In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori

BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phenolic compounds.The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality(C-score=0.09)and was validated using parameters from the MolProbity platform.The GRaSP online platform identified 24 residues(phenylalanine and leucine)as potential binding sites on the CagA oncoprotein.Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein.No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds;however,all phenolic compounds interacted with the central region of the oncoprotein.Phenolic compounds and CagA exhibited significant affinity energy(-7.9 to-9.1 kcal/mol):CagA/kaempferol formed 28 chemical bonds,CagA/myricetin formed 18 chemical bonds,CagA/quercetin formed 16 chemical bonds,CagA/ponciretin formed 13 chemical bonds,and CagA/chlorogenic acid formed 17 chemical bonds.Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif,all of them bound to residues,mostly positively or negatively charged,located near this region.CONCLUSION In silico,the tested phenolic compounds formed stable complexes with CagA.Therefore,they could be tested in vitro and/or in vivo to validate the findings,and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).

Application of Isogeometric Analysis Method in Three-Dimensional Gear Contact Analysis

Gears are pivotal in mechanical drives,and gear contact analysis is a typically difficult problem to solve.Emerging isogeometric analysis(IGA)methods have developed new ideas to solve this problem.In this paper,a threedimensional body parametric gear model of IGA is established,and a theoretical formula is derived to realize single-tooth contact analysis.Results were benchmarked against those obtained from commercial software utilizing the finite element analysis(FEA)method to validate the accuracy of our approach.Our findings indicate that the IGA-based contact algorithmsuccessfullymet theHertz contact test.When juxtaposed with the FEA approach,the IGAmethod demonstrated fewer node degrees of freedomand reduced computational units,all whilemaintaining comparable accuracy.Notably,the IGA method appeared to exhibit consistency in analysis accuracy irrespective of computational unit density,and also significantlymitigated non-physical oscillations in contact stress across the tooth width.This underscores the prowess of IGA in contact analysis.In conclusion,IGA emerges as a potent tool for addressing contact analysis challenges and holds significant promise for 3D gear modeling,simulation,and optimization of various mechanical components.

A Hybrid Optimization Approach of Single Point Incremental Sheet Forming of AISI 316L Stainless Steel Using Grey Relation Analysis Coupled with Principal Component Analysiss

We investigated the parametric optimization on incremental sheet forming of stainless steel using Grey Relational Analysis(GRA) coupled with Principal Component Analysis(PCA). AISI 316L stainless steel sheets were used to develop double wall angle pyramid with aid of tungsten carbide tool. GRA coupled with PCA was used to plan the experiment conditions. Control factors such as Tool Diameter(TD), Step Depth(SD), Bottom Wall Angle(BWA), Feed Rate(FR) and Spindle Speed(SS) on Top Wall Angle(TWA) and Top Wall Angle Surface Roughness(TWASR) have been studied. Wall angle increases with increasing tool diameter due to large contact area between tool and workpiece. As the step depth, feed rate and spindle speed increase,TWASR decreases with increasing tool diameter. As the step depth increasing, the hydrostatic stress is raised causing severe cracks in the deformed surface. Hence it was concluded that the proposed hybrid method was suitable for optimizing the factors and response.

A Comparative Analysis of the New -3(-n) - 1 Remer Conjecture and a Proof of the 3n + 1 Collatz Conjecture

This scientific paper is a comparative analysis of two mathematical conjectures. The newly proposed -3(-n) - 1 Remer conjecture and how it is related to and a proof of the more well known 3n + 1 Collatz conjecture. An overview of both conjectures and their respective iterative processes will be presented. Showcasing their unique properties and behavior to each other. Through a detailed comparison, we highlight the similarities and differences between these two conjectures and discuss their significance in the field of mathematics. And how they prove each other to be true.

Multiscale analysis of fine slag from pulverized coal gasification in entrained-flow bed

Fine slag(FS)is an unavoidable by-product of coal gasification.FS,which is a simple heap of solid waste left in the open air,easily causes environmental pollution and has a low resource utilization rate,thereby restricting the development of energy-saving coal gasification technologies.The multiscale analysis of FS performed in this study indicates typical grain size distribution,composition,crystalline structure,and chemical bonding characteristics.The FS primarily contained inorganic and carbon components(dry bases)and exhibited a"three-peak distribution"of the grain size and regular spheroidal as well as irregular shapes.The irregular particles were mainly adsorbed onto the structure and had a dense distribution and multiple pores and folds.The carbon constituents were primarily amorphous in structure,with a certain degree of order and active sites.C 1s XPS spectrum indicated the presence of C–C and C–H bonds and numerous aromatic structures.The inorganic components,constituting 90%of the total sample,were primarily silicon,aluminum,iron,and calcium.The inorganic components contained Si–O-Si,Si–O–Al,Si–O,SO_(4)^(2−),and Fe–O bonds.Fe 2p XPS spectrum could be deconvoluted into Fe 2p_(1/2) and Fe 2p_(3/2) peaks and satellite peaks,while Fe existed mainly in the form of Fe(III).The findings of this study will be beneficial in resource utilization and formation mechanism of fine slag in future.

Seismic fragility analysis of three-tower cable-stayed bridges with different connection configurations

Seismic fragility analysis of three-tower cable-stayed bridges with three different structural systems,including rigid system(RS),floating system(FS),and passive energy dissipation system(PEDS),is conducted to study the effects of connection configurations on seismic responses and fragilities.Finite element models of bridges are established using OpenSees.A new ground motion screening method based on the statistical characteristic of the predominant period is proposed to avoid irregular behavior in the selection process of ground motions,and incremental dynamic analysis(IDA)is performed to develop components and systems fragility curves.The effects of damper failure on calculated results for PEDS are examined in terms of seismic response and fragility analysis.The results show that the bridge tower is the most affected component by different structural systems.For RS,the fragility of the middle tower is significantly higher than other components,and the bridge failure starts from the middle tower,exhibiting a characteristic of local failure.For FS and PEDS,the fragility of the edge tower is higher than the middle tower.The system fragility of RS is higher than FS and PEDS.Taking the failure of dampers into account is necessary to obtain reliable seismic capacity of cable-stayed bridges.

The prediction of projectile-target intersection for moving tank based on adaptive robust constraint-following control and interval uncertainty analysis

To improve the hit probability of tank at high speed,a prediction method of projectile-target intersection based on adaptive robust constraint-following control and interval uncertainty analysis is proposed.The method proposed provides a novel way to predict the impact point of projectile for moving tank.First,bidirectional stability constraints and stability constraint-following error are constructed using the Udwadia-Kalaba theory,and an adaptive robust constraint-following controller is designed considering uncertainties.Second,the exterior ballistic ordinary differential equation with uncertainties is integrated into the controller,and the pointing control of stability system is extended to the impact-point control of projectile.Third,based on the interval uncertainty analysis method combining Chebyshev polynomial expansion and affine arithmetic,a prediction method of projectile-target intersection is proposed.Finally,the co-simulation experiment is performed by establishing the multi-body system dynamic model of tank and mathematical model of control system.The results demonstrate that the prediction method of projectile-target intersection based on uncertainty analysis can effectively decrease the uncertainties of system,improve the prediction accuracy,and increase the hit probability.The adaptive robust constraint-following control can effectively restrain the uncertainties caused by road excitation and model error.

A Contrastive Analysis of English and Chinese Idioms About Color Words & Their Cultural Connotations

There are many idioms related to color words in English and Chinese.The use of color words in idioms adds beauty and vividness to the language.Due to the cultural differences,“color idioms”have gained different cultural connotations with the development of English and Chinese languages.It is of great significance to accurately understand and grasp the meanings and differences of color-related idioms in Chinese and English.This paper intends to analyze and expound the cultural connotations of English and Chinese idioms related to several widely used basic color words with the aim of helping English learners know and use the idioms about color words better.

Feasibility Analysis of IMA Configuration Design Tool

With the widespread application of integrated modular aviation(IMA)electronic systems,the requirements of IMA characteristic analysis and configuration generation have also improved significantly."Configuration and design system based on AADL models(real-time,reliability,interactive complexity,and schedulability)analysis of the AADL model"mainly get through key characteristic analysis for optimization,combined with input of component parameter information and constraint information,assist designers in generating system configuration information,and form a comprehensive modular avionics system resource configuration strategy generation platform.Also,the tool can generate configuration plans for avionics system software and hardware physical architecture configuration.The analysis of the avionics system model mainly involves designers inputting the existing system model architecture for multi characteristic analysis,it can realize the multi-character analysis based on software intensive system architecture models for software dense systems.Inter-complexity and schedulability analysis,and according to characteristic constraint analysis、system model assessment parameters and system architecture constraint parameters to generate configuration scheme information that meets the requirements.The system can meet domestic and foreign software-intensive systems and meet its quality requirements.

Ecological Discourse Analysis Based on the Corpus-A Case Study on the Environmental Discourse of 21st Century

Language learning materials not only provide language input for learners but also subtly disseminate ideology and influence readers’behavior.This study,based on the framework of ecological discourse analysis,quantitatively analyzes and qualitatively describes the ecological significance of environmental texts in the 21st Century.The aim is to provide references for the compilation of environmental discourse in language learning materials,promote the construction of more ecologically beneficial discourse,and facilitate the widespread dissemination of the ecological philosophy of“Diversity and Harmony,Interaction and Co-existence”among young readers.The initial findings of this study are as follows:In the environmental texts of the publication,a large number of relational processes and action processes are used to objectively represent the natural environment;the discourse tends to be ambiguous and beneficial,generally aligning with the ecological philosophy of“Diversity and Harmony,Interaction and Co-existence.”This can guide readers to correctly understand and face environmental issues,which is conducive to the healthy development of natural ecosystems.

Conceptual Analysis of Self-Management in Patients with Hypertension

Objective:To clarify the concept of self-management in hypertensive patients by analyzing the definition,attributes,and measurement tools through a literature review.Methods:An Internet-based search of the databases was conducted using Academic Search Complete,Medical Line,CINAHL,Health Source:Nursing/Scholarly Edition,and Google Scholar.In the search process,keywords or free text were combined by using Boolean operators,with the search terms“self of management”or“self-management,”“concept*analysis”or“concept*definition,”and Walker and Avant’s concept analysis method was used.Results:Analysis of relevant literature summarized the conceptual attributes of self-management in hypertensive patients as the active participation of patients in the treatment process;the presence of interaction provided by patients and health care providers;the use of certain health management tools;and the aim of maintaining and improving the health status and living capacity of hypertensive patients.Conclusion:The concept of self-management for hypertensive patients was clarified,which helps to promote the application of hypertensive self-management in clinical work and improve outcomes and quality of life for patients with hypertension.

Correlation Analysis between Well-cellar Early Transplanting of Robust Seedlings and Diseases in Shiyan Tobacco-growing Area

[Objectives]The paper was to investigate the relationship between the well-cellar early transplanting of robust seedlings and the prevalence of diseases in the Shiyan tobacco-growing area.[Methods]The relationship between disease occurrence and meteorological factors during the field growth period was examined by analyzing the prevalence of flue-cured tobacco virus diseases,brown spot,and total disease in the Shiyan tobacco-growing area before(2013-2017)and after(2018-2022)the well-cellar early transplanting of robust tobacco seedlings.[Results]The implementation of a well-cellar early transplanting technique of robust seedlings resulted in a reduction in the average incidence of tobacco virus disease,brown spot,and total disease by 0.83%,8.85%,and 7.91%,respectively,in comparison to the incidence observed prior to early transplanting.These findings suggest that early transplanting can significantly reduce the incidence of flue-cured tobacco diseases.Prior to the well-cellar early transplanting of robust tobacco seedlings,there was a significant(including highly significant)positive correlation between the incidence of brown spot and total disease and precipitation in August and September.The incidence of brown spot and total disease in tobacco plants was found to be significantly positively correlated with May precipitation and significantly negatively correlated with May sunshine hours following the well-cellar early transplanting of robust seedlings.The advancement of the transplanting period by 20 d resulted in a reduction in the growing period of tobacco plants in the field under autumn rains(late August to November)in western China.This effectively circumvented the suitable conditions for disease occurrence and can reduce the incidence of disease.[Conclusions]This study offers a framework for enhancing the quality and efficiency of flue-cured tobacco production in the northwest tobacco-growing area of Hubei.

Conceptual Metaphor Analysis in Advertising Slogans about Coffee Brands

This paper delves into the strategic use of conceptual metaphors in advertising slogans for coffee brands,exploring how these linguistic devices influence consumer perception and brand appeal.By employing cognitive linguistic theories,this study categorizes eight global coffee brand slogans into five distinct metaphorical patterns,revealing the underlying conceptual mappings that enhance brand messaging.The analysis underscores the importance of metaphorical language in simplifying complex ideas,evoking emotional responses,and establishing a connection between the product and the consumer’s everyday experiences.This paper concludes that the judicious application of conceptual metaphors in advertising is a powerful tool for creating memorable and impactful slogans that resonate with the target audience.

A Building Information Modeling-Life Cycle Cost Analysis Integrated Model to Enhance Decisions Related to the Selection of Construction Methods at the Conceptual Design Stage of Buildings

Life Cycle Cost Analysis (LCCA) provides a systematic approach to assess the total cost associated with owning, operating, and maintaining assets throughout their entire life. BIM empowers architects and designers to perform real-time evaluations to explore various design options. However, when integrated with LCCA, BIM provides a comprehensive economic perspective that helps stakeholders understand the long-term financial implications of design decisions. This study presents a methodology for developing a model that seamlessly integrates BIM and LCCA during the conceptual design stage of buildings. This integration allows for a comprehensive evaluation and analysis of the design process, ensuring that the development aligns with the principles of low carbon emissions by employing modular construction, 3D concrete printing methods, and different building design alternatives. The model considers the initial construction costs in addition to all the long-term operational, maintenance, and salvage values. It combines various tools and data through different modules, including energy analysis, Life Cycle Assessment (LCA), and Life Cycle Cost Analysis (LCCA) to execute a comprehensive assessment of the financial implications of a specific design option throughout the lifecycle of building projects. The development of the said model and its implementation involves the creation of a new plug-in for the BIM tool (i.e., Autodesk Revit) to enhance its functionalities and capabilities in forecasting the life-cycle costs of buildings in addition to generating associated cash flows, creating scenarios, and sensitivity analyses in an automatic manner. This model empowers designers to evaluate and justify their initial investments while designing and selecting potential construction methods for buildings, and enabling stakeholders to make informed decisions by assessing different design alternatives based on long-term financial considerations during the early stages of design.

Preliminary electromagnetic analysis of the COOL blanket for CFETR

The supercritical CO_(2)cOoled Lithium-Lead(COOL)blanket has been designed as one advanced blanket candidate for the Chinese Fusion Engineering Test Reactor(CFETR).This work focuses on the electromagnetic(EM)loads(Maxwell force and Lorentz force)acting on the COOL blanket,which are important mechanical loads in further structural analysis of the COOL blanket.A 3D electromagnetic analysis is performed using the ANSYS finite element method to obtain EM loads on the COOL blanket in this study.At first,the magnetic scalar potential(MSP)method is used to obtain the magnetic field and the Maxwell force on the COOL blanket.Then,the magnetic vector potential(MVP)method is performed during a plasma disruption event to get the eddy current distribution.At last,a multi-step method is adopted for the calculation of the Lorentz force and the torque.The maximum Lorentz forces of inboard and outboard blanket structural components are 5624 kN and 2360 kN respectively.

SFGA-CPA: A Novel Screening Correlation Power Analysis Framework Based on Genetic Algorithm

Correlation power analysis(CPA)combined with genetic algorithms(GA)now achieves greater attack efficiency and can recover all subkeys simultaneously.However,two issues in GA-based CPA still need to be addressed:key degeneration and slow evolution within populations.These challenges significantly hinder key recovery efforts.This paper proposes a screening correlation power analysis framework combined with a genetic algorithm,named SFGA-CPA,to address these issues.SFGA-CPA introduces three operations designed to exploit CPA characteris-tics:propagative operation,constrained crossover,and constrained mutation.Firstly,the propagative operation accelerates population evolution by maximizing the number of correct bytes in each individual.Secondly,the constrained crossover and mutation operations effectively address key degeneration by preventing the compromise of correct bytes.Finally,an intelligent search method is proposed to identify optimal parameters,further improving attack efficiency.Experiments were conducted on both simulated environments and real power traces collected from the SAKURA-G platform.In the case of simulation,SFGA-CPA reduces the number of traces by 27.3%and 60%compared to CPA based on multiple screening methods(MS-CPA)and CPA based on simple GA method(SGA-CPA)when the success rate reaches 90%.Moreover,real experimental results on the SAKURA-G platform demonstrate that our approach outperforms other methods.

Evaluation of the seismic behavior of reinforced concrete structures with flat slab-column gravity frame and shear walls through nonlinear analysis methods

This paper presents an investigation of the seismic behavior of reinforced concrete(RC)structures in which shear walls are the main lateral load-resisting elements and the participation of flat slab floor systems is not considered in the seismic design procedure.In this regard,the behavior of six prototype structures(with different heights and plan layouts)is investigated through nonlinear static and time history analyses,implemented in the OpenSees platform.The results of the analyses are presented in terms of the behavior of the slab-column connections and their mode of failure at different loading stages.Moreover,the global response of the buildings is discussed in terms of some parameters,such as lateral overstrength due to the gravity flat slab-column frames.According to the nonlinear static analyses,in structures in which the slab-column connections were designed only for gravity loads,the slab-column connections exhibited a punching mode of failure even in the early stages of loading.However,the punching failure was eliminated in structures in which a minimum transverse reinforcement recommended in ACI 318(2019)was provided in the slabs at joint regions.Furthermore,despite neglecting the contribution of gravity flat slab-column frames in the lateral load resistance of the structures,a relatively significant overstrength was imposed on the structures by the gravity frames.

Stability Analysis of Inverse Lax-Wendroff Procedure for a High order Compact Finite Difference Schemes

This paper considers the finite difference(FD)approximations of diffusion operators and the boundary treatments for different boundary conditions.The proposed schemes have the compact form and could achieve arbitrary even order of accuracy.The main idea is to make use of the lower order compact schemes recursively,so as to obtain the high order compact schemes formally.Moreover,the schemes can be implemented efficiently by solving a series of tridiagonal systems recursively or the fast Fourier transform(FFT).With mathematical induction,the eigenvalues of the proposed differencing operators are shown to be bounded away from zero,which indicates the positive definiteness of the operators.To obtain numerical boundary conditions for the high order schemes,the simplified inverse Lax-Wendroff(SILW)procedure is adopted and the stability analysis is performed by the Godunov-Ryabenkii method and the eigenvalue spectrum visualization method.Various numerical experiments are provided to demonstrate the effectiveness and robustness of our algorithms.

Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis

BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.