Search

Abstract The protease activated receptor 2 (Par2) plays a pivotal role in various damage models, influencing injury, proliferation, inflammation, and regeneration. Despite extensive studies, its binary roles— EITHER aggravating injury or promoting recovery—make a conclusive translational decision on its modulation strategy elusive. Analyzing two liver regeneration models, autoimmune hepatitis and direct hepatic damage, we discovered Par2’s outcome depends on the injury’s nature. In immune-mediated injury, Par2 exacerbates damage, while in direct tissue injury, it promotes regeneration. Subsequently, we evaluated the clinical significance of this finding by investigating Par2’s expression in the context of autoimmune diabetes. We found that the absence of Par2 in all lymphocytes provided full protection against the autoimmune destruction of insulin-producing β-cells in mice, whereas the introduction of a β-cell-specific Par2 null mutation accelerated the onset of autoimmune diabetes. This pattern led us to hypothesize whether these observations are universal. A comprehensive review of recent Par2 publications across tissues and systems confirms the claim drafted above: Par2’s initial activation in the immune system aggravates inflammation, hindering recovery, whereas its primary activation in the damaged tissue fosters regeneration. As a membrane-anchored receptor, Par2 emerges as an attractive drug target. Our findings highlight a crucial translational modulation strategy in regenerative medicine based on injury type.

Background: Type 1 diabetes (T1D) is a challenging autoimmune disease, characterized by an immune system assault on insulin-producing β-cells. As insulin facilitates glucose absorption into cells and tissues, β-cell deficiency leads to elevated blood glucose levels on one hand and target-tissues starvation on the other. Despite efforts to halt β-cell destruction and stimulate recovery, success has been limited. Our recent investigations identified Protease-Activated Receptor 2 (Par2) as a promising target in the battle against autoimmunity. We discovered that Par2 activation’s effects depend on its initial activation site: exacerbating the disease within the immune system but fostering regeneration in affected tissue. Methods: We utilized tissue-specific Par2 knockout mice strains with targeted Par2 mutations in β-cells, lymphocytes, and the eye retina (as a control) in the NOD autoimmune diabetes model, examining T1D onset and β-cell survival. Results: We discovered that Par2 expression within the immune system accelerates autoimmune processes, while its presence in β-cells offers protection against β-cell destruction and T1D onset. This suggests a dual-strategy treatment for T1D: inhibiting Par2 in the immune system while activating it in β-cells, offering a promising strategy for T1D. Conclusions: This study highlights Par2's potential as a drug target for autoimmune diseases, particularly T1D. Our results pave the way for precision medicine approaches in treating autoimmune conditions through targeted Par2 modulation.

Abstract The quantum internet is a cutting‐edge paradigm that uses the unique characteristics of quantum technology to radically alter communication networks. This new network type is expected to collaborate with 6G networks, creating a synergy that will fundamentally alter how we communicate, engage, and trade information. The improved security, increased speed, and increased network capacity of the quantum internet will lead to the emergence of a broad variety of new applications and services. The current state of quantum technology and its integration with 6G networks are summarised in this study, with an emphasis on the key challenges and untapped possibilities. The main goal is to get knowledge about how the quantum internet might impact communication in the future and alter several economic and societal sectors.

Summary: Biofilm formation, a major concern for healthcare systems, is initiated when bacteria adhere to surfaces. Escherichia coli adhesion is mediated by appendages, including type-1 fimbriae and curli amyloid fibers. Antifouling surfaces prevent the adhesion of bacteria to combat biofilm formation. Here, we used single-cell force-spectroscopy to study the interaction between E. coli and glass or two antifouling surfaces: the tripeptide DOPA-Phe(4F)-Phe(4F)-OMe and poly(ethylene glycol) polymer-brush. Our results indicate that both antifoulants significantly deter E. coli initial adhesion. By using two mutant strains expressing no type-1 fimbriae or curli amyloids, we studied the adhesion mechanism. Our results suggest that the bacteria adhere to different antifoulants via separate mechanisms. Finally, we show that some bacteria adhere much better than others, illustrating how the variability of bacterial cultures affects biofilm formation. Our results emphasize how additional study at the single-cell level can enhance our understanding of bacterial adhesion, thus leading to novel antifouling technologies.

Abstract L−3,4-dihydroxyphenylalanine is an important molecule in the adhesion of mussels, and as an oxidative precursor of natural melanin, it plays an important role in living system. Here, we investigate the effect of the molecular chirality of 3,4-dihydroxyphenylalanine on the properties of the self-assembled films by tyrosinase-induced oxidative polymerization. The kinetics and morphology of pure enantiomers are completely altered upon their co-assembly, allowing the fabrication of layer-to-layer stacked nanostructures and films with improved structural and thermal stability. The different molecular arrangements and self-assembly mechanisms of the L+D-racemic mixtures, whose oxidation products have increased binding energy, resulting in stronger intermolecular forces, which significantly increases the elastic modulus. This study provides a simple pathway for the fabrication of biomimetic polymeric materials with enhanced physicochemical properties by controlling the chirality of monomers.

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease that continues to develop new variants. A crucial step in the quest to reduce the infection is the development of rapid and reliable virus detectors. Here, we report a chip scale photonic sensing device consisting of a silicon-nitride double microring resonator (MRR) for detecting SARS-CoV-2 in clinical samples. The sensor is implemented by surface activation of one of the MRRs, acting as a probe, with DNA primers for SARS-CoV-2 RNA, whereas the other MRR is used as a reference. The performance of the sensor is determined by applying different amounts of SARS-CoV-2 complementary RNA. As will be shown in the paper, our device detects the RNA fragments at concentrations of 10 cp/μL and with sensitivity of 750 nm/RIU. As such, it shows a promise toward the implementation of label-free, small form factor, CMOS compatible biosensor for SARS-CoV-2, which is also environment, temperature, and pressure independent. Our approach can also be used for detecting other SARS-CoV-2 genes, as well as other viruses and pathogens.

Abstract Background Different factors may lead to hepatitis. Among which are liver inflammation and poisoning. We chose two hepatitis models, typical for these two underlying causes. Thus, we aimed to characterize the role of protease-activated receptor 2 (Par2) in liver regeneration and inflammation to reconcile Par2 conflicting role in many damage models, which sometimes aggravates the induced damage and sometimes alleviates it. Methods WT and knockout (Par2KO) mice were injected with concanavalin A (ConA) to induce immune-mediated hepatitis or with carbon tetrachloride (CCl4) to elicit direct hepatic damage. To distinguish the immune component from the liver regenerative response, we conducted bone marrow (BM) replacements of WT and Par2KO mice and repeated the damage models. Results ConA injection caused limited damage in Par2KO mice livers, while in the WT mice severe damage followed by leukocyte infiltration was evident. Reciprocal BM replacement of WT and Par2KO showed that WT BM-reconstituted Par2KO mice displayed marked liver damage, while in Par2KO BM-reconstituted WT mice, the tissue was generally protected. In the CCl4 direct damage model, hepatocytes regenerated in WT mice, whereas Par2KO mice failed to recover. Reciprocal BM replacement did not show significant differences in hepatic regeneration. In Par2KO mice, hepatitis was more apparent, while WT recovered regardless of the BM origin. Conclusions We conclude that Par2 activation in the immune system aggravates hepatitis and that Par2 activation in the damaged tissue promotes liver regeneration. When we incorporate this finding and revisit the literature reports, we reconciled the conflicts surrounding Par2’s role in injury, recovery, and inflammation.

Abstract Antiviral compounds are important for generating sterile surfaces. Here, two extremely short peptides, DOPA‐Phe‐NH2 and DOPA‐Phe(4F)‐NH2 that can self‐assemble into spherical nanoparticles with antiviral activity are presented. The peptide assemblies possess excellent antiviral activity against bacteriophage T4 with antiviral minimal inhibitory concentrations of 125 and 62.5 µg mL−1, for DOPA‐Phe‐NH2 and DOPA‐Phe(4F)‐NH2, respectively. When the peptide assemblies are applied on a glass substrate by drop‐casting, they deactivate more than 99.9% of bacteriophage T4 and Canine coronavirus. Importantly, the peptide assemblies have low toxicity toward mammalian cells. Overall, the findings can provide a novel strategy for the design and development of antiviral coatings for a decreased risk of viral infections.

A transmission delay is a critical metric when dealing with ad hoc networks in 5G, particularly for real-time applications and multimedia. In this paper, we describe the challenge of managing mobile ad-hoc networks (MANET) based on multi-hop time-slotted time-division multiple access (TDMA) under routing delay minimization with heterogeneous traffic flows. In particular, we consider the challenge of request scheduling and power control in TDMA, for minimizing the overall weighted end-to-end packet delay when the weights are determined according to the priorities of the requests. A delay minimization network that uses deep learning is also introduced (DMNet). Simulations show that DMNet outperforms other state-of-art methods. Our approach is one of the first to utilize a DNN to solve end-to-end delay minimization through scheduling and power control.

Abstract Introduction Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. Methods For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. Results We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. Conclusion In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.

In March 2020, the World Health Organization announced a pandemic attributed to SARS-CoV-2, a novel beta-coronavirus, which spread widely from China. As a result, the need for antiviral surfaces has increased significantly. Here, the preparation and characterization of new antiviral coatings on polycarbonate (PC) for controlled release of activated chlorine (Cl+) and thymol separately and combined are described. Thin coatings were prepared by polymerization of 1-[3-(trimethoxysilyl)propyl] urea (TMSPU) in ethanol/water basic solution by modified Stöber polymerization, followed by spreading the formed dispersion onto surface-oxidized PC film using a Mayer rod with appropriate thickness. Activated Cl-releasing coating was prepared by chlorination of the PC/SiO2-urea film with NaOCl through the urea amide groups to form a Cl-amine derivatized coating. Thymol releasing coating was prepared by linking thymol to TMSPU or its polymer via hydrogen bonds between thymol hydroxyl and urea amide groups. The activity towards T4 bacteriophage and canine coronavirus (CCV) was measured. PC/SiO2-urea-thymol enhanced bacteriophage persistence, while PC/SiO2-urea-Cl reduced its amount by 84%. Temperature-dependent release is presented. Surprisingly, the combination of thymol and chlorine had an improved antiviral activity, reducing the amount of both viruses by four orders of magnitude, indicating synergistic activity. For CCV, coating with only thymol was inactive, while SiO2-urea-Cl reduced it below a detectable level.

Abstract Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic–mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated. The second pattern observed in one fetus was characterized by callosal dysgenesis, reduced white matter, and pontine hypoplasia. The identification of these features should alert clinicians to offer a prenatal L1CAM testing.

This study analyzes the development of the unique Law of Return (LOR) of the State of Israel. The LOR is aimed at enabling the immigration of all Jews to Israel and can be viewed as an expression of Israel’s ethno-religious self-definition. The analysis includes amendments made to the LOR since its implementation in 1950 to today, and how different groups of Jewish immigrants have been affected by the law. Moreover, this paper introduces a case study that so far has not received the scholarly attention it deserves; the exodus from Venezuela and the particular case of nine Venezuelan converts to Judaism in accordance with the Conservative branch of the religion. The research uncovers that the LOR contains a core contradiction. While it should be assumed that everyone is treated equally before the law, discrepancies in the treatment of different individuals and groups of people with regard to the LOR continue taking place. The differences in treatment are due to the fact that terms such as ‘Jew’ and ‘Jewish convert’ are subjective in accordance with Weber’s theory on ethnicity and the terms have been given different meanings by Jewish religious law, the Supreme Court, and the legislative power. While recognizing that the definition of these terms form the identity of the State of Israel, which is heavily contested between Orthodox religious and secular forces since its establishment as a Jewish State – this study offers suggestions for approaches to dealing with the randomness of the LOR. These consist of two main points: clarifying who should be responsible for verifying the question of who is a Jew, and listing a set of criteria that a person should meet in order to be eligible for the LOR.