Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed...Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.展开更多
Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of ext...Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.展开更多
尽管阿尔金南缘长沙沟-清水泉一带在空间上彼此分隔的4个镁铁-超镁质岩体（或岩体群）在岩石学、岩相学、地球化学上存在着差异,但它们的形成时代均为中奥陶世（465 M a左右）。其中,分布于阿尔金南缘主断裂南侧的清水泉南—长沙沟中段...尽管阿尔金南缘长沙沟-清水泉一带在空间上彼此分隔的4个镁铁-超镁质岩体（或岩体群）在岩石学、岩相学、地球化学上存在着差异,但它们的形成时代均为中奥陶世（465 M a左右）。其中,分布于阿尔金南缘主断裂南侧的清水泉南—长沙沟中段—黄土泉的岩体,超镁铁岩（包括纯橄岩-橄榄岩-辉橄岩-橄辉岩）中的橄榄石Fo值较高（变化于95-85）,且自东向西呈现非常有规律的递减;而北侧的清水泉北岩体辉橄岩中橄榄石的Fo值较低（变化于81~79）。结合各岩体的岩石地球化学特征和岩浆演化过程及橄榄石中N i的含量变化规律,对这些杂岩体形成的地质背景和Cu-N i-PGE含矿可能性作简要讨论。展开更多
The Zhou＇an PGE-Cu-Ni deposit was recently discovered in the Qinling orogenic belt bound by the Yangtze and the North China Cratons. It is a blind deposit thoroughly covered by the Cenozoic alluvial sediments in the ...The Zhou＇an PGE-Cu-Ni deposit was recently discovered in the Qinling orogenic belt bound by the Yangtze and the North China Cratons. It is a blind deposit thoroughly covered by the Cenozoic alluvial sediments in the Nanyang Basin. As the first large PGE-Cu-Ni deposit discovered in the Qinling-Dabie-Sulu orogenic belt, its geological and geochemical characteristic, isotope age, genesis and tectonic setting are of wide concern in both scientific studies and ore exploration. In this contribution, we report the results obtained from a pioneering study. The Zhou＇an ultramafic complex is ferruginous, with m/f = 4.79-5.08, and shows the nature of tholeiite series. It is rich in light rare earth elements, Rb, Th, U, La, Sm, Zr and Hf, and poor in heavy rare earth elements, Nd and Ta, suggesting an intraplate setting. It has high S7Sr/S6Sr and low 143Nd/144Nd ratios. The ratios of Zr/Nb, La/Nb, Ba/ Nb, Rb/Nb, Th/Nb, Th/La and Ba/La, suggest the magma originated from lithosphere mantle. The Fo values of olivine and Pd/Ir-Ni/Cu diagram suggest primary magma was High Mg basalt. The laser ablation inductively coupled plasma atomic emission spectroscopy zircon U-Pb age is 641.5 ± 3.7 Ma.展开更多
The origin of PGE—Cu—Ni sulfide deposits of Norilsk and Talnakh located in the northwest flank of the Triassic basalt trap formation of Siberia is considered.It is shown that ore elements of these deposits（probably...The origin of PGE—Cu—Ni sulfide deposits of Norilsk and Talnakh located in the northwest flank of the Triassic basalt trap formation of Siberia is considered.It is shown that ore elements of these deposits（probably,except Fe） are derived from the crust rather than from the mantle.They entered the basalts owing to a remobilization（recycling） of ore elements from the Paleoproterozoic sediments and from the rocks of the Siberian platform＇s basement.Prospecting criteria for similar deposits are as follows：（1） a presence of a large Paleoproterozoic aulacogen and a related magmatic sulfide Cu—Ni mineralization;（2） a confinement of perspective areas to troughs associated with long-lived deep fault zones：（3） association with mobile orogenic belts,island-arc systems and tectonomagmatic activation zones;（4） temporal association with boundaries of global periods characterized by active processes of continental breakup and large-scale trap magmatism.A combination of several factors（the first one is obligatory） is favorable for the discovery of a large ore body.展开更多
基金This research was supported by NIH National Institute on Aging under Award Number R01 AG076783,R01 AG068997 and P01 AG066603(to X.C.).
文摘Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.
基金supported by Sichuan Province Science and Technology Support Program(NO.2020JDJQ0063,NO.2020YFS0566 and NO.2021JDKY0037,A-2021N-Z-5).
文摘Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.
文摘尽管阿尔金南缘长沙沟-清水泉一带在空间上彼此分隔的4个镁铁-超镁质岩体（或岩体群）在岩石学、岩相学、地球化学上存在着差异,但它们的形成时代均为中奥陶世（465 M a左右）。其中,分布于阿尔金南缘主断裂南侧的清水泉南—长沙沟中段—黄土泉的岩体,超镁铁岩（包括纯橄岩-橄榄岩-辉橄岩-橄辉岩）中的橄榄石Fo值较高（变化于95-85）,且自东向西呈现非常有规律的递减;而北侧的清水泉北岩体辉橄岩中橄榄石的Fo值较低（变化于81~79）。结合各岩体的岩石地球化学特征和岩浆演化过程及橄榄石中N i的含量变化规律,对这些杂岩体形成的地质背景和Cu-N i-PGE含矿可能性作简要讨论。
基金granted by the National Natural Science Fund of China (No. 41072058)the Scientific Research Special Subject for Public Welfare Profession (200911007 and201011058)China central college fund(CHD2011TD007)
文摘The Zhou＇an PGE-Cu-Ni deposit was recently discovered in the Qinling orogenic belt bound by the Yangtze and the North China Cratons. It is a blind deposit thoroughly covered by the Cenozoic alluvial sediments in the Nanyang Basin. As the first large PGE-Cu-Ni deposit discovered in the Qinling-Dabie-Sulu orogenic belt, its geological and geochemical characteristic, isotope age, genesis and tectonic setting are of wide concern in both scientific studies and ore exploration. In this contribution, we report the results obtained from a pioneering study. The Zhou＇an ultramafic complex is ferruginous, with m/f = 4.79-5.08, and shows the nature of tholeiite series. It is rich in light rare earth elements, Rb, Th, U, La, Sm, Zr and Hf, and poor in heavy rare earth elements, Nd and Ta, suggesting an intraplate setting. It has high S7Sr/S6Sr and low 143Nd/144Nd ratios. The ratios of Zr/Nb, La/Nb, Ba/ Nb, Rb/Nb, Th/Nb, Th/La and Ba/La, suggest the magma originated from lithosphere mantle. The Fo values of olivine and Pd/Ir-Ni/Cu diagram suggest primary magma was High Mg basalt. The laser ablation inductively coupled plasma atomic emission spectroscopy zircon U-Pb age is 641.5 ± 3.7 Ma.
文摘The origin of PGE—Cu—Ni sulfide deposits of Norilsk and Talnakh located in the northwest flank of the Triassic basalt trap formation of Siberia is considered.It is shown that ore elements of these deposits（probably,except Fe） are derived from the crust rather than from the mantle.They entered the basalts owing to a remobilization（recycling） of ore elements from the Paleoproterozoic sediments and from the rocks of the Siberian platform＇s basement.Prospecting criteria for similar deposits are as follows：（1） a presence of a large Paleoproterozoic aulacogen and a related magmatic sulfide Cu—Ni mineralization;（2） a confinement of perspective areas to troughs associated with long-lived deep fault zones：（3） association with mobile orogenic belts,island-arc systems and tectonomagmatic activation zones;（4） temporal association with boundaries of global periods characterized by active processes of continental breakup and large-scale trap magmatism.A combination of several factors（the first one is obligatory） is favorable for the discovery of a large ore body.
