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Abstract: Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase III clinical studies, and some solid deuterium compounds have entered phase I and II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs.

Abstract: Purine, one of the nucleotides, is an important substance for the metabolism and regulation of the body. Purine plays a key role not only in the composition of coenzymes but also in the supply of energy. Since purine was artificially synthesized, it has always been an important scaffold for respiratory diseases, cardiovascular diseases, and anti- tumor and anti-viral drugs. In addition to being widely used as competitive antagonists in the treatment of diseases, purines can be used in combination with other drugs and as precursors to benefit human life. Unfortunately, few new discoveries have been made in recent years. In this article, purine drugs in the market have been classified according to their different targets. In addition, their mechanism of action and structure-activity relationship have also been introduced. This paper provides details of the signaling pathways through which purine drugs can bind to the respective receptors on the surface of cells and cause consequent reactions within the cell, which finally affect the targeted diseases. The various receptors and biological reactions involved in the signaling for respective disease targets within the cells are discussed in detail.

Abstract: Amide proton transfer (APT) imaging is a technique that reflects the level of amide proton transport of hydrogen ions in water to peptides and proteins within the tumour by using magnetic resonance imaging without contrast administration. This technique can more accurately reflect the protein level, pH value, and other relevant information within the tumour. Currently, APT is widely used in glioma research. In this paper, we briefly describe the research progress on this technique.

Multipotent mesenchymal stromal cells (MSCs) expand in vitro and undergo replicative senescence, thereby restricting their clinical utilization. Thus, an effective strategy is required to impede MSC senescence. Since spermidine (SPD) supplementation can prolong the lifespan of yeast by inhibiting oxidative stress, spermidine is a potential option for delaying MSC senescence. In this study, to test our hypothesis, we first isolated primary human umbilical cord mesenchymal stem cells (hUCMSCs). Subsequently, the appropriate SPD dose was administered during continuous cell cultivation. Next, we evaluated the antisenescence effects by SA-β-gal staining, Ki67 expression, reactive oxygen species (ROS) levels, adipogenic or osteogenic ability, senescence-associated markers, and DNA damage markers. The results revealed that early SPD intervention significantly delays the replicative senescence of hUCMSCs and constrains premature H2O2-induced senescence. Additionally, by silencing SIRT3, the SPD-mediated antisenescence effects disappear, further demonstrating that SIRT3 is necessary for SPD to exert its antisenescence effects on hUCMSCs. Besides, the findings of this study also suggest that SPD in vivo protects MSCs against oxidative stress and delays cell senescence. Thus, MSCs maintain the ability to proliferate and differentiate efficiently in vitro and in vivo, which reflects the potential clinical utilization of MSCs in the future.

Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Compared with HFD mice, PS not only increased the antioxidant activity of the liver but also regulated the mRNA expression levels of enzymes and receptors related to cholesterol metabolism. The hypolipidemic effect of PS was abolished by antibiotic (Abx) intervention and reproduced by fecal transplantation (FMT) intervention. The results of 16S rRNA sequencing analysis showed that PS modulated the gut microbiota of mice. PS reduced the relative abundance of Lactobacillus and other bile salt hydrolase- (BSH-) producing gut microbiota in HFD mice, which are potentially related to cholesterol metabolism. These findings partially explain the mechanisms by which PS regulates cholesterol metabolism. This implies that regulation of the gut microbiota would be a potential target for the treatment of HLP.

Spacecraft electromagnetic docking has many potential advantages, such as no propellant consumption and plume contamination, while providing high-precision, continuous, reversible, synchronous, and noncontacting control capabilities. With these advantages, there are strong dynamic nonlinearity and coupling, which are not friendly to controller design. Electromagnetic actuation has capabilities of force/torque symmetry and self-alignment, which could be exploited not only to simplify the controller but also to reduce the demand of relative motion measurement and improve control precision. In this paper, based on the theoretical derivation of nonlinear relative motion dynamic models, the magnetic force/torque symmetries and the self-alignment capability are analyzed, and then the self-attraction magnetic dipoles are solved. In addition, several numerical simulation cases are given to verify these capabilities and dipole solutions.

The online freight platform, also called freight resource sharing platform or freight O2O platform, developed rapidly lately, has gradually become the leaders in China’s road freight market in recent years, especially in the intracity freight market. The platform’s revenue mainly comes from the registration fee and commission, of which the commission is extracted from the freight rate. Therefore, how to determine the registration fee and freight rate becomes a key issue for the platform. Our research focuses on analyzing the pricing strategy by considering the charging mode, game model, and affecting factors. Based on the two-sided market theory and the classic Hotelling model, a tripartite game model of online freight platform-carrier-consignor is constructed. Furthermore, a game model of consignor and alternative carriers is built by introducing the platform user’s psychological pressure and satisfaction priority into the model. Finally, through mathematical derivation and numerical experiment, we analyze the effects of various factors on platform profits, platform registration fees, and freight rate, and propose some suggestions to promote the orderly development of online freight platforms for the intracity freight market.

Objective. COVID-19 has evolved into a major global public health event. The number of people reporting insomnia is growing exponentially during the pandemic. This study aimed to explore the relationship between aggravated insomnia and COVID-19-induced psychological impact on the public, lifestyle changes, and anxiety about the future. Methods. In this cross-sectional study, we used the questionnaires from 400 subjects who were obtained from the Department of Encephalopathy of the Wuhan Hospital of Traditional Chinese Medicine between July 2020 and July 2021. The data collected for the study included demographic characteristics of the participants and psychological scales consisting of the Spiegel Sleep Questionnaire, the Fear of COVID-19 Scale (FCV-19S), the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). The independent sample t-test and one-way ANOVA were used to compare the results. Correlation analysis of variables affecting insomnia was performed using Pearson correlation analysis. The degree of influence of the variables on insomnia was determined using linear regression, and a regression equation was derived. Results. A total of 400 insomnia patients participated in the survey. The median age was 45.75 ± 15.04 years. The average score of the Spiegel Sleep Questionnaire was 17.29 ± 6.36, that of SAS was 52.47 ± 10.39, that of SDS was 65.89 ± 8.72, and that of FCV-19S was 16.09 ± 6.81. The scores of FCV-19S, SAS, and SDS were closely related to insomnia, and the influencing degree was in the following order: fear, depression, and anxiety (OR = 1.30, 0.709, and 0.63, respectively). Conclusion. Fear of COVID-19 can be one of the primary contributors to worsening insomnia.

This paper is concerned with a class of fractional Schrödinger equation with Hardy potential ( − Δ ) s u + V ( x ) u − κ | x | 2 s u = f ( x , u ) , x ∈ R N , where s ∈ ( 0 , 1 ) and κ ⩾ 0 is a parameter. Under some suitable conditions on the potential V and the nonlinearity f, we prove the existence of ground state solutions when the parameter κ lies in a given range by using the non-Nehari manifold method. Moreover, we investigate the continuous dependence of ground state energy about κ. Finally, we are able to explore the asymptotic behavior of ground state solutions when κ tends to 0.

The DArk Matter Particle Explorer (DAMPE) is well suitable for searching for monochromatic and sharp $\gamma$-ray structures in the GeV$-$TeV range thanks to its unprecedented high energy resolution. In this work, we search for $\gamma$-ray line structures using five years of DAMPE data. To improve the sensitivity, we develop two types of dedicated data sets (including the BgoOnly data which is the first time to be used in the data analysis for the calorimeter-based gamma-ray observatories) and adopt the signal-to-noise ratio optimized regions of interest (ROIs) for different DM density profiles. No line signals or candidates are found between 10 and 300 GeV in the Galaxy. The constraints on the velocity-averaged cross section for $\chi\chi \to \gamma\gamma$ and the decay lifetime for $\chi \to \gamma\nu$, both at 95% confidence level, have been calculated and the systematic uncertainties have been taken into account. Comparing to the previous Fermi-LAT results, though DAMPE has an acceptance smaller by a factor of $\sim 10$, similar constraints on the DM parameters are achieved and below 100 GeV the lower limits on the decay lifetime are even stronger by a factor of a few. Our results demonstrate the potential of high-energy-resolution observations on dark matter detection., Comment: 14 pages, 8 figures. Update the content to keep up with the published version

The increasing demand for data and the rapid increase in the number of wireless connected devices make the shortage of energy and spectrum resources more serious. This paper considers a wireless powered communication network (WPCN) composed of N wireless devices (WDs) installed with single-antenna and a hybrid access point (HAP) equipped with multi-antenna, where HAP sends wireless energy to WDs in the downlink and receives information transmission from WDs in the uplink. To overcome “double near and far” problem, this paper adopts a clustering cooperative transmission method to enhance some WDs’ throughput performance far from the HAP, i.e., one of N WDs is selected as a cluster head (CH) and the remaining (N − 1) WDs as cluster members (CMs), and the CH helps relay CMs’ information to transmit. However, because the CH needs to transmit N WDs’ information, its energy consumed during information transmission will be the bottleneck of the system performance. To achieve a tradeoff between energy and data rate, this paper adopts multi-antenna energy beamforming technology to concentrate more energy to transmit the CH, so as to balance the energy consumption among all WDs. Considering the influence of in-phase/orthogonal imbalance,nonlinear amplification amplitude and phase noise on those physical transceivers of low-cost sensor nodes, nonlinear energy harvesting technology is employed to improve throughput performance of the WPCN system. Particularly, the proposed scheme’s throughput performance is derived, and simulation results demonstrate that this scheme can be effective to increase the WPCN system’s throughput fairness and spectral efficiency.