Pressure and temperature dependence of second-order elastic constants from third-order elastic constants in TMC (TM=Nb,Ti, V,Zr)

In this paper, we present an efficient and effective method to predict the pressure dependence and temperature dependence of second-order elastic constants (SOECs) by introducing third-order elastic constants (TOECs) in the monocarbide ultrahigh temperature ceramics. The method is validated by comparing with experiments and previous calculations in four TMCs (TM = Nb, Ti, V, Zr). Using this method, we investigate the derivatives of SOECs against pressure and temperature as well as the anisotropic properties of polycrystalline modulus. In addition, we fit the SOECs with pressure and temperature under the framework of CALPHAD for practice usage.     

Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets

Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (CO_G) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of CO_G on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, CO_G did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by CO_G or CORM-A1, was dependent on sGC. We conclude that the source (CO_G vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.     

Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.     

高稳高效海上风电安装平台关键制造技术研究

海上风电作为可再生清洁能源之一,受到世界各国的高度重视与大力发展。我国将海上风电提升至解决能源危机、减缓气候变化、调整能源结构的国家战略高度,到2030年我国单位国内生产总值二氧化碳排放将比2005年下降65%以上,非化石能源占一次能源消费比重将达到25%左右。安装平台不足将是我国海上风电场无法如期建成投产的主要障碍。对自升自航式海上风电安装平台系列高端装备及其设计制造的三大技术难题——腿站立作业易“失稳”、大平台大跨距大倾覆力矩自升易“失控”、高空吊装巨型叶片逾百螺栓精准定位易“失准”,以及焊缝缺陷修复和局部裂纹损伤的激光锻造修复再制造进行了介绍,研制的具有不同规格的系列装备在中国、英国、丹麦、德国等国家的著名海上风电场建设应用情况良好。     

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。     

Understanding the asymmetric perceptions of smartphone security from security feature perspective: A comparative study

Smartphones are being used and relied on by people more than ever before. The open connectivity brings with it great convenience and leads to a variety of risks that cannot be overlooked. Smartphone vendors, security policy designers, and security application providers have put a variety of practical efforts to secure smartphones, and researchers have conducted extensive research on threat sources, security techniques, and user security behaviors. Regrettably, smartphone users do not pay enough attention to mobile security, making many efforts futile. This study identifies this gap between technology affordance and user requirements, and attempts to investigate the asymmetric perceptions toward security features between developers and users, between users and users, as well as between different security features. These asymmetric perceptions include perceptions of quality, perceptions of importance, and perceptions of satisfaction. After scoping the range of smartphone security features, this study conducts an improved Kano-based method and exhaustively analyzes the 245 collected samples using correspondence analysis and importance satisfaction analysis. The 14 security features of the smartphone are divided into four Kano quality types and the perceived quality differences between developers and users are compared. Correspondence analysis is utilized to capture the relationship between the perceived importance of security features across different groups of respondents, and results of importance-satisfaction analysis provide the basis for the developmental path and resource reallocation strategy of security features. This article offers new insights for researchers as well as practitioners of smartphone security.     

功能性小麦品种的概念、类别和发展前景（网络首发、推荐阅读）

结合全球倡导的营养导向型农业和功能性食品的内容，首次提出“功能性小麦品种”的概念，将其定义为“含有对人体健康有益的活性成分，可调节人体有益代谢，能给人体健康带来某种益处或满足特定人群的特殊需求，同时可以作为日常食物的口感正常、无毒副作用的小麦品种类型”；结合疫情警示和我国进入后工业时代后，人们需求必将由“吃得饱”、“吃得好”向“吃得健康”转变，因而提出继高产品种、优质品种之后培育“功能性小麦品种”的育种目标。根据多年关于小麦淀粉、蛋白、酯类和其他成分的功能研究结果，介绍新育成的“麦黄酮”、“高色素”、“高抗性淀粉”、“富锌”、“低醇溶蛋白”和“低植酸”等功能性小麦新品种（系）的营养特性和农艺产量状况；根据“健康中国2030”规划等国家战略，进行“功能性品种培育是解决我国功能性食品‘卡脖子’的关键基础，一种功能性品种可以形成一类功能性食品，多种功能性品种可以形成我国功能性面制品产业，推动我国整个食品工业的发展”的前景展望；根据功能性品种及其食品的稳定性和可靠性是产品和市场的“生命线”，从对消费者负责的高度，提出关于“功能性农作物品种审定导向和组建功能性成分检测机构；编制有关功能性品种和食品的国家或行业标准，设立功能性食品和功能性农作物品种的商业标志，保证我国功能性农作物品种及其食品健康发展”等方面的具体建议。