BINA

This review discusses, in brief, the various synthetic methods of two widely-used nanofillers; phyllosilicate and graphene. Both are 2D fillers introduced into hydrogel matrices to achieve mechanical robustness and water uptake behavior. Both the fillers are inserted by physical and chemical gelation methods where most of the chemical gelation, i.e., covalent approaches, results in better physical properties compared to their physical gels. Physical gels occur due to supramolecular assembly, van der Waals interactions, electrostatic interactions, hydrophobic associations, and H-bonding. For chemical gelation, in situ radical triggered gelation mostly occurs.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT are still limited in their success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) are conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy. The AuNP-mTHPC complex is biocompatible, soluable, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650 nm laser which decreased mitochondrial membrane potential (∆ψm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Hence, applying our AuNP-mTHPC may be a potential treatment of cancer in the biomedical field.

CRISPR-Cas technology has revolutionized gene editing, but concerns remain due to its propensity for off-target interactions. This, combined with genotoxicity related to both CRISPR-Cas9-induced double-strand breaks and transgene delivery, poses a significant liability for clinical genome-editing applications. Current best practice is to optimize genome-editing parameters in preclinical studies. However, quantitative tools that measure off-target interactions and genotoxicity are costly and time-consuming, limiting the practicality of screening large numbers of potential genome-editing reagents and conditions. Here, we show that flow-based imaging facilitates DNA damage characterization of hundreds of human hematopoietic stem and progenitor cells per minute after treatment with CRISPR-Cas9 and recombinant adeno-associated virus serotype 6. With our web-based platform that leverages deep learning for …

Digital image devices have been widely applied in many fields, such as individual recognition and remote sensing. The captured image is a degraded image from the latent observation, where the degradation processing is affected by some factors, such as lighting and noise corruption. Specifically, noise is generated in the processing of transmission and compression from the unknown latent observation. Thus, it is essential to use image denoising techniques to remove noise and recover the latent observation from the given degraded image. In this research, a supervised encoder–decoder convolution neural network was used to fix image distortion stemming from the limited accuracy of inverse filter methods (Wiener filter, Lucy–Richardson deconvolution, etc.). Particularly, we will correct image degradation that mainly stems from duplications arising from multiple-pinhole array imaging.

Neural activity research has recently gained significant attention due to its association with sensory information and behavior control. However, the current methods of brain activity sensing require expensive equipment and physical contact with the tested subject. We propose a novel photonic-based method for remote detection of human senses. Physiological processes associated with hemodynamic activity due to activation of the cerebral cortex affected by different senses have been detected by remote monitoring of nano‐vibrations generated by the transient blood flow to the specific regions of the human brain. We have found that a combination of defocused, self‐interference random speckle patterns with a spatiotemporal analysis, using Deep Neural Network, allows associating between the activated sense and the seemingly random speckle patterns.

It is well known that for sub-recoiled laser cooled atoms L\'evy statistics and deviations from usual ergodic behaviour come into play.Here we show how tools from infinite ergodic theory describe the cool gas.Specifically, we derive the scaling function and the infinite invariant density of a stochastic model for the momentum of the atoms using two approaches.The first is a direct analysis of the master equation and the second following the analysis of Bertin and Bardou using the lifetime dynamics. The two methods are shown to be identical, but yield different insights into the problem. In the main part of the paper we focus on the case where the laser trapping is strong, namely the rate of escape from the velocity trap is for and .We construct a machinery to investigate the time averages of physical observables and their relationt o ensemble averages. The time averages are given in terms of functionals of the …

We report on stabilization of Li–S cells with different types of composite sulfur cathodes using ethereal LiTFSI/LiNO 3/DOL/DME electrolyte solutions containing a-priori 0.1 M Li 2 S 8. These electrolyte solutions enable an improved cycling behavior for Li–S cells compared to Li 2 S 8-free electrolyte solutions, thanks to the presence of LiS x species from the beginning of operation. We show that Li anodes cycled in Li∣ S cells with solutions containing Li 2 S 8 possess flatter and more uniform surface, higher dimensions of the surface structures in average and, as a result, a lower surface area. This surface morphology ensures a low rate of parasitic surface reactions of the electrolyte components on the Li anodes' surface, slower depletion of the electrolyte solution in the cells and stabilization of the cells cycling. Besides, the presence of Li 2 S 8 maintains a better integrity of composite sulfur/carbon/PVdF cathodes …

The loss of energy homeostasis seen during aging, is causally linked to multiple age-related pathologies. The AMP-activated protein kinase (AMPK) directly senses cellular energy levels, which are reflected in the ratio between AMP:ATP. However, the genetic regulation of vertebrate aging by the AMPK pathway remains poorly understood. Here, we manipulate ATP production by mutating APRT, a key enzyme in AMP biosynthesis, and extend vertebrate lifespan in a male-specific manner. Using a multi-omics approach, we demonstrate that the APRT mutation restores metabolic plasticity, and identify a distinct transcriptional signature linking mitochondria with the sex-related differences in longevity. Accordingly, APRT mutant cells display a reduction in mitochondrial functions and ATP levels, and an increase in AMPK activity, resembling a persistent state of energy starvation. In-vivo, a fasting-like response was observed exclusively in male mutants, including resistance to a high-fat diet. Finally, intermittent fasting eliminated the longevity benefits mediated by the APRT mutation in males. Together, these data identify AMP biosynthesis as a sex-specific mediator of vertebrate longevity and metabolic health.

T and B cell repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of T and B cell receptors (TCRs and BCRs, respectively) are challenging to decipher due to repetitive elements and undocumented structural variants. To confront this challenge, AIRR-seq-based methods have been developed recently for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. Applying these methods to AIRR-seq data reveals a plethora of undocumented genomic variations. However, this approach relies on complete coverage of the receptors9 variable regions, and most T cell studies sequence only a small fraction of the variable region. Here, we adapted BCR inference methods to full and partial TCR sequences, and identified 38 undocumented polymorphisms in TRBV, 15 of them were also observed in genomic data assemblies. Further, we identified 31 undocumented 59 UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found the two documented TRBD2 alleles to be equally abundant in the population, and show that the single nucleotide that differentiates them is strongly associated with dramatic changes in the expressed repertoire. Our findings expand the knowledge of genomic variation in the TRB (T Cell Receptor Beta) locus and …

Identifying and investigating protein–DNA interactions, which play significant roles in many biological processes, is essential for basic and clinical research. Current techniques for identification of protein–DNA interactions are laborious, time-consuming, and suffer from nonspecific binding and limited sensitivity. To overcome these challenges and assess protein–DNA interactions, we use a magnetic modulation biosensing (MMB) system. In MMB, one of the interacting elements (protein or DNA) is immobilized to magnetic beads, and the other is coupled to a fluorescent molecule. Thus, the link between the magnetic bead and the fluorescent molecule is established only when binding occurs, enabling detection of the protein–DNA interaction. Using magnetic forces, the beads are concentrated and manipulated in a periodic motion in and out of a laser beam, producing a detectable oscillating signal. Using MMB, we …

Transition-metal dichalcogenides (TMDCs) are unique layered materials with exotic properties. So, examining their structures holds tremendous importance. 2H-MoSe2 (analogous to MoS2; Gr. 6 TMDC) is a crucial optoelectronic material studied extensively using Raman spectroscopy. In this regard, low-frequency Raman (LFR) spectroscopy can probe this material’s structure as it reveals distinct vibration modes. Here, we focus on understanding the microstructural evolution of different 2H-MoSe2 morphologies and their layers using LFR scattering. We grew phase-pure 2H-MoSe2 (with variable microstructures) directly on a Mo foil using a two-furnace ambient-pressure chemical vapor deposition (CVD) system by carefully controlling the process parameters. We analyzed the layers of exfoliated flakes after ultrasonication and drop-cast 2H-MoSe2 of different layer thicknesses by choosing different concentrations of …

The sluggish kinetics of the anodic oxygen evolution reaction (OER) limit the overall efficiency of green hydrogen production. The proposed strategy to overcome this is to replace OER with other kinetically favorable anodic reactions like urea oxidation reaction (UOR). Herein, we develop an organometallic synthesis of nickel nitride nanoparticles supported on carbon (Ni3N–C) as the catalyst for both UOR and hydrogen evolution reaction (HER). A precious group metal-free electrolyzer based on Ni3N–C catalyst (as both anode and cathode) is implemented for the first time, and the urea electrolyzer cell has a 200 mV lower overpotential compared to that of the water electrolyzer.

The nucleolus is a sub-nuclear compartment whose primary function is the biogenesis of ribosomal subunits. Certain viral infections affect the morphology and composition of the nucleolar compartment and influence ribosomal RNA (rRNA) transcription and maturation. However, no description of nucleolar morphology and function during infection with Kaposi’s sarcoma-associated herpesvirus (KSHV) is available to date. Using immunofluorescence microscopy, we documented extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. This was manifested by redistribution of key nucleolar proteins, including the rRNA transcription factor, UBF, the essential pre-rRNA processing factor Fibrillarin, and the nucleolar multifunctional phosphoproteins Nucleophosmin (NPM1) and Nucleolin. Distinct delocalization patterns were evident; certain nucleolar proteins remained together whereas others dissociated, implying that nucleolar proteins undergo nonrandom programmed dispersion. Of note, neither Fibrillarin nor UBF colocalized with promyelocytic leukemia (PML) nuclear bodies or with the viral protein LANA-1, and their redistribution was not dependent on viral DNA replication or late viral gene expression. No significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found by RT-qPCR and Northern blot analysis, respectively. Furthermore, fluorescent in situ hybridization (FISH), combined with immunofluorescence, revealed an overlap between Fibrillarin and internal transcribed spacer 1 (ITS1), which represents the primary product of the pre-rRNA, suggesting that the …

Near-infrared (NIR) fluorescence lifetime imaging (FLI) provides a unique contrast mechanism to monitor biological parameters and molecular events in vivo. Single-photon avalanche photodiode (SPAD) cameras have been recently demonstrated in FLI microscopy (FLIM) applications, but their suitability for in vivo macroscopic FLI (MFLI) in deep tissues remains to be demonstrated. Herein, we report in vivo NIR MFLI measurement with SwissSPAD2, a large time-gated SPAD camera. We first benchmark its performance in well-controlled in vitro experiments, ranging from monitoring environmental effects on fluorescence lifetime, to quantifying Förster Resonant Energy Transfer (FRET) between dyes. Next, we use it for in vivo studies of target-drug engagement in live and intact tumor xenografts using FRET. Information obtained with SwissSPAD2 was successfully compared to that obtained with a gated-ICCD camera, using two different approaches. Our results demonstrate that SPAD cameras offer a powerful technology for in vivo preclinical applications in the NIR window.

Forward stimulated Brillouin scattering in standard single‐mode fibers draws increasing interest toward sensing and signal processing applications. The process takes place through two classes of guided acoustic modes: purely radial ones and torsional‐radial modes with twofold azimuthal symmetry. The latter case cannot be described in terms of scalar models alone. In this work, the polarization attributes of forward stimulated Brillouin scattering in single‐mode fibers are investigated in analysis and experiment. Torsional‐radial acoustic modes are stimulated by orthogonally polarized pump tones, a first such report in standard single‐mode fibers. The scattering of optical probe waves by torsional‐radial modes may take up the form of phase modulation, cross‐polarization coupling, or a combination of both, depending on polarization. Lastly, this analysis predicts that circular and orthogonal pump tones may …

The functionality of a nanoscale silicon-based optoelectronic modulator is deeply analyzed while it appears that two competing processes, thermal and photonic, are occurring at the same time, and are preventing the optimization of the electro-optics coupling. While an incident illumination-beam first process is translated into photons, generating pairs of electrons–holes, a second process of thermal generation, creating phonons enables a loss of energy. Complementary studies, combining strong analytical models and numerical simulations, enabled to better understand this competition between photonic and thermal activities, in order to optimize the modulator. Moreover, in order to prevent unnecessary heating effects and to present a proposed solution, a picosecond pulsed laser is suggested and demonstrated as the ultimate solution so no energy will be wasted in heat, and still the photonic energy will be fully …

Copper is a trace element vital to many cellular functions. Yet its abnormal levels are toxic to cells, provoking a variety of severe diseases. The high affinity Copper Transporter 1 (CTR1), being the main in-cell copper (Cu(I)) entry route, tightly regulates its cellular uptake via a still elusive mechanism. Here, all-atoms simulations unlock the molecular terms of Cu(I) transport in eukaryotes disclosing that the two Methionine triads, forming the selectivity filter, play an unprecedented dual role both enabling selective Cu(I) transport and regulating its uptake-rate thanks to an intimate coupling between the conformational plasticity of their bulky side chains and the number of bound Cu(I) ions. Namely, the Met residues act as a gate reducing the Cu(I) import-rate when two ions simultaneously bind to CTR1. This may represent an elegant autoregulatory mechanism through which CTR1 protects the cells from excessively high, and hence toxic, in-cell Cu(I) levels. Overall, these outcomes resolve fundamental questions in CTR1 biology and open new windows of opportunity to tackle diseases associated with an imbalanced copper uptake.

A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response; however, a causal virus has not been identified. Here we use a mouse model, corroborated with human data, to demonstrate that endogenous dsRNA in beta-cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme ADAR in beta-cells triggers a massive interferon response, islet inflammation and beta-cell failure, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta-cell workload.