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| 1 | SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade显示文摘Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy. | Mingxia Zhao Wenjie Guo Yuanyuan Wu Chenxi Yang Liang Zhong Guoliang Deng Yuyu Zhu Wen Liu Yanhong Gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 18 |
| 2 | Tailoring the secondary phases and mechanical properties of ODS steel by heat treatment显示文摘The oxide dispersion strengthened(ODS) steel with the nominal composition of Fe–14 Cr–2 W–0.3 Ti–0.2 V–0.07 Ta–0.3 Y2O3(wt%) was fabricated by mechanical alloying and hot isostatic pressing(HIP). In order to optimize the relative volume fraction of secondary phases, the as-HIPed ODS steel was annealed at 800°C, 1000°C, 1200°C for 5 h, respectively. The microstructures and different secondary phases of the as-HIPed and annealed ODS samples were identified by scanning electron microscopy(SEM), transmission electron microscopy(TEM), and X-ray diffraction(XRD). The tensile properties of all the ODS steels at room temperature were also investigated. The results indicate that annealing is an effective way to control the microstructure and the integral secondary phases. The annealing process promotes the dissolution of M23C6 particles, thus promoting the precipitation of TiC.No obvious coarsening of Y2Ti2O7 nanoparticles can be observed during annealing. The tensile results indicate that the annealed ODS sample with the optimized secondary phases and high density possesses the best mechanical properties. | Qian Zhao Zongqing Ma Liming Yu Huijun Li Chenxi Liu Chong Li Yongchang Liu | 2019 | Journal of Materials Science & Technology2019，35，6： | 6 |
| 3 | Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression显示文摘Cholangiocarcinoma(CCA)has emerged as an intractable cancer with scanty therapeutic regimens.The aberrant activation of Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)are reported to be common in CCA patients.However,the underpinning mechanism remains poorly understood.Deubiquitinase(DUB)is regarded as a main orchestrator in maintaining protein homeostasis.Here,we identified Josephin domain-containing protein 2(JOSD2)as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner.The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation in vitro and in vivo.Further analysis has highlighted the positive correlation between JOSD2 and YAP abundance in CCA patient samples.Collectively,this study uncovers the regulatory effects of JOSD2 on YAP/TAZ protein stabilities and profiles its contribution in CCA malignant progression,which may provide a potential intervention target for YAP/TAZ-related CCA patients. | Meijia Qian Fangjie Yan Weihua Wang Jiamin Du Tao Yuan Ruilin Wu Chenxi Zhao Jiao Wang Jiabin Lu Bo Zhang Nengming Lin Xin Dong Xiaoyang Dai Xiaowu Dong Bo Yang Hong Zhu Qiaojun He | 2021 | Acta Pharmaceutica Sinica B2021，11，12： | 5 |
| 4 | Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting显示文摘Monoclonal antibodies(m Abs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17 A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17 A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-h IL-17 A antibody. From a large na?ve phage-displayed library, we isolated the anti-IL-17 A m Ab 7 H9 that can neutralize the effects of recombinant human IL-17 A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. In vitro affinity optimization was then used to generate 8 D3 by using yeast-displayed random mutagenesis libraries.This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions(CDRs) of 8 D3 were further grafted onto the stable framework of the hu Fv 4 D5 to improve thermostability. The resulting hybrid antibody9 NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cellbased assays and in vivo analyses in mice indicated that the anti-IL-17 A antibody 9 NT/S efficiently inhibited the secretion of IL-17 A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17 A m Ab might be used as a potential best-in-class candidate for treating IL-17 A related diseases. | Wei Sun Zhaona Yang Heng Lin Ming Liu Chenxi Zhao Xueying Hou Zhuowei Hu Bing Cuin | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 4 |
| 5 | Enhanced grain refinement of Al-Si alloys by novel Al-V-B refiners显示文摘Al-V-B master alloy is promising for refining Al-Si alloys,yet its optimal composition with superior efficacy remains to be explored.In this work,the evolution of refining phases in the Al-10 Si/Al-V-B system with different V:B ratios was evaluated by thermodynamic calculations,based on which the Al-V-B refiners with V:B=1:1 and 5:1 were designed.Refining trails demonstrated that they could significantly reduce the grain size of Al-10 Si(wt.%)alloy from 1736 to 184-245μm with industrial addition amount.Detailed examinations results clarify that when V:B ratio is 1:1 the nucleation particle is(V,Al)B_(2),which has a VB_(2)-AlB_(2) core-shell structure and therefore presents the nucleation capability as AlB_(2) particle.When V:B ratio is as high as 5:1,the nucleation particle is pure VB_(2).Density functional theory(DFT)calculation indicates that(0001)VB_(2)/(111)α-Al interface has the lowest interfacial energy such that highest nucleation potency among other types of diboride/α-Al interfaces under consideration.The outcomes of this work provide fundamental guidance to develop superior V-B based refiners for Al-Si alloys. | Chenxi Zhao Yang Li Jin Xu Qun Luo Ying Jiang Qiling Xiao Qian Li | 2021 | Journal of Materials Science & Technology2021，，35： | 4 |
| 6 | Defects Engineering with Multiple Dimensions in Thermoelectric Materials显示文摘Going through decades of development,great progress in both theory and experiment has been achieved in thermoelectric materials.With the growing enhancement in thermoelectric performance,it is also companied with the complexation of defects induced in the materials.0D point defects,1D linear defects,2D planar defects,and 3D bulk defects have all been induced in thermoelectric materials for the optimization of thermoelectric performance.Considering the distinct characteristics of each type of defects,in-depth understanding of their roles in the thermoelectric transport process is of vital importance.In this paper,we classify and summarize the defect-related physical effects on both band structure and transport behavior of carriers and phonons when inducing different types of defects.Recent achievements in experimental characterization and theoretical simulation of defects are also summarized for accurately determining the type of defects serving for the design of thermoelectric materials.Finally,based on the current theoretical and experimental achievements,strategies engaged with multiple dimensional defects are reviewed for thermoelectric performance optimization. | Chenxi Zhao Zhou Li Tianjiao Fan Chong Xiao Yi Xie | 2020 | Research2020，，1： | 4 |
| 7 | Tailored morphology and highly enhanced phonon transport in polymer fibers:a multiscale computational framework显示文摘Although tremendous efforts have been devoted to enhance thermal conductivity in polymer fibers,correlation between the thermal-drawing conditions and the resulting chain alignment,crystallinity,and phonon transport properties have remained obscure.Using a carefully trained coarse-grained force field,we systematically interrogate the thermal-drawing conditions of bulk polyethylene samples using large-scale molecular dynamics simulations.An optimal combination of moderate drawing temperature and strain rate is found to achieve highest degrees of chain alignment,crystallinity,and the resulting thermal conductivity.Such combination is rationalized by competing effects in viscoelastic relaxation and condensed to the Deborah number,a predictive metric for the thermal-drawing protocols,showing a delicate balance between stress localizations and chain diffusions.Upon tensile deformation,the thermal conductivity of amorphous polyethylene is enhanced to 80% of the theoretical limit,that is,its pure crystalline counterpart.An effective-medium-theory model,based on the serial-parallel heat conducting nature of semicrystalline polymers,is developed here to predict the impacts from both chain alignment and crystallinity on thermal conductivity.The enhancement in thermal conductivity is mainly attributed to the increases in the intrinsic phonon mean free path and the longitudinal group velocity.This work provides fundamental insights into the polymer thermal-drawing process and establishes a complete process–structure–property relationship for enhanced phonon transport in all-organic electronic devices and efficiency of polymeric heat dissipaters. | Shangchao Lin Zhuangli Cai Yang Wang Lingling Zhao Chenxi Zhai | 2019 | npj Computational Materials2019，，1： | 3 |
| 8 | Multicomponent Nanoparticles Synergistic One-Dimensional Nanofibers as Heterostructure Absorbers for Tunable and Efficient Microwave Absorption显示文摘Application of novel radio technologies and equip-ment inevitably leads to electromagnetic pollution.One-dimensional polymer-based composite membrane structures have been shown to be an effective strategy to obtain high-performance microwave absorbers.Herein,we reported a one-dimensional N-doped carbon nanofibers material which encapsulated the hollow Co_(3)SnC_(0.7) nano-cubes in the fiber lumen by electrospinning.Space charge stacking formed between nanoparticles can be channeled by longitudinal fibrous structures.The dielectric constant of the fibers is highly related to the carbonization temperature,and the great impedance matching can be achieved by synergetic effect between Co_(3)SnC_(0.7) and carbon network.At 800℃,the necklace-like Co_(3)SnC_(0.7)/CNF with 5%low load achieves an excellent RL value of−51.2 dB at 2.3 mm and the effective absorption bandwidth of 7.44 GHz with matching thickness of 2.5 mm.The multiple electromagnetic wave(EMW)reflections and interfacial polarization between the fibers and the fibers internal contribute a major effect to attenuating the EMW.These strategies for regulating electromagnetic performance can be expanded to other electromagnetic functional materials which facilitate the development of emerging absorbers. | Chenxi Wang Yue Liu Zirui Jia Wanru Zhao Guanglei Wu | 2023 | Nano-Micro Letters2023，15，1： | 3 |
| 9 | Acoustic properties of closed-cell aluminum foams with different macrostructures显示文摘As structural materials, closed-cell aluminum foams possess obvious advantages in product dimension, strength and process economics compared with open cell aluminum foams. However, as a kind of structure-function integration materials, the application of closed-cell aluminum foams has been restricted greatly in acoustic fields due to the difficulty of sound wave penetration. It was reported that closed-cell foams with macrostructures have important effect on the propagation of sound waves. To date, the relationship between macrostructures and acoustic properties of commercially pure closedcell aluminum foams is ambiguous. In this work, different perforation and air gap types were designed for changing the macrostructures of the foam. Meanwhile, the effect of macrostructures on the sound absorption coefficient and sound reduction index were investigated. The results showed that the foams with half-hole exhibited excellent sound absorption and sound insulation behaviors in high frequency range(>2500 Hz). In addition, specimens with air gaps showed good sound absorption properties in low frequency compared with the foams without air gaps. Based on the experiment results, propagation structural models of sound waves in commercially pure closed-cell aluminum foams with different macrostructures were built and the influence of macrostructures on acoustic properties was discussed. | Xingchuan Xia Zan Zhang Weimin Zhao Chong Li Jian Ding Chenxi Liu Yongchang Liu | 2017 | Journal of Materials Science & Technology2017，33，11： | 3 |
| 10 | Exome sequencing reveals genetic architecture in patients with isolated or syndromic short stature显示文摘Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature. | Xin Fan Sen Zhao Chenxi Yu Di Wu Zihui Yan Lijun Fan Yanning Song Yi Wang Chuan Li Yue Ming Baoheng Gui Yuchen Niu Xiaoxin Li Xinzhuang Yang Shiyu Luo Qiang Zhang Xiuli Zhao Hui Pan Mei Li Weibo Xia Guixing Qiu Pengfei Liu Shuyang Zhang Jianguo Zhang Zhihong Wu James R.Lupski Jennifer E.Posey Shaoke Chen Chunxiu Gong Nan Wu | 2021 | Journal of Genetics and Genomics2021，48，5： | 2 |
| 11 | Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis显示文摘Impairment of glucose(Glu)uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases.Heterogeneous nuclear ribonucleoprotein A1(hnRNP Al)is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions.The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis.Our results showed that conditional deletion of hnRNP Al in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet(HFD).Conditional knockout mice fed a HFD showed exacerbated obesity,insulin resistance,and hepatic steatosis.In vitro interference of hnRNP Al in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake,whereas hnRNP Al overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin.The expression and stability of glycogen synthase(gysl)mRNA were also decreased in the absence of hnRNP A l.Mechanistically,hnRNP Al interacted with gys l and stabilized its mRNA,thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue.Taken together,our findings are the first to show that reduced expression of hnRNP Al in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis. | Mingxia Zhao Lihong Shen Zijun Ouyang Manru Li Guoliang Deng Chenxi Yang Wei Zheng Lingdong Kong Xuefeng Wu Xudong Wu Wenjie Guo Ye Yin Qiang Xu Yang Sun | 2020 | Journal of Molecular Cell Biology2020，12，4： | 2 |
| 12 | Inhibition of furin by bone targeting superparamagnetic iron oxide nanoparticles alleviated breast cancer bone metastasis显示文摘Breast cancer bone metastasis poses significant challenge for therapeutic strategies.Inside the metastatic environment,osteoclasts and tumor cells interact synergistically to promote cancer progression.In this study,the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function.Importantly,the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide(SPIO)nanoparticles.Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion,leading to alleviated osteolysis.Therefore,the bone targeting&furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis. | Yichuan Pang Li Su Yao Fu Fan Jia Chenxi Zhang Xiankun Cao Wenxin He Xueqian Kong Jiake Xu Jie Zhao An Qin | 2021 | Bioactive Materials2021，6，3： | 2 |
| 13 | Engineering tailorable TiO_(2) nanotubes for NIR-controlled drug delivery显示文摘Infectious diseases caused by bacteria are a global threat to the human health. Here, we propose a solvent “irrigation” technique to endow TiO_(2) nanotubes (NTs) to precisely modify with functional nanomaterials, and apply them in constructing a near-infrared (NIR) light controlled drug-delivery system for rapid necrosis of bacteria. In this design, the NIR stimuli-responsive functional shell is located on the external tube wall of TiO_(2) NT;the internal tube wall offers sufficient binding sites for drug loading. Using kanamycin as a model drug, we demonstrate that the reactive oxygen species generated in photocatalysis not only controllably release the loaded drug by scissoring the linked chains, but also effectively compromise bacteria membrane integrity by damaging the cell wall. Benefiting from the damages, antibiotics rapidly enter the bacteria and reach ≥99.9% reduction in Escherichia coli colony within only 2 h. Importantly, such a covalently conjugation-based delivery system can efficiently relieve radical-induced inflammation and cytotoxicity. This study provides an innovative design strategy for engineering delivery systems with tailorable components, enduring stimuli-response by multiple triggers. | Yue Xu Chenxi Zhao Xi Zhang Jingwen Xu Lingling Yang Zhechen Zhang Zhida Gao Yan-Yan Song | 2021 | Nano Research2021，14，11： | 1 |
| 14 | 显示文摘 | ZHAO Baohui LI Chenxi LU Yan | 2005 | Polymer2005，46，： | 1 |
| 15 | Xylose fermentation to biofuels (hydrogen and ethanol) by extreme thermophilic (70oC) mixed cuhure 显示文摘 | CHENXI ZHAO DINITAR KARAKASHEV WENJING LU | 2010 | International Journal of Hydrogen Energy2010，35，8： | 1 |
| 16 | Crystal structures and magnetic properties of two complexes synthesized from manganese and halogenophenyl-substituted nitronyl nitroxide显示文摘 | Zhang Chenxi Zhao Xiangyu Sun Nana | 2011 | Inorg Chim Acta2011，367，1： | 1 |
| 17 | Efficient interlayer charge release for high-performance layered thermoelectrics显示文摘Many layered superlattice materials intrinsically possess large Seebeck coefficient and low lattice thermal conductivity,but poor electrical conductivity because of the interlayer transport barrier for charges,which has become a stumbling block for achieving high thermoelectric performance.Herein,taking Bi Cu Se O superlattice as an example,it is demonstrated that efficient interlayer charge release can increase carrier concentration,thereby activating multiple Fermi pockets through Bi/Cu dual vacancies and Pb codoping.Experimental results reveal that the extrinsic charges,which are introduced by Pb and initially trapped in the charge-reservoir[Bi_(2)O_(2)]^(2+)sublayers,are effectively released into[Cu_(2)Se_(2)]^(2-)sublayers via the channels bridged by Bi/Cu dual vacancies.This efficient interlayer charge release endows dual-vacancy-and Pb-codoped Bi Cu Se O with increased carrier concentration and electrical conductivity.Moreover,with increasing carrier concentration,the Fermi level is pushed down,activating multiple converged valence bands,which helps to maintain a relatively high Seebeck coefficient and yield an enhanced power factor.As a result,a high ZT value of 1.4 is achieved at 823 K in codoped Bi^(0.90)Pb^(0.06)Cu^(0.96)SeO,which is superior to that of pristine Bi Cu Se O and solely doped samples.The present findings provide prospective insights into the exploration of high-performance thermoelectric materials and the underlying transport physics. | Hao Zhu Zhou Li Chenxi Zhao Xingxing Li Jinlong Yang Chong Xiao Yi Xie | 2021 | National Science Review2021，8，2： | 1 |
| 18 | Comparative analysis of chemical components of essential oils from different samples of Rhododendron with the help of chemometrics methods 显示文摘 | ZHAO Chenxi LI Xiaoning LIANG Yizeng | 2006 | Chemom Intell Lab Syst2006，82，12： | 1 |
| 19 | The action mechanisms of plant cryptochromes显示文摘 | Hongtao Liu Bin Liu Chenxi Zhao Michael Pepper Chentao Lin | 2011 | Trends in Plant Science2011，，12： | 1 |
| 20 | Comparative analysis of volatile components from Clematis species growing in China显示文摘 | ZENG Yingxu ZHAO Chenxi LIANG Yizeng | 2007 | Analytica Chimica Acta2007，595，12： | 1 |
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