Amyloid-β aggregation into protofibrillar and fibrillar assemblies is a central hallmark of Alzheimer's disease (AD), making disruption of A β42 protofibrils a promising therapeutic strategy. Here, we assessed the destabilization potential of five naturally occurring biphenolic stilbenoids - Resveratrol, Piceid, Astringin, Piceatannol, and Rhapontigenin - through an integrated in silico approach. Molecular docking, 500 ns all-atom molecular dynamics simulations, MM-PBSA binding free energy calculations, and structural analyses (RMSD, RMSF, radius of gyration, hydrogen-bond and salt-bridge dynamics, intersheet contacts, and principal component analysis) were employed to capture ligand-induced perturbations in fibril stability. Docking revealed preferential binding at β-sheet-forming hotspots (PHE19, PHE20, VAL36, GLY38) along the interchain interface. Among the studied compound, Rhapontigenin exhibited the most favorable binding free energy (ΔGbfe = -16.732±5.807 kcal/mol) and induced pronounced disruption of hydrogen-bond networks, salt-bridge integrity, and fibrillar compactness. Structural descriptors further indicated chain-terminal deformation, elevated RMSD and Rg, and broadened conformational sampling, reflecting loss of fibril rigidity. Piceatannol and Piceid exerted moderate destabilization effects, whereas Astringin and Resveratrol showed minimal impact. These findings identify Rhapontigenin as a potent destabilizer of A β42 protofibrils and highlight naturally derived stilbenoids as promising scaffolds for anti-amyloid drug design, while underscoring the value of simulation-driven strategies for targeting protein aggregates.

Selective Estrogen Receptor Modulators (SERMs) represent a critical therapeutic approach in hormone-dependent breast cancer, specifically in cases fueled by the ER-α. This comprehensive study presents a comparative evaluation of three prominent selective estrogen receptor modulators (SERMs), including two benzothiophene-derived compounds, Raloxifene and Arzoxifene, and one tetrahydronaphthalene-based molecule, Lasofoxifene, using an integrated computational approach. Utilizing advanced computational techniques, the molecular docking investigations identified Lasofoxifene possess the highest binding affinity towards ER-α among the studied SERMs, which were subsequently investigated through extensive molecular dynamics (MD) simulations to elucidate the stability and interaction behavior of the ER-α - SERM complexes over nanosecond timescales. In particular, the ER-α complexes with Lasofoxifene and Arzoxifene exhibit more compactness and structural stability of the receptor, based on their radius of gyration and hydrogen bond analysis data. However, principal component analysis (PCA) reveals the nature of conformational fluctuations in the ER-α - Lasofoxifene complex, indicating a reduced conformational state compared to the other complexes. Further, the binding free energy analysis using the MM-PBSA approach displayed the most favorable energetic profile corresponding to the ER-α - Lasofoxifene complex, governed predominantly by the hydrophobic interactions within the binding pocket. A combined evaluation of docking scores, stability parameters, and energetic profiles consistently identifies Lasofoxifene as forming the most stable complex with ER-α among the investigated ligands. So, the investigations provide a molecular-level understanding of ER-α inhibition and highlight Lasofoxifene as a promising candidate with strong inhibitory potential.

Estrogen receptor alpha (ERα) plays a crucial role in the progression and proliferation of BC cells. Although anti-estrogen treatments such as tamoxifen have significantly improved treatment outcomes, but their prolonged use is associated with therapeutic resistance and adverse effects. These limitations emphasize the urgent necessity for novel, safer ERα targeting molecules. This research investigates pyrimidine derivatives as potential ERα modulators, employing an advanced multi-step computational approach including high-throughput structure-based virtual screening, docking analysis, molecular dynamics simulation, and density functional theory calculation to screen promising inhibitors targeting the ERα ligand-binding domain involved in tumor angiogenesis. A pyrimidine-based dataset containing 2,10,798 molecules was subsequently obtained from PubChem and subjected to structure-based virtual screening, and docked in XP and SP mode, on binding cavity of ERα protein PDB ID 4XI3. Twenty molecules showing favourable docking interactions were shortlisted for further pharmacokinetic profiling and MM-GBSA binding free energy estimation. The multistep screening identified HIT 1 compound with a superior docking score (-13.901 kcal/mol) as compared to standard drug raloxifene (-12.136 kcal/mol), as well as favourable pharmacokinetic properties and enhanced MM-GBSA binding free energies. To examine the dynamic stability of complex, a 500ns molecular dynamic simulation was performed for the ERα-HIT 1 system. In addition, DFT calculations supported its electronic stability and bio-feasibility through analysing its HOMO-LUMO energy gap. These results suggest that the HIT 1 molecule serves as a promising scaffold for the development of a novel ERα modulator with potential to suppress ERα-mediated BC progression and angiogenesis.

Estrogen receptor α (ERα) is primary transcription factor for regulating gene expression, promoting cell migration and cell proliferation, leading into growth and development breast cancer (BC). Azepine derivatives were capable of modulating ERα expression in clinics and shown promise as efficient anti-BC agents. Thereby, present study aims to identify potent, safer azepine derivatives as ERα targeted anti-BC agents to overcome drug-resistance and adverse effects of current BC therapy. A rational in silico drug-discovery approach of 8 independent experiments was carried out consecutively as pharmacophore mapping and phase screening, HTVS and molecular docking, ADME, MM/GBSA, Molecular Dynamics (MD) simulations (500 ns) and MM/PBSA, DFT, PASS activity prediction and toxicity assessment, to identify potential hits. Pharmacophore-screened molecules comprising all traits of AAHHRR_1 model, undergone HTVS, SP and XP docking hierarchically, to yield 6 HITs exhibiting higher predicted binding affinities for ER-α compare to tamoxifen, toremifene and raloxifene. Analyzing drug-likeness, pharmacokinetics and binding free energies of hits and standards revealed HIT4 as most optimistic drug-candidate. MD simulations, MM-PBSA and H-bond analysis certified high predicted binding affinity and stability of HIT4 inside ERα protein. DFT calculations further validated bio-feasibility of HIT4 via HOMO-LUMO energy gap (3.238 eV) estimation. Activity and toxicity prediction study revealed anti-neoplastic and anti-estrogenic potential of HIT4 exhibiting class IV oral toxicity. Findings of pharmacophore modeling, structural analysis and binding mechanism study led us a lead framework for optimizing azepine derivatives as promising anti-estrogens. It is suggested that reducing lipophilicity of HIT4 by replacing hydrophobic alkyl-linkage with electronegative spacers may provide novel azepine-based anti-BC agents.

Numerous ideas and methods have been created since the biological sensor was first established to increase biosensor functionality. The recently produced carbon material known as the “pristine C60 molecule” has unique physicochemical features that enhance the potential for creating highly sensitive biosensors. This study aims to conduct computational investigations on utilization of pristine C60 molecule and the addition of elements as impurities into the same (doped-C60) as sensors for Ferulic acid. The Introduction of impurities into nanomaterial structures increase intermolecular interactions. As an adsorbent, the pristine C60 structure doped with B, Al, Ga, Ge, Si, N, and P has been investigated. The interaction between pristine C60 molecule or a doped heterofullerenes and Ferulic acid is studied using DFT methods. Using the hybrid functional B3LYP and 6-31G(d) basis set, the relationship between the optimized doped structures and the optimized Ferulic acid structure was examined. To the best of our knowledge, this is the first such examination related to the intermolecular interaction between ferulic acid and doped-C60 and its sensitivity. The sensitivity of the doped-C60 towards Ferulic acid were evaluated by the HOMO-LUMO energy gap and CDFT (Conceptual Density Functional Theory). In comparison to the other C60 materials under study, the results indicate that Al-doped heterofullerene has a higher interaction/adsorption potential and sensitivity towards Ferulic acid. Furthermore, Si-doped heterofullerene exhibits the least energy gap and has good reusable biosensor capability. We have calculated the quantum descriptors, DOS plots, ELF plots, Quantum Theory of Atoms in Molecules (QTAIM), and NCI analysis to learn more about the nature of intermolecular interactions during the adsorption phenomena.

Since the invention of the biological sensor, many proposals and techniques have been developed to improve biosensor functionality. Because of its unique physicochemical properties, the recently developed carbon material “fullerene” improves the possibilities for developing highly sensitive biosensors. This study aims to conduct a computational investigations on utilization of fullerene (C60) and the addition of elements as impurities into the same (doped-C60) as sensors for EGCG. The introduction of impurities into nanomaterial structures increases intermolecular interaction. The fullerene structure, doped with Al, Ga, B, Si, Ge, and P, has been studied as an adsorbent. Density Functional Theory (DFT) based methods are used to investigate the interaction between fullerene or doped fullerene and EGCG. The interaction between the optimized doped structures and the optimized EGCG structure was investigated using the hybrid functional B3LYP, and 6-31G(d) basis set. To the best of our knowledge, this is the first such observation related to the intermolecular interaction between EGCG and doped-C60 and its sensitivity. The sensitivity of the doped-C60 towards EGCG were evaluated by the HOMO-LUMO energy gap and Conceptual Density Functional Theory (CDFT). The results depict Al-doped fullerene shows higher interaction/adsorption potential and sensitivity towards EGCG, as compared to the other studied C60 materials. To acquire knowledge about the nature of intermolecular interactions during the adsorption phenomena, we have computed the Quantum Descriptors, Density of States(DOS) plots, Quantum Theory of Atoms in Molecules (QTAIM), and Non-Covalent Interaction (NCI) analysis. By creating high-sensitivity sensors for bioactive molecules like polyphenolic compounds (EGCG) in exploration of variety of dopants can be used in drug delivery, public health, and environmental monitoring. So, this study aims to improve biosensor technology and lays the foundations for future modular and accurate molecular sensor designs.

Breast cancer is among the most prevalent causes of death in women worldwide. About 70-75% of these cancers are hormone-dependent, expressing estrogen receptors (ERs), mainly ER-α, making it an essential target for managing breast cancer. Potentilla genus has been traditionally used worldwide for its diverse biological activities, including antidiabetic, anti-inflammatory, antioxidant, etc. In the present study, phytochemicals isolated from various species of the Potentilla species were evaluated for their in silico ER-α inhibitory activity through molecular docking, molecular dynamic simulation, Density Functional Theory calculations and free energy calculations. Four hundred seventy-one molecules were used through ligand preparation and docked inside the generated grid on ER-α protein cavity and the standard drug tamoxifen. Fourteen molecules have shown better dock (-14.42 to -12.57 kcal/mol) scores than tamoxifen (-10.71 kcal/mol). Most of the molecules belong to the category of flavonoid glycosides. Molecules with good binding free energy (-78.81 to -12.94 kcal/mol) indicate stability inside the binding pocket. Further, based on dock score, pharmacokinetic parameters, and binding free energy, two hit molecules, 1 and 2, were selected for their molecular dynamic simulation, MM/PBSA and DFT calculations for assessing their stability and structural dynamics inside the binding cavity as well as their reactivity. Through MD simulation analysis, it was evaluated that Compound 1 could distort the protein to a greater extent. In contrast, compound 2 was stable throughout the simulation time of 150 ns and can be further explored in vitro and in vivo studies as ER-α inhibitors in breast cancer.

With increasing antibiotic resistance and hospital acquired microbial infections, there has been a growing interest to explore alternate antimicrobial approaches. This is particularly challenging when aiming to protect surfaces over...

AIM:Previous studies have demonstrated that contact lenses coated with the antimicrobial cationic peptide Mel4, a derivative of melimine, can reduce the occurrence of keratitis. However, the antimicrobial activity of Mel4 weakened over time due to its susceptibility to proteolytic degradation. Oligo-N-substituted glycine peptoids such as TM5 and TM18 possess antimicrobial properties and are resistant to proteolytic breakdown. This study focused on exploring methods for covalently attaching these peptoids to contact lenses to enhance their durability and performance in vitro. METHODS:The peptoids TM5 and TM18 were covalently attached to etafilcon lenses via carbodiimide chemistry (EDC/NHS), oxazoline plasma, and plasma ion immersion implantation (PIII). The lenses were analysed using X-ray photoelectron spectroscopy (XPS), surface charge, and hydrophobicity. Inhibition of adhesion of multidrug-resistant Pseudomonas aeruginosa and cytotoxicity on corneal epithelial cells were evaluated. The impact of moist heat sterilization on activity was also assessed. RESULTS:XPS confirmed peptoid binding to lenses. Peptoid coatings slightly increased contact angles (≤23°) without affecting overall charge. Peptoids, bound via carbodiimide, inhibited P. aeruginosa adhesion by over 5 log10 CFU per lens, outperforming melimine, which required six times the concentration for a 3 log10 reduction. Peptoids attached via oxazoline or PIII reduced adhesion by > 5 log10 CFU. All covalent methods significantly reduced bacterial adhesion compared to untreated lenses (P < 0.0001). Peptoid-bound lenses were non-toxic to corneal epithelial cells. Sterilization did not affect carbodiimide-treated lenses but reduced the activity of oxazoline and PIII surfaces by 1-2 log10 CFU. CONCLUSION:Peptoids TM5 and TM18 effectively reduced P. aeruginosa adhesion on lenses, with carbodiimide-bound surfaces retaining activity post-sterilization, showing promise for the development of antimicrobial contact lenses.

Cancer is one of the most prominent causes of death worldwide and tubulin is a crucial protein of cytoskeleton that maintains essential cellular functions including cell division as well as cell signalling, that makes an attractive drug target for cancer drug development. 1,3,4-oxadiazoles disrupt microtubule causing G2-M phase cell cycle arrest and provide anti-proliferative effect. In this study, field-based 3D-QSAR models were developed using 62 bioactive anti-tubulin 1,3,4-oxadiazoles. The best model characterized by PLS factor 7 was rigorously validated using various statistical parameters. Generated 3D-QSAR model having high degree of confidence showed favourable and unfavourable contours around 1,3,4-oxadiazole core that assisted in defining proper spatial positioning of desired functional groups for better bioactivity. A five featured pharmacophore model (AAHHR_1) was developed using same ligand library and validated through enrichment analysis (BEDROC160.9 value = 0.59, Average EF 1% = 27.05, and AUC = 0.74). Total 30,212 derivatives of 1,3,4-oxadiazole obtained from PubChem database was prefiltered through validated pharmacophore model and docked in XP mode on binding cavity of tubulin protein (PDB code: 1SA0) which led into the identification of 11 HITs having docking scores between -7.530 and -9.719 kcal/mol while the reference compound Colchicine exerted docking score of -7.046 kcal/mol. Following the analysis of MM-GBSA and ADME studies, HIT1 and HIT4 emerged as the two promising hits. To verify their thermodynamic stability at the target site, molecular dynamic simulations were carried out. Both HITs were further subjected to DFT analysis to determine their HOMO-LUMO energy gap for ensuring their biological feasibility. Finally, molecular docking based structural exploration for 1,3,4-oxadiazoles to set up a lead of Formula I for further advancements of tubulin polymerization inhibitors as anti-cancer agents.Communicated by Ramaswamy H. Sarma.

Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition.

We have fabricated and characterized novel bioactive nanocomposite interpenetrating polymer network (IPN) scaffolds to treat bone defects by loading mesoporous silica nanoparticles (MSNs) into blends of Konjac glucomannan, polyvinyl alcohol, and polycaprolactone. By loading MSNs, we developed a porous nanocomposite scaffold with mechanical strengths comparable to cancellous bone. In vitro cell culture studies proved the cytocompatibility of the nanocomposite scaffolds. RT-PCR studies confirmed that these scaffolds significantly upregulated major osteogenic markers. The in vivo chick chorioallantoic membrane (CAM) assay confirmed the proangiogenic activity of the nanocomposite IPN scaffolds. In vivo studies were performed using Wistar rats to evaluate the scaffolds' compatibility, osteogenic activity, and proangiogenic properties. Liver and renal function tests confirmed that these scaffolds were nontoxic. X-ray and mu-CT results show that the bone defects treated with the nanocomposite scaffolds healed at a much faster rate compared to the untreated control and those treated with IPN scaffolds. H&E and Masson's trichrome staining showed angiogenesis near the newly formed bone and the presence of early-stage connective tissues, fibroblasts, and osteoblasts in the defect region at 8 weeks after surgery. Hence, these advantageous physicochemical and biological properties confirm that the nanocomposite IPN scaffolds are ideal for treating bone defects.

BACKGROUND:Ocular infections caused by antibiotic-resistant pathogens can result in partial or complete vision loss. The development of pan-resistant microbial strains poses a significant challenge for clinicians as there are limited antimicrobial options available. Synthetic peptoids, which are sequence-specific oligo-N-substituted glycines, offer potential as alternative antimicrobial agents to target multidrug-resistant bacteria. METHODS:The antimicrobial activity of synthesised peptoids against multidrug-resistant (MDR) ocular pathogens was evaluated using the microbroth dilution method. Hemolytic propensity was assessed using mammalian erythrocytes. Peptoids were also incubated with proteolytic enzymes, after which their minimum inhibitory activity against bacteria was re-evaluated. RESULTS:Several alkylated and brominated peptoids showed good inhibitory activity against multidrug-resistant Pseudomonas aeruginosa strains at concentrations of ≤15 μg mL-1 (≤12 µM). Similarly, most brominated compounds inhibited the growth of methicillin-resistant Staphylococcus aureus at 1.9 to 15 μg mL-1 (12 µM). The N-terminally alkylated peptoids caused less toxicity to erythrocytes. The peptoid denoted as TM5 had a high therapeutic index, being non-toxic to either erythrocytes or corneal epithelial cells, even at 15 to 22 times its MIC. Additionally, the peptoids were resistant to protease activity. CONCLUSIONS:Peptoids studied here demonstrated potent activity against various multidrug-resistant ocular pathogens. Their properties make them promising candidates for controlling vision-related morbidity associated with eye infections by antibiotic-resistant strains.

DNA combing is a powerful technique for studying replication profile, fork-directionality and fork velocity. At present, there is requirement of a methodology to comb DNA present in a single human cell for studying replication dynamics at early embryonic stage. In our study, a surface having dual characteristics i.e., affinity towards negatively charged single DNA molecules and a hydrophobic gradient for self propelled droplet motion of combing solution was developed. The surface was made by coating of TCOS (trichloro-octylsilane) by vapor diffusion on APTES (Aminopropyl-triethoxysilane) coated glass slides. A gradient surface having high deposition efficiency (DE) was developed on which 5 picogram DNA equivalent to genomic DNA present in one single human cell can be combed. The gradient surface was thermostable in nature having the ability to sustain boiling temperature for two hours and sustain anisotropy in 70 % ethanol for 80 h. Applicability for multiple runs was enhanced such that the surface can be used for 13-14 times. Factors associated with gradient surface are unidirectional movement of combing solution droplet over the gradient surface for combing straight DNA molecules and a longer gradient surface of more than 1 cm such that long size DNA molecules can be combed. Ellipsometry and contact angle hysteresis confirmed the presence of hydrophobic gradient. XPS (X-ray photoelectron spectroscopy) and FTIR (Fourier Transform Infrared Spectroscopy) confirmed the presence of characteristic affinity towards negatively charged DNA molecules on the gradient surface. Combing solution was optimized for increasing deposition efficiency and for increasing the applicability of gradient surface for multiple runs. High temperature of combing solution was found to increase Deposition Efficiency. Combing solution was also optimized for combing single DNA molecules over the gradient surface. Single DNA molecules were combed by reducing pH and lowering concentration of triton-X in the combing solution. Dye: bp ratio was optimized for high fluorescent intensity and low surface background.

Antibiotic resistance is a growing global health problem when the discovery and development of novel antibiotics are diminishing. Various strategies have been proposed to address the problem of growing antibacterial resistance. One such strategy is the development of hybrid antibiotics. These therapeutic systems have been designed for two or more pharmacophores of known antimicrobial agents. This review highlights the latest development of antibiotic hybrids comprising two antibiotics (cleavable and non-cleavable) and combinations of biocidal and novel compounds to treat bacterial infections. The approach of dual-acting hybrid compounds has a promising future in overcoming drug resistance in bacterial pathogens.

The biomimetic scaffolds were fabricated using two natural biopolymers; Konjac glucomannan (KGM) and Silk fibroin (SF). The various proportions of KGM (1%) and SF (1%-2%) solutions were cross-linked using citric acid as a cross linker and then lyophilized to prepare the fibrous scaffolds. The physicochemical properties of the KGM/SF scaffolds were investigated using FT-IR analysis, TGA analysis, SEM, porosity, swelling, in vitro biodegradation, and mechanical characterization. FTIR spectra revealed the presence of characteristic functional moieties in the KGM/SF scaffolds. The improved thermal stability was observed for KGM/SF scaffolds compared to the control. The SEM images revealed that the scaffolds exhibited a porous morphology. The biodegradation of KGM/SF scaffolds was almost 77% until day 21, showing the biodegradable nature of the KGM/SF scaffolds. The compression strength of KGM/SF scaffolds was significantly higher than the KGM scaffold and eligible for soft tissue engineering. The KGM/SF scaffolds were further characterized by in vitro cell viability and cell attachment in fibroblast cells, demonstrating the non-toxicity of scaffolds. Finally, in vivo CAM assay was successfully performed and determined the efficacy of KGM/SF scaffolds in vascularization. Overall, the results demonstrated that the KGM/SF scaffolds are biocompatible and capable of promoting vascularization in tissue engineering and biomedical applications.

A facile one-step catalyst free methodology has been developed for the regioselective functionalization of 4,6-diphenylpyrimidin-2(1H)-ones under mild conditions. Selectivity towards the O-regioisomer was achieved by using Cs2CO3 in DMF without use of any coupling reagents. A total of 14 regioselective O-alkylated 4,6-diphenylpyrimidines were synthesized in 81-91% yield. In the DFT studies it was observed that the transition state for the formation of the O-regioisomer is more favourable with Cs2CO3 as compared to K2CO3. Furthermore, this methodology was extended to increase the O/N ratio for the alkylation of 2-phenylquinazolin-4(3H)-one derivatives.

XMM-Newton, a European Space Agency observatory, has been observing the X-ray, ultra-violet and optical sky for 23 years. During this time, astronomy has evolved from mainly studying single sources to populations and from a single wavelength, to multi-wavelength or messenger data. We are also moving into an era of time domain astronomy. New software and methods are required to accompany evolving astronomy and prepare for the next generation X-ray observatory, Athena. Here we present XMM2ATHENA, a programme funded by the European Union's Horizon 2020 research and innovation programme. XMM2ATHENA builds on foundations laid by the XMM-Newton Survey Science Centre (XMM-SSC), including key members of this consortium and the Athena Science ground segment, along with members of the X-ray community. The project is developing and testing new methods and software to allow the community to follow the X-ray transient sky in quasi-real time, identify multi-wavelength or messenger counterparts of XMM-Newton sources and determine their nature using machine learning. We detail here the first milestone delivery of the project, a new online, sensitivity estimator. We also outline other products, including the forthcoming innovative stacking procedure and detection algorithms to detect the faintest sources. These tools will then be adapted for Athena and the newly detected or identified sources will enhance preparation for observing the Athena X-ray sky.

Soft materials in nature are formed through reversible supramolecular assembly of biological polymers into dynamic hierarchical networks. Rational design has led to self-assembling peptides with structural similarities to natural materials. However, recreating the dynamic functional properties inherent to natural systems remains challenging. Here we report the discovery of a short peptide based on the tryptophan zipper (trpzip) motif, that shows multiscale hierarchical ordering that leads to emergent dynamic properties. Trpzip hydrogels are antimicrobial and self-healing, with tunable viscoelasticity and unique yield-stress properties that allow immediate harvest of embedded cells through a flick of the wrist. This characteristic makes Trpzip hydrogels amenable to syringe extrusion, which we demonstrate with examples of cell delivery and bioprinting. Trpzip hydrogels display innate bioactivity, allowing propagation of human intestinal organoids with apical-basal polarization. Considering these extensive attributes, we anticipate the Trpzip motif will prove a versatile building block for supramolecular assembly of soft materials for biotechnology and medicine.

Platelets play a significant role in the pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and mean platelet volume (MPV) are the two significant parameters that affect the functions of platelets. In the current study, MPV and PLT count was evaluated using flow cytometry and a cell counter. SonoClot analysis was carried out to evaluate activated clot timing (ACT), clot rate (CR), and platelet function (PF). Genotyping was carried out using GSA and Sanger sequencing, and expression analysis was performed using RT-PCR. In silico analysis was carried out using the GROMACS tool and UNAFold. The interaction of significant proteins with other proteins was predicted using the STRING database. Ninety-six genes were analyzed, and a significant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated significantly with increased MPV, decreased PLT count, and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both genes. In silico analysis revealed that mutation in the THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two significant proteins interact with many other proteins, especially the ones involved in platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements, suggesting that they could be important players in the determination of MPV values. In conclusion, the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes, and higher MPV can be targeted for better therapeutic outcomes.