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| 1 | Roles of mechanosensitive channel Piezo 1/2 proteins in skeleton and other tissues显示文摘Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments.The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells.The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far.The regulation of two family members,Piezol and Piezo2#has been reported to have essential functions in mechanosensation and transduction in different organs and tissues.Recently,the predominant contributions of the Piezo family were reported to occur in the skeletal system,especially in bone development and mechano-stimulated bone homeostasis.Here we review current studies focused on the tissue-specific functions of Piezol and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell mechanotransduction.In this review,we emphasize the diverse functions of Piezol and Piezo2 and related signaling pathways in osteoblast lineage cells and chondrocytes.We also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases. | Lei Qin Tailin He Sheng Chen Dazhi Yang Weihong Yi Huiling Cao Guozhi Xiao | 2021 | Bone Research2021，9，4： | 14 |
| 2 | Osteoarthritis:pathogenic signaling pathways and therapeutic targets显示文摘Osteoarthritis(OA)is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide.OA was believed to be caused by the wearing and tearing of articular cartilage,but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues,which leads to the histological and structural changes of the joint and ends up with the whole tissue dysfunction.Currently,there is no cure for OA,partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the disease.Therefore,a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development.In this review,we first summarize the epidemiology of OA,including its prevalence,incidence and burdens,and OA risk factors.We then focus on the roles and regulation of the pathological signaling pathways,such as Wnt/β-catenin,NF-κB,focal adhesion,HIFs,TGFβ/ΒΜP and FGF signaling pathways,and key regulators AMPK,mTOR,and RUNX2 in the onset and development of OA.In addition,the roles of factors associated with OA,including MMPs,ADAMTS/ADAMs,and PRG4,are discussed in detail.Finally,we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA.Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies. | Qing Yao Xiaohao Wu Chu Tao Weiyuan Gong Mingjue Chen Minghao Qu Yiming Zhong Tailin He Sheng Chen Guozhi Xiao | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 11 |
| 3 | Jigsaw-like mini-pillar platform for multi-mode biosensing显示文摘The multiple sensing provides booming options to eliminate interference and ensure the accuracy of detection by mutually coupling and validating multiple data sets.Here,we integrate the jigsaw-like multifunctional mini-pillar platform to perform multi-mode(electrochemical,fluorescence,surface-enhanced Raman scattering(SERS)and colorimetric)sensing in individual microdroplets.Each mini-pillar connector can parallelize together by specific concave-convex interface to form integrated jigsaw-like platform for multi-mode sensing,and each specific mini-pillar can be modified into the individual sensing unit to read the prescribed signals.We successfully implemented electrochemical,fluorescence,SERS and colorimetric detection by multiple signals coupling to reduce the false positive analysis.Such platform brings a promising clue of in-situ analysis and point-of-care testing for disease diagnosis and health monitoring. | Yongchao Song Dongdong Wang Zehua Li Lirong Wang Chuan Fan Xuecheng He Tailin Xu Xueji Zhang | 2022 | Chinese Chemical Letters2022，33，8： | 1 |
| 4 | Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprint显示文摘Wearable sweat sensors with various sensing systems can provide noninvasive medical diagnostics and healthcare monitoring.Here,we demonstrate a wearable microfluidic nanoplasmonic sensor capable of refreshable and portable recognition fingerprint information of targeted biomarkers including urea,lactate,and pH in sweat.A miniature,thin plasmonic metasurface with homogeneous mushroom-shaped hot spots and high surface-enhanced Raman scattering(SERS)activity is designed and integrated into a microfluidics platform.Compared to conventional wearable SERS platforms with the risk of mixed effect between new and old sweat,the microfluidic SERS system allows sweat administration in a controllable and high temporal-resolution fashion,providing refreshable SERS analysis.We use a portable and customized Raman analyzer with a friendly human-machine interface for portable recognition of the spectroscopic signatures of sweat biomarkers.This study integrates epidermal microfluidics with portable SERS molecular recognition,presenting a controllable,handy,and dynamical biofluid sensing system for personalized medicine. | Xuecheng He Chuan Fan Yong Luo Tailin Xu Xueji Zhang | 2022 | npj Flexible Electronics2022，6，1： | 1 |
| 5 | A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis显示文摘Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke,but how to control the overactive neuroinflammation is still a long-standing challenge.Here,we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia,which were abolished by silencing SIRT6.RNA-seq screening identified the forkhead box C1 (Foxc1) is a key gene evoked by MDL-811stimulation and is required for the anti-inflammatory effects of MDL-811.We found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of Foxc1 and upregulate its expression to modulate inflammation.Moreover,our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS,but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional recovery.Importantly,MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients,underlying an interesting translational perspective.Taken together,MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation. | Tailin He Jialin Shang Chenglong Gao Xin Guan Yingyi Chen Liwen Zhu Luyong Zhang Cunjin Zhang Jian Zhang Tao Pang | 2021 | Acta Pharmaceutica Sinica B2021，11，3： | 1 |
| 6 | Roles of focal adhesion proteins in skeleton and diseases显示文摘The skeletal system,which contains bones,joints,tendons,ligaments and other elements,plays a wide variety of roles in body shaping,support and movement,protection of internal organs,production of blood cells and regulation of calcium and phosphate metabolism.The prevalence of skeletal diseases and disorders,such as osteoporosis and bone fracture,osteoarthritis,rheumatoid arthritis,and intervertebral disc degeneration,increases with age,causing pain and loss of mobility and creating a huge social and economic burden globally.Focal adhesions(FAs)are macromolecular assemblies that are composed of the extracellular matrix(ECM),integrins,intracellular cytoskeleton and other proteins,including kindlin,talin,vinculin,paxillin,pinch,Src,focal adhesion kinase(FAK)and integrin-linked protein kinase(ILK)and other proteins.FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell–environment communications and modulates important processes,such as cell attachment,spreading,migration,differentiation and mechanotransduction,in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways.This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases. | Sheng Chen Tailin He Yiming Zhong Mingjue Chen Qing Yao Di Chen Zengwu Shao Guozhi Xiao | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 0 |
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