Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway.

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD's inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

Compound sophora decoction alleviates ulcerative colitis by regulating macrophage polarization through cGAS inhibition: network pharmacology and experimental validation.

INTRODUCTION: Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS: A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS: A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION: We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

Network pharmacology-based research on the effect of Scutellaria baicalensis on osteosarcoma and the underlying mechanism.

To explore the anti-tumor effects of Scutellaria baicalensis on osteosarcoma and its mechanism. Network pharmacology and molecular docking techniques were applied to investigate the effect and mechanism of Scutellaria baicalensis on osteosarcoma (OS). We analyzed the protein-protein interaction (PPI) network for potential targets of Scutellaria baicalensis for treating osteosarcoma and identified hub targets. We used KM curves to screen for hub targets that could effectively prolong the survival time of OS patients. We systematically performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the Scutellaria baicalensis potential targets and predicted the Scutellaria baicalensis molecular mechanism and function in treating osteosarcoma. Through molecular docking, the binding process between the hub targets, which could prolong the survival time of sarcoma patients, and Scutellaria baicalensis was simulated. PPI network analysis of potential therapeutic targets discriminated 12 hub targets. The KM curves of the hub targets showed that upregulation of RXRA, RELA, ESR1, TNF, IL6, IL1B, and RB1 expression, and downregulation of MAPK1, VEGFA, MAPK14, CDK1, and PPARG expression were effective in improving the 5-year survival rate of OS patients. GO and KEGG enrichment demonstrated that Scutellaria baicalensis regulated multiple signaling pathways of OS. Molecular docking results indicated that Scutellaria baicalensis could bind freely to the above hub target, which could prolong the survival time of sarcoma patients. Scutellaria baicalensis acted on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Scutellaria baicalensis appears to have the potential to serve as a therapeutic drug for osteosarcoma and to prolong the survival of OS patients.

Safety comparisons among monoamine oxidase inhibitors against Parkinson's disease using FDA adverse event reporting system.

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.

Exploration on the scientific rationality of low-carbon investment projects from the perspective of supply chain: a case study of CS thermal power plant.

Climate warming has gradually become a major problem threatening human survival, and countries have begun to pay attention to carbon emissions. Energy conservation and emission reduction has become a central task in China's economic development since the 14th Five-Year Plan. As the main force of carbon emissions in China, thermal power industry is bound to become the focus of attention in China's low-carbon development strategy and energy conservation and emission reduction. Moreover, with the marketization of the power industry, the state has joined the market competition at the power generation sectors and the power sale sectors, and implemented the "opening the middle of the two pipes." Therefore, the coverage of influence of carbon emissions and carbon investment behavior of power generation companies is not limited to itself, but will also be extended to the supply chain level. Based on the above background, this paper evaluates the scientific rationality of low-carbon investment projects of thermal power enterprises from the perspective of low-carbon supply chain, which not only can help enterprises achieve a win-win situation of economic and environmental benefits, but also contribute to the carbon emission reduction of the entire supply chain, thereby promoting China's entire social and economic energy conservation and emission reduction work.

DTAmetasa: An R shiny application for meta-analysis of diagnostic test accuracy and sensitivity analysis of publication bias.

Meta-analysis of diagnostic test accuracy (DTA) is a powerful statistical method for synthesizing and evaluating the diagnostic capacity of medical tests and has been extensively used by clinical physicians and healthcare decision-makers. However, publication bias (PB) threatens the validity of meta-analysis of DTA. Some statistical methods have been developed to deal with PB in meta-analysis of DTA, but implementing these methods requires high-level statistical knowledge and programming skill. To assist non-technical users in running most routines in meta-analysis of DTA and handling with PB, we developed an interactive application, DTAmetasa. DTAmetasa is developed as a web-based graphical user interface based on the R shiny framework. It allows users to upload data and conduct meta-analysis of DTA by "point and click" operations. Moreover, DTAmetasa provides the sensitivity analysis of PB and presents the graphical results to evaluate the magnitude of the PB under various publication mechanisms. In this study, we introduce the functionalities of DTAmetasa and use the real-world meta-analysis to show its capacity for dealing with PB.

Numerical Modeling of Transient Flow Characteristics on the Top Surface of a Steel Slab Continuous Casting Strand Using a Large Eddy Simulation Combined with Volume of Fluid Model.

In the current study, the transient flow characteristics on the top surface of a steel slab continuous casting strand were numerically investigated using a large eddy simulation combined with volume of fluid (LES + VOF) model. The validation of numerical simulation was verified via nail board measurement in the industrial continuous casting mold. The effects of casting speed on the top surface level profile and the instantaneous distribution of vortex were discussed. The level variation profile migrated after a period of time, moving from one side of the wide face of the mold to the other. The wave height and transient variation degree of the standing wave increased with an increase in the casting speed. The region near the SEN was more likely to promote the formation of vortices. The vortex generation became easier when the vorticity peaks were concentrated on the outer edge of the low-speed confluence area near the submerged entry nozzle. In addition, the effect of surface velocity on the instantaneous level fluctuation was analyzed. The frequency of level fluctuations was highest at 3~4 mm, and the high-frequency range of velocity fluctuation was 20~60 mm/s at 0.9 m/min casting speed for a 1500 mm × 200 mm caster section. The linear relationship between the level fluctuation and surface velocity magnitude was obtained. The present work aimed at evaluating the dynamic problem of the standing wave at the liquid powder-molten steel interface on the top surface of the mold, which is helpful in optimizing the casting parameters for regular casting practice and improving the quality of the steel slabs.

Simulation of Spatial Distribution of Multi-Size Bubbles in a Slab Continuous-Casting Mold Water Model.

In this paper, a fully coupled large eddy simulation model, including the volume of fluid model, the discrete phase model, the bubble-collision model, and the bubble-breakup model was used to simulate the spatial distribution of multi-size bubbles and its impact on the instantaneous two-phase flow in a slab continuous-casting mold. The influence of the bubble-interaction model on the bubbles' three-dimensional spatial distribution and size distribution, as well as on two-phase flow was discussed. By comparison with the velocity on the meniscus and the average bubble diameter inside a continuous-casting slab water model, the appropriate numerical model was recommended to accurately simulate the two-phase flow and characteristics of discrete bubbles. The submerged entry nozzle and the area around it saw bubble coalescence and breakage more frequently than other areas. The key interaction between the bubbles was their bouncing in the deep region of the mold. In the mold, the average bubble diameter was 0.741 mm, and 44.5% of the total number of bubbles had an approximately average diameter.

Genetic algorithm-based feature selection with manifold learning for cancer classification using microarray data.

BACKGROUND: Microarray data have been widely utilized for cancer classification. The main characteristic of microarray data is "large p and small n" in that data contain a small number of subjects but a large number of genes. It may affect the validity of the classification. Thus, there is a pressing demand of techniques able to select genes relevant to cancer classification. RESULTS: This study proposed a novel feature (gene) selection method, Iso-GA, for cancer classification. Iso-GA hybrids the manifold learning algorithm, Isomap, in the genetic algorithm (GA) to account for the latent nonlinear structure of the gene expression in the microarray data. The Davies-Bouldin index is adopted to evaluate the candidate solutions in Isomap and to avoid the classifier dependency problem. Additionally, a probability-based framework is introduced to reduce the possibility of genes being randomly selected by GA. The performance of Iso-GA was evaluated on eight benchmark microarray datasets of cancers. Iso-GA outperformed other benchmarking gene selection methods, leading to good classification accuracy with fewer critical genes selected. CONCLUSIONS: The proposed Iso-GA method can effectively select fewer but critical genes from microarray data to achieve competitive classification performance.

Migration electric-field assisted electrocoagulation with sponge biochar capacitive electrode for advanced wastewater phosphorus removal.

Migrating electric field-assisted electrocoagulation (MEAEC) is a three-electrode electrochemical system, including waste flour-derived sponge biochar (SBC) as an adsorption electrode for efficient phosphorus removal from wastewater. The SBC was applied in the MEAEC system as a pseudo capacitance electrode with low energy consumption and reached an excellent effluent level (0.12 mg/L) with a 200-s treatment time in 1 mg/L phosphate synthetic wastewater. The SBC adsorption electrode had a total charge capacitance of 1.14 F/g with abundant micropores. Continuous charging and discharging at a constant voltage over 100 cycles demonstrated the excellent durability of the biochar electrodes. The energy demand of SBC-MEAEC was only 0.0058 kWh/m3 for 90% phosphate removal, which was 65% less than that of the control. The use of SBC in the MEAEC system greatly enhanced phosphate removal at low concentrations. In the SBC-MEAEC system, the electro-desorption synchronous electrocoagulation process demonstrated efficient concentration and release of ions after electro-adsorption. These results indicate that MEAEC with an SBC electrode could achieve a high level of phosphate removal with a much lower energy consumption than in previous studies. The recovered concentrated phosphorus flocs also contained fewer metal impurities than those in previous electrochemical approaches. The proposed desorption synchronous electrocoagulation utilizing waste-derived SBC electrodes provides a cost-effective pathway to treat low phosphorous-containing wastewater.

The Efficacy of Golimumab Against Non-Infectious Uveitis: A PRISMA-Compliant Systematic Review and Meta-Analysis.

PURPOSE: In this PRISMA-compliant systematic review and meta-analysis, we aimed to assess the efficacy of golimumab (GOL) against non-infectious uveitis (NIU). METHODS: We included eight articles in the meta-analysis. The primary outcome was inflammation remission. Secondary outcomes were changes in the number of uveitis relapses/attacks, mean best-corrected visual acuity, central macular thickness, and systemic corticosteroid-sparing effects. RESULTS: In total, eight case series with 172 patients (43.6% female) were collected. Patients had 75% (95% CI: 56-87%) of remission; 42% (0.12-0.80) of patients showed improved visual acuity. The average central macular thickness decline was 38 µm (-56.51-18.54). The pooled results showed a significant decrease in the use of systemic corticosteroids. CONCLUSION: This study was limited by the use of non-RCT designs, limited sample sizes for outcomes, and heterogenetic underlying diseases. Our results suggest that GOL is effective against NIU. However, further evidence and analyses are required. (Funding: None; PROSPERO registration: CRD42021266214.).

Cadmium Accumulation in the Goat Liver and Kidney Is Partially Promoted by the Upregulation of Metal Transporter Genes.

Metal transporters, including divalent metal-ion transporter-1 (DMT1), Zrt-/Irt-like protein 8 and 14 (ZIP8 and ZIP14), and ferroportin-1 (FPN1), reportedly participate in cellular cadmium (Cd) uptake, but those in farm animals remain unclarified. This study aimed to examine the growth, plasma biochemical indices, Cd accumulation, and expression of metal transporter genes in the liver, kidney, and muscle of goats exposed to rice paddies contaminated with different levels of Cd. Twenty-four goats were randomly assigned across three dietary treatments: 0.23, 0.63, and 1.07 mg of Cd/kg of dry matter (DM) for 60 days. The results showed that dietary Cd exposure increased (p < 0.05) both Cd accumulation and the mRNA expressions of metal transporter genes (DMT1, ZIP, and FPN1) in the liver and kidney but not in the muscle, suggesting dietary Cd exhibited different deposition rates between goat liver, kidney, and muscle. These outcomes suggest that high levels of dietary Cd stimulated the expression of metal transporter genes and thereby enhanced the uptake and accumulation of Cd in the goat liver and kidney. As such, higher Cd concentrations in the liver and kidney observed with Cd diets could be partly explained by upregulation of metal transport genes expression.

Numerical Modeling of Transient Two-Phase Flow and the Coalescence and Breakup of Bubbles in a Continuous Casting Mold.

The multiphase flow and spatial distribution of bubbles inside a continuous casting (CC) mold is a popular research issue due to its direct impact on the quality of the CC slab. The behavior of bubbles in the mold, and how they coalesce and break apart, have an important influence on the flow pattern and entrapment of bubbles. However, due to the limitations of experiments and measurement methods, it is impossible to directly observe the multiphase flow and bubble distribution during the CC process. Thus, a three-dimensional mathematical model which combined the large eddy simulation (LES) turbulent model, VOF multiphase model, and discrete phase model (DPM) was developed to study the transient two-phase flow and spatial distribution of bubbles in a continuous casting mold. The interaction between the liquid and bubbles and the coalescence, bounce, and breakup of bubbles were considered. The measured meniscus speed and bubble diameter were in good agreement with the measured results. The meniscus speed increased first and then decreased from the nozzle to the narrow face, with a maximum value of 0.07 m/s, and appeared at 1/4 the width of the mold. The current mathematical model successfully predicted the transient asymmetric two-phase flow and completely reproduced the coalescence, bounce, and breakup of bubbles in the mold. The breakup mainly occurred near the bottom of the submerged entry nozzle (SEN) due to the strong turbulent motion of the molten steel after hitting the bottom of the SEN. The average bubble diameter was about 0.6 mm near the nozzle and gradually decreased to 0.05 mm from the nozzle to the narrow face. The larger bubbles floated up near the SEN due to the effect of their greater buoyancy, while the small bubbles were distributed discretely in the entire mold with the action of the molten steel jet. Overall, the bubbles were distributed in a fan shape. The largest concentration of bubbles was in the lower part of the SEN and the upper edge of the SEN outlet.

Safety, efficacy, and cost-effectiveness of insulin degludec U100 versus insulin glargine U300 in adults with type 1 diabetes: a systematic review and indirect treatment comparison.

BACKGROUND: Clinical differences between degludec U100 (Deg-100) and glargine U300 (Gla-300) in type 1 diabetes (T1D) were unknown. AIM: To indirectly compare the safety, efficacy, and cost-effectiveness between Deg-100 and Gla-300 in T1D adults via systematic review. METHOD: Medline, the Cochrane Library, ClinicalTrials.gov, and Google Scholar were searched (October 2021). Randomized controlled trials comparing Deg-100 or Gla-300 vs. glargine U100 in T1D adults (follow-up ≥ 12 weeks) were selected and analyzed using a frequentist network meta-analysis. Cost-effectiveness analysis (CEA) was conducted over a 1-year time horizon from societal perspectives. RESULTS: Nine trials were included. Efficacy analysis suggested that Deg-100 was non-inferior to Gla-300 in reducing HbA1c (MD 0.03 [95% CI - 0.09 to 0.15]; P = 0.60), FPG (MD - 1.12 [- 2.19 to - 0.04]; P = 0.04), and pre-breakfast SMBG (MD - 0.71 [- 1.46 to 0.03]; P = 0.06). Safety analysis suggested that Deg-100 appeared to have lower rates of both severe (HR 0.44 [0.25-0.78]; P = 0.005) and nocturnal severe (HR 0.19 [0.08-0.44]; P < 0.001) hypoglycemia, with lower total (MD - 0.07 [- 0.13 to - 0.01]; P = 0.02) and basal (MD - 0.08 [- 0.12 to - 0.04]; P < 0.001) insulin doses compared with Gla-300. No significant differences were observed for other hypoglycemia outcomes, adverse events, serious adverse events, bolus insulin dose, and body weight. The CEA showed that Deg-100 appeared to be a dominant treatment in Japan (+ 0.0283 QALYs, ¥26,266 [$228] per patient) and the United States (+ 0.0267 QALYs, $986 per patient). CONCLUSION: Low-certainty indirect evidence suggested that Deg-100 appeared to have a favorable reduction in rates of severe hypoglycemia and more cost-effective compared with Gla-300 in T1D adults.

Predicting the side effects of drugs using matrix factorization on spontaneous reporting database.

The severe side effects of some drugs can threaten the lives of patients and financially jeopardize pharmaceutical companies. Computational methods utilizing chemical, biological, and phenotypic features have been used to address this problem by predicting the side effects. Among these methods, the matrix factorization method, which utilizes the side-effect history of different drugs, has yielded promising results. However, approaches that encapsulate all the characteristics of side-effect prediction have not been investigated to date. To address this gap, we applied the logistic matrix factorization algorithm to a database of spontaneous reports to construct a prediction with higher accuracy. We expressed the distinction in the importance of drug-side effect pairs by a weighting strategy and addressed the cold-start problem via an attribute-to-feature mapping method. Consequently, our proposed model improved the prediction accuracy by 2.5% and efficiently handled the cold-start problem. The proposed methodology is expected to benefit applications such as warning systems in clinical settings.

Efficacy and safety among second-generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta-analysis.

We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12 weeks of follow-up comparing efficacy (HbA1c) or safety (hypoglycemia and weight gain) between second-generation basal insulins vs. other basal insulins in T1D adults were included. Bayesian network meta-analyses were used to estimate risk ratio, hazard ratio, and mean difference. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to appraise evidence certainty.Eighteen RCTs (≥ 24 weeks of follow-up) involving 7283 randomized participants were included for main analysis. Moderate to high certainty evidence suggested that second-generation basal insulins showed equivalent HbA1c reduction compared with NPH and first-generation basal insulins. Compared with second-generation basal insulins, low to high certainty evidence suggested that NPH was associated with a higher risk of patients experiencing severe hypoglycemia; NPH and first-generation basal insulins were associated with a higher rate of nocturnal confirmed hypoglycemic events. For the weight gain, glargine U300 was comparable to detemir (low certainty), but degludec U100 was greater than detemir (moderate certainty).In conclusion, second-generation basal insulins maintained equivalent efficacy of glycemic control (moderate to high certainty), with differences in safety (low to high certainty) compared with NPH and first-generation basal insulins during ≥ 24 weeks of follow-up in T1D adults.

Intermolecular Interaction Analyses on SARS-CoV-2 Spike Protein Receptor Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor-Blocking Antibody/Peptide Using Fragment Molecular Orbital Calculation.

The spike glycoprotein (S-protein) mediates SARS-CoV-2 entry via intermolecular interaction with human angiotensin-converting enzyme 2. The receptor binding domain (RBD) of the S-protein has been considered critical for this interaction and acts as the target of numerous neutralizing antibodies and antiviral peptides. This study used the fragment molecular orbital method to analyze the interactions between the RBD and antibodies/peptides and extracted crucial residues that can be used as epitopes. The interactions evaluated as interfragment interaction energy values between the RBD and 12 antibodies/peptides showed a fairly good correlation with the experimental activity pIC50 (R2 = 0.540). Nine residues (T415, K417, Y421, F456, A475, F486, N487, N501, and Y505) were confirmed as being crucial. Pair interaction energy decomposition analyses showed that hydrogen bonds, electrostatic interactions, and π-orbital interactions are important. Our results provide essential information for understanding SARS-CoV-2-antibody/peptide binding and may play roles in future antibody/antiviral drug design.

Knowledge, attitudes, and practices toward COVID-19 among university students in Japan and associated factors: An online cross-sectional survey.

The coronavirus disease (COVID-19) pandemic has greatly altered peoples' daily lives, and it continues spreading as a crucial concern globally. Knowledge, attitudes, and practices (KAP) toward COVID-19 are related to individuals' adherence to government measures. This study evaluated KAP toward COVID-19 among university students in Japan between May 22 and July 16, 2020, via an online questionnaire, and it further investigated the associated determining KAP factors. Among the eligible respondents (n = 362), 52.8% were female, 79.0% were undergraduate students, 32.9% were students whose major university subjects were biology-related, 35.4% were from the capital region, and 83.7% were Japanese. The overall KAP of university students in Japan was high. All respondents (100%) showed they possessed knowledge on avoiding enclosed spaces, crowded areas, and close situations. Most respondents showed a moderate or higher frequency of washing their hands or wearing masks (both at 96.4%). In addition, 68.5% of respondents showed a positive attitude toward early drug administration. In the logistic regressions, gender, major subjects, education level, nationality, residence, and psychological factors (private self-consciousness and extroversion) were associated with knowledge or attitudes toward COVD-19 (p < 0.05). In the logistic and multiple linear regressions, capital regions, high basic knowledge, high information acquisition, correct information explanations contributed positively to preventative action (p < 0.05). Non-capital regions, male gender, non-bio-backgrounds, high public self-consciousness, high advanced knowledge, incorrect information explanations, and high extroversion contributed negatively to self-restraint (p < 0.05). Moreover, self-restraint was decreasing over time. These findings clarify the Japanese university students' KAP and the related factors in the early period of the COVID-19 pandemic, and they may help university managers, experts, and policymakers control the future spread of COVID-19 and other emerging infections.

A Comparison between the Cycloadditions of Allenyl- and Vinyl-Cyclopentanes Using Density Functional Theory and GRRM Program.

Cycloaddition catalyzed by transition metals such as rhodium (I) is an important way to synthesize functionalized molecules in medicinal chemistry. When the reagent has a saturated ring containing more than five carbons (or heavy atoms), the reaction can progress when the compound has an allenyl group, but not for a vinyl group. Here, we constructed two computational models for allenylcyclopentane-alkyne and vinylcyclopentane-alkyne, and obtained their reaction pathways using density functional theory (DFT). From the reaction pathways, we confirmed that the former model has a much lower reaction energy than the latter. We also found that the molecular orbitals of the transition state structure at the rate-controlling step contribute significantly to the difference in reactivity between the two models.