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2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy

Bioactive Materials 2022年第8期7卷 76-85页

作者： Yunjie Xu Yingwei Wang Jusung An Adam C.Sedgwick Mingle Li Jianlei Xie Weibin Hu Jianlong Kang Sajal Sen Axel Steinbrueck Bin Zhang Lijun Qiao Swelm Wageh jonathan f.arambula Liping Liu Han Zhang jonathan L.Sessler Jong Seung Kim Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of EducationShenzhen Institute of Translational MedicineDepartment of OtolaryngologyShenzhen Second People’s HospitalThe First Affiliated HospitalCollege of Optoelectronic EngineeringShenzhen UniversityShenzhen518060China Department of Chemistry Korea UniversitySeoul02841South Korea Department of Hepatobiliary and Pancreatic Surgery Shenzhen People’s HospitalSecond Clinical Medical College of Jinan UniversityShenzhen518020China Department of Chemistry The University of Texas at AustinAustinTX78712-1224USA Hunan Key Laboratory of Nanophotonics and Devices School of Physics and ElectronicsCentral South University932 South Lushan RoadChangsha410083China Institute of Translation Medicine Shenzhen Second People’s Hospital first Affiliated Hospital of Shenzhen University Shenzhen518035China Department of Physics Faculty of ScienceKing Abdulaziz UniversityJeddah21589Saudi Arabia

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

关键词： 2D MXene Nanomedicine Prodrug Iron chelation Photothermal therapy

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Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth

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The Innovation 2024年第2期5卷 107-114页

作者： Johan Gustafsson fariba Roshanzamir Anders Hagnestål Sagar M.Patel Oseeyi I.Daudu Donald f.Becker jonathan L.Robinson Jens Nielsen Department of Life Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia AB SE-43854 HindåsSweden Department of Biochemistry and Redox Biology Center University of Nebraska-LincolnLincolnNE 68588USA BioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation,but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo.Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types.Here,we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model.In addition,we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human cells.The combined modeling reproduced severe hypoxic conditions and the Warburg effect,and we found that limitations in enzymatic capacity contribute to cancer cells’preferential use of glutamine as a substrate to the citric acid cycle.furthermore,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer cells.We identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts,but when limiting to metabolites previously identified to participate in such collaboration,no growth advantage was observed.Our work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

关键词： metabolism effect limitations

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Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 79-87页

作者： Jeremy P.Tervo Patricia T.Jacobson Brandon J.Vilarello Tiana M.Saak francesco f.Caruana Liam W.Gallagher Joseph B.Gary David A.Gudis Paule V.Joseph D.P.Devanand Terry E.Goldberg jonathan B.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-Head and Neck Surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID.Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function.few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery.Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell.This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD.Methods:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time points.Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available.Results:Baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up assessment.Among participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year follow-up.Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points.The total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at 1-year.Improvements in threshold,but not discrimination or identification,most significantly mediate improvement of total TDI score at follow-up.

关键词： long COVID olfaction post-COVID condition smell dysfunction

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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel jonathan Grossberg Daniel L.Barrow Matthew f.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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Management of Severely Malnourished Children Aged 6 - 59 Months Hospitalized in the Pediatric Ward of Kayanza Hospital/Burundi

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Open Journal of Pediatrics 2024年第1期14卷 11-21页

作者： Michel Baseka jonathan Niyukuri Alice Ndayishimiye Sedki Az-Eddine Vestine Ntakarutimana Department of Health Nutrition Doctoral School University of Burundi Bujumbura Burundi food Science and Technology Research Center (CRSTA) Department of Food Science and Technology (STA) Faculty of Agronomy and Bioengineering (FABI) University of Burundi Bujumbura Burundi East African Institute of Nutritional Sciences Bujumbura Burundi faculty of Medicine University of Burundi Bujumbura Burundi Department of Biology Semlalia Faculty of Science Cadi Ayyad University Marrakech Morocco Centre de recherche en sciences naturelles et environnementales Faculty of Science University of Burundi Bujumbura Burundi

The implementation of WHO guidelines has significantly reduced hospital mortality due to severe malnutrition. Nevertheless, severe acute malnutrition in children under five remains a major public health problem in all low-income countries and is little studied. The study aimed to assess the nutritional status and quality of management of severe acute malnutrition in children aged 06 to 59 months hospitalized in the pediatric ward of Kayanza Hospital. This is a prospective study with descriptive and analytical aims over 6 months from february 10 to July 9, 2023. All children aged 6 to 59 months admitted for severe acute malnutrition are included in this study. The results show that the most affected age group is 12 to 23 months (42.55%). Marasmus is the most common clinical form, at 70.2%. Housewives and mothers from rural areas are the most affected, with rates ranging from 69.14% to 91.49%. The study shows that the reasons for consultation are respectively: edema (29.78%), diarrhea (26.59%), vomiting (19.14%), and fever (14.89%). Dehydration and hypothermia were the main complications observed in 45.74% and 22.34% respectively. Medical treatment was provided by antibiotics (44.68%), artesunate (31.91%), and resomal (21.27%). Nutritional treatment consisted of f75 100% milk and f100 100% milk. Pathologies observed were: anemia 38.29%, malaria 37.23%, urinary tract infection 12.7%, measles 11.7%. The national protocol for integrated management of acute malnutrition (PCIMA) was followed. This study shows that 72.3% of children were successfully treated, with 9.5% dropping out and dying, and 8.5% not responding. We found that malnutrition remains a public health problem, affecting mostly children aged 12 to 24 months. The main complications or pathologies associated with malnutrition are diarrhea, malaria, and fever, and the majority of children suffer from marasmus.

关键词： Severe Acute Malnutrition Child Burundi

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Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

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World Journal of Hepatology 2024年第2期16卷 193-210页

作者： jonathan Soldera Leandro Luis Corso Matheus Machado Rech Vinícius Remus Ballotin Lucas Goldmann Bigarella fernanda Tomé Nathalia Moraes Rafael Sartori Balbinot Santiago Rodriguez Ajacio Bandeira de Mello Brandão Bruno Hochhegger Post Graduate Program at Acute Medicine and Gastroenterology University of South WalesCardiff CF371DLUnited Kingdom Postgraduate Program in Pathology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil Department of Engineering Universidade de Caxias do SulCaxias do Sul 95070-560Brazil School of Medicine Universidade de Caxias do SulCaxias do Sul 95070-560Brazil Postgraduate Program in Hepatology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and f1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excell

关键词： Liver transplantation Major adverse cardiac events Machine learning Myocardial perfusion imaging Stress test

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Predictive factors of Renal failure in COVID-19 Patients at the Anti-COVID Center in Lome, Togo

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Open Journal of Nephrology 2024年第2期14卷 125-135页

作者： Kossi Akomola Sabi Yoan Makafui Amekoudi Awéréou Kotosso Laune Odilon Blatome Badomta Dolaama Ayodélé jonathan Sabi Oscar Gnirimi Gbahbang Loutou Ahoub-Laye Affo Béfa Noto-Kadou-Kaza Nephrology-Hemodialysis Department of CHU Sylvanus Olympio University of Lom Lom Togo faculty of Health Sciences University of Lom Lom Togo Nephrology Department of the CHU Kara University of Kara Kara Togo Centre Hospitalier Universitaire Pointe--Pitre Pointe--Pitre Guadeloup

Background: Angiotensin-converting enzyme 2 has been identified as the receptor that allows the entry of SarsCov2 into the human cell. Its expression in the kidney is 100 times higher than in the lung;thus, making the kidney an excellent target for SarsCov2 infection manifesting as renal failure (Rf). The objective of this study was to determine the predictive factors of Rf during COVID-19 in the Togolese context. Patients and Methods: This was a retrospective descriptive and analytical study conducted at the Lomé Anti-COVID Center including the records of patients hospitalized for COVID-19, of age ≥ 18 years and having performed a creatinemia. Rf was defined by a GfR 2 calculated according to the MDRD formula. Patients were randomized into 2 groups according to GfRResults: 482 patients were selected for this study with a mean age of 58.02 years. Sixty-five percent of the patients were men, i.e., a sex ratio of 1.88. fifty-two patients had Rf, i.e., a frequency of 10.8%.There were 65% men (315 cases), for a sex ratio (M/f) of 1.88. Risk factors for renal failure in COVID-19 were age ≥ 65 years (ORa 2.42;CIa95% [1.17 - 4.95];p = 0.016), anemia (ORa 2.49;CIa95% [1.21 - 5.26];p = 0.015), moderate (ORa 13;CIa95% [2.30 - 2.44];p = 0.017), severe (ORa 26.2;CIa95% [4.85 - 4.93];p = 0.002) and critical (ORa 108;CIa95% [16.5 - 21.76];p Conclusion: Renal failure would therefore be related to the severity of COVID-19 and is the most formidable factor, conditioning the course of the disease and the patient’s vital prognosis.

关键词： COVID-19 Renal failure Risk factors Togo

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Searching for ductile superconducting Heusler X_(2)YZ compounds

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npj Computational Materials 2023年第1期9卷 919-927页

作者： Noah Hoffmann Tiago f.T.Cerqueira Pedro Borlido Antonio Sanna jonathan Schmidt Miguel A.L.Marques Institut für Physik Martin-Luther-Universität Halle-WittenbergD-06099 HalleGermany CfisUC Department of PhysicsUniversity of CoimbraRua Larga 3004-516 CoimbraPortugal Max-Planck-Institut für Mikrostrukturphysik Weinberg 2D-06120 HalleGermany

Heusler compounds attract a great deal of attention from researchers thanks to a wealth of interesting properties,among which is superconductivity.Here we perform an extensive study of the superconducting and elastic properties of the cubic(full-)Heusler family using a mixture of ab initio methods,as well as interpretable and predictive machine-learning models.By analyzing the statistical distributions of these properties and comparing them to anti-perovskites,we recognize universal behaviors that should be common to all conventional superconductors while others turn out to be specific to the material family.In total,we discover a total of eight hypothetical materials with critical temperatures above 10 K to be compared with the current record of T_(c)=4.7 K in this family.furthermore,we expect most of these materials to be highly ductile,making them potential candidates for the manufacture of wires and tapes for superconducting magnets.

关键词： ductile compounds superconducting

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Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures

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World Journal of Gastroenterology 2022年第30期28卷 4089-4101页

作者： Mahasish Shome Lusheng Song Stacy Williams Yunro Chung Vel Murugan Jin G Park William faubion Shabana f Pasha jonathan A Leighton Joshua LaBaer Ji Qiu Virginia G.Piper Center for Personalized Diagnostics Biodesign InstituteArizona State UniversityTempeAZ 85281United States Department of Internal Medicine Mayo ClinicRochesterMN 55902United States Department of Internal Medicine Division of Gastroenterology and HepatologyMayo Clinic ArizonaScottsdaleAZ 85259United States Division of Gastroenterology Mayo Clinic School of MedicineScottsdaleAZ 85259United States

BACKGROUND The healthcare burden of inflammatory bowel disease(IBD)is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.AIM To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.METHODS We performed serological profiling of 100 Crohn’s disease(CD)patients,100 ulcerative colitis(UC)patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays.The study subjects were randomly divided into discovery(n=150)and validation(n=150)sets.Statistical analysis was performed using R packages.RESULTS Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses.We identified novel antibodies against the antigens of Bacteroidetes vulgatus(BVU_0562)and Streptococcus pneumoniae(SP_1992)showing higher prevalence in CD patients relative to healthy controls.We also identified antibodies against the antigen of Streptococcus pyogenes(SPy_2009)showing higher prevalence in healthy controls relative to UC patients.Using these novel antibodies,we built biomarker panels with area under the curve(AUC)of 0.81,0.87,and 0.82 distinguishing CD vs control,UC vs control,and CD vs UC,respectively.Subgroup analysis revealed that penetrating CD behavior,colonic CD location,CD patients with a history of surgery,and extensive UC exhibited highest antibody prevalence among all patients.We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.CONCLUSION We have identified antibody signatures for CD and UC using a comprehensive analysis of antimicrobial antibody response in IBD.These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and,after future validation,should aid early and accurate d

关键词： Inflammatory bowel disease Anti-microbial antibody Protein microarray Crohn’s disease Ulcerative colitis Gut microbiome

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Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

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Bioactive Materials 2022年第3期7卷 541-553页

作者： Yuhan Zhou Ting Ye Chengzhi Ye Chao Wan Siyue Yuan Yushuai Liu Tianyu Li fagang Jiang jonathan f.Lovell Honglin Jin Jing Chen Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022PR China Department of Pediatrics Renmin Hospital of Wuhan UniversityWuhan430060PR China Department of Ophthalmology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022PR China Department of Biomedical Engineering University at BuffaloState University of New York.BuffaloNew York14260USA College of Biomedicine and Health and College of Life Science and Technology Huazhong Agricultural UniversityWuhan430070China

Autologous tumor cells and cell-derived secretions(CDS)can induce antitumor immune responses.The conditions in which cells are cultured and treated impact CDS,and cellular insults alter their composition and function.In this study,we generated CDS from tumor cells exposed to normal culture conditions,hypoxia,cisplatin,radiotherapy,photodynamic therapy,or hypochlorous acid(HOCl).In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia,cisplatin,radiotherapy or photodynamic therapy.To improve HOCl-CDS activity at the tumor site,we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold.When injected intratumorally,the HOCl-CDS hydrogel promoted tumor cell death,cytotoxic T lymphocyte infiltration,and tumor-associated macrophage reprogramming towards an M1 phenotype.The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-f10 melanoma.furthermore,hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade.These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.

关键词： Cancer immunotherapy Hydrogel Melittin Anti-PD-1 Cell-derived secretions

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