NA Molecules Research Articles

Mobility and transport of pharmaceuticals nalidixic acid and niflumic acid in saturated soil columns

Pharmaceutical compounds often coexist in mixtures rather than as individual entities. However, little is known about their co-adsorption and co-mobility in soil and groundwater. In this study, we investigated the adsorption of a quinolone antibiotic (nalidixic acid, NA) and an anti-inflammatory agent (niflumic acid, NFA) onto two soils from France and Sweden in water-saturated soil columns. Despite its lower hydrophobicity, adsorption of NA is much greater than NFA, which can be ascribed to the presence of both carbonyl and carboxylic groups in NA molecule. The data suggest that chemical adsorption to soil components can mainly take place through hydrogen bonding and surface complexation mechanisms, prevailing over hydrophobic interactions. Accordingly, more sorption of NA and NFA was observed in the Swedish soil because it contains more clay content, and much greater Al and Fe contents than the French soil. Injection of NA/NFA mixture in the column did not modify the breakthrough behavior compared to single systems, although cooperative adsorption was observed under static batch conditions. Ca2+ inhibited NA adsorption by forming a soluble NA-Ca2+ complex but promoted NFA adsorption both in single and binary systems. Their mobility in soil columns was well predicted using a new transport model that accounts for both kinetics and binding reactions of NA and NFA to soil constituents. This work will help in accurately predicting the mobility of coexisting pharmaceutical compounds in soils.

Unraveling the mechanisms of wider negative voltage window in single-layer graphene/DMSO-H2O hybrid electrolyte interface by the theoretical study of the sodium-ion solvation sheath interfacial model

Graphene has demonstrated to be a great candidate as electrode materials in applications of electrical double-layer (EDL) capacitors. However, for graphene/electrolyte EDL, the hydrogen evolution reaction (HER)-dominated negative voltage window has become the challenge to obtain devices with high energy density. The introduction of dimethyl sulfoxide (DMSO) in water solvent for co-solvent electrolyte has been demonstrated to be an efficient strategy to suppress HER because the O atom in DMSO acts as a hydrogen bond acceptor to anchor a water molecule. However, the role of DMSO in broadening the negative voltage window still needs further explanation. Here, we employ ab initio molecular dynamics simulations on a model system composed of single-layer graphene/co-solvent NaCl electrolyte interface to describe the co-solvent based Na+ solvation sheath interfacial model. It is found that a passivation layer has been constructed on the electrode surface, where DMSO replaces part of water molecules and tunes the adsorption structure of the remaining interfacial water molecules in Na+ solvation sheath (Na·H2O). Our calculation elucidates that the interaction between DMSO and water molecules is stronger than that between interfacial water molecules and negatively-charged electrode. Thus, the interfacial water molecules in Na+ solvation sheath no longer evolve to 0-coordinated Na·H2O state and have less HER activity. Moreover, we relate the amount of Na·H2O with high HER activity to the operating negative voltage window. Our work provides new insights into the mechanism of the co-solvent electrolyte in broadening negative voltage window and the formation of the practical negative voltage window during electrochemical processes.

Effect of fluoro and hydroxy analogies of diglyme on sodium-ion storage in graphite: a computational study.

Diglyme co-intercalation with sodium ion (Na+) into graphite can enable the use of graphite as a potential anode for sodium-ion batteries (NIBs). However, the presence of diglyme molecules in Na+ intercalated graphite limits Na+ storage capacity and increases volume changes. In this work, the effect of functionalising diglyme molecules with fluoro and hydroxy groups on Na+ storage properties in graphite were computationally studied. It was found that the functionalisation can significantly alter the binding between sodium and the solvent ligand as well as between the sodium-solvent complex and the graphite. The hydroxy-functionalised diglyme exhibits the strongest binding to the graphite of the other functionalised diglyme compounds considered. The calculations also reveal that the graphene layer affects the electron distribution on the diglyme molecule and Na, so the diglyme complexed Na binds more strongly to the graphene layer than the Na alone. We also propose a mechanism for the early stages of the intercalation mechanism that involves a reorientation of the sodium-diglyme complex and suggest how the solvent can be designed to optimise the co-intercalation process.

Understanding the origin of the wide voltage window of microporous carbon electrodes with oxygen-containing defects by modulating surface chemistry

Benefiting from the specific microporous carbon/electrolyte interface with O-containing defect, the interfacial water molecules in Na+ solvation shell lose HER activity. Thus, the EDL structure has wide operating voltage window.

DNA damage response inhibition‐based combination therapies in cancer treatment: Recent advances and future directions

AbstractDNA molecules are subject to various lesions that can be detrimental to the cells. DNA damage response (DDR) pathways encompass a variety of mechanisms that cells employ in response to DNA damage. While DDR promotes genomic stability in normal cells, it also protects cancer cells from DNA lesions, particularly against exogenous DNA‐damaging agents. Therefore, DDR pathways can be exploited to account for resistance to chemotherapy and radiotherapy and have the potential to be targeted in cancer treatment. Apart from the poly (ADP‐ribose) polymerase (PARP) inhibitors used in BRCA‐mutant cancers, other DDR inhibitors are being developed and tested in clinical trials. Based on the synthetic lethality theory, combination therapies utilizing DDR inhibitors have been explored and are currently undergoing clinical trials, with promising results in cancer treatment. Combination therapies typically employ a DDR inhibitor to sensitize cancer cells to traditional chemotherapeutic agents, radiotherapy, immunotherapy, and even PARP inhibitors. Herein, we focus on recent advances in DDR inhibitor‐based combination therapies other than PARP inhibitors, explore the advantages and disadvantages of the strategies, and discuss the current challenges and future perspectives.

Non-radioactive In Vivo Labeling of RNA with 4-Thiouracil.

RNA molecules and their expression dynamics play essential roles in the establishment of complex cellular phenotypes and/or in the rapid cellular adaption to environmental changes. Accordingly, analyzing RNA expression remains an important step to understand the molecular basis controlling the formation of cellular phenotypes, cellular homeostasis or disease progression. Steady-state RNA levels in the cells are controlled by the sum of highly dynamic molecular processes contributing to RNA expression and can be classified in transcription, maturation and degradation. The main goal of analyzing RNA dynamics is to disentangle the individual contribution of these molecular processes to the life cycle of a given RNA under different physiological conditions. In the recent years, the use of nonradioactive nucleotide/nucleoside analogs and improved chemistry, in combination with time-dependent and high-throughput analysis, have greatly expanded our understanding of RNA metabolism across various cell types, organisms, and growth conditions.In this chapter, we describe a step-by-step protocol allowing pulse labeling of RNA with the nonradioactive nucleotide analog, 4-thiouracil , in the eukaryotic model organism Saccharomyces cerevisiae and the model archaeon Haloferax volcanii .

Folding Stability and Self‐Association of a Triplet‐Repeat (CAG)20 RNA Hairpin in Cytomimetic Media

AbstractRNA molecules with trinucleotide repeat expansions are involved in the pathology of various neurodegenerative diseases, such as Huntington's disease. A central research objective is to understand how trinucleotide repeat RNAs fold and function in disease progression. Studies that investigate the sequence structure, stability and self‐assembly of such RNAs mainly focused on in vitro methods in dilute aqueous solution. Functional studies in cells reveal further aspects of transport, protein association or assembly in phase separated compartments. Our study aims to understand governing factors for folding stability of trinucleotide repeats on the cellular level by assessing the influence of key components of the cellular medium in vitro. We investigate (CAG)20 RNA in complex and cytomimetic media using Fast Relaxation Imaging. Using distinct cosolutes we analyze the different enthalpic and entropic contributions that determine folding stability. We find a remarkable destabilization and aggregation of the RNA in cellular lysate that can be attributed to specific and non‐specific interactions with the unfolded state.

Cold-atom–dimer reaction rates with He4, Li6,7 , and Na23

Atom-dimer exchange and dissociation reaction rates are predicted for different combinations of two $^4$He atoms and one of the alkaline species among $^{6}$Li, $^{7}$Li and $^{23}$Na, by using three-body scattering formalism with short-range two-body interactions. Our study was concerned with low-energy reaction rates in which the $s-$, $p-$ and $d-$ wave contributions are the relevant ones. The $^4$He is chosen as one of the atoms in the binary mixture, in view of previous available investigations and laboratory accessibilities. Focusing on possible experimental cold-atom realizations with two-atomic mixtures, in which information on atom-dimer reaction rates can be extracted, we predict the occurrence of a dip in the elastic reaction rate for colliding energies smaller than 20 mK, when the dimer is the $^4$He$^{23}$Na molecule. We are also anticipating a zero in the elastic $p-$wave contribution for the $^4$He + $^4$He$^7$Li and $^4$He + $^4$He$^{23}$Na reaction processes. With weakly-bound molecules reacting with atoms at very low colliding energies, we interpret our results on the light of Efimov physics which supports model independence and robustness of our predictions. Specific sensitivities on the effective range were evidenced, highlighted by the particular inversion role of the $p-$ and $d-$waves in the atom exchange and dissociation processes.

Thermal Decomposition of Ternary Sodium Graphite Intercalation Compounds.

Graphite intercalation compounds (GICs) are often used to produce exfoliated or functionalised graphene related materials (GRMs) in a specific solvent. This study explores the formation of the Na‐tetrahydrofuran (THF)‐GIC and a new ternary system based on dimethylacetamide (DMAc). Detailed comparisons of in situ temperature dependent XRD with TGA‐MS and Raman measurements reveal a series of dynamic transformations during heating. Surprisingly, the bulk of the intercalation compound is stable under ambient conditions, trapped between the graphene sheets. The heating process drives a reorganisation of the solvent and Na molecules, then an evaporation of the solvent; however, the solvent loss is arrested by restacking of the graphene layers, leading to trapped solvent bubbles. Eventually, the bubbles rupture, releasing the remaining solvent and creating expanded graphite. These trapped dopants may provide useful property enhancements, but also potentially confound measurements of grafting efficiency in liquid‐phase covalent functionalization experiments on 2D materials.

Integrative characterization of G-Quadruplexes in the three-dimensional chromatin structure

ABSTRACTDNA molecules are highly compacted in the eukaryotic nucleus where distal regulatory elements reach their targets through three-dimensional chromosomal interactions. G-quadruplexes, stable four-stranded non-canonical DNA structures, can change local chromatin organization through the exclusion of nucleosomes. However, the relationship between G-quadruplexes and higher-order genome organization remains unknown. Here, we found that G-quadruplexes are significantly enriched at boundaries of topological associated domains (TADs). Architectural protein occupancy, which plays critical roles in the formation of TADs, was highly correlated with the content of G-quadruplexes at TAD boundaries. Moreover, adjacent boundaries containing G-quadruplexes frequently interacted with each other because of the high enrichment of architectural protein binding sites. Similar to CCCTC-binding factor (CTCF) binding sites, G-quadruplexes also showed strong insulation ability in the separation of adjacent regions. Additionally, the insulation ability of CTCF binding sites and TAD boundaries was significantly reinforced by G-quadruplexes. Furthermore, G-quadruplex motifs on different strands were associated with the orientation of CTCF binding sites. These findings suggest a potential role for G-quadruplexes in loop extrusion. The enrichment of transcription factor binding sites (TFBSs) around regulatory elements containing G-quadruplexes led to frequent interactions between regulatory elements containing G-quadruplexes. Intriguingly, more than 99% of G-quadruplexes overlapped with TFBSs. The binding sites of CTCF and cohesin proteins were preferentially located surrounding G-quadruplexes. Accordingly, we proposed a new mechanism of long-distance gene regulation in which G-quadruplexes are involved in distal interactions between enhancers and promoters.

On the exclusion of the negative contribution to the molecular partition function

ABSTRACTThe article presents classical mechanics approach to thermodynamic properties of molecules at high temperatures which is based on a specific realisation of the idea of excluded volume and in the end avoids the use of second virial coefficient (in contrary to other approaches). The aim of this approach is to remove the negative contribution to the molecular partition function. The influence of the negative part on the partition function is investigated for the ground state of Na molecule. The full molecular partition functions (with bound, resonance and scattering contributions) are compared with the ones with negative contribution excluded. Additionally the applicability of the hard spheres repulsion is investigated and the comparison with an exact free (scattering) contribution is made.

Scattering of cold He4 on He4Li6,7 and He4Na23 molecules

We predict $s-$wave elastic cross-sections $\sigma$ for low-energy atom-molecule collisions with kinetic energies up to 40 mK, for the $^4$He collision with weakly bound diatomic molecules formed by $^4$He with $^7$Li, $^6$Li and $^{23}$Na. Our scattering calculations are performed by using diatomic and triatomic molecular binding energies obtained from several available realistic models as input in a renormalized zero-range model, as well as a finite-range one-term separable potential in order to quantify the relevance of range corrections to our predictions. Of particular relevance for possible experimental realization, we show the occurrence of a zero in $\sigma$ for the collision of cold $^4$He on $^4$He$-^{23}$Na molecule below 20 mK. Also our results for the elastic collision $^4$He on $^4$He$-^{6,7}$Li molecules suggest that $\sigma$ varies considerably for the realistic models studied. As the chosen molecules are weakly bound and the scattering energies are very low, our results are interpreted on the light of the Efimov physics, which explains the model independent and robustness of our predictions, despite some sensitivity on the potential range.

A Versatile Multiple Target Detection System Based on DNA Nano-assembled Linear FRET Arrays.

DNA molecules have been utilized both as powerful synthetic building blocks to create nanoscale architectures and as inconstant programmable templates for assembly of biosensors. In this paper, a versatile, scalable and multiplex detection system is reported based on an extending fluorescent resonance energy transfer (FRET) cascades on a linear DNA assemblies. Seven combinations of three kinds of targets are successfully detected through the changes of fluorescence spectra because of the three-steps FRET or non-FRET continuity mechanisms. This nano-assembled FRET-based nanowire is extremely significant for the development of rapid, simple and sensitive detection system. The method used here could be extended to a general platform for multiplex detection through more-step FRET process.

Nanofabrication of a Solid-State, Mesoporous Nanoparticle Composite for Efficient Photocatalytic Hydrogen Generation.

Room-temperature self-assembly was used to fabricate a periodic array of uniformly sized Al3+ -doped SiO2 nanoparticles (Al-SiO2 NPs, 20-30 nm). The uniform mesoporous structure was suitable for uniformly incorporating and distributing Pt nanoparticles (PtNPs), which were used as hydrogen-evolution catalysts in artificial photosynthetic systems, without agglomeration during the catalytic reaction. When the surfaces of the Al-SiO2 NPs were covered with an organic photocatalyst (2-phenyl-4-(1-naphthyl)quinolinium ion, QuPh+ -NA), each PtNP was surrounded by multiple QuPh+ -NA ions. The structure allowed the PtNP to receive multiple electrons from QuPh. -NA molecules, which were generated by reduction of the photoexcited state of QuPh+ -NA ions (QuPh. -NA. + ) with β-dihydronicotinamide adenine dinucleotide (NADH), thereby resulting in efficient photocatalytic H2 evolution.

Acid dissociation constants and cytotoxicity test of a series of omega-aminoalkyl phosphates

Abstract We synthesised a series of ω -aminoalkyl sodium hydrogen phosphates (AAP- n -Na, n = 3, 4, 5, 6, purity > 99%), which have potential applications as bioactive cosmetic ingredients and surface modifiers of bone minerals ( i.e. hydroxyapatites). Results from Fourier transformed infrared (FTIR), nuclear magnetic resonance (NMR) and high resolution mass spectroscopy, and elemental analysis all matched their chemical structures. The acid dissociation constants (p K a's) of each AAP- n (acid form of AAP- n -Na, n = 2–6) were measured by potentiometric titration, showing a general increasing trend with an increase in the chain length of AAP- n . However, the p K a 3 constant, which corresponds to the deprotonation of the ammonium group in AAP- n -Na, displayed an unusual decrease when n = even. This odd–even effect can be explained by the pairwise self-association of AAP- n -Na molecules in water where intermolecular hydrogen bonding in case of n = even is weaker than that in case of n = odd. All AAP- n -Na at concentrations up to 0.1% (w/v) were non-toxic to L929 fibroblasts and MG 63 osteoblast-like cells in terms of cell growth and morphology. These basic data were important for applications of AAP- n and their salts in biomedical engineering.

Evolution of RNA-Based Networks.

RNA molecules have served for decades as a paradigmatic example of molecular evolution that is tractable both in in vitro experiments and in detailed computer simulation. The adaptation of RNA sequences to external selection pressures is well studied and well understood. The de novo innovation or optimization of RNA aptamers and riboswitches in SELEX experiments serves as a case in point. Likewise, fitness landscapes building upon the efficiently computable RNA secondary structures have been a key toward understanding realistic fitness landscapes. Much less is known, however, on models in which multiple RNAs interact with each other, thus actively influencing the selection pressures acting on them. From a computational perspective, RNA-RNA interactions can be dealt with by same basic methods as the folding of a single RNA molecule, although many details become more complicated. RNA-RNA interactions are frequently employed in cellular regulation networks, e.g., as miRNA bases mRNA silencing or in the modulation of bacterial mRNAs by small, often highly structured sRNAs. In this chapter, we summarize the key features of networks of replicators. We highlight the differences between quasispecies-like models describing templates copied by an external replicase and hypercycle similar to autocatalytic replicators. Two aspects are of importance: the dynamics of selection within a population, usually described by conventional dynamical systems, and the evolution of replicating species in the space of chemical types. Product inhibition plays a key role in modulating selection dynamics from survival of the fittest to extinction of unfittest. The sequence evolution of replicators is rather well understood as approximate optimization in a fitness landscape for templates that is shaped by the sequence-structure map of RNA. Some of the properties of this map, in particular shape space covering and extensive neutral networks, give rise to evolutionary patterns such as drift-like motion in sequence space, akin to the behavior of RNA quasispecies. In contrast, very little is known about the influence of sequence-structure maps on autocatalytic replication systems.

Rapid Crystallization of Poly(lactic acid) by Using Tailor-Made Oxalamide Derivatives as Novel Soluble-Type Nucleating Agents

The crystallization rate and crystallinity of poly(lactic acid) (PLA) was significantly increased by the incorporation of 0.25–1.0 wt % of tailor-made oxalamide derivatives (NAs). The nucleation effect and nucleation mechanisms of the NAs were studied via diferential scanning calorimetry (DSC), polarized optical microscopy (POM), and wide-angle X-ray diffraction (WAXD) techniques. The experimental results convincingly revealed that the NA molecules are soluble in a PLA melt and are capable of self-organizing into fibrils upon cooling. The fibrils as efficient nucleation sites induced rapid growth of α-form PLA crystal along the fibrils, forming shish-kebab-like structures. In isothermal crystallization, very fine PLA sperrulites with high density were obtained in the presence of NAs. The high nucleation efficiency and the simple synthetic routes of the NAs make them promising to be a new generation of nucleating agents for (bio)polymers, e.g., PLA.

Ion Binding to Quadruplex DNA Stems. Comparison of MM and QM Descriptions Reveals Sizable Polarization Effects Not Included in Contemporary Simulations.

Molecular mechanical (MM) force fields are commonly employed for biomolecular simulations. Despite their success, the nonpolarizable nature of contemporary additive force fields limits their performance, especially in long simulations and when strong polarization effects are present. Guanine quadruplex D(R)NA molecules have been successfully studied by MM simulations in the past. However, the G-stems are stabilized by a chain of monovalent cations that create sizable polarization effects. Indeed, simulation studies revealed several problems that have been tentatively attributed to the lack of polarization. Here, we provide a detailed comparison between quantum chemical (QM) DFT-D3 and MM potential energy surfaces of ion binding to G-stems and assess differences that may affect MM simulations. We suggest that MM describes binding of a single ion to the G-stem rather well. However, polarization effects become very significant when a second ion is present. We suggest that the MM approximation substantially limits accuracy of description of energy and dynamics of multiple ions inside the G-stems and binding of ions at the stem-loop junctions. The difference between QM and MM descriptions is also explored using symmetry-adapted perturbation theory and quantum theory of atoms in molecules analyses, which reveal a delicate balance of electrostatic and induction effects.

Modulation of the cardiac sodium/bicarbonate cotransporter by the renin angiotensin aldosterone system: pathophysiological consequences

The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na+ per 1 molecule of HCO−3 (electroneutral isoform; NBCn1) and the other one that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO−3 (electrogenic isoform; NBCe1). Both isoforms are important to maintain intracellular pH (pHi) and sodium concentration ([Na+]i). In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). The renin-angiotensin-aldosterone system (RAAS) is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II) exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pHi and [Na+]i, which indirectly, due to the stimulation of reverse mode of the Na+/Ca2+ exchanger (NCX), conduces to an increase in the intracellular Ca2+ concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pHi and [Na+]i, which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

Regulation of the Cardiac Sodium/Bicarbonate Cotransporter by Angiotensin II: Potential Contribution to Structural, Ionic and Electrophysiological Myocardial Remodelling

The sodium/ bicarbonate cotransporter (NBC) is, with the Na+/H+ exchanger (NHE), an important alkalinizing mechanism that maintains cellular intracellular pH (pHi). In the heart exists at least three isoforms of NBC, one that promotes the co-influx of 1 molecule of Na+ per 1molecule of HCO3-(electroneutral isoform; nNBC) and two others that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO3- (electrogenic isoforms; eNBC). In addition, the eNBC generates an anionic repolarizing current that modulate the cardiac action potential (CAP), adding to such isoforms the relevance to modulate the electrophysiological function of the heart. Angiotensin II (Ang II) is one of the main hormones that regulate cardiac physiology. The alkalinizing mechanisms (NHE and NBC) are stimulated by Ang II, increasing pHi and intracellular Na+ concentration, which indirectly, due to the stimulation of the Na+/Ca2+ exchanger (NCX) operating in the reverse form, leads to an increase in the intracellular Ca2+ concentration. Interestingly, it has been shown that Ang II exhibits an opposite effect on NBC isoforms: it activates the nNBC and inhibits the eNBC. This inhibition generates a CAP prolongation, which could directly increase the intracellular Ca2+ concentration. The regulation of the intracellular Na+ and Ca2+ concentrations is crucial for the cardiac cellular physiology, but these ions are also involved in the development of cardiac hypertrophy and the damage produced by ischemia-reperfusion, suggesting a potential role of NBC in cardiac diseases.