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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO tian YUCAI CHENG wenFANG YI ZEFAN DU tianwen li YUCHEN wen liNDI li YONG liU CHUN CHEN Pediatric Hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Research on denoising of joint detection signal of water quality with multi-parameter based on IEEMD

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Optoelectronics Letters 2024年第2期20卷 107-115页

作者： li wen li Dejian MA Yongyue tian Wang wen Xin li Jie Institute of Mechanical and Electrical Engineering North China University of TechnologyBeijing 100144China1

An improved ensemble empirical mode decomposition(IEEMD) is suggested to process water quality spectral signals in order to address the issue that noise interference makes it difficult to extract and evaluate water quality spectral signals.This algorithm effectively solves the problems of modal mixing,poor reconstruction accuracy in the empirical mode decomposition(EMD),and a large amount of calculation in the ensemble empirical mode decomposition(EEMD).Based on EEMD,IEEMD firstly preprocesses the original water quality spectral signals,then performs Savitzky-Golay(S-G) smoothing on the decomposed effective intrinsic mode function(IMF) components,and finally reconstructs them to obtain the denoised signals.Water sample data at different concentrations can be accurately analyzed based on the noise-reduced spectral signals.In this paper,three water quality parameters are used as research objects:benzene(C_(6)H_(6)),benzo(b)fluoranthene(C_(20)H_(12)),and chemical oxygen demand(COD).The original water quality multi-parameter(C_(6)H_(6),C_(20)H_(12),COD) spectral signals were subjected to denoising based on the IEEMD and the water quality multi-parameter joint detection technology.The signal-to-noise ratio(SNR) and the correlation coefficient(R^(2)) of the fitted curves obtained from the processing of the IEEMD were compared and analyzed with those obtained from the processing of the EMD and the EEMD.The experimental results show that the SNR of the spectral signals and the R^(2) of the fitting curve in three water quality parameters have been significantly improved.Therefore,the IEEMD effectively improves the phenomenon of modal mixing,reduces the amount of calculation,improves the reconstruction accuracy,and provides an important guarantee for the effective extraction of multi-parameter spectral signals of water quality.

关键词： signal parameter noise

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An analytical model of hot rolling force for a thick plate by combining globally optimal approximation yield criterion and egg-circular velocity field

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Journal of Iron and Steel Research(International) 2024年第3期31卷 647-659页

作者： Shun-hu Zhang Yi Zhang wen-hao tian Yan li Shagang School of Iron and Steel Soochow UniversitySuzhou 215021JiangsuChina

For the sake of solving the problem that it is difficult to be integrated for the Mises specific plastic power due to its nonlinearity,a new linear criterion,named the globally optimal approximation criterion,is constructed by the polygonal approximation to the Mises circle.The new criterion is proved to be the linear function of the principal stress componentsσ1,σ2 andσ3 and the trajectory of it on theπ-plane is a non-equiangular but equilateral dodecagon intersecting the Mises circle.The theoretical results of the current criterion described by the Lode stress parameters are in excellent accordance with the experimental results.Meanwhile,according to the trend that the metallic flow velocity between rollers aggrandizes gradually from the inlet to the outlet during the hot rolling of a thick plate,a biomimetic velocity field is proposed in which the horizontal velocity component fits the egg-circular curve distribution.The velocity field and its simulated results agree quite well.Subsequently,using the determined linear criterion,energy analysis of the constructed velocity field is utilized to obtain the interior deformation power,while the vector decomposition approach is utilized to obtain the frictional power and shear power.On this basis,the overall power is obtained and the analytical solutions are generated for the rolling torque,rolling force and the coefficient of the stress state under different egg curves by minimizing the neutral angle.Furthermore,the parameter optimization of the characteristic parameterρwhich affects the slope of the egg-circular curve is carried out and the best egg-circular curve which can minimize the energy consumption is determined.The best agreement between the theoretical and observed values of rolling force and rolling torque is under this curve,and the mean relative errors of the rolling torque and rolling force are no more than 2.93%,while the maximum error is no more than 8.35%.

关键词： Yield criterion Plastic deformation Rolling force Velocity field Analytical solution

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A new integrated model of deformation resistance and its application in prediction of rolling force of a thick plate

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Journal of Iron and Steel Research(International) 2024年第4期31卷 882-893页

作者： Shun-hu Zhang Yan li li-zhi Che wen-hao tian Shagang School of Iron and Steel Soochow UniversitySuzhou 215021JiangsuChina

The prediction accuracy of existing models of the rolling force of a thick plate is always very low.To address this problem,a high-precision genetic algorithm-backpropagation network(GA-BP)model of deformation resistance was built,and its integration with the traditional fitted model was further established.Then,a novel rolling force model was obtained by embedding the integration model of deformation resistance in the original model of rolling force.According to this research idea,the industrial data are normalized at first.On this basis,the interactions among the process parameters were disclosed through the variance analysis,and then described by various virtual factors.These factors are set as part of input parameters.Then,the optimal structure of the GA-BP model of deformation resistance was determined and an integration model of deformation resistance was built.Finally,a novel rolling force model is obtained by substituting the traditional fitted deformation resistance into the Sims model with the integration model of the deformation resistance.The results proves that the introduction of virtual factors can increase the hit rate of±5%from 75.8%to 78%and can reduce the root mean square error from 4.72%to 4.48%.Besides,it is found that the mean relative error of the traditional fitted deformation resistance is 0.142,while that of the modified deformation resistance is only 0.03.In addition,the mean relative error in the original rolling force model is 0.145,while that of the present model is only 0.03.

关键词： Integration model-Deformation resistance Variance analysis Virtual factor Genetic algorithm-backpropagation network model

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Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1019-1028页

作者： Jun-Jie Shen Min-Chang li Shao-Qi tian wen-Ming Chen Department of Oncology Jiangxi Hospital of Integrated Chinese and Western MedicineNanchang 330000Jiangxi ProvinceChina Department of Hepatopancreatobiliary Surgery Jiangxi Hospital of Integrated Chinese and Western MedicineNanchang 330000Jiangxi ProvinceChina Clinical Medical School Jining Medical UniversityJining 272000Shandong ProvinceChina Department of Oncology Jining No.1 People’s HospitalJining 272011Shandong ProvinceChina

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.***.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://***/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with s

关键词： Long non-coding RNA GATA6-AS1 N6-methyladenine modification Fat mass and obesity-associated protein Gastric cancer

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Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of Chinese Medicine

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Chinese Journal of Integrative Medicine 2024年第5期30卷 468-479页

作者： ZHONG Yi li Xin-yue liANG tian-jun DING Bao-zhu MA Ke-xin REN wen-xuan liANG wen-jie College of Integrated Traditional Chinese and Western Medicine Hebei University of Chinese MedicineHebei Key Laboratory of Integrated Traditional Chinese and Western Medicine in Liver and Kidney DiseasesInstitute of Integrated Traditional Chinese and Western MedicineShijiazhuang 050200China Department of Cardiovascular Internal Medicine the Second Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi Province 332000China Graduate School Hebei Medical UniversityShijiazhuang 050017China Rural Physician College Hebei Medical UniversityShijazhuang 050017China Medical Department the First Hospital of Hebei Medical UniversityShijiazhuang 050030China

Activation of the NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases(CVDs),such as diabetic cardiomyopathy,ischemia/reperfusion injury,myocardial infarction,heart failure and hypertension.Noncoding RNAs(nc RNAs)are important regulatory factors.Many Chinese medicine(CM)compounds,including their effective components,can regulate pyroptosis and exert myocardium-protecting effects.The mechanisms underlying this protection include inhibition of inflammasome protein expression,Toll-like receptor 4–NF-κB signal pathway activation,oxidative stress,endoplasmic reticulum stress(ERS),and mixed lineage kinase 3 expression and the regulation of silent information regulator 1.The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM.Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

关键词： pyroptosis cardiovascular diseases Chinese medicine NOD-like receptor protein 3 mechanisms

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Pt nanoclusters modified porous g-C_(3)N_(4)nanosheets to significantly enhance hydrogen production by photocatalytic water reforming of methanol

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Chinese Journal of Chemical Engineering 2024年第2期66卷 40-50页

作者： Yi-Fei liang Jin-Rong Lu Shang-Kun tian wen-Quan Cui li liu Hebei Provincial Key Laboratory of Environmental Photocatalytic and Electrocatalytic Materials College of Chemical EngineeringNorth China University of Science and TechnologyTangshan 063210China

For the use of green hydrogen energy,it is crucial to have efficient photocatalytic activity for hydrogen generation by water reforming of methanol under mild conditions.Much attention has been paid to gC_(3)N_(4)as a promising photocatalyst for the generation of hydrogen.To improve the separation of photogenerated charge,porous nanosheet g-C_(3)N_(4)was modified with Pt nanoclusters(Pt/g-C_(3)N_(4))through impregnation and following photo-induced reduction.This catalyst showed excellent photocatalytic activity of water reforming of methanol fo r hydrogen production with a 17.12 mmol·g^(-1)·h^(-1)rate at room temperature,which was 311 times higher than that of the unmodified g-C_(3)N_(4).The strong interactions of Pt-N in Pt/g-C_(3)N_(4)constructed effective electron transfer channels to promote the separation of photogenerated electrons and holes effectively.In addition,in-situ infrared spectroscopy was used to investigate the intermediates of the hydrogen production reaction,which proved that methanol and water eventually turn into H_(2)and CO_(2)via formaldehyde and formate.This study provides insights for understanding the photocatalytic hydrogen production in the water reforming of methanol.

关键词： Water reforming of methanol Photocatalysis g-C_(3)N_(4) Pt nanoclusters Hydrogen production

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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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Nano polystyrene microplastics could accumulate in Nile tilapia(Oreochromis niloticus):Negatively impacts on the intestinal and liver health through water exposure

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Journal of Environmental Sciences 2024年第3期137卷 604-614页

作者： Di Wu Xing Lu li-Xue Dong Juan tian Jin Deng Lei Wei Hua wen Shan Zhong Ming Jiang School of Basic Medical Sciences Wuhan UniversityWuhan 430071China Key Laboratory of Freshwater Biodiversity Conservation Ministry of Agriculture and Rural AffairsYangtze River Fisheries Research InstituteChinese Academy of Fishery SciencesWuhan 430223China Hubei Province Key Laboratory of Allergy and Immunology Wuhan 430071China

Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group.Ed U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group.The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group.The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group.In conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity.All the above lay the foundation for further study on the pathological damage of MPs to other organisms.

关键词： Microplastics(MPs) Intestinal toxicity liver toxicity Gut microbiome lipid metabolism

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Energy beam-based direct and assisted polishing techniques for diamond:A review

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International Journal of Extreme Manufacturing 2024年第1期6卷 93-124页

作者： Zhuo li Feng Jiang Zhengyi Jiang Zige tian tian Qiu Tao Zhang Qiuling wen Xizhao Lu Jing Lu Hui Huang Institute of Manufacturing Engineering Huaqiao UniversityXiamen 361021People’s Republic of China School of Mechanical MaterialsMechatronic and Biomedical EngineeringUniversity of WollongongWollongongNSW 2522Australia College of Mechanical Engineering and Automation Huaqiao UniversityXiamen 361021People’s Republic of China State Key Laboratory of High Performance Tools Huaqiao UniversityXiamen 361021People’s Republic of China

Diamond is a highly valuable material with diverse industrial applications,particularly in the fields of semiconductor,optics,and high-power electronics.However,its high hardness and chemical stability make it difficult to realize high-efficiency and ultra-low damage machining of diamond.To address these challenges,several polishing methods have been developed for both single crystal diamond(SCD)and polycrystalline diamond(PCD),including mechanical,chemical,laser,and ion beam processing methods.In this review,the characteristics and application scope of various polishing technologies for SCD and PCD are highlighted.Specifically,various energy beam-based direct and assisted polishing technologies,such as laser polishing,ion beam polishing,plasma-assisted polishing,and laser-assisted polishing,are summarized.The current research progress,material removal mechanism,and infuencing factors of each polishing technology are analyzed.Although some of these methods can achieve high material removal rates or reduce surface roughness,no single method can meet all the requirements.Finally,the future development prospects and application directions of different polishing technologies are presented.

关键词： single crystal diamond polycrystalline diamond energy beam polishing technology material removal mechanism influencing factors

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