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Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK

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International Journal of Oral Science 2024年第3期16卷 471-485页

作者： Dexuan Zhuang Shuangshuang Wang Huiting Deng Yuxin Shi Chang Liu Xue Leng Qun Zhang Fuxiang Bai Bin Zheng Jing Guo Xunwei Wu School and Hospital of Stomatology Cheeloo College of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration&Shandong Provincial Clinical Research Center for Oral DiseasesJinanChina Engineering Laboratory for Biomaterials and tissue regeneration Ningbo Stomatology HospitalSavaid Stomatology SchoolHangzhou Medical CollegeNingboChina Cedars-Sinai Cancer Institute Department of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesCAUSA

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new *** has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC *** found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in ***-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC ***,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC ***,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of *** summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell *** study supports the potential clinical utility of phenformin for OSCC treatment in the future.

关键词： drugs treatment AMPK DDI

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Flexible wearable sensors:An emerging platform for monitoring of bacterial infection in skin wounds

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Engineered regeneration 2024年第2期5卷 186-198页

作者： Hao Meng Weicheng Zhong Kui Ma Jianlong Su Liqian Ma Yaying Hao Yufeng Jiang Xi Liu Xiaobing Fu Cuiping Zhang Research Center for tissue Repair and regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical CollegeBeijing 100048PR China PLA Key Laboratory of tissue Repair and Regenerative Medicine Beijing 100048PR China Beijing Key Research Laboratory of Skin Injury Repair and RegenerationBeijing 100048PR China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China Department of tissue regeneration and Wound Repair PLA General HospitalBeijingPR China

Persistent inflammatory responses often occur when bacteria and other microorganisms frequently invade and colonize open wounds and eventually result in the formation of chronic ***,achieving real-time detection of invasive bacteria accurately and promptly is essential for efficient wound management and accelerat-ing the healing ***,flexible wearable sensors have garnered significant attention,especially those designed for monitoring real-time biophysical or biochemical signals in wound sites in a minimally invasive *** provide more precise and continuous monitoring data,making them as emerging tools for clinical *** this review,we first discuss the species and community distribution of different types of bacteria in chronic ***,we introduce currently developed techniques for detecting bacteria at wound ***-lowing that,we discuss the recent progress and unresolved issues of various flexible wearable sensors in detecting bacteria at wound *** believe that this review can provide meaningful guidance for the development of flexible wearable sensors for bacteria detection.

关键词： Flexible wearable sensors Chronic wounds Bacterial infections Real-time detection

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Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

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Neural regeneration Research 2024年第1期19卷 55-61页

作者： Paula lzquierdo-Altarejos Victoria Moreno-Manzano Vicente Felipo Laboratory of Neurobiology Centro Investigación Príncipe FelipeValenciaSpain Neuronal and tissue regeneration Laboratory Centro Investigación Príncipe FelipeValenciaSpain

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive *** vesicles play an important role in intercellular communication and in the modulation of the immune system and *** cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological *** vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative *** vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the *** contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative *** mechanisms involved are beginning to be unde *** example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal *** the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early *** contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor *** extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target *** vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and

关键词： extracellular vesicles inflammation cognitive function mesenchymal stem cells neurodegenerative diseases neuroinflammation therapy transforming growth factor-β

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Fabrication of patterned transparent conductive glass via laser metal transfer for efficient electrical heating and antibacteria

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Nano Research 2024年第3期17卷 1578-1584页

作者： Xiaoyan Liu Ting Zhang Mengchen Xu Yang Li Haiqing Wang Yuke Chen Xuzihan Zhang Zenan Wang Xiaoyan Li Weijia Zhou Hong Liu Institute for Advanced Interdisciplinary Research(iAIR) School of Chemistry and Chemical EngineeringUniversity of JinanJinan 250022China School of Physics and Technology University of JinanJinan 250024China Department of Endodontics School and Hospital of StomatologyCheeloo College of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue RegenerationJinan 250012China School of Information Science and Engineering University of JinanJinan 250022China Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055China

Vapor deposition and three-dimensional(3D)printing technology are considered to be conventional methods to achieve patterned metal film preparation through the assistance of masks and high ***,there are still some challenges in fabricating metal films in template-free and normal temperature *** this work,we report a flexible and rapid laser metal transfer(LMT)technique for fabricating the various metal films(Cu,Ni,Sn,Al,Fe,and Ag)with different patterns without templates on arbitrary substrates(glass,polyimide(PI)films,and aluminum nitride(AlN)ceramic).Especially,the obtained transparent conductive glass displays high transmittance(more than 90%)and adjustable resistances(≈5Ω).According to the Joule effect,the interface resistance between Cu particles and copper oxide coating produces the high temperature approximately 280℃ at 2 V in a short time(≈60 s)and remains stable at 120℃ over 12 *** last,the multifunctional glass with Cu patterns also shows excellent bactericidal activity(≈95%).This work demonstrates that laser metal transfer is an exceeding effective means of fabricating the micro/nano structures with potential applications in functional devices.

关键词： laser metal transfer(LMT) transparent conductive glass electrical heating copper pattern antibacterial

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Enhanced multifunctional liquid metal-based hydrogels with vinyl silica nanoparticles for advanced strain sensing applications

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Science China Materials 2024年第10期67卷 3309-3320页

作者： Bingyan Wang Wenxia Liu Zhaoping Song Guodong Li Dehai Yu Xiaona Liu Huili Wang Shaohua Ge State Key Laboratory of Biobased Materials and Green Papermaking Qilu University of TechnologyShandong Academy of ScienceJinan 250353China Department of Periodontology School and Hospital of StomatologyCheeloo College of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue RegenerationJinan 250012China

Conductive hydrogels have garnered considerable interest for their applications in wearable electronic skins,owing to their superior ***,challenges persist,including low sensitivity,poor cyclic stability,and limited tolerance to extreme *** study develops a novel liquid metal-based conductive hydrogel with a dual cross-linked polyacrylic acid(PAA)matrix,employing both“soft”coordination and“hard”covalent cross-linking *** hybrid network is formulated using guar gum(GG)-stabilized gallium(Ga)droplets,which catalyze the copolymerization of vinyl-hybrid silica nanoparticles(VSNPs)and acrylic acid(AA).The resultant Ga3+ions interact with carboxyl groups in the PAA,forming soft coordination links that enhance the hydrogel’s rapid *** incorporation of VSNPs significantly enhances the hydrogel’s elasticity,toughness,and low-temperature resilience without ***,its intrinsic moldability,adhesion,and self-healing properties are *** as a strain sensor,this hydrogel demonstrates a high gauge factor(GF)of 17.4,responsive time of 250 ms for both activation and recovery,an ultra-low detection limit of 0.1%,and excellent durability over 800 cycles at 100%***-term immersion in a glycerol solution(20 min)further augments its stretchability to 2688%and GF to 28.1 across a strain range of 1325%–1450%,broadening its operational ranges to 0–1450%at−18°*** exposure(4 h)also improves water retention and high-temperature resistance,making this hydrogel a promising material for sustainable,high-performance wearable electronics.

关键词： vinyl silica nanoparticles liquid metals guar gum hydrogel strain sensor

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Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel

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Regenerative Biomaterials 2024年第3期3卷 56-67页

作者： Ming Ke Wenhui Xu Yansha Hao Feiyang Zheng Guanyuan Yang Yonghong Fan Fangfang Wang Zhiqiang Nie Chuhong Zhu Department of Anatomy Third Military Medical UniversityChongqing 400038China State Key Laboratory of Trauma Burn and Combined InjuryChongqing 400038China Department of Plastic and Aesthetic Surgery Southwest HospitalThird Military Medical UniversityChongqing 400038China Engineering Research Center of tissue and Organ regeneration and Manufacturing Ministry of EducationChongqing 400038China

Engineering myocardium has shown great clinal potential for repairing permanent myocardial ***,the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical *** prepared a mixed gel containing fibrin(5 mg/ml)and collagen I(0.2 mg/ml)and verified that human umbilical vein endothelial cells(HUVECs)and human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)could fom microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of ***-CMs and HUVECs in the mixed gel formed self-organized cell clusters,which were then cultured in different media using a three-phase *** successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of *** tissue exhibited autonomous beats that occured at a frequency similar to a normal human heart *** internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in *** summary,we propose a simple method for constructing vascularized engineered myocardial tissue,through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation *** constructed tissue has potential value for clinical use after preliminary evaluation.

关键词： engineered myocardium vascularized hiPSC-CM HUVEC fibrin

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Lateral circumflex femoral artery perforator flap for the reconstruction of head soft tissue defects:Cross-region venous anastomosis

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Chinese Journal of Plastic and Reconstructive Surgery 2024年第3期6卷 111-115页

作者： Gongxue Zhang Wenhu Jin Ziyang Zhang Lei Shi Rui Yang Dali Wang Department of Burn and Plastic Surgery Affiliated Hospital of Zunyi Medical UniversityZunyi563000GuizhouChina Collaborative Innovation Center of tissue Damage Repair and regeneration Medicine Zunyi Medical UniversityZunyi563000GuizhouChina

Background:Owing to its unique characteristics,the lateral circumflex femoral artery perforator(LCFAP)flap is often preferred for repairing head wounds with exposed ***,given the vascular distribution in the head,particularly the veins,can lead to postoperative complications such as venous congestion of the *** rates of vascular exploration and necrosis in these flaps are significantly higher than in other body ***,it is crucial to identify a safe and effective method for venous anastomosis of free flaps in the head ***:This retrospective case series study included 10 patients with large head soft tissue defects treated at the Burn and Plastic Surgery Department of the Affiliated Hospital of Zunyi Medical University from January 2020 to December *** head defects were reconstructed using LCFAP flaps,with flap veins anastomosed to the external jugular vein in the neck,either directly or via a bridging ***:Among the 10 adult patients with massive head wound defects,7(70%)were *** patients’mean age was 53.0 years(48–59 years).The wound defects were caused by trauma in 6(60%)patients and by tumors in 4(40%)***,no significant complications occurred,and all LCFAP flap survived without ***:The descending branch of the LCFAP flap effectively repairs massive head wound *** venous anastomosis method for this flap is associated with a low incidence of venous complications and a high patency rate,making it a clinically valuable reference.

关键词： Descending branch of lateral External jugular vein Wound repair Perforator flap

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An aptamer-driven DNA nanodevice for improved delivery of synthetic immunostimulants

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Nano Research 2024年第10期17卷 9078-9083页

作者： Dejie Lu Zhenghan Di Lele Li Jian Zhao Li Zheng Guangxi Engineering Center in Biomedical Materials for tissue and Organ regeneration Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and ApplicationGuangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Efficient delivery of therapeutics to immune cells remains a formidable challenge for cancer *** this work,we demonstrate that an aptamer-driven DNA nanodevice,constructed through linkage of a synthetic immunostimulant(Toll-like receptor 9 agonist:CpG motif)to an aptamer,could significantly enhance the immunostimulatory activity by facilitating the uptake and retention of therapeutics in *** administration of the DNA nanodevice results in efficient tumor growth inhibition in both breast cancer and melanoma mouse *** studies suggest that the DNA nanodevice leads to reeducation of tumor-associated macrophages and ultimately to reversing the tumor immune *** strategy for aptamer-mediated and vehicle-free delivery of immunostimulatory oligonucleotides provides a potential platform for cancer immunotherapy.

关键词： aptamer immunostimulatory oligonucleotides DNA nanodevice tumor-associated macrophages cancer therapy

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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

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Neural regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of DaytonDaytonOHUSA Premedical Program University of DaytonDaytonOHUSA Center for tissue regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA The Integrative Science and Engineering Center University of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe acute respiratory syndrome(SARS),cognitive dysfunction like brain fog,and cardiovascular ***-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer's disease remain *** the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye,we found that misexpression of nonstructural protein 3(Nsp3),a papain-like protease,ablates the eye and generates dark necrotic *** misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters,terminal deoxynucleotidyl transferase(TdT)dUTP Nick-end labeling(TUNEL)assay,and dihydroethidium ***,Nsp3 misexpression activates both apoptosis and autophagy mechanism(s)to regulate tissue *** expression of SARS-CoV2 Nsp3 in murine neuroblastoma,Neuro-2a cells,significantly reduced the metabolic activity of these cells and triggers cell *** of SARS-CoV2 Nsp3 in an Alzheimer's disease transgenic fly eye model(glass multiple repeats[GMR]>amyloidβ42)further enhances the neurodegenerative rough eye phenotype due to increased cell *** findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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Skeletal stem cells in bone development,homeostasis,and disease

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Protein & Cell 2024年第8期15卷 559-574页

作者： Guixin Yuan Xixi Lin Ying Liu Matthew B.Greenblatt Ren Xu The First Affliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cell State Key Laboratory of Cellular Stress BiologySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361005China Xiamen Key Laboratory of regeneration Medicine Fujian Provincial Key Laboratory of Organ and Tissue RegenerationOrgan Transplantation InstituteSchool of MedicineXiamen UniversityXiamen 361102China Department of Pathology and Laboratory Medicine Weill Cormell Medical CollegeNew YorkNY 10065USA Research Division Hospital for Special SurgeryNew YorkNY10065USA

tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem *** studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and *** investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time ***,recent studies have shed light on the characteristics of ssCs in both physiological and pathological *** review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

关键词： skeletal stem cells bone development endochondral ossification intramembranous ossification lineage tracing

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