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A zwitterionic polymer-inspired material mediated efficient CRISPR-Cas9 gene editing

Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 666-678页

作者： lingmin zhang Langyu Yang Jionghua Huang Sheng Chen Chuangjia Huang Yinshan Lin Ao Shen ZhouYikang Zheng Wenfu Zheng Shunqing Tang Key Laboratory of Molecular Target&Clinical Pharmacology and the State&NMPA Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences&The Third and Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China Department of Biomedical Engineering Jinan UniversityGuangzhou 510632China CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety National Center for NanoScience and TechnologyBeijing 100190China

The typeⅡ prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR/Cas9) adaptive immune system is a cutting-edge genome-editing toolbox.However,its applications are still limited by its inefficient transduction.Herein,we present a novel gene vector,the zwitterionic polymer-inspired material with branched structure (ZEBRA) for efficient CRISPR/Cas9 delivery.Polo-like kinase 1 (PLK1) acts as a master regulator of mitosis and overexpresses in multiple tumor cells.The Cas9 and single guide sgRNA (sgRNA)-encoded plasmid was transduced to knockout Plk1 gene,which was expected to inhibit the expression of PLK1.Our studies demonstrated that ZEBRA enabled to transduce the CRISPR/Cas9 system with large size into the cells efficiently.The transduction with ZEBRA was cell line dependent,which showed~10-fold higher in CD44-positive cancer cell lines compared with CD44-negative ones.Furthermore,ZEBRA induced highlevel expression of Cas9 proteins by the delivery of CRISPR/Cas9 and efficient gene editing of Plk1 gene,and inhibited the tumor cell growth significantly.This zwitterionic polymerinspired material is an effective and targeted gene delivery vector and further studies are required to explore its potential in gene delivery applications.

关键词： CRISPR/Cas9 Gene editing Zwitterionic polymers CD44 PLK1

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Aminosaccharide-gold nanoparticle assemblies as narrow-spectrum antibiotics against methicillin-resistant Staphylococcus aureus

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Nano Research 2018年第12期11卷 6237-6243页

作者： Xinglong Yang lingmin zhang Xingyu Jiang CAS Center for Excellence in Nanoscience CAS Key Lab for Biological Effects of Nanomatefials and NanosafetyBeijing Engineering Research Center for BioNanotechnologyNational Center for NanoScience and TechnologyBeijing 100190China School of Chemistry and Chemical Engineering University of JinanJinan 250022China University of Chinese Academy of Sciences Beijing 100049China

Bacterial infection has continued to be a leading cause of death or disability worldwide because of antibiotic resistance. Antibiotic agents specific to certain taxa of bacteria, i.e., narrow-spectrum antibiotics, have become useful because they can kill bacteria without resulting in broad-spectrum drug resistance. In this study, we describe a series of antibiotics based on combining gold nanoparticles (AuNPs) with aminosaccharides, even though these AuNPs or aminosaccharides by themselves are ineffective against any bacteria. The AuNP-based multivalent aminosaccharides can effectively and selectively inhibit the growth of Gram-positive bacteria (including drug-resistant superbacteria). In particular, aminosaccharide-modified AuNPs are effective against methicillin-resistant Staphylococcus aureus (MRSA), a particularly hard-to-treat strain. This report carves out a way to explore antibiotics by combining AuNPs and an aminosaccharide as multivalent nanostructures, neither of which by itself is effective as an antibiotic.

关键词： gold nanoparticles multivalent aminosaccharides antibacterial activity methicillin-resistant Staphylococcus aureus (MRSA) antibiotics

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The construction of drug-resistant cancer cell lines by CRISPR/Cas9 system for drug screening

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Science Bulletin 2018年第21期63卷 1411-1419页

作者： lingmin zhang Ying Li Qinghua Chen Yong Xia Wenfu Zheng Xingyu Jiang CAS Center for Excellence in Nanoscience Beijing Engineering Research Center for BioNanotechnologyCAS Key Laboratory for Biological Effects of Nanomaterials and NanosafetyNational Center for NanoScience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Guangdong Provincial Key Laboratory of Molecular Target &Clinical Pharmacology School of Pharmaceutical Sciences and the Third &Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China

Cancer therapy is often hampered by the rapid emergence of drug resistance. Drug-resistant cellular models are essential for understanding the drug resistance and developing new therapeutics. The low efficiency and long time required in creating these models are major obstacles hindering drug resistance research and drug screening. Herein, we report an approach that can accelerate(shortening the time from years to 3 weeks) the establishment of cancer cell line-based, inheritable drug resistance models by specific knockout of MED12 gene using CRISPR/Cas9 system. The resultant MED12^(KO) A375(melanoma)cell line was resistant to inhibitors of B-Raf proto-oncogene, serine/threonine kinase(BRAF), whereas the resultant MED12^(KO) PC9(non-small cell lung cancer) cell line was resistant to inhibitors of epidermal growth factor receptor(EGFR). Evaluation of anti-cancer drugs and their combinations shows that certain combinations of BRAF inhibitors and TGF-β receptor(TGF-βR) inhibitors are active in suppressing the growth of MED12^(KO) A375 cells, and a few combinations of EGFR inhibitors and TGF-βR inhibitors were active in suppressing the growth of MED12^(KO) PC9 cells. The drug-resistant models will be useful in screening novel drugs and drug combinations for multi-drug-resistant cancer therapy.

关键词： CRISPR/Cas9 Drug resistance Cancer Cell line Gene editing

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Road map for, and technical challenges of, carbon-nanotube integrated circuit technology

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National Science Review 2024年第3期11卷 14-16页

作者： Jia Si Panpan zhang Zhiyong zhang Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics School of Electronics Peking University State Key Laboratory of Information Photonics and Optical Communications Beijing University of Posts and Telecommunications

The past decade has witnessed an explosion of research on carbon-nanotube(CNT) electronics due to their outstanding properties, including an ultrathin body, a high carrier mobility and a high saturation velocity.

关键词： TRANSISTORS

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New structure transistors for advanced technology node CMOS ICs

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National Science Review 2024年第3期11卷 24-41页

作者： Qingzhu zhang Yongkui zhang Yanna Luo Huaxiang Yin Integrated Circuit Advanced Process R&D Center Institute of Microelectronics of Chinese Academy of Sciences(IMECAS) State key Lab of Fabrication Technologies for Integrated Circuits Institute of Microelectronics of Chinese Academy of Sciences School of Integrated Circuits University of Chinese Academy of Sciences

Over recent decades, advancements in complementary metal-oxide-semiconductor integrated circuits(ICs)have mainly relied on structural innovations in transistors. From planar transistors to the fin field-effect transistor(FinFET) and gate-all-around FET(GAAFET), more gate electrodes have been added to three-dimensional(3D) channels with enhanced control and carrier conductance to provide higher electrostatic integrity and higher operating currents within the same device footprint. Beyond the 1-nm node, Moore's law scaling is no longer expected to be applicable to geometrical shrinkage. Vertical transistor stacking, e.g. in complementary FETs(CFET), 3D stack(3DS) FETs and vertical-channel transistors(VFET), for enhanced density and variable circuit or system design represents a revolutionary scaling approach for sustained IC development. Herein, innovative works on specific structures, key process breakthroughs, shrinking cell sizes and design methodologies for transistor structure research and development are reviewed. Perspectives on future innovations in advanced transistors with new channel materials and operating theories are also discussed.

关键词： transistor CMOS GAAFET CFET 3DS FET

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Advances in methane emissions from agricultural sources:Part I.Accounting and mitigation

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Journal of Environmental Sciences 2024年第6期140卷 279-291页

作者： Xiaokun Wu Ying zhang Yinghui Han Yagang zhang Yuhang zhang Xiaodan Cheng Pei Zhong Xue Yuan Yuanxun zhang Zhengqiang Li State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources North China Electric Power UniversityBeijing 102206China Hebei Key Laboratory of Physics and Energy Technology North China Electric Power UniversityBaoding 071003China College of Resources and Environment University of Chinese Academy of SciencesBeijing 101408China Interdisciplinary Mathematics Institute University of South CarolinaColumbiaSC 29208United States Aerospace Information Research Institute Chinese Academy of SciencesBeijing 100094China

Methane is one of the major greenhouse gases(GHGs)and agriculture is recognized as its primary emitter.Methane accounting is a prerequisite for developing effective agriculture mitigation strategies.In this review,methane accounting methods and research status for various agricultural emission source including rice fields,animal enteric fermentation and livestock and poultry manure management were overview,and the influencing factors of each emission source were analyzed and discussed.At the same time,it analyzes the different research efforts involving agricultural methane accounting and makes recommendations based on the actual situation.Finally,mitigation strategies based on accounting results and actual situation are proposed.This review aims to provide basic data and reference for agriculture-oriented countries and regions to actively participate in climate action and carry out effective methane emission mitigation.

关键词： Methane emission Agricultural sources Accounting methodology Mitigation Emission influencing factors

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Interface Engineering of Titanium Nitride Nanotube Composites for Excellent Microwave Absorption at Elevated Temperature

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Nano-Micro Letters 2024年第9期16卷 147-160页

作者： Cuiping Li Dan Li Shuai zhang Long Ma Lei zhang* Jingwei zhang Chunhong Gong College of Chemistry and Molecular Sciences Henan UniversityKaifeng 475004People’s Republic of China National and Local Joint Engineering Research Center for Applied Technology of Hybrid Nanomaterials Henan UniversityKaifeng 475004People’s Republic of China

Currently,the microwave absorbers usually suffer dreadful electromagnetic wave absorption(EMWA)performance damping at elevated temperature due to impedance mismatching induced by increased conduction loss.Consequently,the development of high-performance EMWA materials with good impedance matching and strong loss ability in wide temperature spectrum has emerged as a top priority.Herein,due to the high melting point,good electrical conductivity,excellent environmental stability,EM coupling effect,and abundant interfaces of titanium nitride(TiN)nanotubes,they were designed based on the controlling kinetic diffusion procedure and Ostwald ripening process.Benefiting from boosted heterogeneous interfaces between TiN nanotubes and polydimethylsiloxane(PDMS),enhanced polarization loss relaxations were created,which could not only improve the depletion efficiency of EMWA,but also contribute to the optimized impedance matching at elevated temperature.Therefore,the TiN nanotubes/PDMS composite showed excellent EMWA performances at varied temperature(298-573 K),while achieved an effective absorption bandwidth(EAB)value of 3.23 GHz and a minimum reflection loss(RLmin)value of−44.15 dB at 423 K.This study not only clarifies the relationship between dielectric loss capacity(conduction loss and polarization loss)and temperature,but also breaks new ground for EM absorbers in wide temperature spectrum based on interface engineering.

关键词： TiN nanotubes Interface engineering Polarization loss Impedance matching Electromagnetic wave absorption performance

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Environmental arsenic(As)and its potential relationship with endemic disease in southwestern China

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Journal of Environmental Sciences 2024年第5期139卷 46-59页

作者： Donglin Li Hucai zhang Fengqin Chang Lizeng Duan Yang zhang Institute for Ecological Research and Pollution Control of Plateau Lakes School of Ecology and Environmental ScienceYunnan UniversityKunming 650500China Southwest United Graduate School Kunming 650500China

Many cases of an unknown disease exhibiting the clinical features of limb gangrene,blisters,ulceration,and exfoliation have been reported in Daping village(DV)in southwestern China.However,the pathogenesis is unknown and has puzzled doctors for many years.A preliminary study on heavy metals and symptoms indicated that arsenic might pose the greatest threat to the health of local residents.Here,to explore the sources of and factors influencing arsenic enrichment in DV,whose residents exhibit signs of arsenic poisoning,the As contents in soil,water,and plants were systematically measured.The results indicated high As contents in plant and soil samples obtained from the area,and the source of As may be linked to the weathering of black shale rock.Ingestion of soil and consumption of plants were the two main As exposure pathways among children and adults,respectively,and children exhibited a higher health risk than adults.We presume and emphasize that when extreme drought events occur,humans might face unusual risks resulting from exposure to toxic elements and the direct consumption of highly polluted water.Our study provides a new perspective and sheds light on the environmental geochemistry and health links of this disease.

关键词： Endemic disease Arsenic(As) Risk assessment Black shale Climate change

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N-doped graphene quantum dot-decorated N-TiO2/P-doped porous hollow g-C_(3)N_(4) nanotube composite photocatalysts for antibiotic photodegradation and H2 production

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 165-178页

作者： Jingshu Yuan Yao zhang Xiaoyan zhang Junjie zhang Shen’gen zhang Institute for Advanced Materials and Technology University of Science and Technology BeijingBeijing 100083China Xi’an Fanyi University Xi’an 710105China Shunde Graduate School of University of Science and Technology Beijing Foshan 528399China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao SAR 820000China

Exclusive responsiveness to ultraviolet light (~3.2 eV) and high photogenerated charge recombination rate are the two primary drawbacks of pure TiO_(2). We combined N-doped graphene quantum dots (N-GQDs), morphology regulation, and heterojunction construction strategies to synthesize N-GQD/N-doped TiO_(2)/P-doped porous hollow g-C_(3)N_(4) nanotube (PCN) composite photocatalysts (denoted as G-TPCN). The optimal sample (G-TPCN doped with 0.1wt% N-GQD, denoted as 0.1% G-TPCN) exhibits significantly enhanced photoabsorption, which is attributed to the change in bandgap caused by elemental doping (P and N), the improved light-harvesting resulting from the tube structure, and the upconversion effect of N-GQDs. In addition, the internal charge separation and transfer capability of0.1% G-TPCN are dramatically boosted, and its carrier concentration is 3.7, 2.3, and 1.9 times that of N-TiO_(2), PCN, and N-TiO_(2)/PCN(TPCN-1), respectively. This phenomenon is attributed to the formation of Z-scheme heterojunction between N-TiO_(2) and PCNs, the excellent electron conduction ability of N-GQDs, and the short transfer distance caused by the porous nanotube structure. Compared with those of N-TiO_(2), PCNs, and TPCN-1, the H2 production activity of 0.1%G-TPCN under visible light is enhanced by 12.4, 2.3, and 1.4times, respectively, and its ciprofloxacin (CIP) degradation rate is increased by 7.9, 5.7, and 2.9 times, respectively. The optimized performance benefits from excellent photoresponsiveness and improved carrier separation and migration efficiencies. Finally, the photocatalytic mechanism of 0.1% G-TPCN and five possible degradation pathways of CIP are proposed. This study clarifies the mechanism of multiple modification strategies to synergistically improve the photocatalytic performance of 0.1% G-TPCN and provides a potential strategy for rationally designing novel photocatalysts for environmental remediation and solar energy conversion.

关键词： N-doped TiO_(2) N-doped graphene quantum dots P-doped g-C_(3)N_(4) porous hollow nanotube heterojunction photocatalysis

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Chronic administration of triclosan leads to liver fibrosis through hepcidin-ferroportin axis-mediated iron overload

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Journal of Environmental Sciences 2024年第3期137卷 144-154页

作者： Jing Liu Lecong zhang Fang Xu Ping zhang Yang Song College of Eco-Environmental Engineering Guizhou Minzu UniversityGuiyang 550025China The Institute of Karst Wetland Ecology Guizhou Minzu UniversityGuiyang 550025China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Triclosan(TCS)has been manufactured as an antibacterial compound for half a century.Currently,it is widely used in various personal care products;however,its potential adverse effects raise a lot of attention.Here,we create a long-term oral administration mouse model and identify the corresponding hepatotoxicity of TCS.We discover that daily intragastric administration of 10 mg/kg TCS to mice for 12 weeks results in severe hepatic fibrosis.Further study displays that hepatic iron increased 18%,23%and 29%upon oral TCS treatment for4,8 and 12 weeks,respectively.Accompanied by hepatic iron variation,splenic and duodenal iron are increased,which indicates systemic iron disorder.Not only excessive iron accumulated in the liver,abnormal hepatic malondialdehyde,prostaglandin synthase 2 and glutathione peroxidase 4 are pointed to ferroptosis.Additional study uncovers that hepcidin expression increases 7%,10%,4%in serum and 2.4-,4.8-,and 2.3-fold on transcriptional levels upon TCS exposure for 4,8 and 12 weeks,individually.Taken together,the mice in the TCS-treated group show disordered systemic iron homeostasis via the upregulated hepatic hepcidin-ferroportin axis.Meanwhile,both hepatic iron overload(systemic level)and hepatocyte ferroptosis(cellular level)are accused of TCS-induced liver fibrosis.Ferriprox■,an iron scavenger,significantly ameliorates TCS-induced liver fibrosis.In summary,this study confirms the impact of TCS on liver fibrosis;a critical signal pathway is also displayed.The significance of the current study is to prompt us to reevaluate the“pros and cons”of TCS applications.

关键词： Triclosan Iron metabolism Hepcidin Hepatotoxicity Liver fibrosis

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