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Emerging nanozymes for potentiating radiotherapy and radiation protection

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Chinese Chemical Letters 2022年第7期33卷 3315-3324页

作者： Yu Chong Jiayu Ning Shengyi Min Jiaquan Ye Cuicui Ge State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences(RAD-X)Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123China

While radiotherapy is a mainstay therapeutic modality for malignant tumor,the intrinsic tumor resistance to radiotherapy,as well as the concomitant radiation injury to adjacent healthy tissues,greatly limits the efficacy of cancer radiotherapy.As a result,the development of novel radioenhancers and radioprotectants is highly desired for clinical radiotherapy.In recent years,nanozymes have inspired ever-growing research interest because of their multi-enzyme activities and microenvironment-responsive feature.In view of the significant progress of nanozymes in radiation medicine,we,in this review,systematically illustrate the impressive progress of nanozymes for potentiating radiotherapy and radiation protection.First,the types of nanozymes used in tumor radiotherapy are briefly discussed.Subsequently,the main strategies of nanozymes to enhance the radiotherapy efficiency,including promoting the generation of reactive oxygen species(ROS),relieving hypoxia in tumor microenvironment and combining with other cancer therapeutic regimens,are summarized.Finally,the advances of typical nanozymes for preventing radiation-induced hematopoietic damage and gastrointestinal damage are highlighted.

关键词： Nanozyme radiation therapy Radiosensitization ROS Hypoxia

FeF_(x) and Fe_(2)ZrO_(5) Co-modified hematite for highly efficient solar water splitting

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Journal of Energy Chemistry 2022年第6期31卷 414-420,I0012页

作者： Xiaoquan Zhao Cheng Lu Shuo Li Yufeng Chen Gaoteng Zhang Duo Zhang Kun Feng Jun Zhong Institute of Functional Nano and Soft Materials laboratory(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou 215123JiangsuChina State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and ProtectionSoochow UniversitySuzhou 215123JiangsuChina

Hematite is an excellent catalyst for photoelectrochemical (PEC) water splitting but its performance has been highly limited by poor conductivity and high charge recombination.Here by a Zr-based treatment to create bulk Fe_(2)ZrO_(5) in hematite and a F-based treatment to form an ultrathin surface FeF_(x) layer,the charge transfer can be highly improved and the charge recombination can be significantly suppressed.As a result,the FeF_(x) /Zr-Fe_(2)O_(3) photoanode presents an enhanced PEC performance with a photocurrent density of 2.43 m A/cm^(2)at 1.23 V vs.RHE,which is around 3 times higher than that of the pristine Fe_(2)O_(3) .The FeF_(x) /Zr-Fe_(2)O_(3) photoanode also shows a low onset potential of 0.77 V vs.RHE (100 mV lower than the pristine hematite).The performance is much higher than that of the sample treated by Zr or F alone,suggesting the synergistic effect between bulk Fe_(2)ZrO_(5) and surface FeF_(x) .By coupling with the FeNiOOH co-catalyst,the final photoanode can achieve a high photocurrent density of 2.81 mA/cm^(2) at 1.23 V vs.RHE.The novel design of Zr and F co-modified hematite can be used as a promising way to prepare efficient catalysts for solar water splitting.

关键词： Hematite Fe_(2)ZrO_(5) Fluorination Solar water splitting

RegVar:Tissue-specific Prioritization of Non-coding Regulatory Variants

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Genomics, Proteomics & Bioinformatics 2023年第2期21卷 385-395页

作者： Hao Lu Luyu Ma Cheng Quan Lei Li Yiming Lu Gangqiao Zhou Chenggang Zhang Beijing Institute of radiation medicine State Key Laboratory of ProteomicsBeijing 100850China

Non-coding genomic variants constitute the majority of trait-associated genome variations;however,the identification of functional non-coding variants is still a challenge in human genetics,and a method for systematically assessing the impact of regulatory variants on gene expression and linking these regulatory variants to potential target genes is still lacking.Here,we introduce a deep neural network(DNN)-based computational framework,RegVar,which can accurately predict the tissue-specific impact of non-coding regulatory variants on target genes.We show that by robustly learning the genomic characteristics of massive variant-gene expression associations in a variety of human tissues,RegVar vastly surpasses all current non-coding variant prioritization methods in predicting regulatory variants under different circumstances.The unique features of RegVar make it an excellent framework for assessing the regulatory impact of any variant on its putative target genes in a variety of tissues.

关键词： Non-coding variant Variantprioritization Expressionregulation Expressionquantitative trait locus Deep neural network

Dinitrogen cleavage and hydrogenation to ammonia with a uranium complex

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National Science Review 2023年第2期10卷 165-173页

作者： Xiaoqing Xin Iskander Douair Yue Zhao Shuao Wang Laurent Maron Congqing Zhu state key laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials School of Chemistry and Chemical EngineeringNanjing University School of medicine and Holistic Integrative medicine Nanjing University of Chinese Medicine LPCNO CNRS and INSA Université Paul Sabatier State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow University

The Haber-Bosch process produces ammonia(NH3) from dinitrogen(N2) and dihydrogen(H2),but re quires high temperature and pressure.Before iron-based catalysts were exploited in the current industrial Haber-Bosch process,uranium-based materials served as effective catalysts for production of NH3from N2.Although some molecular uranium complexes are known to be capable of combining with N2,further hydrogenation with H2forming NH3has not been reported to date.Here,we describe the first example of N2cleavage and hydrogenation with H2to NH3with a molecular uranium complex.The N2cleavage product contains three uranium centers that are bridged by three imido μ2-NH ligands and one nitridoμ3-N ligand.Labeling experiments with15N demonstrate that the nitrido ligand in the product originates from N2.Reaction of the N2-cleaved complex with H2or H+forms NH3under mild conditions.A synthetic cycle has been established by the reaction of the N2-cleaved complex with trimethylsilyl chloride.The isolation of this trinuclear imido-nitrido product implies that a multi-metallic uranium assembly plays an important role in the activation of N2.

关键词： N

PIG3 downregulation enhances the radiosensitivity of NSCLC cells by promoting G_(2)/M cell cycle arrest and apoptosis

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radiation medicine and protection 2023年第1期4卷 19-25页

作者： Hao Zhou Linfeng Tang Zeng-Fu Shang Ping-Kun Zhou Ming Li State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and ProtectionMedical College of Soochow UniversitySuzhou 215123China Collaborative Innovation Center of radiation medicine of Jiangsu Higher Education Institutions Soochow UniversitySuzhou 215123China Department of radiation Toxicology and Oncology Beijing Key Laboratory for RadiobiologyBeijing Institute of Radiation MedicineBeijing 100850China

Objective:To investigate the mechanism of p53-induced gene 3(PIG3)-regulation of radioresistance in human non-small cell lung cancer(NSCLC)cells,in order to explore new biomarkers and therapeutic targets to combat radioresistance and improve the 5-year survival rate.Methods:The PIG3 gene was knocked down in A549 cells using siRNA,and was overexpressed in H1299 cells using a PIG3 expression plasmid.After confirming PIG3 knockdown and overexpression through the Western blot analysis,the radiosensitivity,DNA damage,cell cycle distribution,and apoptosis in these cells were analyzed using colony formation assay,immunofluorescence staining forγH2AX,and flow cytometry,respectively.Results:PIG3 silencing markedly increased the radiosensitivity of NSCLC cells,with radiosensitization ratios of 1.12 and 1.25.Compared with the corresponding negative control,PIG3 knockdown significantly enhanced G2/M phase arrest(siNC:26.12±2.50,siPIG3#1:34.98±4.19,siPIG3#2:37.79±3.53,Pradiation-induced apoptosis(siNC:14.61±1.85,siPIG3#1:17.26±1.14,siPIG3#2:20.70±2.04,Pradiation(P<0.05).Conversely,PIG3 overexpression markedly decreased the radiosensitivity of NSCLC cells,as evidenced by the reduction of G2/M phase arrest(NC:33.18±2.11 vs.PIG3:24.21±3.09,P<0.05)and apoptosis(NC:15.49±0.56 vs.PIG3:12.79±0.29,P<0.05),and increased DNA damage(P<0.05).Conclusions:PIG3 downregulation increases the radiosensitivity of NSCLC cells,and PIG3-upregulation leads to the progression in radioresistance.Therefore,PIG3 is a potential target for radiotherapy for NSCLC.

关键词： Radioresistance PIG3 Non-small cell lung cancer Cell cycle Apoptosis

Flexible interdigitated layered framework with multiple accessible active sites for high-performance CH_(3)I capture

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Science China Chemistry 2024年第5期67卷 1569-1577页

作者： Bo Tai Baoyu Li Linwei He Zhonglin Ma Shujing Lin Mingxing Zhang Junchang Chen Fuqi Wu Long Chen Xing Dai Fuyin Ma Zhifang Chai Shuao Wang State Key Laboratory of Radiation Medicine and Protection School for Radiological and interdisciplinary Sciences(RAD-X)and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123China

The development of adsorbent materials for effective capture of radioactive iodomethane(CH_(3)I) from the off-gas of used nuclear fuel reprocessing, remains a significant and challenging line of research because currently state-of-art adsorbents still suffer from low binding affinity with CH_(3)I. Here, we proposed a brand-new adsorption topological structure by developing a 2D interdigitated layered framework, named SCU-20, featuring slide-like channel with multiple active sites for CH_(3)I capture. The responsive rotating-adaptive aperture of SCU-20 enables the optimal utilization of all active sites within the pore for highly selective recognition and capture of CH_(3)I. A record-breaking CH_(3)I uptake capacity of 1.84 g/g was achieved under static sorption conditions with saturated CH_(3)I vapor. Both experimental and theoretical findings demonstrated that the exceptional uptake of SCU-20 towards CH_(3)I can be attributed to the confined physical electrostatic adsorption of F sites, coupled with the chemical nitrogen methylation reaction with uncoordinated N atoms of pyrazine. Moreover, dynamic CH_(3)I uptake capacity potentially allows for the capture of CH_(3)I in simulated real-world off gas reprocessing conditions. This study highlights the potential of SCU-20 as a promising candidate for efficient capture of iodine species and contributes to the development of effective solutions for radioactive iodine remediation.

关键词： 2D interdigitated layered framework iodomethane dual-sites electrostatic interaction physisorption and chemisorption

Orchestration of the balance in liver metabolism by c-Fos

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Orchestration of the balance in liver metabolism by c-Fos

增强T/NK细胞抗肿瘤免疫治疗的小结构大方案

中国毒理学会第十次全国毒理学大会

作者： Zhisen Zhang Lei Chang State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection (SRMP) of Soochow University

Non-alcoholic fatty liver disease(NAFLD) is a dietary disease associate with obesity and diabetes mellitus, which can develop into nonalcoholic steatohepatitis(NASH) without effective restrictions. However, there is no therapies available. People who favor high calories food and sugar water are more susceptible to NAFLD, which may due to the disequilibrium of lipid accumulation and metabolism. Many HCC patients express c-Fos, a component of the AP-1 transcription factor. Here, we found that when treated with high fat diet, liver specific c-Fos knock out could alleviate the body weight gain and lipid aggregation through inhibiting the sterol regulatory element-binding protein-1c(SREBP-1c) cleavage. SREBP-1c is a core transcription factor that regulate the lipid synthesis, and the cleaved SREBP-1c could translocate into nucleus to orchestrate the de novo lipogenesis(DNL) related genes such as Fasn, Scd-1. Our data identifies the component of AP-1 transcription factor, c-Fos as a key regulator upstream of lipid synthesis and provide a potential target for the NAFLD treatment. METHODS Animals: The c-Fosfl/fl, AlbCreERT2mice were maintained on a C57BL/6J background, and crossed to generate the c-FosΔLimice. Mice were housed in a specific pathogen-free facility, with normal or high fat diet(60% kCal/fat HFD,D12492, Research Diets) and water ad libitum, in a 12 hr light/12 hr dark cycle. If not indicated specifically, 6-8 weeks male mice was fed with HFD. HISTOLOGY H&E staining were performed using standard procedures. qRT-PCR/Immunoblot Analysis: qRT-PCR was performed on Life Technologies ViiA 7 with SYBR mix. Relative expression levels were calculated using the ΔCtmethod. All the data were normalized to 36b4, a house keeping gene. Western Blot analysis was performed with standard protocols and following antibodies: β-Actin, Srebp1. CONCLUSION Liver specific knock out of c-Fos could prevent mice from non-alcoholic fatty liver disease through downregulating the cleavage of SREBP1 and its target genes that control the de

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Science Bulletin 2024年第4期69卷 437-440页

作者：王婷婷张浩韩要宝韩孟晓李桢 Center for Molecular Imaging and Nuclear medicine State Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences(RAD-X)Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123China

The anti-tumor immunotherapy is primarily reliant on the host’s own immune system.After treatment with immunotherapy,the tumor can be inhibited for a longer term potentially or even cured completely because of the systemic immunotherapy response.This response can trigger a long-term memory to inhibit the recurrence and malignant progression of tumor.

关键词： inhibited immunotherapy tumor

The role of crm-1 in ionizing radiation-induced nervous system dysfunction in Caenorhabditis elegans

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Neural Regeneration Research 2023年第6期18卷 1386-1392页

作者： Hui-Qiang Long Jin Gao Shu-Qing He Jian-Fang Han Yu Tu Na Chen Suzhou Medical College of Soochow University SuzhouJiangsu ProvinceChina State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and ProtectionSoochow UniversitySuzhouJiangsu ProvinceChina Collaborative Innovation Center of radiation medicine of Jiangsu Higher Education Institutions SuzhouJiangsu ProvinceChina

Ionizing radiation can cause changes in nervous system function.However,the underlying mechanism remains unclear.In this study,Coenorhabditis elegans(C.elegans)was irradiated with 75 Gy of ^(60)Co whole-body γ radiation.Behavioral indicators(head thrashes,touch avoidance,and foraging),and the development of dopaminergic neurons related to behavioral function,were evaluated to assess the effects of ionizing radiation on nervous system function in C.elegans.Various behaviors were impaired after whole-body irradiation and degeneration of dopamine neurons was observed.This suggests that 75 Gy of γ radiation is sufficient to induce nervous system dysfunction.The genes nhr-76 and crm-1,which are reported to be related to nervous system function in human and mouse,were screened by transcriptome sequencing and bioinformatics analysis after irradiation or sham irradiation.The expression levels of these two genes were increased after radiation.Next,RNAi technology was used to inhibit the expression of crm-1,a gene whose homologs are associated with motor neuron development in other species.Downregulation of crm-1 expression effectively alleviated the deleterious effects of ionizing radiation on head thrashes and touch avoidance.It was also found that the expression level of crm-1 was regulated by the nuclear receptor gene nhr-76.The results of this study suggest that knocking down the expression level of nhr-76 can reduce the expression level of crm-1,while down-regulating the expression level of crm-1 can alleviate behavioral disorders induced by ionizing radiation.Therefore,inhibition of crm-1 may be of interest as a potential therapeutic target for ionizing radiation-induced neurological dysfunction.

关键词： behavior Caenorhabditis elegans degeneration disorder dysfunction nerve injury nervous system neurodevelopment neuron radiation