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| 1 | Increasing the efficiency of CRISPR/Cas9-based gene editing by suppressing RNAi in plants显示文摘Dear Editor,CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated)-based genome editing is a powerful and widely adopted technology for introducing specific mutations in animal and plant systems. | Xiaoyan Wang Jiayun Lu Kangwen Lao Suikang Wang Xiaowei Mo Xintong Xu Xuemei Chen Beixin Mo | 2019 | Science China(Life Sciences)2019,62,7: | 4 |
| 2 | Facile Synthesis of FePS3 Nanosheets@MXene Composite as a High-Performance Anode Material for Sodium Storage显示文摘Searching for advanced anode materials with excellent electrochemical properties in sodium-ion battery is essential and imperative for next-generation energy storage system to solve the energy shortage problem.In this work,two-dimensional(2D)ultrathin FePS3 nanosheets,a typical ternary metal phosphosulfide,are first prepared by ultrasonic exfoliation.The novel 2D/2D heterojunction of FePS3 nanosheets@MXene composite is then successfully synthesized by in situ mixing ultrathin MXene nanosheets with FePS3 nanosheets.The resultant FePS3 nanosheets@MXene hybrids can increase the electronic conductivity and specific surface area,assuring excellent surface and interfacial charge transfer abilities.Furthermore,the unique heterojunction endows FePS3 nanosheets@MXene composite to promote the diffusion of Na^+ and alleviate the drastic change in volume in the cyclic process,enhancing the sodium storage capability.Consequently,the few-layered FePS3 nanosheets uniformly coated by ultrathin MXene provide an exceptional reversible capacity of 676.1 mAh g^−1 at the current of 100 mA g^−1 after 90 cycles,which is equivalent to around 90.6% of the second-cycle capacity(746.4 mAh g^−1).This work provides an original protocol for constructing 2D/2D material and demonstrates the FePS3@MXene composite as a potential anode material with excellent property for sodium-ion batteries. | Yonghao Ding Yu Chen Na Xu Xintong Lian Linlin Li Yuxiang Hu Shengjie Peng | 2020 | Nano-Micro Letters2020,12,4: | 2 |
| 3 | Zeolite templated carbon nanodots for broadband ultrafast pulsed fiber laser generation显示文摘Carbon nanodots(C-dots) with a uniform size of about 2 nm are synthesized via in situ pyrolysis of n-propylamine that is confined in the nanochannels of zeolite Linde Type A(LTA). The as-synthesized C-dots@LTA composite shows nonlinear optical saturable absorption properties in a broad wavelength band and can be used as saturable absorber(SA) to generate ultrafast pulsed fiber lasers. By inserting a zeolite LTA single crystal hosting C-dots into the fiber laser cavity, mode-locked fiber lasers with long-term operation stability at 1.5 μm and 1 μm are achieved. These results show that the C-dots@LTA are a promising SA material for ultrafast pulsed fiber laser generation in a broad wavelength band. To the best of our knowledge, this is the first demonstration of a C-dots@LTA-based mode-locked fiber laser. | XINTONG XU JIAQI CHEN WENTAO SHI DALIN SUN SHAOWEN CHU LANG SUN WENFEI ZHANG YANPING CHEN JIANPANG ZHAI SHUANGCHEN RUAN ZIKANG TANG | 2019 | Photonics Research2019,7,10: | 2 |
| 4 | Facile active control of a pulsed erbium-doped fiber laser using modulation depth tunable carbon nanotubes显示文摘Short pulsed fiber lasers have been widely made using single-walled carbon nanotubes as a saturable absorber(SA). However, most of the currently used devices can only operate in one determined operation state with an unchangeable modulation SA depth in the cavity, which significantly limits their application in photonic devices.In this paper, well-aligned carbon nanotube arrays are synthesized using zeolite AlPO_4-5 as a template, which features anisotropic optical absorption. The linear optical absorption of the as-synthesized carbon nanotube arrays can easily be tuned by adjusting a polarization controller, thus providing a tunable modulation depth for the carbon nanotube SA. By exploiting this SA in an erbium-doped fiber laser cavity, both Q-switched and modelocked pulsed lasers are achieved by simply adjusting a polarization controller under a fixed pump power of 330 mW. In addition, the repetition rate of the Q-switching and pulse duration of the mode-locking can be tuned according to the variation of modulation depth. Moreover, soliton molecules can be obtained when the modulation depth of the SA is 4.5%. | XINTONG XU SHUANGCHEN RUAN JIANPANG ZHAI LING LI JIHONG PEI ZIKANG TANG | 2018 | Photonics Research2018,,11: | 1 |
| 5 | Workflow optimization algorithm based on virtualization and nonlinear production quality under time constraints显示文摘Balancing time,cost,and quality is crucial in intelligent manufacturing.However,finding the optimal value of production parameters is a challengingnon-deterministic polynomial(NP)-hard problem.In the actual production process,the production process has the characteristics of multi-stage parallel.Therefore,aiming at the difficult problem of multi-stage nonlinear production process optimization,this paper proposes a workflow optimization algorithm based on virtualization and nonlinear production quality under time constraints(T-OVQT).The algorithm proposed in this paper first abstracts the actual production process into a virtual workflow model,which is divided into three layers:The bottom production process collection layer,the middle layer of service node partial order composition layer,and the high level of virtual node collection layer.Then,the virtual technology is used to reconstruct the node set and divide the task interval.The optimal solution is obtained through inverse iterative normalization and forward scheduling,and the global optimal solution is obtained by algorithm integration.Experimental results demonstrate that this algorithm better meets actual production requirements than the traditional minimum critical path(MCP)algorithm. | Luo Zhiyong Tan Shanxin Xu Haifeng Liu Xintong | 2023 | The Journal of China Universities of Posts and Telecommunications2023,30,4: | 0 |
| 6 | The nuclear export receptor OsXPO1 is required for rice development and involved in abiotic stress responses显示文摘The transport of proteins to and from the nucleus is necessary for many cellular processes and is one of the ways plants respond to developmental signals and environmental stresses.Nucleocytoplasmic trafficking of proteins is mediated by the nuclear transport receptor(NTR).Although NTR has been extensively studied in humans and Arabidopsis,it has rarely been identified and functionally characterized in rice.In this study,we identified exportin 1 in rice(OsXPO1)as a nuclear export receptor.OsXPO1shares high protein identity with its functional homologs in Arabidopsis and other organisms.OsXPO1localized to both the nucleus and the cytoplasm,directly interacted with the small GTPases OsRAN1and OsRAN2 in the nucleus,and mediated their nuclear export.Loss-of-function osxpo1 mutations were lethal at the seedling stage.Suppression of OsXPO1 expression in RNA interference lines produced multifaceted developmental defects,including arrested growth,premature senescence,abnormal inflorescence,and brown and mouth-opened spikelets.Overexpression of OsXPO1 in rice reduced plant height and seed-setting rate,but increased plant tolerance in response to PEG-mimicked drought stress and salt stress.These results indicate that OsXPO1 is a nuclear export receptor and acts in regulating plant development and abiotic stress responses. | Qiufei Peng Jieyu Qiu Xintong Li Xuezhong Xu Xinxiang Peng Guohui Zhu | 2023 | The Crop Journal2023,11,1: | 0 |
| 7 | NTP4 modulates miRNA accumulation via asymmetric modification of miRNA/miRNA duplex显示文摘Dear Editor.MicroRNAs(miRNAs)are endogenous small RNAs(sRNAs)that play crucial regulatory roles in gene expression.In plants,the transcribed primary miRNAs(pri-miRNAs)are sequentially processed by DICER-LIKE 1(DCL1)into precursor miRNAs(pre-miRNAs),and eventually miRNA/miRNA*duplexes(Wang et al.,2019).The methyltransferase HUA ENHANCER 1(HEN1)confers 2’-Omethylation on the 3’terminal ribose of each strand within the miRNA/miRNA*duplexes(Yu et al.,2005).Once methylated,miRNA duplexes are loaded onto ARGONAUTE1(AGO1),with one strand referred to as miRNA which is stabilized to form RNA-induced silencing complexes(RISCs),whereas the other strand becomes miRNA*that is eliminated and degraded. | Wenwen Kong Xianxin Dong Yongbing Ren Yuan Wang Xintong Xu Beixin Mo Yu Yu Xiaoyan Wang | 2021 | Science China(Life Sciences)2021,64,5: | 0 |
| 8 | Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart显示文摘The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury. | Xintong ZHANG Xiaoxue GAI Lihua XU Wenxue MA Qiaohan LIU Bendong SHI Cheng FANG Jingzeng CAI Ziwei ZHANG | 2023 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2023,24,5: | 0 |
| 9 | Biochar and organic substitution improved net ecosystem economic benefit in intensive vegetable production显示文摘Biochar amendment and substituting chemical fertilizers with organic manure(organic substitution)have been widely reported to increase crop production and decrease reactive nitrogen(Nr)loss including nitrous oxide(N_(2)O),nitric oxide(NO),and ammonia(NH3)emissions,and N runoff and leaching.However,few comprehensive evalua-tions have been performed on the environmental and economic aspects of biochar amendment or organic sub-stitution.Here,we studied the comprehensive effects of biochar amendment,organic substitution,and biochar amendment combined with organic substitution on crop production,Nr loss,and net ecosystem economic benefit(NEEB)in intensive vegetable production by integrating life-cycle assessment for Nr footprints,empirical models for NH3 volatilization and N runoff and leaching derived from peer-reviewed publications and validated by the current measurements and direct field measurement for N_(2)O and NO emissions during 5 consecutive years of vegetable crop rotations.Five fertilization treatments were applied(SN:synthetic fertilizer application;SNB:SN plus 20 t ha^(−1)biochar amendment;SNM:substituting 50%of chemical N fertilizer with organic manure;SNMB:SNM plus 20 t ha^(−1)biochar amendment;and CK:no fertilizer or biochar addition).Compared with the SN,the SNB increased vegetable yield(28.4%,p<0.05;interannually varying from−10 to 74.9%)and nitrogen use efficiency(29.2%,interannually varying from−39.7 to 150.4%),and decreased field Nr loss(45.4%,p<0.01;interannually varying from−40.3 to 78.4%),and thus improved NEEB by 7.1%;meanwhile,the SNM increased vegetable yield(11.6%,interannually varying from−5.4 to 27.1%)and nitrogen use efficiency(45.7%,p<0.05;interannually varying from 2.3 to 154%),reduced field Nr loss(34.9%,p<0.01;interannually varying from 8.4-39.0%),and thus improved NEEB by 17.8%(p<0.05)compared to the SN,being 56.0×10^(3)Chinese Yuan(CNY)ha^(−1)crop^(−1).Due to the high foreground Nr loss during organic manure production and high input costs of biochar production,the SNMB decreased the NEEB by 8.0%as compared to the SN.Moreover,the SNB and SNM improved vegetable qualities by increasing protein,soluble sugar,and vitamin C contents while decreasing nitrate content(p<0.05).Therefore,single application of biochar amendment or organic substitution would achieve better NEEB and product quality in vegetable production. | Ruiyu Bi Qianqian Zhang Liping Zhan Xintong Xu Xi Zhang Yubing Dong Xiaoyuan Yan Zhengqin Xiong | 2022 | Biochar2022,4,1: | 0 |
| 10 | Two-step model of paleohexaploidy, ancestral genome reshuffling and plasticity of heat shock response in Asteraceae显示文摘An ancient hexaploidization event in the most but not all Asteraceae plants,may have been responsible for shaping the genomes of many horticultural,ornamental,and medicinal plants that promoting the prosperity of the largest angiosperm family on the earth.However,the duplication process of this hexaploidy,as well as the genomic and phenotypic diversity of extant Asteraceae plants caused by paleogenome reorganization,are still poorly understood.We analyzed 11 genomes from 10 genera in Asteraceae,and redated the Asteraceae common hexaploidization(ACH)event∼70.7–78.6 million years ago(Mya)and the Asteroideae specific tetraploidization(AST)event∼41.6–46.2 Mya.Moreover,we identified the genomic homologies generated from the ACH,AST and speciation events,and constructed a multiple genome alignment framework for Asteraceae.Subsequently,we revealed biased fractionations between the paleopolyploidization produced subgenomes,suggesting the ACH and AST both are allopolyplodization events.Interestingly,the paleochromosome reshuffling traces provided clear evidence for the two-step duplications of ACH event in Asteraceae.Furthermore,we reconstructed ancestral Asteraceae karyotype(AAK)that has 9 paleochromosomes,and revealed a highly flexible reshuffling of Asteraceae paleogenome.Of specific significance,we explored the genetic diversity of Heat Shock Transcription Factors(Hsfs)associated with recursive whole-genome polyploidizations,gene duplications,and paleogenome reshuffling,and revealed that the expansion of Hsfs gene families enable heat shock plasticity during the genome evolution of Asteraceae.Our study provides insights on polyploidy and paleogenome remodeling for the successful establishment of Asteraceae,and is helpful for further communication and exploration of the diversification of plant families and phenotypes. | Xiangming Kong Yan Zhang Ziying Wang Shoutong Bao Yishan Feng Jiaqi Wang Zijian Yu Feng Long Zejia Xiao Yanan Hao Xintong Gao Yinfeng Li Yue Ding Jianyu Wang Tianyu Lei Chuanyuan Xu Jinpeng Wang | 2023 | Horticulture Research2023,10,6: | 0 |
| 11 | Microenvironment components and spatially resolved single-cell transcriptome atlas of breast cancer metastatic axillary lymph nodes显示文摘As an indicator of clinical prognosis,lymph node metastasis of breast cancer has drawn great attention.Many reports have revealed the characteristics of metastatic breast cancer cells,however,the effect of breast cancer cells on the microenvironment components of lymph nodes and spatial transcriptome atlas remains unclear.In this study,by integrating single-cell RNA sequencing(scRNA-seq)and spatial transcriptomics,we investigate the transcriptional profiling of six surgically excised lymph node samples and the spatial organization of one positive lymph node.We identify the existence of osteoclast-like giant cells(OGC)which have high expressions of CD68 and CD163,the biomarkers of tumor-associated macrophages(TAMs).Through a spatially resolved transcriptomic method,we find that OGCs are scattered among metastatic breast cancer cells.In the lymph node microenvironment with breast cancer cell infiltration,TAMs are enriched in protumoral pathways including NF-kB signaling pathways and NoD-like receptor signaling pathways.Further subclustering demonstrates the potential differentiation trajectory in which macrophages develop from a state of active chemokine production to a state of active lymphocyte activation.This study is the first to integrate scRNA-seq and spatial transcriptomics in the tumor microenvironment of axillary lymph nodes,offering a systematic approach to delve into breast cancer lymph node metastasis. | Kun Xu Runtian Wang Qin Chen Yiqiu Liu Xintong Li Ling Mao Cenzhu Wang Fangyan Gao Longfei Hu Hui Xie Cong Wang Guohua Zhou Xiaoxiang Guan | 2022 | Acta Biochimica et Biophysica Sinica2022,54,9: | 0 |
| 12 | Efficacy and safety of monoclonal antibodies in neuromyelitis optica spectrum disorders:A survival meta-analysis of randomized controlled trials显示文摘Background Monoclonal antibodies such as rituximab(RTX),eculizumab,inebilizumab,satralizumab,and tocilizumab have been found to be effective therapies for neuromyelitis optica spectrum disease(NMOSD)in several clinical randomized controlled trials.Objective The purpose of this meta-analysis of randomized controlled trials was to assess the efficacy and safety of monoclonal antibodies in the treatment of NMOSD.Methods We searched the following databases for relevant English language literature from the establishment of the database to June 2021:PubMed,Embase,Cohorane Library,the Central Register of Controlled Trials(CENTRAL),and Web of Science.Randomized controlled trials of monoclonal antibodies were the targets of the review.Results We included seven trials containing 775 patients(485 in the monoclonal antibody group and 290 in the control group).Patients in the monoclonal group(HR 0.24,95%CI:0.14 to 0.40,P<0.00001),as well as patients with seropositive AQP4-IgG(HR 0.18,95%CI:0.11 to 0.29,P<0.00001),both had a higher free recurrence rate than that in the control group.In the first year(HR 0.25,95%CI:0.09 to 0.71,P=0.009)and the second year(HR 0.32,95%CI:0.13 to 0.81,P=0.02),no relapses were documented.The average changes of the expanded disability status scale(EDSS)score decreased by 0.29(95%CI:−0.09 to 0.51,P=0.005).Upper respiratory tract infection(OR 1.52,95%CI:0.76 to 3.04,P=0.24),urinary tract infection(OR 0.79,95%CI:0.51 to 1.21,P=0.27),and headache(OR 1.30,95%CI:0.78 to 2.17,P=0.31)were three most frequent adverse reactions.Conclusions Monoclonal antibodies are particularly effective treatments in avoiding recurrence for NMOSD patients,according to this meta-analysis.The associated adverse responses are not significantly different from those seen with traditional immunosuppressants. | Xintong Xu Lindan Xie Lili Wei Meixuan Li Hao Wang Huanfen Zhou Mingming Sun Mo Yang Quangang Xu Kehu Yang Shihui Wei | 2022 | Advances in Ophthalmology Practice and Research2022,2,3: | 0 |
| 13 | Research trends of worldwide ophthalmologic randomized controlled trials in the 21st century:A bibliometric study显示文摘Background:Randomized controlled trials(RCTs)are often considered the gold standard and the cornerstone for clinical practice.However,bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet.This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century.Methods:Global ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection.The number of publications,country/region,institution,author,journal,and research hotspots of RCTs were analyzed using HistCite,VOSviewer,CiteSpace,and Excel software.Results:2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs,with the United States leading in the number of volumes and research field,and the Moorfields Eye Hospital contributing to the most publications.Ophthalmology received the greatest number of publications and co-citations.Jeffrey S.Heier owned the most publications and Jost B.Jonas owned the most cocitations.The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy,glaucoma,dry eye disease(DED),and cataracts,and anti-vascular endothelial growth factor(VEGF)therapy(ranibizumab),topical ocular hypotensive medication,laser trabeculoplasty.Anti-VEGF therapy for age-related macular degeneration(AMD),DME(diabetic macular edema),and DED,the use of new diagnostic tools,and myopia were the hottest research highlights.Anti-VEGF therapy,prompt laser,triamcinolone,and verteporfin photodynamic therapy for AMD,DME,and CNV(choroidal neovascularization),DED,myopia,and open-angle glaucoma were the research hotspots with the longest duration.The future research hotspots might be DED and the prevention and control of myopia.Conclusions:Overall,the number of global ophthalmologic RCTs in the 21st century was keeping growing,there was an imbalance between the regions and institutions,and more efforts are required to raise the quantity,quality,and global impact of high-quality clinical evidence in developing countries/regions. | Hao Wang Qiang Ye Weihe Xu Jing Wang Jianhan Liu Xintong Xu Wenfang Zhang | 2023 | Advances in Ophthalmology Practice and Research2023,3,4: | 0 |
| 14 | Accuracy optimization of virtual iterative reduction algorithm under time constraint显示文摘The factors like production accuracy and completion time are the determinants of the optimal scheduling of the complex products work-flow,so the main research direction of modern work-flow technology is how to assure the dynamic balance between the factors.Based on the work-flow technology,restraining the completion time,and analyzing the deficiency of traditional minimum critical path algorithm,a virtual iterative reduction algorithm(VIRA)was proposed,which can improve production accuracy effectively with time constrain.The VIRA with simplification as the core abstracts a virtual task that can predigest the process by combining the complex structures which are cyclic or parallel,finally,by using the virtual task and the other task in the process which is the iterative reduction strategy,determines a path which can make the production accuracy and completion time more balanced than the minimum critical path algorithm.The deadline,the number of tasks,and the number of cyclic structures were used as the factors affecting the performance of the algorithm,changing the influence factors can improve the performance of the algorithm effectively through the analysis of detailed data.Consequently,comparison experiments proved the feasibility of the VIRA. | Luo Zhiyong Liu Xintong Xu haifeng Xie Zhiqiang Li Jie | 2023 | The Journal of China Universities of Posts and Telecommunications2023,30,2: | 0 |
| 15 | Au nanoparticles based ultra-fast “Turn-On” fluorescent sensor for detection of biothiols and its application in living cell imaging显示文摘Au or other metal nanostructures have the ability to strongly quench the fluorescence of fluorophores.This feature has made AuNP-conjugates attractive for the construction of platforms for various bioanalytes to overcome the limitations of small molecule fluorophores(poor solubility,long reaction time).In this paper,an ultrafast'Turn-On'fluo rescent sensor for biothiols was constructed.The sensor is based on the fluorescent resonance energy transfer(FRET)effect between the fluorophore(PN)and AuNPs,which effectively quenches the fluorescence of the fluorophore.In the presence of thiols,PN is displaced and released from AuNP surfaces,and thus,the fluorescence is rapidly restored.The sensor features appreciable water solubility and ultrafast response time(a few seconds for Cys).In addition,it exhibits high selectivity and a detection limit as low as 12 nmol/L for Hcy.Moreover,the sensor presents good biocompatibility and has been successfully applied for imaging biothiols in living cells. | Hailiang Zhang Pengfei Xu Xintong Zhang Xiaozheng Cao Wenxiu Han Meihui Liu Xiaohui Liu Wenbin Zeng | 2020 | Chinese Chemical Letters2020,31,5: | 0 |
| 16 | Coordination of a Socially Responsible Supply Chain with Cause Marketing Campaigns显示文摘This paper explores the coordination problem of a socially responsible supply chain,in which the supplier contributes corporate social responsibility by donating a specific amount of money to a cause marketing and the retailer cares for consumer surplus in addition to its own profit.We consider two donation formats:absolute amount donation and percentage of profit donation.For each donation format,the optimal solutions for the centralized and decentralized decisions are derived,and the effects of system parameters on the optimal decisions and other outcome variables are investigated.Moreover,a two-part tariff contract and a quantity discount plus cost sharing contract are proposed to coordinate the socially responsible supply chain.This study may provide theoretical support and operational procedures for supply chain managers to integrate corporate social responsibility into business routines. | Xin Li Minghui Xu Xintong Shi | 2021 | Journal of Systems Science and Systems Engineering2021,30,6: | 0 |
| 17 | Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression显示文摘Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC. | Runtian Wang Gaigai Li Fangyan Gao Feng Xu Xintong Li Jian Zhang Jinbo Li Xiaoxiang Guan | 2024 | Science China(Life Sciences)2024,67,4: | 0 |
| 18 | Inhibition of MYC suppresses programmed cell death ligand-1 expression and enhances immunotherapy in triple-negative breast cancer显示文摘Background:Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer(TNBC).One of the immunosuppressive pathways involves programmed cell death-1(PD-1)and programmed cell death ligand-1(PD-L1),but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment.Prior research has shown that MYC,a master transcription amplifier highly expressed in TNBC cells,can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy.This study aims to investigate the regulatory relationship between MYC and PD-L1,and whether a cyclin-dependent kinase(CDK)inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy.Methods:Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1.The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting.A patient-derived tumor xenograft(PDTX)model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression.Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine(EdU)cell proliferation and cell migration assays.Tumor xenograft models were established for in vivo verification.Results:A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells(TIICs).The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients.Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein.In addition,antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1.Conclusions:The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect,which might offer new insight for enhancing immunotherapy in TNBC. | Xintong Li Lin Tang Qin Chen Xumin Cheng Yiqiu Liu Cenzhu Wang Chengjun Zhu Kun Xu Fangyan Gao Jinyi Huang Runtian Wang Xiaoxiang Guan | 2022 | Chinese Medical Journal2022,135,20: | 0 |
| 19 | Optimization of depreciation subsidy policy strategies for electric two-wheelers for improving traffic safety显示文摘To improve the traffic safety of electric two-wheelers(ETW),China has promulgated ETW standardization policies.This policy requires local governments to take measures to guide the illegal ETWs out of use.Governments have implemented a depreciation subsidy scheme to encourage users to scrap illegal ETWs early.When designing the subsidy scheme,effectively improving the ETWs’traffic safety at the road network level while saving government expenses is essential for the sustainable implementation of the policy.This study proposes an optimization method for depreciation subsidy design incorporating traffic safety evaluation.Based on the policy scheme,this study formulates a risk assessment model for the ETW traffic network to characterize the effect of the subsidy on improving safety.Then,we use the bi-level programming approach to model the subsidy strategy design problem.The upper-level problem reflects the goal of policymakers to maximize safety improvement and minimize government expenses.The lower-level problem describes the route choices of ETW users.The optimal subsidy design under different safety-expense trade-offs is analysed based on the Nguyen and Dupuis network and a real network extracted from Changsha City in China.The results show that specific subsidy schemes effectively improve road safety without a large government spending.When themarket price or service life of ETWs increases,the government spending on the same safety goal increases.The government should comprehensively consider the safety effect of financial expense and the situation of the local ETW market before selecting reasonable subsidy strategies. | Xintong Li Helai Huang Chunyang Han Guangming Xu Jaeyoung Lee Cheng Hu | 2022 | Transportation Safety and Environment2022,4,3: | 0 |
| 20 | Cell-free expression of NO synthase and P450 enzyme for the biosynthesis of an unnatural amino acid L-4-nitrotryptophan显示文摘Cell-free system has emerged as a powerful platform with a wide range of in vitro applications and recently has contributed to express metabolic pathways for biosynthesis.Here we report in vitro construction of a native biosynthetic pathway for L-4-nitrotryptophan(L-4-nitro-Trp)synthesis using an Escherichia coli-based cell-free protein synthesis(CFPS)system.Naturally,a nitric oxide(NO)synthase(TxtD)and a cytochrome P450 enzyme(TxtE)are responsible for synthesizing L-4-nitro-Trp,which serves as one substrate for the biosynthesis of a nonribosomal peptide herbicide thaxtomin A.Recombinant coexpression of TxtD and TxtE in a heterologous host like E.coli for L-4-nitro-Trp production has not been achieved so far due to the poor or insoluble expression of TxtD.Using CFPS,TxtD and TxtE were successfully expressed in vitro,enabling the formation of L-4-nitro-Trp.After optimization,the cell-free system was able to synthesize approximately 360μM L-4-nitro-Trp within 16 h.Overall,this work expands the application scope of CFPS for study and synthesis of nitro-containing compounds,which are important building blocks widely used in pharmaceuticals,agrochemicals,and industrial chemicals. | Xintong Tian Wan-Qiu Liu Huiling Xu Xiangyang Ji Yushi Liu Jian Li | 2022 | Synthetic and Systems Biotechnology2022,7,2: | 0 |