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A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2263-2280页

作者： Leilei Wang Shanshan he Rong Liu Yuan xue Yuan Quan Rongying Shi xueying Yang Qing Lin Xun Sun Zhirong Zhang ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Chemotherapeutics can induce immunogenic cell death(ICD)in tumor cells,offering new possibilities for cancer therapy.However,the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment(TME).here,we developed a pH/reactive oxygen species(ROS)dual-response system to enhance chemoimmunotherapy for melanoma.The system productively accumulated in tumors by specific binding of phenylboronic acid(PBA)to sialic acids(SA).The nanoparticles(NPs)rapidly swelled and released quercetin(QUE)and doxorubicin(DOX)upon the stimulation of tumor microenvironment(TME).The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice,significantly enhancing the effects of the combination.Our study revealed DOX was an ICD inducer,stimulating immune responses and promoting maturation of dendritic cells(DCs).Additionally,QUE served as a TME regulator by inhibiting the cyclooxygenase-2(COX2)-prostaglandin E2(PGE2)axis,which influenced various immune cells,including increasing cytotoxic T cells(CLTs)infiltration,promoting M1 macrophage polarization,and reducing regulatory T cells(Tregs)infiltration.The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment.This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

关键词： Quercetin Nanoparticle Responsiveness Chemoimmunotherapy Tumor immune microenvironment

Application of total keratometry in ten intraocular lens power calculation formulas in highly myopic eyes

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Eye and Vision 2024年第2期10卷 22-30页

作者： ling Wei Kaiwen Cheng Wenwen he Xiangjia Zhu Yi Lu Department of Ophthalmology and Eye Institute Eye and ENT Hospital of Fudan UniversityShanghai 200031China Key Laboratory of Myopia(Fudan University)Key Laboratory of MyopiaShanghai Key Laboratory of Visual Impairment and Restoration National Health CommissionChinese Academy of Medical ScienceShanghai 200031China State Key Laboratory of Medical Neurobiology Fudan UniversityShanghai 200031China

Background:The accuracy of using total keratometry(TK)value in recent IOL power calculation formulas in highly myopic eyes remained unknown.Methods:Highly myopic patients who underwent uneventful cataract surgery were prospectively enrolled in this prospective comparative study.At one month postoperatively,standard deviation(SD)of the prediction errors(PEs),mean and median absolute error(MedAE)of 103 highly myopic eyes were back-calculated and compared among ten formulas,including XGboost,RBF 3.0,Kane,Barrett Universal II,Emmetropia Verifying Optical 2.0,Cooke K6,Haigis,SRK/T,and Wang-Koch modifications of Haigis and SRK/T formulas,using either TK or standard keratometry(K)value.Results:In highly myopic eyes,despite good agreement between TK and K(P>0.05),larger differences between the two were associated with smaller central corneal thickness(Phe refractive errors,TK method showed no differences compared to K method.The XGBoost,RBF 3.0 and Kane ranked top three when considering SDs of PEs.Using TK value,the XGboost calculator was comparable with the RBF 3.0 formula(P>0.05),which both presented smaller MedAEs than others(all Phe percentage of eyes within±0.50 D or±0.75 D of PE,the XGBoost TK showed comparable percentages with the RBF 3.0 TK formula(74.76%vs.66.99%,or 90.29%vs.87.38%,P>0.05),and statistically larger percentages than the other eight formulas(Phe XGboost enhancement calculator and RBF 3.0 formula using TK showed the most promising outcomes in highly myopic eyes.

关键词： High myopia Total keratometry Cataract surgery IOL power calculation

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

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Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui ling he Jing Wang Regenerative Medicine Program Ottawa Hospital Research InstituteOttawaONCanada Department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada Department of Pediatrics and Medicine Johns Hopkins Medical SchoolBaltimoreMDUSA Department of Cellular and Molecular Medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

The response of structure and nitrogen removal function of the biofilm on submerged macrophytes to high ammonium in constructed wetlands

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Journal of Environmental Sciences 2024年第8期142卷 129-141页

作者： xue Jiang Mengmeng Wang Shunqing Yang Di he Fei Fang Liuyan Yang State Key Laboratory of Pollution Control and Resource Reuse School of the EnvironmentNanjing UniversityNanjing 210023China School of Resources and Environment Anqing Normal UniversityAnqing 246133China

The ammonium exceedance discharge from sewage treatment plants has a great risk to the stable operation of subsequent constructed wetlands(CWs).The effects of high ammonium shocks on submerged macrophytes and epiphytic biofilms on the leaves of submerged macrophytes in CWs were rarely mentioned in previous studies.In this paper,the 16S rRNA sequencing method was used to investigate the variation of the microbial communities in biofilms on the leaves of Vallisneria natans plants while the growth characteristics of V.natans plants were measured at different initial ammonium concentrations.The results demonstrated that the total chlorophyll and soluble sugar synthesis of V.natans plants decreased by 51.45%and 57.16%,respectively,and malondialdehyde content increased threefold after8 days if the initial NH_(4)^(+)-N concentration was more than 5 mg/L.Algal density,bacterial quantity,dissolved oxygen,and pH increased with high ammonium shocks.The average removal efficiencies of total nitrogen and NH_(4)^(+)-N reached 73.26%and 83.94%,respectively.The heat map and relative abundance analysis represented that the relative abundances of phyla Proteobacteria,Cyanobacteria,and Bacteroidetes increased.The numbers of autotrophic nitrifiers and heterotrophic nitrification aerobic denitrification(HNAD)bacteria expanded in biofilms.In particular,HNAD bacteria of Flavobacterium,Hydrogenophaga,Acidovorax,Acinetobacter,Pseudomonas,Aeromonas,and Azospira had higher abundances than autotrophic nitrifiers because there were organic matters secreted from declining leaves of V.natans plants.The analysis of the nitrogen metabolic pathway showed aerobic denitrification was the main nitrogen removal pathway.Thus,the nitrification and denitrification bacterial communities increased in epiphytic biofilms on submerged macrophytes in constructed wetlands while submerged macrophytes declined under ammonium shock loading.

关键词： Ammonium shock loading Biofilm Autotrophic nitrifiers heterotrophic nitrification aerobic denitrification bacteria Submerged macrophyte

Acute Bacillus cereus endophthalmitis caused by ocular perforation injury and occult intravitreal cilium implantation:a case report

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 976-978页

作者： ling Zhang Bin Chen Wei-Min he Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Ophthalmology the People’s Hospital of LeshanLeshan 614000Sichuan ProvinceChina

Dear Editor,We present a case of acute Bacillus cereus(B.cereus)endophthalmitis in a patient with an intraocular perforation injury combined with occult intravitreal cilium implantation.B.cereus endophthalmitis is a severe intraocular infection commonly caused by post-traumatic injuries.It often leads to significant vision loss or even eye loss within 12-48h[1].The presence of an intraocular foreign body(IOFB)increases the risk of infection,while early surgical removal of IOFBs can prevent endophthalmitis,some IOFBs are difficult to detect preoperatively.The Medical Ethics Review Board of West China Hospital of Sichuan University waived application for a clinical study because this was a retrospective report of a single patient based on imaging and because no human experimentation was involved.The patient provided written informed consent to use the imaging data for publication.

关键词： endophthalmitis ilium injuries

Electrolyte effect on electrochemical behaviors of manganese fluoride material for aqueous asymmetric and symmetric supercapacitors

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Rare Metals 2024年第3期43卷 1048-1061页

作者： Zheng-Hua he Jian-Fei Gao ling-Bin Kong State Key Laboratory of Advanced Processing and Recycling of Non-Ferrous Metals Lanzhou University of TechnologyLanzhou730050China School of Materials Science and Engineering Lanzhou University of TechnologyLanzhou730050China

Exploring wide voltage window materials is not only an available measure to enhance the energy density of hybrid supercapacitor(HSCs),but also avoids the dynamic mismatch caused by different energy storage mechanisms of two electrodes in assembled symmetrical HSC.However,there are few reports about the wide potential window materials except Bi_(2)O_(3)and VO_(2).Therefore,the MnF_(2)synthesized by solvothermal reaction was served as the electrode for HSC.The MnF_(2)exhibited electrochemical activity in alkaline solution in three-electrode system,especially with a wide potential window from-0.8 to+0.5 V in 2 mol·L^(-1)NaOH.Furthermore,the assembled MnF_(2)//MnF_(2)symmetrical HSC had a potential window of 1.5 V,and it exhibited outstanding long-cycle capability.Meanwhile,when MnF_(2)was taken as the negative and positive respectively,the potential windows of asymmetric devices CoMoO_(4)//MnF_(2)and MnF_(2)//Activated Carbon(AC)could reach 1.3 and 1.45 V,respectively,showing excellent cycle stability.This work shows that MnF_(2)material has great research value in HSC,and provides a new research direction for developing high-performance devices.

关键词： Manganese fluoride Potential window Hybrid supercapacitors Electrochemical performance

Immune checkpoint inhibitors break whose heart? Perspectives from cardio-immuno-oncology

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Genes & Diseases 2024年第2期11卷 807-818页

作者： Yingying he Hui Yu Shuang Dai Miao he ling Ma Zihan Xu Feng Luo Li Wang Oncology Department Deyang People's HospitalDeyangSichuan 618000China Department of Medical Oncology Lung Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610000China Cardiovascular Department Mianyang Central HospitalMianyangSichuan 621000China Department of Rheumatology and Immunology Deyang People's HospitalDeyangSichuan 618000China

Immune checkpoint inhibitors (ICIs) are monoclonal antibody antagonists,which can block cytotoxic T lymphocyte antigen-4 (CTLA-4),programmed death-1/ligand-1 (PD-1/PD-L1) pathways,and other molecules exploited by tumor cells to evade T cell-mediated immune response.ICIs have transformed the treatment landscape for various cancers due to their amazing efficacy.Many anti-tumor therapies,including targeted therapy,radiotherapy,and chemotherapy,combine ICIs to make the treatment more effective.However,the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ systems.Among irAEs,cardiotoxicity induced by ICIs,uncommon but fatal,has greatly offset survival benefits from ICIs,which is heartbreaking for both patients and clinicians.Consequently,such cardiotoxicity requires special vigilance,and it has become a common challenge both for patients and clinicians.This article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clinicians,elaborated on the underlying mechanisms in conjunction with animal studies,and then attempted to propose management strategies from a cardio-immuno-oncology multidisciplinary perspective.

关键词： Cancer management Cardio-immuno-oncology multidisciplinary Cardiotoxicity Immune checkpoint inhibitors Immune tolerance

Nitric oxide assists nitrogen reduction reaction on 2D MBene: A theoretical study

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Chinese Chemical Letters 2024年第5期35卷 428-433页

作者： Chaozheng he Jia Wang ling Fu Wei Wei henan Engineering Center of New Energy Battery Materials College of Chemistry and Chemical EngineeringShangqiu Normal UniversityShangqiu 476000China School of Chemistry and Chemical Engineering Shandong Provincial Key Laboratory/Collaborative Innovation Center of Chemical Energy Storage&Novel Cell TechnologyLiaocheng UniversityLiaocheng 252059China Institute of Environment and Energy Catalysis Shaanxi Key Laboratory of Optoelectronic Functional Materials and DevicesSchool of Materials Science and Chemical EngineeringXi’an Technological UniversityXi’an 710021China College of Resources and Environmental Engineering Tianshui Normal UniversityTianshui 741001China

Electrocatalytic synthesis of ammonia as an environment-friendly and sustainable development method has received widespread attention in recent years.Two-dimensional(2D)materials are a promising catalyst for ammonia synthesis due to their large surface area.In this work,we have constructed a series of 2D metal borides(MBenes)with transition metal(TM)defects(TMd-MBenes)and comprehensively calculated the reactivity of electrocatalytic synthesis of ammonia-based on density functional theory.The results have demonstrated that the TMd-MBenes can effectively activate nitrogen oxide(NO)and nitrogen(N2)molecules thermodynamically.Particularly interesting,the co-chemisorption of O atoms,dissociated from NO,can facilitate the spilled of the inert N2 molecules into single N atoms,which can further hydrogenate into ammonia easily with an ultralow limiting potential of 0.59 V on TMd-MnB.Our research has not only provided clues for catalyst design for experimental study but also paved the way for the industrial application of electrocatalytic ammonia synthesis.

关键词： 2D mbenes Nitrogen electro-reduction DFT N_(2)activation Ammonia synthesis

Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

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Bio-Design and Manufacturing 2024年第3期7卷 307-319页

作者： Sen Wang Siqi Yao Na Pei Luge Bai Zhiyan Hao Dichen Li Jiankang he J.Miguel Oliveira Xiaoyan xue ling Wang Xinggang Mao State Key Laboratory for Manufacturing System Engineering Xi’an Jiaotong UniversityXi’an 710054China School of Mechanical Engineering Xi’an Jiaotong UniversityXi’an 710054China NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices Xi’an Jiaotong UniversityXi’an 710054China 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/Guimar˜aesPortugal Department of Pharmacology School of PharmacyFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China

Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

关键词： Hypoxia Glioma Three-dimensional glioma model In vitro