Plants have a natural protective process of altering their genetic molecules in response to changing environments. To uncover the genetic potential of plants, it is crucial to understand how they adapt to adverse conditions by analyzing their genetic molecules. In the study, we focused on understanding the responsive genes of tomatoes under drought conditions. We analyzed RNASeq data from different Tomato genotypes, tissue types, and different drought durations. We used a time series scale to identify early and late drought-responsive gene modules and applied a machine learning method to identify the best responsive genes. We found six candidate genes of Tomato (ASCT, FLA2, BAG5, DCL2b, NFP7.3, and ADC1) that were responsive to drought. We further constructed their protein-protein interaction network to identify their potential interactors and found them drought responsive proteins. The candidate genes can help to explore the adaptation of tomato plants under drought conditions. The identification of these candidate genes and modules can have far-reaching implications for molecular breeding and genome editing in Tomato, providing insights into the molecular mechanisms that underlie drought adaptation. This research underscores the importance of the genetic basis of plant adaptation, particularly in changing climates and growing populations.

The search for new antibacterial agents that could decrease bacterial resistance is a subject that is continuously developing. The Gram-negative and Gram-positive bacteria have a metalloproteins group belonging to the M4 family. That is the main virulence factor of these bacteria. In this work, we have used a computational protocol based on the comprehensive analysis of the results of docking, molecular dynamics simulation, MM-PBSA, ligand efficiency, and ADME-Tox properties of ligand designed in silico in the previous manuscript using the Thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family as a target. The principal results obtained were the designed ligands were adequately oriented in the thermolysin active center. The Lig783, Lig2177, and Lig3444 compounds were those with better dynamic behavior, however, when analyzing the results extracted from the ADME-Tox properties, only Lig783 was the best antibacterial agent candidate.

Heterocytous cyanobacteria are among the most prolific source of bioactive secondary metabolites, including anabaenopeptins (APTs). A terrestrial filamentous Brasilonema sp. CT11 collected in Costa Rica bamboo forest, as black mat was studied using a multidisciplinary approach: genome mining and HPLC-HRMS/MS coupled with bionformatic analyses. Herein, we report the nearly complete genome consisting 8.79 Mbp with a GC content of 42.4%. Moreover, we report on three novel tryptophane-containing APTs; anabaenopeptin 788 (1), anabaenopeptin 802 (2) and anabaenopeptin 816 (3). Further, the structure of two homologues, i.e., anabaenopeptin 802 (2a) and anabaenopeptin 802 (2b) was determined by spectroscopic analysis (NMR and MS). Both compounds were shown to exert weak to moderate antiproliferative activity against HeLa cell lines. This study also provides the unique and diverse potential of biosynthetic gene clusters and an assessment of the predicted chemical space yet to be discovered from this genus.

The outbreak across the globe due to coronavirus disease 2019 (COVID-19) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV) at transcriptomic and genomic level. The SARS-CoV and COVID-19 exploits the angiotensin converting enzyme 2 (ACE2) receptor to gain entry inside the cells.We analyzed the entry COVID-19 into host cell due to receptor binding domain (RBD) of spike glycoprotein. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 (ACE2) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2.The said investigation of S-Glycoprotein RBD of COVID-19 or SARS-CoV-2 via ACE2 provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected patients by deadly CoVID-19. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19.

Taste determination in small molecules is critical in food chemistry, but traditional experimental methods can be time-consuming. Consequently, computational techniques have emerged as val-uable tools for this task. In this study, we explore taste prediction using various molecular feature representations and assess the performance of different machine learning algorithms on a dataset comprising 2,601 molecules. The results reveal that GNN-based models outperform other ap-proaches in taste prediction. Moreover, consensus models that combine diverse molecular repre-sentations demonstrate improved performance. Among these, molecular fingerprints + GNN con-sensus model emerges as the top performer, highlighting the complementary strengths of GNNs and molecular fingerprints. These findings have significant implications for food chemistry research and related fields. By leveraging these computational approaches, taste prediction can be expedited, leading to advancements in understanding the relationship between molecular structure and taste perception in various food components and related compounds.

Currently, large cell neuroendocrine carcinoma of the lung (LCNEC) is classified as a rare lung cancer subtype, but given the high incidence of lung cancer, the overall number of cases is considerable. The pathologic diagnosis is based on the microscopic appearance of the tumor cells, the amount of intra-tumoral necrosis, the mitotic rate, and the presence of positive neuroendocrine markers identified by immunohistochemistry. Recently, a subdivision into two main categories was proposed based on mutation signatures involving the RB1, TP53, KRAS, and STK11/LKB1 genes, into SCLC-like (small cell lung cancer-like) and NSCLC-like (non-small cell lung cancer-like) LCNEC. In terms of treatment, surgery remains the best option for resectable, stage I–IIIA cases. Chemotherapy and radiotherapy have conflicting evidence. Etoposide/platinum remains the standard chemotherapy regimen. However, based on the newly proposed LCNEC subtypes, some retrospective series report better outcomes using a pathology-driven chemotherapy approach. Encouraging outcomes have also been reported for immunotherapy and targeted therapy, but the real impact of these strategies is still being determined in the absence of adequate prospective clinical trials. The current paper scrutinizes the epidemiology, reviews the reliability of pathologic diagnosis, discusses the need for molecular subtyping, and reviews the heterogeneity of treatment algorithms in LCNEC.

In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1-17) and evaluated for their α-amylase inhibitory potential. All compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. The remaining analogs showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR. Structure activity relationship (SAR) has been recognized for all newly synthesized analogs. Through molecular docking study, binding mode of active analogs with α-amylase enzyme was confirmed.

Phosphate (Pi) deficiency reduces nodule formation and development in different legume species including common bean. Despite the significant progress in the understanding of the genetic responses underlying the adaptation of nodules to Pi deficiency, it is still unclear whether this nutritional deficiency interferes with the molecular dialog between legumes and rhizobia, if so, what part of the molecular dialog is impaired? In this study, we provide evidence demonstrating that Pi deficiency negatively affects critical early molecular and physiological responses required for a successful symbiosis between common bean and rhizobia. We demonstrated that the infection thread formation and the expression of PvNSP2, PvNIN, and PvFLOT2, genes controlling the nodulation process, were significantly reduced in Pi-deficient common bean seedlings. Further transcriptional analysis revealed that the expression of hormones-related genes is compromised in Pi-deficient seedlings inoculated with rhizobia. Additionally, we showed that regardless of the presence or absence of rhizobia, the expression of PvRIC1 and PvRIC2, two genes participating in the autoregulation of nodule number, was higher in Pi-deficient seedlings than in control seedlings. The data presented in this study shed light on the understanding of how Pi deficiency impacts the early steps of the symbiosis between common bean and rhizobia.

Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratifcation of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies and thereby the treatment will be more personalized and efficient. Phase I clinical evaluation of two scaffold protein-based imaging probes, [99mTc]Tc-(HE)3-G3 and [99mTc]Tc-ADAPT6, demonstrated that their injections are safe, well-tolerated and cause low level of absorbed and equivalent doses. The goal of this preclinical study was to select the best probe for patients’ stratification and for response monitoring. Biodis-tribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 ex-pression and MDA-MB-468 xenografts with very low expression. Changes in accumulation of both probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 permitted high contrast imaging of HER2-expressing tumors and clear discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [99mTc]Tc-(HE)3-G3 is capable to sense the decrease of HER2 expression on re-sponse to trastuzumab therapy only 24 h after injection of loading dose. This indicates that this tracer would be better for monitoring early response to such treatment. Results of this study should be considered in planning of further clinical development of HER2 imaging probes.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

The successive steps of the oxidation mechanism of crocin, major compound of saffron, by the free OH• radical are investigated by the pulse radiolysis, steady-state (gamma) radiolysis methods and molecular simulations. The optical absorption properties of the transient species and their reaction rate constants are determined. The absorption spectrum of the oxidized radical of crocin resulting from the H-abstraction presents a maximum at 678 nm and a band at 441 nm, almost as intense as that of crocin. The spectrum of the covalent dimer of this radical contains an intense band at 441 nm and a weaker one at 330 nm. The final oxidized crocin, issued from radical disproportionation, absorbs weaker with a maximum at 330 nm. The molecular simulation results suggest that the OH• radical is electrostatically attracted by the terminal sugar and is scavenged predominantly by the neighbor methyl site of the polyene chain as in a sugar-driven mechanism. Based on detailed experimental and theoretical investigations, the antioxidant properties of crocin are highlighted.

The evidence is presented for the long-range previtreous changes of two static properties: dielectric constant ( ) and its strong electric field related counterpart - the nonlinear dielectric effect (NDE). Notable is the evidence for the functional characterizations of (T) temperature changes by the ‘Mossotti Catastrophe’ formula, and NDE vs. T evolution by the relations resembling one developed for critical liquids. The analysis of dynamic properties based on the activation energy index excluded the Vogel-Fulcher-Tammann (VFT) relation as a validated tool for portraying the evolution of the primary relaxation time. Such a result questions the commonly applied ‘Stickel operator’ routine as the reliable tool for determining the dynamic crossover temperature. It is worth stressing that the strong electric field radically affects the distribution of relaxation times, the form of the evolution of the primary relaxation time as well as the fragility. Obtained results support the concept of a possible semi-continuous phase transition hidden below Tg. Studies were carried out in supercooled squalene, the material with extremely low electric conductivity, strongly elongated molecule, and vitally important for biology and medicine related issues.

Globally, rice is utilized as staple food, belongs to the family Poaceae. From the past few decades under variable climate conditions, it greatly affected by the bacterial leaf blight (BLB) disease caused by a bacterium Xanthomonas oryzae pv. oryzae (Xoo). Scientists studied causes of the disease and found more than 61 isolates of Xoo. About 39 Xa genes were noted that cause race specifically resistance either individually or in pairs against Xoo. The canvas on the characterization of these genes is still unrevealed. In this study, amino acid sequences of Xa15, Xa19, Xa20 and Xa21 were mined and used for motif-domain identification, characterization, and comparative analysis. It includes screening of physical and chemical characteristics, sequence comparison to find sequence similarity between them and their phylogenetic comparison with other Xa genes and other species based upon LRR and S_TKc domains to find evolutionary relationship among them. The comparison-based modeling was performed and assessed by different tools to gain better understanding and structural evaluation. The results showed identified domains are specific in function, each domain involved in resistance against biotic and abiotic stresses through regulating different cellular processes. This study also revealed high similarity (>98% sequence identity) between these genes and encode a similar leucine-rich repeat receptor kinase like protein. It will optimize the breeding programs as it will be useful for the selection of effective genes to produce resistance in rice varieties against the specific strains of Xoo that will be more effective against BLB than the other Xa genes.

This work examines atomic and molecular signatures in laser-induced plasma in standard ambient temperature and pressure environments, including background contributions to the spectra that depend on the laser pulse-width. Investigations include solids, gases, and nano-particles. Abel inversions of measured line-of-sight data reveal insight into the radial plasma distribution. For nominal 6 nanosecond laser pulses and for pulse-energies in the range of 100 to 800 mJ, expansion dynamics and turbulence due to shock phenomena are elucidated to address local equilibrium details that are frequently assumed in spatially averaged emission spectroscopy. Chemical equilibrium computations reveal temperature dependence of selected plasma species. Specific interests include atomic hydrogen (H) and cyanide (CN). Atomic hydrogen spectra indicate axisymmetric shell structures and isentropic expansion of the plasma kernel over and above the usual shockwave. The recombination radiation of CN emanates within the first 100 nanoseconds for laser-induced breakdown in a 1:1 CO2:N2 gas mixture when using nanosecond laser pulses to create the micro-plasma. The micro-plasma is generated using 1064 nm, 150 mJ, 6 ns Q-switched Nd:YAG laser radiation. Measurements of the optical emission spectra utilize a 0.64 m Czerny-Turner type spectrometer and an intensified charge-coupled device.

The limited information available on the structure of complexes involving transcription factors and cognate DNA response elements represents a major obstacle in the quest to understand their mechanism of action at the molecular level. We implemented a concerted structural proteomics approach, which combined hydrogen-deuterium exchange (HDX), quantitative protein-protein and protein-nucleic acid cross-linking (XL), and homology analysis, to model the structure of the complex between the full-length DNA binding domain (DBD) of FOXO4 and its DNA binding element (DBE). The results confirmed that FOXO4-DBD assumes the characteristic forkhead topology shared by these types of transcription factors, but its binding mode differs significantly from those of other members of the family. The results showed that the binding interaction stabilized regions that were rather flexible and disordered in the unbound form. Surprisingly, the conformational effects were not limited only to the interface between bound components but extended also to distal regions that may be essential to recruiting additional factors to the transcription machinery. In addition to providing valuable new insights into the binding mechanism, this project provided an excellent evaluation of the merits of structural proteomics approaches in the investigation of systems that arematerial not directly amenable to traditional high-resolution techniques.

Explosive boiling is a fast phase transition from an ultra-thin liquid film to vapor under an extremely high heat flux, which typically has been studied using molecular dynamics simulation (MDS) method. The present MDS study investigated the explosive boiling of a liquid argon nanofilm over different solid copper surfaces with different nanowall patterns including parallel and cross nanowalls. For each surface, atomic motion trajectories, number of liquid and vapor argon atoms, heat flux, and, mainly, onset time of explosive boiling were investigated. The simulation results indicated that explosive boiling occurs earlier on parallel and cross nanowall surfaces than on an ideally smooth surface, regardless of the topology and configuration of nanowalls. Moreover, the results revealed that by using the cross nanowall surfaces, the onset time of explosive boiling decreased by 0.7–4% compared to the parallel nanowall surfaces. In addition, it was found that the onset time of explosive boiling strongly depends on the potential energy barrier and the movement space between nanowalls for both parallel and cross nanowall surfaces. Furthermore, simulation findings showed that even though increasing the height of cross nanowalls increases heat flux and temperature of the fluid argon domain, it does not necessarily result in a shorter onset time of explosive boiling. These findings demonstrate the capability of cross nanowall surfaces for explosive boiling, thereby could be utilized in future surface design for thermal management applications.

The increased cultivation of Cannabis sativa L. in North America, represented by high Δ9-tetrahydrocannabinol-containing (high-THC) cannabis genotypes and low THC-containing hemp genotypes, has been impacted by an increasing number of plant pathogens. These include fungi which destroy roots, stems and leaves, in some cases causing a build-up of populations and mycotoxins in the inflorescences that can negatively impact quality. Viroids and viruses have also increased in prevalence and severity and can reduce plant growth and product quality. Rapid diagnosis of the occurrence and spread of these pathogens is critical. Techniques in the area of molecular diagnostics have been applied to study these pathogens in both cannabis and hemp. These include polymerase chain reaction (PCR)-based technologies, including RT-PCR, multiplex RT-PCR, RT-qPCR, and ddPCR, as well as whole genome sequencing (NGS) and bioinformatics. In this study, examples of how these technologies have enhanced the rapidity and sensitivity of pathogen diagnosis on cannabis and hemp will be illustrated. These molecular tools have also enabled studies on the diversity and origins of specific pathogens, specifically viruses and viroids, and these will be illustrated. Comparative studies on the genomics and metabolomics of healthy and diseased plants are urgently needed to provide insight into their impact on quality and composition of cannabis and hemp-derived products. Management of these pathogens will require monitoring of their spread and survival using the appropriate technologies to allow accurate detection, followed by appropriate implementation of disease control measures.

Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not discern adequately patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study is to evaluate the predictive value of the biomarkers midregional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-Reactive Protein (CRP), and lactate for 28-day mortality in patients with sepsis and a SOFA score ≤ 6. 284 patients were included, with a 28-day all-cause mortality of 8.45 % (N=24). Non-survivors were older (p=0.003), required mechanical ventilation (p=0.04) and were ventilated for longer (p=0.02), had a higher APACHE II (p=0.015) and SOFA (p=0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55–0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57–0.84) for SOFA, and 0.70 (0.58–0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned with 100% sensibility survivors from non-survivors at 28 days. In patients with community acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-concerted [2n+2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the more favourable regioisomeric transition state structure (TS) is located 8.5 kcal•mol⁻¹ below the reagents, in complete agreement with the high polar character of the TS. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pra-type of reactivity.

The human serotonin transporter (hSERT) terminates neurotransmission by removing serotonin from the synaptic cleft, which is an essential process plays an important role in depression. In addition to substrate serotonin, hSERT is also the target of drugs of abuse like cocaine and clinically used antidepressants such as escitalopram and paroxetine. To date, few studies attempt to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of hSERT. The high-resolution X-ray structure of hSERT resolved recently enables us to theoretically study the unbinding of the above four ligands against the S1 or S2 site of hSERT, by means of molecular docking, molecular dynamics (MD) and potential of mean force (PMF) simulations. We proved that for either the S1 or S2 site, the other three ligands (cocaine, escitalopram and paroxetine) are much more favorable than the original substrate serotonin, whether in kinetics along the unbinding pathways or in thermodynamics at the equilibrium states. Furthermore, the S1 site is much more favorable than the S2 site, for each ligand. Interestingly, inspection revealed that there are ~ 3Å lengths between the allosteric site of serotonin and cocaine, and an unseen un-binding pathway for escitalopram at the S1 site except for verification of the broadest trail.

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the Phosphatidylserine and the docking of 3 mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA-Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score, so mutations in this position were evaluated to observe the differences in intermolecular forces of the CagA-Phosphatidylserine complex. We evaluated the docking of 3 mutations: K636A, K636R and K636N. The models of the crystal and mutations presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG (χ²(1) = 93.82, p-value < 2.2 × 10⁻¹⁶) and the H-bonds (χ²(1) = 91.93, p-value < 2.2 × 10⁻¹⁶). In all the data, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA-Phosphatidylserine complex interaction.

Topological indices are invariant numerical fields of a graph that give facts about the structure of graphs and are found to be very helpful in predicting the physical properties of aluminophosphates. The characteristics of the aluminophosphates are similar to those of zeolites. Two examples of current applications are natural gas dehydration and humidity sensor. New frameworks are being synthesised by researchers in chemistry and materials science. There are many layers and holes in these substances. In this study, Vertex version of distance-based topological indices, the entropy of topological indices and their numerical analysis are explained.

Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

Objective: To observe the effect of the combination of fluid-increasing decoction, low molecular heparin sodium and aspirin in the treatment of oligohydramnios in pregnancy. Methods: In this study, 114 pregnant women with oligohydramnios during pregnancy admitted to our hospital between May 2019 and March 2022 were selected as objects, and the pregnant women were equally divided into the observation group and the experimental group by random number table method, with 57 cases in each group. The observation group received conventional fluid infusion, low molecular heparin sodium and aspirin, while the experimental group was treated with fluid-increasing decoction on the basis of the observation group. The treatment effect, S/D level, amniotic fluid index, maximum vertical pocket (MVP), coagulation indexes (plasma prothrombin time (PT), plasma activated partial thromboplastin time (APTT), fibrinogen (FIB)), pregnancy outcome and adverse reactions were compared between the two groups. Results: The total effective rate of treatment was obviously better in the experimental group than that in the observation group (P＜0.05); the S/D level after treatment in the experimental group was remarkably lower than that in the observation group (P＜0.05). The amniotic fluid index and MVP were remarkably higher in the experimental group than in the observation group after treatment (P < 0.05). No significant differences in PT, APTT and FIB were found between the two groups before and after treatment (P > 0.05). The rate of oligohydramnios at delivery, cesarean section rate, neonatal weight status and preterm delivery rate were dramatically better in the experimental group than in the observation group (P < 0.05). Post-partum haemorrhage rate, neonatal asphyxia rate, amniotic fluid contamination rate and incidence of adverse events were not significantly different between the two groups of pregnant women (P > 0.05). Conclusion: The combination of fluid-increasing decoction, low molecular heparin sodium and aspirin is clinically effective and safe in the treatment of pregnant women with oligohydramnios during pregnancy. The combination is effective in reducing the S/D ratio of fetal umbilical blood flow, enhancing the amniotic fluid index and MVP in pregnant women with oligohydramnios during pregnancy, whilst not adversely influencing the coagulation function of the mother, thus contributing to a reduction in the risk of adverse pregnancy outcomes.

The nature of bone homeostasis is the coordination between the osteoblasts (OBs) and osteoclasts (OCs). However, abnormal activation of osteoclasts (OCs) could compromise the bone homeostasis. Thus, it is imperatively urgent to explore effective medical interventions for patients. NO/guanylate cyclase (GC)/cGMP signaling cascade has been widely reported in regulating bone metabolism, and GC plays a significantly critical role. Vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, has been firstly reported in 2020 to treat patients with heart failure. However, the effect of Vericiguat on the function of OCs has not been explored. In this present study, we found that the concentration range of Vericiguat between 0-8uM was none- cytotoxic to BMMs. Vericiguat could enhance differentiation of OCs at concentration of 500nM, whereas it inhibited differentiation at 8 uM in terms of the number and size of OCs. In addition, Veirciguat also showed dural effect on RANKL‐induced OC fusion and bone resorption in a concentration‐dependent manner. Further, molecular assay suggested that the dually regulatory effect of Vericiguat on OCs was mediated by the bidirectional activation of IκB-α/NF-κB signaling pathway. Taken together, our present study demonstrated the dual effects of Vericiguat on the formation of functional OCs in a concentration-dependent manner. The regulatory effect of Vericiguat on OCs was mediated by the bidirectional activation of IκB-α/ NF-κB signaling pathway, and a potential balance between IκB-α/ NF-κB signaling pathway and sGC/cGMP/VASP may exist.

Raman scattering has been employed to study in detail the concentration dependence of the vibrational modes for the hexamethylenetetramine (HMTA) aqueous solutions. The formation of protonated and/or aggregated species has been clarified by comparing the experimental with the theoretically predicted vibrational spectra by means of quantum mechanical calculations. The analysis has shown that the vibrational modes of the solutions arise from a contribution of the vibrational modes of the HMTA self-aggregates and hetero-aggregates of HMTA with water molecules that are formed in the low- and intermediate-concentration region, respectively. The protonation of HMTA is ruled out due to the large differences between the experimental and the theoretically calculated spectra of the protonated molecules of HTMA in the fingerprint region. In the low-concentration solutions, the hetero-aggregation reaction of HMTA with water is the dominant mechanism, while at higher concentrations a self-aggregation mechanism occurs. Ultrasonic absorption and velocity measurements were carried out for hexamethylenetetramine aqueous solutions. The acoustic spectra reveal the presence of only one single Debye-type relaxation process that is assigned to the aggregation mechanism of HMTA. The sound absorption data follow two different dependencies on HMTA mole fraction. The crossover 0.018 mole fraction signifies two separate regions with distinct structural characteristics. The relaxation mechanism observed in dilute solutions is attributed to hetero-association of HMTA with water molecules, while at higher concentrations the observed relaxation process is assigned to the self-association reaction of HMTA molecules. This structural transformation is also reflected in several physicochemical properties of the system, including the kinematic viscosity, the mass density, the sound speed, and the adiabatic compressibility of the HMTA aqueous solutions. The combination of vibrational and acoustic spectroscopies with molecular orbital calculations allowed us to disentangle the underlying processes and to elucidate the observed relaxation mechanism in the HMTA aqueous solutions.

Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO₂) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. In cases of hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO₂ for more vital organs. As a result, a measure related to skin tissue oxygenation is likely to be more sensitive to inadequate breathing during sleep than pulse oximetry. Energy Conversion Monitoring (ECM) provides a method for measuring skin tissue oxygen-dependent energy conversion and, as such, is promising for more sensitively detecting sleep disordered breathing (SDB) events compared to pulse oximetry. We hypothesized that ECM would detect hypoxia occurring with SDB events associated with drops in SpO₂ but also would detect hypoxic challenge occurring with SDB events not associated with drops in SpO₂ (hypopneas defined by a drop in nasal pressure occurring in conjunction with an arousal, respiratory-related arousals, and primary snoring). Primary snoring is of particular interest with respect to the potential of ECM because it is statistically associated with co-morbidities of SDB, such as hypertension, but is not considered pathological because of the lack of a proximal measure of pathology occurring with PSG. In this article we review ECM technology and methodology, present preliminary data indicating that it detects hypoxia occurring in the skin during SDB events that is not detected as blood desaturation by pulse oximetry, and make the case that it is a promising tool for identifying pathology occurring at the mild end of the SDB spectrum.

A variational analysis of dispersion medium (electrolytes and surfactants) was carried out for the best nucleotide interactions with the presence of nanoparticles and the ability to formation of homogeneous coatings upon drying / lyophilization. Using UV-spectroscopy and transmission electron microscopy, the processes of immobilization of nucleotides on the surface of nanoparti-cles of the composition ZrO2-3mol% Y2O3 (YSZ) in the presence of various dispersing agents were investigated. Promising dispersing agents were established, the optimal composition of suspen-sions based on DNA nucleotides and YSZ nanoparticles, which is potentially suitable for adaptive technologies of bionanoelectronics, was selected. The aim of the work is to obtain and study functional media for molecular electronics based on heterojunctions biological molecule – wide-gap dielectric.

We report a detailed investigation of vibrational modes, structure, and dynamics of glutathione (GSH) solutions using ultrasonic relaxation spectroscopy, FT-IR vibrational spectroscopy and electronic absorption measurements. The experimental data were analyzed in view of density functional theory (DFT) and molecular docking calculations. Three distinct Debye-type relaxation processes are resolved in the acoustic spectra, which are assigned to conformational changes between GSH conformers, self-association of GSH, and protonation processes. The standard volume changes for each process were estimated both experimentally and theoretically revealing a close resemblance among them. The higher the effect of the relaxation process in the structure, the greater the induced volume changes. From the temperature dependence of specific acoustic parameters, the thermodynamic characteristics of each process were determined. The experimental FT-IR spectra were compared with the corresponding theoretically predicted vibrational spectra revealing that the GSH dimers and extended conformers dominate the structure of GSH solutions in the high concentration region. The absorption spectra in the ultraviolet region confirmed the gradual aggregation mechanism that takes place in the aqueous GSH solutions. The results of the present study were discussed and analyzed in the framework of the current phenomenological status of the field.

Shut-in after fracturing is generally adopted for wells in shale oil reservoirs, and imbibition occurring in matrix nanopores has been proven as an effective way to improve recovery. In this research, the molecular dynamics (MD) simulation was used to investigate the effects of wettability and pressure on nanopores imbibition during shut-in for a typical shale reservoir Jimsar. The results indicate that the microscopic advancement mechanism of the imbibition front is the competitive adsorption between “interfacial water molecules” at the imbibition front and “adsorbed oil molecules” on the pore wall. The essence of spontaneous imbibition involves the adsorption and aggregation of water molecules onto the hydroxyl groups on the pore wall. The flow characteristics of shale oil suggest that the overall push of the injected water to the oil phase is the main reason for the displacement of adsorbed oil molecules. Thus, shale oil especially the heavy hydrocarbon component in the adsorbed layer tends to slip on the walls. However, the weak slip ability of heavy components on the wall surface is an important reason that restricts the displacement efficiency of shale oil during spontaneous imbibition. The effectiveness of spontaneous imbibition is strongly dependent on the hydrophilicity of the matrix pore's wall. The better hydrophilicity of the matrix pore's wall facilitates higher levels of adsorption and accumulation of water molecules on the pore wall and requires less time for “interfacial water molecules” to compete with adsorbed oil molecules. During the forced imbibition process, the pressure difference acts on both the bulk oil and the boundary adsorption oil, but mainly on the bulk oil, which leads to the occurrence of wetting hysteresis. Meanwhile, shale oil still existing in the pore always maintains a good stratified adsorption structure. Because of the wetting hysteresis phenomenon, as the pressure difference increases, the imbibition effect gradually increases, but the actual capillary pressure gradually decreases and there is a loss in the imbibition velocity relative to the theoretical value. Simultaneously, the decline in hydrophilicity further weakens the synergistic effect of pressure difference because of the more pronounced wetting hysteresis. Thus, selecting an appropriate well pressure enables cost savings and maximizes the utilization of the formation's natural power for EOR.

In Benin, Xanthomonas oryzae pv. oryzae (Xoo) causing bacterial blight (BLB) was first described in 2013 on wild rice Oryza longistaminata. No studies have been conducted on Beninese Xoo strains and resistant rice varieties. The aim of this study is to check whether Xoo has already spread to cultivated varieties and to screen some rice accessions for the main resistance genes detection. To achieve this aim, rice leaves showing typical BLB symptoms were collected from various rice fields in Benin and analyzed by PCR to identify Xoo-specific sequences. In addition, seventy-five rice accessions were examined to identify Xoo resistance genes. The results showed that Xanthomonas oryzae (Xo) had been identified in Banikouara and Malanville. In addition, Sphingomonas sp was detected in several rice fields. A Xo-Sphingomonas Sp co-infection was also noted. 47 of 75 rice accessions examined (62.66%) carried Xoo resistance genes with 3 (4%) and 40 (53.33%) of xa5 and Xa21 respectively. None of the accessions had neither Xa7 nor Xa13 resistance genes. Three accessions had both xa5 and Xa21 genes. In addition, the rice isogenic lines IRBB60 and IRBB21used as positive controls, were found to be susceptible. These results indicate that Xo has evolved from a wild rice to cultivated varieties in northern Benin. Consequently, a varietal improvement program must be implemented with varieties having resistance genes to prevent a BLB pandemic in Benin.

The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 mg/mL. The compound 5f bearing a 2,6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking to the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron related deleterious side effects observed with existing antifungal compounds.

COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, TMPRSS2, and AP2-associated protein kinase 1. In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of drug candidates to target receptors, providing insight into their potential efficacy. However, it is crucial to consider both the advantages and limitations of these studies and to complement them with experimental validation to ensure the efficacy and safety of identified drug candidates.

Marburg virus disease (MVD) is a hemorrhagic fever and cause death up to 88% of people and is the same as Ebola virus, It is transmitted through skin contact or mucous membrane in the eyes, nose or mouth with blood or body fluids like urine, saliva sweat, feces and by object contaminated with body fluids. Despite these facts, yet there is no approved vaccine have been developed for the eradication of Marburg virus infections. Therefore, this study described a multi epitope-based peptide vaccine against Marburg virus viral protein 35, using several immunoinformatics tools combined with molecular docking studies. Utilizing Vaxijen 2.0 server, the V35 protein revealed to be antigenic with a score of 0.4316. Prediction of the T-cell and B-cell epitopes was then conducted. RTFDAFLGV epitope was found to be the most promising one with binding affinity to the highest numbers of MHC I alleles, a positive score in the Class I immunogenicity study and non-allergen. These results were further confirmed by the good interaction of RTFDAFLGV to the groove of HLA-A*02:01 with binding energy of -8.1 kcal/mole. Finally, the vaccine was cloned in silico to ensure its validity and efficiency of expression. To ensure its safety and immunogenic profile, in-vitro and in-vivo bioassays are recommended to confirm these findings.

The study aims to evaluate the Quorum Sensing (QS) system inhibition against some Gram-positive and Gram-negative bacteria detected by molecular modeling of R. cathartica L. plant extract. R. cathartica L. methanol extract was evaluated in vitro. The research was carried out for the possible role and mechanism of R. cathartica L. The antibacterial activity of R. cathartica L. seed extract on some Gram-positive and Gram-negative strains was evaluated using culture-based and computational analysis. Gentamicin (CN; 30 µg/ml, Bioanalyse) was used as an antibacterial control of the extract on the production potential of QS-dependent virulence factors on Pseudomonas aeruginosa PAO1 was investigated. Phytochemical analysis resulted in the identification of 23 phenolic phytochemicals. R. cathartica L. extract was observed to have antimicrobial activity against Gram-positive and Gram-negative bacteria at different rates (11.3 mm-16 mm). The inhibitory effect of R. cathartica L. extract on P. aeruginosa PAO1 (elastase 61%, pyocyanin 18%, and biofilm 61%) was recorded moderately. Phytochemical analysis revealed that the main component of the extract is kaempferol. Therefore, the binding potential of kaempferol on QS system receptors was investigated via molecular docking. Computational analysis showed that kaempferol can inhibit the QS system by preventing competitive ligands from connecting to LasR. This study explored the activity and mechanism of action for a new green alternative against resistance. might provide a mechanism for R. cathartica L. seed extract components and thus provide a new avenue for using R. cathartica L. seed extract as a green antibacterial agent.

I demonstrate that the ionization energy (IE) and the electron affinity (EA) of organic molecular crystals can be predicted from first-principles. Here, I describe the induced electronic polarization and the electrostatic effects upon crystalline IE and EA. I also demonstrate that the electronic polarization mainly originates from the screened coulomb interaction inside the crystalline bulk phase, and that the electrostatic contribution to IE and EA crucially depends on the orientation of the molecule at the surface. The former is well described by the GW approximation, while the latter is reasonably estimated by the difference in frontier orbital energy between the gas phase and the surface at the level of a generalized gradient approximation to the density functional theory. The present methodology enables to demonstrate the impact of the electrostatic effect upon the energy level of the injected charge at a multi-monolayer surface of an organic semiconductor thin film.

Turbulence is a fluid dynamic problem refractory to mathematical treatment. Examining a theoretical model of liquid water flowing in a cylinder at different Raleigh numbers, we propose a novel approach to elucidate the first stages of turbulent flows. The weakly bonded molecular assemblies of liquid water form a fluctuating branched polymer in which every micro-cluster displays different density. Against the common view of liquid water as an incompressible and continuous fluid, we suggest that the occurrence of transient local aggregates could be able to generate the vortices and eddies that are the hallmarks of turbulence. We quantify the local changes in velocity, diameter and density required to engender “obstacles” to the average flow. Then, we show how these microstructures, equipped with different Raleigh numbers and characterized by high percolation index, could generate boundary layers that contribute to micro-vortices production. We conclude that the genesis of turbulence cannot be assessed in terms of collective phenomena, rather is sustained, among many other factors, by the underrated microscopic inhomogeneities of fluids like liquid water.

Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can provide predictions, reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.

Agaricus bisporus is belonging to family agaricaceae, which is widely acceptable and mostly cultivated among the all mushrooms. It has great nutritional values and it is rich in proteins, vitamins, carbohydrates, fibers, minerals and amino acids. It is effective in antimicrobial, anticancer, antidiabetic, antihypercholesterolemic, antihypertensive, hepatoprotective and antioxidant activities. As it is effective in anticancer property, we check the effects of chemical constituents of Agaricus Bisporus on DNA damaging protein which results its activity PARP inhibiting or vise-versa. We choose the molecular docking technique to check the effects of different chemical constituents of Agaricus Bisporus on DNA damaging protein. For that different PARP inhibitory drugs taken as the standard. We perform the molecular docking of the chemical constituents of Agaricus Bisporus, using 4UND protein with the help of PyRx software and BIOVIA Discovery studio software. Along with that PARP inhibitor drugs also run against the same protein. The results of molecular docking shows the some of the constituents of Agaricus Bisporus has better binding affinity than the standard taken PARP inhibitor drugs. The ergosterol shows the better binding affinity than the niraparib and rucaparib on the same proteins. On other hands the naringenin, quercetin, anthocyanin, folate and myricetin shows the better results than the rucaparib. That means the ergosterol shows the better results as PARP inhibitor than the niraparib and rucaparib.

Binderless zeolite macrostructures in the form of ZK-4 microspheres were prepared using anion exchange resin beads as shape directing macrotemplates. The particles were synthesized under hydrothermal conditions at different temperatures and treatment times. The influence of the different synthesis parameters was investigated by X-ray diffraction, scanning electron microscopy, fluorescence X, nitrogen adsorption measurements and ²⁹Si solid NMR. Fully crystalline spheres similar in size and shape to the original resin beads were obtained by a hydrothermal treatment at the highest temperatures (150 - 180 °C) for a short treatment time of 24 h. The synthesized microspheres showed to be promising in the molecular decontamination of Volatile Organic Compounds (VOCs).

Staphylococcus aureus are commensal bacteria present on skin and mucosae in both humans and animals, but they can also be found in food, water and in various environments. They are also considered a major pathogen having a great morbidity leading to a wide range of infections. They are included in the list of most virulent and antimicrobic resistant bacterial pathogens (ESKAPE, Escherichia coli, Staphylococcus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecalis and faecium)) by the Center for Disease Control and Prevention (CDC), and S. aureus is part of the worldwide threat represented by the presence of antimicrobial resistance (AMR). The outcomes of an epidemiological investigation on 26,430 S. aureus isolates from a global public database (NPDIB; NCBI Pathogen Detection Isolate Browser) support the evidence of significant differences in the distribution of isolates and ARGs (Antimicrobial Resistance Genes) clusters among geographical areas of origin and among sources of the isolates. Moreover, the ARGs cluster patterns suggest an association between the isolates from human and animal populations. This outcome and the large diffusion of the pathogens among human and animal populations support the importance of gaining information on the epidemiology of these infections with a One Health approach.

A variational analysis of dispersion medium (electrolytes and surfactants) was carried out for the best nucleotide interactions with the presence of nanoparticles and the ability to formation of homogeneous coatings upon drying / lyophilization. Using UV-spectroscopy and transmission electron microscopy, the processes of immobilization of nucleotides on the surface of nanoparti-cles of the composition ZrO2-3mol% Y2O3 (YSZ) in the presence of various dispersing agents were investigated. Promising dispersing agents were established, the optimal composition of suspen-sions based on DNA nucleotides and YSZ nanoparticles, which is potentially suitable for adaptive technologies of bionanoelectronics, was selected. The aim of the work is to obtain and study functional media for molecular electronics based on heterojunctions biological molecule – wide-gap dielectric.

The molecular dynamics simulation has been used to investigate the structural and transport properties of (Ba_0.5-xSr_x)La_0.5InO_3-δ (x=0, 0.1, 0.2) oxygen-ion conductor. The previous studies reported that the ionic conductivity of Ba-doped LaInO3 decreases because Ba dopant forms narrow oxygen path in the lattice, which could hinder the diffusion of oxygen ion. In this study, we reveal the mechanism to improve the ionic conductivity by Ba and Sr co-doping on La site in LaInO3 perovskite oxide. The results show that the ionic conductivity of (Ba_0.5-xSr_x)La_0.5InO_3-δ increases with increasing numbers of Sr ions, which oxygen diffusion paths including Sr ion have larger critical radius than Ba ions. The RDF calculations showed the heights of peak in composition including Sr ions is lower and broaden, so oxygen ions moved easily into other oxygen sites.

Hoechst 33342 (H33342) is a fluorescent probe that is commonly used to stain DNA of living cells. To do so, it needs to interact with and permeate through cell membranes. The pH of biological media may vary quite significantly and this influences H33342 ionization state, and may change its rate of permeation through biomembranes. In this work, we address the effect of pH in the association of H33342 with lipid bilayers using a combined experimental and computational approach. The partition of H33342 to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid membranes was experimentally quantified using fluorescence spectroscopy and isothermal titration calorimetry (ITC) measurements. Quantum chemical calculations were performed to select the most stable isomer of H33342 for the overall charges 0, +1, and +2, expected to predominate across the 5 &lt; pH &lt; 10 range. The interaction of these isomers with POPC bilayers was then studied by both unrestrained and umbrella sampling molecular dynamics simulations. While probe insertion occurs for all ionization states, with similar overall equilibrium location, orientation was found to depend on the probe charge, with the neutral form lying mostly parallel and the doubly charged displaying a significant tilt relative to the membrane plane. Both experimental results and computational free energy profiles indicate that the partition coefficient of H33342 displays a small variation over a wide pH range, not exceeding one order of magnitude. The enthalpy of interaction is negative and is larger at lower pH values. This suggests efficient hydrogen bonding between the probe and the lipid, namely for the protonated +2 form. The relatively high lipophilicity obtained for the charged species contrasts with the decrease in their general hydrophobicity as estimated from water and octanol partition. This highlights the distinction between lipophilicity and hydrophobicity, and the importance of considering association with lipid bilayers when predicting the affinity for biomembranes.

The main objective of this work is to study the effects of carbon nanotubes (CNT) on the strength and electrical properties of cement mortar. Molecular dynamic simulations (MDS) were carried out for the mechanical and electrical properties of the cementitious composite and the associated mechanisms. To model the atomic structure of the Calcium-Silicate-Hydrates (C-S-H) gel, tobermorite 11Å was chosen. Single-walled carbon nanotubes (SWCNTs) embedded in tobermorite structure were tested numerically. In particular, the effect of the concentration of CNT in cement paste was studied. An innovative experiment of electrical characterization of a cementitious composite of carbon nanotubes has been developed.

Hepatocellular carcinoma (HCC) is characterized by uncontrolled cellular proliferation driven by aberrant signal transduction. Cells respond to potential carcinogenic signals by inducing cellular senescence (CS) as a defense mechanism. However, assessing CS levels in various tumors is challenging due to heterogeneity and the lack of universal CS markers. This study integrates single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from HCC samples to analyze gene expression profiles. HCC-specific senescence-related pathways are identified, and genes from these pathways distinguish molecular subtypes associated with senescence in HCC. These subtypes exhibit significant variations in biological and clinical attributes. A specific CS risk model is developed, revealing associations between CS scores and prognosis, clinical staging, immune infiltration, immunotherapy response, and drug sensitivity. The key gene G6PD is identified as a potential senescence-related target in liver cancer. Molecular experiments confirm the effective suppression of HepG2 cell proliferation, invasion, and migration upon G6PD knockdown. In summary, this analysis enhances our understanding of HCC-specific senescence molecular features and introduces a novel senescence-related biomarker, offering promising implications for future research.

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

In the last two decades, plant taxonomy has bloomed, following the development of a novel technique, namely DNA Barcoding. DNA barcodes are standardized sequences, ideally unique, coding or non-coding, either from the genome of the organism or from its organelles, that are used to identify/classify an organismal group; in short the method includes amplification of the DNA barcode, sequencing and comparison with a reference database containing the relevant sequences from different species. In plants, the use a universal DNA barcode, such as COI which is used in animals, has not been achieved so far. Several DNA barcodes from single loci as well as combinations of barcodes have been successfully used in various settings; additionally, as next generation sequencing becomes affordable, very long sequences- super barcodes, such as the chloroplast genome are being used successfully especially to distinguish between close species. In this review we summarize the work done on DNA barcoding in plants and discuss different approaches used so far.

The exact, non perturbative, response theory developed within the field of nonequilibrium molecular dynamics, also known as TTCF (Transient Time Correlation Function) applies to quite general dynamical systems. Its key element is called dissipation function, because it represents the power dissipated by external fields acting on the particle system of interest, whose coupling with the environment is given by deterministic thermostats. This theory has been initially developed for time independent external perturbations, and then it has been extended to time dependent perturbations. It has also been applied to dynamical systems of different nature, and to oscillator models undergoing phase transitions, which cannot be treated withe.g. linear response theory. The present work includes time dependent stochastic perturbations, in the theory, using the Karhunen-Loeve theorem. This leads to three different investigations of a given process. One in which a single realization of the stochastic coefficients is fixed, and averages are taken only over the initial conditions, as in a deterministic process. In the second, the initial condition is fixed, and averages are taken with respect to the distribution of stochastic coefficients. In the last investigations, one averages over both initial conditions and stochastic coefficients. We conclude illustrating the applicability of the resulting exact response theory with simple examples.

We measured the anelastic, dielectric and structural properties of the metal-free molecular perovskite (ABX$_{3}$) (MDABCO)(NH$_{4}$)I$_{3}$, which has already been demonstrated to become ferroelectric below $T_{\text{C}}=$ 448~K. Both the dielectric permittivity measured in air on discs pressed from powder and the complex Young's modulus measured on resonating bars in vacuum show that the material starts deteriorating with loss of mass just above $T_{\text{C}}$, introducing defects and markedly lowering $T_{\text{C}}$. The elastic modulus softens of 50\% when heating through the initial $T_{\mathrm{C}}$, contrary to usual ferroelectrics, which are stiffer in the paraelectric phase. This suggests improper ferroelectricity, where the primary order parameter of the transition is not the electric polarization, but the orientational order of the MDABCO molecules. The degraded material presents thermally activated relaxation peaks in the elastic energy loss, whose intensities increase together with the decrease of ~$T_{\mathrm{C}}$. The peaks are much broader than pure Debye, due to the general loss of crystallinity, also apparent from X-ray diffraction, but their relaxation times have parameters typical of point defects. It is argued that the major defects should be of the Schottky type, mainly due to the loss of (MDABCO)$^{2+} $ and I$^{-}$, leaving charge neutrality, and possibly also (NH$_{4}$)$^{+}$ vacancies. The focus is on an anelastic relaxation process peaked around 200~K at $\sim 1$~kHz, whose relaxation time follows the Arrhenius law with $\tau $$_{0}$~$\sim $\ $10^{-13}$\ s and $E\simeq 0.4$~eV. This peak is attributed to I vacancies (V$_{\text{X}}$) hopping around MDABCO vacancies (V$_{\text{A}}$) and its intensity presents a peculiar dependence on temperature and content of defects. The phenomenology is thoroughly discussed in terms of lattice disorder introduced by defects and of partition of V$_{\text{X}}$ among sites that are far from and close to the cation vacancies. A method is proposed for calculating the relative concentrations of V$_{\text{X}}$, that are untrapped, paired with V$_{\text{A}}$ or forming V$_{\text{X}}$--V$_{\text{A}}$--V$_{\text{X}}$ complexes.

Norepinephrine (NE) uptake through the NE transporter (NET) is the primary mechanism to ter-minate the action of this neurotransmitter. Dysregulation of brain NE levels is associated with various conditions, including attention deficits, depression, and Alzheimer's disease. Recently, we identified an interaction between the related dopamine (DA) transporter (DAT) and G protein βγ subunits. Activation of Gβγ in cells and brain slices leads to DA efflux through DAT. However, the potential interaction between Gβγ and NET has not been reported. Here, we used a combina-tion of molecular modeling approaches to elucidate the structural details of the NET/Gβγ inter-action, supported by experimental evidence. Through 1.5µs of molecular dynamic simulation, we observed a favorable NET/Gβγ interaction mediated by the intracellular carboxy terminus of NET. As a consequence, the binding energy of NE for NET also changes resulting in alterations of the electrostatic profile of NET. We propose that these changes mediate the NE efflux effect. Fi-nally, we provide experimental evidence demonstrating that Gβγ physically interacts with NET and that the Gβγ activator mSIRK induces NE efflux through the transporter. These findings identified a novel interaction between Gβγ and NET and highlighted its potential implications in the regulation of NE neurotransmission and associated disorders.

Antibiotic resistance among bacterial pathogens is recognized as a major threat to human health worldwide. The emergence of multidrug-resistant bacteria can also be found in the community settings, apart from hospital environment, which indicates that reservoirs of antibiotic resistance genes do exist outside the hospital. The growth of antibiotic resistance is a consequence of bacterial adaptations in response to selective pressures. To survive in this hostile environment, bacteria develop defence mechanisms such as chemical modification of antibiotics, enzyme-catalysed antibiotic degradation, altered permeability, antibiotic efflux, mutation of target sites and biofilm formation, resulting in resistance to nearly all currently available antibiotics used in the clinical practice. The present review summarizes insights into the molecular mechanisms underlying the antibiotic resistance which is useful for planning strategies to combat antibiotic resistance and devise innovative therapeutic tools to fight against multidrug-resistant bacterial species.

;Yams are economic and medicinal crops with a long growth cycle, spanning between 9-11 months due to the prolonged tuber dormancy. Tuber dormancy has constituted a major constraint in yam production and genetic improvement. In this study, we performed non-targeted comparative metabolomic profiling of tubers of two white yam genotypes, (Obiaoturugo and TDr1100873), to identify metabolites and associated pathways that regulate yam tuber dormancy using gas chromatography-mass spectrometry (GC-MS). Yam tubers were sampled between 42 days after physiological maturity (DAPM) till tuber sprouting. The sampling points include 42-DAPM, 56-DAPM, 87DAPM, 101-DAPM, 115-DAPM, and 143-DAPM. A total of 949 metabolites were annotated, 559 in TDr1100873 and 390 in Obiaoturugo. 39 differentially accumulated metabolites (DAMs) were identified across the studied tuber dormancy stages in the two genotypes. 27 DAMs were conserved between the two genotypes, whereas, 5 DAMs were unique in the tubers of TDr1100873 and 7 DAMs were in the tubers of Obiaoturugo. The differentially accumulated metabolites (DAMs) spread across 14 major functional chemical groups. Amines and biogenic polyamines, amino acids and derivatives, Alcohols, flavonoids, alkaloids, phenols, esters, coumarins and phytohormone positively regulated yam tuber dormancy induction and maintenance, whereas, fatty acids, lipids, nucleotides, carboxylic acids, sugars, terpenoids, benzoquinones, and benzene derivatives positively regulated dormancy breaking and sprouting in tubers of both yam genotypes. Metabolite set enrichment analysis (MSEA) revealed that 12 metabolisms were significantly enriched during yam tuber dormancy stages. Metabolic pathway topology analysis further revealed that six metabolic pathways (linoleic acid metabolic pathway, phenylalanine metabolic pathway, galactose metabolic pathway, starch and sucrose metabolic pathway, alanine-aspartate-glutamine metabolic pathways and purine metabolic pathway) exerted significant impact on yam tuber dormancy regulation. This result provides vital insights into molecular mechanisms regulating yam tuber dormancy.

Molecular communication (MC) is a promising bio-inspired paradigm for exchanging molecule information among nanomachines. This paper proposes a synchronisation-assist photolysis MC system that aims to transmit the bio-sensing signal of the tumour microenvironment, facilitated by mitigating redundant molecules for improved bit error rate (BER) performance. Benefits from bio-compatible MC, biosensors could transmit bio-sensing signals of the tumour in $vivo$ instead of converting them to electrical signals. Due to diffusion motion's slow and stochastic nature, inter-symbol interference (ISI), resulting from previous symbols' residual information molecules, inevitably occurs in diffusion-based MC. ISI is one of the challenges in diffusion-based MC, which significantly impacts signal detection. Inspired by on-off keying (OOK) modulation, the proposed modulation implements a switch of molecules and light alternatively. The light emitted is triggered by a synchronisation signal, and the photolysis reactions could reduce the redundant molecules. An expression for the relevant channel impulse response (CIR) is derived from a hybrid channel model of diffusion and photolysis-reaction. This paper implements the maximum posterior estimation scheme to find the optimal decision threshold and analysis the BER performance in terms of different time intervals of the system. Numerical simulations demonstrate that the proposed method can improve the channel capacity and BER performance. We believe that our work may pave the way for MC application in bio-sensing.

Systematics plays the most crucial role in biodiversity conservation which is at stake due to anthropogenic activities and environmental degradations. The ever-increasing decline of classical taxonomic expertise drives the need to develop molecular marker-based tools for quick, efficient, and reliable detection of organisms, to assess their ecological impacts for deepening our understanding of systematic and evolutionary relationships between organisms which is central to biology. The pace of alpha taxonomy has quickened by its integration with an increasingly fashionable and novel concept called DNA barcoding which utilizes a short genetic marker or barcode to categorize species for enhanced biodiversity assessment. As a supplementary but not complete alternative of systematics research, DNA barcoding, however, not error-free, brings precision in identification by solving existing problems of classical taxonomy and phylogenetics, irrespective of the growth stage of organisms, particularly for known taxa rather than unknown ones. Mitochondrial gene Cytochrome C Oxidase 1 (COI) serves as a universal animal barcode but there is no such universal barcode for plants and developing a suitable one is more challenging. With the recent advancement of Next Generation Sequencing (NGS), DNA metabarcoding technology is advancing rapidly. Still, ambiguity and error prevail with the correct identification of species due to some problems. After extensive analysis of the existing DNA barcoding papers, this review discusses commonly used DNA barcodes in plants and animals, their roles, advantages, limitations to solve existing problems of conservation biology and add the author’s views and recommendations.

Molecular Dynamics (MD) simulations model motion of molecules in atomistic detail and aid in drug design. While simulations on large systems may require several days to complete, analysis of terabytes of data generated in the process could also be time consuming. Recent studies captured exciting and dramatic drug-receptor interactions under cell-like complex conditions. Such advances make simulations of biomolecular interactions more realistic, insightful, and informative and have potential to make drug design more realistic. However, currently available resources and techniques do not provide, in reasonable time, a comprehensive understanding of events seen in simulations. We demonstrate that big data approach results in significant speedups, and provides rapid insights into simulations performed. Advancing this improvement, we propose a scalable, self-tuning, and responsive framework based on Cloud-infrastructure to accomplish the best possible MD studies with given priorities and within available resources.

In this work, a tool for estimating the contact angle from the molecular dynamics simulations is developed and presented. The tool (Achilles) can detect water droplet on hydrophobic and hydrophilic surfaces. The tool can reconstruct the droplets broken across the periodic boundaries. Further a neighbor density based accurate filter is used to find the droplet liquid vapor interface and a circle is fitted using it after removing the dense layers of water next to solid surface. This fitted circle is solved for contact angle and results are outputted in the form of graphical images and text. The entire content of the internal computations of the tool is broken down into 4 phases and users can monitor the outcomes at every phase through output images. The tool is tested using sample molecular dynamics results of water droplet on hydrophobic and hydrophilic surfaces. We believe this tool can be a good addition to the molecular dynamics simulation community who work on the interfacial physics, droplet evaporation, super hydrophobic surfaces, and wettability etc.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

Molecular visualisation is fundamental in the current scientific literature, textbooks and dissemination materials, forming an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Visual exploration has become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. Here we first describe a few Swiss Army knives geared towards protein visualisation for everyday use with an existing large user base, then focus on more specialised tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.

Collisions of low energy electrons with molecules are important for understanding many aspects of the environment and technologies. Understanding the processes that occur in these types of collisions can give insights into plasma etching processes, edge effects in fusion plasmas, radiation damage to biological tissues and more. A radical update of the previous expert system for computing observables relevant to these processes, Quantemol-N, is presented. The new Quantemol Electron Collision (QEC) expert system simplifyies the user experience, improving reliability and implements new features. The QEC GUI interfaces the Molpro quantum chemistry package for molecular target setups and to the sophisticated UKRmol+ codes to generate accurate and reliable cross-sections. These include elastic cross-sections, super elastic cross-sections between excited states, electron impact dissociation, scattering reaction rates, dissociative electron attachment, differential cross-sections, momentum transfer cross-sections, ionization cross sections and high energy electron scattering cross-sections. With this new interface we will be implementing dissociative recombination estimations, vibrational excitations for neutrals and ions, and effective core potentials in the near future.

The combination of wet-lab experimental data on multi-site combinatorial mutations and machine learning is an innovative method in protein engineering. In this study, we present an improved innovative sequence–activity relationship (innov'SAR) methodology based on novel descriptors and digital signal processing (DSP) to construct a predictive model. In this improved approach, 21 experimental (R)-selective amine transaminases from Aspergillus terreus (AT-ATA) were used as an input to predict higher thermostability than that predicted using the existing data. We successfully improved the determination coefficient (R2) of the model from 0.66 to 0.92. In addition, root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were estimated and conformation analysis based on molecular dynamics simulations was performed to verify the enhanced thermal stability of the screened mutants. The improved innov'SAR algorithm enhanced the predictive accuracy, suggesting a method for modifying the stability of AT-ATA, which may help in directed evolutionary screening and open up new avenues for protein engineering.

The incorporation of polycarboxylate ether superplasticizer (PCE) type polymer and silica fume (SF) in high-performance concretes (HPC) leads to the achievement of remarkable rheological and mechanical improvements. In the fresh state, PCEs are adsorbed on cement particles and dispersants, in turn promoting the workability of the concrete. Silica fume enables a very well compacted concrete to be obtained, which is characterized by high mechanical parameters in its hardened state. Some PCEs are incompatible with silica fume, which can result in the loss of slump and in poor rheological behavior. The main objective of the research is the study of the influence of three types of PCEs, which all have a different molecular architecture, on the rheological and mechanical behavior of high-performance concretes containing 10% of SF as a partial replacement of cement. The results show that the carboxylic density of PCE has an influence on its compatibility with SF.

Conclusions: Molecular classification could provide reliable supplementary information for evaluating prognostic and contribute to treatment option decision-making in EEC patients. Fertility-sparing treatment is not recommended for EEC patients with CNH and MSI-H. Furthermore, fertility-sparing treatment can be attempted in EEC patients with CHL, but regular follow-up should be carried out to early detection of EC relapse and prevention of disease progression.

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy, that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for the median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

Polyphenol ellagic acid (EA) possesses anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, remarking it an interesting multi-targeting profile. EA also controls the central nervous system (CNS) since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human α2A-ARs and α2C-AR catalytic pockets, comparing EA behaviour with those ones of known agonist and antagonist. Structurally, the hydrophobic residues surrounding α2A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the α2A-AR, with respect to α2C-AR. Moreover, EA seems to better accommodate within α2A-ARs into TM5 area, closely to S200 and S204 which play a crucial role for activation of aminergic GPCRs such as the α2-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in an yohimbine-sensitive fashion that confirms the engagement of naïve α2-ARs in the EA-mediated effect.

Electrostatic interactions have a determining role in conformational and dynamic behavior of polyelectrolyte molecules [1]. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in water solution with the most commonly used K+ or Na+ counterions were investigated using atomistic molecular dynamics (MD) simulations. Seven common force fields, AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and with the non-bonded fix (NBFIX) and electronic continuum corrections (ECC) to were studied. These corrections have bene introduced to correct for the problem of overbinding of ions to the charged groups of polyelectrolytes. Physical properties, such as molecular sizes, local structure and dynamics, were studied using two types of common counterions, potassium and sodium. The results show that in some cases, the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of ions and charged side chain groups. The local structures and dynamics are more sensitive on dihedral angle parameterization resulting in a preference for defined monomer conformations amd the type of correction used.

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of HEV. Anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old, to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, circulation of the same viral strain for five years was documented. All human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. Sequences from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) predicted using Birth-Death Skyline analysis has fluctuated around 1 over the past 20 years in Russia, but is 10 times higher in Belgorod Region. In conclusion, HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

Zinc finger proteins (ZFP) play important roles in cellular processes. The DNA binding region of ZFP consists of 3 zinc finger DNA binding domains connected by amino acid linkers, the sequence TGQKP connects ZF1 and ZF2, and TGEKP connects ZF2 with ZF3. Linkers act to tune the zinc finger protein in the right position to bind its DNA target, the type of amino acid residues and length of linkers reflect on ZF1-ZF2-ZF3 interactions and contribute to the search and recognition process of ZF protein to its DNA target. Linker mutations and the affinity of the resulting mutants to specific and nonspecific DNA targets were studied by MD simulations and MM_GB(PB)SA. The affinity of mutants to DNA varied with type and position of amino acid residue. Mutation of K in TGQKP resulted in loss in affinity due to the loss of positive K interaction with phosphates, mutation of G showed loss in affinity to DNA, WT protein and all linker mutants showed loss in affinity to a nonspecific DNA target, this finding confirms previous reports which interpreted this loss in affinity as due to ZF1 having an anchoring role, and ZF3 playing an explorer role in the binding mechanism. The change in ZFP-DNA affinity with linker mutations is discussed in view of protein structure and role of linker residues in binding.

This work examines atomic and molecular signatures in laser-induced plasma in standard ambient temperature and pressure environments, including background contributions to the spectra that depend on the laser pulse-width. Investigations include solids, gases, and nano-particles. Abel inversions of measured line-of-sight data reveal insight into the radial plasma distribution. For nominal 6 nanosecond laser pulses and for pulse-energies in the range of 100 to 800 milli-Joules, expansion dynamics and turbulence due to shock phenomena are elucidated to address local equilibrium details that are frequently assumed in spatially averaged emission spectroscopy. Chemical equilibrium computations reveal temperature dependence of selected plasma species. Specific interests include atomic hydrogen (H) and cyanide (CN). The atomic H spectra, collected following optical breakdown in ultra-high-pure hydrogen and 9:1 mixtures of ultra-pure hydrogen and nitrogen gases, indicate spherical shell structures and isentropic expansion of the plasma kernel over and above the usual shockwave. The recombination radiation of CN emanates within the first 100 nanoseconds for laser-induced breakdown in a 1:1 CO₂:N₂ gas mixture when using nanosecond laser pulses to create the micro-plasma. The micro-plasma is generated using 1064 nm, 150 mJ, 6 ns Q-switched Nd:YAG laser radiation. Measurements of the optical emission spectra utilize a 0.64 m Czerny-Turner type spectrometer and an intensified charge-coupled device.

Background: Currently, limited number of therapeutic options are available to treat Diabetes mellitus, and to find a potential candidate, laboratory work takes time and also needs animal studies. So, the aim of this study was to determine the efficacy of some natural phytocompounds with the aid of molecular docking, bioinformatics and in silico drug design approaches. Method: Two proteins (Human CYP3A4 linked to metformin and Human dipeptidyl peptidase-IV) were selected and molecular docking studies were conducted using Pymol, AutoDock Vina, PyRx, and Discovery Studio. Different important pharmacokinetic parameters like ADME and toxicity data were obtained from online databases SwissADME and pkCSM program. Results: It was found that human dipeptidyl peptidase-IV (PDB ID: 4A5S) has exhibited a maximal affinity of -9.7 Kcal/mol for bryonolic acid and hesperidin, but only -6.7 kcal/mol for metformin hydrochloride. Similarly, the highest affinity of hesperidin for human CYP3A4 bound to metformin (PDB ID: 5G5J) is -10.7 Kcal/mol compared to metformin hydrochlor (-6.3 Kcal/mol). Besides, all the compounds have been documented outstanding ADMET profile, and accepted by drug-likeness or Lipinski rule. Conclusions: The present study suggested that these compounds can be further investigated in vitro and in vivo to establish them as lead compounds against Diabetes mellitus..

Emerging viruses description have grown at an unprecedented rate since the beginning of the 21^st century. The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its related illness, Coronavirus Disease 2019 (COVID-19) has been reported as the third highly pathogenic coronavirus introducing itself into human population in the current era after the SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV). Molecular and cellular studies considering the pathogenesis of this novel coronavirus are still in the early stages of research, however, regarding the similarity of SARS-CoV-2 and other coronaviruses, it could be hypothesized that the NF-κB, Cytokine regulation, ERK, and TNF-α signaling pathways are the more likely causes of inflammation upon onset of COVID-19. There are several drugs prescribed and used to alleviate the activity of these inflammatory cellular signaling pathways which might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarized the alteration of cellular signaling pathways affected by coronavirus infection, particularly SARS-CoV and MERS-CoV and tabulated the current therapeutic agents approved for previous human diseases.

The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.

We investigate molecular beam epitaxy growth conditions of micrometers-thick In0.52Al0.48As designed for waveguide of InGaAs/InAlAs/InP quantum cascade lasers. Effect of growth temperature and V/III ratio on the surface morphology and defect structure were studied. The growth conditions which were developed for the growth of cascaded In0.53Ga0.47As/In0.52Al0.48As active region, e.g. growth temperature of TG=520°C and V/III ratio of 12, turned out to be not optimum for the growth of thick In0.52Al0.48As waveguide layers. It has been observed that after exceeding ~1µm thickness the quality of In0.52Al0.48As layers deteriorates. The in-situ optical reflectometry showed increasing surface roughness caused by defect forming, which was further confirmed by High Resolution X-Ray reciprocal space mapping, optical microscopy and atomic force microscopy. The presented optimization of growth conditions of In0.52Al0.48As waveguide layer led to the growth of defect free material, with good optical quality. This has been achieved by decreasing the growth temperature to TG=480 °C with appropriate increasing V/III ratio. At the same time the growth conditions of the cascade active region of the laser were left unchanged. The lasers grown using new recipe have shown lower threshold currents and improved slope efficiency. We relate this performance improvement to reduction of the electron scattering on the interface roughness and decreased waveguide absorption losses.

In Pakistan, bats are one of the dominant mammals that play an important role in the ecosystem in terms of pollination, seed dispersal, and control of pest insects. Bats have also played an im-portant role in the emergence and transmission of zoonotic pathogens; however, most current studies focus on viral pathogens, not potential bacterial pathogens. This study was designed to estimate the prevalence and antibiotic profiling of Staphylococcus (S.) aureus in oral and rectal samples from bats captured in northern Pakistan and to determine the factors associated with in-fection. Two hundred individual bats of five species: Pipistrellus javanicus (n = 17), Pipistrellus pipistrellus (n = 10), Rhinopoma microphyllum (n = 48), Rousettus leschenaultii (n = 124), and Scotophilus kuhlii (n = 1) were captured for non-lethal collection of oral and rectal samples to iso-late S. aureus. Bats were sampled from three sites: a natural cave, a man-made castle, and an an-imal shed, in Khyber Pakhtunkhwa and Punjab provinces. Oral (n = 200) and rectal (n = 200) swabs were collected from each individual bat using sterile cotton swabs specifically for use in bacteriological studies. Each isolate of bacteria was identified by using phenotypic tests and con-firmed as S. aureus based on PCR assay. Out of a cumulative four hundred samples, 80 swabs were positive for S. aureus including 47 rectal and 33 oral swabs. Prevalence of S. aureus infection varied significantly among species, with Rousettus leschenaultii exhibiting the highest prevalence (n = 77; 37.90%). In addition to bat species, prevalence varied significantly among habitats but not between sex, age class, or reproductive status. This study confirmed the occurrence of S. aureus in oral and rectal microbiota of bats in Pakistan. Importantly, S. aureus isolates showed resistance to tetracycline, gentamicin, and erythromycin and carried resistant genes such as TetK, TetM, Erma, and aacA-D. In this regard, efforts should be taken to educate the local communities on how to minimize exposure to an antibiotic-resistant bacterial pathogen through contact with bats while simultaneously increasing the awareness of protecting bats as a vital component of our ecosystem.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 65 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2, and altered expression of growth factor receptors and microRNAs. These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Natural deep eutectic solvents (NADES) have been shown as selective and environmentally friendly solvents for the extraction of bioactive compounds. However, studies on the solubility of low molecular weight carbohydrates (LMWC) in NADES are scarce. In this work, new solubility data of LMWC in NADES are provided and a new approach based on the use of these solvents for the efficient fractionation of bioactive carbohydrates was explored for the first time. Several mono- and disaccharides and three NADES based on choline chloride (ChCl) and different donors [2-ethylene glycol (EtG), glycerol (Gly) and ethanedioic acid dihydrate (Eth)] were considered. While degradation of carbohydrates, mainly ketoses, was detected with ChCl:Eth due to its acidic nature, ChCl:EtG and ChCl:Gly were found to be useful alternatives for selectively separating bioactive ketoses and their corresponding aldoses (e.g. lactulose/lactose and tagatose/galactose) present in equimolar binary mixtures. In addition, the usefulness of ChCl:EtG for the selective enrichment of lactulose to be used as food ingredient or nutraceutical was proven (from a 25% in the reaction mixture to a 56% in the purified sample). NADES could be used for the selective fractionation of value-added carbohydrates from interfering sugars for several applications including food science, engineering or pharmaceuticals.

Matrix Metaloproteinase-2 (MMP-2) is an extracellular Zn²⁺ protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed 10 families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamics cross correlation analysis indicated domain movements corresponding to opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the MMPBSA-interaction entropy analysis method and revealed strong binding energies for the catalytic Zn²⁺ ion 1, Ca²⁺ ion 1, and Ca²⁺ ion 3 with significant conformational stability at the binding sites of Zn²⁺ ion 1 and Ca²⁺ ion 1. Ca²⁺ ion 2 diffuses freely away from its crystallographically defined binding site. Zn²⁺ ion 2 plays a minor role in conformational stability of the catalytic domain while Ca²⁺ ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain.

Inositol poly- and pyrophosphates (InsPs and PP-InsPs) are central eukaryotic messengers. These very highly phosphorylated molecules can exist in two distinct conformations, a canonical one with five phosphoryl groups in equatorial positions, and a “flipped” axial conformation. Using 13C-labeled InsPs / PP-InsPs, the behavior of these molecules was investigated by 2D-NMR under solution conditions reminiscent of a cytosolic environment. Remarkably, the most highly phosphorylated messenger InsP8 readily adopts both conformations at physiological conditions. Environmental factors - such as pH, metal cation composition, and temperature - strongly influence the conformational equilibrium. Thermodynamic data revealed that the transition of InsP8 from the equatorial to the axial conformation is, in fact, an exothermic process. The speciation of InsPs and PP-InsPs also affects their interaction with protein binding partners; addition of Mg2+ decreased the binding constant Kd of InsP8 to an SPX protein domain. The results illustrate that PP-InsP speciation reacts very sensitively to solution conditions, suggesting it might act as an environment-dependent molecular switch.

We performed for the first time to our knowledge fully ab initio molecular dynamics simulations of additive tribochemistry in boundary lubrication conditions. We consider an organophosphourus additive that has been experimentally shown to reduce friction in steel-on-steel sliding contacts thanks to the tribologically-induced formation of an iron phosphide tribofilm. The simulations allow us to observe in real time the molecular dissociation at the sliding iron interface under pressure and to understand the mechanism of iron phosphide formation. We discuss the role played by the mechanical stress by comparing the activation times for molecular dissociation observed in the tribological simulations at different applied loads with that expected on the basis of the dissociation barrier.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds is under clinical investigation for various diseas-es. Especially, marine natural compounds are gaining more attention in the new drug develop-ment process. The present study has aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the four SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds namely Chrysophaentin A (-6.6 kcal/mol), Geodisterol sulfates (-6.6 kcal/mol), Hymenidin (-6.4 kcal/mol), Plinabulin (-6.4 kcal/mol) and Tetrodotoxin (-6.3 kcal/mol) expressed the minimized binding energy and molecular interactions such as covalent and hydrophobic interactions to the SARS CoV-2 Main Protease. Using Molecular dynamic stud-ies, the Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (ROG), and Hydrogen bonds (H-Bonds) values were calculated for SARS-CoV-2 Main Protease with Hymenidin docked complex. Additionally, in silico Druglikeness and pharmaco-kinetic property assessments of the compounds demonstrated favorable druggability. These re-sults suggested that marine natural compounds are capable of fighting SARS-CoV-2. Further, in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target actin-binding protein gelsolin that is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP2-binding domain of gelsolin in the gelsolin-actin complex through extensive ten microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP2-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex.

The adsorption of proteins on polymer is widely used in biosensors. Here, molecular dynamics (MD) simulation was used to study the immobilization of angiotensin converting enzyme II (ACE2) with six initial orientations proposed on polystyrene (PS) at the ambient conditions of pH (4.5, 6, 7, 8, 9.5) and NaCl (0.01, 0.05, 0.1, 0.15, 0.2, 0.25 M). ACE2 immobilization under favorable ambient conditions was characterized by minimum distance (short), settlement time (fast), interaction energy (substantial) and protein configuration (stable). ACE2 orientations proposed in 0.15M NaCl were respectively preferable to (90, 0, 0), (0, 0, 0) and (0, 270, 0), (180, 0, 0) and (0, 90, 0), (90, 0, 0) at pH 4.5, 6, 7, 9.5. ACE2 immobilization was further evaluated at pH 7 by optimizing NaCl concentration. Its proposed orientations of (i) (0, 270, 0), (ii) (0, 0, 0) and (90, 0, 0), and (iii) (0, 90, 0) and (90, 0, 0) were preferable in 0.05, 0.1 and 0.2 M NaCl, respectively. The great significance of cubic-orientation settlement mode provides tangible improvement for the microfabrication of biochips for rapid diagnosis of severe acute respiratory syndrome coronavirus II (SARS-CoV-2).

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD) with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol-1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study allows establishing that the depopulation of the NNC core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

Introduction: Coronaviruses are zoonotic viruses that include human epidemic pathogens such as the Middle East Respiratory Syndrome virus (MERS-CoV), and the Severe Acute Respiratory Syndrome virus (SARS-CoV), among others (e.g., COVID-19, the recently emerging coronavirus disease). The role of animals as potential reservoirs for such pathogens remains an unanswered question. No systematic reviews have been published on this topic to date. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess MERS-CoV and SARS-CoV infection in animals and its diagnosis by serological and molecular tests. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 6,493articles were retrieved (1960-2019). After screening by abstract/title, 50 articles were selected for full-text assessment. Of them, 42 were finally included for qualitative and quantitative analyses. From a total of 34 studies (n=20,896 animals), the pool prevalence by RT-PCR for MERS-CoV was 7.2% (95%CI 5.6-8.7%), with 97.3% occurring in camels, in which pool prevalence was 10.3% (95%CI 8.3-12.3). Qatar was the country with the highest MERS-CoV RT-PCR pool prevalence, 32.6% (95%CI 4.8-60.4%). From 5 studies and 2,618 animals, for SARS-CoV, the RT-PCR pool prevalence was 2.3% (95%CI 1.3-3.3). Of those, 38.35% were reported on bats, in which the pool prevalence was 14.1% (95%CI0.0-44.6%). Discussion: A considerable proportion of infected animals tested positive, particularly by nucleic acid amplification tests (NAAT). This essential condition highlights the relevance of individual animals as reservoirs of MERS-CoV and SARS-CoV. In this meta-analysis, camels and bats were found to be positive by RT-PCR in over 10% of the cases for both; thus, suggesting their relevance in the maintenance of wild zoonotic transmission.

Chicken collagen is a promising raw material source to produce gelatins and hydrolysates. Gelatins and hydrolysates can be prepared biotechnologically using proteolytic enzymes produced by submerged fermentation of genetically modified microorganisms. By choosing the appropriate process conditions, such changes can be achieved at the molecular level of collagen, making it possible to prepare products with targeted properties for advanced cosmetic, pharmaceutical, medical or food applications. The research aims to investigate: i) antioxidant activity (DPPH and ABTS) in model samples of chicken collagen products (gelatin and hydrolysates); ii) distribution of molecular weights by the GPC-RID analysis method; iii) functional groups and configuration of polypeptide chains related to molecular level properties using FTIR; iv) the microbiological properties on SDA, PCA, TSA and VRBL microbial populations using MALDI method. Antioxidant activity towards ABTS radicals of more than 80% was found for all samples. The molecular weights of all gelatin samples showed typical α- and β-chains. FTIR analysis confirmed that the samples showed all typical vibrational regions for collagen cleavage products, Amide A and B, Amide I, II, and III at characteristic values. Microbiological analysis of the prepared samples showed no undesirable bacteria that would limit advanced applications of the prepared products. Gelatins and hydrolysates from chicken stomachs represent a promising alternative to products made from standard collagen tissues of terrestrial animals.

The emergence of multidrug-resistant pathogens such as Listeria monocytogenes and Shiga toxin-producing Escherichia coli (STEC) poses public health challenges, and this has led to a continuous search for effective novel antimicrobial agents. This study aimed to isolate marine actinomycetes from South Africa, evaluate their in vitro antimicrobial activity against Listeria and STEC, and characterize their mechanisms of action. Marine actinoymcetes were isolated and identified by 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical constituents of bioactive actinomycetes secondary metabolites. Antibacterial activity of the secondary metabolites was assessed by the broth microdilution method and their mode of actions were predicted using computational docking. While five strains showed antibacterial activity during primary screening, only Nocardiopsis dassonvillei strain SOD(B)ST2SA2 exhibited activity during secondary screening for antibacterial activity. GC-MS identified five major bioactive compounds: 1-octadecene, diethyl phthalate, pentadecanoic acid, 6-octadecenoic acid, and tri-fluoroacetoxy hexadecane. SOD(B)ST2SA2`s extract demonstrated the minimum inhibitory con-centration and minimum bactericidal concentration ranging from 0.78–25 mg/ml and 3.13 to > 25 mg/ml, respectively. Diethyl phthalate displayed the lowest bacterial protein binding energies (kcal/mol): −7.2, dihydrofolate reductase; −6.0, DNA gyrase B, and −5.8, D-alanine:D-alanine lig-ase. Thus, marine N. dassonvillei SOD(B)ST2SA2 is a potentially good source of antibacterial compounds that can be used to control STEC and Listeria monocytogenes.

In previous studies regarding the osseointegration of zirconia (ZrO2) implants, a lack of consistency was observed in the surface topographies of the ZrO2 and Ti samples because of the difficult processability of ZrO2 surfaces. To resolve this problem, we used the molecular precursor method (wet process), which is a surface-modifying technique that can easily change the surface chemistry without changing the surface topography. A roughened Ti surface was prepared using sandblasting (large-grit) and acid treatment. We were able to create ZrO2-coated Ti implants with the same topography as that of roughened Ti substrates using the molecular precursor method, which solution contained a Zr complex. The uniform presence of tetragonal Zr was confirmed, and the apparent zeta potential of the surface of the ZrO2-coated Ti implant was higher than that of Ti. In animal experiments, ZrO2-coated Ti implants showed an equivalent or higher bone-to-implant contact ratio compared to that of the non-coated implants inserted into the femur bone defects of the rats. ZrO2 with the same surface topography as that of roughened Ti exhibits a promotion of osteogenesis equivalent to or better than that of Ti in the early stages of bone formation.

Molecular dynamics(MD) simulations are carried out to characterize the mechanicalproperties and failure behavior of van der Waals heterostructures composed ofgraphene and hexagonal boron nitride(hBN) single layer sheets. The graphene–hBNand hBN–graphene–hBN heterostructures simulations are carried out under tensileand shear deformation. Accordingly, stress versus strain curves of each systemare plotted and various properties of heterostructures, namely elastic modulusand shear modulus as well as failure stress and failure strain, are evaluatedand compared with one another as well as with the pristine graphene and hBNsheets. Subsequently, the failure mechanism/characterization of each sheet in theheterostructures is described. Alternatively, the elastic and shear modulus of eachheterostructure are computed by means of rule of mixture(ROM) which are in goodagreement with results that are obtained from MD simulations.

Mechanochemical technology is developing rapidly, judging by the scientific information in both basic and applied studies. However, many issues and points of view remain to be discussed. This review presents some new key issues for the optimization of mechanochemical processes in theoretical and practical aspects. Emphasis is placed on powder technology aspects, which are not always discussed compared to functional or microscopic viewpoints. The transfer of chemical species across the interparticle interface between organic and inorganic species during the mechanosynthesis of nanocomposite oxides offers many new possibilities, which are discussed here in detail. Since all material transport is preceded by charge transfer, its driving force has been searched for using terminology beyond the well-established electrochemical ones. The role of organic compounds during the whole process is emphasized, regardless of their survival in the final product. The similarity with the pharmaceutical phenomena is pointed out, although its mentality is very different from that of the synthesis of nanocomposites. Not only for the rational amorphization of the active pharmaceutical ingredient, but also for the stabilization of molecular dispersion states with the participation of excipients are discussed. The effects of liquids, either added or formed by mechanochemical auto-liquefaction, are presented with reference to the comparison between wet and dry grinding. Finally, mechanisms of apparent stabilization of mechanically activated states of products are elucidated to investigate the practical applicability of mechanochemically synthesized products

Entamoeba histolytica, throughout its lifecycle, encounters a variety of stressful conditions. This parasite possesses Heat Shock Response Elements (HSEs) which are crucial for regulating the ex-pression of various genes, aiding in its adaptation and survival. These HSEs are regulated by Heat Shock Transcription Factors (EhHSTFs). Our research has identified seven such factors in this parasite, designated as EhHSTF1 through EhHSTF7. Significantly, under heat shock condi-tions and in the presence of the antiamoebic compound emetine, EhHSTF5, EhHSTF6, and EhHSTF7 show overexpression, highlighting their essential role in gene response to these stressors. Currently, only EhHSTF7 has been confirmed to recognize the HSE in the promoter of the EhPgp5 gene (HSE_EhPgp5), leaving the binding potential of the other EhHSTFs to HSE yet to be explored. Consequently, our study aimed to examine both in vitro and in silico the oligomeri-zation and binding capabilities of the recombinant EhHSTF5 protein (rEhHSTF5) to HSE_EhPgp5. The in vitro results indicate that the oligomerization of rEhHSTF5 is concentration-dependent, with its dimeric conformation showing a higher affinity for HSE_EhPgp5 than its monomeric state. In silico analysis suggests that the alpha 3 α-helix (α3-helix) of the DNA-binding domain (DBD5) of EhHSTF5 is crucial in binding to the major groove of HSE, primarily through hydro-gen bonding and salt-bridge interactions. In summary, our results highlight the importance of oligomerization in enhancing the affinity of rEhHSTF5 for HSE_EhPgp5 and demonstrate its abil-ity to specifically recognize structural motifs within HSE_EhPgp5. These insights significantly contribute to our understanding of one of the potential molecular mechanisms employed by the parasite to efficiently respond to various stressors, thereby enabling successful adaptation and survival within its host environment.

Excitotoxicity related to the dysfunction of the N-methyl-d-aspartate receptor (NMDAR) has been indicated to play an integral role in the pathophysiology of multiple disease states, including neurodegenerative disorders such as Parkinson’s disease. There is a notable gap in the market for novel NMDAR antagonists, however current methods to analyze potential antagonists rely on indirect measurements of calcium flux and hazardous radioligand binding assays. Recently, a fluorescent NMDAR ligand, N-adamantan-1-yl-dimethylamino-1-naphthalenesulfonic acid, known as AM-DAN was developed by our group. Additional studies on this ligand is necessary to evaluate its potential as a biological tool in NMDAR research. Therefore, this study was aimed at conducting structural analyses, fluorescence experiments, high-accuracy NMDAR molecular modelling and NMDAR phencyclidine (PCP) site competition binding studies using AM-DAN. Results revealed that AM-DAN has appropriate structural properties, significant fluorescent ability in various solvents and is able to bind selectively and compete for the PCP-binding site of the NMDAR. Therefore, AM-DAN holds promise as a novel fluorescent ligand to measure the affinity of prospective drugs binding at the NMDAR PCP-site and may circumvent the use of radioligands.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

As a widely used plastic, the aging and degradation of polyethylene (PE) are inevitable problems, whether the goal is to prolong the life of PE products or address the issue of white pollution. Molecular simulation is a vital scientific tool in elucidating the mechanisms and processes of chemical reactions. To obtain the distribution and evolution process of PE's thermal oxidation products, this work employs the self-consistent charge density functional tight binding (SCC-DFTB) method to perform molecular simulations of the thermal oxidation of PE with different crystallinity and branched structures. We discovered that crystallinity does not affect the thermal oxidation mechanism of PE, but higher crystallinity makes PE more susceptible to cross-linking and carbon chain growth, reducing the degree of PE carbon chain breakage. The branched structure of PE results in differences in pore size between the carbon chains, with larger pores leading to a concentrated distribution of O2 and free radicals subsequently formed. The breakdown of PE is slowed down when free radicals are localized in low-density regions of the carbon chain. The specifics and mechanism of PE's thermal oxidation are clearly revealed in this paper, which is essential for understanding the process in-depth and for the development of anti-aging PE products.

Never in mitosis gene A-related kinase 2 (NEK2) a member of serine-threonine kinase protein mainly involved in the cell cycle process. Clinical studies revealed NEK2 overexpression in various tumour types, also NEK2 was reported for their association with genetic abnormalities like mitotic machinery deregulation and chromosomal instability. Besides NEK2 plays a key role in maintaining the transformed phenotype of cancer cells and chemo-resistance of several tumour types. Thus, NEK2 transcriptional profile is important for diagnosis, treatment, and prognosis stages of cancer studies. Screening of novel NEK2 inhibitor would be beneficial in developing the specific lead molecules. Our studies involved NEK2 transcriptional profile search, screening of druggable cavities in NEK2, Drug likeliness of mangrove derived naphthoquinone derivatives avicennoneA , avicennoneB , avicennoneC , avicennoneD , avicenoneE , avicennone F , and avicennone G , avicequinone A, stenocarpoquinone B , avicequinone C , avicenol A , avicenol C,brugine, apigenin, chrysin and molecular docking studies to assess MNC compounds binding efficacy towards NEK2. Mangrove derived compounds conferred the intermolecular hydrogen bond, Pi-alkyl,pi-cation interactions with NEK2 kinase domain region residues Tyr 19, Lys 37, Arg 164, Lys174. Nearly 200 kinase proteins contained this promising Cys 22 residue as its positioned in the catalytic site like NEK family proteins. Avicenna A, Avicennone G, Chrysin and Brugine formed the irreversible covalent binding with NEK2 through Cys 22, thus they can be considered as potential kinase inhibitors with the limited off-target response. But these MNC compounds need to be tested further in invitro and invivo studies to propose as potent NEK2 inhibitors.

Titanium dioxide nanoparticles have risen concerns about their possible toxicity and the European Food Safety Authority recently banned the use of TiO2 nano-additive in food products. Following the intent of relating nanomaterials atomic structure with their toxicity without having to conduct large scale experiments on living organisms, we investigate the aggregation of titanium dioxide nanoparticles using a multi-scale technique: starting from ab initio Density Functional Theory to get an accurate determination of the energetics and electronic structure, we switch to classical Molecular Dynamics simulations to calculate the Potential of Mean Force for the connection of two identical nanoparticles in water; the fitting of the latter by a set of mathematical equations is the key for the upscale. Lastly, we perform Brownian Dynamics simulations where each nanoparticle is a spherical bead. This coarsening strategy allows studying the aggregation of a few thousand nanoparticles. Applying this novel procedure, we find three new molecular descriptors, namely, the aggregation free energy and two numerical parameters used to correct the observed deviation from the aggregation kinetic described by the Smoluchowski theory. Molecular descriptors can be fed into QSAR models to predict the toxicity of a material knowing its physicochemical properties, without having to conduct large scale experiments on living organisms.

The effect of graphene (GR) on Ni surface relaxation and reconstruction in three different substrate orientations: {111}, {001}, {011}, at two different temperatures: 300K and 400K was studied using Molecular Dynamics simulation. The change of the interplanar distances of the substrate and redistribution of Ni and C atoms in direction perpendicular to the surface were compared with the equilibrium state of GR and bulk Ni, in the absence of the counterpart. The surface reconstruction for GR/Ni system was analyzed base on the calculated radial pair distribution function of Ni and C atoms. The surface roughness was visualized using 2D atomic distribution maps. For the studied substrate orientations and temperatures, it was found that the most densely packed orientation of the Ni base {111} provides minimal changes of the structural parameters of both counterparts at 400 K.

Phenotypes are driven by regulated gene expression, which in turn are mediated by complex interactions between diverse biological molecules. Protein-DNA interactions such as histone and transcription factor binding are well studied, along with RNA-RNA interactions in short RNA silencing of genes. In contrast, lncRNA-protein interaction (LPI) mechanisms are comparatively unknown, likely driven by the difficulties in studying LPI. However, LPI are emerging as key interactions in epigenetic mechanism, playing a role in development and disease. Their importance is further highlighted by their conservation across kingdoms. Hence, interest in LPI research is increasing. We therefore review the current state of the art in lncRNA-protein interactions. We specifically surveyed recent computational methods and databases which researchers can exploit for LPI investigation. We discovered that algorithm development is heavily reliant on a few generic databases containing curated LPI information. We show that early methods predict LPI using molecular docking, have limited scope and are slow, creating a data processing bottleneck. Recently, machine learning has become the strategy of choice in LPI prediction, likely due to the rapid growth in machine learning infrastructure and expertise. While many of these methods have notable limitations, machine learning is expected to be the basis of modern LPI prediction algorithms.

Bimetallic nanoparticles are of interest since they lead to many interesting electrical, chemical, catalytic, and optical properties. They are particularly important in the field of catalysis since they show superior catalytic properties than their monometallic counterparts. The structures of bimetallic nanoparticles depend mainly on the synthesis conditions and the miscibility of the two components. In this work, PdPt alloyed-bimetallic nanoparticles (NPs) were synthesized through the polyol method, and characterized using spherical aberration (Cs) corrected scanning transmission electron microscopy (STEM). High-angle annular dark-field (HAADF)-STEM images of bimetallic nanoparticles were obtained. The contrast of images shows that nanoparticles have an alloy structure with an average size of 8.2 nm. Together with the characterization of nanoparticles, a systematic molecular dynamics simulations study, focused on the structural stability and atomic surface segregation trends in 923-atom PdPt alloyed-bimetallic NPs was carried out.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.