Infectiousness of places - Impact of multiscale human activity places in the transmission of COVID-19.

COVID-19 raises attention to epidemic transmission in various places. This study analyzes the transmission risks associated with human activity places at multiple scales, including different types of settlements and eleven types of specific establishments (restaurants, bars, etc.), using COVID-19 data in 906 urban areas across four continents. Through a difference-in-difference approach, we identify the causal effects of activities at various places on epidemic transmission. We find that at the micro-scale, though the transmission risks at different establishments differ across countries, sports, entertainment, and catering establishments are generally more infectious. At the macro-scale, contradicting common beliefs, it is consistent across countries that transmission does not increase with settlement size and density. It is also consistent that specific establishments play a lesser role in transmission in larger settlements, suggesting more transmission happening elsewhere. These findings contribute to building a system of knowledge on the linkage between places, human activities, and disease transmission.

Gaultheria leucocarpa var. yunnanensis for Treating Rheumatoid Arthritis-An Assessment Combining Machine Learning-Guided ADME Properties Prediction, Network Pharmacology, and Pharmacological Assessment.

Background: Dianbaizhu (Gaultheria leucocarpa var. yunnanensis), a traditional Chinese/ethnic medicine (TC/EM), has been used to treat rheumatoid arthritis (RA) for a long time. The anti-rheumatic arthritis fraction (ARF) of G. yunnanensis has significant anti-inflammatory and analgesic activities and is mainly composed of methyl salicylate glycosides, flavonoids, organic acids, and others. The effective ingredients and rudimentary mechanism of ARF remedying RA have not been elucidated to date. Purpose: The aim of the present study is to give an insight into the effective components and mechanisms of Dianbaizhu in ameliorating RA, based on the estimation of the absorption, distribution, metabolism, and excretion (ADME) properties, analysis of network pharmacology, and in vivo and in vitro validations. Study design and methods: The IL-1ß-induced human fibroblast-like synoviocytes of RA (HFLS-RA) model and adjuvant-induced arthritis in the rat model were adopted to assess the anti-RA effect of ARF. The components in ARF were identified by using UHPLC-LTQ-Orbitrap-MSn. The quantitative structure-activity relationship (QSAR) models were developed by using five machine learning algorithms, alone or in combination with genetic algorithms for predicting the ADME properties of ARF. The molecular networks and pathways presumably referring to the therapy of ARF on RA were yielded by using common databases and visible software, and the experimental validations of the key targets conducted in vitro. Results: ARF effectively relieved RA in vivo and in vitro. The five optimized QSAR models that were developed showed robustness and predictive ability. The characterized 48 components in ARF had good biological potency. Four key signaling pathways were obtained, which were related to both cytokine signaling and cell immune response. ARF suppressed IL-1ß-induced expression of EGFR, MMP 9, IL2, MAPK14, and KDR in the HFLS-RA . Conclusions: ARF has good druggability and high exploitation potential. Methyl salicylate glycosides and flavonoids play essential roles in attuning RA. ARF may partially attenuate RA by regulating the expression of multi-targets in the inflammation-immune system. These provide valuable information to rationalize ARF and other TC/EMs in the treatment of RA.

Distinguishing ionic and radical mechanisms of hydroxylamine mediated electrocatalytic alcohol oxidation using NO-H bond dissociation energies.

The mechanism of N-oxyl radical catalyzed oxidation is a long-standing scientific problem. In this work, radical or ionic mechanisms in electrocatalytic oxidation of alcohols are discussed on the NO-H bond dissociation energy (BDE) scale. A thermodynamic model was built to outline the range of BDEs for the catalysts that react via the two mechanisms. The N-oxyl radical catalyzed electrocatalytic benzyl alcohol oxidations with NO-H BDEs smaller than 74 kcal mol-1 reacted by an ionic mechanism, and with BDEs greater than 78 kcal mol-1 reacted by a radical mechanism. Oxidizing aliphatic alcohols via a radical mechanism requires catalysts with BDEs even greater than that of N-hydroxyphthalimide (NHPI), and the ionic mechanism requires catalysts with BDEs smaller than 74 kcal mol-1. With either the ionic or radical mechanism, catalysts with larger BDEs correspond to a smaller activation energy of the key step. Future design of N-oxyls with catalytic activity in alcohol oxidation can be streamlined by our efforts.

Landscape of the structure-O-H bond dissociation energy relationship of oximes and hydroxylamines.

The relationship between the homolytic O-H bond dissociation enthalpies (BDEs) and the structures of N-oxyl radical precursors (i.e. hydroxylamines and oximes) is important to predict their reactivity. Yet several crucial facts remain hidden to complete the picture such as the substituent electronic effects on the BDEs of oximes. In this work, the O-H BDEs of 120 hydroxylamines and 120 oximes have been calculated. It was found that the majority of the iminoxyl radicals are σ radicals, except for some π radicals. The resonance effect dominates the electronic effects on the BDEs of oximes, and electron-donating conjugation increases the BDE. However, both the resonance and the inductive effects are important in the BDEs of hydroxylamines; meanwhile, the BDEs increase with the increase of the electron-withdrawing ability of the substituents. Besides, the ΔBDEs of oximes and hydroxylamines with two substituents almost equal the algebraic sum of the ΔBDEs of single substituents. In addition, dipole-dipole repulsion is responsible for the difference in the BDEs of open chain and cyclic acyl hydroxylamines. Although the ring strain affects the N-O bonding property of nitroxide radicals, it has negligible effect on the BDEs of oximes. These new rules provide a complete and precise understanding of the structure-bond energy relationship of N-oxyl radical precursors.

Designing an anion-functionalized fluorescent ionic liquid as an efficient and reversible turn-off sensor for detecting SO2.

A novel anion-functionalized fluorescent ionic liquid was designed and prepared, which was capable of capturing sulphur dioxide with high capacity and could also be used as a good colorimetric and fluorescent SO2 sensor. Compared to conventional fluorescent sensors, this fluorescent ionic liquid did not undergo aggregation-caused quenching or aggregation-induced emission, and the fluorescence was quenched when exposed to SO2, and the fluorescence would quench when exposed to SO2. The experimental absorption, spectroscopic investigation, and quantum chemical calculations indicated that the quenching of the fluorescence originated from SO2 physical absorption, not chemical absorption. Furthermore, this fluorescent ionic liquid exhibited high selectivity, good quantification, and excellent reversibility for SO2 detection, and showed potential for an excellent liquid sensor.

Modification of the Onsager Reaction Field and Its Application on Spectral Parameters.

Solvent polarity is an important solvent property. The Onsager's theory of reaction field was the most classic model to describe solvent effects and was widely used in relating dielectric constant and other solvent polarity parameters. In this study, a modified semi-empirical reaction field was presented to relate electron transition energies or hyperfine coupling constants with the dielectric constants of solvents. In previous work, this relationship was well established by traditional Onsager reaction field for nonhydrogen-bonding systems but failed for hydrogen-bonding systems. In this modified reaction field model, the radius of the field was replaced by that of the primary solvation shell or the molecular fragment rather than that of the probe. In this way, the molecular volume of the solvent which contains information of the molecular size and overall interactions is involved in the reaction field. The 154 sets of electron transition energies and 44 sets of nitrogen isotropic hyperfine coupling constants were used to verify the modified model, indicating it works far better than the traditional model for hydrogen-bonding systems.

Tuning the basicity of ionic liquids for efficient synthesis of alkylidene carbonates from CO2 at atmospheric pressure.

A strategy to achieve the efficient synthesis of alkylidene carbonates from CO2 at atmospheric pressure by tuning the basicity of ionic liquids was developed. Excellent yields were obtained due to basic ionic liquids' dual roles both as absorbents and as activators. The reaction mechanism was investigated through a combination of NMR spectroscopy, controlled experiments and quantum calculations, indicating the importance of a moderate basicity.

Trigeminal Cardiac Reflex Caused by Onyx Embolization of Intracranial Dural Arteriovenous Fistula.

Trigeminocardiac reflex (TCR) is a reflexive response of bradycardia, hypotension and gastric hypermotility which is observed upon mechanical stimulation in the distribution of the trigeminal nerve. Previous articles have described TCR during intracranial operations, ophthalmic surgery, microcompression of the trigeminal ganglion and radiofrequency lesioning of the trigeminal ganglion. TCR may occur during transarterial embolization of dural arteriovenous fistula (DAVF) with Onyx, leading to a significant decrease in heart rate under a standard anesthetic protocol. TCR may also occur due to chemical stimulus of dimethyl sulfoxide (DMSO) in transvenous Onyx embolization of dural cavernous sinus fistula. Slow rate of injection may give DMSO enough time to dissipate in the blood stream which is important for the prevention of toxicity. This report confirms that the reflex was blunted by the anticholinergic effects of atropine and there was no harm to patients if stopped immediately.

Theoretical studies on muti-hydroxyimides as highly efficient catalysts for aerobic oxidation.

N,N-dihydroxypyromellitimide (NDHPI) and N,N',N''-trihydroxyisocyanuric acid (THICA) have been recently demonstrated to act as better carbon-radical-producing catalysts than the popular N-hydroxyphthalimide (NHPI). To gain a mature understanding of these particular catalysts, herein their geometrical, electronic, and thermochemical properties, as well as their catalytic activities, have been systemically investigated by a theoretical analysis. It appears that THICA, unlike NDHPI and NHPI, is unsuitable for solvent-free catalysis or catalysis in aprotic solvents due to its favorable coexistent planar conformer. Besides, the more remarkable catalytic efficiencies of NDHPI and THICA compared to NHPI can be ascribed to the lower barriers and the endothermicity in the H-abstraction processes by their radicals, especially by their multi-radicals which show stronger electron-withdrawing effects. Furthermore, the generation of THICA radicals would be much feasible at high temperature without co-catalysts. This study provides a new perspective towards the rational design of reactive hydroxyimide organocatalysts for industrial applications.