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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Department of Hepatic Surgery and Liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial Key Laboratory of Liver Disease Research Guangzhou 510630China Department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR Liver cancer

Predicting distant metastasis in nasopharyngeal carcinoma using gradient boosting tree model based on detailed magnetic resonance imaging reports

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World Journal of Radiology 2024年第6期16卷 203-210页

作者： Yu-Liang Zhu Xin-Lei Deng Xu-Cheng Zhang Li Tian Chun-Yan Cui Feng Lei Gui-Qiong Xu Hao-Jiang Li Li-Zhi Liu Hua-Li Ma Department of Nasopharyngeal Head and Neck Tumor Radiotherapy Zhongshan City People's HospitalZhongshan 528400Guangdong ProvinceChina School of Public Health Sun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Department of Radiology Sun Yatsen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Development of distant metastasis(DM)is a major concern during treatment of nasopharyngeal carcinoma(NPC).However,studies have demonstrated im-proved distant control and survival in patients with advanced NPC with the addition of chemotherapy to concomitant ***,precise prediction of metastasis in patients with NPC is *** To develop a predictive model for metastasis in NPC using detailed magnetic resonance imaging(MRI)*** This retrospective study included 792 patients with non-distant metastatic NPC.A total of 469 imaging variables were obtained from detailed MRI *** were stratified and randomly split into training(50%)and testing *** boosting tree(GBT)models were built and used to select variables for predicting DM.A full model comprising all variables and a reduced model with the top-five variables were *** performance was assessed by area under the curve(AUC).RESULTS Among the 792 patients,94 developed DM during *** number of metastatic cervical nodes(30.9%),tumor invasion in the posterior half of the nasal cavity(9.7%),two sides of the pharyngeal recess(6.2%),tubal torus(3.3%),and single side of the parapharyngeal space(2.7%)were the top-five contributors for predicting DM,based on their relative importance in GBT *** testing AUC of the full model was 0.75(95%confidence interval[CI]:0.69-0.82).The testing AUC of the reduced model was 0.75(95%CI:0.68-0.82).For the whole dataset,the full(AUC=0.76,95%CI:0.72-0.82)and reduced models(AUC=0.76,95%CI:0.71-0.81)outperformed the tumor node-staging system(AUC=0.67,95%CI:0.61-0.73).CONCLUSION The GBT model outperformed the tumor node-staging system in predicting metastasis in *** number of metastatic cervical nodes was identified as the principal contributing variable.

关键词： Nasopharyngeal carcinoma Distant metastasis Machine learning Detailed magnetic resonance imaging report Gradient boosting tree model

Association of E-cadherin and β-catenin with metastasis in nasopharyngeal carcinoma

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Chinese Medical Journal 2004年第8期117卷 1232-1239页

作者：李智任艺林素暇梁英杰梁惠珍 Department of Pathology sun yatsen Medical College Sun Yatsen UniversityGuangzhou510089China Department of Surgery Queen Mary hospital University of HongKongHongKongChina

Background This study was designed to detect methylation of E-cadherin gene promoter and gene mutation of β-catenin in exon 3 and their expression of protein and mRNA in primary tumor and lymph node metastatic tumor of nasopharyngeal carcinoma (NPC), and investigate the mechanism of invasion and metastasis of neoplastic cells in NPC Methods Fourty-two fresh biopsy samples were taken from untreated NPC patients at the Affiliated hospital of sun Yat-sen Medical College, sun Yat-sen University, Guangzhou, China during the period of 1999-2002 Among them 21 were taken from primary tumors and the other 21 from lymph node metastatic tumors The gene promoter methylation of E-cadherin was detected by methylation-specific PCR (MSP) The mutation in exon 3 of β-catenin was detected by direct sequencing analysis RT-PCR, Western blot and immunohistochemical staining were used to detect the mRNA and protein expression patterns in both primary and metastatic tumors of NPC Results Down-regulated expression of E-cadherin in metastatic tumor was compared with that in primary tumor Reduced expression of E-cadherin was found to be correlated with lymph node metastatic tumor of NPC ( P =0 004); but there was no obvious correlation between primary and metastatic tumors in the expression of β-catenin ( P =0 698) The mRNA expression level of E-cadherin in metastatic tumors decreased significantly compared with that in primary tumors However, little change was observed in the mRNA level of β-catenin in different tumor tissues Only 4 samples (19 1%) displayed gene promoter methylation of E-cadherin in primary tumor and 10 samples (47 6%) showed methylated form of E-cadherin The gene promoter methylation of E-cadherin was more common in metastatic tumor than in primary tumor of NPC ( P =0 024) Only 2 (4 76%) of the 42 samples showed mutations in exon 3 of β-catenin at 41 (T41A, ACCGCC) and codon 47 (S47T, AGTACT) The cytoplasmic and nuclear expression

关键词： nasopharyngeal tumor ·E-cadherin ·β-catenin methylation mutation ·invasion and metastasis

Application of artifcial intelligence in cataract management:current and future directions

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Eye and Vision 2024年第1期10卷 21-30页

作者： Laura Gutierrez Jane Sujuan Lim Li Lian Foo Wei Yan Ng Michelle Yip Gilbert Yong San Lim Melissa Hsing Yi Wong Allan Fong Mohamad Rosman Jodhbir Singth Mehta Haotian Lin Darren Shu Jeng Ting Daniel Shu Wei Ting Singapore Eye Research Institute SingaporeSingapore Singapore National Eye Center 11 Third Hospital AvenueSingapore 168751Singapore Academic Ophthalmology School of MedicineUniversity of NottinghamNottinghamUK Zhongshan Ophthalmic Center Sun Yet Sen UniversityGuangzhouChina

The rise of artifcial intelligence(AI)has brought breakthroughs in many areas of *** ophthalmology,AI has delivered robust results in the screening and detection of diabetic retinopathy,age-related macular degeneration,glaucoma,and retinopathy of *** management is another feld that can beneft from greater AI *** is the leading cause of reversible visual impairment with a rising global clinical *** diagnosis,monitoring,and surgical management are necessary to address this *** addition,patients in large developing countries often sufer from limited access to tertiary care,a problem further exacerbated by the ongoing COVID-19 *** on the other hand,can help transform cataract management by improving automation,efcacy and overcoming geographical ***,AI can be applied as a telediagnostic platform to screen and diagnose patients with cataract using slit-lamp and fundus *** utilizes a deep-learning,convolutional neural network(CNN)to detect and classify referable cataracts ***,some of the latest intraocular lens formulas have used AI to enhance prediction accuracy,achieving superior postoperative refractive results compared to traditional ***,AI can be used to augment cataract surgical skill training by identifying diferent phases of cataract surgery on video and to optimize operating theater workfows by accurately predicting the duration of surgical ***,some AI CNN models are able to efectively predict the progression of posterior capsule opacifcation and eventual need for YAG laser *** advances in AI could transform cataract management and enable delivery of efcient ophthalmic *** key challenges include ethical management of data,ensuring data security and privacy,demonstrating clinically acceptable performance,improving the generalizability of AI models across heterogeneous populations,and improving the trust of e

关键词： Artifcial intelligence Telemedicine Cataract Cataract screening Cataract surgery IOL calculations Biometry Machine learning

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

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Frontiers of Medicine 2024年第2期18卷 303-314页

作者： Yi Ding Xiaoli Xu Zhuojun Xin Qiuyu Cao Jiaojiao Huang Xianglin Wu Yanan Huo Qin Wan Yingfen Qin Ruying Hu Lixin Shi Qing Su Xuefeng Yu Li Yan Guijun Qin Xulei Tang Gang Chen Min Xu Tiange Wang Zhiyun Zhao Zhengnan Gao Guixia Wang Feixia Shen Zuojie Luo Li Chen Qiang Li Zhen Ye Yinfei Zhang Chao Liu Youmin Wang Tao Yang Huacong Deng Lulu Chen Tianshu Zeng Jiajun Zhao Yiming Mu Shengli Wu Yuhong Chen Jieli Lu Weiqing Wang Guang Ning Yu Xu Yufang Bi Mian Li Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Jiangxi Provincial People’s hospital Affiliated to Nanchang UniversityNanchang330000China Department of Endocrinology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou310000China Department of Endocrinology Affiliated Hospital of Guiyang Medical UniversityGuiyang550000China Xinhua hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200000China Tongji hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China sun Yat-sen memorial hospital Sun Yat-sen UniversityGuangzhou510000China Department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Department of Endocrinology The First Hospital of Lanzhou UniversityLanzhou730000China Fujian Provincial hospital Fujian Medical UniversityFuzhou350000China Dalian Municipal Central hospital Affiliated of Dalian Medical UniversityDalian116000China Department of Endocrinology The First Hospital of Jilin UniversityChangchun130000China Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Qilu hospital of Shandong University Jinan250000China Department of Endocrinology The Second Affiliated Hospital of Harbin Medical UniversityHarbin150000China Department of Endocrinology Cen

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with *** included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life *** isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD ***-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working *** stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long *** pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active *** U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical *** divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词： sleep physical activity chronic kidney disease isotemporal substitution behavioral pattern

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing sun Yuanyuan Chen Ming Chen Department of Radiation Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation Oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation Oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation Oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of Radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Oncology Maoming People’s HospitalMaoming 525000China Department of Radiation Oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier Radiotherapy Technology of sun Yat-sen University&Chinese Academy of Sciences Ion Medical Technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus

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The Innovation 2024年第1期5卷 98-108页

作者： Zongshan Shen Shuhong Kuang Yong Zhang Jiayao Chen Shuting Wang Congfei Xu Yunjia Huang Min Zhang Shuheng Huang Jun Wang ChuanJiang Zhao Zhengmei Lin Xuetao Shi Bin Cheng hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhou 510060China National Engineering Research Centre for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou 510006China School of Biomedical Science and Engineering South China University of TechnologyGuangzhou 510650China The First Affiliated hospital Sun Yat-sen UniversityGuangzhou 510080China

Cognitive decline has been linked to periodontitis through an undetermined pathophysiological *** study aimed to explore the mechanism underlying periodontitis-related cognitive decline and identify therapeutic strategies for this *** single-nucleus RNA sequencing we found that changes in astrocyte number,gene expression,and cell‒cell communication were associated with cognitive decline in mice with *** addition,activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome was observed to decrease the phagocytic capability of macrophages and reprogram macrophages to a more proinflammatory state in the gingiva,thus aggravating *** further investigate this finding,lipid-based nanoparticles carrying NLRP3 siRNA(NPsiNLRP3)were used to inhibit overactivation of the NLRP3 inflammasome in gingival macrophages,restoring the oral microbiome and reducing periodontal ***,gingival injection of NPsiNLRP3 reduced the number of Serpina3nhigh astrocytes in the hippocampus and prevented cognitive *** study provides a functional basis for the mechanism by which the destruction of periodontal tissues can worsen cognitive decline and identifies nanoparticle-mediated restoration of gingival macrophage function as a novel treatment for periodontitis-related cognitive decline.

关键词： NLRP3 periodontal number

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

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Neural Regeneration Research 2024年第3期19卷 650-656页

作者： Jie Li Wen Jiang Yuefang Cai Zhenqiu Ning Yingying Zhou Chengyi Wang Sookja Ki Chung Yan Huang Jingbo sun Minzhen Deng Lihua Zhou Xiao Cheng Guangzhou University of Traditional Chinese Medicine GuangzhouGuangdong ProvinceChina State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Research on Emergency in TCM GuangzhouGuangdong ProvinceChina Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anatomy Sun Yat-Sen School of MedicineSun Yat-Sen UniversityShenzhenGuangdong ProvinceChina Faculty of Medicine Macao University of Science and TechnologyMacao Special Administration RegionChina

Vascular etiology is the second most prevalent cause of cognitive impairment ***-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of ***,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well ***,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery *** proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic ***,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway *** chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic ***,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

关键词： astrocytic endothelin-1 dentate gyrus differentially expressed proteins hippocampus ischemic stroke learning and memory deficits lipid metabolism neural stem cells neurogenesis proliferation

Click-hydrogel delivered aggregation-induced emissive nanovesicles for simultaneous remodeling and antibiosis of deep burn wounds

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Aggregate 2024年第1期5卷 244-256页

作者： Xu Chen Meijiao Zhao Qihu Xie Sitong Zhou Xiaoping Zhong Judun Zheng Ronghua Yang Xianjin Du Jinyu Xia Yuhui Liao Department of Infectious Diseases The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina Molecular Diagnosis and Treatment Center for Infectious Diseases Dermatology HospitalSouthern Medical UniversityGuangzhouChina Department of Burns and Plastic Surgery The Second Affiliated Hospital of Shantou University Medical CollegeShantouChina Department of Dermatology TheFirst People’s Hospital of FoshanFoshanChina Department of Burn and Plastic Surgery Guangzhou First People’s HospitalSouth China University of TechnologyGuangzhouChina Department of Critical Care Medicine Renmin Hospital of Wuhan UniversityWuhanChina

As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent *** this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry *** aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating *** addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on *** hydrogel could be injected to conform to the wound morphology while responding to the acidic *** vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen *** study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.

关键词： aggregation-induced emission burn wounds nanovesicles