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The R2R3-MYB transcription factor GaPC controls petal coloration in cotton 被引量:1
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作者 Caiping Cai Fan Zhou +4 位作者 Weixi Li Yujia Yu Zhihan Guan baohong zhang Wangzhen Guo 《The Crop Journal》 SCIE CSCD 2023年第5期1319-1330,共12页
Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified ... Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified a gene(named GaPC) controlling petal coloration in Gossypium arboreum and following a heritable recessive epistatic genetic model. Petal coloration is controlled by a single dominant gene,GaPC. A loss-of-function mutation of GaPC leads to a recessive gene Gapc that masks the phenotype of other color genes and shows recessive epistatic interactions. Map-based cloning showed that GaPC encodes an R2R3-MYB transcription factor. A 4814-bp long terminal repeat retrotransposon insertion at the second exon led to GaPC loss of function and disabled petal coloration. GaPC controlled petal coloration by regulating the anthocyanin and flavone biosynthesis pathways. Expression of core genes in the phenylpropanoid and anthocyanin pathways was higher in colored than in white petals. Petal color was conferred by flavonoids and anthocyanins, with red and yellow petals rich in anthocyanin and flavonol glycosides, respectively. This study provides new insight on molecular mechanism of recessive epistasis,also has potential breeding value by engineering GaPC to develop colored petals or fibers for multifunctional utilization of cotton. 展开更多
关键词 COTTON Petal color R2R3-MYB transcription factor LTR-RT insertion Flavonoid/anthocyanin biosynthesis Recessive epistasis
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Membrane fluidity regulates high shear stress-induced FAK activation at different subcellular compartments
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作者 FEI XIE baohong zhang +3 位作者 WENFENG XU XIAOLING LIAO QIUHONG HUANG BO LIU 《BIOCELL》 SCIE 2017年第2期45-53,共9页
Focal adhesion kinase(FAK)plays a vital role in mediating the adaptability of tumor cells under mechanical stimuli.Previous studies revealed that FAK can locate to different cell compartments,and its regulation is hig... Focal adhesion kinase(FAK)plays a vital role in mediating the adaptability of tumor cells under mechanical stimuli.Previous studies revealed that FAK can locate to different cell compartments,and its regulation is highly dependent on its subcellular localization.However,the local FAK activities and its regulation mechanism in different cell compartments of tumor cells in response to fluid shear stress are still unclear.In this study,5 dyn/cm^(2) and 20 dyn/cm^(2) of shear stress was applied to HeLa cells for 30 min.The activities of FAK targeting different subcellular compartments(lipids rafts,non-rafts,focal adhesions and cytoplasm)were investigated with fluorescence resonance energy transfer(FRET)technology.Results showed that the activity of FAK in response to high shear stress at focal adhesion sites was lower than that of other three areas,while no difference among four areas was observed in response to low shear stress.Furthermore,high shear stress-induced distinct FAK activation at different compartments was inhibited by decreasing membrane fluidity,but Src inhibition prevented high shear stress-induced FAK activation only in the cytoplasm.This study revealed the spatiotemporal characteristics of FAK under the different magnitude of shear stress,which provides a deeper understanding of mechanotransduction in tumor cells. 展开更多
关键词 FAK activity shear stress FRET biosensor
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Transcriptional landscape of cotton roots in response to salt stress at single-cell resolution 被引量:2
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作者 Pengtao Li Qiankun Liu +20 位作者 Yangyang Wei Chaozhu Xing Zhongping Xu Fang Ding Yuling Liu Quanwei Lu Nan Hu Tao Wang Xiangqian Zhu Shuang Cheng Zhaoguo Li Zilin Zhao Yanfang Li Jiangping Han Xiaoyan Cai Zhongli Zhou Kunbo Wang baohong zhang Fang Liu Shuangxia Jin Renhai Peng 《Plant Communications》 SCIE CSCD 2024年第2期46-66,共21页
Increasing soil salinization has led to severe reductions in plant yield and quality,and investigating the mo-lecular mechanism of salt stress response is therefore an urgent priority.In this study,we systematically a... Increasing soil salinization has led to severe reductions in plant yield and quality,and investigating the mo-lecular mechanism of salt stress response is therefore an urgent priority.In this study,we systematically analyzed the response of cotton roots to salt stress using single-cell transcriptomics technology;56281 high-quality cells were obtained from 5-day-old lateral root tips of Gossypium arboreum under natural growth conditions and different salt treatments.Ten cell types with an array of novel marker genes were identified and confirmed by in situ RNA hybridization,and pseudotime analysis of some specific cell types revealed their potential differentiation trajectories.Prominent changes in cell numbers under salt stress were observed for outer epidermal and inner endodermal cells,which were significantly enriched in response to stress,amide biosynthetic process,glutathione metabolism,and glycolysis/gluconeogenesis.Analysis of differentially expressed genes identified in multiple comparisons revealed other functional ag-gregations concentrated on plant-type primary cell wall biogenesis,defense response,phenylpropanoid biosynthesis,and metabolic pathways.Some candidate differentially expressed genes encoding transcrip-tion factors or associated with plant hormones also responsive to salt stress were identified,and the func-tion of Ga03G2153,annotated as auxin-responsive GH3.6,was confirmed by virus-induced gene silencing.The GaGH3.6-silenced plants showed a severe stress-susceptible phenotype,and physiological and biochemical measurements indicated that they suffered more significant oxidative damage.These results suggest that GaGH3.6 might participate in cotton salt tolerance by regulating redox processes.We thus construct a transcriptional atlas of salt-stressed cotton roots at single-cell resolution,enabling us to explore cellular heterogeneity and differentiation trajectories and providing valuable insights into the mo-lecular mechanisms that underlie plant stress tolerance. 展开更多
关键词 cotton salt stress scRNA-seq root cell types virus-induced gene silencing
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Unlocking supercapacitive energy storage potential:Catalyzing electrochemically inactive manganese oxides to active MnO_(2)via heterostructure reconstruction
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作者 baohong zhang Tao Jiang +3 位作者 Xinyan Zhou Xiaoyu Fan Binbin Jia Lidong Li 《Nano Research》 SCIE EI CSCD 2024年第7期5897-5906,共10页
Advancing supercapacitor system performance hinges on the innovation of novel electrode materials seamlessly integrated within distinct architectures.Herein,we introduce a direct approach for crafting nanorod arrays f... Advancing supercapacitor system performance hinges on the innovation of novel electrode materials seamlessly integrated within distinct architectures.Herein,we introduce a direct approach for crafting nanorod arrays featuring crystalline/amorphous CuO/MnO_(2)−x.This reconfigured heterostructure results in an elevated content of electrochemically active MnO_(2).The nanorod arrays serve as efficient capacitive anodes and are easily prepared via low-potential electrochemical activation.The resulting structure spontaneously forms a p–n heterojunction,developing a built-in electric field that dramatically facilitates the charge transport process.The intrinsic electric field,in conjunction with the crystalline/amorphous architecture,enables a large capacitance of 1.0 F·cm^(−2)at 1.0 mA·cm^(−2),an ultrahigh rate capability of approximately 85.4%at 15 mA·cm^(−2),and stable cycling performance with 92.4%retention after 10,000 cycles.Theoretical calculations reveal that the presence of heterojunctions allows for the optimization of the electronic structure of this composite,leading to improved conductivity and optimized OH−adsorption energy.This work provides new insights into the rational design of heterogeneous nanostructures,which hold great potential in energy storage applications. 展开更多
关键词 RECONFIGURATION active MnO_(2) crystalline/amorphous structure p-n heterojunction SUPERCAPACITOR
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Widespread incomplete lineage sorting and introgression shaped adaptive radiation in the Gossypium genus
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作者 Yanchao Xu Yangyang Wei +14 位作者 Zhongli Zhou Xiaoyan Cai Scott ABoden Muhammad Jawad Umer Luqman BSafdar Yuling Liu Dingsha Jin Yuqing Hou Yuhong Wang Sarah Brooke Wall Kunbo Wang Shuxun Yu baohong zhang Renhai Peng Fang Liu 《Plant Communications》 SCIE CSCD 2024年第2期185-197,共13页
Cotton(Gossypium)stands as a crucial economic crop,serving as the primary source of naturalfiber for the textile sector.However,the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolv... Cotton(Gossypium)stands as a crucial economic crop,serving as the primary source of naturalfiber for the textile sector.However,the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolved.In this investigation,we leveraged 25 Gossypium genomes and introduced four novel assem-blies—G.harknessii,G.gossypioides,G.trilobum,and G.klotzschianum(Gklo)—to delve into the speciation history of this genus.Notably,we encountered intricate phylogenies potentially stemming from introgres-sion.These complexities are further compounded by incomplete lineage sorting(ILS),a factor likely to have been instrumental in shaping the swift diversification of cotton.Our focus subsequently shifted to the rapid radiation episode during a concise period in Gossypium evolution.For a recently diverged lineage comprising G.davidsonii,Gklo,and G.raimondii,we constructed afinely detailed ILS map.Intriguingly,this analysis revealed the non-random distribution of ILS regions across the reference Gklo genome.Moreover,we identified signs of robust natural selection influencing specific ILS regions.Noteworthy variations per-taining to speciation emerged between the closely related sister species Gklo and G.davidsonii.Approxi-mately 15.74%of speciation structural variation genes and 12.04%of speciation-associated genes were esti-mated to intersect with ILS signatures.Thesefindings enrich our understanding of the role of ILS in adaptive radiation,shedding fresh light on the intricate speciation history of the Gossypium genus. 展开更多
关键词 cotton speciation Gossypium genus incomplete lineage sorting ILS phylogenetic analysis gene tree resolution
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Unlocking single-atom catalysts via amorphous substrates
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作者 Bohua Sun Mingyuan Xu +5 位作者 Xiaoxia Li baohong zhang Rui Hao Xiaoyu Fan Binbin Jia Dingshun She 《Nano Research》 SCIE EI CSCD 2024年第5期3533-3546,共14页
Single-atom catalysts(SACs)reveal great potential for application in catalysis due to their fully exposed active sites.In general,single atoms(SAs)and the coordination substrates need to have strong interactions or ch... Single-atom catalysts(SACs)reveal great potential for application in catalysis due to their fully exposed active sites.In general,single atoms(SAs)and the coordination substrates need to have strong interactions or charge transfer to ensure the atomic dispersion,which requires the selection of a suitable substrate to stabilize the target atoms.Recent studies have demonstrated that amorphous materials with abundant defects and coordinatively unsaturated sites can be used as substrates for more efficient capturing SAs,further enhancing the catalytic performance.In this review,we discuss recent research progress of SAs loaded on amorphous substrates for enhanced catalytic activity.Firstly,we summarize the commonly used amorphous substrates for stabilizing SAs.Subsequently,we present several advanced applications of amorphous SACs in the field of catalysis,including electrocatalysis and photocatalysis.And then,we also clarify the synergistic mechanism between SAs and amorphous substrate on catalytic process.Finally,we summarize the challenges with our personal views and provide a critical outlook on how amorphous SACs continue to evolve. 展开更多
关键词 single-atoms amorphous substrate synthetic strategy CATALYSIS
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Advance in 3D self-supported amorphous nanomaterials for energy storage and conversion 被引量:3
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作者 baohong zhang Yanhong Li +3 位作者 Haoze Bai Binbin Jia Di Liu Lidong Li 《Nano Research》 SCIE EI CSCD 2023年第7期10597-10616,共20页
The advancement of next-generation energy technologies calls for rationally designed and fabricated electrode materials that have desirable structures and satisfactory performance.Three-dimensional(3D)self-supported a... The advancement of next-generation energy technologies calls for rationally designed and fabricated electrode materials that have desirable structures and satisfactory performance.Three-dimensional(3D)self-supported amorphous nanomaterials have attracted great enthusiasm as the cornerstone for building high-performance nanodevices.In particular,tremendous efforts have been devoted to the design,fabrication,and evaluation of self-supported amorphous nanomaterials as electrodes for energy storage and conversion devices in the past decade.However,the electrochemical performance of devices assembled with 3D self-supported amorphous nanomaterials still remains to be dramatically promoted to satisfy the demands for more practical applications.In this review,we aim to outline the achievements made in recent years in the development of 3D self-supported amorphous nanomaterials for a broad range of energy storage and conversion processes.We firstly summarize different synthetic strategies employed to synthesize 3D nanomaterials and to tailor their composition,morphology,and structure.Then,the performance of these 3D self-supported amorphous nanomaterials in their corresponding energy-related reactions is highlighted.Finally,we draw out our comprehensive understanding towards both challenges and prospects of this promising field,where valuable guidance and inspiration will surely facilitate further development of 3D self-supported amorphous nanomaterials,thus enabling more highly efficient energy storage and conversion devices that play a key role in embracing a sustainable energy future. 展开更多
关键词 three-dimensional(3D)self-supported amorphous nanomaterials synthetic strategy energy storage energy conversion
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Construction of amorphous/crystalline heterointerfaces for enhanced electrochemical processes 被引量:3
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作者 Binbin Jia baohong zhang +3 位作者 Zhi Cai Xiuyi Yang Lidong Li Lin Guo 《eScience》 2023年第2期60-76,共17页
Amorphous nanomaterials have emerged as potential candidates for energy storage and conversion owing to their amazing physicochemical properties.Recent studies have proved that the manipulation of amorphous nanomater... Amorphous nanomaterials have emerged as potential candidates for energy storage and conversion owing to their amazing physicochemical properties.Recent studies have proved that the manipulation of amorphous nanomaterials can further enhance electrochemical performance.To date,various feasible strategies have been proposed,of which amorphous/crystalline(a-c)heterointerface engineering is deemed an effective approach to break through the inherent activity limitations of electrode materials.The following review discusses recent research progress on a-c heterointerfaces for enhanced electrochemical processes.The general strategies for synthesizing ac heterojunctions are first summarized.Subsequently,we highlight various advanced applications of a-c heterointerfaces in the field of electrochemistry,including for supercapacitors,batteries,and electrocatalysts.We also elucidate the synergistic mechanism of the crystalline phase and amorphous phase for electrochemical processes.Lastly,we summarize the challenges,present our personal opinions,and offer a critical perspective on the further development of a-c nanomaterials. 展开更多
关键词 NANOCOMPOSITES Amorphous/crystalline heterogeneous INTERFACES Synthetic strategy Electrochemical process
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Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector(VSV_(MT))in golden syrian hamster
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作者 Yong Ke En zhang +8 位作者 Jianming Guo Xiaoxiao zhang Lei Wang Duo Chen Xinkui Fang Jianwei Zhu Feng Li Tao Sun baohong zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第12期4856-4874,共19页
COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which i... COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which inducing potent and comprehensive immunities.Currently,there are two clinical trials investigating COVID-19vaccines based on VSV vectors.These vaccines were developed with spike protein of WA1 which administrated intramuscularly.Although intranasal route is ideal for activating mucosal immunity with VSV vector,safety is of concern.Thus,a highly attenuated rVSV with three amino acids mutations in matrix protein(VSV_(MT))was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern.It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently.VSV_(MT) indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein.With a single-dosed intranasal inoculation of rVSV_(ΔGMT)-S_(Δ21),potent SARS-CoV-2specific neutraliza-tion antibodies could be stimulated in animals,particularly in term of mucosal and cellular immunity.Strikingly,the chimeric VSV encoding S_(Δ21) of Delta-variant can induce more potent immune responses compared with those encoding S_(Δ21) of Omicron-or WA1-strain.VSV_(MT) is a promising platform to develop a mucosal vaccine for countering COVID-19. 展开更多
关键词 COVID-19 Vesicular stomatitisvirus Matrix protein mutant Mucosal Vaccine Spike protein Variants of concerns Intranasal inoculation Cellular immunity
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Computational Tools and Resources for CRISPR/Cas Genome Editing
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作者 Chao Li Wen Chu +6 位作者 Rafaqat Ali Gill Shifei Sang Yuqin Shi Xuezhi Hu Yuting Yang Qamar U.Zaman baohong zhang 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2023年第1期108-126,共19页
The past decade has witnessed a rapid evolution in identifying more versatile clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)nucleases and their functional variants,as ... The past decade has witnessed a rapid evolution in identifying more versatile clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)nucleases and their functional variants,as well as in developing precise CRISPR/Cas-derived genome editors.The programmable and robust features of the genome editors provide an effective RNAguided platform for fundamental life science research and subsequent applications in diverse scenarios,including biomedical innovation and targeted crop improvement.One of the most essential principles is to guide alterations in genomic sequences or genes in the intended manner without undesired off-target impacts,which strongly depends on the efficiency and specificity of single guide RNA(sgRNA)-directed recognition of targeted DNA sequences.Recent advances in empirical scoring algorithms and machine learning models have facilitated sgRNA design and off-target prediction.In this review,we first briefly introduce the different features of CRISPR/Cas tools that should be taken into consideration to achieve specific purposes.Secondly,we focus on the computer-assisted tools and resources that are widely used in designing sgRNAs and analyzing CRISPR/Cas-induced on-and off-target mutations.Thirdly,we provide insights into the limitations of available computational tools that would help researchers of this field for further optimization.Lastly,we suggest a simple but effective workflow for choosing and applying web-based resources and tools for CRISPR/Cas genome editing. 展开更多
关键词 Genome editing Efficiency and specificity CRISPR/Cas9 sgRNA Computational tool Algorithm
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CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement 被引量:8
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作者 Chao LI Eleanor BRANT +1 位作者 Hikmet BUDAK baohong zhang 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2021年第4期253-284,共32页
Since it was first recognized in bacteria and archaea as a mechanism for innate viral immunity in the early 2010 s,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)has ra... Since it was first recognized in bacteria and archaea as a mechanism for innate viral immunity in the early 2010 s,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)has rapidly been developed into a robust,multifunctional genome editing tool with many uses.Following the discovery of the initial CRISPR/Cas-based system,the technology has been advanced to facilitate a multitude of different functions.These include development as a base editor,prime editor,epigenetic editor,and CRISPR interference(CRISPRi)and CRISPR activator(CRISPRa)gene regulators.It can also be used for chromatin and RNA targeting and imaging.Its applications have proved revolutionary across numerous biological fields,especially in biomedical and agricultural improvement.As a diagnostic tool,CRISPR has been developed to aid the detection and screening of both human and plant diseases,and has even been applied during the current coronavirus disease 2019(COVID-19)pandemic.CRISPR/Cas is also being trialed as a new form of gene therapy for treating various human diseases,including cancers,and has aided drug development.In terms of agricultural breeding,precise targeting of biological pathways via CRISPR/Cas has been key to regulating molecular biosynthesis and allowing modification of proteins,starch,oil,and other functional components for crop improvement.Adding to this,CRISPR/Cas has been shown capable of significantly enhancing both plant tolerance to environmental stresses and overall crop yield via the targeting of various agronomically important gene regulators.Looking to the future,increasing the efficiency and precision of CRISPR/Cas delivery systems and limiting off-target activity are two major challenges for wider application of the technology.This review provides an in-depth overview of current CRISPR development,including the advantages and disadvantages of the technology,recent applications,and future considerations. 展开更多
关键词 Genome editing Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas) Coronavirus disease 2019(COVID-19) Cancer Precision breeding Crop improvement Gene knock-out/in Gene repair/replacement
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Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement 被引量:2
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作者 Zhidi Pan Jie Chen +11 位作者 Xiaodong Xiao Yueqing Xie Hua Jiang baohong zhang Huili Lu Yunsheng Yuan Lei Han Yuexian Zhou Huifang Zong Lei Wang Rui Sun Jianwei Zhu 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第4期1928-1942,共15页
T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of... T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of the specificity of T cell receptor.Tissue factor(TF)is a TAA that involved in tumor progression.Here,we designed and characterized a novel TCB targeting TF(TF-TCB)for the treatment of TF-positive tumors.In vitro,robust T cell activation,tumor cell lysis and T cell proliferation were induced by TF-TCB.The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB,and was related to TF expression level of tumor cells.In vivo,in both tumor cell/human peripheral blood mononuclear cells(PBMC)co-grafting model and established tumor models with poor T cell infiltration,tumor growth was strongly inhibited by TF-TCB.T cell infiltration into tumors was induced during the treatment.Furthermore,efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors.For the first time,our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment. 展开更多
关键词 T cell engaging bispecific antibody IMMUNOTHERAPY Tissue factor Solid tumor Pancreatic cancer Lung cancer PD-1 antibody
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Direct induction of cotton somatic embryogenesis 被引量:2
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作者 baohong zhang Rong Feng +1 位作者 Fang Liu Changbing Yao 《Chinese Science Bulletin》 SCIE EI CAS 1999年第8期766-767,共2页
COMPARED with indirect somatic embryogenesis,direct somatic embryogenesis apprars to be assoeiated with greater genetic and cytological uniformity,and it takes less time to induce direct embutogenesis
关键词 ROOT ZT
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Mutational escape prevention by combination of four neutralizing antibodies that target RBD conserved regions and stem helix
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作者 Haoneng Tang Yong Ke +10 位作者 Yunji Liao Yanlin Bian Yunsheng Yuan Ziqi Wang Li Yang Hang Ma Tao Sun baohong zhang Xiaoju zhang Mingyuan Wu Jianwei Zhu 《Virologica Sinica》 SCIE CAS CSCD 2022年第6期860-873,共14页
New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2... New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2’s adaptability so as to seek for strategies to mitigate the emergence of new variants, herein we investigated the viral adaptation in the presence of broadly neutralizing antibodies and their combinations. First, we selected four broadly neutralizing antibodies, including pan-sarbecovirus and pan-betacoronavirus neutralizing antibodies that recognize distinct conserved regions on receptor-binding domain(RBD) or conserved stem-helix region on S2 subunit.Through binding competition analysis, we demonstrated that they were capable of simultaneously binding.Thereafter, a replication-competent vesicular stomatitis virus pseudotyped with SARS-CoV-2 spike protein was employed to study the viral adaptation. Twenty consecutive passages of the virus under the selective pressure of individual antibodies or their combinations were performed. It was found that it was not hard for the virus to adapt to broadly neutralizing antibodies, even for pan-sarbecovirus and pan-betacoronavirus antibodies. The virus was more and more difficult to escape the combinations of two/three/four antibodies. In addition, mutations in the viral population revealed by high-throughput sequencing showed that under the selective pressure of three/four combinational antibodies, viral mutations were not prone to present in the highly conserved region across betacoronaviruses(stem-helix region), while this was not true under the selective pressure of single/two antibodies.Importantly, combining neutralizing antibodies targeting RBD conserved regions and stem helix synergistically prevented the emergence of escape mutations. These studies will guide future vaccine and therapeutic development efforts and provide a rationale for the design of RBD-stem helix tandem vaccine, which may help to impede the generation of novel variants. 展开更多
关键词 SARS-CoV-2 ADAPTATION Spike protein Stem helix Broadly neutralizing antibody
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