Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study

Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.     

Oxidative Precipitation Synthesis of Calcium-Doped Manganese Ferrite Nanoparticles for Magnetic Hyperthermia

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (Ca_xMn_1−xFe₂O₄) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.     

The Intratumor Bacterial and Fungal Microbiome Is Characterized by HPV,Smoking, and Alcohol Consumption in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) tumor phenotypes and clinical outcomes are significantly influenced by etiological agents, such as HPV infection, smoking, and alcohol consumption. Accordingly, the intratumor microbiome has been increasingly implicated in cancer progression and metastasis. However, few studies characterize the intratumor microbial landscape of HNSCC with respect to these etiological agents. In this study, we aimed to investigate the bacterial and fungal landscape of HNSCC in association with HPV infection, smoking, and alcohol consumption. RNA-sequencing data were extracted from The Cancer Genome Atlas (TCGA) regarding 449 tissue samples and 44 normal samples. Pathoscope 2.0 was used to extract the microbial reads. Microbe abundance was compared to clinical variables, oncogenic signatures, and immune-associated pathways. Our results demonstrated that a similar number of dysregulated microbes was overabundant in smokers and nonsmokers, while heavy drinkers were characterized by an underabundance of dysregulated microbes. Conversely, the majority of dysregulated microbes were overabundant in HPV+ tumor samples when compared to HPV- tumor samples. Moreover, we observed that many dysregulated microbes were associated with oncogenic and metastatic pathways, suggesting their roles in influencing carcinogenesis. These microbes provide insights regarding potential mechanisms for tumor pathogenesis and progression with respect to the three etiological agents.     

Mechanics of Reversible Deformation during Leaf Movement and Regulation of Pulvinus Development in Legumes

Plant cell deformation is a mechanical process that is driven by differences in the osmotic pressure inside and outside of the cell and is influenced by cell wall properties. Legume leaf movements result from reversible deformation of pulvinar motor cells. Reversible cell deformation is an elastic process distinct from the irreversible cell growth of developing organs. Here, we begin with a review of the basic mathematics of cell volume changes, cell wall function, and the mechanics of bending deformation at a macro scale. Next, we summarize the findings of recent molecular genetic studies of pulvinar development. We then review the mechanisms of the adaxial/abaxial patterning because pulvinar bending deformation depends on the differences in mechanical properties and physiological responses of motor cells on the adaxial versus abaxial sides of the pulvinus. Intriguingly, pulvini simultaneously encompass morphological symmetry and functional asymmetry along the adaxial/abaxial axis. This review provides an introduction to leaf movement and reversible deformation from the perspective of mechanics and molecular genetics.     

The Role of TGFβ and Other Cytokines in Regulating Mast Cell Functions in Allergic Inflammation

Mast cells (MC) are a key effector cell in multiple types of immune responses, including atopic conditions. Allergic diseases have been steadily rising across the globe, creating a growing public health problem. IgE-mediated activation of MCs leads to the release of potent mediators that can have dire clinical consequences. Current therapeutic options to inhibit MC activation and degranulation are limited; thus, a better understanding of the mechanisms that regulate MC effector functions in allergic inflammation are necessary in order to develop effective treatment options with minimal side effects. Several cytokines have been identified that play multifaceted roles in regulating MC activation, including TGFβ, IL-10, and IL-33, and others that appear to serve primarily anti-inflammatory functions, including IL-35 and IL-37. Here, we review the literature examining cytokines that regulate MC-mediated allergic immune responses.     

钢水喷镁精炼及其对钢性能的影响

由于镁对钢的脱氧、脱硫、净化钢水及转变夹杂物形态的良好作用,近年来许多冶金工作者致力于加镁精炼钢水的研究工作,但因在冶金温度下镁的蒸汽压很高,而其在钢水的溶解度又极小,加入困难,这方面的研究多归于失败。本文利用阿亨大学热力学数据库计算了以氩作为载气喷镁的脱氧、脱硫作用,以及压力和氩量对其影响,通过实验制定了行之有效的喷吹工艺,选择了合适的控制参数。
在1-3大压下,氩量为0.1-0.3N.L/m:n,可以向钢水成功地喷入镁。经过镁精炼的钢水,氧含量可降至4ppm,硫含量降至10ppm,氧化物及硫化物的评级均为0级,其尺寸均在5μm之下。随着喷镁量的增加(钢水重量的0.062至%0.56%),夹杂物中镁的氧化物及硫化物量增加,夹杂物总量减少且呈球形,此种夹杂物在热形变中不变形。因此在通常材料中所存在的各向异性完全消失,特别是缺口冲击韧性横向性能值提高了2~3倍。文章对材料在不同温度下的冲击韧性、过渡温度及断口夹杂物的形态进行了研究和论述。     

氮在渣-钢间传质系数的测定

使用Al₂O₃坩埚在真空感应炉内测定了1600℃时氮在含C还原渣和钢液之间的总传质系数β_o.研究表明,β_o与气相中氮分压P_N2的大小有关,随着P_N2的增加β_o增大.由物料平衡计算得出,在本实验条件下,β_o为3.7×10^-4 cm/S.     

Study of the Effect of Vibration Treatment of Porous Sintered Workpiece Treatment on Structure and Properties of Hot-Forged Powder Object Surface Layer

Metallurgist - A number of combine-harvester components are produced by mass production of hot-forged sintered powder blanks in the at “Rostsel’mash” plant. With the aim of...     

Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery

A key challenge for stem cell therapies is the delivery of therapeutic cells to the repair site. Magnetic targeting has been proposed as a platform for defining clinical sites of delivery more effectively. In this paper, we use a combined in vitro experimental and mathematical modelling approach to explore the magnetic targeting of mesenchymal stromal cells (MSCs) labelled with magnetic nanoparticles using an external magnet. This study aims to (i) demonstrate the potential of magnetic tagging for MSC delivery, (ii) examine the effect of red blood cells (RBCs) on MSC capture efficacy and (iii) highlight how mathematical models can provide both insight into mechanics of therapy and predictions about cell targeting in vivo. In vitro MSCs are cultured with magnetic nanoparticles and circulated with RBCs over an external magnet. Cell capture efficacy is measured for varying magnetic field strengths and RBC percentages. We use a 2D continuum mathematical model to represent the flow of magnetically tagged MSCs with RBCs. Numerical simulations demonstrate qualitative agreement with experimental results showing better capture with stronger magnetic fields and lower levels of RBCs. We additionally exploit the mathematical model to make hypotheses about the role of extravasation and identify future in vitro experiments to quantify this effect.     

Shear analysis of rice husk ash (RHA) reinforced tin-0.7-copper composite solders on electroless nickel/immersion silver (ENIAg) surfaces

In this study, the mechanical performance of the rice husk ash-reinforced tin-0.7 copper composite solder was investigated. 0.01 wt.%, 0.05 wt.% and 0.1 wt.% of rice husk ash (RHA) were added to the solder matrix to prepare the composite solders. In order, to replace the costly electroless nickel immersion gold surface finish on the copper substrate, the effect of electroless nickel immersion silver (ENIAg) as the surface finish was studied. The differential scanning calorimetry (DSC) analysis showed that the composite solder exhibited lower melting temperature relative to the plain solder owing to the inclusion of rice husk ash. Shear strength analysis was carried out to investigate the influence of rice husk ash and electroless nickel immersion silver surface finish on the shear strength of the developed composite solders. The results proved that the rice husk ash failed to enhance the shear strength of tin-0.7 copper lead-free solder with the plain solder exhibiting the highest shear strength.