Research and development of liquid hydrogen (LH2) temperature monitoring system for marine applications

Monitoring the temperature in liquid hydrogen (LH₂) storage tanks on ships is important for the safety of maritime navigation. In addition, accurate temperature measurement is also required for commercial transactions. Temperature and pressure define the density of liquid hydrogen, which is directly linked to trading interests. In this study, we developed and tested a liquid hydrogen temperature monitoring system that uses platinum resistance sensors with a nominal electrical resistance of approximately 1000 Ω at room temperature, PT-1000, for marine applications. The temperature measurements were carried out using a newly developed temperature monitoring system under different pressure conditions. The measured values are compared with a calibrated reference PT-1000 resistance thermometer. We confirm a measurement accuracy of ±50 mK in a pressure range of 0.1 MPa–0.5 MPa.     

Nano-Al doped-MoO3 high-energy composite films with excellent hydrophobicity and thermal stability

Developing the thermal stability of metal-based ceramic composites or their films has always been challenging and bottlenecks for the utilization of energy. In this paper, the novel mesh-like functional Al doped-MoO₃ nanocomposite film with even distribution and high purity was firstly fabricated by the high-efficiency electrophoretic deposition and surface modification. The optimal suspension turned out to be the mixture of isopropanol and the additives of polyethyleneimine and benzoic acid. The microtopography, crystalline structure, environmental resistance and thermal stability were analyzed by field emission scanning electron microscope (FESEM), energy dispersive X-ray (EDX), X-ray diffractometer (XRD), exposure and droplet-impacting test, DSC analysis and ignition test, respectively. The water contact angle and sliding angle of product can reach ~170° and <1°, indicating the excellent anti-wetting property. In addition, the high heat-release (~3180 J/g) of product all kept almost unchangeable after six months exposure experiments, demonstrating the outstanding thermostability. The exquisite design idea here can perfectly match microelectromechanical system (MEMS), providing the valuable reference for fabricating other metal-based high-energy composites with long lifespan for real industrial applications.     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

Nanolayer CrAlN/TiSiN coating designed for tribological applications

With the goal to produce a hard and tough coating intended for tribological applications, CrAlN/TiSiN nanolayer coating was prepared by alternative deposition of CrAlN and TiSiN layers. In the first part of the article, a detailed study of phase composition, microstructure, and layer structure of CrAlN/TiSiN coating is presented. In the second part, its mechanical properties, fracture and tribological behavior are compared to the nanocomposite TiSiN coating. An industrial magnetron sputtering unit was used for coating deposition. X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used for compositional and microstructural analysis. Mechanical properties and fracture behavior were studied by instrumented indentation and focused ion beam techniques. Tribological properties were evaluated by ball-on-disk test in a linear reciprocal mode. A complex layer structure was found in the nanolayer coating. The TiSiN layers were epitaxially stabilized inside the coating which led to formation of dislocations at interfaces, to introduction of disturbances in the coating growth, and as a result, to development of fine-grained columnar microstructure. Indentation load required for the onset of fracture was twice lower for the nanolayer CrAlN/TiSiN, compared to the nanocomposite TiSiN coating. This agrees very well with their mechanical properties, with H³/E² being twice higher for the TiSiN coating. However, the nanolayer coating experienced less severe damage, which had a strong impact on tribological behavior. A magnitude of order lower wear rate and four times lower steady state friction coefficient were found for the nanolayer coating.     

Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

Preparation and electrochemical characterization of Ti-based amorphous metallic glass with high strength

Ti-based amorphous metallic glasses have excellent mechanical, physical, and chemical properties, which is an important development direction and research hotspot of metal composite reinforcement. As a stable, simple, efficient, and large-scale preparation technology of metallic powders, the gas atomization process provides an effective way of preparing amorphous metallic glasses. In this study, the controllable fabrication of a Ti-based amorphous powder, with high efficiency, has been realized by using gas atomization. The scanning electron microscope, energy-dispersive spectrometer, and X-ray diffraction are used to analyze surface morphology, element distribution, and phase structure, respectively. A microhardness tester is used to measure the mechanical property. An electrochemical workstation is used to characterize corrosion behavior. The results show that as-prepared microparticles are more uniform and exhibit good amorphous characteristics. The mechanical test shows that the hardness of amorphous powder is significantly increased as compared with that before preparation, which has the prospect of being an important part of engineering reinforced materials. Further electrochemical measurement shows that the corrosion resistance of the as-prepared sample is also significantly improved. This study has laid a solid foundation for expanding applications of Ti-based metallic glasses, especially in heavy-duty and corrosive domains.