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Acceptor-engineering tailored type-Ⅰ photosensitizer with aggregation-induced NIR-II emission for cancer multimodal phototheranostics

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science China Chemistry 2024年第8期67卷 2647-2660页

作者： Jiangao Li Niu Niu Deliang Wang Xue Liu Yi Qin Lei Wang Ben Zhong Tang Dong Wang Center for AIE Research Shenzhen Key Laboratory of Polymer Science and TechnologyGuangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China Guangzhou Municipal and Guangdong Provincial Key laboratory of Molecular Target Clinical Pharmacologythe State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Shenzhen 518172China

Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline(ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared(NIR-II) emission. Experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole(BBTD) and 6,7-diphenylthiadiazoloquinoxaline(DPTQ), ITQ-based photosensitizer(TITQ) showed superior aggregation-induced emission(AIE) characteristics, much stronger type-I reactive oxygen species(ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.

关键词： phototheranostics aggregation-induced emission NIR-Ⅱfluorescence acceptor engineering photodynamic-photothermal therapy

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Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy

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Chinese Chemical Letters 2024年第8期35卷 229-234页

作者： Jin Wang Xiaoyan Pan Junyu Zhang Qingqing Zhang Yanchen Li Weiwei Guo Jie Zhang School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China Center of Advanced pharmaceuticals and Biomaterials State Key Laboratory of Natural MedicineChina Pharmaceutical UniversityNanjing 210009China

Tumor vascular normalization has emerged as a promising strategy for synergistic therapy *** on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic ***,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic ***,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.

关键词： Tumor vasculature normalization Diagnosis and treatment Cytotoxicity Depleting glutathione Ferroptosis Immune activation

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing Key laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier science Center for Stem Cell Research School of Life Sciences and Technology Tongji University School of pharmaceutical science Wenzhou Medical University Institute of Life sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

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ZnGa_(2)S_(4):an infrared nonlinear optical material with large second-harmonic generation response and wide band gap

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Rare Metals 2024年第1期43卷 395-401页

作者： Chen-Yang Zhang Xiao-Nan Niu Yan-Feng Wei Shu-Xing Zhou Da-Qing Yang Ying Wang Jian Wang Bing-Bing Zhang College of Chemistry and Materials science Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationState Key Laboratory of New Pharmaceutical Preparations and ExcipientsHebei UniversityBaoding 071002China Hubei Key laboratory of Low Dimensional Optoelectronic Materials and Devices Hubei University of Arts and ScienceXiangyang 441053China Hubei Longzhong laboratory Xiangyang 441000China Department of Chemistry and Biochemistry Wichita State UniversityKansas 67260USA

High-performance nonlinear optical(NLO)crystals are crucial devices to convert wavelength of solid-state *** play an indispensable role in the research of infrared NLO *** this work,ternary chalcogenide ZnGa_(2)S_(4) ... 详细信息

关键词： optical nonlinear harmonic

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Ganoderma Lucidum Spore Oil enhances the effect of cyclophosphamide via inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice

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Journal of Traditional Chinese Medicine 2024年第4期44卷 652-659页

作者： JIANG Zhaojian CAI Hongfei YUAN Cheng CAO Lin XU Wendong HAN Yaming ZHANG Qin LI Jing WANG Qin LIU Juyan Guangzhou HanFang pharmaceutical Company Limited National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug InnovationGuangdong Provincial Key Laboratory of Medicinal Lipids Zhongshan Medical College Sun Yat-sen University Guangzhou pharmaceutical Holdings Limited National Engineering Research Center of pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation

OBJECTIVE: To investigate the effect of Ganoderma Lucidum Spore Oil(GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide(CTX), and explore the underlying ***: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST), urea(UREA) and creatinine(CRE). Western blot analysis was performed to detect Programmed Death-1(PD-1), Programmed Death Ligand 1(PD-L1), Janus Kinase 2(JAK2),phosphorylated Signal Transducer and Activator of Transcription 3(p-STAT3), and Signal Transducer and Activator of Transcription 3(STAT3) expression. RESULTS: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue. CONCLUSION: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumorbearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

关键词： Ganoderma Lucidum Spore Oil carcinoma, hepatocellular cyclophosphamide programmed cell death 1 receptor survival

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Hydrophobic tag tethering degrader as a promising paradigm of protein degradation:Past,present and future perspectives

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Chinese Chemical Letters 2024年第8期35卷 187-200页

作者： Si Ha Jiacheng Zhu Hua Xiang Guoshun Luo State Key laboratory of Natural Medicines and Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China

Small molecule inhibitors have dominated the pharmaceutical landscape for a long time as the primary therapeutic paradigm targeting pathogenic ***,their efficacy heavily relies on the amino acid composition and spatial constitution of proteins,rendering them susceptible to drug resistance and failing to target undruggable *** recent years,the advent of targeted protein degradation(TPD)technology has captured substantial attention from both industry and *** an event-driven mode,TPD offers a novel approach to eliminate pathogenic proteins by promoting their degrada-tion,thus circumventing the limitations associated with traditional small molecule ***-bic tag tethering degrader(HyTTD)technology represents one such TPD approach that is currently in the burgeoning *** employ endogenous protein degradation systems to induce the degrada-tion of target proteins through the proteasome pathway,which displays significant potential for medical *** this review,we provide a comprehensive overview of the development history and the reported mechanism of action of ***,we delve into the physiological roles,structure-activity re-lationships,and medical implications of HyTTDs targeting various disease-associated ***,we propose insights into the challenges that necessitate resolution for the successful development of HyTTDs,with the ultimate goal of initiating a new age of clinical treatment leveraging the immense po-tential of HyTTDs.

关键词： Targeted protein degradation(TPD) Hydrophobic tag Degrader Hydrophobic tag tethering degrader(HyTTD) Targeted therapy

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Genetic association analysis-based networks and classification of human UCP1 polymorphisms

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Genes & Diseases 2024年第3期11卷 63-65页

作者： Donghai Li State Key laboratory of pharmaceutical Biotechnology School of Life SciencesNanjing UniversityJiangsu 210023China

Uncoupling protein 1(UCP1,also known as thermogenin or SLC25A7)plays an important role in the uncoupling of oxidative phosphorylation and adaptive non-shivering thermogenesis(NST).The genomic location for UCP1 is chromosome 4 q31.1:140,555,770--140,568,961(GRCh38/hg38)and its size is 13,192 bases split into 6 *** dbSNP,3650 short genetic variations of human UCP1 are *** this study,UCP1 serves as an example to construct polymorphism-trait networks and enable a func-tional classification.

关键词： classification. UCP1 networks

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Oxygen‑Coordinated Single Mn Sites for Efficient Electrocatalytic Nitrate Reduction to Ammonia

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Nano-Micro Letters 2024年第1期16卷 147-159页

作者： Shengbo Zhang Yuankang Zha Yixing Ye Ke Li Yue Lin Lirong Zheng Guozhong Wang Yunxia Zhang Huajie Yin Tongfei Shi Haimin Zhang laboratory of Materials Physics Centre for Environmental and Energy NanomaterialsAnhui Key Laboratory of Nanomaterials and NanotechnologyCAS Center for Excellence in NanoscienceInstitute of Solid State PhysicsHFIPSChinese Academy of SciencesHefei 230031People’s Republic of China University of science and Technology of China Hefei 230026People’s Republic of China Key laboratory of Agricultural Sensors Ministry of AgricultureSchool of Information and ComputerAnhui Agricultural UniversityHefei 230026People’s Republic of China Hefei National Research Center for Physical sciences at the Microscale University of Science and Technology of ChinaHefei 230026People’s Republic of China Beijing Synchrotron Radiation Facility Institute of High Energy PhysicsChinese Academy of Sciences19B Yuquan RoadBeijing 100049People’s Republic of China

Electrocatalytic nitrate reduction reaction has attracted increasing attention due to its goal of low carbon emission and environmental ***,we report an efficient NitRR catalyst composed of single Mn sites with atomically dispersed oxygen(O)coordination on bacterial cellulose-converted graphitic carbon(Mn-O-C).Evidence of the atomically dispersed Mn-(O-C_(2))_(4)moieties embedding in the exposed basal plane of carbon surface is confirmed by X-ray absorption *** a result,the as-synthesized Mn-O-C catalyst exhibits superior NitRR activity with an NH_(3)yield rate(RNH_(3))of 1476.9±62.6μg h^(−1)cm^(−2)at−0.7 V(*** hydrogen electrode,RHE)and a faradaic efficiency(FE)of 89.0±3.8%at−0.5 V(***)under ambient ***,when evaluated with a practical flow cell,Mn-O-C shows a high RNH_(3)of 3706.7±552.0μg h^(−1)cm^(−2)at a current density of 100 mA cm−2,2.5 times of that in the H *** in situ FT-IR and Raman spectroscopic studies combined with theoretical calculations indicate that the Mn-(O-C_(2))_(4)sites not only effectively inhibit the competitive hydrogen evolution reaction,but also greatly promote the adsorption and activation of nitrate(NO_(3)^(−)),thus boosting both the FE and selectivity of NH_(3)over Mn-(O-C_(2))_(4)sites.

关键词： Atomically dispersed Oxygen coordination Nitrate reduction reaction In situ spectroscopic studies Hydrogen evolution reaction

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Residual levels and health risk assessment of trace metals in Chinese resident diet

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Journal of Environmental sciences 2024年第2期136卷 451-459页

作者： Yubing Dai Shuai Sun Rong Cao Haijun Zhang Jiping Chen Ningbo Geng CAS Key laboratory of Separation science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Shenyang pharmaceutical University Shenyang 110016China University of Chinese Academy of sciences Beijing 100049China

Large-scale metal contamination across the food web is an intractable problem due to increasing pollutant emissions,atmospheric transport,and dry and wet deposition of *** present study focus on several trace metals that are rarely studied but have special toxicity,including tin(Sn),antimony(Sb),gold(Au),hafnium(Hf),palladium(Pd),platinum(Pt),ruthenium(Ru),tellurium(Te)and iridium(Ir).We investigated trace metals residues and distribution characteristics,and further evaluated the potential health risks from major daily food intakes in 33 cities in ***,Sb,Ir,Hf,and Au were frequently detected in food samples with the concentrations ranged from ND(not detected)to 24.78μg/kg ww(wet weight).Eggs exhibited the highest residual level of all detected metals(13.70±14.70μg/kg ww in sum),while the lowest concentrations were observed in vegetables(0.53±0.17μg/kg ww in sum).Sn accounting for more than 50%of the total trace metals concentration in both terrestrial and aquatic animal origin *** terrestrial plant origin foods,Sn and Ir were the most abundant *** and Au were the most abundant elements in egg *** addition,Sb and Ir showed a clear trophic dilution effect in terrestrial environments,while in aquatic ecosystems,Sn,Hf,and Au exhibited obvious trophic amplification *** calculated average estimated daily intake(EDI)via food consumption in five regions of China was 0.09μg/(kg·day),implying the health risk of aforementioned elements was acceptable.

关键词： Trace metals Accumulation characteristics Dietary exposure Estimated daily intake(EDI)

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Decoding aging: examining the non-evolutionary event from an evolutionary perspective

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science China Life sciences 2024年第9期67卷 2026-2029页

作者： Yannan Guo Kang Xu Jianping Cai Zhao Wang Protein science Key laboratory of the Ministry of Education School of Pharmaceutical Sciences Tsinghua University Beijing Institute of Geriatrics Beijing HospitalNational Center of Gerontology National Health Commission

In an era marked by increased longevity,a deeper understanding of the older population is vital. By introducing an overlooked evolutionary perspective on aging, this article challenges traditional biogerontology, which primarily focuses on biological and clinical aspects. It articulately differentiates between chronological and physiological aging, suggesting that aging is an evolutionary byproduct rather than a direct evolutionary event.

关键词： LIFE

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