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Introducing urea into tirapazamine derivatives to enhance anticancer therapy

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National Science Review 2024年第4期11卷 245-253页

作者： Yajun Xu Jianlin lv Chaoying Kong Ya Liu Kun Wang Zhaohui tang Xuesi Chen Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences School of Applied Chemistry and Engineering University of Science and Technology of China

Tirapazamine（TPZ） has been approved for multiple clinical trials relying on its excellent anticancer potential.However,as a typical hypoxia-activated prodrug（HAP）,TPZ did not exhibit survival advantages in Phase Ⅲ clinical trials when used in combination therapy due to the insufficient hypoxia levels in patients' tumors.In this study,to improve the therapeutic effects of TPZ,we first introduced urea to synthesize a series of urea-containing derivatives of TPZ.All urea-containing TPZ derivatives showed increased hypoxic cytotoxicity（9.51-30.85-fold） compared with TPZ,while maintaining hypoxic selectivity.TPZP,one of these derivatives,showed 20-fold higher cytotoxicity than TPZ while maintaining a similar hypoxic cytotoxicity ratio.To highly efficiently deliver TPZP to the tumors and reduce its side effects on healthy tissues,we further prepared TPZP into a nanodrug with fibrin-targeting ability:FT11-TPZP-NPs.CA4-NPs,a vascular disrupting agent,was used to increase the fibrin level within tumors and exacerbate tumor hypoxia.By being combined with CA4-NPs,FT11-TPZP-NPs can accumulate in the hypoxia-aggravated tumors and activate sufficiently to kill tumor cells.After a single-dose treatment,FT11-TPZP-NPs+CA4-NPs showed a high inhibition rate of 98.1% against CT26 tumor models with an initial volume of ～480 mm3and four out of six tumors were completely eliminated;it thereby exerted a significant antitumor effect.This study provides a new strategy for improving the therapeutic effect of TPZ and other HAPs in anticancer therapy.

关键词： tirapazamine vascular disrupting agent hypoxia-activated prodrug combretastatin A4 urea

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

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Zoological Research 2024年第3期45卷 648-662页

作者： Dan Yang Bin-Bin Nie Jin-Gang He zong-Qiang lv Feng-Feng Mo Si-Yi Ouyang Jie Wang Ju-Xiang Chen Tao Tao Department of Anesthesiology Central People’s Hospital of ZhanjiangZhanjiangGuangdong 524045China Key Laboratory of Nuclear Radiation and Nuclear Energy Technology Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsWuhanHubei 430071China Department of Neurosurgery Changhai HospitalNaval Medical UniversityShanghai 200082China Department of Nutrition and Food Hygiene Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Institute of Neuroscience and Brain Diseases/Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceXiangyangHubei 441021China Songjiang Hospital and Songjiang Research Institute Shanghai Jiao Tong University School of MedicineShanghai 201600China Department of Anesthesiology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

关键词： Post-traumatic headache(PTH) Mild traumatic brain injury(mTBI) Metabolic kinetics fMRI Cerebellum

Cooperative NHC/Photoredox Catalysis:Three-Component Reaction of Aroyl Fluorides,Styrenes and Oxalates

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Chinese Journal of Chemistry 2024年第5期42卷 511-515页

作者： Zheng Lin Guanghui lv Jianghong Liu Jiangyan tang Binsong Mu Jian Chen Tianle Huang Zhongzhen Yang Yong Wu Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengduSichuan610041 China Department of Pharmacy Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem CellsTaihe HospitalHubei University of MedicineShiyanHubei442000 China

Cooperative NHC/photoredox catalysis has emerged as an important research field in recent years.Herein,this article describes the use of cesium salt derivatives of tert-alcohols as alkyl radical precursors in a three-component reaction with styrene and aromatic acyl fluorides to synthesizeα-arylalkyl aryl ketones.The aroyl fluoride reacts with the NHC catalyst,leading to the formation of an acyl azolium ion.This acyl azolium ion can then be reduced by the photoredox catalyst,generating the corresponding ketyl radical anion.The C-radical generated from oxalate oxidation undergoes an addition reaction with the styrene derivative,followed by cross-coupling of the addition radical with the ketone radical,which is fragmented by NHC to give the target ketone.

关键词： Three-component Photoredox NHC Aryl ketones Iridium Radical C—C coupling Amides

Poor oral health was associated with higher risk of gastric cancer: Evidence from 1431677 participants

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 585-595页

作者： Fei Liu Shi-Jun tang Zi-Wei Li Xu-Rui Liu Quan lv Wei Zhang Dong Peng Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Pediatric Dentistry Stomatological Hospital of Guizhou Medical UniversityGuizhou 550000Guizhou ProvinceChina

BACKGROUND In recent years,the association between oral health and the risk of gastric cancer(GC)has gradually attracted increased interest.However,in terms of GC incidence,the association between oral health and GC incidence remains contro-versial.Periodontitis is reported to increase the risk of GC.However,some studies have shown that periodontitis has no effect on the risk of GC.Therefore,the present study aimed to assess whether there is a relationship between oral health and the risk of GC.AIM To assess whether there was a relationship between oral health and the risk of GC.METHODS Five databases were searched to find eligible studies from inception to April 10,2023.Newcastle-Ottawa Scale score was used to assess the quality of included studies.The quality of cohort studies and case-control studies were evaluated separately in this study.Incidence of GC were described by odds ratio(OR)and 95%confidence interval(CI).Funnel plot was used to represent the publication bias of included studies.We performed the data analysis by StataSE 16.RESULTS A total of 1431677 patients from twelve included studies were enrolled for data analysis in this study.According to our analysis,we found that the poor oral health was associated with higher risk of GC(OR=1.15,95%CI:1.02-1.29;I2=59.47%,P=0.000.01),gingivitis(OR=1.19,95%CI:0.71-1.67;I2=0.00%,P>0.01),dentures(OR=1.27,95%CI:0.63-1.19;I2=68.79%,P>0.01),or tooth brushing(OR=1.25,95%CI:0.78-1.71;I2=88.87%,P>0.01)had no influence on the risk of GC.However,patients with periodontitis(OR=1.13,95%CI:1.04-1.23;I2=0.00%,P<0.01)had a higher risk of GC.CONCLUSION Patients with poor oral health,especially periodontitis,had a higher risk of GC.Patients should be concerned about their oral health.Improving oral health might reduce the risk of GC.

关键词： Oral health Tooth loss Periodontitis Gastric cancer Risk factor

Photocatalytic oxidation of methane to methanol over zinc titanate supported silver catalysts

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Journal of Rare Earths 2024年第5期42卷 899-906,I0004页

作者： Yuyan Gan Jinbi Huang Qian lv Yanru Li Lizhi Wu YU tang Yuanxing Fang Pengfei Zhu Li Tan Institute of Molecule Catalysis and In-Situ/Operando Studies State Key Laboratory of Photocatalysis on Energy and EnvironmentCollege of ChemistryFuzhou UniversityFuzhou350108China School of Environmental Science and Engineering Shaanxi University of Science and TechnologyXi'an 70021China

The direct activation of methane under mild condition to achieve highly selective of oxygenates is a challenging project.In this study,a well dispersed silver supported ZnTiO_(3) catalyst was prepared to achieve selective preparation of methanol from methane and water under mild condition.X-ray diffraction,transmission electron microscopy and X-ray photoelectron spectroscopy characterizations demonstrate that silver species are uniformly dispersed on ZnTiO_(3) surface in the form of metallic silver nanoparticles.The photoelectric characterizations reveal that the addition of silver species enhances light absorption and promotes charge separation of the catalysts.Under the reaction conditions of 50℃and 3 MPa,the methanol is obtained as the only liquid product over the designed Ag/ZnTiO_(3) catalyst under light irradiation.In this photocatalytic process,the holes generated by ZnTiO_(3) activate water to produce intermediate·OH,which further reacts with methane to synthesize methanol.The silver species as co-catalysts extend the light absorption range of ZnTiO_(3) as well as promote charge separation.

关键词： Photocatalytic Methane oxidation Zinc titanate Silver Methanol

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella(MMAF)and ICSI outcomes

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Asian Journal of Andrology 2024年第1期26卷 91-98页

作者： Zhong-Mei Shao Yu-Tong Zhu Meng Gu Sen-Chao Guo Hui Yu Kuo-Kuo Li Dong-Dong tang Yu-Ping Xu Ming-Rong lv Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Obstetrics and Gynecology Fuyang Hospital of Anhui Medical UniversityFuyang 236112China NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University) Hefei 230032China Key Laboratory of Population Health Across Life Cycle(Anhui Medical University) Ministry of Education of the People'sRepublicof ChinaHefei 230032China

Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in sperm head deformation.However,whether DNAH6 is also involved in human acrosome biogenesis remains unknown.The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella.Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure.Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants.We identified three novel deleterious variants in DNAH6 among three unrelated families.The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants.Additionally,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 variants.The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot.After intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful pregnancy.Overall,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.

关键词： asthenoteratospermia DNAH6 intracytoplasmic sperm injection male infertility

Transcriptomic analysis reveals the effects of maternal exposure to bisphenol AF on hypothalamic development in male neonatal mice

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Journal of Environmental Sciences 2024年第7期141卷 304-313页

作者： Lin lv Yuanyuan Li Xuanyue Chen Zhanfen Qin State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing.We found that maternal exposure to approximately 50μg/(kg·day)BPAF from postanal day(PND)0 to PND 15 altered the hypothalamic transcriptome,primarily involving the pathways and genes associated with extracellular matrix(ECM)and intercellular adhesion,neuroendocrine regulation,and neurological processes.Further RNA analysis confirmed the changes in the expression levels of concerned genes.Importantly,we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin(POMC)neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue.All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism.Interestingly,5000μg/(kg·day)BPAF caused slighter,non-significant or even inverse alterations than the low dose of 50μg/(kg·day),displaying a dose-independent effect.Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose.Overall,our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.

关键词： Bisphenol AF Hypothalamus Transcriptomic alteration Pro-opiomelanocortin(POMC)neurons White adipose tissue browning

A fast forward computational method for nuclear measurement using volumetric detection constraints

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Nuclear Science and Techniques 2024年第2期35卷 47-63页

作者： Qiong Zhang Lin-lv Lin University of Electronic Science and Technology of China Chengdu 610000China

Owing to the complex lithology of unconventional reservoirs,field interpreters usually need to provide a basis for interpretation using logging simulation models.Among the various detection tools that use nuclear sources,the detector response can reflect various types of information of the medium.The Monte Carlo method is one of the primary methods used to obtain nuclear detection responses in complex environments.However,this requires a computational process with extensive random sampling,consumes considerable resources,and does not provide real-time response results.Therefore,a novel fast forward computational method(FFCM)for nuclear measurement that uses volumetric detection constraints to rapidly calculate the detector response in various complex environments is proposed.First,the data library required for the FFCM is built by collecting the detection volume,detector counts,and flux sensitivity functions through a Monte Carlo simulation.Then,based on perturbation theory and the Rytov approximation,a model for the detector response is derived using the flux sensitivity function method and a one-group diffusion model.The environmental perturbation is constrained to optimize the model according to the tool structure and the impact of the formation and borehole within the effective detection volume.Finally,the method is applied to a neutron porosity tool for verification.In various complex simulation environments,the maximum relative error between the calculated porosity results of Monte Carlo and FFCM was 6.80%,with a rootmean-square error of 0.62 p.u.In field well applications,the formation porosity model obtained using FFCM was in good agreement with the model obtained by interpreters,which demonstrates the validity and accuracy of the proposed method.

关键词： Nuclear measurement Fast forward computation Volumetric constraints

Microbial-driven ectopic uranium extraction with net electrical energy production

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Frontiers of Environmental Science & Engineering 2024年第1期18卷 49-58页

作者： Xin tang Yin Ye Chunlin Wang Bingqian Wang Zemin Qin Cui Li Yanlong Chen Yuheng Wang Zhiling Li Miao lv Aijie Wang Fan Chen School of Ecology and Environment Northwestern Polytechnical UniversityXi’an 710129China School of Materials Science and Engineering Xi’an University of Architecture and TechnologyXi’an 710055China State Key Laboratory of Urban Water Resource and Environment School of EnvironmentHarbin Institute of TechnologyHarbin 150090China Faculty of Geosciences and Environmental Engineering Southwest Jiaotong UniversityChengdu 611756China

The extraction of uranium (U) from U-bearing wastewater is of paramount importance for mitigating negative environmental impacts and recovering U resources. Microbial reduction of soluble hexavalent uranium (U(VI)) to insoluble tetravalent uranium (U(IV)) holds immense potential for this purpose, but its practical application has been impeded by the challenges associated with managing U-bacterial mixtures and the biotoxicity of U. To address these challenges, we present a novel spontaneous microbial electrochemical (SMEC) method that spatially decoupled the microbial oxidation reaction and the U(VI) reduction reaction. Our results demonstrated stable and efficient U extraction with net electrical energy production, which was achieved with both synthetic and real wastewater. U(VI) removal occurred via diffusion-controlled U(VI)-to-U(IV) reduction-precipitation at the cathode, and the UIVO_(2) deposited on the surface of the cathode contributed to the stability and durability of the abiotic U(VI) reduction. Metagenomic sequencing revealed the formation of efficient electroactive communities on the anodic biofilm and enrichment of the key functional genes and metabolic pathways involved in electron transfer, energy metabolism, the TCA cycle, and acetate metabolism, which indicated the ectopic reduction of U(VI) at the cathode. Our study represents a significant advancement in the cost-effective recovery of U from U(VI)-bearing wastewater and may open a new avenue for sustainable uranium extraction.

关键词： U(VI)bioreduction Electricity production Reaction decoupling Uranium-bearing wastewater Biofilm microbiome