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As known silicon nitride ceramics is considered as a candidate material for inert matrix fuel hosts used for transmutation of minor actinides. Unfortunately, by now very limited data is devoted to investigate of its stability under high energy heavy ion irradiation simulating fission fragment impact. Aim of our present study is a comparative analysis of parameters of latent tracks induced with swift Xe ion irradiation in polycrystalline Si3N4 using molecular dynamic (MD) simulation and high resolution transmission electron microscopy (TEM). Silicon nitride samples were irradiated with 220 MeV xenon ions at room temperature to fluence 5 × 10 11 cm-2 that correspond to ion track non overlapping regime and allows to analyze single ion track regions. The calculated MD and experimental TEM values of track diameter for 220 MeV Xe irradiation are found to be in a good agreement and equal about 2 nm, whereas the threshold ionizing energy loss for track formation predicted by MD is lower than threshold value from TEM measurements (11.5 keV/nm vs 15 keV/nm). The averaging of all presented data gives the threshold energy loss level ∼ 13 ± 2 keV/nm

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus identified as the cause of the coronavirus outbreak in December 2019 (COVID-19). Like all the RNA viruses, SARS-CoV-2 constantly evolves through mutations in its genome, accumulating 1–2 nucleotide changes every month, giving the virus a selective advantage through enhanced transmissibility, greater pathogenicity, and the possibility of circumventing immunity previously acquired by an individual either by natural infection or by vaccination. Several SARS-CoV-2 variants of concern (VoC) have been identified, among which we find Alpha (Lineage B.1.1.7), Beta (Lineage B.1.351), and Gamma (Lineage P.1) variants. Most of the mutations occur in the spike (S) protein, a surface glycoprotein that plays a crucial role in viral infection; the S protein binds the host cell receptor, the angiotensin-converting enzyme of type 2 (ACE2) via the receptor binding domain (RBD) and catalyzes the fusion of the viral membrane with the host cell. In this work, we present the development of a simplified system that would afford to study the change in the SARS-CoV-2 S RBD/ACE2 binding related to the frequent mutations. In particular, we synthesized and studied the structure of short amino acid sequences, mimicking the two proteins’ critical portions. Variations in the residues were easily managed through the one-point alteration of the sequences. Nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopies provide insights into ACE2 and SARS-CoV-2 S RBD structure with its related three variants (Alpha, Beta, and Gamma). Spectroscopy data supported by molecular dynamics lead to the description of an ACE2/RBD binding model in which the effect of a single amino acid mutation in changing the binding of S protein to the ACE2 receptor is predictable.

Although modeling of fractures in solid materials has been within the focus of researchers for decades, a generally applicable and reliable numerical description is still an open topic. The complexity of fracture description hides within its multiscale nature, whereby the nano- and macroscale material behavior often vary significantly, and the transfer between these scales seems to constitute a very challenging task. Thus, in this contribution, we present the possibility of using the framework of self-organized criticality (SOC) as a scale-invariant phenomenon that allows for a physically meaningful connection between the scales. In doing so, we firstly introduce the problem of nanoscale plasticity of amorphous solids using a two-dimensional model network glass. We apply an athermal quasistatic deformation procedure that allows for macroscopic simulation time windows and extracts a power-law distribution regarding the fracture process. Secondly, a macroscale phase-field method (PFM) is applied to simulate fractures in anisotropic viscoelastic materials under quasistatic and dynamic conditions. Together with the fracture width and depth measures during crack propagation, the power-law exponent is discussed to determine whether SOC can be captured using this approach. Numerical examples support the conclusions about the existence/absence of SOC in these models and open the door for a new research topic with PFM for fracture modeling.

Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide (1) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1λ6,2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide (5), which was employed as a key precursor for synthesizing a novel series of small molecules bearing different moieties of monosaccharides, aldehydes, and anhydrides. Potent biological activities were found against Staphylococcus and Escherichia coli, and the results indicated that compounds 6c and 10a were the most active analogs with an inhibition zone diameter of 30–35 mm. In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound 10a was the most potent analog with IC50 values of 7.64 ± 0.01 and 8.66 ± 0.01 µM, respectively. The Petra Orisis Molinspiration (POM) theoretical method was used to calculate the drug score of tested compounds and compare them with their experimental screening data. Theoretical DFT calculations were carried out in a gas phase in a set of B3LYP 6-311G (d,p). Molecular docking studies utilizing the MOE indicated the best binding mode with the highest energy interaction within the binding sites. The molecular docking for Ovcar-3 was carried out on the ovarian cancer protein (3W2S), while the molecular docking for M-14 melanoma was carried out on the melanoma cancer protein (2OPZ). The MD performed about 2ns simulations to validate selected compounds’ theoretical studies.

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.

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.

In this paper, we report high-pressure Raman experiments (0 − 28 GPa) in two different systems, i.e. , linear carbon chains encapsulated by multi-walled (C n @MWCNTs) and double-walled (C n @DWCNTs) carbon nanotubes. By running high-pressure cycles, it is observed basically two changes in the Raman spectra of chains that are the softening and disappearance of C n modes. We attributed the irreversible redshift of the C n band to the coalescence between adjacent chains. On the other hand, the disappearance of the C n band at the onset of the CNT collapse pressure is assigned to the tube-chain cross-linking. This effect appears to be independent of the C n length and the number of walls of the tubes, depending only on the innermost CNT diameter. We show that the pressure to coalesce longer chains is higher than 10 GPa. Density functional theory and molecular dynamics calculations were performed in order to support the interpretation of experimental data. The calculations show an irreversible pressure-induced softening of frequency of the confined linear carbon chain. Furthermore, molecular dynamics calculations showed that coalescence between the shorter chains occurs in a region of lower pressure than that of the longer chains, thus supporting the experimental observations. Our findings shed new light on the understanding of the C n @CNT system stability and pave the way for using high-pressure to obtain ultra-long chains (at lower pressures) and ultra-hard composites (at higher pressures). [Display omitted] [ABSTRACT FROM AUTHOR]

This work provides a molecular-level insight into the structural and dynamical processes of H2SO4/H2O molecules on anatase TiO2 (101) surface using the self-consistent-charge density-functional tight-binding molecular dynamics (SCC-DFTB/MD) method. The structural simulation model has been carried out at a constant temperature of 298.15 K for 20 ps. The integration algorithm used is velocity − verlet with Berendsen thermostat as a temperature controller. As a result, we find that radial distribution function (RDF) analyses exhibit the Ti5c-Os bond showing the highest peak at a distance of 2.02 Å, while the Ti-Ow bond is located at a distance of 2.1 Å. In the analysis of the number of bonds adsorbed on the surface of the titania, it was found that two bonds for Ti-Os and nine bonds for Ti-Ow were observed at the simulation time up to 20 ps. The proposed mechanism of sulfated titania formation is revealed via DFTB calculations. The obtained results suggest that the TiO2 surface is activated at Bronsted acid sites on the metal surface (Ot–Hs). Subsequently, the bisulfate ion is formed when a proton (H+) is lost from a deprotonated sulfuric acid molecule. Furthermore, this work is expected to give some light on the mechanism of sulfated titania formation and may provide some insights into the mechanisms of other superacid catalysts. [ABSTRACT FROM AUTHOR]

In this work, we studied the effects of different reinforcements on a metal matrix composite (MMC) using molecular dynamics (MD) simulations, where graphene was chosen as the two-dimensional (2D) material and diamond was selected as the three-dimensional (3D) material. Sintering and tensile processes were conducted on the MMC models containing reinforcements of various sizes, and the effects of reinforcements with the same surface area were compared. The results indicated that the 2D material was more beneficial for sintering at the heating stage, producing a higher-density structure. The volume of Al atoms fell from 752 to 736 nm3 as the graphene size in the composite system increased. However, a slight increase from 749 to 755 nm3 was observed when the diamond radius was small. Converted to relevant metrics in the experiments, the density of the composite reached 2.84 g/cc with a 3.3 wt.% addition of single-layer graphene (SLG) and 2.87 g/cc with a 15.4 wt.% addition of diamond, and the results were slightly higher than the experimental reports. Both SLG and diamond could reduce the number of arranged Al atoms from 43,550 to approximately 35,000, and bilayer graphene (BLG) with the largest size could further decrease the number of arranged atoms to nearly 30,000, implying that grain refinement could be obtained by increasing the surface area of reinforcements. Considering the scale of these models, the reinforcement size and pore location in the initial structures were deemed to have an impact on the mechanical properties. The composite with the largest proportion of SLG showed an increase of more than 1.6 GPa in tensile strength; however, BLG showed a significant drop of 1.9 GPa when stretched in the normal direction, as the large interlayer space acted as a large hole in tension. The diamond size did not appear to affect the strengthening effects. Nevertheless, the elongation values of composites with graphene were generally 35% higher than the Al-diamond composites. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulation of Al2O3 and Al2O3·2SiO2 at amorphous and liquid states was applied to investigate structural characteristics. The results showed that the first peak of Al-Al pair radial distribution function (PRDF) in Al2O3.2SiO2 (AS2) splits into two peaks at r1 = 2.74 Å (pre-peak) and r2 = 3.16 Å (main peak). This does not appear in AS2 at liquid state as well as in Al2O3 at both states. The origin of the first peak splitting that relates to the existence of number of edge-sharing (ES) bonds is explained in this work. We found that most of the Al and Si atoms are four-coordinated by oxygen atoms in Al2O3 and AS2 at both states to form SiO4 and AlO4 tetrahedra units. Structure of AS2 also exists a significant fraction of AlO3 units and a small one of AlO5 units. Meanwhile, there are a significant fraction of AlO5 units and a small one of AlO3 units in structure of Al2O3. The links between two adjacent SiOx units and between AlOx and SiOx units (x = 3–5) in AS2 at 600 K and 3500 K are mainly corner-sharing (CS) and edge-sharing (ES) bonds. The AlOx units link to each other by CS bonds in Al2O3; meanwhile, the ones link to each other by both CS and ES bonds in AS2. The diffusivity in AS2 liquid is much slower than the one in Al2O3 liquid. The self-diffusion coefficient of individual atomic species is also calculated and discussed in detail. [ABSTRACT FROM AUTHOR]

Forty-four bicyclo ((aryl) methyl) benzamides, acting as glycine transporter type 1 (GlyT1) inhibitors, are developed using molecular modeling techniques. QSAR models generated by multiple linear and non-linear regressions affirm that the biological inhibitory activity against the schizophrenia disease is strongly and significantly correlated with physicochemical, geometrical and topological descriptors, in particular: Hydrogen bond donor, polarizability, surface tension, stretch and torsion energies and topological diameter. According to in silico ADMET properties, the most active ligands (L6, L9, L30, L31 and L37) are the molecules having the highest probability of penetrating the central nervous system (CNS), but the molecule 32 has the highest probability of being absorbed by the gastrointestinal tract. Molecular docking results indicate that Tyr124, Phe43, Phe325, Asp46, Phe319 and Val120 amino acids are the active sites of the dopamine transporter (DAT) membrane protein, in which the most active ligands can inhibit the glycine transporter type 1 (GlyT1). The results of molecular dynamics (MD) simulation revealed that all five inhibitors remained stable in the active sites of the DAT protein during 100 ns, demonstrating their promising role as candidate drugs for the treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Polarons influence decisively the performance of lithium niobate for optical applications. In this work, the formation of (defect) bound polarons in lithium niobate is studied by ab initio molecular dynamics. The calculations show a broad scatter of polaron formation times. Rising temperature increases the share of trajectories with long formation times, which leads to an overall increase of the average formation time with temperature. However, even at elevated temperatures, the average formation time does not exceed the value of 100 femtoseconds, i.e., a value close to the time measured for free, i.e., self-trapped polarons. Analyzing individual trajectories, it is found that the time required for the structural relaxation of the polarons depends sensitively on the excitation of the lithium niobate high-frequency phonon modes and their phase relation. [ABSTRACT FROM AUTHOR]

Amaç: Glokomlu hastalarda optik sinir (OS), optik trakt (OT) ve optik radyasyonda (OR) nörodejenerasyonun tespitinde difüzyon tensör görüntülemenin (DTG) tanı performasını değerlendirmek ve DTG parametreleri ile glokom evresi arasında uyumu belirlemek. Gereç ve Yöntem: Primer açık açılı glokomlu 33 hastanın (17 erkek, 16 kadın, 29-81 yaşında) 65 gözü ve 37 hastalığı bulunmayan gönüllünün 74 gözü çalışmaya dâhil edilmiştir. Tüm çalışmaya katılanlar optik koherens tomografinin de dâhil olduğu tam göz muayenesinden geçirilmiş olup Hodapp-Anderson-Parrish sınıflamasına göre evrelere ayrılmışlardır. 3T cihazla elde edilen görüntülerden otomatik olarak MD ve FA haritaları oluşturularak ortalama difüzivite (MD), fraksiyonel anizotropi (FA), radyal ve aksiyel difüzivite (RD ve AD) ölçümleri yapılmıştır. İstatistik analizi için SPSS kullanılmıştır. p

• Ten 2-substitutedamino-1,3,4-thiadiazoles (4a-4j) were synthesized and evaluated for their antibacterial and anti-urease activities. • Compound 4h was determined as the most potent antibacterial agent. • All the synthesized compounds (IC 50 = 1.732 ± 0.186 - 3.786 ± 0.300 μM) showed higher anti-urease activity than standard drug thiourea (IC 50 = 11.008 ± 0.932 μM). • Compounds 4d , 4h and 4i showed significant inhibitory effects against urease with IC 50 values of 1.981 ± 0.265, 1.732 ± 0.186 and 1.937 ± 0.173 μM, respectively. • In silico molecular docking study showed the critical interactions of compound 4h with the active site of the urease. • Molecular Dynamics simulations were performed to assess the energetic features of the urease in complex with compound 4h. • According to DFT, compounds 4j and 4d (with low ΔE=4.536 eV and 4.629 eV values, respectively) are more chemically reactive than the other compounds. A series of 2-substitutedamino-1,3,4-thiadiazoles (4a-4j) were synthesized starting from various isothiocyanate derivatives. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, and elemental analysis. All compounds were tested for antibacterial activity against Proteus vulgaris (ATCC 7829) via the microbroth dilution technique. Among them, compound 4h emerged as the most potent antibacterial agent with MIC value of 4.1 μM. All synthetic compounds were additionally evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC 50 values in the range of 1.732 ± 0.186 - 3.786 ± 0.300 μM as compared to the standard thiourea (IC 50 = 11.008 ± 0.932 μM). Compounds 4d , 4h and 4i showed significant inhibitory effects with IC 50 values of 1.981 ± 0.265, 1.732 ± 0.186 and 1.937 ± 0.173 μM, respectively. In silico molecular docking study showed the critical interactions of compound 4h with the active site of the urease. According to DFT, compounds 4j and 4d (with low ΔE=4.536 eV and 4.629 eV values, respectively) are more chemically reactive than the other molecules, in which consistent with their inhibitory potentials against the urease enzyme. Molecular Dynamics simulations also were performed to assess the energetic features of the urease in complex with compound 4h. Furthermore, the predicted ADMET characteristics of the compound 4h was calculated using QikProp to gain insights into its pharmacokinetic properties. These newly identified inhibitors of the urease enzyme can serve as leads for further antibacterial drug research and development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel tension–compression device reveals asphalt's asymmetric mechanical properties. • Atomic force microscope and molecular dynamics simulations show lower compressive strength compared to tensile strength. • Tensile stress decreases roughness and increases adhesion; compression has the opposite effect. • Different migration rates of asphalt components change surface morphology under stress. • Findings enhance theoretical support for improved asphalt pavement design and maintenance. Load-induced stress is a one of the major causes of asphalt pavement failure. It is, therefore, necessary to understand the changes in stress on the microscopic mechanical properties of asphalt in improving pavement design. While much research been carried out concerning effects brought about by tensile, the effects that compressive stress would have on the microscopic mechanical properties of asphalt remains less explored. In the current study, a custom-designed tension–compression device was developed and atomic force microscopy (AFM), complemented by molecular dynamics (MD) simulations, to investigate the microscopic properties of asphalt in both undeformed and deformed states. The findings reveal that asphalt exhibits significantly weaker compressive strength compared to tensile strength. Under tensile stress, the various components in asphalt align loosely in the direction of tension, while asphaltenes are affected the least. These changes in apparent morphology reflect different migration rates of the various components. Under compressive stress, the asphalt surface is more compact, and this reduces the area of the "bee" structure. Under varying stress conditions, asphalt exhibits a smoothing of the rough region with an associated loss in adhesion. Specifically, increased tensile strain leads to smoother topography and increased adhesion, while increasing compressive strain has the opposite effect. These results provide valuable theoretical insights for the design and maintenance of more durable asphalt pavements. [ABSTRACT FROM AUTHOR]

Alloy 800H is currently used as structural material in light-water cooled nuclear reactors, and it is also considered as candidate materials for various advanced reactor designs. Under operation, the exposure of alloy 800H to neutron irradiation results in the formation of helium (He), mainly from Ni by the transmutation reaction (n, α). In this work, we present a molecular dynamics (MD) simulation study of the behavior and effects of He on the microstructure and mechanical properties of alloy 800H. Our results show that the population of clusters made of 5 to 9 He atoms is nearly constant throughout the simulation time (10 ns), while the population of larger clusters increases as the simulation time increases. The growth of clusters is controlled by either the dissociation and diffusion of smaller clusters towards nearby larger clusters or the merging of larger clusters initially located nearby to each other. A significant accumulation of He is observed at the grain boundaries (GB), while a depletion zone is found at the neighboring regions. As a result, the density of He cluster is significantly higher at the GBs as compared to the intra-granular regions. The nucleation and growth of He clusters also results in the formation of Frenkel pairs (FP), whose associated self-interstitial atoms (SIA) agglomerate into interstitial clusters in the alloy 800H matrix. As a consequence, dislocation segments, mostly of the Shockley type, are generated in the microstructure, and often located next to He clusters. The combination of the aforementioned defect structures and the high density of He clusters at the GBs results in a substantial degradation of the mechanical properties of alloy 800H single crystal and bicrystals. [ABSTRACT FROM AUTHOR]

• The article describes the synthesis, characterization, molecular docking, and quantum computational studies of the novel compound. • Hirshfeld surface analysis, molecular electrostatic potential, molecular docking are studied in detail. • DFT calculations are performed to optimize the molecular geometry. • HOMO, LUMO frontier molecular orbitals are analyzed. • The compound was investigated as an inhibitor for SARS CoV-2 protease using in-silico molecular docking analysis. The novel series of hydrazones carrying both pyrazole and triazole moiety were synthesized and characterized using single crystal X-ray diffraction studies. It is found that the compound crystallizes in the triclinic system in the space group P1̅. Hirshfeld analysis was carried out to visualize the noncovalent intermolecular interactions which are responsible for molecular packing in the crystal. Further, density functional theory (DFT) calculations were used to calculate optimized molecular structure, stability, and a few of the quantum chemical parameters. Derived results are in good agreement with the experimentally obtained results. Analysis of frontier molecular orbitals (HOMO and LUMO) and their energy gap of the optimized structure revealed that the compound is stable in the gaseous state. Molecular electron densities, and electrostatic potential maps provide the reactive site and charge distribution of triazole group. Quantum theory of atoms in molecules (QTAIM) and reduced density gradient (RDG) analysis were carried out to explore the weak interactions present in the molecule. In addition, the synthesized compound was investigated as an inhibitor for SARS CoV-2 protease using in-silico molecular docking analysis to understand the mode of binding. The docking results showed the good binding score with Mpro protease 6LU7. Further, molecular dynamics (MD) were carried out for the best hit docked complexes. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to determine whether racial/ethnic differences in psychosocial measures, independent of economic status, exist among a large population of pregnant nulliparas. Methods Between October 2010 and September 2013, nulliparous women at eight U.S. medical centers were followed longitudinally during pregnancy and completed validated instruments to quantify several psychosocial domains: Cohen Perceived Stress Scale, trait subscale of the Spielberger Anxiety Inventory, Connor-Davidson Resilience Scale, Multidimensional Scale of Perceived Social Support, Krieger Racism Scale, Edinburgh Postnatal Depression Scale, and the Pregnancy Experience Scale. Scores were stratified and compared by self-reported race, ethnicity, and income. Results Complete data were available for 8,128 of the 10,038 women enrolled in the study. For all measures, race and ethnicity were significantly associated (p  0.05) except on the Krieger racism survey and the Edinburgh depression survey, which were exacerbated among NHB women with higher income (interaction, p

Objective:To compare tractional anisotropy (FA) and mean diffusivity (MD) values obtained from corpus callosum (CC), basal ganglion, thalamus, frontal and parietal white matter in NF1 patients compared to the control group and to investigate the correlation with CC volume.Methods:Thirty three cases diagnosed with NF1 and 21 healthy control groups were included in the study. CC volume was measured in both groups. Using tensor imaging (DTI), MD and FA values were calculated from CC genu and splenium, globus pallidum, caudate nucleus, putamen, thalamus, parietal and frontal white matter.Results:CC volume increased significantly in cases with NF1. There was a significant difference in MD and FA values obtained from CC genu and splenium compared to the control group. MD values obtained from frontal and parietal white matter, globus pallidum, putamen, thalamus and caudate nucleus were significantly higher than the control group. FA values decreased in caudate nucleus and putamen while FA values in globus pallidum were higher than control group. There was a negative correlation between CC volume and MD values obtained from KK splenium, putamen, thalamus and caudate nucleus.Conclusion:Increased MD in areas of involvement in NF1 cases can be explained by impaired myelination and demyelination. Heterogeneity in FA values suggests that it is caused by microstructural differences resulting from the breakdown of myelin sheaths or axonal disruption in different locations of the brain. In cases with NF1, DTI findings will help us to understand the occurrence of the disease and the physiopathology of clinical findings in more detail.

As the intersecting line of three grain boundaries (GBs), triple line is in non-equilibrium state with large stress concentration and extra energy, which makes it the optimal site for twin nucleation. However, it is very difficult to verify this conjecture by direct experiments, so no one has done it so far. In present work, we try to use molecular dynamics (MD) simulation on nanocrystalline Cu to confirm such hypothesis. We found that 25 out of 28 twins were emitted from triple lines. The related atomic micro-mechanism has been analysed. Stress relaxation and energy reduction were considered to be the driving factors for twinning from triple lines. This could be proved by changes of dihedral angles, relative GB energy sum, average atomic von Mises shear stress and average atomic energy. Experimentally, the transmission Kikuchi diffraction (TKD) characterization on nanocrystalline Cu revealed that the fraction of the triple junction-twin intersection was 81.7% in all twinned nanograins. The underestimation of experimental results might be caused by invisible triple lines in the orientation mapping.

Membrane distillation is an emerging promising desalination method that requires further improvement in order to become industrially viable. Due to the fact that evaporation is the primary process in membrane distillation, one strategy to boost membrane permeate flux is to optimize the energy supply to the water interface by increasing mixing in the hot channel via the use of optimized spacers. Contemporary spacer designs predominantly induce turbulence, resulting in elevated pumping energy requirements. This study introduces novel spacer geometries, inspired by industrial mixer designs, to surmount the limitations of conventional spacer configurations. The mixing efficiency, thermal performance, and pressure drop induced by the two novel geometries are studied and compared to those of commonly utilized spacer designs. It is confirmed, that the first of these novel geometries significantly enhances mixing, whereas the other causes a lower pressure drop and appears to be a viable solution when a spacer is a necessary structural component. In the course of the analysis, it is also shown that the coefficient of variation coupled with the Nusselt number at the membrane can be used to assess spacers' performance. • CFD simulation of a channel filled with spacers in MD systems. • Spacer geometry effect on the mixing performance and heat transfer. • Mixer geometry spacers exhibit a pronounced ability to enhance flow turbulence effectively. • Spiral geometry spacers show minimal pressure drop, requiring less pumping power. [ABSTRACT FROM AUTHOR]

Prediction of dislocation depth during ultra-precision grinding of monocrystalline silicon is a major challenge. To provide atomistic perspective, a single grain scratching molecular dynamics (MD) model of monocrystalline silicon is established to analyze the initiation and slip mechanism of dislocation. The simulation results show that the initiation of dislocations depends on the normal scratching force, and the dislocation length decreases with the decrease of scratching force and the increase of scratching velocity. Besides, the active slip system was identified by calculating Schmid factor, and the slip stress τ (111) [110],p (i.e. Peierls stress) of 2 GPa for ±1/2[110] dislocation on (1 1 ‾ 1) plane was obtained. Furthermore, a prediction model for dislocation depth was established based on the analysis of shear stress τ (111) [110]. Finally, a set of nano-scratch experiments were carried out, and the depth and slip direction of dislocation that close to the predicted were obtained by TEM method. This study provides a new method for predicting and controlling dislocation damage of monocrystalline silicon during ultra-precision grinding. [Display omitted] • The initiation of dislocations depends on the normal scratching force. • The slip stress τ (1-11)[110],p (i.e. Peierls stress) of ±1/2[110] dislocation in (1 1 ‾ 1) plane was obtained. • A prediction model for dislocation depth was established based on the analysis of shear stress τ (1 1 ‾ 1) [110] in slip system. • The depth and slip direction of dislocation that close to the predicted results were obtained by TEM method. [ABSTRACT FROM AUTHOR]

This study employs molecular dynamics (MD) simulations with Stillinger-Weber (SW) and Embedded Atom Method (EAM) potentials to investigate the tribological behavior of WS 2 coatings on a copper substrate against spherical alumina indenter. Various loads, rotational speeds, and temperatures are explored to analyze their effects on tribological properties. The investigation reveals compelling insights: load-dependent frictional behavior, elucidation of non-linear stress patterns with rotational speeds, and the discernment of temperature-induced alterations in friction coefficient. Furthermore, through detailed analysis utilizing Radial Distribution Function (RDF) methodology, molecular rearrangement dynamics are unveiled, enriching our understanding of the WS 2 -copper interplay. This research contributes to understanding the intricate dynamics of WS 2 coatings and copper interactions, crucial for optimizing tribological performance in practical applications. • MD simulations elucidated tribological behavior of WS 2 coatings on copper substrates under varied loads, speeds, and temperatures. • Increasing applied loads lead to higher frictional forces and coefficient. • Non-linear relationship was observed between rotational speeds and stress distribution. • Ambient temperatures impact friction performance via thermal effects. • The analysis of the microscopic information in the friction process provides a new insight into the mechanism of friction interaction under different conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rotational potential barriers were estimated for water, acetone, THF, chloroform, benzene and toluene. • Greenish patches indicate weak hydrogen bonds in both gas and solvent phases on the RDG plot, reflecting frail connections. • Gas phase, Polar and non-polar solvents are used to investigate the electronic solvation properties. • Drug- Receptor interactions were conveyed through molecular docking investigations. The potential antiallergic compound bendiocarb was studied theoretically by polar and non-polar (six) solvents (IEFPCM model) by quantum chemical DFT calculations. Rotational potential barriers were estimated for water, acetone, THF, chloroform, benzene, and toluene are 12.62, 12.45, 12.55, 12.69, 12.74 and 12.57 kJ/mol. Analysis was done on the variations in geometries brought about by the electronegative atom's replacement as well as the intramolecular interactions caused by the benzodioxol ring. NBO analysis as well as geometrical equilibrium have been performed using DFT employing the B3LYP technique with the 6-311G++(d, p) basis set. In vibrational analysis, CH stretching of bendiocarb was theoretically estimated within 3207–3181 cm−1 (gas), 3207–3184 cm−1 (acetone and water), 3207–3182 cm−1 (benzene and toluene), and 3207–3183 cm−1 (chloroform and THF) due to CN vibrations is challenging because of the overlapping and appearance of multiple bands in similar regions. Energy gaps for Bendiocarb in different solvents for water (5.719 eV), acetone (5.716 eV), THF (5.722 eV), chloroform (5.724 eV), benzene (5.731 eV), toluene (5.730 eV), and gas phase (5.746 eV). Lipinski's rule of five was exploited to guide research on drug similarity and oral action. Using docking simulation against the antiallergic protein, a binding energy of −5.22 kcal/mol, 4P5M has been examined. The protein 4P5M exhibits variations between 0.12 and 0.155 nm for RMSD in molecular dynamic simulation. One can infer information about the pharmacokinetic features of the target molecule from its drug similarity, absorption, distribution, metabolism, excretion, and toxicity properties. [ABSTRACT FROM AUTHOR]

When using HCl to remove oxidation from metal surfaces, there is a risk of significant corrosion to the metal substrate. As a common industrial practice, organic or polymer coatings in corrosive environments protect metals from corrosion by providing a barrier on the metal surface within the corrosive medium. However, the limited solubility of polymers in aqueous corrosive mediums restricts their effectiveness. Herein, a highly water-soluble polyfluorene derivative, Poly(9,9-bis{3′-[(N , N -dimethyl)- N -ethylammonium}-propyl]-2,7-fluorene dibromide) (PFDN-Br), was synthesized as a HCl corrosion inhibitor to solve the corrosion problem of Q235 steel. The protective performance of the synthesized coatings was evaluated through electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) curves. The results of electrochemical testing demonstrate that the addition of PFDN-Br significantly reduces the corrosion rate of mild steel compared to the results without PFDN-Br. The average inhibition efficiency is 92.7 %. Additionally, the results of PDP indicate that PFDN-Br acts as a mixed-type corrosion inhibitor, with its adsorption on the surface of carbon steel following the Langmuir adsorption isotherm model. Quantum chemistry calculations (QC) and molecular dynamics simulations (MD) were employed to investigate the interaction mechanism between PFDN-Br and the surface. The excellent inhibitory performance of PFDN-Br may be attributed to its high-density side chains. This study provides insights into the development of polymer coatings with high water solubility and superior corrosion resistance. • Synthesized a highly water-soluble cationic Polyfluorene PFDN-Br. • PFDN-Br coating protects metals from acid corrosion. • After 10 h of immersion, PFDN-Br maintains a corrosion inhibition rate of 93 %. • The adsorption mechanism of PFDN-Br was elucidated through theoretical calculations. [ABSTRACT FROM AUTHOR]

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 IC 50 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 (C 6 H 5 SO 2 -) 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. [ABSTRACT FROM AUTHOR]

Phosphatase and tensin homologue (PTEN) and SH2-containing inositol 5′-phosphatase 2 (SHIP2) are structurally and functionally similar. They both consist of a phosphatase (Ptase) domain and an adjacent C2 domain, and both proteins dephosphorylate phosphoinositol-tri(3,4,5)phosphate, PI(3,4,5)P3; PTEN at the 3-phophate and SHIP2 at the 5-phosphate. Therefore, they play pivotal roles in the PI3K/Akt pathway. Here, we investigate the role of the C2 domain in membrane interactions of PTEN and SHIP2, using molecular dynamics simulations and free energy calculations. It is generally accepted that for PTEN, the C2 domain interacts strongly with anionic lipids and therefore significantly contributes to membrane recruitment. In contrast, for the C2 domain in SHIP2, we previously found much weaker binding affinity for anionic membranes. Our simulations confirm the membrane anchor role of the C2 domain in PTEN, as well as its necessity for the Ptase domain in gaining its productive membrane-binding conformation. In contrast, we identified that the C2 domain in SHIP2 undertakes neither of these roles, which are generally proposed for C2 domains. Our data support a model in which the main role of the C2 domain in SHIP2 is to introduce allosteric interdomain changes that enhance catalytic activity of the Ptase domain.

Favipiravir (FP) and Ebselen (EB) belong to a broad range of antiviral drugs that have shown active potential as medications against many viruses. Employing molecular dynamics simulations and machine learning (ML) combined with van der Waals density functional theory, we have uncovered the binding characteristics of these two antiviral drugs on a phosphorene nanocarrier. Herein, by using four different machine learning models (i.e., Bagged Trees, Gaussian Process Regression (GPR), Support Vector Regression (SVR), and Regression Trees (RT)), the Hamiltonian and the interaction energy of antiviral molecules in a phosphorene monolayer are trained in an appropriate way. However, training efficient and accurate models for approximating the density functional theory (DFT) is the final step in using ML to aid in the design of new drugs. To improve the prediction accuracy, the Bayesian optimization approach has been employed to optimize the GPR, SVR, RT, and BT models. Results revealed that the GPR model obtained superior prediction performance with an R2 of 0.9649, indicating that it can explain 96.49% of the data’s variability. Then, by means of DFT calculations, we examine the interaction characteristics and thermodynamic properties in a vacuum and a continuum solvent interface. These results illustrate that the hybrid drug is an enabled, functionalized 2D complex with vigorous thermostability. The change in Gibbs free energy at different surface charges and temperatures implies that the FP and EB molecules are allowed to adsorb from the gas phase onto the 2D monolayer at different pH conditions and high temperatures. The results reveal a valuable antiviral drug therapy loaded by 2D biomaterials that may possibly open a new way of auto-treating different diseases, such as SARS-CoV, in primary terms.

As a member of the class I PI3K family, phosphoinositide 3-kinase δ (PI3Kδ) is an important signaling biomolecule that controls immune cell differentiation, proliferation, migration, and survival. It also represents a potential and promising therapeutic approach for the management of numerous inflammatory and autoimmune diseases. We designed and assessed the biological activity of new fluorinated analogues of CPL302415, taking into account the therapeutic potential of our selective PI3K inhibitor and fluorine introduction as one of the most frequently used modifications of a lead compound to further improve its biological activity. In this paper, we compare and evaluate the accuracy of our previously described and validated in silico workflow with that of the standard (rigid) molecular docking approach. The findings demonstrated that a properly fitted catalytic (binding) pocket for our chemical cores at the induced-fit docking (IFD) and molecular dynamics (MD) stages, along with QM-derived atomic charges, can be used for activity prediction to better distinguish between active and inactive molecules. Moreover, the standard approach seems to be insufficient to score the halogenated derivatives due to the fixed atomic charges, which do not consider the response and indictive effects caused by fluorine. The proposed computational workflow provides a computational tool for the rational design of novel halogenated drugs.

Aminoacylation of a primordial RNA minihelix composed of D-ribose shows L-amino acid preference over D-amino acid without any ribozymes or enzymes. This preference in the amino acylation reaction likely plays an important role in the establishment of homochirality in L-amino acid in modern proteins. However, molecular mechanisms of the chiral selective reaction remain unsolved mainly because of difficulty in direct observation of the reaction at the molecular scale by experiments. For seeking a possible mechanism of the chiral selectivity, quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics (MD) simulations of the aminoacylation reactions in a modeled RNA were performed to investigate differences in their free-energy profiles along the reactions for L- and D-alanine and its physicochemical origin. The reaction is initiated by approaching a 3′-oxygen of the RNA minihelix to the carbonyl carbon of an aminoacyl phosphate oligonucleotide. The QM/MM umbrella sampling MD calculations showed that the height of the free-energy barrier for L-alanine aminoacylation reaction was 17 kcal/mol, which was 9 kcal/mol lower than that for the D-alanine system. At the transition state, the distance between the negatively charged 3′-oxygen and the positively charged amino group of L-alanine was shorter than that of D-alanine, which was caused by the chirality difference of the amino acid. These results indicate that the transition state for L-alanine is more electrostatically stabilized than that for D-alanine, which would be a plausible mechanism previously unexplained for chiral selectivity in the RNA minihelix aminoacylation.

Neurofibromin, the main RasGAP in the nervous system, is a 2818 aa protein with several poorly characterized functional domains. Mutations in the NF1-encoding gene lead to an autosomal dominant syndrome, neurofibromatosis, with an incidence of 1 out of 3000 newborns. Missense mutations spread in the Sec14-PH-encoding sequences as well. Structural data could not highlight the defect in mutant Sec14-PH functionality. By performing molecular dynamics simulations at different temperatures, we found that the lid-lock is fundamental for the structural interdependence of the NF1 bipartite Sec14-PH domain. In fact, increased flexibility in the lid-lock loop, observed for the K1750Δ mutant, leads to disconnection of the two subdomains and can affect the stability of the Sec14 subdomain. [ABSTRACT FROM AUTHOR]

Cognitive aging, especially cognitive control, and processing speed aging have been well-documented in the literature. Most of the evidence was reported based on cross-sectional data, in which inter-individual age effects were shown. However, there have been some studies pointing out the possibility of overlooking intra-individual changes in cognitive aging. To systematically examine whether age-related differences and age-related changes might yield distinctive patterns, this study directly compared cognitive control function and processing speed between different cohorts versus follow-up changes across the adult lifespan. Moreover, considering that cognitive aging has been attributed to brain disconnection in white matter (WM) integrity, this study focused on WM integrity via acquiring diffusion-weighted imaging data with an MRI instrument that are further fitted to a diffusion tensor model (i.e., DTI) to detect water diffusion directionality (i.e., fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity, AxD). Following data preprocessing, 114 participants remained for further analyses in which they completed the two follow-up sessions (with a range of 1–2 years) containing a series of neuropsychology instruments and computerized cognitive control tasks. The results show that many significant correlations between age and cognitive control functions originally shown on cross-sectional data no longer exist on the longitudinal data. The current longitudinal data show that MD, RD, and AxD (especially in the association fibers of anterior thalamic radiation) are more strongly correlated to follow-up aging processes, suggesting that axonal/myelin damage is a more robust phenomenon for observing intra-individual aging processes. Moreover, processing speed appears to be the most prominent cognitive function to reflect DTI-related age (cross-sectional) and aging (longitudinal) effects. Finally, converging the results from regression analyses and mediation models, MD, RD, and AxD appear to be the representative DTI measures to reveal age-related changes in processing speed. To conclude, the current results provide new insights to which indicator of WM integrity and which type of cognitive changes are most representative (i.e., potentially to be neuroimaging biomarkers) to reflect intra-individual cognitive aging processes. [ABSTRACT FROM AUTHOR]

Melanocytic tumors are a type of cancer that is most commonly found on the skin. The melanoma prevalence rate has risen dramatically over the last 50 years. As a result, the discovery of new therapeutic agents is critical. The BRAF kinase is one of the receptors involved in cell apoptosis. Dabrafenib is a selective BRAF inhibitor with common side effects such as rash, photosensitivity, and hyperkeratosis. Meanwhile, Acalypha indica is a plant that has been widely reported as a source of antiproliferative and proapoptotic compounds. However, the phytochemicals in A. indica that play an important role in melanocytic tumors have yet to be discovered. Molecular docking is a structure-based drug design method that is used to identify potential hits during the drug discovery process. The aims of this study are to obtain candidate lead compounds for BRAF kinase based on binding mode interaction and binding stability by using AutoDock 4.2 and GROMACS 2019.6, respectively, for molecular docking and molecular dynamics (MD). The native ligand, SM5, has estimated free energy of binding and an inhibitory constant of -5.93 kcal/mol and 45.30 µM, respectively. 2-Methyl anthraquinone, chrysin, stigmasterol, and γ-sitosterol have higher binding energy, with an estimated free energy of binding of -6.24, -6.67, -6.35, and -6.14 kcal/mol, respectively. According to the MD simulation, stigmasterol and γ-sitosterol will be more effective at stabilizing the 6XFP complex during 100 ns. Finally, stigmasterol and γ-sitosterol are potential lead compounds as BRAF inhibitors. [ABSTRACT FROM AUTHOR]

The powder metallurgy process of the Al–graphene system is conducted by molecular dynamics (MD) simulations to investigate the role of graphene. During the sintering process, graphene is considered to reduce the pore size and metal grain size based on the volume change and atomic configuration of the Al parts in the composite. Compared with the pure Al system, the space occupied by the same number of Al atoms in the sintered composite is 15–20 nm3 smaller, and the sintered composite has about 5000 fewer arranged atoms. Because these models are carefully designed to avoid a serious deformation of graphene in the tension of sandwich-like composite models, the strengthening mechanism close to the experimental theory where graphene just serves to transfer a load can be studied dynamically. The boundary comprising of two phases is confirmed to hinder the motion of dislocations, while the crack grows along the interface beside graphene, forming a fracture surface of orderly arranged Al atoms. The results indicate that single-layer graphene (SLG) gives rise to an increase of 1.2 or 0.4 GPa in tensile strength when stretched in in-plane or normal direction, while bilayer graphene (BLG) brings a clear rise of 1.2–1.3 GPa in both directions. In both in-plane and normal stretching directions, the mechanical properties of the composite can be improved clearly by graphene giving rise to a strong boundary, new crack path, and more dense structure. [ABSTRACT FROM AUTHOR]

In this paper, a multi-scale coupling mathematical model is suggested for simulating the polymer filling process in the weld line region on a micro scale. The model considers two aspects: one is the coupling model based on stresses in the whole cavity region; the other is the multi-scale coupling model of continuum mechanics (CM) and the molecular dynamics (MD) in a weldline region. A weak variational formulation is constructed for the finite element method (FEM), which is coupled with the Verlet algorithm based on the domain decomposition technique. Meanwhile, an overlap region is designed so that the FEM and the MD simulations are consistent with each other. The molecular backbone orientation of the whole cavity is illustrated and the position of the weld line is determined by the characteristics of the molecular backbone orientation. Finally, the properties of the polymer chain in the weld line region are studied conformationally and dynamically. The conformational changes and movement process elucidate that the polymer chains undertake stretching, entangling and orientating. Moreover, the effect of the number of chains and melt temperature on the spatial properties of chain conformation are investigated. [ABSTRACT FROM AUTHOR]

A new and innovative various plants extracts Trigonella foenum graecum (Fenugreek), Punica granatum (Pomegranate), Sinapis alba (Mustard), and Piper nigrum (Black pepper) were prepared to study their anti-corrosion action against the carbon steel in 8 M H 3 PO 4 as green inhibitors using Galvano-static polarization measurements. The structure of extract phytochemicals was characterized by Fourier Transform Infrared Analysis (FT-IR) and Gas chromatography/mass spectroscopy (GC–MS). The resulted data suggested that the rise in concentration of Punica granatum (Pomegranate) concentration in the solution (0.45 g/l), as well as the temperature to 313 K, increased the inhibition efficiency proportionally which maximized to 62.08% as mass transfer increased. Adsorption process follows Villamile, Florry-Huggins, and kinetic adsorption isotherm. E a , Q ads , ΔG ads values, and according to the nature of the green inhibitors mixed phenomenon of physisorption and chemisorption was assured. The surface studies were carried out by scanning electron microscope (SEM) and surface roughness (profilometer) technique ensure the plant extract effectiveness in Carbone steel surface damage/ roughness reduction. The plant extract chemical structure and its existence on the carbon steel surface were certified via UV–Vis analysis and EDX (Energy Dispersive X-Ray). Besides, molecular dynamics simulations (MD) supported the adsorption of plant extract compounds on the metal-based adsorbent. [ABSTRACT FROM AUTHOR]

The corrosion behavior of mild steel in a 1 M aqueous sulfuric acid medium in the presence and absence of the drug Pantoprazole was investigated using potentiodynamic polarization and quantum chemical calculations as well as Monte Carlo and molecular dynamic simulations. The potentiodynamic experiments indicated that this molecule, as a result of its adsorption on a mild steel surface, functioned as a mixed inhibitor. The goal of the study was to use theoretical calculations to acquire a better understanding of how inhibition works. The adsorption behavior of the examined compounds on the Fe (1 1 0) surface was calculated using a Monte Carlo simulation. Furthermore, the molecules were studied using density functional theory (DFT), especially the PBE functional, to determine the relationship between the molecular structure and the corrosion inhibition behavior of the chemical under research. The adsorption energies of Pantoprazole (in its three different protonation states) iron were calculated more precisely using molecular mechanics with periodic boundary conditions (PBC). The predicted theoretical parameters were found to be in agreement with the experimental data, which was a considerable help in understanding the corrosion inhibition mechanism displayed by this chemical. [ABSTRACT FROM AUTHOR]

Introduction: This particular coronavirus disease is a pandemic giving rise to great global affliction and uncertainty, even among those who have dedicated their lives to health care or the study of disease, or both. Notwithstanding those directly affected, the lives of all people have been turned upside down. Each person has to cope with her or his personal situation and a story is taking shape for everyone on earth. Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 virus, the source of the 2020 pandemic. This paper contains brief highlights from a duplicable PubMed search of the COVID-19 literature published from January 1 to March 31, 2020, as well as a duplicable search of past influenza-related publications. Excerpts from select papers are highlighted. The main focus of this paper is a descriptive analysis of influenza and other respiratory viruses based on a 16-year population-based dataset. In addition, the paper includes analyses based on the presence or absence of mental disorder (MD) in relation to influenza and all other respiratory viruses. Methods: The investigation is descriptive and exploratory in nature. Employing a case-comparison design, a 16-year population-based dataset was analyzed to both understand the present and plan for the future. While not all viral infections are equal, this paper focuses on system responses by describing the epidemiology of respiratory viruses, such as influenza. Influenza is established in the global population and has caused epidemics in the past. Where possible direct comparisons are made between COVID-19, influenza, and other respiratory viruses. Results: Those with MD had a higher rate of viral infection per 100,000 capita compared to those with the viral infection and no MD. Further, the postviral infection MD rate was not higher compared to the MD per capita rate before viral infection. The postinfluenza rate of MD among those who were without mental disorder before influenza represents an estimate of postinfection mental health burden. Conclusions: In summary, those with preinfluenza MD are at greater risk for viral infection. Further, while the postviral infection MD rate was not higher compared to the MD per capita rate before viral infection, this independent estimate may inform the degree to which services may need to undergo a sustained increase to address the bio psychosocial needs of each served population were COVID-19 to persist and become established in the global population.

The binding mode of aromatic sulphonamides and clinically licenced drugs to the three carbonic anhydrase (CA, EC 4.2.1.1) isoforms from the human pathogen V. cholerae was here thouroghly characterised by a joint docking and molecular dynamics in silico protocol. In fact, VchCA, VchCAβ, and VchCAγ are crucial in the pathogen life cycle and growth and represent innovative targets to fight V. cholerae proliferation overcoming the spreading chemoresistance to the available drugs. A set of 40 sulphonamides/sulfamates VchCAs inhibitors was studied using the proteins homology built 3 D models unveiling the key and stable interactions responsible for a potent CA inhibition. This study has the aim to offer insights and guidelines for the future rational design of potent and selective inhibitors targeting CA isoforms from V. cholerae or other human pathogens.

Fragment-based lead discovery (FBLD) is one of the most efficient methods to develop new drugs. We present here a new computational protocol called High-Throughput Supervised Molecular Dynamics (HT-SuMD), which makes it possible to automatically screen up to thousands of fragments, representing therefore a new valuable resource to prioritise fragments in FBLD campaigns. The protocol was applied to Bcl-XL, an oncological protein target involved in the regulation of apoptosis through protein–protein interactions. Initially, HT-SuMD performances were validated against a robust NMR-based screening, using the same set of 100 fragments. These independent results showed a remarkable agreement between the two methods. Then, a virtual screening on a larger library of additional 300 fragments was carried out and the best hits were validated by NMR. Remarkably, all the in silico selected fragments were confirmed as Bcl-XL binders. This represents, to date, the largest computational fragments screening entirely based on MD.

We identified two glass phases formed in three undercooled liquids of elemental Ag, binary Cu-Ag, and binary Cu-Zr alloys using molecular dynamics (MD) simulations: 1) The homogeneous L-phase arises from quenching quickly from high temperature liquid. 2) The heterogeneous solid-like G-phase arises from the isothermal equilibration at temperatures below the melting point. The G-phase exhibits a core-shell structure with the ordered cores surrounded by percolating liquid-like shells. The distinguishable structures between these two phases are expected to different mechanical behavior. The present study reports MD simulations to compare the shear deformation of these two phases in binary Cu2Zr system. At room temperature, the G-phase exhibits a higher critical stress, a higher critical strain, and higher shear modulus than the L-phase, suggesting that the G-phase has improved strength and rigidity compared to the homogeneous L-phase. The plastic yielding mechanism of both the G-phase and L-phase is accompanied by shear band formation. However, the formation of shear band in G-phase is confined by the cores to a highly localized region and characterized by local mechanical melting. In contrast, the shear band in L-phase exhibits greater width and much more homogenous character. We conclude that the mechanical properties of a metallic glass will vary significantly according to the type of glassy phase formed during processing.

Cognitive aging, especially cognitive control, and processing speed aging have been well-documented in the literature. Most of the evidence was reported based on cross-sectional data, in which inter-individual age effects were shown. However, there have been some studies pointing out the possibility of overlooking intra-individual changes in cognitive aging. To systematically examine whether age-related differences and age-related changes might yield distinctive patterns, this study directly compared cognitive control function and processing speed between different cohorts versus follow-up changes across the adult lifespan. Moreover, considering that cognitive aging has been attributed to brain disconnection in white matter (WM) integrity, this study focused on WM integrity via acquiring diffusion-weighted imaging data with an MRI instrument that are further fitted to a diffusion tensor model (i.e., DTI) to detect water diffusion directionality (i.e., fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity, AxD). Following data preprocessing, 114 participants remained for further analyses in which they completed the two follow-up sessions (with a range of 1–2 years) containing a series of neuropsychology instruments and computerized cognitive control tasks. The results show that many significant correlations between age and cognitive control functions originally shown on cross-sectional data no longer exist on the longitudinal data. The current longitudinal data show that MD, RD, and AxD (especially in the association fibers of anterior thalamic radiation) are more strongly correlated to follow-up aging processes, suggesting that axonal/myelin damage is a more robust phenomenon for observing intra-individual aging processes. Moreover, processing speed appears to be the most prominent cognitive function to reflect DTI-related age (cross-sectional) and aging (longitudinal) effects. Finally, converging the results from regression analyses and mediation models, MD, RD, and AxD appear to be the representative DTI measures to reveal age-related changes in processing speed. To conclude, the current results provide new insights to which indicator of WM integrity and which type of cognitive changes are most representative (i.e., potentially to be neuroimaging biomarkers) to reflect intra-individual cognitive aging processes.

Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is gaining much interest for its regulating role in the central nervous system and its value as a drug target. Structures of CB1 in inactive and active states have revealed conformational change details that are not common in other GPCRs. Here, we performed molecular dynamics simulations of CB1 in different ligand binding states and with mutations to reveal its activation mechanism. The conformational change of the “twin toggle switch” residues F2003.36 and W3566.48 that correlates with ligand efficacy is identified as a key barrier step in CB1 activation. Similar conformational change of residues 3.36/6.48 is also observed in melanocortin receptor 4, showing this “twin toggle switch” residue pair is crucial for the activation of multiple GPCR members.