Darstellung,Kristallstrukturen, Schwingungsspektren und Normalkoordinatenanalyse von cis‐ und trans‐(n‐Bu4N)2[PtF2(ox)2] und (n‐Bu4N)2[PtF4(ox)]

Synthesis, Crystal Structure, Vibrational Spectra, and Normal Coordinate Analysis of cis‐ and trans‐(n‐Bu₄N)₂[PtF₂(ox)₂] and (n‐Bu₄N)₂[PtF₄(ox)] By treatment of trans‐(n‐Bu₄N)₂[PtCl₂(ox)₂] and (n‐Bu₄N)₂[PtCl₄(ox)] with XeF₂ in propylene carbonate cis‐ and trans‐(n‐Bu₄N)₂[PtF₂(ox)₂] ( 1 , 2 ) and (n‐Bu₄N)₂[PtF₄(ox)] ( 3 ) are formed which have been isolated by ion exchange chromatography on diethylaminoethyl cellulose. The crystal structure of trans(n‐Bu₄N)₂[PtF₂(ox)₂] ( 2 ) (tetragonal, space group P4₂/n, a = 15.5489(9), b = 15.5489(9), c = 17.835(1)Å, Z = 4) und Cs₂[PtF₄(ox)] ( 3 ) (monoclinic, space group C2/m, a = 14.5261(7), b = 6.2719(4), c = 9.6966(9)Å, β = 90.216(8)°, Z = 4) reveal complex anions with nearly D_2h and C_2v point symmetry. The average bond lengths in the symmetrical coordinated axes are Pt—F = 1.93 ( 2 , 3 ) and Pt—O = 1.987 ( 2 ) and in the F^•—Pt—O′‐axes Pt—F^• = 1.957 and Pt—O′ = 1.977Å ( 3 ). The oxalato ligands are nearly planar with a maximum displacement of the ring atoms of 0.05 ( 2 ) und 0.01Å ( 3 ) to the calculated best planes. In the vibrational spectra the symmetric and antisymmetric PtF stretching vibrations are observed at 583 and 586 ( 2 ) and 576 and 568 cm^—1 ( 3 ). The PtF^• modes appear at 565 and 562 ( 1 ) and 560 cm^—1 ( 3 ). The PtO and PtO′ stretching vibrations are coupled with internal modes of the oxalato ligands and appear in the range of 400—800 cm^—1. Based on the molecular parameters of the X‐ray determinations ( 2 , 3 ) and estimated data ( 1 ) the IR and Raman spectra are assigned by normal coordinate analysis. The valence force constants are f_d(PtF) = 3.55 ( 2 ) and 3.38 ( 3 ), f_d(PtF^•) = 3.23 ( 1 ) and 3.20 ( 3 ), f_d(PtO) = 2.65 ( 1 ) and 2.84 ( 2 ) and f_d(PtO′) = 2.97 ( 1 ) and 3.00 mdyn/Å ( 3 ). Taking into account increments of the trans influence a good agreement between observed and calculated frequencies is achieved. The NMR shifts are δ(¹⁹⁵Pt) = 8485 ( 1 ), 8597 ( 2 ) and 10048 ppm ( 3 ), δ(¹⁹F) = —350 ( 2 ) and —352 ( 3 ) and δ(¹⁹F^•) = —323 ( 1 ) and —326 ppm ( 3 ) with the coupling constants ¹J(PtF) = 1784 ( 2 ) and 1864 ( 3 ) and ¹J(PtF^•) = 1525 ( 1 ) and 1638 Hz ( 3 ).     

Network Autoregressive Model for the Prediction of COVID-19 Considering the Disease Interaction in Neighboring Countries

Predicting the way diseases spread in different societies has been thus far documented as one of the most important tools for control strategies and policy-making during a pandemic. This study is to propose a network autoregressive (NAR) model to forecast the number of total currently infected cases with coronavirus disease 2019 (COVID-19) in Iran until the end of December 2021 in view of the disease interactions within the neighboring countries in the region. For this purpose, the COVID-19 data were initially collected for seven regional nations, including Iran, Turkey, Iraq, Azerbaijan, Armenia, Afghanistan, and Pakistan. Thenceforth, a network was established over these countries, and the correlation of the disease data was calculated. Upon introducing the main structure of the NAR model, a mathematical platform was subsequently provided to further incorporate the correlation matrix into the prediction process. In addition, the maximum likelihood estimation (MLE) was utilized to determine the model parameters and optimize the forecasting accuracy. Thereafter, the number of infected cases up to December 2021 in Iran was predicted by importing the correlation matrix into the NAR model formed to observe the impact of the disease interactions in the neighboring countries. In addition, the autoregressive integrated moving average (ARIMA) was used as a benchmark to compare and validate the NAR model outcomes. The results reveal that COVID-19 data in Iran have passed the fifth peak and continue on a downward trend to bring the number of total currently infected cases below 480,000 by the end of 2021. Additionally, 20%, 50%, 80% and 95% quantiles are provided along with the point estimation to model the uncertainty in the forecast.     

“新冠肺炎”疫情环境下实验教学形式多样化的运用

实验教学的主要授课形式在科技的发展下已经变得多样化,实验课程不仅是学生实践与研究的基础,也是从知识理解向科学研究的转化,在教学中占据着不可缺少的地位。全国“新型冠状病毒肺炎”(简称“新冠肺炎”)疫情的爆发极具偶然性,给实验教学带来了前所未有的压力。在突发困难面前,通过直/录播线上教学、数字化资源的运用、授课形式的转变、评价体系的调整等一系列应急措施,在实验教学中取得了较好的效果。这不仅与理论课程形成了良好的配合,充分保障了实验教学的内容和质量,而且大大促进了学生的自主学习能力,还引发了对高校实验教学发展的思考,即,不应在疫情等特殊情况下才思考求变,实验教学应坚持不懈地着力于学生培养和持续改革。     

岩浆活动对渤中19-6潜山油气成藏的影响

渤海湾盆地是中国东部重要含油气盆地。2018年中国东部最大整装凝析气田—渤中19-6气田的发现,一举打开了渤海湾盆地深层天然气勘探的新领域,展现了油型盆地天然气勘探的巨大潜力。渤中19-6构造带具有上油下气的分布特征,为了研究该构造带油气的成藏机理,从烃源岩生排烃史、构造热演化史、岩浆活动、流体包裹体显微荧光与测温技术等方面系统分析渤中19-6构造带油气成藏史,深入研究其形成机理,认为：渤中19-6构造带凝析气田不同深度的包裹体具有相似的盐度和均一温度分布范围,且不同深度的均一温度主峰温度相同,均表现为高于地层的温度,显示了油气充注属于事件性成藏,具有穿层、瞬时、高温的特征;渤中19-6构造带岩浆活动发育,岩浆侵入加速了有机质的成熟,促进了烃源岩生排烃作用,烃源岩在短时间内大量形成凝析油气;渤中19-6潜山构造带早期形成的古油藏,受新构造运动的影响,向上调整为渤中19-4油田,同时构造活动造成岩浆上涌,伴随的超临界状态幔源CO₂液体,加速了油气运移过程,凝析油气快速充注进入渤中19-6潜山圈闭,形成现今的渤中19-6凝析气田。     

Effects of Vaccination Efficacy on Wealth Distribution in Kinetic Epidemic Models

The spread of the COVID-19 pandemic has highlighted the close link between economics and health in the context of emergency management. A widespread vaccination campaign is considered the main tool to contain the economic consequences. This paper will focus, at the level of wealth distribution modeling, on the economic improvements induced by the vaccination campaign in terms of its effectiveness rate. The economic trend during the pandemic is evaluated, resorting to a mathematical model joining a classical compartmental model including vaccinated individuals with a kinetic model of wealth distribution based on binary wealth exchanges. The interplay between wealth exchanges and the progress of the infectious disease is realized by assuming, on the one hand, that individuals in different compartments act differently in the economic process and, on the other hand, that the epidemic affects risk in economic transactions. Using the mathematical tools of kinetic theory, it is possible to identify the equilibrium states of the system and the formation of inequalities due to the pandemic in the wealth distribution of the population. Numerical experiments highlight the importance of the vaccination campaign and its positive effects in reducing economic inequalities in the multi-agent society.     

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.     

Thiazole/Thiadiazole/Benzothiazole Based Thiazolidin-4-One Derivatives as Potential Inhibitors of Main Protease of SARS-CoV-2

Since the time of its appearance until present, COVID-19 has spread worldwide, with over 71 million confirmed cases and over 1.6 million deaths reported by the World Health Organization (WHO). In addition to the fact that cases of COVID-19 are increasing worldwide, the Delta and Omicron variants have also made the situation more challenging. Herein, we report the evaluation of several thiazole/thiadiazole/benzothiazole based thiazolidinone derivatives which were chosen from 112 designed derivatives by docking as potential molecules to inhibit the main protease of SARS-CoV-2. The contained experimental data revealed that among the fifteen compounds chosen, five compounds (k3, c1, n2, A2, A1) showed inhibitory activity with IC₅₀ within the range of 0.01–34.4 μΜ. By assessing the cellular effects of these molecules, we observed that they also had the capacity to affect the cellular viability of human normal MRC-5 cells, albeit with a degree of variation. More specifically, k3 which is the most promising compound with the higher inhibitory capacity to SARS-CoV-2 protease (0.01 μΜ) affects in vitro cellular viability only by 57% at the concentration of 0.01 μM after 48 h in culture. Overall, these data provide evidence on the potential antiviral activity of these molecules to inhibit the main protease of SARS-CoV-2, a fact that sheds light on the chemical structure of the thiazole/thiadiazole/benzothiazole based thiazolidin-4-one derivatives as potential candidates for COVID-19 therapeutics.     

Isolation and In Silico Anti-SARS-CoV-2 Papain-Like Protease Potentialities of Two Rare 2-Phenoxychromone Derivatives from Artemisia spp.

Two rare 2-phenoxychromone derivatives, 6-demethoxy-4`-O-capillarsine (1) and tenuflorin C (2), were isolated from the areal parts of Artemisia commutata and A. glauca, respectively, for the first time. Being rare in nature, the inhibition potentialities of 1 and 2 against SARS-CoV-2 was investigated using multistage in silico techniques. At first, molecular similarity and fingerprint studies were conducted for 1 and 2 against co-crystallized ligands of eight different COVID-19 enzymes. The carried-out studies indicated the similarity of 1 and 2 with TTT, the co-crystallized ligand of COVID-19 Papain-Like Protease (PLP), (PDB ID: 3E9S). Therefore, molecular docking studies of 1 and 2 against the PLP were carried out and revealed correct binding inside the active site exhibiting binding energies of −18.86 and −18.37 Kcal/mol, respectively. Further, in silico ADMET in addition to toxicity evaluation of 1 and 2 against seven models indicated the general safety and the likeness of 1 and 2 to be drugs. Lastly, to authenticate the binding and to investigate the thermodynamic characters, molecular dynamics (MD) simulation studies were conducted on 1 and PLP.     

Fullerenes against COVID-19: Repurposing C60 and C70 to Clog the Active Site of SARS-CoV-2 Protease

The persistency of COVID-19 in the world and the continuous rise of its variants demand new treatments to complement vaccines. Computational chemistry can assist in the identification of moieties able to lead to new drugs to fight the disease. Fullerenes and carbon nanomaterials can interact with proteins and are considered promising antiviral agents. Here, we propose the possibility to repurpose fullerenes to clog the active site of the SARS-CoV-2 protease, M^pro. Through the use of docking, molecular dynamics, and energy decomposition techniques, it is shown that C₆₀ has a substantial binding energy to the main protease of the SARS-CoV-2 virus, M^pro, higher than masitinib, a known inhibitor of the protein. Furthermore, we suggest the use of C₇₀ as an innovative scaffold for the inhibition of SARS-CoV-2 M^pro. At odds with masitinib, both C₆₀ and C₇₀ interact more strongly with SARS-CoV-2 M^pro when different protonation states of the catalytic dyad are considered. The binding of fullerenes to M^pro is due to shape complementarity, i.e., vdW interactions, and is aspecific. As such, it is not sensitive to mutations that can eliminate or invert the charges of the amino acids composing the binding pocket. Fullerenic cages should therefore be more effective against the SARS-CoV-2 virus than the available inhibitors such as masinitib, where the electrostatic term plays a crucial role in the binding.     

Anthelmintic Effect of Leucaena leucocephala Extract and Its Active Compound,Mimosine, on Vital Behavioral Activities in Caenorhabditis elegans

Helminth infections continue to be a neglected global threat in tropical regions, and there have been growing cases of anthelmintic resistance reported towards the existing anthelmintic drugs. Thus, the search for a novel anthelmintic agent has been increasing, especially those derived from plants. Leucaena leucocephala (LL) is a leguminous plant that is known to have several pharmacological activities, including anthelmintic activity. It is widely known to contain a toxic compound called mimosine, which we believed could be a potential lead candidate that could exert a potent anthelmintic effect. Hence, this study aimed to validate the presence of mimosine in LL extract and to investigate the anthelmintic effect of LL extract and mimosine on head thrashing, egg-laying, and pharyngeal pumping activities using the animal model Caenorhabditis elegans (C. elegans). Mimosine content in LL extract was confirmed through an HPLC analysis of spiking LL extract with different mimosine concentrations, whereby an increasing trend in peak heights was observed at a retention time of 0.9 min. LL extract and mimosine caused a significant dose-dependent increase in the percentage of worm mortality, which produced LC50s of 73 mg/mL and 6.39 mg/mL, respectively. Exposure of C. elegans to different concentrations of LL extract and mimosine significantly decreased the head thrashing, egg-laying, and mean pump amplitude of pharyngeal pumping activity. We speculated that these behavioral changes are due to the inhibitory effect of LL extract and mimosine on an L-type calcium channel called EGL-19. Our findings provide evidential support for the potential of LL extract and its active compound, mimosine, as novel anthelmintic candidates. However, the underlying mechanism of the anthelmintic action has yet to be elucidated.