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Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti-PD-1 therapy in colorectal cancer

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Signal Transduction and Targeted Therapy 2021年第2期6卷 447-460页

作者： Jing chen Hong-Wei Sun Yan-Yan Yang hai-tian chen Xing Juan Yu Wen Chao Wu Yi-Tuo Xu LiLian Jin Xiao-Jun Wu Jing Xu Limin Zheng State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina MOE Key Laboratory of Gene Function and Regulation School of Life SciencesSun Yat-sen UniversityGuangzhouChina First Afliated Hospital Sun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Dana Farber Cancer InstituteBostonMA.USA

Overcoming local immunosuppression is critical for immunotherapy to produce robust anti-tumor responses.Myeloid-derived suppressor cells(MDSCS)are key regulators of immunosuppressive networks and promote tumor progression.However,it remains unclear whether and how tumor-infltrating MDSCS are shaped in response to anti-PD-1 treatment and what their impact on therapeutic efficacy is in colorectal cancer(CRC).In this study,the levels of infltrating MDSCS were significantly higher in the non-responding organoids and were selectively reduced in the responding group,with MDSCS showing increased apoptosis and attenuated functional activity after anti-PD-1 treatment.A negative correlation between T-cell activation and MDSC function was also observed in fresh human CRC tissues.Mechanistic studies revealed that autocrine IFN-α/B upregulated TRAIL expression on activated T cells to elicit MDSC apoptosis via the TRAIL-DR5 interaction and acted synergistically with TNF-α to inhibit MDSC function of suppressing the T-cell response through the JNK NMDAR-ARG-1 pathway.Moreover,blockade of IFNa/βand TNF-α abolished the therapeutic efficacy of anti-PD-1 treatment by preserving the frequency and suppressive activity of infltrating MDSCS in a CRC mouse model.This result suggested that reprogramming MDSCS by IFN-α/βand TNF-α from activated T cells was necessary for succesful anti-PD-1 treatment and might serve as a novel strategy to improve the response and efficacy of anticancer therapy.

关键词： colorectal cancer programming

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Maternal Thyroid-Stimulating Hormone Level and Thyroid Peroxidase Antibody Status in the First and Second Trimester of Pregnancy and Their Relationship with the Risk of Gestational Diabetes Mellitus

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Maternal-Fetal Medicine 2019年第2期1卷 81-85页

作者： Song-Qing Deng hai-tian chen Dong-Yu Wang Bin Liu Han-Qing chen Zi-Lian Wang Department of Obstetrics and Gynecology The First Affiliated HospitalSun Yat-senUniversityGuangzhouGuangdong 510080China

Objective:To investigate thyroid-stimulating hormone(TSH)levels and thyroid peroxidase antibody(TPOAb)in early pregnancy and to estimate the risk of development of gestational diabetes mellitus(GDM).Methods:The levels of TSH,free thyroxine,free triiodothyronine,and TPOAb were retrospectively evaluated in 2333 pregnant women.All women recruited were divided into groups of TSH high(H),TSH low(L),TSH(H)TPOAb positive(+),TSH(H)TPOAb negative(-),TSH normal(N)TPOAb(+),TSH(L)TPOAb(+),TSH(L)TPOAb(-),and estimated the risk of GDM.Results:TSH level(X^(2)=13.0024,P=0.0015)and TSH combined TPOAb(X^(2)=20.0038,P=0.0012)were correlated to development of GDM.The level of TSH in 95 women was increased,and in 216 women were decreased.Of the 2333 pregnant women,546 patients were diagnosed with GDM,with a prevalence of 23.40%.The prevalence of GDM was 35.78%and 28.70%for the TSH high(H)and TSH low(L)pregnant women,respectively.The increased TSH(P=0.0013,odds ratio:2.09,confidence interval:1.34-3.28)was correlated to increase GDM incidence.TSH(H)TPOAb(+)(n=29),TSH(H)TPOAb(-)(n=58),TSH normal(N)TPOAb(+)(n=265),TSH(L)TPOAb(+)(n=30),TSH(L)TPOAb(-)(n=154)were in this study.The prevalence of GDM was 51.72%,29.31%,23.02%,26.67%,and 29.87%for the TSH(H)TPOAb(+),TSH(H)TPOAb(-),TSH(N)TPOAb(+),TSH(L)TPOAb(+),and TSH(L)TPOAb(-)pregnant women,respectively.Only the TSH(H)TPOAb(+)pregnant women had a significant higher incidence of GDM(P=0.0018,odds ratio:3.63,confidence interval:1.62-8.16).Trimester specific results showed that only second trimester had higher GDM risk either analyze TSH or the combination of TSH and TPOAb.Conclusion:Elevated TSH level and TPOAb positive in the second trimester of pregnancy were correlated to an increased risk of GDM.

关键词： Diabetes,gestational Thyrotropin Pregnancy trimester,first Pregnancy trimester,second

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SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei tian Xiaohong chen hai Zhang Ke Wang Zhinan chen Ruo chen National Translational Science Center for Molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

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Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1192-1203页

作者： Jian-Ping chen Ri-Hui Yang tian-Hui Zhang Li-An Liao Yu-Ting Guan hai-Yang Dai Department of Intervention Meizhou People’s HospitalMeizhou 514031Guangdong ProvinceChina Department of Medical Imaging Meizhou People’s HospitalMeizhou 514031Guangdong ProvinceChina Department of Medical Imaging Huizhou Municipal Central HospitalHuizhou 516001Guangdong ProvinceChina

BACKGROUND Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma(HCC)has great significance for patient prognosis.AIM To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)combined with clinical features in predicting early recurrence of HCC after resection.METHODS A total of 161 patients with pathologically confirmed HCC were enrolled.The patients were divided into early recurrence and non-early recurrence group based on the follow-up results.The clinical,laboratory,pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed.RESULTS Of 161 patients,73 had early recurrence and 88 were had non-early recurrence.Univariate analysis showed that patient age,gender,serum alpha-fetoprotein level,the Barcelona Clinic Liver Cancer stage,China liver cancer(CNLC)stage,microvascular invasion(MVI),pathological satellite focus,tumor size,tumor number,tumor boundary,tumor capsule,intratumoral necrosis,portal vein tumor thrombus,large vessel invasion,nonperipheral washout,peritumoral enhancement,hepatobiliary phase(HBP)/tumor signal intensity(SI)/peritumoral SI,HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation.Multivariate logistic regression analysis showed that patient age,MVI,CNLC stage,tumor boundary and large vessel invasion were independent predictive factors.External data validation indicated that the area under the curve of the combined predictors was 0.861,suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC.CONCLUSION Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

关键词： Hepatocellular carcinoma Enhanced magnetic resonance imaging Microvascular invasion Hepatobiliary phase Recurrence

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Visual test paper based on Au/δ-MnO_(2) hollow nanosphere oxidase-like activity regulation using hexavalent chromium as a smart switch

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Rare Metals 2024年第2期43卷 711-722页

作者： Wen-Chang Zhuang hai-Yue Zhang Zhen-Yang chen Wen-Jing cheng Wei-Dan Na Zhao Li Lin tian School of Materials and Chemical Engineering Xuzhou University of TechnologyXuzhou221018China School of Chemistry and Environmental Science Yili Normal UniversityYining835000China

Paper-based sensing platform is a point of need analytical toolkit for safety testing.However,the sensitivity,specificity,and simplicity are still challenging.Herein,we report a novel strategy(Au/δ-MnO_(2) hollow nanosphere and 3,3′,5,5′-tetramethylbenzidine(TMB)induced test strips for signal-on detection)that can be utilized for hexavalent chromium(Cr^(6+))detection.Interestingly,Cr^(6+)(CrO_(4)^(2−)) as a smart switch can remarkably enhance the oxidase-like activity of Au/δ-MnO_(2) hollow nanosphere.The presence of Cr^(6+) can regulate the surface electronic redistribution of Au/δ-MnO_(2) and adjust the geometric configuration,which leads to the improvement in oxidase-like activity of Au/δ-MnO_(2).As a proof-of-concept application,a visual paper-based sensing platform of Cr^(6+) along with quantitative analysis by the test strips was successfully constructed.This paper-based sensing platform exhibits a linear range with excellent selectivity for other interfering substances and lower limit of detection of 0.09μmol·L^(−1),providing a promising toolkit at-home Cr^(6+) measurement and environmental monitoring.

关键词： Point of need Colorimetric biosensing platform Au/δ-MnO_(2) hollow nanosphere Test strip Cr^(6+)

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Development of lithium-free P2-type high-sodium content cathode materials with enhanced cycle and air stability for sodium-ion batteries

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Rare Metals 2024年第1期43卷 113-123页

作者： Jin-Lv tian Lin-Rong Wu hai-Jun Zhao Shou-Dong Xu Liang chen Ding Zhang Xiao-Chuan Duan College of Chemical Engineering and Technology Taiyuan University of TechnologyTaiyuan 030024China College of Chemistry Taiyuan University of TechnologyTaiyuan 030024China School of Chemical Engineering and Pharmacy Wuhan Institute of TechnologyWuhan 430205China

The effect of partial substitution of Mg for Ni on a high-sodium and lithium-free layered P2-type Na_(45/54)Mg_(6)/_(54)Ni_(12/54)Mn_(34/54)O_(2) cathode with high initial Coulombic efficiency and excellent cyclic stability has been investigated in this study.Based on the crystal structural analysis,the Mg doping can retain the P2 structure up to 4.3 V,thus restraining the detrimental phase transformation of P2-02during the Na-ion intercalation/deintercalation process.Therefore,the obtained Mg-doped P2-type cathode exhibits a reversible specific capacity of 109 mAh·g^(-1) at 0.1C between 2.0 and 4.3 V and a retention rate of 81.5% after 200cycles at 1C.In addition,the full cell consisting of Mg-doped P2-type cathode and hard carbon anode shows a capacity retention rate of 85.6% after 100 cycles.This study provides new insight into the development of durable cathode materials for sodium-ion batteries.

关键词： Sodium-ion batteries Cathode material High sodium content Air stability

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Surface engineering of Li-and Mn-rich layered oxides for superior Li-ion battery

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Tungsten 2024年第1期6卷 259-268页

作者： Lu-Xiang Ma tian-Dong chen Chun-Xi hai Sheng-De Dong Xin He Qi Xu Hang Feng AXin Ji-Tao chen Yuan Zhou College of Materials and Chemistry and Chemical Engineering Chengdu University of TechnologyChendu 610000China Qinghai Building and Materials Research Co. LtdXining 810000China Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

The Li-and Mn-rich layered oxides(R-LNCM)are considered as promising cathode materials for high-energy density lithium-ion batteries(LIBs).However,the interface side reaction aggravates the voltage and capacity fading between cathode material and electrolyte at high voltage,which severely hinders the practical application of LIB s.Herein,lithium polyacrylate(LiPAA)as the binder and coating agent is applied to suppress the voltage and capacity fading of R-LNCM electrode.The flexible LiPAA layers with high elasticity are capable of impeding cathode cracks on the particle surface via mechanical stress relief.Thus,superior voltage and capacity fading suppression on R-LNCM electrode is finally achieved.As a result,LiPAA-R-LNCM cathode exhibits a remarkable specific capacity of 186 mA·h·g^(-1)with~73%retention at 1℃after 200cycles.Further,the corresponding average discharge potential is maintained to~3.1 V with only~0.4 V falling.

关键词： LiPAA interphase layer Interface side reaction Cathode cracks Capacity and voltage fading suppression Liand Mn-rich cathode

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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong Zhang Jing Qiao Hongming Zhu Li chen hai Fang Tong Yin Zhu chen Qiang tian Saijuan chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly understood.Here,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy.Our study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma composition.One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA.Furthermore,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins.Overall,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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Evolution of suspension bridge structural systems,design theories,and shape-finding methods:A literature survey

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第2期11卷 225-244页

作者： Wenming Zhang Genmin tian Yupeng chen Key Laboratory of Concrete and Pre-stressed Concrete Structures of Ministry of Education Southeast UniversityNanjing 210096China State Key Laboratory of Safety Durability and Healthy Operation of Long Span BridgesSoutheast UniversityNanjing 210096China

Modern suspension bridges exhibit a trend of lighter structures,more diversified structural forms,and longer spans,the latter already exceeding two kilometers.Bridge performance under dead and live loads depends on their structural and main cable systems,while cablesupported bridges especially rely on the design analysis and construction control of the main cable.This literary survey systematically analyzes the research progress and state-ofthe-art status quo in the structural systems and design theories of suspension bridges,focusing on the structural systems,main cable shape analyses,live load effect analyses,and emerging lucrative research directions.More than 100 reliable references have been surveyed.(1)Multi-span or multi-main cable schemes appeal to increasing attention,which may become a better choice in terms of structural systems in scenarios with extremely long spans and heavy loads.The cable layouts,such as spatial main cables and hybrid cable-stayed suspension systems have also become feasible approaches for enhancing structural stiffness.(2)The shape-finding analysis during the construction phase is more complex and has more essential factors than that of the completed bridge state.Refined theories combining analytical methods and finite element methods are more suitable for the shape-finding analysis of complex cable systems than any single theory of the two,especially for novel cable systems.(3)The live load effect analysis methods based on traditional deflection theory or modified/improved deflection theories still have wide applications,but the refined theory of treating hangers as discrete members is also constantly developing,which is expected to provide new ideas for more complex structural analysis under the different types of live loads and their distribution forms.

关键词： Suspension bridges Structural system Cable analysis Shape-finding analysis Construction control and calculation Live load effect

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Ovarian function in patients with systemic lupus erythematosus:Pathogenesis,drug application and prospective therapies

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World Journal of Experimental Medicine 2024年第2期14卷 29-34页

作者： Min Xu Li-Li tian Xiao-Liu Li cheng Bao hai-Wei Zhang Hong-Wei chen Department of Rheumatology and Immunology Nanjing Drum Tower HospitalClinical College of Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina School of Life Science Nanjing Normal UniversityNanjing 210023Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Drum Tower HospitalNanjing 210008Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Pukou People’s HospitalNanjing 211800Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of School of MedicineNanjing UniversityNanjing 210008Jiangsu ProvinceChina

Systemic lupus erythematosus(SLE)is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women.Currently,glucocorticoids and immunosuppressants are widely used to treat SLE patients.However,ovarian dysfunction occurs following the use of these drugs in women with SLE.Here,we summarize recent progress in terms of understanding ovarian injury,the effects of drug application and strategies to improve ovarian function in women with SLE.This review could be helpful to precisely cure SLE in women desiring to have offspring.

关键词： Systemic lupus erythematosus Ovarian reserve Ovarian insufficiency Mesenchymal stem cells Fertility Autoimmune disease

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