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Identification of promising SARS-CoV-2 main protease inhibitor through molecular docking, dynamics simulation, and ADMET analysis
Abstract The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro. A comprehensive analysis of compounds from the ChemDiv and PubChem databases was performed. The physicochemical properties, pharmacokinetics, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles were evaluated to determine drug similarity and safety. Compound 4896 − 4038 proved to be the most promising candidate. It exhibited a favorable balance between molecular weight (491.06) and lipophilicity (logP 3.957), high intestinal absorption (92.119%), and broad tissue distribution (VDss of 0.529), indicating good oral bioavailability and therapeutic potential. Molecular docking studies showed that 4896 − 4038 has a strong binding affinity to the active site of Mpro and forms key interactions, such as hydrogen bonds, carbon-hydrogen bonds, pi-sulfur, and multiple van der Waals and pi-pi stacked bonds. The binding energy was comparable to that of the reference drug X77, indicating potential efficacy. Molecular dynamics simulations over 300 ns confirmed the stability of the Mpro/4896 − 4038 complex of protein-ligand. Free energy landscape mapping and MM/PBSA calculations further substantiated the favorable binding and stability of the complex. Importantly, 4896 − 4038 exhibited a comparatively favorable safety profile. In summary, compound 4896 − 4038 shows significant potential as a potent SARS-CoV-2 Mpro inhibitor, combining potent inhibitory activity with favorable pharmacokinetic and safety profiles. These results support the further development of 4896 − 4038 as a promising therapeutic agent in the fight against COVID-19 that warrants experimental validation and clinical investigation.
Promoting in-situ stability of hydroxide exchange membranes by thermally conductive network for durable water electrolysis
What emotions does music express? Structure of affect terms in music using iterative crowdsourcing paradigm
Music is assumed to express a wide range of emotions. The vocabulary and structure of affects are typically explored without the context of music in which music is experienced, leading to abstract notions about what affects music may express. In a series of three experiments utilising three separate and iterative association tasks including a contextualisation with typical activities associated with specific music and affect terms, we identified the plausible affect terms and structures to capture the wide range of emotions expressed by music. The first experiment produced a list of frequently nominated affect terms (88 out of 647 candidates), and the second experiment established and confirmed multiple factor structures, ranging from 21, to 14, and 7 dimensions. The third experiment compared the terms with external datasets looking at discrete emotions and emotion dimensions, which verified the 7-factor structure and identified a compact 4-factor structure. These structures of affects expressed by music did not conform to music-induced emotion structures, nor could they be explained by basic emotions or affective circumplex. The established affect structures were largely positive and contained concepts such as “romantic” and “free”, and terms such as “in love”, “dreamy”, and “festive” that have rarely featured in past research.
Detection and genomic characterisation of foot-and-mouth disease virus serotypes circulating in Cameroon using environmental sampling
Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines
Abstract Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N-monoalkylation and reductive amination, suffer from limitations such as poor chemoselectivity and complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the efficient synthesis of α-branched secondary amines. Our method leverages triflic anhydride-mediated semi-reduction of amides to imines, followed by a photochemical radical alkylation step. This approach broadens the synthetic utility of amides, facilitating late-stage modifications of drug-like molecules and the synthesis of saturated N-substituted heterocycles. The pivotal role of flow technology in developing a scalable and robust process underscores the practicality of this method, significantly expanding the organic chemist’s toolbox for complex amine synthesis.
Reliability of artificial intelligence-driven markerless motion capture in gait analyses of healthy adults
The KinaTrax markerless motion capture system, used extensively in the analysis of baseball pitching and hitting, is currently being adapted for use in clinical biomechanics. In clinical and laboratory environments, repeatability is inherent to the quality of any diagnostic tool. The KinaTrax system was assessed on within- and between-session reliability for gait kinematic and spatiotemporal parameters in healthy adults. Nine subjects contributed five trials per session over three sessions to yield 135 unique trials. Each trial was comprised of a single bilateral gait cycle. Ten spatiotemporal parameters for each session were calculated and compared using the intraclass correlation coefficient (ICC), Standard Error of the Measurement (SEM), and minimal detectable change (MDC). In addition, seven kinematic waveforms were assessed from each session and compared using the coefficient of multiple determination (CMD). ICCs for between-session spatiotemporal parameters were lowest for left step time (0.896) and left cadence (0.894). SEMs were 0.018 (s) and 3.593 (steps/min) while MDCs were 0.050 (s) and 9.958 (steps/min). Between-session average CMDs for joint angles were large (0.969) in the sagittal plane, medium (0.554) in the frontal plane, and medium (0.327) in the transverse plane while average CMDs for segment angles were large (0.860), large (0.651), and medium (0.561), respectively. KinaTrax markerless motion capture system provides reliable spatiotemporal measures within and between sessions accompanied by reliable kinematic measures in the sagittal and frontal plane. Considerable strides are necessary to improve methodological comparisons, however, markerless motion capture poses a reliable application for gait analysis within healthy individuals.
A novel RRT*-Connect algorithm for path planning on robotic arm collision avoidance
Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit
Coordinated human-exoskeleton locomotion emerges from regulating virtual energy
Lower-limb exoskeletons have demonstrated great potential for gait rehabilitation in individuals with motor impairments; however, maintaining human-exoskeleton coordination remains a challenge. The coordination problem, referred to as any mismatch or asynchrony between the user’s intended trajectories and exoskeleton desired trajectories, leads to sub-optimal gait performance, particularly for individuals with residual motor ability. Here, we investigate the virtual energy regulator (VER)’s ability to generate coordinated locomotion in lower limb exoskeleton. Contribution: (1) In this paper, we experimented VER on a group of nine healthy individuals at different speeds (0.6 m / s − 0.85 m / s ) to study the resultant gait coordination and naturalness on a large group of users. (2) The resultant assisted gait is compared to the natural and passive (zero-torque exoskeleton) walking conditions in terms of muscle activities, kinematic, spatiotemporal and kinetic measures, and questionnaires. (3) Moreover, we presented the VER’s convergence proof considering the user contribution to the gait and introduced a metric to measure the user’s contribution to gait. (4) We also compared VER performance with the phase-based path controller in terms of muscle effort reduction and joint kinematics using three able-bodied individuals. Results: (1) The results from the VER demonstrate the emergence of natural, coordinated locomotion, resulting in an average muscle effort reduction ranging from 13.1% to 17.7% at different speeds compared to passive walking. (2) The results from VER revealed improvements in all indicators towards natural gait when compared to walking with a zero-torque exoskeleton, for instance, an enhancement in average knee extension ranging from 3.9 to 4.1 degrees. All indicators suggest that the VER preserves natural gait variability and user engagement in locomotion control. (3) Using VER also yields in 13.9%, 15.1%, and 7.0% average muscle effort reduction when compared to the phase-based path controller. (4) Finally, using our proposed metric, we demonstrated that the resultant locomotion limit cycle is a linear combination of human-intended limit cycle and the VER’s limit cycle. These findings may have implications for understanding how the central nervous system controls our locomotion.
Retraction Note: Association between cytochrome P4501A1 (CYP1A1) gene polymorphisms and the risk of renal cell carcinoma: a meta-analysis
Local polar order controls mechanical stress and triggers layer formation in Myxococcus xanthus colonies
Abstract Colonies of the social bacterium Myxococcus xanthus go through a morphological transition from a thin colony of cells to three-dimensional droplet-like fruiting bodies as a strategy to survive starvation. The biological pathways that control the decision to form a fruiting body have been studied extensively. However, the mechanical events that trigger the creation of multiple cell layers and give rise to droplet formation remain poorly understood. By measuring cell orientation, velocity, polarity, and force with cell-scale resolution, we reveal a stochastic local polar order in addition to the more obvious nematic order. Average cell velocity and active force at topological defects agree with predictions from active nematic theory, but their fluctuations are substantially larger than the mean due to polar active forces generated by the self-propelled rod-shaped cells. We find that M. xanthus cells adjust their reversal frequency to tune the magnitude of this local polar order, which in turn controls the mechanical stresses and triggers layer formation in the colonies.
Cohort profile: A prospective cohort study on newlywed couples in rural and poor urban Bangladesh
Sexual and Reproductive Health and Rights (SRHR) aim to enhance quality of life through safe sexual experiences, reproductive autonomy, and protection against gender-based violence. However, existing SRHR research and interventions in low- and middle-income countries like Bangladesh predominantly focus on women, often understating men and neglecting the nuanced contextual issues faced by married couples. This study contributes to filling this gap by examining SRHR dynamics among newlyweds in rural and poor urban areas of Bangladesh, especially focusing on marital satisfaction, fertility preferences, and post-marriage adaptation mechanisms. Employing a prospective cohort design across four Health and Demographic Surveillance Systems (HDSS) managed by icddr,b, the study spans from November 2021 to March 2025, with data collection starting in December 2022. Of the 2011 newlywed couples identified, 666 who met eligibility criteria (married for ≤6 months, first marriage, and no pregnancy history) were enrolled. Participants will undergo six quantitative interview sessions over a two-year period. Additionally, 44 in-depth qualitative interviews were conducted with 22 purposefully selected couples. Demographic data reveal that a significant proportion of husbands (67.3% in rural areas, 71.8% in poor urban areas) are aged 20–29 years, while a majority of wives (67.9% in rural areas, 84.8% in poor urban areas) are adolescents. Education levels varied, with a higher proportion of poor urban husbands lack formal education compared to their rural counterparts (7.2% vs. 3.0%), while no significant variation was observed among wives (0.6% vs 1.0%). Arranged marriages are more common among rural couples (80%) compared to those in poor urban areas (50%). Moreover, poor urban participants tend to marry at a younger age than the rural participants, with poor urban wives marrying earlier than rural wives (60.4% vs 39.7%). This pioneering study provides valuable insights into the SRHR needs of newlywed couples in Bangladesh. The findings will be instrumental for designing targeted interventions aimed at improving SRHR service utilization and enhancing overall well-being, particularly in rural and poor urban areas of the country.
E-cigarettes are not associated with post-acute COVID-19 syndrome among US adults
Densely populated macrocyclic dicobalt sites in ladder polymers for low-overpotential oxygen reduction catalysis
Long-term dynamics of density dependence reveals a more stable effect of the neighborhood on tree growth than tree survival
Density dependence is a vital mechanism for explaining tree species diversity. Empirical studies worldwide have demonstrated that neighbor density influences plant survival and growth in various communities. However, it remains unclear how neighbor density affects plant survival and growth over extended periods. We used data from tree censuses collected every five years from 1981 to 2015 (seven intervals) to assess how density dependence affects adult tree survival and growth by using generalized linear mixed models and the coefficients of variation in Barro Colorado Island plot. Linear regression models were used to assess whether the effects of density dependence on tree survival and growth correlated with species abundance. The results indicated that the effects of tree size (DBH) on tree survival and growth differed across all intervals. We found that the effects of heterospecific neighbor density on tree survival varied over time and consistently had significant negative impacts on tree growth. Conspecific neighbor densities had significant negative effects on tree survival and growth across all intervals. The effect of density dependence on tree growth was more stable than its impact on tree survival. Additionally, the relationship of species abundance and the effect of negative conspecific and heterospecific neighbor densities significantly affected tree growth but not survival, with negative and positive correlations to tree abundance over time, respectively. Our results revealed that neighboring density dependence can predict more accurately of tree growth than survival.
Evaluating survival outcomes and treatment recommendations in resectable gastric cancer
Abstract No consensus exists on the optimal therapy for resectable gastric cancer (GC) and gastroesophageal junction (GEJ) tumors, including the effectiveness of chemoradiotherapy versus perioperative chemotherapy (PC). Our study aimed to compare overall survival (OS) outcomes associated with the recommended treatment modalities for GC and GEJ tumors and evaluate treatment trends from 2010 to 2020. A national registry cohort identified patients with ≥ cT2 nonmetastatic GC and GEJ cancer. Treatment modalities were classified as neoadjuvant chemotherapy (NC), neoadjuvant chemoradiotherapy (NCR), PC, adjuvant chemotherapy (AC), and adjuvant chemoradiation (ACR). Kaplan-Meier curve and multivariable Cox regression models evaluated factors associated with OS. A cohort of 7665 patients were included. Patients who received PC had the highest OS (median 86.80 months, 95% CI 73.40-NE), while chemoradiotherapy in the neoadjuvant and adjuvant settings had worse OS than PC and NC (NCR median 47.15 months, 95% CI 44.58–52.27, and ACR median 52.67 months, 95%CI 42.78–63.93). The Cox proportional hazards model showed that NCR and NC had worse survival than PC (HR 1.74, 95% CI 1.50–2.02, p < 0.001 and HR 1.26, 95% CI 1.10–1.44, p = 0.0008, respectively). Additionally, the most utilized modality during 2020 was NC (35.8%), followed by PC (28.0%) and NCR (24.9%). The utilization of PC and NC had the most substantial rise between 2010 and 2020, increasing by 11.0%. The study demonstrates the association of PC with improved OS outcomes for nonmetastatic GC and GEJ tumors. Therapies combining radiation with chemotherapy and extended lymph node dissection correlated with a worse prognosis compared to PC and NC. Despite the association with improved outcomes, national data reveals low utilization rates for PC.
RNA folding kinetics control riboswitch sensitivity in vivo
Transfer accuracy of partially enclosed single hard vacuum-formed trays with 3D-printed models for lingual bracket indirect bonding: A prospective in-vivo study
Objective This study aims to evaluate the clinical transfer accuracy of partially enclosed single hard vacuum-formed trays based on three-dimensional (3D) printed models for lingual bracket indirect bonding. Materials and methods Thirty-two consecutive patients receiving lingual orthodontic treatment were enrolled. Digital models with ideal bracket positions were 3D-printed, followed by fabrication of partially enclosed single hard vacuum-formed trays. Digital impressions captured actual bracket positions and were compared to the ideal positions. One-tailed t-tests assessed if errors were within clinically acceptable thresholds of 0.5 mm for linear measurements and 2° for angular measurements. Results Mean bracket transfer errors were 0.052 mm, 0.076 mm, 0.106 mm, 0.795°, 1.344°, and 2.485° for mesiodistal, buccolingual, occlusogingival, rotation, tip, and torque, respectively. Transfer errors were statistically below the clinically acceptable thresholds for all dimensions except torque. Frequencies of acceptable transfer errors were 100%, 100%, 99.3%, 93.1%, 78.3%, and 54.0%, respectively. Conclusion Partially enclosed single hard vacuum-formed trays with 3D-printed models transfer lingual brackets with high accuracy in the mesiodistal, buccolingual, and occlusogingival dimensions, rotation, and tip. However, the transfer of torque remains questionable.