The Pathophysiology of Long COVID throughout the Renin-Angiotensin System

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people’s lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.     

An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.     

Antiinflammation Derived Suzuki-Coupled Fenbufens as COX-2 Inhibitors: Minilibrary Construction and Bioassay

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9–17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and bioactive disubstituted compound encompasses one electron-withdrawing methyl and one electron-donating fluoro groups in one arene. COX-2 is selective but not COX-2 to bioactive compounds that contain both two electron-withdrawing groups; disubstituted analogs with both resonance-formable electron-donating dihydroxy groups display high COX-2 activity but inferior COX-2 selectivity. In silico simulation and modeling for three COX-2 active—p-fluoro, p-hydroxy and p-amino—fenbufens show a preferable docking to COX-2 than COX-1. The most stabilization by the p-hydroxy fenbufen with COX-2 predicted by theoretical simulation is consistent with its prominent COX-2 inhibition resulting from experiments.     

Improvement of amine-modification with piperazine for the adsorption of CO2

Both selectivity and capacity of CO₂ adsorption were considerably increased when PZ (piperazine) was added in MDEA (methyldiethylamine) that used to modify the surface of silica gels. The adsorbent saturated with CO₂ was regenerated at ambient temperature through nitrogen purge. A set of PSA (pressure swing adsorption) operation with 200 cycles was carried out and applicability of the modified adsorbent was thus illustrated. The CO₂ content in the column-top stream decreased from 13% to below 0.05% at steady state.     

Functional neuroimaging of inner fields-of-view with 2D-selective RF excitations

Echo-planar imaging is widely used in functional neuroimaging but suffers from its pronounced sensitivity to field inhomogeneities that cause geometric distortions and image blurring which both limit the effective in-plane resolution achievable. In this work, it is shown how inner-field-of-view techniques based on 2D-selective RF excitations (2DRF) can be applied to reduce the field-of-view in the phase-encoding direction without aliasing and increase the in-plane resolution accordingly. Free-induction-decay (FID) EPI and echo-train-shifted (T2*-weighted) and standard (T2-weighted) spin-echo (SE) EPI with in-plane resolutions of up to 0.5×1.0 mm² (slice thickness 5 mm) were acquired at 3 T. Unwanted signal contributions of 2DRF side excitations were shifted out of the object (FID-EPI) or of the refocusing plane by tilting the excitation plane (SE-EPI). Brain activation in healthy volunteers was investigated with checkerboard and finger-tapping block-design paradigms. Brain activation could be detected with all sequences and contrasts, most reliably with FID-EPI due to its higher signal amplitude and the longer 2DRF excitation that are more sensitive to magnetic field inhomogeneities. In conclusion, inner-FOV EPI based on 2DRF excitations could help to improve the spatial resolution of fMRI of focal target regions, e.g. for applications in the spinal cord.     

DFT Investigations of Aun Nano-Clusters Supported on TiO2 Nanotubes: Structures and Electronic Properties

TiO₂ nanotubes (TiO₂NTs) are beneficial for photogenerated electron separation in photocatalysis. In order to improve the utilization rate of TiO₂NTs in the visible light region, an effective method is to use Au_n cluster deposition-modified TiO₂NTs. It is of great significance to investigate the mechanism of Au_n clusters supported on TiO₂NTs to strengthen its visible-light response. In this work, the structures, electronic properties, Mulliken atomic charge, density of states, band structure, and deformation density of Au_n (n = 1, 8, 13) clusters supported on TiO₂NTs were investigated by DMOL3. Based on published research results, the most stable adsorption configurations of Au_n (n = 1, 8, 13) clusters supported with TiO₂NTs were obtained. The adsorption energy increased as the number of Au adatoms increased linearly. The Au_n clusters supported on TiO₂NTs carry a negative charge. The band gaps of the three most stable structures of each adsorption system decreased compared to TiO₂NTs; the valence top and the conduction bottom of the Fermi level come mainly from the contribution of 5d and 6s-Au. The electronic properties of the 5d and 6s impurity orbitals cause valence widening and band gap narrowing.     

Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.     

热处理条件对PVA薄膜阻氢性能的影响

采用XRD测定了PVA薄膜在不同热处理条件下的结晶度,并用自行设计的渗氢系数测量系统研究了在不同热处理条件下的PVA薄膜阻氢性能的变化规律。结果表明,PVA薄膜的热处理温度越高,其结晶度越高,越有利于提高PVA薄膜的阻氢性能,但热处理温度宜选择在180℃以下,以防止PVA薄膜热降解,另一方面,在PVA的玻璃化转变温度以下进行热处理同样能够提高PVA薄膜的阻氢性能,而醇解度较低的PVA薄膜在玻璃化转变温度以下经热处理后的阻氢性能提高的幅度较大。     

单层2H-MoTe2光电效应的理论研究

材料的禁带宽度是影响光电探测器探测范围的重要因素.单层2H-MoTe2因具有合适的禁带宽度引起了科研人员广泛的研究兴趣.本文基于非平衡态格林函数-密度泛函理论,采用第一性原理方法,研究了单层2H-MoTe2的光电效应.结果表明:在线性偏振光照射下,MoTe2产生的光电流函数与唯象理论相吻合;在光子能量范围1.6～1.8...