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Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing

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National Science Review 2024年第4期11卷 254-270页

作者： Yutong Yang Jiaxin Wang Shengfei Huang Meng Li Jueying Chen Dandan Pei Zhen Tang Baolin Guo State Key laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and Technology and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of Stomatology Xi'an Jiaotong University Department of orthopedics Tangdu Hospital Fourth Military Medical University Department of orthopedics The First Affiliated Hospital of Xi'an Jiaotong University

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, p H-responsive H2O2self-supplying composite nanozyme（MSCO） and p H/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase（PPEL） were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan（CA） and phenylboronic acid-modified oxidized dextran（ODP） to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide（NO） release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound *** self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.

关键词： bacterial response hydrogel dressing multiple nanozyme activity biofilm elimination infected motion wound healing

Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

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Nano Research 2024年第8期17卷 7376-7393页

作者： Aoao Wang Xinbo Ma Yafeng Yang Guoliang Shi Liwei Han Xiantong Hu Rui Shi Jun Yan Quanyi Guo Yantao Zhao Senior Department of orthopedics the Fourth Medical Center of PLA General HospitalBeijing 100048China Department of Chemistry Capital Normal UniversityBeijing 100048China National Center for Orthopaedics Beijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Xijing 986 Hospital Department The Fourth Military Medical UniversityXi'an 710032China Institute of orthopedics Chinese PLA General HospitalBeijing Key Laboratory of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events,including pathogen clearance,immunological modulation,and *** this study,we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial,immunomodulatory,and osteogenic effects using electrospinning *** scaffold’s piezoelectric signal output under ultrasound(US)control can be similar to the physiological electrical signals of healthy bone tissue,creating a truly biomimetic electrical microenvironment in the bone *** vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation,migration,and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ***,the scaffold exhibits inhibitory effects on the growth of *** and ***,as well as the ability to induce M2 macrophage polarization,indicating potent antibacterial and immunomodulatory *** vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats,effectively inhibit bacterial colonization,and reduce inflammatory ***,this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing,thus providing a simple and effective solution for bone defects.

关键词： piezoelectricity bone defect bacterial infection ZnO nanoparticles immunomodulation osteogenesis

Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 513-528页

作者： Miao CHU Guangdong CHEN Kai CHEN Pengfei ZHU Zhen WANG Zhonglai QIAN Huaqiang TAO Yaozeng XU Dechun GENG Department of orthopedics the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of orthopedics Yixing People’s HospitalYixing 214200China Department of orthopedics Hai’an People’s HospitalHai’an 226600China Department of orthopedics Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedicineSuzhou 215028China

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the *** activation plays a crucial role in the occurrence of subchondral bone loss in early ***,the specific mechanism of osteoclast differentiation in OA remains *** our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)***2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral ***,fourteen DEGs that are associated with oxidative stress were *** first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further *** results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of *** was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in ***,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in *** research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of *** HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

关键词： Osteoclast Oxidative stress Osteoarthritis(OA) Heme oxygenase 1(HMOX1) Carnosol

Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

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Neural Regeneration Research 2024年第2期19卷 434-439页

作者： Chenxi Zhao Tiangang Zhou Ming Li Jie Liu Xiaoqing Zhao Yilin Pang Xinjie Liu Jiawei Zhang Lei Ma Wenxiang Li Xue Yao Shiqing Feng Department of orthopedics Tianjin Medical University General HospitalTianjinChina International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Orthopedic Research Center of Shandong University Cheeloo College of MedicineDepartment of OrthopedicsQilu Hospital of Shandong UniversityJinanShandong ProvinceChina

Argatroban is a synthetic thrombin inhibitor approved by *** and Drug Administration for the treatment of ***,whether it plays a role in the repair of spinal cord injury is *** this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive *** results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal *** sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar *** blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal *** also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal *** together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.

关键词： argatroban astrogliosis JAK/STAT signaling pathway protease-activated receptor-1 spinal cord injury thrombin vimentin

Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

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Genes & Diseases 2024年第2期11卷 1050-1065页

作者： Xiaoxuan Wang Lijuan Luo Jingtao Xu Qiuping Lu Haichao Xia Yanran Huang Lulu Zhang Liping Xie Habu Jiwa Shiqiong Liang Xiaoji Luo Jinyong Luo Key laboratory of Diagnostic Medicine Designated By the Chinese Ministry of Education School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China

Bladder cancer (BC) is one of the most common malignant tumors in the urinary *** to the poor prognosis and high mortality rate of the disease,it is urgent to develop new drugs with high efficacy and low toxicity to treat *** (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor ***,we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular *** found that Ecnin vitro inhibited the proliferation,migration,and invasion,arrested the cell cycle at the G2/M phase,and promoted apoptosis in BC ***,Ecn had no notable cytotoxicity towards human normal *** subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo .Mechanistically,Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway,while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC ***,Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC *** summary,our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling *** meaningfully,our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.

关键词： Bladder cancer Combination chemotherapy Echinatin p38 Wnt/β-catenin

A"messenger zone hypothesis"based on the visual three-dimensional spatial distribution of motoneurons innervating deep limb muscles

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Neural Regeneration Research 2024年第7期19卷 1559-1567页

作者： Chen Huang Shen Wang Jin Deng Xinyi Gu Shuhang Guo Xiaofeng Yin MoE Key laboratory for Trauma Treatment and Nerve Regeneration Peking UniversityBeijingChina Department of orthopedics and Trauma Peking University People’s HospitalBeijingChina

Coordinated contraction of skeletal muscles relies on selective connections between the muscles and multiple classes of the spinal motoneuro *** r,current research on the spatial location of the spinal motoneurons innervating differe nt muscles is *** this study,we investigated the spatial distribution and relative position of different motoneurons that control the deep muscles of the mouse hindlimbs,which were innervated by the obturator nerve,femoral nerve,inferior gluteal nerve,deep pe roneal nerve,and tibial *** were visualized by combining a multiplex retrograde tracking technique compatible with three-dimensional imaging of solvent-cleared o rgans(3DISCO)and 3-D imaging technology based on lightsheet fluorescence microscopy(LSFM).Additionally,we propose the hypothesis that"messenger zones"exist as interlaced areas between the motoneuron pools that dominate the synergistic or antagonist muscle *** hypothesize that these interlaced neurons may participate in muscle coordination as messenger *** revealed the precise mutual positional relationships among the many motoneurons that innervate different deep muscles of the *** only do these findings update and supplement our knowledge regarding the overall spatial layout of spinal motoneurons that control mouse limb muscles,but they also provide insights into the mechanisms through which muscle activity is coordinated and the architecture of motor circuits.

关键词： 3-D imaging motoneurons multiple retrograde tracing muscle coordination skeletal muscle spatial distribution optical tissue clearing

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han Department of Trauma and orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine BeijingChina Key laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Department of orthopedics China-Japan Friendship HospitalBeijingChina Department of Central laboratory and Institute of Clinical Molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

Metal ion metabolism and osteoporosis:possible implications for pharmaceutical biotechnology and tissue engineering

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Science China(Life Sciences) 2024年第8期67卷 1763-1765页

作者： Huaqiang Tao Qiufei Wang Kai Chen Pengfei Zhu Ye Gu Dechun Geng Department of orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of orthopedics Changshu Hospital Affiliated to Soochow UniversityFirst People’s Hospital of Changshu CityChangshu 215506China Department of orthopedics Hai’an People’s HospitalHai’an 226600China

Osteoporosis(OP)is a systemic metabolic bone disease characterized by low bone mass,damage to bone microstructure and increased bone *** imbalance of functional coupling between osteoblasts and osteoclasts contributes to the pathological progression of the disease(Rachner et al.,2011).The pathogenesis of OP is precisely controlled by the complex regulatory network of the bone *** elements,although present in small amounts in the body,are essential for their influence on the physiological activities of *** ions act as effective catalysts and have applications in all stages of cell biochemical evolution(Qian et al.,2021).Bone tissue contains various metal elements,and metal ions play indispensable roles in bone metabolism at the molecular and cellular levels(Luo et al.,2023).However,it is important to note that these metal ions can also contribute to the progression of OP by influencing multiple cellular pathways either directly or indirectly.

关键词： metabolism biotechnology indispensable

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ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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Nano Research 2024年第3期17卷 1772-1784页

作者： Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu Department of orthopedics Orthopedic Laboratory of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Luzhou 646699China Department of orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China Department of orthopedics Chongqing University Three Gorges HospitalChongqing 404000China Department of Geriatrics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025China Beijing Key laboratory of Lignocellulosic Chemistry College of Material Science and TechnologyBeijing Forestry UniversityBeijing 100083China

Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high *** article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug *** can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS *** produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS *** the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of *** vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS *** in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS ***,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关键词： zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis