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A simple, rapid, highly sensitive and selective spectrophotometric method has been developed for the determination of fluoride present in glass. The sample is decomposed at low temperature with NaOH and interfering species such as silica are separated as zinc silicate and alumina by extraction with TBP (tri-n-butyl phosphate) plasticized polyurethane foam (PUF). The amount of fluoride in the aqueous medium is subsequently determined spectrophotometrically based on the mixed ligand complex of thorium fluoride-alizarin complexone. The molar absorptivity was calculated to be 1⋅79x10³ l mol-1cm-1. The method obeys Beer's law in the range 0⋅20-20⋅0 µg F/ml. The developed method has been successfully applied to different glasses. [ABSTRACT FROM AUTHOR]

The movement of molecules (i.e. diffusion) within angstrom-scale pores of porous materials such as metal-organic frameworks (MOFs) and zeolites is influenced by multiple complex factors that can be challenging to assess and manipulate. Nevertheless, understanding and controlling this diffusion phenomenon is crucial for advancing energy-economic membrane-based chemical separation technologies, as well as for heterogeneous catalysis and sensing applications. Through precise assessment of the factors influencing diffusion within a porous metal-organic framework (MOF) thin film, we have developed a chemical strategy to manipulate and reverse chemical isomer diffusion selectivity. In the process of cognizing the molecular diffusion within oriented, angstrom-scale channels of MOF thin film, we have unveiled a dynamic chemical interaction between the adsorbate (chemical isomers) and the MOF using a combination of kinetic mass uptake experiments and molecular simulation. Leveraging the dynamic chemical interactions, we have reversed the haloalkane (positional) isomer diffusion selectivity, forging a chemical pathway to elevate the overall efficacy of membrane-based chemical separation and selective catalytic reactions., (© 2024. The Author(s).)

The aggregation of the protein α-synuclein into amyloid deposits is associated with multiple neurological disorders, including Parkinson's disease. Soluble amyloid oligomers are reported to exhibit higher toxicity than insoluble amyloid fibrils, with dimers being the smallest toxic oligomer. Small molecule drugs, such as fasudil, have shown potential in targeting α-synuclein aggregation and reducing its toxicity. In this study, we use atomistic molecular dynamics simulations to demonstrate how fasudil affects the earliest stage of aggregation, namely dimerization. Our results show that the presence of fasudil reduces the propensity for intermolecular contact formation between protein chains. Consistent with previous reports, our analysis confirms that fasudil predominantly interacts with the negatively charged C-terminal region of α-synuclein. However, we also observe transient interactions with residues in the charged N-terminal and hydrophobic NAC regions. Our simulations indicate that while fasudil prominently interacts with the C-terminal region, it is the transient interactions with residues in the N-terminal and NAC regions that effectively block the formation of intermolecular contacts between protein chains and prevent early dimerization of this disordered protein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proteins occurring in significantly high concentrations in cellular environments (over 100 mg/ml) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here, we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein aggregates. We show that ATP prevents both condensation of aggregation-prone intrinsically disordered protein Aβ40 and promotes dissolution of preformed aggregates. Computer simulation links ATP's solubilizing role to its ability to modulate protein's structural plasticity by unwinding protein conformation. We show that ATP is positioned as a superior biological solubilizer of protein aggregates over traditional chemical hydrotropes, potentially holding promises in therapeutic interventions in protein-aggregation-related diseases. Going beyond its conventional activity as energy currency, the amphiphilic nature of ATP enables its protein-specific interaction that would enhance ATP's efficiency in cellular processes., Competing Interests: SS, SG, CM, DD, JM No competing interests declared, (© 2024, Sarkar et al.)

Within the framework of liquid-liquid phase separation (LLPS), biomolecular condensation orchestrates vital cellular processes, and its dysregulation is implicated in severe pathological conditions. Recent studies highlight the role of intrinsically disordered proteins (IDPs) in LLPS, yet the influence of microenvironmental factors has remained a puzzling factor. Here, via computational simulation of the impact of solution conditions on LLPS behavior of neurologically pathogenic IDP Aβ40, we chanced upon a salt-driven reentrant condensation phenomenon, wherein Aβ40 aggregation increases with low salt concentrations (25-50 mM), followed by a decline with further salt increments. An exploration of the thermodynamic and kinetic signatures of reentrant condensation unveils a nuanced interplay between protein electrostatics and ionic strength as potential drivers. Notably, the charged residues of the N-terminus exhibit a nonmonotonic response to salt screening, intricately linked to the recurrence of reentrant behavior in hydrophobic core-induced condensation. Intriguingly, our findings also unveil the reappearance of similar reentrant condensation phenomena under varying temperature conditions. Collectively, our study illuminates the profoundly context-dependent nature of Aβ40s liquid-liquid phase separation behavior, extending beyond its intrinsic molecular framework, where microenvironmental cues wield significant influence over its aberrant functionality.

The potential to produce high-purity C 2 H 4 has made ethylene-selective adsorbents for ethane (C 2 H 6 )/ethylene (C 2 H 4 ) gas mixture separation appealing as viable substitutes for traditional cryogenic distillation. In this aspect, porous organic polymers (POPs) are anticipated to become the next-generation potential adsorbent due to their easily customizable functions and functional sites suitable for gas separation. This article reports the selective C 2 H 4 adsorption over C 2 H 6 using microporous copper(I)-coordinated POP ( Cu@Di-POP ) via fine-tuning of the π complexation and pore size. The specially designed adsorbent has the ideal pore size and coordinated Cu(I) ions to form π-complexation with C 2 H 4 molecules, which enabled it to adsorb C 2 H 4 (at 1 bar, 24.9, 18.9, and 13.4 cm 3 g -1 at 273, 298, and 323 K, respectively) while significantly reducing C 2 H 6 adsorption (at 1 bar, 16.9, 12.7, and 8.8 cm 3 g -1 at 273, 298, and 323 K, respectively). At 1 bar, Cu@Di-POP exhibited IAST selectivities of 6.09, 5.60, and 4.13 for C 2 H 4 /C 2 H 6 at 273, 298, and 323 K, respectively, suggesting its C 2 H 4 selective behavior, which was further confirmed from the experimental breakthrough measurement. Furthermore, the computational studies carried out with density functional theory highlighted an enhanced charge distribution leading to dπ-pπ conjugation between C 2 H 4 π-electrons and Cu d-electrons, thereby showing a relatively higher interaction energy of -37.23 kcal/mol with C 2 H 4 as compared to -16.06 kcal/mol with C 2 H 6 gas molecules.

Adenosine triphosphate (ATP), ubiquitous in all living organisms, is conventionally recognized as a fundamental energy currency essential for a myriad of cellular processes. While its traditional role in energy metabolism requires only micromolar concentrations, the cellular content of ATP has been found to be significantly higher at the millimolar level. Recent studies have attempted to correlate this higher concentration of ATP with its nonenergetic role in maintaining protein homeostasis, leaving the investigation of ATP's nontrivial activities in biology an open question. Here, by coupling computer simulations and experiments, we uncover new insights into ATP's role as a cryoprotectant against cold-salt stress, highlighting the necessity for higher cellular ATP concentrations. We present direct evidence at charged silica interfaces, demonstrating ATP's ability to restore native intersurface interactions disrupted by combined cold-salt stress, thereby inhibiting cold-responsive aggregation in high-salt conditions. ATP desorbs salt cations from negatively charged surfaces through predominant interactions between ATP and the salt cations. Although the mode of ATP's action remains unchanged with temperature, the extent of interaction scales with temperature, requiring less ATP activity at lower temperatures, justifying the reason for reduction in cellular ATP content due to the cold effect, reported in previous experimental studies. The trend observed in inorganic nanostructures is recurrent and robustly transferable to charged protein interfaces. A thorough comparison of ATP's cryoprotective activity with traditionally known biological cryoprotectants (glycine and betaine) reveals ATP's greater efficiency. In retrospect, our findings highlight ATP's additional biological role in cryopreservation, expanding its potential biomedical applications by offering effective protection of cells from cryoinjuries and avoiding the significant challenges associated with the toxicity of organic cryoprotectants.

High dimensional nature of the chromosomal conformation contact map ('Hi-C Map'), even for microscopically small bacterial cell, poses challenges for extracting meaningful information related to its complex organization. Here we first demonstrate that an artificial deep neural network-based machine-learnt (ML) low-dimensional representation of a recently reported Hi-C interaction map of archetypal bacteria Escherichia coli can decode crucial underlying structural pattern. The ML-derived representation of Hi-C map can automatically detect a set of spatially distinct domains across E. coli genome, sharing reminiscences of six putative macro-domains previously posited via recombination assay. Subsequently, a ML-generated model assimilates the intricate relationship between large array of Hi-C-derived chromosomal contact probabilities and respective diffusive dynamics of each individual chromosomal gene and identifies an optimal number of functionally important chromosomal contact-pairs that are majorly responsible for heterogenous, coordinate-dependent sub-diffusive motions of chromosomal loci. Finally, the ML models, trained on wild-type E. coli show-cased its predictive capabilities on mutant bacterial strains, shedding light on the structural and dynamic nuances of ΔMatP30MM and ΔMukBEF22MM chromosomes. Overall our results illuminate the power of ML techniques in unraveling the complex relationship between structure and dynamics of bacterial chromosomal loci, promising meaningful connections between ML-derived insights and biological phenomena., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Natural selection has driven the convergence toward a selected set of osmolytes, endowing them with the necessary efficiency to manage stress arising from salt diversity. This study combines atomistic simulations and experiments to investigate how two osmolytes, glycine and betaine, individually modulate the Hofmeister ion ordering of alkali metal salts (LiCl, KCl, and CsCl) near a charged silica interface. Both osmolytes are found to prevent salt-induced aggregation of the charged entities, yet their mode and degree of relative modulation depend on their intricate interplay with specific salt cations. Betaine's ion-mediated surface interaction maintains Hofmeister ion ordering, whereas glycine alters the relative Hofmeister order of the cation by salt-specific ion desorption from the surface. Experimental validation through surface-enhanced Raman spectroscopy supports these findings, elucidating osmolyte-mediated alterations in interfacial water structures. These observations based on an inorganic interface are reciprocated in amyloid beta 40 dimerization dynamics, highlighting osmolytes' efficacy in mitigating salt-induced aggregation. A molecular analysis suggests that the differential modes of interaction, as found here for glycine and betaine, are prevalent across classes of zwitterionic osmolytes.

The energy sector has demonstrated significant enthusiasm for investigating post-combustion CO 2 capture, storage, and separation. However, the practical application of current porous adsorbents is impeded by challenges related to cost competitiveness, stability, and scalability. Intregation of heteroatoms in the porous organic polymers (POPs) dispense it more susceptible for CO 2 adsorption to attenuate green house gases. In this regard, two hydroxy rich hypercrosslinked POPs, namely Ph/Tt-POP have been developed by one-pot condensation polymerization using a facile synthetic strategy. The high surface areas of both the Ph/Tt-POP (1057 and 893 m 2 g -1 , respectively), and the heteroatom functionality in the POP framework instigated us to explore our material for CO 2 adsorption study. The CO 2 uptake capacities in Ph/Tt-POP are found to be 2.45 and 2.2 mmol g -1 , at 273 K respectively. Further, in-situ static 13 C NMR experiment shows that CO 2 molecules in Tt-POP appear to be less mobile than those in Ph-POP which probably due to the presence of triazine functional groups along with high abundant -OH groups in the Tt-POP framework. An in-depth study of the CO 2 adsorption mechanism by density functional theory (DFT) calculations also shows that CO 2 adsorption at the cages formed by two benzyl rings represents the most stable interaction and CO 2 molecule is more favorably adsorbed on the Ph-POP with the more negative interaction energies values compared to that of Tt-POP. Further, Non-covalent interaction (NCI) plot reveals that CO 2 molecules adsorb more on the Ph-POP than Tt-POP, which can be explain by hydrogen bond formation in case of Tt-POP repeating units turning aside CO 2 molecule to interact with the Ph component. Overall, our present study reflects the comprising effects of surface area of the solid adsorbents as well as their functionality can be beneficial for developing efficient hypercrosslinked porous polymers as solid CO 2 adsorbent., (© 2024 Wiley-VCH GmbH.)

Banana ( Musa paradisiaca ) farming generates huge quantities of biomass, all of which goes to waste due to the non-availability of suitable technology for its commercial application. The potential solution to this issue could be the conversion of pseudo-stems into valuable assets by converting them into fibres for various textile and non-textile applications. The specific characteristics of banana pseudo-stem fibre i.e. high absorptivity, breathability and biodegradability made it sustainable as well as suitable for the development of diversified products and blending with other natural fibres. However, non-uniformity in availability, obscurity of its intended uses and lack of knowledge for assessment of fibre quality posed a biggest hurdle to reach the fibre into the textile markets. Hence, a novel sensor-based digital instrument for assessing the quality parameters i.e. bundle strength and fineness along with overall grade of banana pseudo-stem fibre is presented in this research article. The developed instrument mainly consists of a fibre bundle strength measurement unit, fineness measuring unit and visual interface cum data acquisition unit. Test results indicated that bundle strength and fineness measured by developed instrument varied from 20.92 g/tex to 28.31 g/tex and 5.63 tex to 6.41 tex respectively. Furthermore, a good correlation between the measured and actual outputs of bundle strength ( One-Way ANOVA, F 28,2  =  3.914, P  =  0.224 ), fineness ( One-Way ANOVA, F 51,2  =  4.730, P  =  0.190 ) and overall quality of fibre ( Independent sample T-Test, F 34,1  =  0.95, P  =  0.190 ). Was observed at 5 % level of significance. The present study also introduced a grading system for quality assessment of banana fibre based on the well-established and well-recognized grading system of jute fibre developed by Indian Standard (IS: 271 2020). The developed instrument is easy to build as well as easy to use and have an approximate cost of $1800.00. The combination of developed instrument and grading system is an accurate, feasible and time-ordered technique for the assessment of the overall quality of the banana fibre and well suited for the actual conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Nature has ingeniously developed specialized water transporters that effectively reject ions, including protons, while transporting water across membranes. These natural water channels, known as aquaporins (AQPs), have inspired the creation of Artificial Water Channels (AWCs). However, replicating superfast water transport with synthetic molecular structures that exclude salts and protons is a challenging task. This endeavor demands the coexistence of a suitable water-binding site and a selective filter for precise water transportation. Here, we present small-molecule hydrazides 1 b-1 d that self-assemble into a rosette-type nanochannel assembly through intermolecular hydrogen bonding and π-π stacking interactions, and selectively transport water molecules across lipid bilayer membranes. The experimental analysis demonstrates notable permeability rates for the 1 c derivative, enabling approximately 3.18×10 8 water molecules to traverse the channel per second. This permeability rate is about one order of magnitude lower than that of AQPs. Of particular significance, the 1 c ensures exclusive passage of water molecules while effectively blocking salts and protons. MD simulation studies confirmed the stability and water transport properties of the water channel assembly inside the bilayer membranes at ambient conditions., (© 2024 Wiley-VCH GmbH.)

Intrinsically disordered protein α-synuclein (αS) is implicated in Parkinson's disease due to its aberrant aggregation propensity. In a bid to identify the traits of its aggregation, here we computationally simulate the multi-chain association process of αS in aqueous as well as under diverse environmental perturbations. In particular, the aggregation of αS in aqueous and varied environmental condition led to marked concentration differences within protein aggregates, resembling liquid-liquid phase separation (LLPS). Both saline and crowded settings enhanced the LLPS propensity. However, the surface tension of αS droplet responds differently to crowders (entropy-driven) and salt (enthalpy-driven). Conformational analysis reveals that the IDP chains would adopt extended conformations within aggregates and would maintain mutually perpendicular orientations to minimize inter-chain electrostatic repulsions. The droplet stability is found to stem from a diminished intra-chain interactions in the C-terminal regions of αS, fostering inter-chain residue-residue interactions. Intriguingly, a graph theory analysis identifies small-world-like networks within droplets across environmental conditions, suggesting the prevalence of a consensus interaction patterns among the chains. Together these findings suggest a delicate balance between molecular grammar and environment-dependent nuanced aggregation behavior of αS., Competing Interests: AW, SM, JM No competing interests declared, (© 2024, Wasim et al.)

Breast cancer is the most prevalent cancer among women and the leading cause of cancer-related deaths in this population. Recent advances in Immunotherapy, or combined immunotherapy, offering a more targeted and less toxic approach, expand the survival rate of patients more than conventional treatment. Notably, hydrogels, a versatile platform provided promising avenues to combat breast cancer in preclinical studies and extended to clinical practices. With advantages such as the alternation of tumor microenvironment, immunomodulation, targeted delivery of therapeutic agents, and their sustained release at specific sites of interest, hydrogels can potentially be used for the treatment of breast cancer. This review highlights the advantages, mechanisms of action, stimuli-responsiveness properties, and recent advancements of hydrogels for treating breast cancer immunotherapy. Moreover, post-treatment and its clinical translations are discussed in this review. The integration of hydrogels in immunotherapy strategies may pave the way for more effective, personalized, and patient-friendly approaches to combat breast cancer, ultimately contributing to a brighter future for breast cancer patients., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Small modifications in the chemical structure of ligands are known to dramatically change their ability to inhibit the activity of a protein. Unraveling the mechanisms that govern these dramatic changes requires scrutinizing the dynamics of protein-ligand binding and unbinding at the atomic level. As an exemplary case, we have studied Glycogen Synthase Kinase-3β (GSK-3β), a multifunctional kinase that has been implicated in a host of pathological processes. As such, there is a keen interest in identifying ligands that inhibit GSK-3β activity. One family of compounds that are highly selective and potent inhibitors of GSK-3β is exemplified by a molecule termed COB-187. COB-187 consists of a five-member heterocyclic ring with a thione at C 2 , a pyridine substituted methyl at N 3 , and a hydroxyl and phenyl at C 4 . We have studied the inhibition of GSK-3β by COB-187-related ligands that differ in a single heavy atom from each other (either in the location of nitrogen in their pyridine ring, or with the pyridine ring replaced by a phenyl ring), or in the length of the alkyl group joining the pyridine and the N 3 . The inhibition experiments show a large range of half-maximal inhibitory concentration (IC 50 ) values from 10 nM to 10 μM, implying that these ligands exhibit vastly different propensities to inhibit GSK-3β. To explain these differences, we perform Markov State Modeling (MSM) using fully atomistic simulations. Our MSM results are in excellent agreement with the experiments in that they accurately capture differences in the binding propensities of the ligands. The simulations show that the binding propensities are related to the ligands' ability to attain a compact conformation where their two aromatic rings are spatially close. We rationalize this result by sampling numerous binding and unbinding events via funnel metadynamics simulations, which show that indeed while approaching the bound state, the ligands prefer to be in their compact conformation. We find that the presence of nitrogen in the aromatic ring increases the probability of attaining the compact conformation. Protein-ligand binding is understood to be dictated by the energetics of interactions and entropic factors, like the release of bound water from the binding pockets. This work shows that changes in the conformational distribution of ligands due to atom-level modifications in the structure play an important role in protein-ligand binding.

A combined experimental and simulation study of dielectric relaxation (DR) of a deep eutectic solvent (DES) composed of betaine, urea, and water with the composition [Betaine:Urea:Water = 11.7:12:1 (weight ratio) and 9:18:5 (molar ratio)] was performed to explore and understand the interaction and dynamics of this system. Temperature-dependent (303 ≤ T / K ≤ 343) measurements were performed over 9 decades of frequency, combining three different measurement setups. Measured DR, comprising four distinct steps with relaxation times spreading over a few picoseconds to several nanoseconds, was found to agree well with simulations. The simulated total DR spectra, upon dissection into three self (intraspecies) and three cross (interspecies) interaction contributions, revealed that the betaine-betaine self-term dominated (∼65%) the relaxation, while the urea-urea and water-water interactions contributed only ∼7% and ∼1%, respectively. The cross-terms (betaine-urea, betaine-water, and urea-water) together accounted for <30% of the total DR. The slowest DR component with a time constant of ∼1-10 ns derived dominant contribution from betaine-betaine interactions, where betaine-water and urea-water interactions also contributed. The subnanosecond (0.1-0.6 ns) time scale originated from all interactions except betaine-water interaction. An extensive interaction of water with betaine and urea severely reduced the average number of water-water H-bonds (∼0.7) and heavily decreased the static dielectric constant of water in this DES (ε s ∼ 2). Furthermore, simulated first rank collective single particle reorientational relaxations ( C 1 ( t )) and the structural H-bond fluctuation dynamics ( C HB ( t )) exhibited multiexponential kinetics with time scales that corresponded well with those found both in the simulated and measured DR.

Harvesting solar energy to produce value-added chemicals from carbon dioxide (CO 2 ) presents a promising route for addressing the complexities of sustainable energy systems and environmental issues. In this context, the development of metal-coordinated porous organic polymers (POPs) offers a vital avenue for improving the photocatalytic performance of organic motifs. The current study presents a metal-integrated photocatalytic system (namely, Zn@BP-POP ) developed via a one-pot Friedel-Crafts (F.C.) acylation strategy, for solid-gas phase photochemical CO 2 reduction to CO (CO 2 RR). The postsynthetic incorporation of metal (Zn) active sites on the host polymeric backbone of BP-POP significantly influences the catalytic activity. Notably, Zn@BP-POP demonstrates good photocatalytic performance in the absence of any cocatalyst and photosensitizer yielding CO while impeding the competitive hydrogen evolution reaction (HER) from water. The experimental findings collectively propose that the observed catalytic activity and selectivity arise from the synergistic interplay between the singular zinc catalytic centers and the light-harvesting capacity of the highly conjugated polymeric backbone. Further, X-ray absorption spectroscopy (XAS) analysis has significantly highlighted the prominent role played by the ZnN 2 O 4 single sites in the polymeric framework for activating the gaseous CO 2 molecules. Further, time-dependent density functional theory (DFT) analysis also reveals the thermodynamic feasibility of CO 2 RR over HER under optimized reaction conditions. This work cumulatively presents an effective strategy to demonstrate the importance of metal-active sites and effectively establish their structure-activity relationship during photocatalysis.

Aim: The point of search of present study was to assess intracanal viability of cold saline, curcumin as an irrigant, and ordinary saline as last irrigant in lessening post endodontic torment., Material and Method: In total, 60 individuals were chosen and divided into 3 groups: Group I: intracanal cryotherapy using 2.5°C cold saline, Group II: curcumin irrigant, and Group III: ordinary saline. After the biomechanical preparation, the above mentioned irrigant was used. On the visual analogue scale, participants were asked to rank the intensity of their discomfort following the procedure before, after 6 h and 24 h after the procedure. The outcomes were dissected utilizing ANOVA test., Result: Both the regimens were successful in reducing post endodontic soreness associated with infected teeth., Conclusion: Curcumin and cryotherapy both the regimens were successful in lessening post endodontic torment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)