Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

Thermodynamic Evaluations of Amines as Hydrides or Two Hydrogen Ions Reductants and Imines as Protons or Two Hydrogen Ions Acceptors, as Well as Their Application in Hydrogenation Reactions.

Since the hydrogenation of imines (X) and the dehydrogenation of amines (XH2) generally involve the two hydrogen ions (H- + H+) transfer, the thermodynamic abilities of various amines releasing hydrides or two hydrogen ions as well as various imines accepting protons or two hydrogen ions are important and characteristic physical parameters. In this work, the pKa values of 84 protonated imines (XH+) in acetonitrile were predicted. Combining Gibbs free energy changes of amines releasing hydrides in acetonitrile from our previous work with the pKa(XH+) values, the Gibbs free energy changes of amines releasing two hydrogen ions and imines accepting two hydrogen ions were derived using Hess's law by constructing thermochemical cycles, and the thermodynamic evaluations of amines as hydrides or two hydrogen ions reductants and imines as protons or two hydrogen ions acceptors are well compared and discussed. Eventually, the practical application of thermodynamic data for amines and imines on hydrogenation feasibility, mechanism, and possible elementary steps was shown and discussed in this paper from the point of thermodynamics.

Theoretical Study for Evaluating and Discovering Organic Hydride Compounds as Potential Novel Methylation Reagents.

Methylation reaction is a fundamental chemical reaction that plays an important role in the modification of drug molecules, DNA, as well as proteins. This work focuses on seeking potential novel methylation reagents through a systematic investigation of the thermodynamics and reactivity of methyl-substituted organic hydride radical cations (XH•+s). In this work, 45 classical and important XH•+s were designed to investigate the relationship between their structure and reactivity, to find excellent or potential methylation reagents. The Gibbs free energy and activation free energy of XH•+ to release the methyl radical in MeCN at 298.15 and 355 K are calculated with the density functional theory (DFT) method to quantitatively measure the reactivity of XH•+ as a methylation reagent in this work. The relationships between structures and reactivities on XH•+s as methylation reagents are well examined. Since we have calculated the Gibbs free energy and activation free energy of trifluoromethyl-substituted organic hydride compound radical cations (X'H•+) releasing trifluoromethyl radicals in MeCN with the DFT method in our previous work, accordingly, the relationship of thermodynamics and reactivity between X'H•+ releasing trifluoromethyl radical and XH•+ releasing methyl radical is discussed in detail. Excitingly, 4 XH•+s (1H•+, 3H•+∼4H•+, and 44H•+) are found to be excellent methyl radical reagents, while 9 XH•+s (5H•+, 6H•+, 9H•+, 10H•+, 12H•+, 13H•+, 15H•+, 43H•+, and 45H•+) are found to be potential methyl radical reagents in chemical synthesis. The molecular library and reactivity database of novel methylation reagents could be established for synthetic chemists to query and use. Our work may offer a theoretical basis and reference experience for screening different substituted organic hydride compounds (YRHs) as alkylation reagents.

Identification of novel genetic biomarkers and treatment targets for arteriosclerosis-related abdominal aortic aneurysm using bioinformatic tools.

A large number of epidemiological studies have confirmed that arteriosclerosis (AS) is a risk factor for abdominal aortic aneurysm (AAA). However, the relationship between AS and AAA remains controversial. The objective of this work is to better understand the association between the two diseases by identifying the co-differentially expressed genes under both pathological conditions, so as to identify potential genetic biomarkers and treatment targets for atherosclerosis-related aneurysms. Differentially-expressed genes (DEGs) shared by both AS and AAA patients were identified by bioinformatics analyses of Gene Expression Omnibus (GEO) datasets GSE100927 and GSE7084. These DEGs were then subjected to bioinformatic analyses of protein-protein interaction (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the identified hub genes were further validated by qRT-PCR in AS (n = 4), AAA (n = 4), and healthy (n = 4) individuals. Differential expression analysis revealed a total of 169 and 37 genes that had increased and decreased expression levels, respectively, in both AS and AAA patients compared with healthy controls. The construction of a PPI network and key modules resulted in the identification of five hub genes (SPI1, TYROBP, TLR2, FCER1G, and MMP9) as candidate diagnostic biomarkers and treatment targets for patients with AS-related AAA. AS and AAA are indeed correlated; SPI1, TYROBP, TLR2, FCER1G and MMP9 genes are potential new genetic biomarkers for AS-related AAA.

Infection fatality ratio and case fatality ratio of COVID-19.

The infection fatality ratio (IFR) is the risk of death per infection and is one of the most important epidemiological parameters. Enormous efforts have been undertaken to estimate the IFR for COVID-19. This study examined the pros and cons of several approaches. It is found that the frequently used approaches using serological survey results as the denominator and the number of confirmed deaths as the numerator underestimated the true IFR. The most typical examples are South Africa and Peru (before official correction), where the confirmed deaths are one-third of the excess deaths. We argue that the RT-PCR-based case fatality ratio (CFR) is a reliable indicator of the lethality of COVID-19 in locations where testing is extensive. An accurate IFR is crucial for policymaking and public-risk perception.

Use of percutaneous transluminal renal angioplasty in atherosclerotic renal artery stenosis: a systematic review and meta-analysis.

OBJECTIVE: For patients with atherosclerotic renal artery stenosis (ARAS), the role of percutaneous transluminal renal angioplasty (PTRA) remains inconclusive. This study aimed to comparatively evaluate the benefits of best medical therapy (BMT) plus PTRA and BMT alone in treating ARAS. METHODS: We performed a systematic review and meta-analysis, and searched for all randomized, controlled trials that reported patients with ARAS. The effectiveness and safety in the BMT plus PTRA and BMT alone groups were estimated, taking into account hypertension, stroke, renal events, cardiac events, and mortality. RESULTS: Nine randomized, controlled trials involving 2309 patients were included. In the BMT plus PTRA group, the incidence of refractory hypertension was significantly lower compared with that in the BMT alone group (odds ratio 0.09; 95% confidence interval 0.01, 0.70). However, there were no significant differences in the rates of stroke, renal events, cardiac events, cardiac mortality, and all-cause mortality between the two groups. CONCLUSIONS: PTRA plus BMT improves blood pressure in patients with ARAS, but there is insufficient evidence for this therapy in improving stroke, renal events, cardiac events, and cardiac and all-cause mortality.

Hemodynamic Effects of Multiple Overlapping Uncovered Stents on Aortic Dissection: Surgical Strategies and Implications for False Lumen Thrombosis.

PURPOSE: Multiple overlapping uncovered stents (MOUS) are employed to promote false lumen thrombosis in the aortic dissections (AD), when the tears are in close vicinity to the branch vessels. However, the overall rate of false lumen thrombosis remains unsatisfactory. This study was performed to investigate the hemodynamic influence of MOUS on aortic dissection to shed some light on the mechanism of post-stenting false lumen thrombosis. METHODS: An anatomically accurate computational fluid dynamics model was developed to investigate the hemodynamics of AD. A parametric study was carried out to demonstrate the hemodynamic influence of MOUS in various post-surgery scenarios featuring the representative surgical strategies involving MOUS. RESULTS: The use of reduced-porosity MOUS slowed the blood flow in the false lumen and decreased the wall shear stress. MOUS depressed the false lumen and enlarged the true lumen, without significantly altering the blood outflow distribution among the branch vessels. Compared with MOUS-alone and stent graft-alone scenarios, the combination of MOUS and stent graft generated a substantially large region of stagnant flow. The active flow was confined to an area in close vicinity to the tears covered by the MOUS, which perfuse the right renal artery in the false lumen. CONCLUSIONS: MOUS helps to generate a favored hemodynamic environment for thrombus formation in the false lumen. Application of MOUS along with covered stent grafts may represent a more effective treatment for AD than utilizing MOUS or stent graft alone.