BINA

The majority of human genetic diseases are caused by single nucleotide variants (SNVs) in the genome sequence. Excitingly, new genomic techniques known as base editing have opened efficient pathways to correct erroneous nucleotides. Due to reliance on deaminases, which have the capability to convert A to I(G) and C to U, the direct applicability of base editing might seem constrained in terms of the range of mutations that can be reverted. In this evaluation, we assess the potential of DNA and RNA base editing methods for treating human genetic diseases. Our findings indicate that 62% of pathogenic SNVs found within genes can be amended by base editing; 30% are G>A and T>C SNVs that can be corrected by DNA base editing, and most of them by RNA base editing as well, and 29% are C>T and A>G SNVs that can be corrected by DNA base editing directed to the complementary strand. For each, we …

With an increasing demand for high-energy-density lithium-ion batteries (LIBs), nickel-rich cathodes such as LiNi0.9Mn0.05Co0.05O2 (NMC90) have gained significant interest due to their relatively low cobalt and high specific energy. However, cycling stability is compromised due to parasitic reactions at the electrode–electrolyte interfaces of NMC90. Herein, we demonstrate improved electrochemical properties of NMC90 using di-tert-butylmethyl adamantoyl silane (RSiCOAd: R is tBu(CH3)2 and Ad is 1-Ad) as an additive in a commercial electrolyte. Upon detailed electrochemical and spectroscopic analysis, we demonstrate that the RSiCOAd additive undergoes in situ decomposition to form a fluorinated organosiloxane passivation layer on the NMC90 surface and enhanced fluorination on the lithium anode surface. This phenomenon could significantly mitigate the parasitic reactions at the cathode–electrolyte …

Superparamagnetic nanoparticle-arrested hydrogel matrices have immense significance in smart soft biomaterials. Herein, we report the synthesis of superparamagnetic nanoparticle-loaded magneto-responsive tough elastomeric hydrogels for dual-responsive drug delivery. In the first phase of work, we carried out room-temperature synthesis of amine-functionalized superparamagnetic iron oxide nanoparticles (IONPs), and in the second phase of work, we demonstrated that IONPs could act as a toughening agent as well as a viscosity modifier for poly(acrylic acid-co-hydroxyethyl methacrylate) copolymer hydrogels. The hydrogel was tested by Fourier transformed infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and continuous-wave-electron paramagnetic resonance (CW-EPR). Moreover, the IONPs affect its gelation time and elasticity significantly, which was also evaluated from its …

Rechargeable magnesium batteries (RMBs) have the potential to contribute towards alternative energy storage due to their low cost, high abundance, dendrites free deposition of Mg and high volumetric energy density. Organometallic complex-based electrolytes in ethereal solutions have been extensively studied in the context of RMBs due to their ability to facilitate highly reversible magnesium deposition in rechargeable magnesium batteries, while demonstrating wide enough electrochemical stability windows. However, these solutions containing unique mixture of organo-halo aluminate complexes have detrimental effect on the anodic stability of metallic current collectors for cathodes, like Ni and Al foils. In this work, we were able to synthesize and isolate Mg2Cl3(THF)(6)Ph2AlCl2/THF electrolyte as the sole electroactive species using simple precursors: Ph2AlCl and MgCl2 in THF, via atom efficient mono …

With an increasing demand for high-energy-density lithium-ion batteries (LIBs), nickel-rich cathodes such as LiNi0.9Mn0.05Co0.05O2 (NMC90) have gained significant interest due to their relatively low cobalt and high specific energy. However, cycling stability is compromised due to parasitic reactions at the electrode–electrolyte interfaces of NMC90. Herein, we demonstrate improved electrochemical properties of NMC90 using di-tert-butylmethyl adamantoyl silane (RSiCOAd: R is tBu(CH3)2 and Ad is 1-Ad) as an additive in a commercial electrolyte. Upon detailed electrochemical and spectroscopic analysis, we demonstrate that the RSiCOAd additive undergoes in situ decomposition to form a fluorinated organosiloxane passivation layer on the NMC90 surface and enhanced fluorination on the lithium anode surface. This phenomenon could significantly mitigate the parasitic reactions at the cathode–electrolyte …

Overcoming the diffraction limit is crucial for obtaining high-resolution images and observing fine microstructures. With this conventional difficulty still puzzling us and the prosperous development of wave dynamics of light interacting with gravitational fields in recent years, how spatial curvature affects the diffraction limit is an attractive and important question. Here we investigate the issue of the diffraction limit and optical resolution on two-dimensional curved space—surfaces of revolution (SORs) with constant or variable spatial curvature. We show that the diffraction limit decreases and the resolution is improved on SORs with positive Gaussian curvature, opening a new avenue to super-resolution. The diffraction limit is also influenced by the propagation direction, as well as the propagation distance in curved space with variable spatial curvature. These results provide a possible method to control the optical …

IntroductionAnalysis of an individual’s immunoglobulin (IG) gene repertoire requires the use of high-quality germline gene reference sets. When sets only contain alleles supported by strong evidence, AIRR sequencing (AIRR-seq) data analysis is more accurate and studies of the evolution of IG genes, their allelic variants and the expressed immune repertoire is therefore facilitated.MethodsThe Adaptive Immune Receptor Repertoire Community (AIRR-C) IG Reference Sets have been developed by including only human IG heavy and light chain alleles that have been confirmed by evidence from multiple high-quality sources. To further improve AIRR-seq analysis, some alleles have been extended to deal with short 3’ or 5’ truncations that can lead them to be overlooked by alignment utilities. To avoid other challenges for analysis programs, exact paralogs (e.g. IGHV1-69*01 and IGHV1-69D*01) are only represented once in each set, though alternative sequence names are noted in accompanying metadata.Results and discussionThe Reference Sets include less than half the previously recognised IG alleles (e.g. just 198 IGHV sequences), and also include a number of novel alleles: 8 IGHV alleles, 2 IGKV alleles and 5 IGLV alleles. Despite their smaller sizes, erroneous calls were eliminated, and excellent coverage was achieved when a set of repertoires comprising over 4 million V(D)J rearrangements from 99 individuals were analyzed using the Sets. The version-tracked AIRR-C IG Reference Sets are freely available at the OGRDB website (https://ogrdb.airr-community.org/germline_sets/Human) and will be regularly updated to include newly …

Organometallic complex-based magnesium electrolytes in ethereal solutions have been extensively studied in the context of rechargeable magnesium batteries (RMBs) due to their ability to facilitate highly reversible magnesium deposition while demonstrating wide enough electrochemical stability windows. However, these solutions containing a unique mixture of organo-halo aluminate complexes have a detrimental effect on the anodic stability of metallic current collectors for cathodes, like Ni and Al foils. We were able to synthesize and isolate Mg2Cl3(THF)6Ph2AlCl2/THF electrolyte as the sole electroactive species using simple precursors: Ph2AlCl and MgCl2 in THF, via atom efficient mono-chloro abstraction Schlenk technique. We characterized the anodic stability of Ni, Ni@C, Al, and Al@C current collectors by monitoring their electrochemical behavior. Additionally, we investigated the anodic stability …

The fogging of transparent surfaces—condensation of water vapor in the air to a small liquid surface at specific environmental conditions—scatters incident light, creating a blurry vision. Fogging presents a significant challenge in various industries, adversely affecting numerous applications including plastic packaging, agricultural films, and various optical devices. Superhydrophobic or superhydrophilic coatings are the main strategies used to induce antifogging to minimize light scattering. Here, an innovative approach is introduced to mitigate fogging by modifying the surface properties of polymeric films, focusing on corona-treated polyethylene as a model. Coatings were prepared in two successive steps: the addition of radical co-polymerization of methacryloxypropyltriethoxysilane and N-vinylpyrrolidone followed by the step-growth Stöber polymerization of the formed silane monomer. The polymeric dispersion was spread on oxidized films via a Mayer rod and dried. Scanning and force microscopy, FIB, XPS, and UV-vis spectroscopy revealed a thin coating composed of cross-linked siloxane (Si-O-Si) covalently bonded to surface hydroxyls exposing pyrrolidone groups. Contact angle measurements, hot-fog examination, and durability tests indicated a durable antifogging activity.

Stress granules (SGs) are cytoplasmic assemblies formed under various stress conditions as a consequence of translation arrest. SGs contain RNA-binding proteins, ribosomal subunits and messenger RNAs (mRNAs). It is well known that mRNAs contribute to SG formation; however, the connection between SG assembly and nuclear processes that involve mRNAs is not well established. Here, we examine the effects of inhibiting mRNA transcription, splicing and export on the assembly of SGs and the related cytoplasmic P body (PB). We demonstrate that inhibition of mRNA transcription, splicing and export reduces the formation of canonical SGs in a eukaryotic initiation factor 2α phosphorylation-independent manner, and alters PB size and quantity. We find that the splicing inhibitor madrasin promotes the assembly of stress-like granules. We show that the addition of synthetic mRNAs directly to the cytoplasm …

Understanding enzyme mechanisms is essential for unraveling the complex molecular machinery of life. In this review, we survey the field of computational enzymology, highlighting key principles governing enzyme mechanisms and discussing ongoing challenges and promising advances. Over the years, computer simulations have become indispensable in the study of enzyme mechanisms, with the integration of experimental and computational exploration now established as a holistic approach to gain deep insights into enzymatic catalysis. Numerous studies have demonstrated the power of computer simulations in characterizing reaction pathways, transition states, substrate selectivity, product distribution, and dynamic conformational changes for various enzymes. Nevertheless, significant challenges remain in investigating the mechanisms of complex multistep reactions, large-scale conformational changes …

Herpesviruses are promising candidates as therapeutic vectors. During the progression of herpes simplex virus type 1 infection, the growth of nuclear replication compartments leads to the marginalization of chromatin to the nuclear periphery. By using a combination of fluorescence imaging, EM, and soft X-ray tomography along with machine learning we have described how virusinduced chromatin marginalization leads to changes in chromatin organization and local density. In addition, live cell single-particle tracking of capsid motion showed that the viral capsid movement during their nuclear exit was restricted by the nuclear chromatin. The capsid diffusion coefficient was lower inside than outside the chromatin, but as the infection proceeded, the chromatin became more permissive and the probability of capsids to enter the chromatin was increased. In this work, we use live cell FLIM-FRET to measure the DNA …

Polymeric electrolytes are currently at the forefront of research for the next generation of lithium all-solid-state batteries. Polyethylene oxide (PEO), a commonly used polymer for these batteries, operates at elevated temperatures at which it reacts with active metal electrodes (e.g., lithium). Rich surface chemistry is developed at the Li-PEO interfaces, thereby controlling these batteries' electrochemical behavior. Interfacial studies are essential to comprehend batteries' stabilization or capacity fading mechanisms. For that, post-mortem analysis with an emphasis on interfaces is a necessary approach to underpinning these mechanisms. While it can be readily done with liquid electrolytes, post-mortem characterization of similar interfaces with solid electrolytes is hampered by the Li-PEO stack firm adhesion, which is impossible to separate. Here, various methods were attempted to separate polymer electrolytes from …

Rechargeable magnesium batteries (RMBs) have the potential to contribute towards alternative energy storage due to their low cost, high abundance, dendrites free deposition of Mg and high volumetric energy density. Organometallic complex-based electrolytes in ethereal solutions have been extensively studied in the context of RMBs due to their ability to facilitate highly reversible magnesium deposition in rechargeable magnesium batteries, while demonstrating wide enough electrochemical stability windows. However, these solutions containing unique mixture of organo-halo aluminate complexes have detrimental effect on the anodic stability of metallic current collectors for cathodes, like Ni and Al foils. In this work, we were able to synthesize and isolate Mg 2 Cl 3 (THF) 6 Ph 2 AlCl 2/THF electrolyte as the sole electroactive species using simple precursors: Ph 2 AlCl and MgCl 2 in THF, via atom efficient mono …

Superparamagnetic nanoparticle-arrested hydrogel matrices have immense significance in smart soft biomaterials. Herein, we report the synthesis of superparamagnetic nanoparticle-loaded magneto-responsive tough elastomeric hydrogels for dual-responsive drug delivery. In the first phase of work, we carried out room-temperature synthesis of amine-functionalized superparamagnetic iron oxide nanoparticles (IONPs), and in the second phase of work, we demonstrated that IONPs could act as a toughening agent as well as a viscosity modifier for poly(acrylic acid-co-hydroxyethyl methacrylate) copolymer hydrogels. The hydrogel was tested by Fourier transformed infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and continuous-wave-electron paramagnetic resonance (CW-EPR). Moreover, the IONPs affect its gelation time and elasticity significantly, which was also evaluated from its …

In biological, glassy, and active systems, various tracers exhibit Laplace-like, i.e., exponential, spreading of the diffusing packet of particles. The limitations of the central limit theorem in fully capturing the behaviors of such diffusive processes, especially in the tails, have been studied using the continuous time random walk model. For cases when the jump length distribution is super-exponential, e.g., a Gaussian, we use large deviations theory and relate it to the appearance of exponential tails. When the jump length distribution is sub-exponential the packet of spreading particles is described by the big jump principle. We demonstrate the applicability of our approach for finite time, indicating that rare events and the asymptotics of the large deviations rate function can be sampled for large length scales within a reasonably short measurement time.

Hard x-ray imaging is indispensable across diverse fields owing to its high penetrability. However, the resolution of traditional x-ray imaging modalities, such as computed tomography (CT) systems, is constrained by factors including beam properties, the absence of optical components, and detection resolution. As a result, typical resolution in commercial imaging systems is limited to a few hundred microns. This study advances high-photon-energy imaging by extending the concept of computational ghost imaging to multipixel ghost imaging with x-rays. We demonstrate a remarkable enhancement in resolution from 500 microns to approximately 20 microns for an image spanning 0.9 by 1 cm^2, comprised of 400,000 pixels and involving only 1000 realizations. Furthermore, we present a high-resolution CT reconstruction using our method, revealing enhanced visibility and resolution. Our achievement is facilitated by an innovative x-ray lithography technique and the computed tiling of images captured by each detector pixel. Importantly, this method can be scaled up for larger images without sacrificing the short measurement time, thereby opening intriguing possibilities for noninvasive high-resolution imaging of small features that are invisible with the present modalities.

Biofilms comprising sessile microorganisms attached to surfaces are increasingly researched for their importance in medicine and industry. Current studies focus on development of antibiotics that unfortunately can lead to resistance and environmental pollution. Phosphonium cations are known to exhibit significant activity with less resistance. Here, silane-phosphonium thin coatings are applied by Stöber polymerization of new silane-phosphonium monomer onto oxidized polypropylene film to eliminate phosphonium leaching and reduce the risk of environmental pollution. The composition and morphology were investigated by infrared spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy and contact angle measurements. Coating durability was assessed by adhesion test. The significant anti-biofilm activity against S. aureus and E. coli suggests applications in medicine and agriculture.

This review focuses on the application of nuclear magnetic resonance (NMR) spectroscopy in the study of lithium and sodium battery electrolytes. Lithium-ion batteries are widely used in electronic devices, electric vehicles, and renewable energy systems due to their high energy density, long cycle life, and low self-discharge rate. The sodium analog is still in the research phase, but has significant potential for future development. In both cases, the electrolyte plays a critical role in the performance and safety of these batteries. NMR spectroscopy provides a non-invasive and non-destructive method for investigating the structure, dynamics, and interactions of the electrolyte components, including the salts, solvents, and additives, at the molecular level. This work attempts to give a nearly comprehensive overview of the ways that NMR spectroscopy, both liquid and solid state, has been used in past and present studies …

Water pollution caused by hazardous substances, particularly heavy metal (HM) ions, poses a threat to human health and the environment. Traditional methods for measuring HM in water are expensive and time-consuming and require extensive sample preparation. Therefore, developing robust, simple, and sensitive techniques for the detection and classification of HM is needed. We propose an optical approach that exploits the full scattering profile, meaning the angular intensity distribution, and utilizes the iso-pathlength (IPL) point. This point appears where the intensity is constant for different scattering coefficients, while the absorption coefficient is set. The absorption does not affect the IPL point position, it only reduces its intensity. In this paper, we explore the wavelength influence on the IPL point both in Monte Carlo simulations and experimentally. Next, we present the characterization of ferric chloride (FeCl2 …

Compressing light into nanocavities substantially enhances light–matter interactions, which has been a major driver for nanostructured materials research. However, extreme confinement generally comes at the cost of absorption and low resonator quality factors. Here we suggest an alternative optical multimodal confinement mechanism, unlocking the potential of hyperbolic phonon polaritons in isotopically pure hexagonal boron nitride. We produce deep-subwavelength cavities and demonstrate several orders of magnitude improvement in confinement, with estimated Purcell factors exceeding 108 and quality factors in the 50–480 range, values approaching the intrinsic quality factor of hexagonal boron nitride polaritons. Intriguingly, the quality factors we obtain exceed the maximum predicted by impedance-mismatch considerations, indicating that confinement is boosted by higher-order modes. We expect that our …