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We investigate the vertical electron attachment energy (VAE) of 1-methyl-4-nitroimidazole, a model radiosensitizer, employing quantum mechanics/molecular mechanics (QM/MM) and QM/polarized continuum (QM/PCM) solvation models. We considered the solvent-excluded surface (QM/PCM-SES) and Van der Waals (QM/PCM-VDW) cavities within the PCM framework, the electrostatic embedding QM/MM (EE-QM/MM) model, and the self-consistent sequential QM/MM polarizable electrostatic embedding (scPEE-S-QM/MM) model. Due to slow VAE convergence concerning the number of QM solvent molecules, full QM calculations prove inefficient. Ensemble averages in these calculations do not align with VAEs computed for the representative solute–solvent configuration. QM/MM and QM/PCM calculations show agreement with each other for sufficiently large QM regions, although the QM/PCM-VDW model exhibits artifacts linked to the cavity. QM/MM models demonstrate good agreement between ensemble averages and VAEs calculated with the representative configuration. Notably, the VAE computed with the scPEE-S-QM/MM model achieves faster convergence concerning the number of QM water molecules compared to the EE-QM/MM model, attributed to enhanced efficiency from MM charge polarization in the scPEE-S-QM/MM approach. This emphasizes the importance of QM/classical models with accurate solute–solvent and solvent–solvent mutual polarization for obtaining converged VAEs at a reasonable computational cost. The full-QM approach is very inefficient, while the microsolvation model is inaccurate. Computational savings in QM/MM models result from electrostatic embedding and the representative configuration, with the scPEE-S-QM/MM approach emerging as an efficient tool for describing bulk-solvated anions within the QM/MM framework. Its potential extends to improving transient anion state descriptions in biomolecules and radiosensitizers, especially given the frequent employment of microsolvation models. [ABSTRACT FROM AUTHOR]

Click chemistry refers to selective reactions developed for grafting of bio(macro)molecules in their biological media. Caged click compounds have been employed to spatiotemporally control click reactions. Here, we survey the uncaging of photo-dibenzocyclooctyne-OH (photoDIBO-OH) to its click-chemistry active form DIBO-OH, with particular attention to its conversion timescale and efficiency. Ultraviolet pump–infrared probe experiments reveal a stepwise decarbonylation: first, carbon monoxide (C≡O) is released within 1.8 ps, and then, it converts, within 10 ps, to DIBO-OH. Completion of uncaging is achieved with an efficiency of ∼50%. A successful demonstration of two-photon uncaging of photoDIBO-OH at long wavelength (700 nm) confers enhanced in vivo compatibility and proceeds on the same timescale. [ABSTRACT FROM AUTHOR]

Phase separation of biomolecules can facilitate their spatiotemporally regulated self-assembly within living cells. Due to the selective yet dynamic exchange of biomolecules across condensate interfaces, condensates can function as reactive hubs by concentrating enzymatic components for faster kinetics. The principles governing this dynamic exchange between condensate phases, however, are poorly understood. In this work, we systematically investigate the influence of client–sticker interactions on the exchange dynamics of protein molecules across condensate interfaces. We show that increasing affinity between a model protein scaffold and its client molecules causes the exchange of protein chains between the dilute and dense phases to slow down and that beyond a threshold interaction strength, this slowdown in exchange becomes substantial. Investigating the impact of interaction symmetry, we found that chain exchange dynamics are also considerably slower when client molecules interact equally with different sticky residues in the protein. The slowdown of exchange is due to a sequestration effect, by which there are fewer unbound stickers available at the interface to which dilute phase chains may attach. These findings highlight the fundamental connection between client–scaffold interaction networks and condensate exchange dynamics. [ABSTRACT FROM AUTHOR]

The projector augmented wave (PAW) method of Blöchl linearly maps smooth pseudo wavefunctions to the highly oscillatory all-electron DFT orbitals. Compared to norm-conserving pseudopotentials (NCPP), PAW has the advantage of lower kinetic energy cutoffs and larger grid spacing at the cost of having to solve for non-orthogonal wavefunctions. We earlier developed orthogonal PAW (OPAW) to allow the use of PAW when orthogonal wavefunctions are required. In OPAW, the pseudo wavefunctions are transformed through the efficient application of powers of the PAW overlap operator with essentially no extra cost compared to NCPP methods. Previously, we applied OPAW to DFT. Here, we take the first step to make OPAW viable for post-DFT methods by implementing it in real-time time-dependent (TD) DFT. Using fourth-order Runge–Kutta for the time-propagation, we compare calculations of absorption spectra for various organic and biological molecules and show that very large grid spacings are sufficient, 0.6–0.7 bohr in OPAW-TDDFT rather than the 0.4–0.5 bohr used in traditional NCPP-TDDFT calculations. This reduces the memory and propagation costs by around a factor of 3. Our method would be directly applicable to any post-DFT methods that require time-dependent propagations such as the GW approximation and the Bethe–Salpeter equation. [ABSTRACT FROM AUTHOR]

In the folded state, biomolecules exchange between multiple conformational states crucial for their function. However, most structural models derived from experiments and computational predictions only encode a single state. To represent biomolecules accurately, we must move towards modeling and predicting structural ensembles. Information about structural ensembles exists within experimental data from X-ray crystallography and cryo-electron microscopy. Although new tools are available to detect conformational and compositional heterogeneity within these ensembles, the legacy PDB data structure does not robustly encapsulate this complexity. We propose modifications to the macromolecular crystallographic information file (mmCIF) to improve the representation and interrelation of conformational and compositional heterogeneity. These modifications will enable the capture of macromolecular ensembles in a human and machine-interpretable way, potentially catalyzing breakthroughs for ensemble-function predictions, analogous to the achievements of AlphaFold with single-structure prediction.

Polymer models describing the statistics of biomolecules under confinement have applications to a wide range of single-molecule experimental techniques and give insight into biologically relevant processes in vivo. In this paper, we determine the transverse position and bending correlation functions for a wormlike chain confined within slits and cylinders (with one and two confined dimensions, respectively) using a mean-field approach that enforces rigid constraints on average. We show the theoretical predictions accurately capture the statistics of a wormlike chain from Monte Carlo simulations in both confining geometries for both weak and strong confinement. We also show that the longitudinal correlation function is accurately computed for a chain confined to a slit and leverages the accuracy of the model to suggest an experimental technique to infer the (often unobservable) transverse statistics from the (directly observable) longitudinal end-to-end distance. [ABSTRACT FROM AUTHOR]

The ability to accurately monitor chiral biological molecules is of great significance for their potential applications in disease diagnosis and virus detection. As the existing chiral detection technologies are mainly relying on an optical method by using left/right circularly polarized light, the universality is low and the operation is complicated. Moreover, large quantity of chiral molecules is required, causing low detection efficiency. Here, a self-assembled monolayer of polypeptides has been fabricated to realize trace detection of chirality based on spin selectivity of photon–electron interaction. We have utilized Kerr technique to detect the rotation angle by the molecular monolayer, which indicates the chirality of polypeptides. The chiral structure of a biological molecule could result in spin-selectivity of electrons and thus influence the interaction between electron spin and light polarization. A Kerr rotation angle of ∼3° has been obviously observed, equivalent to the magneto-optic Kerr effect without magnetic material or magnetic field. Furthermore, we have provided a novel solution to achieve chirality discrimination and amplification simultaneously through an optical fiber. The proposed design is applicable for chiral detection via increasing their differential output signal, which clearly demonstrates a useful strategy toward chirality characterization of biological molecules. [ABSTRACT FROM AUTHOR]

Synthetic multiblock copolymers are an interesting class of polymeric chains and have emerged as promising materials to mimic the function of complex biomolecules. In this work, we use Wang–Landau sampling to study sequences of multiblock ( A n B n ) m copolymers on the simple cubic lattice, where n represents the block length and m represents the number of blocks. We first compare to the thermodynamic and structural properties of four sequences previously studied in the continuum [W. Wang et al., J. Chem. Phys. 141, 244907 (2014)] to observe the differences that arise during the collapse process. We then focus on the structural transitions that occur at temperatures below the coil-to-globule transition in the lattice. Moreover, by studying additional sequences, we detail the relationship between the block length, number of blocks, and, thus, overall polymer length with respect to said structural transitions. Finally, we observe how the formation and shape of a ground state core of the more strongly interacting monomer type affect the procession of structural changes that occurs as temperature increases. [ABSTRACT FROM AUTHOR]

An unsupervised computational protocol is proposed with the aim of obtaining accurate structures of large molecules in the gas phase at the cost of standard density functional theory (DFT) computations. The whole workflow is fully automated and provides optimized equilibrium geometries and ground state rotational constants to be directly compared with experiments. The results for a panel of molecules of biological or medicinal interest show that the accuracy of the results delivered by the new tool at the cost of a single DFT geometry optimization is close to that delivered by state-of-the-art composite wavefunction methods for small semi-rigid molecules. [ABSTRACT FROM AUTHOR]

Exploring the structures and spectral features of proteins with advanced quantum chemical methods is an uphill task. In this work, a fragment-based molecular tailoring approach (MTA) is appraised for the CAM-B3LYP/aug-cc-pVDZ-level geometry optimization and vibrational infrared (IR) spectra calculation of ten real proteins containing up to 407 atoms and 6617 basis functions. The use of MTA and the inherently parallel nature of the fragment calculations enables a rapid and accurate calculation of the IR spectrum. The applicability of MTA to optimize the protein geometry and evaluate its IR spectrum employing a polarizable continuum model with water as a solvent is also showcased. The typical errors in the total energy and IR frequencies computed by MTA vis-à-vis their full calculation (FC) counterparts for the studied protein are 5–10 millihartrees and 5 cm−1, respectively. Moreover, due to the independent execution of the fragments, large-scale parallelization can also be achieved. With increasing size and level of theory, MTA shows an appreciable advantage in computer time as well as memory and disk space requirement over the corresponding FCs. The present study suggests that the geometry optimization and IR computations on the biomolecules containing ∼1000 atoms and/or ∼15 000 basis functions using MTA and HPC facility can be clearly envisioned in the near future. [ABSTRACT FROM AUTHOR]

Iron plays vital roles in important biological processes in fish, but can be toxic in high concentrations. The information on metalloproteins that participate in maintenance of Fe homeostasis in an esocid fish, the northern pike, as an important freshwater bioindicator species, are rather scarce. The aim of this study was to identify main cytosolic constituents that sequester Fe in the northern pike liver. The method applied consisted of two-dimensional HPLC separation of Fe-binding biomolecules, based on anion-exchange followed by size-exclusion fractionation. Apparent molecular masses of two main Fe-metalloproteins isolated by this procedure were ~360 kDa and ~50 kDa, with the former having more acidic pI, and indicated presence of ferritin and hemoglobin, respectively. MALDI-TOF-MS provided confirmation of ferritin subunit with a m/z peak at 20.65 kDa, and hemoglobin with spectra containing main m/z peak at 16.1 kDa, and smaller peaks at 32.1, 48.2, and 7.95 kDa (single-charged Hb-monomer, dimer, and trimer, and double-charged monomer, respectively). LC-MS/MS with subsequent MASCOT database search confirmed the presence of Hb-β subunits and pointed to close relation between esocid and salmonid fishes. Further efforts should be directed towards optimization of the conditions for metalloprotein analysis by mass spectrometry, to extend the knowledge on intracellular metal-handling mechanisms. [ABSTRACT FROM AUTHOR]

Carbohydrates are synthetically challenging molecules with vital biological roles in all living systems. To better understand the biological functions of this fundamentally important class of molecules, novel methodologies are needed, including site-selective functionalization and glycosylation reactions. This account describes our efforts toward the development of novel methodologies for site-selective functionalization of carbohydrates and stereoselective glycosylation through various acylation reactions. [ABSTRACT FROM AUTHOR]

Biomarkers are valuable tools in clinical research where they allow to predict susceptibility to diseases, or response to specific treatments. Likewise, biomarkers can be extremely useful in the biomanufacturing of therapeutic proteins. Indeed, constraints such as short timelines and the need to find hyper-productive cells could benefit from a data-driven approach during cell line and process development. Many companies still rely on large screening capacities to develop productive cell lines, but as they reach a limit of production, there is a need to go from empirical to rationale procedures. Similarly, during bioprocessing runs, substrate consumption and metabolism wastes are commonly monitored. None of them possess the ability to predict the culture behavior in the bioreactor. Big data driven approaches are being adapted to the study of industrial mammalian cell lines, enabled by the publication of Chinese hamster and CHO genome assemblies which allowed the use of next-generation sequencing with these cells, as well as continuous proteome and metabolome annotation. However, if these different -omics technologies contributed to the characterization of CHO cells, there is a significant effort remaining to apply this knowledge to biomanufacturing methods. The correlation of a complex phenotype such as high productivity or rapid growth to the presence or expression level of a specific biomarker could save time and effort in the screening of manufacturing cell lines or culture conditions. In this review we will first discuss the different biological molecules that can be identified and quantified in cells, their detection techniques, and associated challenges. We will then review how these markers are used during the different steps of cell line and bioprocess development, and the inherent limitations of this strategy. • Biomarkers characterize the physiological state of cells and help predict their behavior. • A biomarker can consist of any macromolecule present in the cell that can be detected and quantified. • Discovering and identifying biomarkers requires specific and customized methods. • In an industrial context, biomarkers enable a more rational and efficient approach to bioprocessing. • Biomarkers are often specific to environmental conditions and, as such, have limitations. [ABSTRACT FROM AUTHOR]

Extreme longevity in humans is known to be a heritable trait. In a well‐established twin erythrocyte metabolomics and proteomics database, we identified the longevity factor spermidine and a cluster of correlated molecules with high heritability estimates. Erythrocyte spermidine is 82% heritable and significantly correlated with 59 metabolites and 22 proteins. Thirty‐eight metabolites and 19 proteins were >20% heritable, with a mean heritability of 61% for metabolites and 49% for proteins. Correlated metabolites are concentrated in energy metabolism, redox homeostasis, and autophagy pathways. Erythrocyte mean cell volume (MCV), an established heritable trait, was consistently negatively correlated with the top 25 biomolecules most strongly correlated with spermidine, indicating that smaller MCVs are associated with higher concentrations of spermidine and correlated molecules. Previous studies have linked larger MCVs with poorer memory, cognition, and all‐cause mortality. Analysis of 432,682 unique patient records showed a linear increase in MCV with age but a significant deviation toward smaller than expected MCVs above age 86, suggesting that smaller MCVs are associated with extreme longevity. Consistent with previous reports, a subset of 78,158 unique patient records showed a significant skewing toward larger MCV values in a deceased cohort compared to an age‐matched living cohort. Our study supports the existence of a complex, heritable phenotype in erythrocytes associated with health and longevity. [ABSTRACT FROM AUTHOR]

Nature uses complex self‐assembly pathways to access distinct functional non‐equilibrium self‐assemblies. This remarkable ability to steer same set of biomolecules into different self‐assembly states is done by avoiding thermodynamic pit. In synthetic systems, on demand control over 'Pathway Complexity' to access self‐assemblies different from equilibrium structures remains challenging. Here we show versatile non‐equilibrium assemblies of the same monomer via alternate assembly pathways. The assemblies nucleate using non‐classical or classical nucleation routes into distinct metastable (transient hydrogels), kinetic (stable hydrogels) and thermodynamic structures [(poly)‐crystals and 2D sheets]. Initial chemical and thermal inputs force the monomers to follow different assembly pathways and form soft‐materials with distinct molecular arrangements than at equilibrium. In many cases, equilibrium structures act as thermodynamic sink which consume monomers from metastable structures giving transiently formed materials. This dynamics can be tuned chemically or thermally to slow down the dissolution of transient hydrogel, or skip the intermediate hydrogel altogether to reach final equilibrium assemblies. If required this metastable state can be kinetically trapped to give strong hydrogel stable over days. This method to control different self‐assembly states can find potential use in similar biomimetic systems to access new materials for various applications. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide, accounting for about one among six deaths, so the quest for new and improved therapies is of crucial importance. The discovery of cisplatin as an anticancer agent has paved the way for the development of other metal-based therapeutic agents and Re(I)-based candidates have been recently found to show promising results. It is known as well that chirality plays a central role in the interactions of metal-based drugs with intrinsically chiral biomolecules such as membrane transport proteins or DNA. To further exploit this property, we have developed a series of diastereomeric dinuclear Re(I) complexes with chiral ligands containing pinene-bipyridine units. These complexes offer unique insights into the relation between stereochemistry and biological activity. Single-crystal X-ray diffraction studies, spectroscopic analysis, including UV-Vis and circular dichroism (CD), confirmed the chiral structures of these complexes. Biological activity assessments were carried out against various cancer cell lines, with a particular focus on breast and colon cancer. The diastereomers exhibited distinct anticancer activities, with some displaying promising results. Notably, one diastereomer showed exceptional cytotoxicity against HCT116 and MCF-7 cancer cells. This research underscores the significance of chirality in the design of novel anticancer agents, providing insights into the potential of dinuclear Re(I) complexes as effective candidates for cancer treatment. [ABSTRACT FROM AUTHOR]

Molecular photoswitches provide interesting tools to reversibly control various biological functions with light. Thanks to its small size and easy introduction into the biomolecules, azobenzene derivatives have been widely employed in the field of photopharmacology. All visible‐light switchable azobenzenes with controllable thermostability are highly demanded. Based on the reported tetra‐o‐chloroazobenzenes, we synthesized push‐pull systems, by introducing dialkyl amine and nitro groups as strong electron‐donating and electron‐withdrawing groups on the para‐positions, and then transformed to push‐push systems by a simple reduction step. The developed push‐pull and push‐push tetra‐o‐chloroazobenzene derivatives displayed excellent photoswitching properties, as previously reported. The half‐life of the Z‐isomers can be tuned from milliseconds for the push‐pull system to several hours for the push‐push system. The n‐π* and π‐π* transitions have better resolution in the push‐push molecules, and excitation at different wavelengths can tune the E/Z ratio at the photostationary state. For one push‐pull molecule, structure and absorption spectra obtained from theoretical calculations are compared with experimental data, along with data on the push‐push counterpart. [ABSTRACT FROM AUTHOR]

Exploring drought stress-responsive genes in rice is essential for breeding drought-resistant varieties. Rice drought resistance is controlled by multiple genes, and mining drought stress-responsive genes solely based on single omics data lacks stability and accuracy. Multi-omics correlation analysis and biological molecular network analysis provide robust solutions. This study proposed a random walk with a multi-restart probability (RWMRP) algorithm, based on the Restarted Random Walk (RWR) algorithm, to operate on rice MultiPlex biological networks. It explores the interactions between biological molecules across various levels and ranks potential genes. RWMRP uses eigenvector centrality to evaluate node importance in the network and adjusts the restart probabilities accordingly, diverging from the uniform restart probability employed in RWR. In the random walk process, it can be better to consider the global relationships in the network. Firstly, we constructed a MultiPlex biological network by integrating the rice protein–protein interaction, gene pathway, and gene co-expression network. Then, we employed RWMRP to predict the potential genes associated with rice tolerance to drought stress. Enrichment and correlation analyses resulted in the identification of 12 drought-related genes. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) analysis on these 12 genes, ultimately identifying 10 genes responsive to drought stress. [ABSTRACT FROM AUTHOR]

Understanding how the process of gene expression can be engineered to biomanufacture proteins for medical, agricultural, and industrial applications provides an opportunity to link basic concepts of molecular biology with applications. Here we present a simple activity that uses commonly available materials to simulate the process by which the bacterium Agrobacterium tumefaciens transfers genes to plants and allows students to visualize the expressed protein of interest. The activity provides an overview of transcription and translation, and how recombinant DNA technology has revolutionized the manufacturing of biological molecules. After students work through the overview worksheet and complete the hands-on activity, they will be able to summarize the roles of transcription and translation in plant gene expression. Students will also be able to explain the process of Agrobacterium-mediated gene expression and describe applications in plant biotechnology. This simulation activity is accessible to a wide range of students, easily adaptable to different proficiency levels, and provides a straightforward approach for students to explore the practical applications of biotechnology. [ABSTRACT FROM AUTHOR]

Nanotechnology offers excellent prospects for application in biology and medicine. It is used for detecting biological molecules, imaging, and as therapeutic agents. Due to nano-size (1-100 nm) and high surface-to-volume ratio, nanomaterials possess highly specific and distinct characteristics in the biological environment. Recently, the use of nanomaterials as sensors, theranostic, and drug delivery agents has become popular. The safety of these materials is being questioned because of their biological toxicity, such as inflammatory responses, cardiotoxicity, cytotoxicity, inhalation problems, etc., which can have a negative impact on the environment. This review paper focuses primarily on the toxicological effects of nanomaterials along with the mechanisms involved in cell interactions and the generation of reactive oxygen species by nanoparticles, which is the fundamental source of nanotoxicity. We also emphasize the greener synthesis of nanomaterials in biomedicine, as it is non-hazardous, feasible, and economical. The review articles shed light on the complexities of nanotoxicology in biosystems and the environment. [ABSTRACT FROM AUTHOR]

MXene is a rapidly emerging group of two-dimensional (2D) multifunctional nanomaterials, drawing huge attention from researchers of a broad scientific field. Reporting the synthesis of MXene was the following breakthrough in 2D materials following the discovery of graphene. MXene is considered the most recent developments of materials, including transition metal carbonitrides, nitrides, and carbides synthesized by etching or mechanical-based exfoliation of selective MAX phases. MXene has a plethora of prodigious properties such as unique interlayer spacing, high ion and electron transport, large surface area, excellent thermal and electrical conductivity, exceptional volumetric capacitance, thermal shock, and oxidation resistance, easily machinable and inherently hydrophilic, and biocompatibility. Owing to the abundance of tailorable surface function groups, these properties can be further enhanced by surface functionalization with covalent and non-covalent modifications via numerous surface functionalization methods. Therefore, MXene finds their way to a plethora of applications in numerous fields including catalysis, membrane separation, energy storage, sensing, and biomedicine. Here, the focus is on reviewing the structure, synthesis techniques, and functionalization methods of MXene. Furthermore, MXene-based detection platforms in different sensing applications are survived. Great attention is given to reviewing the applications of MXene in the detection of biomolecules, pathogenic bacteria and viruses, cancer biomarkers food contaminants and mycotoxins, and hazardous pollutants. Lastly, the future perspective of MXene-based biosensors as a next-generation diagnostics tool is discussed. Crucial visions are introduced for materials science and sensing communities to better route while investigating the potential of MXene for creating innovative detection mechanisms. [ABSTRACT FROM AUTHOR]

FACT is a developed technique for clearing tissues that does not use acrylamide. Since the removal of lipids is crucial for transparency and efficient antibody staining throughout the tissue, especially for microscopy and imaging, it is a harmful process that can cause the loss of important biological molecules such as proteins. The FACT technique overcomes this by chemically bonding the membrane and intracellular proteins with the extracellular matrix, creating a massive 3D hydrogel matrix and providing structural support to fortify the tissue during processing. Compared to other acrylamide-based techniques, the FACT technique requires less labor and harmful chemicals and is therefore considered a more suitable option. In this study, we describe the complete FACT protocol for antibody staining and imaging of whole-cleared tissues while preserving structure and improving image quality. The protocol includes tissue perfusion, fixation, clearing, antibody staining, refractive index matching (RIM) (), microscopy, and imaging. The timing for each step varies depending on the size, weight, and type of tissue, as well as the type of immunostaining. We provide an example of the FACT protocol using mouse brain tissue, which demonstrates its suitability for molecular interrogation analysis of large tissues. The FACT technique has been successfully performed on different types of tissues, making it a favorable choice for a variety of applications. [ABSTRACT FROM AUTHOR]

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100–10 000‐fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1–10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all. [ABSTRACT FROM AUTHOR]

Basing on logical assumptions and necessary steps of complexification along biological evolution, we propose here an evolutionary path from molecules to cells presenting four ages and three major transitions. At the first age, the basic biomolecules were formed and become abundant. The first transition happened with the event of a chemical symbiosis between nucleic acids and peptides worlds, which marked the emergence of both life and the process of organic encoding. FUCA, the first living process, was composed of self-replicating RNAs linked to amino acids and capable to catalyze their binding. The second transition, from the age of FUCA to the age of progenotes, involved the duplication and recombination of proto-genomes, leading to specialization in protein production and the exploration of protein to metabolite interactions in the prebiotic soup. Enzymes and metabolic pathways were incorporated into biology from protobiotic reactions that occurred without chemical catalysts, step by step. Then, the fourth age brought origin of organisms and lineages, occurring when specific proteins capable to stackle together facilitated the formation of peptidic capsids. LUCA was constituted as a progenote capable to operate the basic metabolic functions of a cell, but still unable to interact with lipid molecules. We present evidence that the evolution of lipid interaction pathways occurred at least twice, with the development of bacterial-like and archaeal-like membranes. Also, data in literature suggest at least two paths for the emergence of DNA biosynthesis, allowing the stabilization of early life strategies in viruses, archaeas and bacterias. Two billion years later, the eukaryotes arouse, and after 1,5 billion years of evolution, they finally learn how to evolve multicellularity via tissue specialization. [ABSTRACT FROM AUTHOR]

Per- and poly-fluorinated compounds constitute a wide group of fluorocarbon chemicals with widespread industrial applications, ranging from non-stick coating in cookware to water surfactants, from fire-fighting foams to water-repellent coatings on textiles. Presently, over 12,000 PFAS are known worldwide. In recent years, extensive research has focused on investigating the biological effects of these molecules on various organisms, including humans. Here, we conducted in silico simulations to examine the potential binding of a representative selection of PFAS to various human proteins known to be involved in chemical transportation and accumulation processes. Specifically, we targeted human serum albumin (HSA), transthyretin (TTR), thyroxine binding protein (TBG), fatty acid binding proteins (FABPs), organic anion transporters (OATs), aiming to assess the potential for bioaccumulation. Molecular docking simulations were employed for this purpose, supplemented by molecular dynamics (MD) simulations to account for protein flexibility, when necessary. Our findings indicate that so-called "legacy PFAS" such as PFOA or PFOS exhibit a higher propensity for interaction with the analysed human protein targets compared to newly formulated PFAS, characterised by higher branching and hydrophilicity, and possibly a higher accumulation in the human body. [ABSTRACT FROM AUTHOR]

In this paper, a toroidal metamaterial for achieving highly sensitive sensors in the terahertz (THz) frequency range is proposed. Such a subwavelength structure consists of a pair of mirror-symmetric metal split-ring resonators and a single metal wire. By exciting the structure with vertically incident electromagnetic waves, high-Q transmission peaks are generated at 2.40 and 2.44 THz. Near-field analysis reveals that the reverse-flowing currents in the metal split-ring resonators and the metal wire create a pair of magnetic dipoles connected end to end, resulting in a vortex-like magnetic field known as a toroidal dipole. Calculations of multipole scattering energy further confirm that the rapidly enhanced toroidal dipole is the primary factor responsible for the high-Q transmission peaks. This toroidal metamaterial can be used to design refractive index sensors with a sensitivity of up to 20 GHz/RIU, enabling the detection of subtle changes in the surrounding environment's parameters. Our strategy paves an alternative route to the development of highly sensitive sensors for biological and chemical molecules in the THz frequency range. [ABSTRACT FROM AUTHOR]

The strategies used to associate peptide arginylglycylaspartic acid (RGD) with calcium phosphate grafts to enhance cell–biomaterial interactions have been controversial in the literature. Several works have demonstrated that RGD-functionalized hydroxyapatite (HA) surfaces improve cell adhesion, whereas others claim that RGD-loaded HA has an inhibitory effect when serum is present in the biological medium. To investigate such contradictory results, we associated RGD with the HA surface using physical adsorption and chemical bonding methods and evaluated the cell adhesion and spreading in pre-osteoblasts culture with and without fetal bovine serum (FBS). The effect of functionalization methods on the physicochemical characteristics of both surfaces was analyzed using multiscale techniques. Adsorption assays of serum allowed us to estimate the impact of the association method on the HA surface's reactivity. Physically adsorbed RGD did not increase the number of adhered cells due to the weak interactions between the peptide and the surface. Although chemical binding stabilizes RGD on the HA, the functionalization procedure covered the surface with molecules such as (3-aminopropyl)triethoxysilane (APTEs) and carbodiimide, changing the surface's chemical activity. Serum protein adsorption decreased by 90%, revealing a significant reduction in the surface interactions with molecules of the biological medium. The present study's findings showed that the RGD's physical association with HA did not improve cell adhesion and that this phenomenon is highly dependent on the presence of serum proteins. [ABSTRACT FROM AUTHOR]

Microalgae are naturally rich in carbohydrates, lipids, proteins, pigments, minerals, and vitamins. These metabolites make them a renewable and sustainable source of bioactive compounds in nutraceuticals, food, feed for aquaculture, and biofuels. Genetic engineering of the existing strains remains crucial in utilising and upscaling microalgae-based biorefineries. CRISPR/Cas9, TALENs, ZFNs, and genetic transformation are the established tools utilised in microalgae genetic engineering. The common genetic transformation methods include electroporation, particle bombardment (biolistics), glass-bead agitation, and Agrobacterium-mediated transformation. Expression vectors and promoters are the prerequisites in genetic engineering. The present accessibility of genome sequences and omics datasets from a diverse array of microalgae species holds promise for catalyzing strategic progress in developing a superior microalgae strain suitable for numerous applications. This paper describes the genetic engineering to enhance microalgae biomass and metabolite production, particularly lipids. The advantages and precautions to fulfil the future application of genetically engineered microalgae are also reviewed and addressed.Article highlights: Strategic genetic engineering optimises microalgae strains for enhanced lipid synthesis and biomolecule production. CRISPR/Cas9 enables precise genome modifications in microalgae, enhancing their potential for various applications. Establishing regulatory frameworks for genetically modified (GM) microalgae is crucial for safe deployment. [ABSTRACT FROM AUTHOR]

Background: Based on the outstanding mechanical properties of metallic alloys, they are widely used in a variety of industries including civil engineering. However, corrosion of alloys can shorten the buildings' practical lifelong. Nowadays, corrosion of metallic alloys in harsh chloride-contaminated cement-concrete-based environments (including skyscrapers and bridges) has become one of the major concerns of experts and scientists. Methods: Herein, sodium lignosulfonate, which has been conventionally used as a de-foaming agent in food, was utilized as a biocompatible organic inhibitor for the reinforcement of mild steel in chloride-contaminated corrosive concrete pore solution (CPS). The impact of sodium lignosulfonate was estimated by employing electrochemical polarization and impedance spectroscopy (EIS) methods. Significant findings: Results evidenced that sodium lignosulfonate can substantially retard steel corrosion and its impact was ascended by increasing the concentration. The maintained Electrochemical Impedance Spectroscopy (EIS) results clarified that around 95% of corrosion was eliminated by the inclusion of 1 wt.% sodium lignosulfonate. Also, polarization assessments certified that sodium lignosulfonate can decline steel aggression by mixed inhibition mechanism. The Field Emission Scanning Electron Microscopy (FE-SEM) micrographs disclosed that corrosion products disappeared and the corrosion rate prosperously declined upon sodium lignosulfonate inclusion in the CPS. Meanwhile, the Raman and Grazing X-ray Diffraction (GXRD) outcomes declared that the sodium lignosulfonate-based layer successfully developed over the immersed sample surface. [ABSTRACT FROM AUTHOR]

This study introduces a biosensor employing a dielectric-modulated dual material gate tunnel field effect transistor (DM-DMG TFET) in 10 nanometer technology. To detect diverse bio molecules, the biosensor incorporates a nano gap cavity formed through gate overlap on the drain side. The variation in ambipolar current serves as the sensing parameter, influenced by altering the dielectric constants of immobilized bio molecules within the nano cavity. In this paper, the simulation results of biosensor employing a dielectric-modulated dual material gate tunnel field effect transistor with different dielectric constants imposed in nano cavity. A comprehensive examination of the biosensor's performance is conducted, exploring various positions and filling factors of bio molecules within the nano cavity region. This analysis involves a thorough investigation into the device's performance, considering a range of parameters such as drain current, electric field distribution, variations in surface potential, configurations of energy bands, behaviors of carrier concentration, and the Ion/Ioff ratio. The simulations are done using the Silvaco TCAD Atlas tool. [ABSTRACT FROM AUTHOR]

Microbial biosurfactant is an emerging vital biomolecule of the 21st century. They are amphiphilic compounds produced by microorganisms and possess unique properties to reduce surface tension activity. The use of microbial surfactants spans most of the industrial fields due to their biodegradability, less toxicity, being environmentally safe, and being synthesized from renewable sources. These would be highly efficient eco‐friendly alternatives to petroleum‐derived surfactants that would open up new approaches to research on the production of biosurfactants. In the upcoming era, biobased surfactants will become a dominating multifunctional compound in the world market. Research on biosurfactants ranges from the search for novel microorganisms that can produce new molecules, structural and physiochemical characterization of biosurfactants, and fermentation process for enhanced large‐scale productivity and green applications. The main goal of this review is to provide an overview of the recent state of knowledge and trends about microbially derived surfactants, various aspects of biosurfactant production, definition, properties, characteristics, diverse advances, and applications. This would lead a long way in the production of biosurfactants as globally successful biomolecules of the current century. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hydroxyl radical‐mediated materials primarily liberate more reactive and acutely lethal hydroxyl radical (•OH) and act as potent bactericidal antibiotics, for example H2O2. Hydroxyl radical possess higher tendency than that of H2O2 to attack various biological molecules such as DNA, proteins and iron–sulfur clusters, and impair their proper functioning, actively leading to strongly potent bactericidal effect. To acquire the desired antimicrobial effect, high concentration of H2O2 is required that has found medically harmful to healthy tissues of humans. RESULTS: We herein report framework nucleic acid‐regulated DNAzyme cluster (FDC) – that is, peroxidase‐like hemin‐bound G‐quadruplex (G4/H) DNAzyme – to amplify the catalytic reduction potential of G4/H complex, leading to high conversion rate of H2O2 to more reactive hydroxyl radical that potentially shows the same antibacterial efficiency at lower and safer H2O2 concentration. Specifically, we have grafted multiple copies of DNAzymes outside framework nucleic acid (FNA) to successively achieve 3–9 orders of magnitude enhancement in catalytic activity and antibacterial efficiency of FDC. CONCLUSION: Our designed FDC has successfully alleviated H2O2 toxicity and increased its efficiency as antibacterial material, as FDC amplified the catalytic reduction potential of G4/H DNAzyme, leading to high conversion rate of H2O2 to more reactive •OH that potentially shows the same antibacterial efficiency at lower and safer H2O2 concentration. © 2024 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

AbstractThe incorporation of sensitive bioactive substances such as proteins or DNA into nanofibers poses a significant problem due to the toxicity of most organic solvents. The main idea of this study is to use alternating current electrospraying to create a suspension consisting of polyvinyl alcohol (PVA) capsules containing a bioactive substance dispersed in a solvent system suitable for a water-insoluble biocompatible polymer. In this suspension consisting of PVA capsules and a chloroform/ethanol mixture, poly (ε-caprolactone) (PCL) was dissolved and spun by needle-free electrospinning. The result is a fibrous PCL structure in which PVA capsules containing the bioactive agent are integrated. The PVA capsules protect the bioactive substance from the organic solvents needed to dissolve the PCL. To verify the efficacy of the capsules’ protection against chloroform, the green fluorescent protein was first encapsulated into the nanofibers, followed by horseradish peroxidase. Both molecules were shown to retain their bioactivity within the nanofibers. [ABSTRACT FROM AUTHOR]

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction. [ABSTRACT FROM AUTHOR]

Cancer is a global issue and hence various efforts are being made. Iron oxide is considered a significant biochemical agent in the biomedical arena for cancer treatment. Marine macroalgae-mediated iron oxides especially, magnetite (Fe3O4) nanoparticles (NPs) are a prospective alternative to diagnose and treat cancer owing to their fluorescent and magnetic properties. We intend to appraise the usability of the aqueous extract of Rosenvingea intricata (R. intricata) in Fe3O4 NPs synthesis and to study their cytotoxic effects against human hepatocarcinoma (Hep3B) and pancreatic (PANC1) cancer cells. In the present study, R. intricata were collected from the coastal region of South Andaman, India. Aqueous extracts of R. intricata were utilized to synthesize Fe3O4 NPs via the co-precipitation method. Phycosynthesized Fe3O4 NPs exhibited wide peak at 400–600 nm from ultraviolet–visible diffused reflectance spectroscopic analysis which validated the formation of NPs. Band edge emission peak at 660 nm in fluorescent spectra confirmed the quantum confinement in Fe3O4 NPs. Fourier transform infrared spectroscopy confirmed the role of R. intricata as a capping and reducing agent with functional groups such as O–H, C–H, C=O, N=O, C=C, C–O, C–N, and C–S arising from amino acids, polysaccharides, aliphatic hydrocarbons, esters, amides, lignins, alkanes, aliphatic amines, and sulfates. Physicochemical properties such as crystallite size (14.36 nm), hydrodynamic size (84.6 nm), irregular morphology, elemental composition, particle size (125 nm), crystallinity, and saturation magnetization (0.90007 emu/g) were obtained from x-ray diffractometer, dynamic light scattering, scanning electron microscopy, energy dispersive x-ray spectrometer, high-resolution transmission electron microscopy, selected area electron diffraction and vibrating sample magnetometer techniques, respectively. The cell viability showed dose-dependent cytotoxic effects and enhanced the apoptosis against Hep3B and PANC1 cancer cells. R. intricata extract capped Fe3O4 NPs could be the most appropriate and effective nanomaterial for cancer treatment and management. [ABSTRACT FROM AUTHOR]

Red fluorescent dyes are usually charged, lipophilic molecules with relatively high molecular weight, which tend to localize in specific intracellular locations, e. g., a cyanine dye Cy5 is biased towards mitochondria. They are often used as markers of biomolecules including nucleic acids and proteins. Since the molecular weight of the dyes is much smaller than that of the biomolecules, the labelling has a negligible effect on the properties of the biomolecules. In contrast, conjugation of the dyes to low molecular weight (pro)drugs can dramatically alter their properties. For example, conjugates of Cy5 with lysosome‐targeting aminoferrocenes accumulate in mitochondria and exhibit no intracellular effects characteristic for the parent (pro)drugs. Herein we tested several neutral and negatively charged dyes for labelling lysosome‐targeting aminoferrocenes 7 and 8 as well as a non‐targeted control 3. We found that a BODIPY derivative BDP‐TR exhibits the desired unbiased properties: the conjugation does not disturb the intracellular localization of the (pro)drugs, their mode of action, and cancer cell specificity. We used the conjugates to clarify the mechanism of action of the aminoferrocenes. In particular, we identified new intermediates, explained why lysosome‐targeting aminoferrocenes are more potent than their non‐targeted counterparts, and evaluated their distribution in vivo. [ABSTRACT FROM AUTHOR]

In this manuscript, a Trench Gate Engineered Junctionless Accumulation Mode Gate-All-Around (TGE-JAM-GAA) BioFET structure has been proposed and critically analyzed for the label-free identification of biomolecules using extensive numerical device simulations. This device is superior in terms of a variety of performance metrics, including higher sensitivity, a larger shift in threshold voltage, drain current, transconductance, and the ION/IOFF current ratio. These improvements are due to both the triple metal gate engineering and the trench gate. A comparative analysis of TGE-JAM-GAA BioFET has been performed with a triple metal normal gate JAM Gate-All-Around FET (TMNG-JAM-GAAFET) and a conventional single metal normal gate JAM Gate-All-Around FET (SMNG-JAM-GAAFET) biosensor. For instance, in the case of APTES biomolecules, the drift in threshold voltage obtained is 236.24 mV, which is 58.75% and 159.18% higher than that of the TMNG-JAM-GAAFET and SMNG-JAM-GAAFET, respectively, demonstrating that the TGE-JAM-GAA BioFET is more suitable for applications in biosensing. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is dynamically regulated by methyltransferases (termed "writers") and demethylases (referred to as "erasers"), facilitating a reversible modulation. Changes in m6A levels significantly influence cellular functions, such as RNA export from the nucleus, mRNA metabolism, protein synthesis, and RNA splicing. They are intricately associated with a spectrum of pathologies. Moreover, dysregulation of m6A modulation has emerged as a promising therapeutic target across many diseases. m6A plays a pivotal role in controlling vital downstream molecules and critical biological pathways, contributing to the pathogenesis and evolution of numerous conditions. This review provides an overview of m6A demethylases, explicitly detailing the structural and functional characteristics of FTO and ALKBH5. Additionally, we explore their distinct involvement in various diseases, examine factors regulating their expression, and discuss the progress in inhibitor development. [ABSTRACT FROM AUTHOR]

The N‐methylation reaction of amines with methanol via the borrowing‐hydrogen strategy is an important method for the construction of C−N bonds. Compared with other C1 sources, such as toxic formaldehyde or expensive formic acid, methanol is more suitable for N‐methylation reactions due to its eco‐friendliness and low price. Using this strategy, various types N‐methylated products, including biological and pharmaceutical molecules have been prepared. Here, we present a thorough survey of decades of articles showing current developments in N‐methylation reactions with methanol. We discuss homogenous, heterogenous and light‐driven catalytic systems for both N‐methylation and N,N‐dimethylation reactions. This review presents the shortcomings of current developments and provides future development progress in N‐methylation reactions with methanol. [ABSTRACT FROM AUTHOR]

Background: More than a century has passed since it was discovered that many bacteria produce indole, but research into the actual biological roles of this molecule is just now beginning. The influence of indole on bacterial virulence was extensively investigated in indole-producing bacteria like Escherichia coli. To gain a deeper comprehension of its functional role, this study investigated how indole at concentrations of 0.5-1.0 mM found in the supernatant of Escherichia coli stationary phase culture was able to alter the virulence of non-indole-producing bacteria, such as Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae, which are naturally exposed to indole in mixed infections with Escherichia coli. Results: Biofilm formation, antimicrobial susceptibility, and efflux pump activity were the three phenotypic tests that were assessed. Indole was found to influence antibiotic susceptibly of Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae to ciprofloxacin, imipenem, ceftriaxone, ceftazidime, and amikacin through significant reduction in MIC with fold change ranged from 4 to 16. Biofilm production was partially abrogated in both 32/45 Pseudomonas aeruginosa and all eight Proteus mirabilis, while induced biofilm production was observed in 30/40 Klebsiella pneumoniae. Moreover, acrAB and oqxAB, which encode four genes responsible for resistance-nodulation-division multidrug efflux pumps in five isolates of Klebsiella pneumoniae were investigated genotypically using quantitative real-time (qRT)-PCR. This revealed that all four genes exhibited reduced expression indicated by 2^−ΔΔCT < 1 in indole-treated isolates compared to control group. Conclusion: The outcomes of qRT-PCR investigation of efflux pump expression have established a novel clear correlation of the molecular mechanism that lies beneath the influence of indole on bacterial antibiotic tolerance. This research provides novel perspectives on the various mechanisms and diverse biological functions of indole signaling and how it impacts the pathogenicity of non-indole-producing bacteria. [ABSTRACT FROM AUTHOR]

Nitrile‐aminothiol conjugation (NATC) stands out as a promising biocompatible ligation technique due to its high chemo‐selectivity. Herein we investigated the reactivity and substrate scope of NAT conjugation chemistry, thus developing a novel pH dependent orthogonal NATC as a valuable tool for chemical biology. The study of reaction kinetics elucidated that the combination of heteroaromatic nitrile and aminothiol groups led to the formation of an optimal bioorthogonal pairing, which is pH dependent. This pairing system was effectively utilized for sequential and dual conjugation. Subsequently, these rapid (≈1 h) and high yield (>90 %) conjugation strategies were successfully applied to a broad range of complex biomolecules, including oligonucleotides, chelates, small molecules and peptides. The effectiveness of this conjugation chemistry was demonstrated by synthesizing a fluorescently labelled antimicrobial peptide‐oligonucleotide complex as a dual conjugate to imaging in live cells. This first‐of‐its‐kind sequential NATC approach unveils unprecedented opportunities in modern chemical biology, showcasing exceptional adaptability in rapidly creating structurally complex bioconjugates. Furthermore, the results highlight its potential for versatile applications across fundamental and translational biomedical research. [ABSTRACT FROM AUTHOR]

A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases. Therapeutic possibilities have emerged for rectifying abnormal biochemical reactions by modulating intermolecular interactions. Here, the authors present a regulatory strategy for capturing biomolecules and preventing enzyme leakage using a chiral-engineered peptide supramolecular gel. [ABSTRACT FROM AUTHOR]

S-Adenosyl-L-methionine (SAM)-mediated methylation of biomolecules controls their function and regulates numerous vital intracellular processes. Analogs of SAM with a reporter group in place of the S-methyl group are widely used to study these processes. However, many of these analogs are chemically unstable that largely limits their practical application. We have developed a new compound, SAM-Ph, which contains an H-phosphinic group (-P(O)(H)OH) instead of the SAM carboxylic group. SAM-PH is significantly more stable than SAM, retains functional activity in catechol-O-methyltransferase and methyltransferase WBSCR27 reactions. The last is associated with Williams-Beuren syndrome. Rac-SAM-PH was synthesized chemically, while (R,S)-SAM-PH and its analogs were prepared enzymatically either from H-phosphinic analogs of methionine (Met-PH) or H-phosphinic analog of S-adenosyl-L-homocysteine (SAH-Ph) using methionine adenosyltransferase 2A or halide methyltransferases, respectively. SAH-PH undergoes glycoside bond cleavage in the presence of methylthioadenosine nucleosidase like natural SAH. Thus, SAM-PH and its analogs are promising new tools for investigating methyltransferases and incorporating reporter groups into their substrates. [ABSTRACT FROM AUTHOR]

The design and optimization of antimicrobial materials (polymers, biomolecules, or nanocomposites) can be significantly advanced by computational methodologies like molecular dynamics (MD), which provide insights into the interactions and stability of the antimicrobial agents within the polymer matrix, and machine learning (ML) or design of experiment (DOE), which predicts and optimizes antimicrobial efficacy and material properties. These innovations not only enhance the efficiency of developing antimicrobial polymers but also enable the creation of materials with tailored properties to meet specific application needs, ensuring safety and longevity in their usage. Therefore, this paper will present the computational methodologies employed in the synthesis and application of antimicrobial polymers, biomolecules, and nanocomposites. By leveraging advanced computational techniques such as MD, ML, or DOE, significant advancements in the design and optimization of antimicrobial materials are achieved. A comprehensive review on recent progress, together with highlights of the most relevant methodologies' contributions to state-of-the-art materials science will be discussed, as well as future directions in the field will be foreseen. Finally, future possibilities and opportunities will be derived from the current state-of-the-art methodologies, providing perspectives on the potential evolution of polymer science and engineering of novel materials. [ABSTRACT FROM AUTHOR]

The limited arsenal of antifungal drugs have prompted the search for novel molecules with biological activity. This study aimed to characterize the antifungal mechanism of action of Eugenia uniflora extract and its synergistic activity with commercially available antifungal drugs on the following Candida species: C. albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. dubliniensis. In silico analysis was performed to predict antifungal activity of the major compounds present in the extract. Minimal inhibitory concentrations (MICs) were determined in the presence of exogenous ergosterol and sorbitol. Yeast cells were grown in the presence of stressors. The loss of membrane integrity was assessed using propidium iodide staining (fluorescence emission). Synergism between the extract and antifungal compounds (in addition to time kill-curves) was determined. Molecular docking revealed possible interactions between myricitrin and acid gallic and enzymes involved in ergosterol and cell wall biosynthesis. Candida cells grown in the presence of the extract with addition of exogenous ergosterol and sorbitol showed 2 to 8-fold increased MICs. Strains treated with the extract revealed greater loss of membrane integrity when compared to their Fluconazole counterparts, but this effect was less pronounced than the membrane damage caused by Amphotericin B. The extract also made the strains more susceptible to Congo red and Calcofluor white. A synergistic action of the extract with Fluconazole and Micafungin was observed. The E. uniflora extract may be a viable option for the treatment of Candida infections. [ABSTRACT FROM AUTHOR]

Surface modification of polymeric materials to control their interaction with proteins has been studied extensively, leading to widespread bio‐applications. However, the development of nonbiological, smart polymer surfaces, mimicking the recognition ability of biomolecules, remains a challenge. The present study presents a thioether‐bridging surface modification of polymeric microspheres as a new approach for mimicking protein A affinity for immunoglobulin G (IgG). The bridge‐modified surface is created through an epoxide linking reaction of porous polymeric microspheres with potassium thioacetate in a 2:1 molar ratio, acting as a protein A ligand, which is essential for industrial IgG purification. This surface exhibits buffer responsiveness and selective high‐affinity binding to the IgG Fc region. Remarkably, a comparison among the binding behaviors of a series of thioether‐modified microspheres indicates that bridging structures composed of β,β′‐dihydroxysulfide play a predominant role in IgG recognition. This straightforward approach can lead to the development of economical and practical nonbiological alternatives to protein A‐conjugated materials, providing solutions for various applications such as biosensors and site‐specific reagents utilizing the affinity of the IgG Fc region. The improved understanding of protein interactions at bridged/non‐bridged interfaces can be valuable in various applications such as implant materials and biomaterials. [ABSTRACT FROM AUTHOR]

For the first time, a new configuration of label-free junctionless semiconductor device is proposed to boost sensitivity in the identification of biomolecule specifies. Instead of creating the nanocavity inside the gate oxide, the nanocavity is created in the channel region which is very useful for the SOI junctionless technology based biodevice having a high current in all operating modes. For better control of the conduction mechanism, a hole trench is created under the channel region just inside the buried oxide. This will help to modulate the energy bands terminating in enhancing the sensing performance. Unlike the conventional biosensors needing a large-scale gate oxide thickness for trapping the biomolecules, the proposed biosensor can work for very low gate oxide thickness. The different biomolecules such as Biotin, Protein A, Bacteriophage T7, and Apomyoglobin have been utilized as targeted biomolecules for evaluating the sensitivity. Comparing the proposed biosensor with the conventional and other biosensors showed an enhanced sensing performance. Practical related issues during the process of sensing in terms of fill factor percentage, steric hindrance of biomolecules, and the charges of biomolecules have been focused in the recommended biodevice. All the results exhibited high superiority of performance of the suggested biodevice as compared to the conventional biosensor. [ABSTRACT FROM AUTHOR]

Cryogenic electron microscopy (cryo-EM) has emerged as a powerful method for the determination of structures of complex biological molecules. The accurate characterisation of the dynamics of such systems, however, remains a challenge. To address this problem, we introduce cryoENsemble, a method that applies Bayesian reweighting to conformational ensembles derived from molecular dynamics simulations to improve their agreement with cryo-EM data, thus enabling the extraction of dynamics information. We illustrate the use of cryoENsemble to determine the dynamics of the ribosome-bound state of the co-translational chaperone trigger factor (TF). We also show that cryoENsemble can assist with the interpretation of low-resolution, noisy or unaccounted regions of cryo-EM maps. Notably, we are able to link an unaccounted part of the cryo-EM map to the presence of another protein (methionine aminopeptidase, or MetAP), rather than to the dynamics of TF, and model its TF-bound state. Based on these results, we anticipate that cryoENsemble will find use for challenging heterogeneous cryo-EM maps for biomolecular systems encompassing dynamic components. [ABSTRACT FROM AUTHOR]