Restoring the dampened expression of the core clock molecule BMAL1 protects against compression-induced intervertebral disc degeneration

The circadian clock participates in maintaining homeostasis in peripheral tissues,including intervertebral discs(IVDs).Abnormal mechanical loading is a known risk factor for intervertebral disc degeneration(IDD).Based on the rhythmic daily loading pattern of rest and activity,we hypothesized that abnormal mechanical loading could dampen the IVD clock,contributing to IDD.Here,we investigated the effects of abnormal loading on the IVD clock and aimed to inhibit compression-induced IDD by targeting the core clock molecule brain and muscle Arnt-like protein-1(BMAL1).In this study,we showed that BMAL1 KO mice exhibit radiographic features similar to those of human IDD and that BMAL1 expression was negatively correlated with IDD severity by systematic analysis based on 149 human IVD samples.The intrinsic circadian clock in the IVD was dampened by excessive loading,and BMAL1 overexpression by lentivirus attenuated compression-induced IDD.Inhibition of the RhoA/ROCK pathway by Y-27632 or melatonin attenuated the compression-induced decrease in BMAL1 expression.Finally,the two drugs partially restored BMAL1 expression and alleviated IDD in a diurnal compression model.Our results first show that excessive loading dampens the circadian clock of nucleus pulposus tissues via the RhoA/ROCK pathway,the inhibition of which potentially protects against compression-induced IDD by preserving BMAL1 expression.These findings underline the importance of the circadian clock for IVD homeostasis and provide a potentially effective therapeutic strategy for IDD.

Mn3O4 nanoparticles@reduced graphene oxide composite:An efficient electrocatalyst for artificial N2 fixation to NH3 at ambient conditions

Currently,industrial-scale NH3 production almost relies on energy-intensive Haber-Bosch process from atmospheric N2 with large amount of CO2 emission,while low-cost and high-efficient catalysts are demanded for the N2 reduction reaction (NRR).In this study,Mn3O4 nanoparticles@reduced graphene oxide (Mn3O4@rGO) composite is reported as an efficient NRR electrocatalyst with excellent selectivity for NH3 formation.In 0.1 M Na2SO4 solution,such catalyst obtains a NH3 yield of 17.4 μg·h^-1·mg^-1cat.and a Faradaic efficiency of 3.52% at-0.85 V vs.reversible hydrogen electrode.Notably,it also shows high electrochemical stability during electrolysis process.Density functional theory (DFT) calculations also demonstrate that the (112) planes of Mn3O4 possess superior NRR activity.

Spatiotemporal trends of PM_(2.5) and its major chemical components at urban sites in Canada

To evaluate the effectiveness of emission control regulations designed for reducing air pollution, chemically resolved PM_(2.5) data have been collected across Canada through the National Air Pollution Surveillance network in the past decade. 24-hr time integrated PM_(2.5) collected at seven urban and two rural sites during 2010-2016 were analyzed to characterize geographical and seasonal patterns and associated potential causes. Site-specific seven-year mean gravimetric PM_(2.5) mass concentrations ranged from 5.7 to 9.6 μg/m^(3). Seven-year mean concentrations of SO_(4)^(2-), NO_(3)^(-), NH_(4)^(+), organic carbon(OC), and elemental carbon(EC) were in the range of 0.68 to 1.6, 0.21 to 1.5, 0.27 to 0.71, 1.1 to 1.9, and 0.37 to 0.71 μg/m^(3), accounting for 10.8%-18.1%, 3.7%-16.7%, 4.7%-7.4%, 18.4%-21.0%, and 6.4%-10.6%, respectively, of gravimetric PM_(2.5) mass. PM_(2.5) and its five major chemical components showed higher concentrations in southeastern Canada and lower values in Atlantic Canada, with the seven-year mean ratios between the two regions being on the order of 1.7 for PM_(2.5) and 1.8-7.1 for its chemical components. When comparing the concentrations between urban and rural sites within the same region, those of SO_(4)^(2-) and NH_(4)^(+) were comparable, while those of NO_(3)^(-), OC, and EC were around 20%, 40%-50%, and 70%-80%, respectively, higher at urban than rural sites, indicating the regional scale impacts of SO_(4)^(2-) and NH_(4)^(+) and effects of local sources on OC and EC. Monthly variations generally showed summertime peaks for SO_(4)^(2-) and wintertime peaks for NO_(3)^(-), but those of NH_(4)^(+), OC, and EC exhibited different seasonality at different locations.