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| 1 | 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 |
| 2 | Sedimentary characteristics of paleo-aeolian dune sands of Salawusu Formation in the Salawusu River Valley显示文摘在 Salawusu 河山谷的 Milanggouwan 节的 Salawusu 形成包括修理 paleo 、修理半的沙丘沙的 paleo 活动的沙丘沙,和 4 层的 7 层。他们的结构被观察了并且他们的谷物尺寸。 | OU Xianjiao LI Baosheng JIN Heling DONG Guangrong David Dian ZHANG WU Zheng WEN Xiaohao ZENG Lanhua OUYANG Chuntao YANG Yi LIU Yufei | 2008 | Journal of Geographical Sciences2008，18，2： | 6 |
| 3 | Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc显示文摘Intervertebral disc(IVD) degeneration(IVDD) is the main cause of low back pain with major social and economic burdens;however, its underlying molecular mechanisms remain poorly defined. Here we show that the focal adhesion protein Kindlin-2 is highly expressed in the nucleus pulposus(NP), but not in the anulus fibrosus and the cartilaginous endplates, in the IVD tissues. Expression of Kindlin-2 is drastically decreased in NP cells in aged mice and severe IVDD patients. Inducible deletion of Kindlin-2 in NP cells in adult mice causes spontaneous and striking IVDD-like phenotypes in lumbar IVDs and largely accelerates progression of coccygeal IVDD in the presence of abnormal mechanical stress. Kindlin-2 loss activates Nlrp3 inflammasome and stimulates expression of IL-1β in NP cells, which in turn downregulates Kindlin-2. This vicious cycle promotes extracellular matrix(ECM) catabolism and NP cell apoptosis. Furthermore, abnormal mechanical stress reduces expression of Kindlin-2, which exacerbates Nlrp3 inflammasome activation, cell apoptosis, and ECM catabolism in NP cells caused by Kindlin-2 deficiency. In vivo blocking Nlrp3 inflammasome activation prevents IVDD progression induced by Kindlin-2 loss and abnormal mechanical stress. Of translational significance, adeno-associated virus-mediated overexpression of Kindlin-2 inhibits ECM catabolism and cell apoptosis in primary human NP cells in vitro and alleviates coccygeal IVDD progression caused by mechanical stress in rat. Collectively, we establish critical roles of Kindlin-2 in inhibiting Nlrp3 inflammasome activation and maintaining integrity of the IVD homeostasis and define a novel target for the prevention and treatment of IVDD. | Sheng Chen Xiaohao Wu Yumei Lai Di Chen Xiaochun Bai Sheng Liu Yongchao Wu Mingjue Chen Yuxiao Lai Huiling Cao Zengwu Shao Guozhi Xiao | 2022 | Bone Research2022，10，1： | 6 |
| 4 | A water-free metal organic deposition method for YBa2Cu3O7?δ thin film fabrication显示文摘 | Rongxia Huang Feng Feng Wei Wu Yunran Xue Yanyi Zhang Kai Shi Timing Qu Yongjie Zhao Xiaohao Wang Xiaowen Zhang Zhenghe Han | 2013 | Superconductor Science and Technology2013，，： | 1 |
| 5 | Off-hour effect is not significant in endovascular treatment for anterior circulation large vessel occlusion in a multicentre registry显示文摘Background and purpose Whether the off-hour effect has an impact on workflow and outcomes of endovascular treatment(EVT)for anterior circulation large vessel occlusion(AC-LVO)remains uncertain.This study aimed to compare the characteristics and outcomes of patients who presented or were treated during off-hour versus on-hour in a multi-center registry.Methods AC-LVO patients from 21 centres were categorised into the off-hour group and the on-hour group.Off-hour(weekends,holidays,and 18:00-7:59 on weekdays)and on-hour(8:00-17:59 on weekdays except for holidays)were defined according to arrival and groin-puncture time points,respectively.Subgroup comparisons between patients both arrived and treated during off-hour(true off-hour)and on-hour(true on-hour)were performed.The primary outcome was the 90-day modified Rankin Scale(mRS)score.Secondary outcomes included favourable outcome(mRS 0-2 at 90 days),EVT-related time metrics,and other clinical outcomes.Ordinary and binary logistic regression and linear regression were taken to adjust for confounding factors.Results Of all 698 patients enrolled,435(62.3%)and 456(65.3%)patients were categorised into the off-hour arrival and off-hour puncture group,respectively.Shorter onset to door time(adjustedßcoefficient:−21.56;95%CI−39.96 to−3.16;p=0.022)was noted in the off-hour arrival group.Ordinal and dichotomous mRS scores at 90 days were comparable between the off-hour group and the on-hour group regardless of off-hour definitions.Other time metrics and outcomes were comparable between the two groups.Of 595 patients both presented and were treated during off-hour or on-hour,394 patients were categorised into the true off-hour group and 201 into the true on-hour group.Time metrics and clinical outcomes were similar between the true off-hour and the true on-hour group.Conclusions The off-hour effect was not significant regarding clinical outcomes and in-hospital workflow in AC-LVO patients receiving EVT in this Chinese multicentre registry. | Mingming Zha Qingwen Yang Shuo Liu Kangmo Huang Xiaohao Zhang Min Wu Haodi Cai Qiushi Lv Rui Liu Dong Yang Xinfeng Liu | 2021 | Stroke & Vascular Neurology2021，6，4： | 1 |
| 6 | Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice显示文摘In vertebrates,the type 1 parathyroid hormone receptor(PTH1R)is a critical regulator of skeletal development and homeostasis;however,how it is modulated is incompletely understood.Here we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult bone.Single-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts,but not mesenchymal stem cells,chondrocytes and fibroblasts,in non-hematopoietic bone marrow cells,with concomitant depletion of osteoblasts on the bone surfaces,especially those stimulated by PTH.Furthermore,haploinsufficiency of Kindlin-2 and Pth1r genes,but not that of either gene,in mice significantly decreases basal and,to a larger extent,PTH-stimulated bone mass,supporting the notion that both factors function in the same genetic pathway.Mechanistically,Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα.Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in bone.Interestingly,PTH promotes Kindlin-2 expression in vitro and in vivo,thus creating a positive feedback regulatory loop.Finally,estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized mice.Thus,we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis. | Xuekun Fu Bo Zhou Qinnan Yan Chu Tao Lei Qin Xiaohao Wu Sixiong Lin Sheng Chen Yumei Lai Xuenong Zou Zengwu Shao Meiqing Wang Di Chen Wenfei Jin Youqiang Song Huiling Cao Ge Zhang Guozhi Xiao | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 7 | Factors Controlling Organic Matter Enrichment in Alkaline Lacustrine Source Rocks:A Case Study of the Late Paleozoic Fengcheng Formation in the Junggar Basin,NW China显示文摘The late Paleozoic Fengcheng Formation shale(LPF shale)in the Junggar Basin,NW China,is the oldest alkaline source rock discovered in the world,providing a unique perspective with which to explore organic matter(OM)enrichment in alkaline lake environments.Combined with the organic carbon isotope profile and paleoenvironmental proxies,this study reveals that the LPF shale was deposited in an arid climate with high salinity and a strong reducing environment,accompanied by frequent volcanic activity.High TOC values are concentrated in two intervals with frequent fluctuations in OM types.A negative excursion due to changes in sedimentary OM source is found in the δ^(13)C_(org) profile.The excursion corresponds to the OM enrichment interval and is accompanied by abnormally high values of Sr/Ba and Sr/Cu.This implies that the extreme arid climate has led to high salinity,resulting in strong reducibility and changes in paleontological assemblages,which in turn controlled the differential enrichment of OM.The Fengcheng Fm.high-quality source rocks are the result of the combined action of climatic events,volcanism,high-salinity water environment and superior hydrocarbon-generating organisms.The results provide new insights into the formation conditions of terrestrial alkaline high-quality source rocks and the factors controlling alkaline OM enrichment. | HUANG Renda JIANG Fujie HU Tao CHEN Di HUANG Liliang LIU Zheyu WANG Xiaohao ZHANG Chenxi LU Jiahao WU Yuping | 2023 | Acta Geologica Sinica(English Edition)2023，97，6： | 0 |
| 8 | Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice显示文摘In vertebrates,the type 1 parathyroid hormone receptor(PTH1R)is a critical regulator of skeletal development and homeostasis;however,how it is modulated is incompletely understood.Here we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult bone.Single-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts,but not mesenchymal stem cells,chondrocytes and fibroblasts,in non-hematopoietic bone marrow cells,with concomitant depletion of osteoblasts on the bone surfaces,especially those stimulated by PTH.Furthermore,haploinsufficiency of Kindlin-2 and Pth1r genes,but not that of either gene,in mice significantly decreases basal and,to a larger extent,PTH-stimulated bone mass,supporting the notion that both factors function in the same genetic pathway.Mechanistically,Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα.Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in bone.Interestingly,PTH promotes Kindlin-2 expression in vitro and in vivo,thus creating a positive feedback regulatory loop.Finally,estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized mice.Thus,we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis. | Xuekun Fu Bo Zhou Qinnan Yan Chu Tao Lei Qin Xiaohao Wu Sixiong Lin Sheng Chen Yumei Lai Xuenong Zou Zengwu Shao Meiqing Wang Di Chen Wenfei Jin Youqiang Song Huiling Cao Ge Zhang Guozhi Xiao | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
| 9 | Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice显示文摘The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint(TMJ) osteoarthritis(OA);however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4(Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore,Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis. | Yumei Lai Wei Zheng Minghao Qu Christopher C.Xiao Sheng Chen Qing Yao Weiyuan Gong Chu Tao Qinnan Yan Peijun Zhang Xiaohao Wu Guozhi Xiao | 2022 | International Journal of Oral Science2022，14，3： | 0 |
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