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The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： yu Fu Jia Li Wenyun cai yulan Huang Xinlong Liu Zhongyi ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li Medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in low-biomass.The accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional one.Therefore,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying mechanisms.Herein,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed biomaterials.We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy Outer membrane vesicles

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen cai Wenjuan ma Long Bai En Luo yunfeng Lin State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China Department of Oral and maxillofacial Surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research Center of Oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

Diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging parameters and serum tumor markers in rectal carcinoma prognosis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1796-1807页

作者： Ren-Qi Mu Jun-Wei Lv cai-yun ma Xiao-Hui ma Dong Xing Hou-Sheng ma Department of Radiology Yantai Mountain HospitalYantai 264001Shandong ProvinceChina Department of Radiology Yantai Yuhuangding HospitalYantai 264000Shandong ProvinceChina Department of Gynaecology Yantai Yuhuangding HospitalYantai 264000Shandong ProvinceChina The First Clinical Medical College Xinjiang Medical UniversityUrumqi 830011Xinjiang Uygur Autonomous RegionChina

BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality of life of patients.At present,dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters and serum carbohydrate antigen 19-9(CA19-9)and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC.However,the accuracy of these evaluation modalities still needs further research.This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC.AIM To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers(TMs)in assessing pathological processes and prognosis of RC patients.METHODS A retrospective analysis was performed on 104 RC patients treated at Yantai yuhuangding Hospital from may 2018 to January 2022.Patients were categorized into stages T1,T2,T3,and T4,depending on their T stage and differentiation degree.In addition,they were assigned to low(L group)and moderate-high differentiation(M+H group)groups based on their differentiation degree.The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared.In addition,the value of DCE-MRI parameters[volume transfer constant(Ktrans),rate constant(Kep),and extravascular extracellular volume fraction(Ve)in assessing the differentiation and T staging of RC patients was discussed.Furthermore,the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed.RESULTS Ktrans,Ve,CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M+H Group,respectively(P<0.05).The areas under the curve(AUCs)of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages,respectively,and 0.672 and 0.725 in diagnosing moderate-high and low differe

关键词： Rectal carcinoma Volume transfer constant Rate constant Extravascular extracellular volume fraction Serum carbohydrate antigen 19-9 Serum carbohydrate antigen 125

Particle residence time distribution and axial dispersion coefficient in a pressurized circulating fluidized bed by using multiphase particle-in-cell simulation

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Chinese Journal of Chemical Engineering 2024年第5期69卷 167-176页

作者： Jinnan Guo Daoyin Liu Jiliang ma cai Liang Xiaoping Chen Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education Southeast UniversityNanjing 210096China

The particle residence time distribution(RTD)and axial dispersion coefficient are key parameters for the design and operation of a pressurized circulating fluidized bed(PCFB).In this study,the effects of pressure(0.1-0.6 MPa),fluidizing gas velocity(2-7 m·s^(-1)),and solid circulation rate(10-90 kg·m^(-2)·s^(-1))on particle RTD and axial dispersion coefficient in a PCFB are numerically investigated based on the multiphase particle-in-cell(MP-PIC)method.The details of the gas-solid flow behaviors of PCFB are revealed.Based on the gas-solid flow pattern,the particles tend to move more orderly under elevated pressures.With an increase in either fluidizing gas velocity or solid circulation rate,the mean residence time of particles decreases while the axial dispersion coefficient increases.With an increase in pressure,the core-annulus flow is strengthened,which leads to a wider shape of the particle RTD curve and a larger mean particle residence time.The back-mixing of particles increases with increasing pressure,resulting in an increase in the axial dispersion coefficient.

关键词： Pressurized circulating fluidized bed MP-PIC method Residence time distribution Axial dispersion coefficient

Hydration lubrication modulated by water structure at TiO2–aqueous interfaces

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Friction 2024年第4期12卷 591-605页

作者： Pingsu ma yuan LIU Ke HAN yu TIAN Liran ma State Key Laboratory of Tribology in Advanced Equipment Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China

The nature of solid-liquid interfaces is of great significance in lubrication.Remarkable advances have been made in lubrication based on hydration effects.However,a detailed molecular-level understanding is still lacking.Here,we investigated water molecule behaviors at the TiO2-aqueous interfaces by the sum-frequency generation vibrational spectroscopy(SFG-VS)and atomic force microscope(AFM)to elucidate the fundamental role of solid-liquid interfaces in lubrication.Combined contributions of water structures and hydration effects were revealed,where water structures played the dominant role in lubrication for TiO2 surfaces of varying hydrophilicity,while hydration effects dominated with the increasing of ion concentrations.Superior lubrication is observed on the initial TiO2 surfaces with strongly H-bonded water molecules compared to the hydrophilic TiO2 surfaces with more disordered water.The stable ordered water arrangement with strong hydrogen bonds and the shear plane occurring between the ordered water layer and subsequent water layer may play a significant role in achieving lower friction.More adsorbed hydrated molecules with the increasing ionic concentration perturb ordered water but lead to the enhancement of hydration effects,which is the main reason for the improved lubrication for both TiO2.This work provides more insights into the detailed molecular-level understanding of the mechanism of hydration lubrication.

关键词： hydration lubrication interfacial water structures hydration effects titanium dioxide(TiO2)

Kinetic-Thermodynamic Promotion Engineering toward High-Density Hierarchical and Zn-Doping Activity-Enhancing ZnNiO@CF for High-Capacity Desalination

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Nano-Micro Letters 2024年第8期16卷 35-50页

作者： Jie ma Siyang Xing Yabo Wang Jinhu Yang Fei yu College of marine Ecology and Environment Shanghai Ocean University201306 ShanghaiPeople’s Republic of China School of Civil Engineering Kashi University844000 KashiPeople’s Republic of China Research Center for Environmental Functional materials College of Environmental Science and EngineeringTongji University1239 Siping Road200092 ShanghaiPeople’s Republic of China School of Chemical Science and Engineering Tongji University1239 Siping Road200092 ShanghaiPeople’s Republic of China Department of Energy Environmental&Chemical EngineeringWashington University in St.LouisSt.LouisMO 63130USA

Despite the promising potential of transition metal oxides(TMOs)as capacitive deionization(CDI)electrodes,the actual capacity of TMOs electrodes for sodium storage is significantly lower than the theoretical capacity,posing a major obstacle.Herein,we prepared the kinetically favorable Zn_(x)Ni_(1−x)O electrode in situ growth on carbon felt(Zn_(x)Ni_(1−x)O@CF)through constraining the rate of OH^(−)generation in the hydrothermal method.Zn_(x)Ni_(1−x)O@CF exhibited a high-density hierarchical nanosheet structure with three-dimensional open pores,benefitting the ion transport/electron transfer.And tuning the moderate amount of redox-inert Zn-doping can enhance surface electroactive sites,actual activity of redox-active Ni species,and lower adsorption energy,promoting the adsorption kinetic and thermodynamic of the Zn_(0.2)Ni_(0.8)O@CF.Benefitting from the kinetic-thermodynamic facilitation mechanism,Zn_(0.2)Ni_(0.8)O@CF achieved ultrahigh desalination capacity(128.9 mgNaCl g^(-1)),ultra-low energy consumption(0.164 kW h kgNaCl^(-1)),high salt removal rate(1.21 mgNaCl g^(-1) min^(-1)),and good cyclability.The thermodynamic facilitation and Na^(+)intercalation mechanism of Zn_(0.2)Ni_(0.8)O@CF are identified by the density functional theory calculations and electrochemical quartz crystal microbalance with dissipation monitoring,respectively.This research provides new insights into controlling electrochemically favorable morphology and demonstrates that Zn-doping,which is redox-inert,is essential for enhancing the electrochemical performance of CDI electrodes.

关键词： Zinc-nickel metal oxide High-density hierarchical Capacitive deionization Zinc-doping

Recent advances and remaining challenges in lung cancer therapy

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Chinese Medical Journal 2024年第5期137卷 533-546页

作者： Tasha Barr Shoubao ma Zhixin Li Jianhua yu Department of Hematology and Hematopoietic Cell Transplantation City of Hope National Medical CenterLos AngelesCalifornia 91010USA Comprehensive Cancer Center City of HopeLos AngelesCalifornia 91010USA Department of Immuno-Oncology Beckman Research InstituteLos AngelesCalifornia 91010USA

Lung cancer remains the most common cause of cancer death.Given the continued research into new drugs and combination therapies,outcomes in lung cancer have been improved,and clinical benefits have been expanded to a broader patient population.However,the overall cure and survival rates for lung cancer patients remain low,especially in metastatic cases.Among the available lung cancer treatment options,such as surgery,radiation therapy,chemotherapy,targeted therapies,and alternative therapies,immunotherapy has shown to be the most promising.The exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer patients.Substantial progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration(FDA)-approved drugs targeting the programmed cell death ligand-1 protein(e.g.,durvalumab,atezolizumab),the programmed cell death-1 receptor(e.g.,nivolumab,pembrolizumab),and cytotoxic T-lymphocyte-associated antigen 4(e.g.,tremelimumab,ipilimumab).Cytokines,cancer vaccines,adoptive T cell therapies,and Natural killer cell mono-and combinational therapies are rapidly being studied,yet to date,there are currently none that are FDA-approved for the treatment of lung cancer.In this review,we discuss the current lung cancer therapies with an emphasis on immunotherapy,including the challenges for future research and clinical applications.

关键词： Lung cancer Therapy Immunotherapy Combination therapy Adoptive T cell therapies

Preoperative serum cortisone levels are associated with cognition in preschool‑aged children with tetralogy of Fallot after corrective surgery:new evidence from human populations and mice

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World Journal of Pediatrics 2024年第2期20卷 173-184页

作者： Si-yu ma yu-Ting Liu yue-Shuang Cun Qiang Wang Ming-Cui Fu Ke-De Wu Xin-yu cai Shu-Ting Cheng Nishant Patel Min Da Liang Hu Zhuoga Deqin Xue-Jun Kang Ming Yang Xu-Ming Mo Department of Cardiothoracic Surgery Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China Department of Radiology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China Key Laboratory of Child Development and Learning Science Research Center For Learning ScienceSchool of Biological Sciences&Medical EngineeringMinistry of EducationSoutheast UniversityNanjing 210096China Medical School of Nanjing University Nanjing 210093China

Background Tetralogy of Fallot(TOF)is the most common cyanotic congenital heart disease.Children with TOF would be confronted with neurological impairment across their lifetime.Our study aimed to identify the risk factors for cerebral morphology changes and cognition in postoperative preschool-aged children with TOF.Methods We used mass spectrometry(MS)technology to assess the levels of serum metabolites,Wechsler preschool and primary scale of intelligence-Fourth edition(WPPSI-Ⅳ)index scores to evaluate neurodevelopmental levels and multimodal magnetic resonance imaging(MRI)to detect cortical morphological changes.Results Multiple linear regression showed that preoperative levels of serum cortisone were positively correlated with the gyrification index of the left inferior parietal gyrus in children with TOF and negatively related to their lower visual spaces index and nonverbal index.Meanwhile,preoperative SpO_(2) was negatively correlated with levels of serum cortisone after adjusting for all covariates.Furthermore,after intervening levels of cortisone in chronic hypoxic model mice,total brain volumes were reduced at both postnatal(P)11.5 and P30 days.Conclusions Our results suggest that preoperative serum cortisone levels could be used as a biomarker of neurodevelopmental impairment in children with TOF.Our study findings emphasized that preoperative levels of cortisone could influence cerebral development and cognition abilities in children with TOF.

关键词： Cognition Cortisone MRI Neurodevelopment Tetralogy of Fallot

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 382-395页

作者： Jing-Yao Ren Meng Xu Xiang-Dong Niu Shi-Xun ma Ya-Jun Jiao Da Wang Miao yu Hui cai School of Clinical Medicine Ningxia Medical UniversityYinchuan 750000Ningxia Hui autonomous regionChina Gansu Provincial Hospital Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Medical College of Jiangsu University Jiangsu UniversityZhenjiang 212013Jiangsu ProvinceChina Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

关键词： Systemic inflammatory response index Prognosis Gastric cancer Complications Meta-analysis