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| 1 | Transforming growth factor-β in stem cells and tissue homeostasis显示文摘TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β. | Xin Xu Liwei Zheng Quan Yuan Gehua Zhen Janet L.Crane Xuedong Zhou Xu Cao | 2018 | Bone Research2018，6，1： | 22 |
| 2 | Mechanically induced Ca^(2+) oscillations in osteocytes release extracellular vesicles and enhance bone formation显示文摘The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin(OPG). However, the mechanisms of osteocyte mechanotransduction remain poorly understood. We've previously shown that osteocyte mechanosensitivity is encoded through unique intracellular calcium (Ca^(2+) ) dynamics. Here, by simultaneously monitoring Ca^(2+) and actin dynamics in single cells exposed to fluid shear flow, we detected actin network contractions immediately upon onset of flow-induced Ca^(2+) transients, which were facilitated by smooth muscle myosin and further confirmed in native osteocytes ex vivo. Actomyosin contractions have been linked to the secretion of extracellular vesicles(EVs), and our studies demonstrate that mechanical stimulation upregulates EV production in osteocytes through immunostaining for the secretory vesicle marker Lysosomal-associated membrane protein 1(LAMP1) and quantifying EV release in conditioned medium, both of which are blunted when Ca^(2+) signaling was inhibited by neomycin. Axial tibia compression was used to induce anabolic bone formation responses in mice, revealing upregulated LAMP1 and expected downregulation of sclerostin in vivo. This load-related increase in LAMP1 expression was inhibited in neomycin-injected mice compared to vehicle.Micro-computed tomography revealed significant load-related increases in both trabecular bone volume fraction and cortical thickness after two weeks of loading, which were blunted by neomycin treatment. In summary, we found mechanical stimulation of osteocytes activates Ca^(2+) -dependent contractions and enhances the production and release of EVs containing bone regulatory proteins. Further, blocking Ca^(2+) signaling significantly attenuates adaptation to mechanical loading in vivo, suggesting a critical role for Ca^(2+) -mediated signaling in bone adaptation. | Andrea E.Morrell Genevieve N.Brown Samuel T.Robinson Rachel L.Sattler Andrew D.Baik Gehua Zhen Xu Cao Lynda F.Bonewald Weiyang Jin Lance C.Kam X.Edward Guo | 2018 | Bone Research2018，6，1： | 13 |
| 3 | B7-H3:Another Molecule Marker for Mo-DCs?显示文摘Using a newly generated monoclonal antibody (2E6) against human B7-H3, we explored the expression of the molecule on dendritic cells derived from monocytes (Mo-DCs). Its expression was examined by means of immunostaining and flow cytometric (FCM) analysis. The results showed that B7-H3 was expressed in the course of Mo-DC maturation induced with interleukin 4 (IL-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF). The expression could be detected at all the stages of Mo-DC differentiation, and remained at a quite stable level. Interestingly, B7-H3 was not expressed by T cells and B cells, even these cells were activated respectively by PHA or PWM. A weak expression could be detected on resting monocytes. These data showed that constitutive expression of B7-H3 at a high level was found on imDCs and mDCs derived from monocytes. Due to no expression on T cells and B cells, we speculate that B7-H3 might be another valuable molecule marker for Mo-DCs. | Guangbo Zhang Qiuming Dong Ying Xu Gehua Yu Xueguang Zhang | 2005 | Cellular & Molecular Immunology2005，2，4： | 7 |
| 4 | Low-temperature NH_(3)-SCR of NO_(x) over MnCeO_(x)/TiO_(2) catalyst:Enhanced activity and SO_(2) tolerance by modifying TiO_(2) with Al_(2)O_(3)显示文摘A series of TiO_(2)-Al_(2)O_(3) composites with Al/Ti molar ratios of 0.1,0.2,and 0.4 were synthesized by a coprecipitation method and used as supports to prepare supported MnCeO_(x) catalysts by an impregnation method.The physico-chemical properties of the samples were extensively characterized by N_(2) physisorption,X-ray diffraction,Raman spectroscopy,scanning electron micro scopy and energy-dispersive Xray spectroscopy element mapping,X-ray photoelectron spectroscopy,H_(2)-temperature programmed reduction,ammonia temperature programmed desorption,and in-situ diffuse reflectance infrared Fourier transform spectroscopy.The catalytic activity and resistance to water vapor and SO_(2) of the asprepared catalysts for the SCR of NO_(x) with NH_(3) were evaluated at 50-250℃ and GHSV of 80000 mL/(gcat·h).The results reveal that MnCeO_(x)/TiO_(2)-Al_(2)O_(3) exhibits higher activity and better SO_(2) tolerance than MnCeO_(x)/TiO_(2).Combining with the characterization results,the enhanced activity and SO_(2) tolerance of MnCeO_(x)/TiO_(2)-Al_(2)O_(3) can be mainly attributed to higher relative concentrations of Mn4+and chemisorbed oxygen species,stronger reducibility,and larger adsorption capacity for NH_(3) and NO,which originate from the larger specific surface area and pore volume,higher dispersion of Mn and Ce species compared with MnCeO_(x)/TiO_(2).Moreover,in situ DRIFTS was used to investigate the reaction mechanism,and the results indicate that the NH_(3)-SCR reaction over MnCeO_(x)/TiO_(2) and MnCeO_(x)/TiO_(2)-Al_(2)O_(3) takes place by both the E-R and L-H mechanisms. | Gang Li Dongsen Mao Mengxi Chao Gehua Li Jun Yu Xiaoming Guo | 2021 | Journal of Rare Earths2021，39，7： | 6 |
| 5 | An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP^(+)mononuclear cells and PDGF-BB secretion显示文摘Osteoporosis(OP)is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures.Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed.We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation.We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment.The secretion of platelet-derived growth factor-BB(PDGF-BB),the number of tartrate-resistant acid phosphatase-positive(TRAP+)mononuclear cells,and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice.The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP-1'cells.These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP4 mononuclear cells.To test the therapeutic potential of the Siglec-15 neutralizing antibody,we injected the antibody in an ovariectomy-induced osteoporotic mouse model,which mimics postmenopausal osteoporosis in women,and in two fracture healing models because fracture is the most serious health consequence of osteoporosis.The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis.Of note,the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models.Thus,the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture. | Gehua Zhen Yang Dan Ruomei Wang Ce Dou Qiaoyue Guo Melissa Zarr Linda N.Liu Lieping Chen Ruoxian Deng Yusheng Li Zengwu Shao Xu Cao | 2021 | Bone Research2021，9，4： | 6 |
| 6 | Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis显示文摘Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis(RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA(STR/Ort)mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OAassociated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis. | Manli Tu Mi Yang Nanxi Yu Gehua Zhen Mei Wan Wenlong Liu Baochao Ji Hairong Ma Qiaoyue Guo Peijian Tong Li Cao Xianghang Luo Xu Cao | 2019 | Bone Research2019，7，3： | 5 |
| 7 | Fine-Tuned Expression of Programmed Death 1 Ligands in Mature Dendritic Cells Stimulated by CD40 Ligand is Critical for the Induction of an Efficient Tumor Specific Immune Response显示文摘During maturation,murine myeloid dendritic cells (DCs) upregulated the expressions of CD11c,CD25,CD40,CD80,CD86,MHC Ⅱ and programmed death 1 ligands 1 and 2 (PD-L1 and PD-L2). Differential expression patterns of PD-L1 and PD-L2 were found when DCs were triggered by CD40 ligand and TNF-α. PD-L1 expression was repressed and PD-L2 expression remained unchanged in mature CD40-ligated DCs,whereas TNF-α stimulated DCs kept high expression of PD-L1 and significantly enhanced PD-L2 expression on DCs. Proliferations of T lymphocytes stimulated by immature DCs were enhanced by blockade of the PD-1 and PD-1 ligand interaction. But inhibitive effects were found in T lymphocytes stimulated by CD40-ligated DCs. With the fine-tuned expressions of PD-L1 and PD-L2,CD40-ligated DCs could sustain a longer activation period and elicit a more efficient T lymphocyte activation. | Tao Gu Yibei Zhu Cheng Chen Min Li Yongjing Chen Gehua Yu Yan Ge Shiyong Zhou Huan Zhou Yong Huang Yuhua Qiu Xueguang Zhang | 2008 | Cellular & Molecular Immunology2008，5，1： | 3 |
| 8 | Regis-tration of challenging image pairs: initialization, es- timation, and decision 显示文摘 | Yang Gehua Stewart C V Sofka M | 2007 | IEEE Transactions onPattern Analysis and Machine Intelligence2007，29，11： | 1 |
| 9 | Johnson Multiplex PCR for Detection of Genes for Staphylococcus aureus Enterotoxins, Exfoliative Toxins, Toxic Shock Syndrome Toxin 1, and Methicillin Resistance显示文摘 | Manisha Mehrotra Gehua Wang Wendy M | 2000 | Journal of Clinical Microbiology2000，38，3： | 1 |
| 10 | A Novel Anti-Human Syndecan-1 (CD138) Monoclonal Antibody 4B3: Characterization and Application显示文摘Syndecan-1 (CD138), a member of integral membrane heparin sulfate proteoglycans, is an essential matrix receptor for maintaining the normal morphological phenotypes. In this study, we generated a specific mouse anti-human syndecan-1 monoclonal antibody (mAb) 4B3 and identified it by competition assay with the available syndecan-1 mAb (BB4). Stained by 4B3, the expression of syndecan-1 was detected on tumor cell lines, such as 8226, U266, XG-1, XG-2, Daudi and Jurkat. The expression was also found on neuron stem cells. It was established that 4B3 mAb could inhibit XG-1 and XG-2 proliferation. The data not only determined that 4B3 mAb was a functional anti-human syndecan-1 mAb, but also indicated that syndecan-1 might be a valuable surface antigen and play an important role in regulation of tumor pathology and differentiation of neural stem cells. This novel antibody 4B3 may be value of study of tumor proliferation/survival mechanism and contributes to diagnosis and treatment of diverse diseases. | Wanping Sun Fengming Wang Fang Xie Guoqing Wang Jin Sun Gehua Yu Yuhua Qiu Xueguang Zhang | 2007 | Cellular & Molecular Immunology2007，4，3： | 1 |
| 11 | Insulin administration protects neurologic function in cerebral ischemia in rats显示文摘 | LeMay DR Gehua L Zelenock GB | | 0，，11： | 1 |
| 12 | Registration of challenging image pairs: initialization, estimation, and decision 显示文摘 | Yang Gehua Stewart C V Sofka M | 2007 | IEEE Trans Pattern Anal Mach Intell2007，29，11： | 1 |
| 13 | Insulin administration protects neurologic function in cerebral ischemia in rats 显示文摘 | Lemay D R Gehua L Zelenock G B | 1988 | Stroke1988，19，11： | 1 |
| 14 | Insulin adminisration Protectsneurclogic function at cerebral ischemia in rats显示文摘 | Lemy DR Gehua BS Gerald B | 1988 | stroke1988，19，： | 1 |
| 15 | Detection in Escherichia coli of the genes encoding the major virulence factors, the genes defining the O157:H7 serotype, and components of the type 2 shiga toxin family by multiplex PCR显示文摘 | WANG Gehua CLIFFORD G C FRANK G R | 2002 | J Clin Microbiol2002，40，10： | 1 |
| 16 | The edge-driven dual-bootstrap iterative closest point algorithm for registration of muhimodal fluoreseein angiogram sequence显示文摘 | TSAI Chialing LI Chunyi YANG Gehua | 2010 | IEEE Transactions on Medical Imaging2010，29，3： | 1 |
| 17 | Multiplex PCR for Detection of Genes for Staphylococcus aureus Enterotoxins, Exfoliative Toxins, Toxic Shock Syndrome Toxin 1, and Methicillin Resistance显示文摘 | Manisha Mehrotra Gehua Wang Wend Y M Johnson | 2000 | Journal of Clinical Microbiology2000，38，3： | 1 |
| 18 | Optimized protocol to reduce variable outcomes for the bilateral common carotid artery occlusion model in mice显示文摘 | Gehua Zhen Sylvain Dor6 | 2007 | J Neurosci Methods2007，166，1： | 1 |
| 19 | Alignment of Challenging Image Pairs:Refinement and Region Growing Starting from a Single Keypoint Correspondence显示文摘 | Yang Gehua Stewart C V Sofka M | 2007 | IEEE Transactions on Pattern Analysis and Machine Intelligence2007，23，11： | 1 |
| 20 | The Edge-driven Dual-bootstrap Iterative Closest Point Algorithm for Registration of Multimodal Fluorescein Angiogram Sequence显示文摘 | Tsai Chia-Ling Li Chun-Yi Yang Gehua | 2010 | IEEE Transactions on Medical Imaging2010，29，3： | 1 |
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