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The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets. Here, the authors perform repurposing screens of the ReFRAME drug library in two cell lines and identify inhibitors of SARS-CoV-2 infection. Antiviral activity of prodrug MK-4482 is confirmed in hamsters.

(1) Background: Surgical phases form the basic building blocks for surgical skill assessment, feedback, and teaching. The phase duration itself and its correlation with clinical parameters at diagnosis have not yet been investigated. Novel commercial platforms provide phase indications but have not been assessed for accuracy yet. (2) Methods: We assessed 100 robot-assisted partial nephrectomy videos for phase durations based on previously defined proficiency metrics. We developed an annotation framework and subsequently compared our annotations to an existing commercial solution (Touch Surgery, Medtronic™). We subsequently explored clinical correlations between phase durations and parameters derived from diagnosis and treatment. (3) Results: An objective and uniform phase assessment requires precise definitions derived from an iterative revision process. A comparison to a commercial solution shows large differences in definitions across phases. BMI and the duration of renal tumor identification are positively correlated, as are tumor complexity and both tumor excision and renorrhaphy duration. (4) Conclusions: The surgical phase duration can be correlated with certain clinical outcomes. Further research should investigate whether the retrieved correlations are also clinically meaningful. This requires an increase in dataset sizes and facilitation through intelligent computer vision algorithms. Commercial platforms can facilitate this dataset expansion and help unlock the full potential, provided that the phase annotation details are disclosed.

The Yucatan Peninsula, located in southern Mexico, is a central honey-producing region with extraordinary biodiversity of melliferous plants. Approximately 900 plant species have been described as being a source of nectar and pollen for bees and other pollinators. They provide ecosystem services that help to keep plant biodiversity high and mitigate the effects of climate change. This study aimed to reveal the diversity of the pollen content in honey through a melissopalynological analysis of 22 honey samples collected in February–August 2021 from the north-central area of Campeche, Mexico. The extraction of pollen from the honey was carried out using standard methods for melissopalynological analysis. The honeys were classified by botanical origin to determine their floral sources and a diverse spectrum of 19 pollen types from 13 families was identified. Only eight were predominant: Milleria quinqueflora, Gymnopodium floribundum, Terminalia buceras, Amaranthus spinosus, Zea mays, Talisia floresii, Guazuma ulmifolia, and Croton icche. Our research shows the high quality of the honey analyzed and highlights the diversity and critical role of local melliferous flora and crops in beekeeping development in southern Mexico. The results in this study are useful for confirming the botanical origins of honey, generating information for designing nature conservation and agroecosystem management strategies, and increasing the knowledge of beekeepers in Campeche, Mexico.

The personality trait of openness has been shown to contribute to a person’s ability to function effectively. Additionally, scholars have suggested that openness to experience and foreign language experience were related to music preference. Extending from earlier scholarship, this study examined the relationship between openness to experience and the various types of musical and language experiences reported by undergraduate music majors in Turkey and the United States. Participants (N = 380) were surveyed using the Openness to Experience domain of the NEO-PI-R and an author-designed survey with questions about participants’ musical backgrounds and interests, foreign language abilities, age, and sex. Results showed that U.S. students rated significantly higher in four of the five dimensions of the Openness domain than their Turkish counterparts (Wilks’λ = .57; F(5, 374) = 55.37, p < .001). Factor analysis results showed that (a) experiences in foreign languages, (b) listening to Turkish traditional, pop, and folk music, and (c) listening to American (pop and folk) and Western classical music cumulatively explained 68.49% of the variance in openness. Correlation analyses suggested that listening to Western classical, American folk, and American pop music was associated with higher openness scores, and listening to Turkish traditional, folk, and pop music was associated with lower openness scores. Additionally, the number of foreign languages participants studied correlated with four of the dimensions. Results suggest that both groups could benefit from increased, broader, and deeper exposure to different musical genres from diverse cultures.

Correctly estimating stem diameter at any height is an essential task in determining the profitability of a commercial forest plantation, since the integration of the cross-sectional area along the stem of the trees allows estimating the timber volume. In this study the ability of four artificial intelligence (AI) models to estimate the stem diameter of Tectona grandis was assessed. Genetic Programming (PG), Gaussian Regression Process (PGR), Category Boosting (CatBoost) and Artificial Neural Networks (ANN) models’ ability was evaluated and compared with those of Fang 2000 and Kozak 2004 conventional models. Coefficient of determination (R2), Root Mean Square of Error (RMSE), Mean Error of Bias (MBE) and Mean Absolute Error (MAE) statistical indices were used to evaluate the models’ performance. Goodness of fit criterion of all the models suggests that Kozak’s model shows the best results, closely followed by the ANN model. However, PG, PGR and CatBoost outperformed the Fang model. Artificial intelligence methods can be an effective alternative to describe the shape of the stem in Tectona grandis trees with an excellent accuracy, particularly the ANN and CatBoost models.

Sixteen irrigation treatments were applied on Persian lime, based on the combination of four soil moisture tensions (SMTs) used to define the start of irrigation: −10, −35, −60, and −85 kPa during the phenological stages (PSs) of flowering (FL) and fruiting (FR). Variables evaluated were, among others: leaf water potential (Ψ), leaf stomatal conductance (gs), fruit weight (FW), fruit juice content (FJC), total soluble solids in juice (TSS), fruit yield (FY), and water footprint (WF). Greater values on the Ψ and gs variables were observed in plants subjected to SMTs of −10 and −35 kPa (p < 0.05). The SMT of −85 kPa during FR produced a low FW value, while the lower SMTs in this PS increased it (p < 0.05). FY was greater in the treatments including −10 kPa or −35 kPa during either of the two PSs, with the exception of those with −85 kPa in one of the stages (p < 0.05). Lower FJC values were obtained at a SMT of −85 kPa in FR, and higher TSS values were observed in the two driest treatments (p < 0.05). The smallest WF values were observed in the −60 kPa FL and −60 kPa FR treatment (p ≤ 0.05). Irrigation management based on the SMT significantly affected almost all the response variables evaluated. It is recommended to irrigate the crop at a SMT of −35 kPa in FL and −60 kPa in FR, the treatment in which the greatest FW, FY, and FJC values and the lowest TSS and WF values were obtained (p < 0.05) and in which only 93 L of water was used by the trees to produce one kilogram of fruit (16% of the amount used in the treatment with the largest WF). The use of blue water is limited by its scarcity and high opportunity cost, an aspect that can be mitigated if blue water is used efficiently in Persian lime production systems, based on the results of this study.

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p=0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin (p = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed with biallelic COQ4 mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation COQ4 (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.

This article presents a tangible model used to help students tackle some misconceptions about enzyme actions, particularly the induced-fit model, enzymesubstrate complementarity, and enzyme inhibition. The model can simulate how substrates induce a change in the shape of the active site and the role of attraction force during enzyme—substrate binding. It can also be used to show how noncompetitive inhibitors work differently from competitive inhibitors. In addition, the model allows students to visualize the random collisions between enzymes and substrates. For kinesthetic learners, this tangible model is likely to foster better comprehension of the unobservable enzyme concepts than computer animations. Uses of the model in the classroom are suggested. The model is readily made using simple materials that school teachers can easily acquire, and detailed production tips are provided.

Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy. Aminoadamantane compounds, delivered to cells via binding to viroporin channels, induce S-nitrosylation of the ACE2 protein, inhibiting binding to SARS-CoV-2 spike protein and viral infection.