Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian cloc...Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.展开更多
Based on the Longuet-Higgins wave model theory, the previews studies have shown that freak waves can be generated in finite space and time successfully. However, as to generating high nonlinear freak waves, the simula...Based on the Longuet-Higgins wave model theory, the previews studies have shown that freak waves can be generated in finite space and time successfully. However, as to generating high nonlinear freak waves, the simulation results will be unrealistic. Therefore, a modified phase modulation method for simulating high nonlinear freak waves was developed. The surface elevations of some wave components at certain time and place are positive by modulating the corresponding random initial phases, then the total surface elevation at the focused point is enhanced and furthermore a freak wave event is generated. The new method can not only make the freak wave occur at certain time and place, but also make the simulated wave surface time series satisfy statistical properties of the realistic sea state and keep identical with the target wave spectrum. This numerical approach is of good precision and high efficiency by the comparisons of the simulated freak waves and the recorded freak waves.展开更多
Accurate characterization of high-power laser parameters,especially the near-field and far-field distributions,is crucial for inertial confinement fusion experiments.In this paper,we propose a method for computational...Accurate characterization of high-power laser parameters,especially the near-field and far-field distributions,is crucial for inertial confinement fusion experiments.In this paper,we propose a method for computationally reconstructing the complex amplitude of high-power laser beams using modified coherent modulation imaging.This method has the advantage of being able to simultaneously calculate both the near-field(intensity and wavefront/phase)and far-field(focal-spot)distributions using the reconstructed complex amplitude.More importantly,the focal-spot distributions at different focal planes can also be calculated.To verify the feasibility,the complex amplitude optical field of the highpower pulsed laser was measured after static aberrations calibration.Experimental results also indicate that the near-field wavefront resolution of this method is higher than that of the Hartmann measurement.In addition,the far-field focal spot exhibits a higher dynamic range(176 dB)than that of traditional direct imaging(62 dB).展开更多
基金supported in part by grants from the National Key R&D Program of China(2021YFC2400400/04 to L.L.C.)the National Natural Science Foundation of China for Key Program Projects(82030070 to L.L.C.)+2 种基金the National Natural Science Foundation of China for Distinguished Young Scholars(22025102 to Q.W.)the National Natural Science Foundation of China(82271036 to Y.F.W.,22277033 to J.Z.,22177034 to L.K.M.)the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001 to Y.F.W.)。
文摘Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.
基金The Key Technology Program,the Ministry of Education of China under contract No.104061
文摘Based on the Longuet-Higgins wave model theory, the previews studies have shown that freak waves can be generated in finite space and time successfully. However, as to generating high nonlinear freak waves, the simulation results will be unrealistic. Therefore, a modified phase modulation method for simulating high nonlinear freak waves was developed. The surface elevations of some wave components at certain time and place are positive by modulating the corresponding random initial phases, then the total surface elevation at the focused point is enhanced and furthermore a freak wave event is generated. The new method can not only make the freak wave occur at certain time and place, but also make the simulated wave surface time series satisfy statistical properties of the realistic sea state and keep identical with the target wave spectrum. This numerical approach is of good precision and high efficiency by the comparisons of the simulated freak waves and the recorded freak waves.
基金supported by the Project of the Ministry of Industry and Information Technology(Grant No.TC220H05L)the National Natural Science Foundation of China(NSFC)(Grant Nos.61905261,61827816 and 11875308)+1 种基金the Shanghai Sailing Program(Grant No.18YF1426600)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA25020306).
文摘Accurate characterization of high-power laser parameters,especially the near-field and far-field distributions,is crucial for inertial confinement fusion experiments.In this paper,we propose a method for computationally reconstructing the complex amplitude of high-power laser beams using modified coherent modulation imaging.This method has the advantage of being able to simultaneously calculate both the near-field(intensity and wavefront/phase)and far-field(focal-spot)distributions using the reconstructed complex amplitude.More importantly,the focal-spot distributions at different focal planes can also be calculated.To verify the feasibility,the complex amplitude optical field of the highpower pulsed laser was measured after static aberrations calibration.Experimental results also indicate that the near-field wavefront resolution of this method is higher than that of the Hartmann measurement.In addition,the far-field focal spot exhibits a higher dynamic range(176 dB)than that of traditional direct imaging(62 dB).
