuan zhang Weimin Jiang Yanan Ma Minghui Chen Xiaolong Hao Ling Li Yueli Tang Gang Lv Yan Zhou Xiaofen Sun Peter E. Brodelius Jocelyn K.C. Rose kexuan Tang Joint International Research Laboratory of Metabolic & Developmental Sciences Key Laboratory of Urban Agriculture (South) Ministry of Agriculture Plant Biotechnology Research Center Fudan-SJTU-Nottingham Plant Biotechnology R&D Center School of Agriculture and Biology Shanghai Jiao Tong University Shanghai 200240 China SWU-TAAHC Medicinal Plant Joint R&D Centre School of Life Sciences Southwest University Chongqing 400715 China Chinese National Human Genome Center at Shanghai Shanghai 201203 China Plant Biology Section School of Integrative Plant Science Cornell University Ithaca NY 14853 USA Department of Chemistry and Biomedical Sciences Linnaeus University 39182 Kalmar Sweden State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing 211198 China

Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemi- sinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on compre- hensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the chal- lenge of increasing global demand of artemisinin.

关键词： Artemisia annua artemisinin genome evolution transcriptome metabolic engineering