Ablation characteristics of insulator under high-temperature gas dual-pulse erosion

This study numerically simulated and investigated the flow field characteristics of a typical dual-pulse solid rocket motor with a soft pulse separation device through thermal insulation ablation under high-temperature dual-pulse erosion.The ablation rate of ethylene-propylene-diene monomer(EPDM)insulator was measured after the experiment.Experimental results were analyzed through scanning electron microscopy and microcomputed tomography.The ablation mechanism of the EPDM insulator under the operation conditions of a dual-pulse solid rocket motor was evaluated by analyzing the results.The results reveal that the internal flow field of the motor with a soft pulse separation device is uniform.The original charred layer existing on the EPDM insulator surface in the first pulse combustor is the decisive factor affecting the final ablation rate of the dual-pulse motor during the second pulse operation,and the ablation characteristic region is easily formed with the exfoliation of the charred layer.The ablation rate difference of the insulator increases with gas velocity.

A Novel Tuning Method for Predictive Control of VAV Air Conditioning System Based on Machine Learning and Improved PSO

The variable air volume(VAV)air conditioning system is with strong coupling and large time delay,for which model predictive control(MPC)is normally used to pursue performance improvement.Aiming at the difficulty of the parameter selection of VAV MPC controller which is difficult to make the system have a desired response,a novel tuning method based on machine learning and improved particle swarm optimization(PSO)is proposed.In this method,the relationship between MPC controller parameters and time domain performance indices is established via machine learning.Then the PSO is used to optimize MPC controller parameters to get better performance in terms of time domain indices.In addition,the PSO algorithm is further modified under the principle of population attenuation and event triggering to tune parameters of MPC and reduce the computation time of tuning method.Finally,the effectiveness of the proposed method is validated via a hardware-in-the-loop VAV system.

Oxygen metabolism-balanced engineered hydrogel microspheres promote the regeneration of the nucleus pulposus by inhibiting acid-sensitive complexes

Intervertebral disc degeneration(IVDD)is commonly caused by imbalanced oxygen metabolism-triggered inflammation.Overcoming the shortcomings of antioxidants in IVDD treatment,including instability and the lack of targeting,remains challenging.Microfluidic and surface modification technologies were combined to graft chitosan nanoparticles encapsulated with strong reductive black phosphorus quantum dots(BPQDs)onto GelMA microspheres via amide bonds to construct oxygen metabolism-balanced engineered hydrogel microspheres(GM@CS-BP),which attenuate extracellular acidosis in nucleus pulposus(NP),block the inflammatory cascade,reduce matrix metalloproteinase expression(MMP),and remodel the extracellular matrix(ECM)in intervertebral discs(IVDs).The GM@CS-BP microspheres reduce H_(2)O_(2) intensity by 229%.Chemical grafting and electrostatic attraction increase the encapsulation rate of BPQDs by 167%and maintain stable release for 21 days,demonstrating the antioxidant properties and sustained modulation of the BPQDs.After the GM@CS-BP treatment,western blotting revealed decreased acid-sensitive ion channel-3 and inflammatory factors.Histological staining in an 8-week IVDD model confirmed the regeneration of NP.GM@CS-BP microspheres therefore maintain a balance between ECM synthesis and degradation by regulating the positive feedback between imbalanced oxygen metabolism in IVDs and inflammation.This study provides an in-depth interpretation of the mechanisms underlying the antioxidation of BPQDs and a new approach for IVDD treatment.

Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity in vivo

HMG-CoA reductase(HMGCR) protein is usually upregulated after statin(HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera(PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC(21 c) comprising a VHL ligand conjugated to lovastatin acid that potently degrades HMGCR in Insig-silenced HepG2 cells(DC50 Z 120 nmol/L) and forms a stable ternary complex, as predicated by a holistic modeling protocol. Most importantly, oral administration of the corresponding lactone 21 b reveled favorable plasma exposures referring to both the parent 21 b and the conversed acid 21 c. Further in vivo studies of 21 b demonstrated robust HMGCR degradation and potent cholesterol reduction in mice with diet-induced hypercholesterolemia, highlighting a promising strategy for treating hyperlipidemia and associated diseases.