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[Display omitted] The development of stable and efficient heterojunction photocatalysts for wastewater environmental purification exhibits a significant challenge. Herien, a promising binary heterojunction complex comprising boron subphthalocyanine bromide/bismuth oxychloride (SubPc-Br/BiOCl) was successfully synthesized using the hydrothermal method, which involved the self-assembled of SubPc-Br on the surface of BiOCl via intermolecular π-π stacking interactions to compose an electron-transporting layer. The photocatalytic efficiency of SubPc-Br/BiOCl for the degradation of tetracycline and the minocycline exhibited a substantial improvement of 29.14% and 53.72%, respectively, compared to the original BiOCl. Experimental characterization and theoretical calculations elucidated that the enhanced photocatalytic performance of the SubPc-Br/BiOCl composite photocatalysts stemmed from the S-scheme electron transport mechanism at the interface between BiOCl and SubPc-Br supramolecules, which broadened the visible light absorption range, increased the carrier molecular efficiency, and accelerated the carriers. Furthermore, molecular dynamic (MD) simulations provided insights into the action trajectories of the two semiconductors, revealing that the presence of SubPc-Br enhances the water and organic pollutant adsorption capabilities of the BiOCl surface within the supramolecular array system. In conclusion, the synthesis and analysis of the binary heterojunction complex SubPc-Br/BiOCl yield valuable insights into the efficient photocatalytic degradation of antibiotics, holding great promise for diverse environmental applications. [ABSTRACT FROM AUTHOR]

π–π stacking are omnipresent interactions, crucial in many areas of chemistry, and often studied using quantum chemical methods. Here, we report a simple and computationally efficient method of estimating the binding energies of stacked polycyclic aromatic hydrocarbons based on steered molecular dynamics. This method leverages the force field parameters for accurate calculation. The presented results show good agreement with those obtained through DFT at the ωB97X-D3/cc-pVQZ level of theory. It is demonstrated that this force field-driven SMD method can be applied to other aromatic molecules, allowing insight into the complexity of the stacking interactions and, more importantly, reporting π–π stacking energy values with reasonable precision. [ABSTRACT FROM AUTHOR]

The corrosion inhibition of Thymus leptobotrys Murb essential oil (TLMEO) is evaluated for mild steel (M-S) in 1M HCl solution using electrochemical and surface analysis. Results showed that TLMEO acted as a potential corrosion inhibitor and shows the highest inhibition efficiency of 91.7% at 2g/l concentration. Electrochemical studies suggest that TLMEO acted as a mixed- and interface-type of corrosion inhibitor. The TLMEO inhibits metallic corrosion through an adsorption mechanism that follows Langmuir's adsorption isotherm model. The adsorption mechanism of corrosion inhibition was further supported using SEM–EDX, and surface studies. In addition, the anti-corrosion mechanism of the main TLMEO compounds was studied using computational techniques: Density Functional Theory (DFT) and Molecular Dynamics (MD) simulations. Theoretical results were consistent with the experimental findings that were reported. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD. [ABSTRACT FROM AUTHOR]

The corrosion inhibition performance of the corrosion inhibitors is related to their adsorption behavior on the metals' surface, in general, most of researchers focus on the Langmuir adsorption isotherm to deduce physisorption and chemisorption of corrosion inhibitors, however, which experiences a serious argument in recent years. Furthermore, the famous researchers in corrosion field believe that it is wrong to use the Langmuir adsorption isotherm to determine the adsorption behavior of corrosion inhibitors. Simulation methods such as density functional theory (DFT) and molecular dynamics simulation (MD) are treated as effective tools to deeply insight and gain the adsorption behavior of corrosion inhibitors, which can well illustrate the corrosion inhibition mechanism. The quantum chemical parameters obtained from DFT simulation and adsorption energy calculated from MD simulation could well confirm the physisorption or chemisorption states between the corrosion inhibitor and metal surface. Thus, we systematically review the advantages of DFT and MD simulations in analyzing and probing the corrosion inhibition mechanisms of the corrosion inhibitor. [ABSTRACT FROM AUTHOR]

L-Glutathione reduced (GSH) is a small molecule peptide found in large quantities in living organisms, particularly in animal liver cells. Its unique structure gives it great potential to act as an environmentally friendly and efficient corrosion inhibitor. The inhibition properties of GSH for mild steel in simulated concrete pore solutions (SCPS) containing chlorine was investigated by electrochemical tests and SEM-EDS surface analysis. According to the experimental results, GSH mainly blocked the cathodic corrosion reaction and has a corrosion inhibition efficiency of up to 92.3% at room temperature, enhancing the corrosion resistance of mild steel. The isothermal adsorption results indicate that the adsorption behavior of GSH on the surface follows the Langmuir isothermal adsorption model. Both quantum chemical calculations (QC) and molecular dynamics simulations (MD) show that GSH can be effectively adsorbed onto mild steel substrates, thus protecting the surface from erosion. Finally, the results of the above experiments and theoretical calculations are combined to elucidate the inhibitive mechanism: GSH molecules binds to the iron surface via the sulfur, nitrogen and oxygen atoms in the molecule, thus adsorbing to the iron surface in a tiled manner and forming a protective film to prevent the corrosive material from contacting the iron surface. [ABSTRACT FROM AUTHOR]

Background: More is to be explored between dietary patterns and sleep quality in the Chinese adult population. Methods: A cross-sectional study including 7987 Shanghai suburban adults aged 20–74 years was conducted. Dietary information was obtained using a validated food frequency questionnaire. Adherence to a priori dietary patterns, such as the Chinese Healthy Eating Index (CHEI), Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet (MD), was assessed. Sleep quality was assessed from self-reported responses to the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Logistic regression models adjusting for confounders were employed to examine the associations. Results: The overall prevalence of poor sleep (PSQI score ≥ 5) was 28.46%. Factor analysis demonstrated four a posteriori dietary patterns. Participants with a higher CHEI (ORQ4 vs. Q1: 0.81, 95% CI: 0.70–0.95), DASH (ORQ4 vs. Q1: 0.70, 95% CI: 0.60–0.82) or MD (ORQ4 vs. Q1: 0.75, 95% CI: 0.64–0.87) had a lower poor sleep prevalence, while participants with a higher "Beverages" score had a higher poor sleep prevalence (ORQ4 vs. Q1: 1.18, 95% CI: 1.02–1.27). Conclusions: In Shanghai suburban adults, healthier dietary patterns and lower consumption of beverages were associated with better sleep quality. [ABSTRACT FROM AUTHOR]

We investigate the nanometrology of sub-nanometre particle sizes in industrially manufactured sodium silicate liquors at high pH using time-resolved fluorescence anisotropy. Rather than the previous approach of using a single dye label, we investigate and quantify the advantages and limitations of multiplexing two fluorescent dye labels. Rotational times of the non-binding rhodamine B and adsorbing rhodamine 6G dyes are used to independently determine the medium microviscosity and the silicate particle radius, respectively. The anisotropy measurements were performed on the range of samples prepared by diluting the stock solution of silicate to concentrations ranging between 0.2 M and 2 M of NaOH and on the stock solution at different temperatures. Additionally, it was shown that the particle size can also be measured using a single excitation wavelength when both dyes are present in the sample. The recovered average particle size has an upper limit of 7.0 ± 1.2 Å. The obtained results were further verified using small-angle X-ray scattering, with the recovered particle size equal to 6.50 ± 0.08 Å. To disclose the impact of the dye label on the measured complex size, we further investigated the adsorption state of rhodamine 6G on silica nanoparticles using molecular dynamics simulations, which showed that the size contribution is strongly impacted by the size of the nanoparticle of interest. In the case of the higher radius of curvature (less curved) of larger particles, the size contribution of the dye label is below 10%, while in the case of smaller and more curved particles, the contribution increases significantly, which also suggests that the particles of interest might not be perfectly spherical. [ABSTRACT FROM AUTHOR]

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Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity is still not fully understood. Default Mode Network (DMN) areas have been recently demonstrated as selectively involved in sCJD, and functional connectivity has never been investigated in prion diseases. We analyzed the grey matter involvement using a quantitatively multi-parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age-matched healthy controls with a group-wise approach. Differences in mean diffusivity were also examined between the cortical (MM(V)1, MM(V)2C, and VV1) and subcortical (VV2 and MV2K) subgroups of sCJD for those with autopsy data available (n = 27, 73%). We also assessed resting-state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs-fMRI dataset available (n = 17). Decreased diffusivity was predominantly present in posterior cortical regions of the DMN, but also outside of the DMN in temporal areas and in a few limbic and frontal areas, in addition to extensive deep nuclei involvement. Both subcortical and cortical sCJD subgroups showed decreased diffusivity subcortically, whereas only the cortical type expressed significantly decreased diffusivity cortically, mainly in parietal, occipital, and medial-inferior temporal cortices bilaterally. Interestingly, we found abnormally increased connectivity in both dorsal and ventral components of the DMN in sCJD subjects compared with healthy controls. The significance and possible utility of functional imaging as a biomarker for tracking disease progression in prion disease needs to be explored further.

Biological phenomena are chemical reactions, which are inherently non-stopping or “flowing” in nature. Molecular dynamics (MD) is used to analyze the dynamics and energetics of interacting atoms, but it cannot handle chemical reactions involving bond formation and breaking. Quantum mechanics/molecular mechanics (QM/MM) umbrella sampling MD simulations gives us a significant clue about transition states of chemical reactions and their energy levels, which are the pivotal points in understanding the nature of life. To demonstrate the importance of this method, we present here the results of our application of it to the elucidation of the mechanism of chiral-selective aminoacylation of an RNA minihelix considered to be a primitive form of tRNA. The QM/MM MD simulation, for the first time, elucidated the “flowing” atomistic mechanisms of the reaction and indicated that the L-Ala moiety stabilizes the transition state more than D-Ala, resulting in L-Ala preference in the aminoacylation reaction in the RNA. The QM/MM method not only provides important clues to the elucidation of the origin of homochirality of biological systems, but also is expected to become an important tool that will play a critical role in the analysis of biomolecular reactions, combined with the development of artificial intelligence.

PurposeTo assess whether the predictive accuracy of machine learning algorithms using Kalman filtering for forecasting future values of global indices on perimetry can be enhanced by adding global retinal nerve fiber layer (RNFL) data and whether model performance is influenced by the racial composition of the training and testing sets.DesignRetrospective, longitudinal cohort study.ParticipantsPatients with open-angle glaucoma (OAG) or glaucoma suspects enrolled in the African Descent and Glaucoma Evaluation Study or Diagnostic Innovation in Glaucoma Study.MethodsWe developed a Kalman filter (KF) with tonometry and perimetry data (KF-TP) and another KF with tonometry, perimetry, and global RNFL data (KF-TPO), comparing these models with one another and with 2 linear regression (LR) models for predicting mean deviation (MD) and pattern standard deviation values 36 months into the future for patients with OAG and glaucoma suspects. We also compared KF model performance when trained on individuals of European and African descent and tested on patients of the same versus the other race.Main outcome measuresPredictive accuracy (percentage of MD values forecasted within the 95% repeatability interval) differences among the models.ResultsAmong 362 eligible patients, the mean ± standard deviation age at baseline was 71.3 ± 10.4 years; 196 patients (54.1%) were women; 202 patients (55.8%) were of European descent, and 139 (38.4%) were of African descent. Among patients with OAG (n = 296), the predictive accuracy for 36 months in the future was higher for the KF models (73.5% for KF-TP, 71.2% for KF-TPO) than for the LR models (57.5%, 58.0%). Predictive accuracy did not differ significantly between KF-TP and KF-TPO (P = 0.20). If the races of the training and testing set patients were aligned (versus nonaligned), the mean absolute prediction error of future MD improved 0.39 dB for KF-TP and 0.48 dB for KF-TPO.ConclusionsAdding global RNFL data to existing KFs minimally improved their predictive accuracy. Although KFs attained better predictive accuracy when the races of the training and testing sets were aligned, these improvements were modest. These findings will help to guide implementation of KFs in clinical practice.

Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The purpose of this study was to describe non-classical gross lesions observed in broilers and laying hens that suggest the disease emergence and re-emergence. The survey was conducted on 10 broiler and 4 laying hen flocks. All of the dead birds were necropsied in order to obtain a comprehensive diagnosis of lesions, analysing both macroscopic and microscopic alterations. Marek's disease occurred in 80% of cases in broilers and 100% of cases in layer hens. The disease struck 26-day-old broilers and hens at 2 weeks of age, causing a total mortality of 6% and 15%, respectively. There were no clinical indications of the classical neurological form of the disease in either rearing type, and tumour lesions were mostly detected in the liver, spleen, and ovarian follicles in layers, and in the proventriculus in broilers. These findings demonstrated that MD is widespread and that its resurgence is primarily manifested in visceral rather than neurological manifestations. Despite MD immunization, biosecurity remains critical.

Human neutrophil elastase (HNE) plays a crucial role in causing tissue damage in various chronic and inflammatory disorders, making it a target for treating inflammatory diseases. While some inhibitors of HNE’s activity have been identified, only a few have made it to clinical trials. In this study, computational methods were employed to identify potential natural products (NPs) capable of targeting the active site of HNE. The protein–ligand complex has been used to generate a pharmacophore model. A library of 449,008 NPs from the SN3 database was screened against the generated model, resulting in 29,613 NPs that matched the pharmacophore hypothesis. These compounds were docked into the protein active site, resulting in the identification of six promising NPs with better docking scores than the bound ligand to HNE. The top two NPs (SN0338951 and SN0436937) were further evaluated for their interaction stability with HNE through molecular dynamics simulations. Further, the pharmacokinetics and toxicity properties of these compounds were predicted. The results indicated that these two compounds have stable interactions with HNE, as well as, acceptable pharmacokinetic properties. These findings pave the path for further in vitro and in vivo studies of SN0338951 and SN0436937 as promising agents against inflammatory diseases.

Carbohydrate analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we explored the various therapeutic potential of methyl α-D-mannopyranoside (MαDM) analogs, including their ability to synthesize and assess their antibacterial, antifungal, and anticancer properties; additionally, molecular docking, molecular dynamics simulation, and ADMET analysis were performed. The structure of the synthesized MαDM analogs was ascertained by spectroscopic techniques and physicochemical and elemental analysis. In vitro antimicrobial activity was assessed and revealed significant inhibitory effects, particularly against gram-negative bacteria along with the prediction of activity spectra for substances (PASS). Concurrently, MαDM analogs showed good results against antifungal pathogens and exhibited promising anticancer effects in vitro, demonstrating dose-dependent cytotoxicity against Ehrlich ascites carcinoma (EAC) cancer cells while sparing normal cells from compound 5, with an IC50 of 4511.65 µg/mL according to the MTT colorimetric assay. A structure–activity relationship (SAR) study revealed that hexose combined with the acyl chains of decanoyl (C-10) and benzenesulfonyl (C6H5SO2-) had synergistic effects on the bacteria and fungi that were examined. Molecular docking was performed against the Escherichia coli (6KZV) and Candida albicans (1EAG) proteins to acquire insights into the molecular interactions underlying the observed biological activities. The docking results were further supported by 100 ns molecular dynamics simulations, which provided a dynamic view of the stability and flexibility of complexes involving MαDM and its targets. In addition, ADMET analysis was used to evaluate the toxicological and pharmacokinetic profiles. Owing to their promising drug-like properties, these MαDM analogs exhibit potential as prospective therapeutic candidates for future development.

Purpose: The focus on treating patients with Menière's Disease (MD) lies on the reduction of vertigo attacks and the preservation of sensory function. Endolympathic hydrops is considered as an epiphenomenon in MD, which can potentially be altered by endolymphatic sac surgery (ESS). Purpose of the study was to investigate the influences on vertigo control through manipulation of the perilymphatic system with or without ESS. Methods: Retrospective data analysis of 86 consecutive patients with MD according to current diagnostic criteria after endolymphatic sac surgery alone (ESSalone; n = 45), cochlear implantation (CI) alone (CIalone; n = 12), and ESS with CI (ESS + CI; n = 29), treated at a tertiary referral center. Main Outcome Measures: vertigo control, speech perception pre- and postoperatively. Results: Gender, side, and preoperative treatment were similar in all groups. Age was younger in the ESSalone-group with 56.2 ± 13.0 years (CIalone = 64.2 ± 11.4 years; ESS + CI = 63.1 ± 9.7 years). Definitive MD was present in all the CIalone, in 79.3% of the ESS + CI and in 59.6% of the ESSalone-patients. Likewise, vertigo control rate was 100% in the CIalone, 89.7% in the ESS + CI and 66.0% in the ESSalone-group. Conclusions: Vertigo control was improved in all three groups, however, superior in groups treated with CI, potentially contributed by the manipulation of both the endo- and perilymphatic systems. A more systematic characterization of the patients with larger case numbers and documentation of follow up data would be needed to evaluate a clinical effect more properly. [ABSTRACT FROM AUTHOR]

In this study, the corrosion inhibition behavior of N,N'-(1,4-phenylene)bis(1,1-di(pyridin-2-yl) methanimine) (PBDPM) on mild steel in 1 M HCl at 30°C was evaluated under steady conditions. The corrosion inhibitor was synthesized by a one-step method. Electrochemical, energy dispersion spectrum (EDS) and water contact angle results revealed the adsorption behavior of the inhibitor at the metal-solution interface. The adsorption of PBDPM obeys the Langmuir adsorption isotherm. It is obvious that PBDPM exhibits good inhibition performance presumably due to its high surface coverage, as it forms a dense protective film on the surface of mild steel. The adsorption configuration and structure-activity relationships of the inhibitor were also explored theoretically by density functional theory (DFT) and molecular dynamics (MD), and the thermodynamic parameters and molecular active sites (the values of electrophilic attack and nucleophilic attack) were calculated. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection's spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds' physical and chemical features, including molecular dynamic (MD) simulations, protein–ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option. [ABSTRACT FROM AUTHOR]

The primary goal of this study is to discover a sustainable, renewable, and ecologically friendly anticorrosive inhibitor. Anticorrosion analysis of Capsicum annuum fruit extract (CAFE) was examined under hydrodynamic solution at 1500 rpm in 15 % on P110 steel. Results of the assessment showed that CAFE inhibits the corrosion of P110 steel and the rate of corrosion is significantly reduced on increasing its dosing amount. CAFE exhibits the maximum anticorrosive efficiency to 89.5 % (CAFE/800 mg/L) and 92.2 % (CAFE + KI/600 mg/L). The CAFE shows the chemical nature of inhibition effect. The maximum and minimum charge transfer resistance (Rct) and double layer capacitance (Cdl) are 239.5 Ω cm−1 and 27 μF/cm2 with the addition of CAFE indicate the corrosion inhibition mitigation. The corrosion mitigation is caused by the adsorption of CAFE molecules on P110 steel surface via Temkin isotherm with chemical mechanism adsorption. The metal surface appearance was visualized via scanning electron microscopy (SEM), atomic force microscopy (AFM), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). The interaction among the most active constituent i.e., Capsaicin (RCM) sulfate reducing bacteria (SRB) protein was examined by molecular docking. Additionally, an atomic level study of RCM was performed using DFT and MD. [ABSTRACT FROM AUTHOR]

Background: Serious games (SGs) are nonpharmacological interventions that are widely applied among older adults. To date, no evidence has been published regarding the effect of digital SGs on cognitive ability, daily behavioral capacity, or depression in older adults with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Objective: This study aimed to assess the effect of SGs on older adults with AD and MCI by summarizing and pooling the results of previous studies. Methods: This meta-analysis examined the effectiveness of digital SGs in improving cognitive ability, enhancing daily behavioral capacity, and alleviating depression in older adults with AD and MCI. We searched the following databases up to December 31, 2023, to identify relevant high-quality randomized controlled trials (RCTs): PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Stata 15.1 and Review Manager 5.3 were used to screen the 14 studies, extract data, code the data, and perform meta-analysis. Mean differences and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. The Cochrane risk-of-bias assessment tool was used to evaluate the risk of bias. Eligibility criteria were developed in accordance with the Population, Intervention, Comparison, Outcomes, and Study Design framework: (1) population (older adults with AD and MCI), (2) intervention (digital SG intervention), (3) comparison (digital SG intervention vs routine health care), (4) outcomes (cognitive ability, daily behavioral capacity, and depression), and (5) study or research design (RCT). Sensitivity analysis was performed, and a funnel plot was constructed. Results: From January 2017 to December 2023, we enrolled 714 individuals across 14 RCTs, with 374 (52.4%) in the severe game group using digital SGs and 340 (47.6%) in the control group using traditional methods. The results of our meta-analysis indicated that using digital SGs in older adults with AD and MCI is more effective than traditional training methods in several key areas. Specifically, digital SG therapy significantly increased cognitive ability, as found in the Mini-Mental State Examination (SMD 2.11, 95% CI 1.42-2.80; P<.001) and the Montreal Cognitive Assessment (SMD 2.75, 95% CI 1.98-3.51; P<.001), significantly increased daily behavioral capacity (SMD 0.53, 95% CI 0.06-0.99; P=.03), and significantly reduced depression (SMD –2.08, 95% CI –2.94 to –1.22; P<.001) in older adults with AD and MCI. No publication bias was detected based on the results of Begg and Egger tests. Conclusions: Digital SGs offer a viable and effective nonpharmacological approach for older adults with AD and MCI, yielding better results compared to traditional formats. However, caution is warranted in interpreting these findings due to limited RCTs, small sample sizes, and low-quality meta-analyzed evidence. Trial Registration: PROSPERO International Prospective Register of Systematic Reviews: CRDCRD42023486090; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=486090 [ABSTRACT FROM AUTHOR]

In order to develop novel unexplored potential corrosion inhibitors, covalently modified singlewalled carbon nanotubes (SWCNT) via benzoic (--PhCOOH) and aniline (--PhNH2) groups are being investigated as corrosion inhibitors for the first time. Utilizing a comprehensive approach, this study employed density functional theory (DFT), Monte Carlo (MC), and molecular dynamics simulations (MD) to assess the adsorption behavior of modified nanotubes as corrosion inhibitors on the Cu(111) surface within a simulated aqueous HCl corrosion medium. The results provided molecular information on the adsorption capability, geometry adsorption centers, and adsorption energies (Eads) of carbon nanotubes on the surface of Cu(111). The adsorption energy values unveiled robust interactions between SWCNT-- PhCOOH and SWCNT--PhNH2 inhibitors and the Cu(111) surface, suggesting a highly effective corrosion protection mechanism. The calculated Eads values exhibited notable ranges, spanning from --260.82 to --308.18 kcal/mol for SWCNT--PhCOOH and --220.92 to --261.01 kcal/mol for SWCNT--PhNH2 with the maximum probability values, representing the most favorable adsorption scenarios, determined to be --292.96 and --229.39 kcal/mol, respectively. A key insight from Monte Carlo simulations underscored the inherent spontaneity of the adsorption process, corroborated by the consistently negative Eads values. These findings collectively underscore the substantial affinity of the inhibitors to the copper surface, contributing to a deeper comprehension of their corrosion inhibition capabilities. [ABSTRACT FROM AUTHOR]

Both nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulations are routinely used in understanding the conformational space sampled by peptides in the solution state. To investigate the role of single-residue change in the ensemble of conformations sampled by a set of heptapeptides, AEVXEVG with X = L, F, A, or G, comprehensive NMR, and MD simulations were performed. The rationale for selecting the particular model peptides is based on the high variability in the occurrence of tri-peptide E*L between the transmembrane β-barrel (TMB) than in globular proteins. The ensemble of conformations sampled by E*L was compared between the three sets of ensembles derived from NMR spectroscopy, MD simulations with explicit solvent, and the random coil conformations. In addition to the estimation of global determinants such as the radius of gyration of a large sample of structures, the ensembles were analyzed using principal component analysis (PCA). In general, the results suggest that the -EVL- peptide indeed adopts a conformational preference that is distinctly different not only from a random distribution but also from other peptides studied here. The relatively straightforward approach presented herein could help understand the conformational preferences of small peptides in the solution state.

Vibrio cholerae causes life-threatening infections in low-income countries due to the rise of antibacterial resistance. Innovative pharmacological targets have been investigated and carbonic anhydrases (CAs, EC: 4.2.1.1) encoded by V. cholerae (VchCAs) emerged as a valuable option. Recently, we developed a large library of para- and meta-benzenesulfonamides characterised by moieties with a different flexibility degree as CAs inhibitors. Stopped flow-based enzymatic assays showed strong inhibition of VchαCA for this library, while lower affinity was detected against the other isoforms. In particular, cyclic urea 9c emerged for a nanomolar inhibition of VchαCA (KI = 4.7 nM) and high selectivity with respect to human isoenzymes (SI≥ 90). Computational studies revealed the influence of moiety flexibility on inhibitory activity and isoform selectivity and allowed accurate SARs. However, although VchCAs are involved in the bacterium virulence and not in its survival, we evaluated the antibacterial activity of such compounds, resulting in no direct activity. [ABSTRACT FROM AUTHOR]

EPI-X4, an endogenous peptide inhibitor, has exhibited potential as a blocker of CXCR4—a G protein-coupled receptor. This unique inhibitor demonstrates the ability to impede HIV-1 infection and halt CXCR4-dependent processes such as tumor cell migration and invagination. Despite its promising effects, a comprehensive understanding of the interaction between EPI-X4 and CXCR4 under natural conditions remains elusive due to experimental limitations. To bridge this knowledge gap, a simulation approach was undertaken. Approximately 150,000 secondary structures of EPI-X4 were subjected to simulations to identify thermodynamically stable candidates. This simulation process harnessed a self-developed reactive force field operating within the ReaxFF framework. The application of the Two-Phase Thermodynamic methodology to ReaxFF facilitated the derivation of crucial thermodynamic attributes of the EPI-X4 conformers. To deepen insights, an ab initio density functional theory calculation method was employed to assess the electrostatic potentials of the most relevant (i.e., stable) EPI-X4 structures. This analytical endeavor aimed to enhance comprehension of the inhibitor's structural characteristics. As a result of these investigations, predictions were made regarding how EPI-X4 interacts with CXCR4. Two pivotal requirements emerged. Firstly, the spatial conformation of EPI-X4 must align effectively with the CXCR4 receptor protein. Secondly, the functional groups present on the surface of the inhibitor's structure must complement the corresponding features of CXCR4 to induce attraction between the two entities. These predictive outcomes were based on a meticulous analysis of the conformers, conducted in a gaseous environment. Ultimately, this rigorous exploration yielded a suitable EPI-X4 structure that fulfills the spatial and functional prerequisites for interacting with CXCR4, thus potentially shedding light on new avenues for therapeutic development. [ABSTRACT FROM AUTHOR]

Marek’s disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus’s mutagenic potential. The purpose of this study was to describe non-classical gross lesions observed in broilers and laying hens that suggest the disease emergence and re-emergence. The survey was conducted on 10 broiler and 4 laying hen flocks. All of the dead birds were necropsied in order to obtain a comprehensive diagnosis of lesions, analysing both macroscopic and microscopic alterations. Marek’s disease occurred in 80% of cases in broilers and 100% of cases in layer hens. The disease struck 26-day-old broilers and hens at 2 weeks of age, causing a total mortality of 6% and 15%, respectively. There were no clinical indications of the classical neurological form of the disease in either rearing type, and tumour lesions were mostly detected in the liver, spleen, and ovarian follicles in layers, and in the proventriculus in broilers. These findings demonstrated that MD is widespread and that its resurgence is primarily manifested in visceral rather than neurological manifestations. Despite MD immunization, biosecurity remains critical. [ABSTRACT FROM AUTHOR]

The main protease (Mpro) of SARS‐CoV‐2 plays an essential role in the virus life cycle and is considered a key target for therapeutic development. This study explores the inhibition mechanism of SARS‐CoV‐2 Mpro by ebselen, an organoselenium drug that shows potent inhibitory activity. By using a combination of multiple computational methods including molecular docking, molecular dynamics simulations, and density functional theory calculations, the complete covalent inhibition process of ebselen is simulated for the first time. Two possible pathways with different bound conformations of ebselen are identified. The hydrolysis of the enzyme‐ebselen adduct is found to be the rate‐determining step. The simulation results show that the behavior of water molecules at the hydrolysis site is crucial to distinguish the two paths energetically. Our simulations, which are in agreement with existing experimental results, provide a theoretical basis for the rational design and mechanism exploration of ebselen‐based inhibitors. [ABSTRACT FROM AUTHOR]

Recently, non-fullerene-based organic solar cells (OSCs) have made great breakthroughs, and small structural differences can have dramatic impacts on the power conversion efficiency (PCE). We take ITIC and its isomers as examples to study their effects on the performance of OSCs. ITIC and NFBDT only differed in the side chain position, and they were used as models with the same donor molecule, PBDB-T, to investigate the main reasons for the difference in their performance in terms of theoretical methods. In this work, a detailed comparative analysis of the electronic structure, absorption spectra, open circuit voltage and interfacial parameters of the ITIC and NFBDT systems was performed mainly by combining the density functional theory/time-dependent density functional theory and molecular dynamics simulations. The results showed that the lowest excited state of the ITIC molecule possessed a larger ∆q and more hybrid FE/CT states, and PBDB-T/ITIC had more charge separation paths as well as a larger kCS and smaller kCR. The reason for the performance difference between PBDB-T/ITIC and PBDB-T/NFBDT was elucidated, suggesting that ITIC is a superior acceptor based on a slight modulation of the side chain and providing a guiding direction for the design of superior-performing small molecule acceptor materials. [ABSTRACT FROM AUTHOR]

Purpose. This in vitro study compared the vertical marginal discrepancy (MD) and absolute marginal discrepancy (AMD) between the zirconia substructure and titanium (Ti)-base abutment before and after cementation. Material and methods. An intraoral scanner (CEREC Omnicam scanner; Dentsply Sirona) was used to scan the dental model of missing tooth 36 and obtain a three-dimensional virtual model. It was designed and milled for 25 zirconia superstructures (inCoris ZI meso F2 L, Dentsply Sirona). The samples were cemented to Ti bases. The MD and AMD were measured for each sample by using a scanning electron microscope (SEM) before and after cementation. Results. The overall mean values of MD measurements before and after cementation were 14.12 μm and 20.28 μm, respectively. The overall mean values of AMD measurements prior to and after substructure cementation on the Ti base were 54.85 μm and 116.0 μm, respectively. ANOVA revealed significant differences in MD (p = 0.001) and AMD (p < 0.001) before and after cementation. Conclusions. Significant differences were observed in MD and AMD values before and after cementation. The MD and AMD values were significantly lower before cementation than after cementation. The mean MD and AMD values were clinically acceptable. [ABSTRACT FROM AUTHOR]

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Herein, the synthesis and characterization methods of natural deep eutectic solvents based on monoterpenoids have been presented. Low viscous fluids with suitable physicochemical properties are produced. The materials are non-toxic, biodegradable, and cost-effective. Thus, they can be used to develop sustainable solvents for various processes and can find their applications in various fields. A theoretical study based on quantum chemistry and classical molecular dynamics is used for the nanoscopic characterization of structure, dynamics, and hydrogen bonding. The reported results help analyze the properties of this new family of solvents. The required information for developing structure–property relationships for proper solvent design to form a sustainable chemistry framework is obtained.

Shuo Li,&ast; Yiding Xiao,&ast; Yang Wang, Ming Bai, Fengzhou Du, Hailin Zhang Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hailin Zhang, Email hailin_pumc@126.comPurpose: Madelung’s disease (MD) is a rare condition of massive deposits of fat accumulations between superficial and deep fascia at typical locations. There is an absence of systematic studies related to MD in the Chinese cohort. Thus, the objective of the study was to investigate the clinical features of the MD cases in our institution and to explore the clinical variables associated with postoperative recurrence.Materials and Methods: We retrospectively analyzed the clinical information of 21 individuals with MD from 2013 to 2021 enrolled in our institution. The paired t-test and χ2 test were, respectively, used to determine the difference between continuous and classified variables. The univariate Kaplan–Meier analysis by log-rank and multivariate stepwise Cox regression analysis were used to explore variables possibly associated with postoperative recurrence in MD individuals.Results: In the current study, 90.48% of the studied patients were male with a mean age of 48.76 years old. About 61.90% exhibited type I MD. MD patients who experienced postoperative recurrence had a higher age, BMI, incidence of chronic complications, and prevalence of alcoholism than the other MD patients without recurrence (P < 0.05). The univariate Kaplan–Meier analysis by log-rank identified that age, BMI, alcoholism, and comorbidities were influencing factors related with postoperative recurrence (P < 0.05).Conclusion: Demographic characteristics of the 21 studied Chinese cases with MD were generally in accordance with previously published data of other foreign populations. The factors possibly influencing the postoperative recurrence for patients with MD were age, BMI, alcoholism, and a combination of comorbidities. This is the first time that a summarization of clinical characteristics and postoperative recurrence variables of Chinese patients with MD has been reported.Keywords: Madelung’s disease, MD, clinicopathological characteristics, recurrence influencing factors, Kaplan–Meier analysis, Cox proportional hazards regression

In epigenetic mechanisms, DNA methyltransferase 3 alpha (DNMT3A) acts as an initiator for DNA methylation and prevents the downstream genes from expressing. Perturbations of DNMT3A functions may cause uncontrolled gene expression, resulting in pathogenic consequences such as cancers. It is, therefore, vitally important to understand the catalytic process of DNMT3A in its biological macromolecule assembly, viz., heterotetramer: (DNMT3A-3 L)dimer. In this study, we utilized molecular dynamics (MD) simulations, Markov State Models (MSM), and quantum mechanics/molecular mechanics simulations (QM/MM) to investigate the de novo methyl transfer process. We identified the dynamics of the key residues relevant to the insertion of the target cytosine (dC) into the catalytic domain of DNMT3A, and the detailed potential energy surface of the seven-step reaction referring to methyl transfer. Our calculated potential energy barrier (22.51 kcal/mol) approximates the former experimental data (23.12 kcal/mol). The conformational change of the 5-methyl-cytosine (5mC) intermediate was found necessary in forming a four-water chain for the elimination step, which is unique to the other DNMTs. The biological assembly facilitates the creation of such a water chain, and the elimination occurs in an asynchronized mechanism in the two catalytic pockets. We anticipate the findings can enable a better understanding of the general mechanisms of the de novo methyl transfer for fulfilling the key enzymatic functions in epigenetics. And the unique elimination of DNMT3A might ignite novel methods for designing anti-cancer and tumor inhibitors of DNMTs.

Context: In this work, the corrosion inhibitive effect of acetoxime derivative of zinc chloride, (ZnCl2.2HON=C(CH3)2) (ZA), was investigated on mild steel in epoxy/polyamide coating. ZA was used to modify diglycidyl ether of bisphenol A (DGEBA) to yield novel anticorrosive coating (epoxy-ZA) with excellent barrier characteristic. The dispersal of ZA may lead to the formation of Zn–O–C and O–Zn–O linkages in the polymer framework which act as inorganic fillers producing a dense structure of hybrid coating. In electrochemical findings, electrochemical impedance spectroscopy (EIS) and Tafel polarization (TP) indicate higher protection efficiency for epoxy-ZA coatings (99.99 and 99.93 % for EIS and TP, respectively) as compared to others. Using surface analysis and electrochemical data, it was concluded that an inhibition synergy was developed when ZA was taken instead of acetoxime or zinc chloride (ZC) alone in the coating formulation. Methods: Fourier transform infrared (FT-IR) was used to investigate epoxy interaction with zinc compounds and scanning electron microscopy (SEM) was used to investigate morphology of the samples. To reinforce the experimental results, reactivity of crosslinked epoxy and epoxy-ZA coatings with metallic surface was also explored using density functional theory (DFT) with basis set B3LYP/6-311G(d,p) and molecular dynamics (MD) methods by using Forcite module. Modification of epoxy with ZA enhances its interaction with steel surface in dry as well as in wet conditions as indicated by the adhesion energy calculated by MD simulations. [ABSTRACT FROM AUTHOR]

BACKGROUND: 4‐Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS: Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2‐(2‐amino‐4‐(4H‐1,2,4‐triazol‐4‐yl) benzoyl)‐3‐hydroxycyclohex‐2‐en‐1‐one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION: In this study, five compounds were obtained through multiple quantitative structure–activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low‐toxicity HPPD inhibitors. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Allergies are a common and increasing health problem affecting millions of people worldwide. This increase is attributed to genetic predisposition, air pollution, climate change, lack of physical activity, and alterations in eating habits. The Mediterranean diet (MD), which includes a lot of fruits and vegetables, whole grains, legumes, nuts, olive oil, and fish, has been linked to a variety of health benefits, including a lower risk of chronic and allergic disease. This paper explores the effects of the dietary components of the MD on food allergies. Electronic databases PubMed, Scopus, Science Direct, and EBSCO were used to conduct this systematic review. Out of 696 studies initially identified, five human and four animal studies were included. Risk of bias was determined using the Office of Health Assessment and Translation tool. In human studies, when the intervention was given during pregnancy and lactation, a beneficial effect was observed. When the intervention was given during pregnancy and until birth or to the infant for six months, no effect was observed. The animal studies indicated a beneficial effect between the food components of the MD and food allergies. Although the results are promising, the limited number of studies highlights the need for more research. [ABSTRACT FROM AUTHOR]

A systematic in-silico study based on molecular modeling techniques was conducted on thirty 3,4-disubstituted pyrrolidine sulfonamides derivatives to identify the drug candidate for treating schizophrenia and impairments associated with NMDA receptor hypofunction, through selective and competitive inhibition of GlyT1. QSAR analysis demonstrates that geometric and constitutional descriptors have a key function in human GlyT1 activity. The in-silico study concluded that the most active ligand labeled C19 was predicted to be a non-toxic inhibitor, with a desired ADME-Toxicity profile and a significant probability to penetrate the central nervous system (CNS). Molecular docking simulations confirmed that the C19 compound was docked to the active sites of drosophila melanogaster dopamine transporter (DAT) protein, creating a variety of chemical bonds towards TYR 124, ASP 475, GLU 480, ALA 479, and VAL 120 amino acids residues. The molecular dynamic (MD) technique combined with the MMGBSA approach confirmed that produced intermolecular interactions for the (DAT protein–C19 ligand) complex remain so stable during 100 ns of MD simulation time. Consequently, the C19 ligand is highly recommended for the treatment of schizophrenia and other disabilities linked to the hypofunction of glutaminergic NMDA receptors.

Kyasanur Forest Disease virus (KFDV), a neglected human pathogenic virus, is a Flavivirus that causes severe hemorrhagic fever in humans. KFDV is transmitted to humans by the bite of the hard tick (Haemaphysalis spinigera), which acts as a reservoir of KFDV. The recent expansion of the endemic area of KFDV is of concern and requires the development of new preventive measures against KFDV. Currently, there is no antiviral therapy against KFDV, and the existing vaccine has limited efficacy. To develop a new antiviral therapy against KFDV, we focused on the nonstructural proteins NS2B and NS3 of KFDV, which are responsible for serine protease activity. Viral proteases have shown to be suitable therapeutic targets in the development of antiviral drugs against many diseases. However, success has been limited in flaviviruses, mainly because of the important features of the active site, which is flat and highly charged. In this context, the present study focuses on the dynamics of NS2B and NS3 to identify potential allosteric sites in the NS2B/NS3 protease of KDFV. To our knowledge, there are no reports on the dynamics of NS2B and NS3 in KFDV, and the crystal structure of the NS2B/NS3 protease of KFDV has not yet been solved. Overall, we created the structure of the NS2B/NS3 protease of KFDV using AlphaFold and performed molecular dynamics simulations with and without NS2B cofactor to investigate structural rearrangements due to cofactor binding and to identify alternative allosteric sites. The identified allosteric site is promising due to its geometric and physicochemical properties and druggability and can be used for new drug development. The applicability of the proposed allosteric binding sites was verified for the best-hit molecules from the virtual screening and MD simulations. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.