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Palindrome-mediated DNA nanotubes with cell-specific aptamers to improve targeted antitumor effects and reduce toxicity on non-small cell lung cancer

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Science China(Life Sciences) 2025年第2期68卷 454-466页

作者： Cheng Zheng Lanlan Song Chang Yu Lingye Zhu Jing Zhang Ning Wang Mengchu Liu Shini Li Liangxing Wang Zhifa Shen Xiaoying Huang Division of Pulmonary medicine the First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Interdiscipline and Translational MedicineWenzhou 325000China Intervention Department the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China Key laboratory of laboratory medicine Ministry of Education of Chinaand Zhejiang Provincial Key Laboratory of Medical GeneticsSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou 325035China

Chemotherapy is regarded as a widely used and effective treatment strategy for lung cancer,although most conventional chemotherapeutics cause severe toxic side-effects due to their indiscriminate attacks on both cancerous and normal *** nucleic acid nanomaterials are emerging as a promising drug delivery strategy,their clinical applications are limited by rapid degradation by nucleases and difficulties in targeting cancer *** this study,we have developed a Rhein-loaded aptamer-based DNA nanotube(DNT-S6@Rhein)for the targeted and efficient therapy of non-small cell lung *** the palindrome segments,two specified oligonucleotides were hybridized and folded into the well-defined nanotubes(DNT-S6),with the S6 aptamer distributed *** obtained nanotubes exhibited excellent serum stability and targeting ability towards A549 cells due to the firm structure and decoration of the S6 ***,as an antitumor drug and DNA intercalator,can be effectively inserted into the *** drug-loaded nanotubes rapidly disassembled in intracellular environment and then the released Rhein was found to activate cellular apoptotic process and significantly suppress proliferation,migration and invasion of A549 ***,DNT-S6@Rhein could efficiently accumulate in tumor regions,offering compelling therapeutic efficacy and biocompatibility under both in vitro and in vivo *** findings of this study provide a promising strategy for mitigating the inevitable systemic side-effects of chemotherapy and expand the potential application of DNA nanostructure on targeted drug delivery.

关键词： DNA nanotube self-assembly Rhein targeted drug delivery cancer therapy

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Associations of multiple metals exposure with immunoglobulin levels in pregnant women:Hangzhou Birth Cohort Study

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Journal of Environmental Sciences 2025年第5期151卷 560-572页

作者： Jiena Zhou Lanfei Jin Yexinyi Zhou Kunhong Zhong Kegui Huang Qi Zhang Jun Tang Xue Zhang Lihe Peng Shuai Li Na Lv Dongdong Yu Qinheng Zhu Jing Guo Qiong Luo Guangdi Chen Department of Public Health and Key Laboratory of Reproductive Genetics(Ministry of Education)Women’s HospitalZhejiang University School of MedicineHangzhou 310058China Department of Clinical laboratory Shaw HospitalZhejiang University School of MedicineHangzhou 310018China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 310051China Jiashan County Center for Disease Control and Prevention JiashanZhejiang 314199China Department of Clinical laboratory Women’s HospitalZhejiang University School of MedicineHangzhou 310020China Department of Obstetrics Women’s HospitalZhejiang University School of MedicineHangzhou 310020China

Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)*** on the Hangzhou Birth Cohort Study,1059 participants were included,and eleven metals in whole blood samples and serum IgA,IgG,IgE and IgM levels were *** regression,quantile-based g-computation(QGC),and Bayesian kernel machine regression(BKMR)models were used to evaluate the *** with the first tertile of metal levels,arsenic(As)was negatively associated with IgE(β=-0.25,95%confidence interval(CI)=-0.48 to-0.02).Moreover,significant associations of manganese(Mn)with IgA,IgG and IgM were demonstrated(β=0.10,95%CI=0.04 to 0.18;β=0.07,95%CI=0.03 to 0.12;β=0.10,95%CI=0.03 to 0.18,respectively).Cadmium(Cd)were associated with higher levels of *** models showed the positive association of the metalmixtures with IgA and IgG,with Mn playing amajor *** and Cd had positive contributions to IgM,while As had negative contributions to *** the BKMR models,the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th ***,exposure to metals was associated with maternal Igs,and mainly showed that Mn was associated with increased levels of IgA,IgG and IgM,and As was associated with low IgE levels.

关键词： Metals Immunoglobulin Pregnant woman Quantile-based g-computation (QGC) Bayesian kernel machine regression (BKMR)

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Total synthesis of(+)-taberdicatine B and(+)-tabernabovine B

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Chinese Chemical Letters 2025年第2期36卷 349-353页

作者： Tengfei Xuan Xinyu Zhang Wei Han Yidong Huang Weiwu Ren Molecular Synthesis Center&Key laboratory of Marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of China laboratory for Marine Drugs and Bioproducts Laoshan Laboratory

The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield, respectively. The prominent features of this efficient synthetic strategy include the following:(1)(+)-Taberdicatine B and(+)-tabernabovine B were accessed from common advanced intermediates by varying the substituents;(2) A one-pot asymmetric bromocyclization/hydrolysis was explored to assemble HPI skeleton;(3) Dieckmann condensation to form β-keto ester for the assembly of seven-membered ring;(4) An ester reduction/amide semireduction/cyclization sequence was applied to form the cage-like framework.

关键词： Asymmetric dearomatization Hexahydropyrrolo[2,3-b]indole Taberdicatine B Tabernabovine B Total synthesis

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The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

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Neural Regeneration Research 2025年第8期20卷 2361-2372页

作者： Shengyang Zhou Ting Li Wei Zhang Jian Wu Hui Hong Wei Quan Xinyu Qiao Chun Cui Chenmeng Qiao Weijiang Zhao Yanqin Shen laboratory of Neurodegenerative and Neuroinjury Diseases Wuxi Medicine SchoolJiangnan UniversityWuxiJiangsu ProvinceChina

Interferon regulatory factor 7 plays a crucial role in the innate immune ***,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains *** we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial *** the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 *** addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and *** together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

关键词： cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease neuroinflammation Parkinson’s disease RU521 STING type I interferon

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Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

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Science China Chemistry 2025年第1期68卷 377-384页

作者： Shiwen Liu Xuerui Wan Meng Zhao Jiaqi Wang Weilan Wu Linlin You Yonggui Yuan Qian Xu Rong Gao Key laboratory of Environmental medicine Engineering Ministry of EducationSchool of Public HealthSoutheast UniversityNanjing 210009China Key laboratory of Modern Toxicology of Ministry of Education Department of Hygienic Analysis and DetectionSchool of Public HealthNanjing Medical UniversityNanjing 211166China Department of Psychosomatics and Psychiatry Zhongda HospitalSchool of MedicineSoutheast UniversityNanjing 210009China

The measurement of amino acid and monoamine neurotransmitters(NTs)in serum plays a central role in the identification and monitoring of clinical panic disorder(PD).However,the strong polarity and chemical heterogeneity of NTs make direct extraction and rapid detection extremely ***,we developed a strategy that integrated solid phase extraction based on magnetic Fe_(3)O_(4)coated with polydopamine(Fe_(3)O_(4)@PDA)and direct analysis of mass spectrometry in real time(DART-MS)for quantification of 10 *** systematically investigated the optimal conditions of this strategy to achieve good accuracy and *** with existing magnetic solid phase extraction methods for NTs detection in biological samples,this strategy could adsorb more targets while having similar adsorption efficiencies,and the total process time was reduced by an average of 69.42%.We rapidly determined the metabolic abnormality of 6 types of NTs in the serum of PD patients and demonstrated their diagnostic *** addition,an outstanding feature of PD in which tryptophan was more metabolized by the KYN pathway and the 5-hydroxytryptamine pathway was inhibited could be elucidated by this *** results highlighted the potential ability of Fe_(3)O_(4)@PDA coupled with DART-MS to assist in the clinical diagnosis of PD.

关键词： neurotransmitters panic disorder magnetic solid phase extraction direct analysis of mass spectrometry in real time

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Liquid-liquid phase separation of TRAF6 promotes anti-TB immunity

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Science Bulletin 2025年第3期70卷 338-341页

作者： Yongjia Duan Yuanna Cheng Mingtong Ma Liru Li Shanshan Liu Liru Guan Jie Wang Hongjie Liu Xiaochen Huang Jianxia Chen Hua Yang Baoxue Ge Lin Wang Shanghai Key laboratory of Tuberculosis Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China Department of Microbiology and Immunology Tongji University School of MedicineShanghai 200433China Clinic and Research Center of Tuberculosis Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China Key laboratory of Pathogen-Host Interaction Ministry of EducationDepartment of Microbiology and ImmunologyTongji University School of MedicineShanghai 200049China

Tumor necrosis factor receptor(TNFR)-associated factor 6(TRAF6)is a key regulator of the innate immune system,activating NF-κB and AP-1 signaling[1].TRAF6 participates in the immune regulation of many diseases,especially in chronic infections caused by pathogenic bacteria,such as Mycobacterium tuberculosis(Mtb)-induced tuberculosis(TB)[2].

关键词： immunity tuberculosis TRAF6

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Radical dehydroxymethylative fluorination of aliphatic primary alcohols and diverse functionalization ofα-fluoroimides via BF_(3)·OEt_(2)-catalyzed C-F bond activation

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Chinese Chemical Letters 2025年第1期36卷 239-243页

作者： Peng Wang Jianjun Wang Ni Song Xin Zhou Ming Li Molecular Synthesis Center Key Laboratory of Marine MedicineChinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and TechnologyQingdao 266237China

Ag_(2)CO_(3)-promoted dehydroxymethylative fluorination of aliphatic alcohols has been achieved with Selectfluor as both oxidant and fluorine *** reaction involvesβ-fragmentation of primary alkoxy radicals,followed by the fluorination of the resulting C-centered radical *** transformation proceeds under mild reaction conditions and exhibits a broad substrate scope,thus opening up a new entrance to the synthesis of fluorinated constructs includingα-fluoroimides and 1-fluoroalkyl benzoates as well as secondary and tertiary alkyl fluorides like versatile 2-fluoro-2-alkyl 1,3-propandiol *** divergent functionalization of the obtainedα-fluoroimides enables an efficient access to amine derivatives through C-F bond activation under the action of BF_(3)·OEt_(2).

关键词： Dehydroxymethylative fluorination Alkoxy radicals β-Fragmentation Silver catalysis C-F Bond activation

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Rapid and scalable preparation of highly quaternized polymer networks to achieve efficient simultaneous adsorption of iodide and pertechnetate

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Science China Chemistry 2025年第1期68卷 337-349页

作者： Meiyun Xu Song Gu Fulong Chen Zhe Zhao Peng Liu Daoben Hua State Key laboratory of Radiation medicine and Protection School of Radiological and Interdisciplinary Sciences(RAD-X)Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123China

The efficient separation of fission products,such as TcO_(4)^(-)and I^(-),holds strategic significance for the management of radioactive wastes and environmental *** this study,we propose an ultrafast strategy for scalable preparation of a highly quaternized organic network to facilitate efficient and synchronous separation of iodide and *** network can be prepared within a few minutes at room temperature,using polyethylenimine and 1,2,4,5-tetrakis(bromomethyl)benzene as building *** chlorine replacement,the network,abundantly decorated with quaternary ammonium groups(Cl@QPN),exhibits an ultrahigh positive charge density of 7.6 mmol/*** enables the rapid and efficient enrichment of target anions through strong electrostatic Coulomb *** a result,Cl@QPN exhibits significantly higher adsorption rate constants of 0.830 g/(mg min)for ReO_(4)^(-)(a nonradioactive surrogate of TcO_(4)^(-))and 0.677 g/(mg min)for I-compared to other ***,it possesses high adsorption capacities,reaching 1,681 mg/g for ReO_(4)^(-)and 917.4 mg/g for I-.Cl@QPN also demonstrates good selectivity towards target ions and shows efficient adsorption for^(99)TcO_(4)^(-).Additionally,Cl@QPN exhibits high dynamic processing capacities,handling up to 3,100 and 7,400 kg of simulated streams per kilogram of material for I-and ReO_(4)^(-),respectively.

关键词： quaternized polymer networks adsorption pertechnetate iodide liquid radioactive streams

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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi school of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina school of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of laboratory medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of laboratory medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina school of Chinese medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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AI empowers exploration of protein universe

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Science China(Life Sciences) 2025年第2期68卷 588-589页

作者： Wuke Wang Xingxu Huang Zhejiang Provincial Key laboratory of Pancreatic Disease The First Affiliated Hospitaland Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China

Deaminases which perform the function of converting cytosine to thymine are ubiquitous in nature with over 120,000 known variants,each exhibiting significant ***,gene editing technologies have remarkably revealed that these deaminases share similar ***,the mining of novel proteins has been conducted through sequence alignment and the categorization of conserved regions to identify functional modules within protein sequences.

关键词： functions powers alignment

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