New Name for Journal of Huazhong University of Science and Technology[Medical Sciences]:Current Medical Science

Journal of Huazhong University of Science and Technology[Medical Sciences]is sponsored by Tongji Medical College,Huazhong University of Science and Technology,a prestigious medical school based in the central part of China.Starting in 1979,it is a peer-reviewed journal that focuses on medical sciences.In China,it is one of the five periodicals that are firstly included in Index Medicus（IM）and is now under the coverage of the Science Citation Index-Expanded（SCI-E）.

Preface:Celebrating the 70th Anniversary of School of Mechanical Science and Engineering,Huazhong University of Science and Technology

Huazhong University of Science and Technology (HUST) is a key research-based comprehensive university in Wuhan, China,under the direct supervision of the Ministry of Education of China. Renowned as the epitome of the development of higher education in new China, it is a “211” Project,“985” Project,“Double First-Class” university in China.

A game-theoretic approach for federated learning:A trade-off among privacy,accuracy and energy

Benefiting from the development of Federated Learning(FL)and distributed communication systems,large-scale intelligent applications become possible.Distributed devices not only provide adequate training data,but also cause privacy leakage and energy consumption.How to optimize the energy consumption in distributed communication systems,while ensuring the privacy of users and model accuracy,has become an urgent challenge.In this paper,we define the FL as a 3-layer architecture including users,agents and server.In order to find a balance among model training accuracy,privacy-preserving effect,and energy consumption,we design the training process of FL as game models.We use an extensive game tree to analyze the key elements that influence the players’decisions in the single game,and then find the incentive mechanism that meet the social norms through the repeated game.The experimental results show that the Nash equilibrium we obtained satisfies the laws of reality,and the proposed incentive mechanism can also promote users to submit high-quality data in FL.Following the multiple rounds of play,the incentive mechanism can help all players find the optimal strategies for energy,privacy,and accuracy of FL in distributed communication systems.

Flow characteristics and hot workability of a typical low-alloy high-strength steel during multi-pass deformation

Heavy components of low-alloy high-strength(LAHS) steels are generally formed by multi-pass forging. It is necessary to explore the flow characteristics and hot workability of LAHS steels during the multi-pass forging process, which is beneficial to the formulation of actual processing parameters. In the study, the multi-pass hot compression experiments of a typical LAHS steel are carried out at a wide range of deformation temperatures and strain rates. It is found that the work hardening rate of the experimental material depends on deformation parameters and deformation passes, which is ascribed to the impacts of static and dynamic softening behaviors. A new model is established to describe the flow characteristics at various deformation passes. Compared to the classical Arrhenius model and modified Zerilli and Armstrong model, the newly proposed model shows higher prediction accuracy with a confidence level of 0.98565. Furthermore, the connection between power dissipation efficiency(PDE) and deformation parameters is revealed by analyzing the microstructures. The PDE cannot be utilized to reflect the efficiency of energy dissipation for microstructure evolution during the entire deformation process, but only to assess the efficiency of energy dissipation for microstructure evolution in a specific deformation parameter state.As a result, an integrated processing map is proposed to better study the hot workability of the LAHS steel, which considers the effects of instability factor(IF), PDE, and distribution and size of grains. The optimized processing parameters for the multi-pass deformation process are the deformation parameters of 1223–1318 K and 0.01–0.08 s^(-1). Complete dynamic recrystallization occurs within the optimized processing parameters with an average grain size of 18.36–42.3 μm. This study will guide the optimization of the forging process of heavy components.

Impact of mica on geotechnical behavior of weathered granitic soil using macro and micro investigations

The micaceous weathered granitic soil(WGS)is frequently encountered in civil engineering worldwide,unfortunately little information is available regarding how mica affects the physico-mechanical behaviors of WGS.This study prepares reconstituted WGS with different mica contents by removing natural mica in theWGS,and then mixes it with commercial mica powders.The geotechnical behavior as well as the microstructures of the mixtures are characterized.The addition of mica enables the physical indices of WGS to be specific combinations of coarser gradation and high permeability but high Atterberg limits.However,high mica content in WGS was found to be associated with undesirable mechanical properties,including increased compressibility,disintegration,and swelling potential,as well as poor compactability and low effective frictional angle.Microstructural analysis indicates that the influence of mica on the responses of mixtures originates from the intrinsic nature of mica as well as the particle packing being formed withinWGS.Mica exists in the mixture as stacks of plates that form a spongy structure with high compressibility and swelling potential.Pores among the plates give the soil high water retention and high Atterberg limits.Large pores are also generated by soil particles with bridging packing,which enhances the permeability and water-soil interactions upon immersion.This study provides a microlevel understanding of how mica dominates the behavior of WGS and provides new insights into the effective stabilization and improvement of micaceous soils.

The History of Controlling and Treating Infectious Diseases in Ancient China

Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.

The role of innate immunity in diabetic nephropathy and their therapeutic consequences

Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting

On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.

On the evolution and formation of discharge morphology in pulsed dielectric barrier discharge

The discharge morphology of pulsed dielectric barrier discharge(PDBD) plays important roles in its applications. Here, we systematically investigated the effects of the voltage amplitude,discharge gap, and O_(2)content on the PDBD morphology, and revealed the possible underlying mechanism of the U-shaped formation. First, the morphological evolution under different conditions was recorded. A unique U-shaped region appears in the middle edge region when the gap is larger than 2 mm, while the entire discharge region remains columnar under a 2 mm gap in He PDBD. The width of the discharge and the U-shaped region increase with the increase in voltage, and decrease with the increase of the gap and O_(2)content. To explain this phenomenon,a two-dimensional symmetric model was developed to simulate the spatiotemporal evolution of different species and calculate the electric thrust. The discharge morphology evolution directly corresponds to the excited-state atomic reduction process. The electric thrust on the charged particles mainly determines the reaction region and strongly influences the U-shaped formation.When the gap is less than 2 mm, the electric thrust is homogeneous throughout the entire region,resulting in a columnar shape. However, when the gap is larger than 2 mm or O_(2)is added, the electric thrust in the edge region becomes greater than that in the middle, leading to the U-shaped formation. Furthermore, in He PDBD, the charged particles generating electric thrust are mainly electrons and helium ions, while in He/O_(2)PDBD those that generate electric thrust at the outer edge of the electrode surface are mainly various oxygen-containing ions.

Clinical Analysis and Mental Health Survey of Hemophilia Carriers:a Cross-sectional Study

Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted males,to the upper limit of normal,and may experience mental health issues.The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs.Additionally,we aimed to investigate the mental health status of HCs in China.Methods:A total of 127 hemophilia mothers,including 93 hemophilia A(HA)mothers and 34 hemophilia B(HB)mothers,were enrolled in this study.Long distance PCR,multiplex PCR,and Sanger sequencing were used to analyze mutations in F8 or F9.Coagulation factor activity was detected by a one-stage clotting assay.The Symptom Checklist 90(SCL-90,China/Mandarin version)was given to HCs at the same time to assess their mental health.Results:A total of 90.6%of hemophilia mothers were diagnosed genetically as carriers,with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers,respectively.The median clotting factor level in carriers was 0.74 IU/mL(ranging from 0.09 to 1.74 IU/mL)compared with 1.49 IU/mL(ranging from 0.93 to 1.89 IU/mL)in noncarriers,of which 14.3%of HCs had clotting factor levels of 0.40 IU/mL or below.A total of 53.8%(7/13)of HA carriers with low clotting factor levels(less than 0.50 IU/mL)had a history of bleeding,while none of the HB carriers displayed a bleeding phenotype.The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00(±60.37)and 1.78(±0.59),respectively.A total of 67.7%of the respondents had psychological symptoms,with obsessive-compulsive disorder being the most prevalent and severe.The pooled estimates of all nine factors were significantly higher than those in the general population(P<0.05).Conclusions:The detection rate of gene mutations in hemophilia mothers was 90.6%,with a median clotting factor level of 0.74 IU/mL,and 14.3%of HCs had a clotting factor level of 0.40 IU/mL or below.A history of bleeding was present in 41.2%of HCs with low clotting factor levels(less than 0.50 IU/mL).Additionally,given the fragile mental health status of HCs in China,it is critical to develop efficient strategies to improve psychological well-being.

Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency

Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.

Self‑Assembly of Binderless MXene Aerogel for Multiple‑Scenario and Responsive Phase Change Composites with Ultrahigh Thermal Energy Storage Density and Exceptional Electromagnetic Interference Shielding

The severe dependence of traditional phase change materials(PCMs)on the temperature-response and lattice deficiencies in versatility cannot satisfy demand for using such materials in complex application scenarios.Here,we introduced metal ions to induce the self-assembly of MXene nanosheets and achieve their ordered arrangement by combining suction filtration and rapid freezing.Subsequently,a series of MXene/K^(+)/paraffin wax(PW)phase change composites(PCCs)were obtained via vacuum impregnation in molten PW.The prepared MXene-based PCCs showed versatile applications from macroscale technologies,successfully transforming solar,electric,and magnetic energy into thermal energy stored as latent heat in the PCCs.Moreover,due to the absence of binder in the MXene-based aerogel,MK3@PW exhibits a prime solar-thermal conversion efficiency(98.4%).Notably,MK3@PW can further convert the collected heat energy into electric energy through thermoelectric equipment and realize favorable solar-thermal-electric conversion(producing 206 mV of voltage with light radiation intensity of 200 mw cm^(−2)).An excellent Joule heat performance(reaching 105℃with an input voltage of 2.5 V)and responsive magnetic-thermal conversion behavior(a charging time of 11.8 s can achieve a thermal insulation effect of 285 s)for contactless thermotherapy were also demonstrated by the MK3@PW.Specifically,as a result of the ordered arrangement of MXene nanosheet self-assembly induced by potassium ions,MK3@PW PCC exhibits a higher electromagnetic shielding efficiency value(57.7 dB)than pure MXene aerogel/PW PCC(29.8 dB)with the same MXene mass.This work presents an opportunity for the multi-scene response and practical application of PCMs that satisfy demand of next-generation multifunctional PCCs.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Effect of gas components on the postdischarge temporal behavior of OH and O of a non-equilibrium atmospheric pressure plasma driven by nanosecond voltage pulses

OH radicals and O atoms are two of the most important reactive species of non-equilibrium atmospheric pressure plasma(NAPP),which plays an important role in applications such as plasma medicine.However,experimental studies on how the gas content affects the postdischarge temporal evolutions of OH and O in the noble gas ns-NAPP are very limited.In this work,the effect of the percentages of O_(2),N_(2),and H_(2)O on the amounts of OH and O productions and their post-discharge temporal behaviors in ns-NAPP is investigated by laser-induced fluorescence(LIF)method.The results show that the productions of OH and O increase and then decrease with the increase of O_(2)percentage.Both OH and O densities reach their maximum when about 0.8%O_(2)is added.Further increase of the O_(2)concentration results in a decrease of the initial densities of both OH and O,and leads to their faster decay.The increase of N_(2)percentage also results in the increase and then decrease of the OH and O densities,but the change is smaller.Furthermore,when the H_(2)O concentration is increased from 100 to 3000 ppm,the initial OH density increases slightly,but the OH density decays much faster,while the initial density of O decreases with the increase of the H_(2)O concentration.After analysis,it is found that OH and O are mainly produced through electron collisional dissociation.O(^(1)D)is critical for OH generation.O_(3)accelerates the consumption processes of OH and O at high O_(2)percentage.The addition of H_(2)O in the NAPP considerably enhances the electronegativity,while it decreases the overall plasma reactivity,accelerates the decay of OH,and reduces the O atom density.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Thermal pretreatment of willow branches impacts yield and pore development of activated carbon in subsequent activation with ZnCl_(2) via modifying cellulose structure

Development of pore structures of activated carbon(AC)from activation of biomass with ZnCl_(2) relies on content and structure of cellulose/hemicellulose in the feedstock.Thermal pretreatment of biomass could induce dehydration and/or aromatization to change the structure of cellulose/hemicellulose.This might interfere with evolution of structures of AC,which was investigated herein via thermal pretreatment of willow branch(WB)from 200 to 360℃and the subsequent activation with ZnCl_(2) at 550℃.The results showed that thermal pretreatment at 360℃(WB-360)could lead to substantial pyrolysis to form biochar,with a yield of 31.9%,accompanying with nearly complete destruction of cellulose crystals and remarkably enhanced aromatic degree.However,cellulose residual in WB-360 could still be activated to form AC-360 with specific surface area of 1837.9 m~2·g^(-1),which was lower than that in AC from activation of untreated WB(AC-blank,2077.8 m~2·g^(-1)).Nonetheless,the AC-200 from activation of WB-200 had more developed pores(2113.9 m~2·g^(-1))and superior capability for adsorption of phenol,due to increased permeability of ZnCl_(2) to the largely intact cellulose structure in WB-200.The thermal pretreatment did increase diameters of micropores of AC but reduced the overall yield of AC(26.8%for AC-blank versus 18.0%for AC-360),resulting from accelerated cracking but reduced intensity of condensation.In-situ infrared characterization of the activation showed that ZnCl_(2) mainly catalyzed dehydration,dehydrogenation,condensation,and aromatization but not cracking,suppressing the formation of derivatives of cellulose and lignin in bio-oil.The thermal pretreatment formed phenolic-OH and C=O with higher chemical innerness,which changed the reaction network in activation,shifting morphology of fibrous structures in AC-blank to“melting surface”in AC-200 or AC-280.

I-DCGAN and TOPSIS-IFP:A simulation generation model for radiographic flaw detection images in light alloy castings and an algorithm for quality evaluation of generated images

The intelligent detection technology driven by X-ray images and deep learning represents the forefront of advanced techniques and development trends in flaw detection and automated evaluation of light alloy castings.However,the efficacy of deep learning models hinges upon a substantial abundance of flaw samples.The existing research on X-ray image augmentation for flaw detection suffers from shortcomings such as poor diversity of flaw samples and low reliability of quality evaluation.To this end,a novel approach was put forward,which involves the creation of the Interpolation-Deep Convolutional Generative Adversarial Network(I-DCGAN)for flaw detection image generation and a comprehensive evaluation algorithm named TOPSIS-IFP.I-DCGAN enables the generation of high-resolution,diverse simulated images with multiple appearances,achieving an improvement in sample diversity and quality while maintaining a relatively lower computational complexity.TOPSIS-IFP facilitates multi-dimensional quality evaluation,including aspects such as diversity,authenticity,image distribution difference,and image distortion degree.The results indicate that the X-ray radiographic images of magnesium and aluminum alloy castings achieve optimal performance when trained up to the 800th and 600th epochs,respectively.The TOPSIS-IFP value reaches 78.7%and 73.8%similarity to the ideal solution,respectively.Compared to single index evaluation,the TOPSIS-IFP algorithm achieves higher-quality simulated images at the optimal training epoch.This approach successfully mitigates the issue of unreliable quality associated with single index evaluation.The image generation and comprehensive quality evaluation method developed in this paper provides a novel approach for image augmentation in flaw recognition,holding significant importance for enhancing the robustness of subsequent flaw recognition networks.

Rapid progress of an iris metastasis from esophageal cancer:a case report and review of literature

This case report details a rare instance of rapid iris metastasis from esophageal cancer in a 59-year-old man.A literature review was conducted to explore recent advances in detecting,diagnosing,and treating intraocular metastatic malignancies.Positron emission tomographycomputed tomography played a crucial role in identifying primary sites and systemic metastases.Local treatment combined with systemic therapy effectively reduced tumor size,preserved useful vision,and improved the patient’s survival rate.A comparison was made of the characteristics of iris metastases from esophageal cancer and lung cancer,including age,gender,tumor characteristics,and treatment.The challenges associated with diagnosis and treatment are discussed,highlighting the implications for clinical practice.

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.