Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

The literature study delves into novel therapeutic strategies in transplantation medicine, highlighting unique approaches that could revolutionize current practices. It emphasizes novel patterns that have the potential to transform the current landscape. Commencing with a thorough examination of the historical environment, it traces crucial advances and changes in transplantation. The focus is on traditional techniques, emphasizing their limitations and challenges. An extensive examination of contemporary transplantation therapies offers valuable insights into the most recent progress in organ, cellular, and tissue transplantation. This analysis examines the immunological obstacles and outlines the current advancements and constraints. The exploration further navigates into novel models and concepts such as immunomodulation, developments in organ preservation techniques, gene editing, biomaterials, scaffold-based solutions, and the integration of precision medicine, artificial intelligence, and machine learning applications. Each section analyzes the potential for change and current progress in various areas, backed by relevant scientific sources up to 2023. The subsequent sections delve into innovative cellular therapies, biotechnological progress, current clinical trials, and case studies demonstrating effective applications. This examination delves into the ethical and regulatory considerations of innovative therapeutic procedures, emphasizing ethical implications, regulatory frameworks, and the importance of balancing innovation with patient welfare. The literature review concludes by offering a forward-looking perspective, emphasizing potential progress, anticipated challenges, and advocating for collaboration and interdisciplinary approaches to overcome limitations in the field of transplantation medicine.

In review, the operating principles of the most common bio sensing devices, detection methods and the identification sensitivity of analyzed molecules were shown. The central focus was done on hybridization analysis of nucleic acids (NA), which are considered to be one of the most important analytes in terms of diagnostic point of view. Constructions enabling to transfer the fact of formation of nucleotide probe/target complex in to detectable signal by optical, electrochemical or micromechanical (piezoelectric) sensors were presented in this review.

We present a study of the radio variability of bright, $S_{1.4}\geq100$ mJy, high-redshift quasars at $z\geq3$ on timescales up to 30--40 years. The study involved simultaneous RATAN-600 measurements at frequencies of 2.3, 4.7, 8.2, 11.2, and 22.3 GHz in 2017--2020. In addition, data from the literature were used. We have found that the variability index $V_S$ of the quasars ranges from 0.02 to 0.96, with about half of the objects in the sample showing a variability index in the range of 0.25--0.50, which is comparable to that of the blazars at lower redshifts. The distribution of $V_S$ at 22.3 GHz is significantly different from that at 2.3--11.2 GHz, which may be attributed to the fact that a compact AGN core dominates at the source's rest frame frequencies greater than 45 GHz, leading to higher variability indices obtained at 22.3 GHz (the $V_S$ distribution peaks around 0.4) compared to the lower frequencies (the $V_S$ distribution peaks around 0.1--0.2). Several source groups with distinctive variability characteristics were found using cluster analysis of quasars. We propose 7 new candidates for gigahertz peaked-spectrum (GPS) sources and 5 new megahertz peaked-spectrum (MPS) sources based on their spectrum shape and variability features. Only 6 out of 23 sources previously reported as GPS demonstrate a low variability level typical of classical GPS sources ($V_{S} < 0.25$) at 4.7--22.3~GHz. When excluding the highly variable peaked-spectrum blazars, we expect no more than 20\% of the sources in the sample to be GPS candidates and no more than 10\% to be MPS candidates.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 65 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2, and altered expression of growth factor receptors and microRNAs. These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Ras is the most frequently mutated oncogene and recent drug development efforts have spurred significant new research interest. Here we will review progress toward understanding how Ras functions in nanoscale, proteo-lipid signaling complexes on the plasma membrane, called nanocluster. We will discuss how G-domain reorientation is plausibly linked to Ras-nanoclustering and -dimerization. We will then look at how these mechanistic features could cooperate in the engagement and activation of RAF by Ras. Moreover, we will show how this structural information can be integrated with microscopy data that provide nanoscale resolution in cell biological experiments. Synthesizing the available data, we propose to distinguish between two types of Ras nanoclusters, an active, immobile RAF-dependent type and an inactive/ neutral membrane anchor-dependent. We conclude that it is possible that Ras reorientation enables dynamic Ras dimerization, while the whole Ras/ RAF complex transits into an active state. These transient di/oligomer interfaces of Ras may be amenable to pharmacological intervention. We close by highlighting a number of open questions including, whether all effectors form active nanoclusters and whether there is an isoform specific composition of Ras nanocluster.

Background. Keyword co-occurrence analysis is a crucial tool for comprehending research trends, identifying relevant studies, and gaining insight into the connections between various concepts and topics. Objective. This study focuses on analyzing the co-occurrence of keywords using FP-growth algorithm and direct search methods. Materials and methods. The methodology involved extracting bibliometric data of Energies journal for 2023-2024 from MDPI publisher platform, keyword lemmatization and keyword co-occurrence estimation. Clustering and visualization were performed using Multidendrograms and Scimago Graphica software. Results. The results showed that the FP-growth algorithm can achieve a close match with the direct search results, which facilitates data preparation for clustering. In addition, finding the co-occurrence of three or more keywords significantly reduced the number of possible combinations, which allowed the identification of specific research topics. Conclusions. This study highlights the usefulness of the FP-growth algorithm in keyword analysis and provides insights into ways to refine search queries to abstract databases for the purpose of designing and writing literature and systematic reviews.

Relevance of the subject. Keyword selection is critical to finding relevant literature and requires justification for querying abstract databases and other sources to ensure accuracy and completeness. The topic of Energy Systems is of great importance due to the introduction of renewable energy sources, modern control methods, and complex energy systems during the energy transition. The aim of this study. The goal of this paper was to identify keywords that would be useful to subject matter experts when collecting literature on a particular topic, based on entries in the IEEE Terms field. Data. Bibliometric data were exported from the IEEE Xplore platform in the following order: for 2019-2023, 2000 records sorted by relevance, for 2024, 1680 records current as of April 11, 2024. Analytical methods applied and software used. VOSviewer, Scimago Graphica implementing the Clauset-Newman-Moore algorithm and agglomerative hierarchical clustering method implemented in Multidendrograms. Results. The main issues of the Energy Systems topic are presented in tabular and graphical formats. The fpgrowth utility offers flexible data preparation options, which makes it worthwhile to conduct a separate study to analyze the score of co-occurrence terms given by its algorithm.

Purpose of publication: - Preparation of bibliometric data exported from the Scilit platform on energy efficiency and conservation for further analysis to identify relevant research topics. - To identify potential issues in the processing of data exported from the Scilit platform. - Providing colleagues with the opportunity to use the prepared data and examples of their analysis for independent research on topical issues of energy efficiency and energy conservation using materials provided by the Scilit platform. Research Materials: Files in CSV and RIS formats exported from Scilit for the query "energy conservation OR efficiency" in Common Fields [Title, Abstract, Keyword], using filters: Content Type → Journal Article; Year→2021-2023; Subject → Industrial Engineering (29.8K), Energy and Fuel Technology (9.8K), Manufacturing Engineering (9.2K). A total of 30K records sorted by their relevance (10K for each year) were exported. Data are current as of 14-03-2024. Methods: Preprocessing of title, annotation, and keyword field texts using lemmatization dictionaries collected on GitHub, removal of keywords taken from GATE and spaCy, and "manual" editing. Using VOSviewer to analyze publication topics by clustering keywords based on their co-occurrence. Using Scimago Graphica to build bubble diagrams.Application of the GSDMM algorithm for clustering bibliometric records by title and annotation texts. Creation of a dictionary for this algorithm using the keyword field.Use of the Carrot2 demo version and the NMF algorithm for a more detailed analysis of the topics of the record clusters obtained from GSDMM. Results: are presented in the form of initial and interim tables and graphs obtained in the course of this study. The full tables are provided as references to the attached materials. Supplementary material for this preprint on figshare: Chigarev, Boris (2024). Supplementary material for preprint "Analyzing the Possibilities of Using the Scilit Platform to Identify Current Energy Efficiency and Conservation Issues". figshare. Dataset. https://doi.org/10.6084/m9.figshare.25574058.v1

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Here we compile a detailed record of eddies and examine their intra-annual variability over the Spitsbergen Bank in the northwestern Barents Sea using spaceborne Sentinel-1 A/B synthetic aperture radar (SAR) data acquired in 2018. Analysis of 3070 SAR images enabled to register 1758 eddy manifestations in the marginal ice zone (MIZ) and 1631 signatures in the open water (OW). Submesoscale and small mesoscale eddies were observed within a range 0.2-40 km with the range of MIZ eddies being twice larger than that of OW eddies. We note a strong seasonal variability of eddy diameters and the ratio of cyclones to anticyclones. The eddies were present in all seasons showing an approximate parity in eddy generation intensity in the surface layer between winter and summer. The peak eddy activity is observed during the first (January to March) and third (July-September) quarters of the year. A well-pronounced seasonality of SAR-derived eddy intensity correlates with that of eddy kinetic energy in the surface layer of the Eurasian Arctic. Eddies were detected most frequently in Storfjorden, south of Edge Island, near Hopen Island and along the entire eastern flank of the Spitsbergen Bank. Very low eddy activity was observed in the central part of the bank. The MIZ eddies were recorded during eight months of the year peaking in February, and being spatially limited by a 200-m isobath. The OW eddies were widely dispersed across the study domain peaking in August and tending to accumulate in regions of relatively weak surface currents. In summer, about 20-25% of them were observed within the Barents Sea Polar Front.

The study of coherent vortices remains an urgent field of singular optics of vortex beams. In this paper, coherent properties of partially coherent vortex Bessel—Gaussian optical beams propagating through a uniform medium (free space) or a turbulent atmosphere are examined theoretically. The consideration is based on analytical solution of the equation for the transverse second-order mutual coherence function of the field of a partially coherent optical radiation in a turbulent atmosphere. For the partially coherent Bessel—Gaussian beam, the second-order mutual coherence function of the source field is taken as a Gaussian Shell-model. In this approximation, we analyze the behavior of the coherence degree and the integral coherence scale of these beams as a function of the propagation pathlength, propagation conditions, and beam parameters, such as the radius of the Gauss factor of the beam, parameter of the Bessel factor of the beam, topological charge, and correlation width of the source field of partially coherent radiation. In addition, the integral coherence scale of the partially coherent vortex Bessel—Gaussian beam is compared with that of the partially coherent Gaussian beam. It is found that as a partially coherent vortex Bessel—Gaussian beam propagates through a turbulent atmosphere, there appear not two (as might be expected: one due to atmospheric turbulence and another due to partial coherence of the source field), but only one ring dislocation of the coherence degree (due to the simultaneous effect of both these factors on the optical radiation). In addition, it is shown that the dislocation of the coherence degree that affects significantly the beam coherence level is formed only for beams, for which the coherence width of the source field is larger than the diameter of the first Fresnel zone.

The chiral optical Tamm state (COTS) is a special localized state at the interface of a handedness-preserving mirror and a structurally chiral medium such as a cholesteric liquid crystal or a chiral sculptured thin film. The spectral behavior of COTS, observed as reflection resonances, is described by the temporal coupled-mode theory. Mode coupling is different for two circular light polarizations because COTS has a helix structure replicating that of the cholesteric. The mode coupling for co-handed circularly polarized light exponentially attenuates with the cholesteric layer thickness since the COTS frequency falls into the stop band. Cross-handed circularly polarized light freely goes through the cholesteric layer and can excite COTS when reflected from the handedness-preserving mirror. The coupling in this case is proportional to anisotropy of the cholesteric and theoretically it is only anisotropy of magnetic permittivity that can ultimately cancel this coupling. These two couplings being equal results in a polarization crossover (the Kopp--Genack effect) for which a linear polarization is optimal to excite COTS. The corresponding cholesteric thickness and scattering matrix for COTS are generally described by simple expressions.

Hydrodynamic modeling and hazard mapping are essential tools for urban flood mitigation and spatial planning. Leveraging software like HEC-RAS (Hydrologic Engineering Center - River Analysis System) and ArcGIS, this study aimed to map flood-prone areas along the Jijia River in the Ungheni administrative unit of Iasi County. Human-induced environmental changes and global climate shifts have heightened flood risks worldwide, particularly in urbanized areas. Hydrological and hydraulic modeling anticipate and assess flood events, while hydrodynamic modeling accurately simulates flow propagation, in-forming flood extent, timing, and volume. Flood hazard maps offer essential insights into flooded areas, water depths, and velocities, assisting in risk assessment and mitigation strategies. Through the use of different scenarios, river modeling aims to accurately replicate real-world conditions. This study focuses on Ungheni commune in Iasi County, Romania, situated along the Prut River's eastern bank. Utilizing a combination of fixed-grid and irregular mesh elements in modeling al-lows for fine-tuning of flow details and optimization of simulation times. Model accuracy, particularly regarding peak river levels, hinges on hydrograph duration. While a 30-minute error is typically accepted, greater tolerances may apply to river basins with longer response times. The extraction and processing of model results, including maximum water depths, flood extents, and velocity maps, are facilitated by ArcGIS, providing valuable data for effective flood management strategies.

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unal-tered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex ter-minates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant con-tributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

Several series of new polymers were synthesized: binary copolyesters of vanillic (VA) and hydroxybiphenylcarboxylic (HBCA) acids, as well as ternary copolyesters additionally containing hydroxybenzoic acid (HBA) and obtained via three different ways (in solution, in melt and in solid state). The high values of logarithmic intrinsic viscosities and insolubility of several samples proved its high molecular weights. It has been shown that the use of vanillic acid leads to the production of copolyesters with a relatively high glass transition temperature (about 130°C). Thermogravimetric analysis revealed onset of weight loss temperatures of ternary copolyesters occurred at 330-350 °C, the temperature of 5% mass loss is in the range of 390-410 °C. Two-stage thermal destruction is observed for all aromatic copolyester of vanillic acid: decomposition begins with VA units at 420-480 °C, and then decomposition of more heat-resistant units demonstrated above 520 °C. The copolyesters are thermotropic and exhibit a typical nematic type of liquid crystalline order. Mechanical characteristics of copolyesters are close to those for semi-aromatic copolyesters, but are much lower than typical values for fully aromatic thermotropic polymers. Thus, vanillic acid is a mesogenic monomer suitable for the synthesis of thermotropic fully aromatic and semi-aromatic copolyester, but resulting processing temperature must not exceed 280°C.

Measurements of temperature and salinity in the Amazon River plume in the open ocean of the western tropical North Atlantic are considered. The measurements were carried out using the AML CTD probe in the upper layer and a flow-through system that measures salinity and turbidity of seawater while the vessel is on the way. Additionally, archive oceanographic data from the WOD18 database, data of satellite altimetry measurements (AVISO), and satellite salinity data from Aquarius and SMOS were used. It is shown that the width of the Amazon plume is about 300–400 km, the depth of desalination is from 50 to 100 m. Surface salinity decreases compared to the background (36 PSU) by 0.5 PSU in February and more than by 3 PSU in September during the period of maximum development of the plume, which is determined from satellite measurements of surface salinity. Lagrangian modeling of the back-in-time advection of passive markers simulating freshwater particles was carried out. It was shown that the source of fresh water in the measurement area is the discharge of the Amazon.

Recent data suggest that K-Ras4B (hereafter K-Ras) can drive cancer cell stemness via calmodulin (CaM)-dependent, non-canonical Wnt-signalling. Here we examined whether another Ca2+-binding protein, the CaM-related centrin1, binds to K-Ras and could mediate some K-Ras functions that were previously ascribed to CaM. While CaM and centrin1 appear to distinguish between peptides that were derived from their classical targets, they both bind to K-Ras in cells. Cellular BRET-data suggest that CaM engages more with K-Ras than centrin1 and that the interaction with the C-terminal membrane anchor of K-Ras is sufficient for this. Surprisingly, binding of neither K-Ras nor its membrane anchor alone to CaM or centrin1 is sensitive to inhibition of prenylation. In support of an involvement of the G-domain of K-Ras in cellular complexes with these Ca2+-binding proteins, we find that oncogenic K-RasG12V displays increased engagement with both CaM and centrin1. This is abrogated by addition of the D38A effector-site mutation, suggesting that K-RasG12V is held together with CaM or centrin1 in complexes with effectors. When treated with CaM-inhibitors the BRET-interaction of K-RasG12V with centrin1 was also disrupted in the low micromolar range, comparable to that with CaM. While CaM predominates in regulating functional membrane anchorage of K-Ras, it has a very similar co-distribution with centrin1 on mitotic organelles. Given these results, a significant overlap of the CaM- and centrin1-dependent functions of K-Ras is suggested.

RAS oncogenes are amongst the most commonly mutated proteins in human cancers. They regulate a wide range of effector pathways that control cell proliferation, survival, differentiation, migration and metabolic status. Including aberrations in these pathways, RAS dependent signaling is altered in more than half of human cancers. Targeting mutant RAS proteins and their downstream oncogenic signaling pathways has been elusive. However, recent results comprising detailed molecular studies, large scale omics studies and computational modeling have painted a new and more comprehensive portrait of RAS signaling that helps us to understand the intricacies of RAS, how its physiological and pathophysiological functions are regulated, and how we can target them. Here, we review these efforts particularly trying to relate the detailed mechanistic studies with global functional studies. We highlight the importance of computational modeling and data integration to derive an actionable understanding of RAS signaling that will allow us to design new mechanism based therapies for RAS mutated cancers.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

Development of K-Ras independence may explain failure of targeted therapy for pancreatic cancer (PC). In this paper active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. Knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism but only K-Ras depletion caused a decrease in G2 cyclins, proteasome inhibition reversed this and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from G2 phase to slow relative to completion of S-phase, suggesting mutant K-Ras may inhibit APC/c prior to anaphase but stabilizes G2 cyclins independently of this. We propose that during tumorigenesis, cancer cells expressing wild type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of cell cycle independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division even in cells where K-Ras is inhibited. Keywords: Pancreatic Ductal Adenocarcinoma, K-Ras, N-Ras, G2 cyclins.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

Organosilicate glass (OSG) films are a vital component in modern electronic devices, with their electrical properties playing a crucial role in device performance. This comprehensive review systematically examines the influence of chemical composition, vacuum ultraviolet (VUV) irradiation, and plasma treatment on the electrical properties of OSG films. Through an extensive survey of literature and experimental findings, we elucidate the intricate interplay between these factors and the resultant alterations in electrical conductivity, dielectric constant, and breakdown strength of OSG films. Key focus areas include the impact of diverse organic moieties incorporated into the silica matrix, the effects of VUV irradiation on film properties, and the modifications induced by various plasma treatment techniques. Furthermore, we discuss the underlying mechanisms governing these phenomena, shedding light on the intricate molecular interactions and structural rearrangements occurring within OSG films under different environmental conditions. This review not only consolidates existing knowledge but also identifies gaps in understanding and suggests avenues for future research, thereby advancing our comprehension of OSG film behavior and paving the way for enhanced performance in next-generation electronic and photonic devices.

Tissue-like phantoms are widely used as a model for mimicking the optical properties of live tissue. This paper presents the results of a diffusion reflection method as well as fluorescence lifetime imaging microscopy measurements of fluorescein-conjugated gold nanorods in solution as well as inserted in solid tissue-imitating phantoms. A lack of consistency between the fluorescence lifetime results of the solutions and the phantoms raises a question about the ability of tissue-like phantoms to maintain the optical properties of inserted contrast agents.

This research focuses on the use of the HEC-RAS model to estimate flash flood risk. It combines advanced hydraulic modeling techniques and precise data entry. The aim is to contribute knowledge to assess flash flood risk and reduce impacts on communities and infrastructure. The selection of study areas with a history of severe flooding, such as the Lam Saphung Basin, Phrom River Basin, and Lam Chern River Basin Part 1 in Thailand, highlights the importance of thorough flash flood risk assessment. By leveraging the HEC-RAS model, the results of this research inform proactive risk management strategies, improve emergency preparedness and help develop sustainable mitigation measures. The results are important in developing emergency response strategies and overall recovery ability in areas at risk of flash floods. The research combines advanced hydrologic modeling and real-world flash flood data. In addition to the flood condition assessment, the extent of the flood area and associated hazards were assessed using a two-case simulation strategy. The study covers future scenarios related to land use changes and retrospective analysis of past flood events. The results have practical implications for improving emergency response strategies, land use planning, and overall resilience in flash flood-prone areas. The integrated approach emphasizes the research output to providing insights and actionable solutions for communities facing ongoing challenges posed by flash floods.

We hypothesis that large earthquakes generate Horndeski-like Gravitational Wave (GW). We find that such a Horndeski-like GW propagates with the speed of sound. The sound waves generated by an earthquake make a local and temporal change to the Earth’s diagravitational medium; therefore, they modify the GW speed in a standard, Alternative-Theory-of-Gravity (ATG) sense. The quantum of the Horndeski-like GW is a massless scalar quasiparticle and cannot exist outside of the propagation region of the P-field. The Horndeski-like GW may be detectable by future GW detectors with a sensitivity of 10−15 Hz^−1/2 in the region of 0.1–1 Hz.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. Germ cell tumors (GCTs) are relatively rare. However, they are the most diagnosed malignancies occurring in the testis (TGCT) among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified few significantly mutated somatic genes, primarily KIT and K-RAS, so affecting, at various levels, the KIT–RAS–RAF–MEK–ERK cascade. This review focuses on the most recent investigations about this signaling pathway in TGCTs concerning their development, natural history, response to standard chemotherapy protocols (i.e., cisplatin-based), and on the efforts being made to identify targetable markers for possible precision medicine approaches.

Atmospheric turbulence characteristics are essential in determining the quality of astronomical images and implementing adaptive optics systems. In this study, the vertical distributions of optical turbulence at the Peak Terskol observatory (43.27472 ° N 42.50083 ° E, 3127 m a.s.l.) using the Era-5 re-analysis and scintillation measurements are investigated. For the closest reanalysis grid node to the observatory, vertical profiles of the structural constant of the air refractive index turbulent fluctuations Cn2 were obtained. The calculated Cn2(z) vertical profiles are compared with the vertical distribution of turbulence intensity obtained from tomographic measurements with Shack-Hartmann sensor. The atmospheric coherence length at the location of Terskol Peak was estimated. Using combination of atmospheric models and scheme paramaterization of turbulence, Cn2(z) profiles at Mt. Kurapdag were obtained. The values of atmospheric coherence length at the Peak Terskol are compared with estimated values of this length at the ten astronomical sites including Ali, Lenghu and Daocheng.

Abstract: Two novel low-dimensional molecular magnetic materials were prepared by a self-assembling of 3d- and 5d-metal complexes. These are the first neutral heterobimetallic cyanobridged compounds involving one anisotropic Mn(III) Schiff base complex and one octacyanotungstate(V) per molecular unit. A slow diffusion of the constituents’ solutions leads to a formation of the 0D crystalline complex 1 due to coordination of a water molecule to the Mn center prevents a polymer formation. A rapid mixing of reagents results in a precipitation of the microcrystalline powder of the complex 2, which on a totality of experimental data possess 1D polymeric structure. The magnetic studies have shown that antiferromagnetic exchange interactions are dominating in 1 J/k_B= -13.1(7) K, D=-3.0(1.3) K, zJ'= -0.16(20) K and g_av=2.00(1); while the presence of the significant intramolecular Mn(III)–W(V) ferromagnetic couplings through cyanide bridges is characteristic for 2 (J/k_B = 46.1(5) K g_Mn = 2.11(3), fixed g_W = 2.0). Due to the weak interchain interactions, zJ'/k_B = –0.8(2) K, compound 2 is a metamagnet with the Néel temperature of 9.5 K undergoing a spin-flip transition at 2 kOe. The slow magnetization dynamics of 2 was investigated at DС field of 0 and 2 kOe, giving the values of τ₀ 32(15) and 36(15) ps respectively, well within the range typical for SCMs. The respective ∆_τ/k_B values were 48.4(1.2) and 44.9(1.0) K.

In this study we discuss critical issues in modelling the structure and function of lymph nodes (LNs), with emphasis on how LN physiology is related to its multi-scale structural organization. In addition to macroscopic domains such as B-cell follicles and the T cell zone, there are vascular networks which play a key role in the delivery of information to the inner parts of the LN, i.e., the conduit and blood microvascular networks. We propose object-oriented computational algorithms to model the 3D geometry of the fibroblastic reticular cell (FRC) network and the microvasculature. Assuming that a conduit cylinder is densely packed with collagen fibers, the computational flow study predicted that the diffusion should be a dominating process in mass transport than convective flow. The geometry models are used to analyze the lymph flow properties through the conduit network in unperturbed- and damaged states of the LN. The analysis predicts that elimination of up to 60–90 % of edges is required to stop the lymph flux. This result suggests a high degree of functional robustness of the network.

Walls-like structured monoclinic WO3 thin films were obtained by spray deposition method for further integration in gas sensors. For sensing applications, it is very important to achieve a high surface-to-volume ratio surface together with a proper thin films structure. The present communication reports on the effect of the sprayed solution volume variation (as a thickness variation element) on the detailed Raman spectroscopy for WO3 thin films with different thicknesses grown from precursor solutions with two different concentrations. Detailed analysis of the two series of samples shows that the growing thickness strongly affects the films morphology while their crystalline structure is only slightly affected. The Raman analysis contribute to refining the structural features clarifications. It was observed that, for both concentrations, the increase in thickness seems to slightly affect the stoichiometry of material and, in association with surface morphology variations, provide new possibilities for fine tuning of films properties towards enhanced as sensing applications. Further studies are ongoing.

River renaturation can be an effective management method for restoring the floodplain's natural capacity and minimizing the effects during high flow periods. A 1D-2D HEC-RAS model, in which the flood plain was considered as 2D and the main channel as 1D, was used to simulate flooding in the restored reach of the Spree River. When computing in this model, finite volume and finite difference approximations using the Preissmann approach are used for the 1D and 2D models, respectively. To comprehend the sensitivity of the parameters and model, several scenarios were simulated using different time steps and grid sizes. Additionally, dykes, dredging, and changes to the vegetation pattern have been used to simulate flood mitigation measures. The model predicted that flooding would occur mostly in the downstream portion of the channel in the majority of the scenarios without mitigation measures, whereas with mitigation measures, flooding in the floodplain would be greatly reduced. By preserving the natural balance on the channel's floodplain, the restored area needs to be kept in good condition. Therefore, mitigating measures that balance the area's economic and environmental aspects must be considered in light of the potential for floods.

The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive models for BRAFV600E and RAS-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the BRAF and RAS genes. Multivariate logistic regression was employed to develop prediction model. Independent predictors for the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology variant, and pERK1/2 levels exceeding 10% (X2=0.128, P&gt;0.05, AUC=0.734, P&lt;0.001). RAS mutation predictive model includes follicular histology variant and pERK1/2 expression &gt;10% (X2=0.174, P&gt;0.05, AUC=0.8, P&lt;0.001). We proposed using the prediction model concurrently with four potential combination group outcomes. PTC cases included in combination of low BRAFV600E-scoring group and high RAS-scoring group are categorized as RAS-like (adjOR=4.857, P=0.01, 95% CI=1.470-16.049). PTCs included in combination of high BRAFV600E-scoring group and low RAS-scoring group are categorized as BRAF-like PTCs (adjOR=3.091, P=0.001, 95% CI=1.594-5.995). The different prediction models indicate variations in biological behaviour between BRAF-like and RAS-like PTCs, necessitating adjustments in treatment approaches.

Background: Biomarker profiles should represent a coherent description of the colorectal cancer (CRC) stage and its evolution. Methods: Using droplet digital PCR, we detected the allelic frequencies (AF) of KRAS, NRAS, BRAF and EGFR mutations from 60 tumors. We employed a pair-wise association approach to estimate the risk involving AF mutations as outcome variables for clinical data and as predicting variables for tumor-staging. We evaluated correlations between mutations AFs and also between the mutations and histopathology features (tumor staging, inflammation, differentiation and invasiveness). Results: KRAS G12/G13 mutations were present in all patients. KRAS Q61 was significantly associated with poor differentiation, high desmoplastic reaction, invasiveness (ypT4) and metastasis (ypM1). NRAS and BRAF were associated with the right-side localization of tumors. Diabetic patients had a higher risk to exhibit NRAS G12/G13 mutations. BRAF’s presence limited the invasiveness in the submucosa, co-existing with NRAS G12/G13 mutations. Conclusions: The associations we found and the mutational AF we reported may help to understand disease processes and may be considered as potential CCR biomarker candidates. In addition, we propose representative mutation panels associated with specific clinical and histopathological features of CRC, as a unique opportunity to refine the degree of personalization of CRC treatment.

This study explored the effects of cryogenic treatment on the microstructure, hardness, and wear-resistance of diamond-like carbon (DLC) by cryogenically treating NAK 80 mold steel coated with DLC. Raman spectroscopy analyzed the structure of the DLC film. Nanoindenter analyzed the hardness and Young’s modulus of the film, and their relationship determined the wear resistance. Wear test assessed the wear rate and friction coefficient of the DLC film. The results showed that cryogenic treatment increased the rate of carbide precipitation and refined the grain structure. Raman spectroscopy indicated that the Raman intensity rate (I_D/I_G) of treated DLC films was smaller than those without cryogenic treatment. When the sp3 bond increased, the hardness and wear-resistance of the DLC film also increased.

Abstract: Oncogenic RAS mutations drive more than half of human cancers, and RAS inhibition is the holy grail of oncology. Thirty years of relentless efforts and harsh disappointments have taught us about the intricacies of oncogenic RAS signalling that allow us to now get a pharmacological grip on this elusive protein. The inhibition of effector pathways, such as the RAF-MEK-ERK pathway, has largely proven disappointing. So far, most of these efforts were aimed at blocking the activation of ERK. Here, we discuss RAF dependent pathways that are regulated through RAF functions independent of catalytic activity and their potential role as targets to block oncogenic RAS signalling. We focus on the now well documented roles of RAF kinase independent functions in apoptosis, cell cycle progression and cell migration.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

Improving photobioreactor performance for microalgae cultivation has attracted many researchers over the past years. One of the primary challenges associated with existing photobioreactors is the light penetration. An effective photobioreactor design should maximize light penetration, ensuring uniform illumination throughout the reactor. This study aims to assess the impact of light intensity on microalgal growth from the perspective of energy efficiency and productivity in two photobioreactors. A novel cactus-like and a cylindrical photobioreactor were designed and fabricated using 3D printing technology. These two photobioreactors were used to cultivate two strains of microalgae. The novel photobioreactor achieved a maximum biomass productivity of 0.99 g/L/d and a maximum energy efficiency of 0.3139 g/d/kWh. The cylindrical photobioreactor reached a maximum biomass productivity of 0.74 g/L/d and 0.2199 g/d/kWh of energy efficiency. The increase in biomass productivity can be linked to enhancements in the photobioreactor's surface-to-volume ratio and better light utilization.

This article is devoted to the results of in-depth analysis of the system of binary-oppositional structures in DNA n-plet alphabets and their algebraic-matrix representations. These results show that the molecular complementary replication of DNA strands is accompanied by the presence of an algebraic version of the principle "like begets like" in matrix representations of DNA alphabets having internal structures. This algebraic version is based on binary-oppositional structures in the genetic molecular system, which can be represented by binary numbers and corresponding matrices of DNA alphabets. The received results allow thinking that the phenomenon "like begets like" (or a complementary replication in a wide sense) is systemic in the genetic organization and is connected with algebraic features of biological organization. Correspondingly, the biological principle "like begets like" can be additionally modeled by algebraic-matrix methods and approaches. Such algebra-matrix modeling of the genetic coding system gives new ways for studying and understanding the key role of the named principle in genetic and other inherited physiological complexes. On this way, the author discovered general rules of stochastic organization of information binary sequences of genomic DNAs of eukaryotes and prokaryotes. The presented rules are connected with information dichotomies of probabilities and corresponding fractal-like trees of probabilities, which fundamentally differ from constructional dichotomies in biological bodies. The received phenomenological data and rules lead to new biological ideas.

Infantile Neuroaxonal Dystrophy (INAD) is a rare neurodegenerative disorder, affecting 1:1,000,000 population. It results from pathogenic variants in the PLA2G6 gene located on chromosome (22q13.1). The onset of symptoms usually occurs between 6 to 18 months, causing developmental regression leading to debilitating symptoms such as muscle weakness, dementia, and loss of basic skills. Eventually, it progresses to life-threatening symptoms including breathing difficulties, which limits the life expectancy to 5-10 years. While potential genetic therapy for treatment is are being developed, they are yet to be approved for use, and management remains essentially supportive. This case report is of a 9-year-old Pakistani girl with INAD. She presented with recurrent chest infections, developmental regression, loss of speech, paralysis, hypertension, and eventually breathing difficulties. Brain magnetic resonance imaging and genetic testing con-firmed the diagnosis. This case posed diagnostic challenges in view of its overlapping clinical presentation. Through this report, we aim to raise awareness about the condition among practitioners, outline the importance of genetic counseling in susceptible couples and suggest potential areas of further research.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

The accumulation of brown algae from the genus Sargassum has been increasing over the years in coastal regions of the Caribbean, Africa, Brazil, and Mexico. This causes harmful effects to the ecosystem, health, economy, and climate due to gas emissions from its decomposition process. There is the possibility of this biomass being reused in civil construction, and few studies have been carried out on its application to common Portland cement mortar. As such, the objective of this study is to evaluate the potential of sargassum ash as a mineral addition to partial replacement of fine aggregates in Portland cement mortar. Characterizations of the raw materials were carried out through X-ray fluorescence spectroscopy, loss on ignition, particle size distribution, Brunauer–Emmett–Teller (BET), real density, X-ray diffraction, scanning electron microscopy, and dispersion spectroscopy of electrons. The mortars were prepared by partially replacing the fine aggregate (sand) with sargassum ash, at 0%, 5%, 10% and 20%. Mortar performance was evaluated through water absorption, apparent porosity, apparent specific mass, compressive strength after 7, 28, and 63 days after curing. Lastly, a life cycle assessment in accordance with ISO standards 14040:2006 and 14044:2006. The results showed that replacing sand with sargassum ash increases water absorption, apparent porosity, and decreases the apparent specific mass and compressive strength as replacement increases. Nevertheless, the compressive strength results after 63 days, for 5 and 10% replacement did not differ statistically from reference values. The life cycle assessment indicates that mortars with partial replacement of sand by sargassum ash showed positive environmental impacts when compared to reference values for most categories regardless of the scenario analyzed, especially for mortar with 10% replacement. As such, the use of sargassum ash at 10% does not alter compressive strength values after 63 days while reducing its environmental impact. The application of this biomass in civil construction materials provides a destination for this algae that has been causing several social, environmental, and economic problems.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

The reaction of berberine derivatives containing at O-9 position N,N-disubstituted acetamide fragments with sodium borohydride in methanol at 0 °C leads to a mild reduction of the "C" cycle with the formation of corresponding tetrahydroberberine derivatives with moderate to good yields.

Thermal expansion of four alkaline-earth borates, namely Ca3B2O6 (0D), CaB2O4 (1D), Sr3B14O24 (2D) and CaB4O7 (3D), have been studied by in situ high-temperature powder X-ray diffraction (HTXRD). Strong anisotropy of thermal expansion is observed for the structures of Ca3B2O6 (0D) and CaB2O4 (1D) built up from BO3 triangles only: these borates exhibit the maximal expansion perpendicular to the BO3 plane, i.e. along the direction of weaker bonding in the crystal structure. Layered Sr3B14O24 (2D) and framework CaB4O7 (3D) built up from various B-O groups expand less anisotropically. Thermal properties of the studied compounds compared to the other alka-line-earth borates are summarized depending on the selected structural characteristics like anion dimensionality, residual charge per one polyhedron (BO3 BO4), cationic size, and structural com-plexity. For the first time these dependencies were established as an average for both types of polyhedra (triangle and tetrahedron) occurring in the same structure at the same time. The most common trends were identified for : (i) Melting temperature decreases as the dimensionality of the borate polyanion, and more precisely, as the residual charge per one polyhedron (triangle or tetrahedron) decreases; (ii) volumetric expansion decreases while the degree of anisotropy in-creases weakly when the residual charge decreases; (iii)both trends (i) and (ii) are most steady within borates built by the triangles only, while the borates built by both triangles and tetrahedra show a larger scatter in values.

Simple Summary: This review explores the origin of Leukemic Stem-Like Cells (LSLCs) from (Very) Small Leukemic Stem-Like Cells ((V)SLSLCs) and Cancer Stem Cells (CSCs) from trans-formed Very Small Embryonic-Like Stem Cells (VSELSCs). Understanding this relation is a step toward uncovering the mechanisms behind cancer and leukemia initiation and development. We explore how these very small precursor cell stages might contribute to the initiation and progres-sion of cancer as well as leukemia with a focus on Acute Myeloid Leukemia (AML) as a model. Abstract: Recent experimental findings indicate that CSCs originate from transformed VSELSCs, which are early precursor stages of healthy stem cells. This discovery marks a crucial step in understanding the mechanisms that drive cancer development and initiation. Our team's follow-up studies on leukemia, lung cancer, and healthy embryonic kidney cells have, for the first time, identified stag-es resembling very small precursor stem cells in continuously growing cell lines. These findings suggest the existence of (Very) Small Cancer Stem Cells ((V)SCSCs) or (V)SLSCs within respective subpopulations of CSCs and LSCs in vivo. In this review, we explore theoretical examples of how leukemia progresses through various stages, highlighting the role of these very small precursor cells as fundament primitive stages. We also discuss the potential implications of further research into these unique cellular stages for advancing cancer and leukemia treatment and prevention strategies.

Nowadays, animal breeders look for effective innovations to care animal health. Use of probiotics, postbiotics, parabiotics and the other beneficial natural substances are dominated. Mundticin-like substance EM 41/3 is thermo-stable bacteriocin (postbiotic) with a broad antimicrobial spectrum. In this study its effect in broiler rabbits was assessed. Rabbits represent food-derived animal and they are also suitable animal model. The parameters tested were analyzed by validated methods. Administration of MLS EM 41/3 produced by non-autochthonous strain Enterococcus mundtii EM 41/3 lead to significant increase of parameter immunity-phagocytic activity, while it did not influence microbiota composition. It also did not influence blood biochemistry and no oxidative stress was noted. Moreover, higher growth parameters were noted and also stimulated hydrolytic activity. Finally, no negative influence on rabbit meat quality was noted. Postbiotic MLS EM 41/3 administration in feeding strategy seems to be contributing fact for rabbit health status maintaining.

Poikilodermatous plaque-like hemangioma (PPH) is a recently described clinical and pathological entity, with only 18 cases reported in the literature. Although uncommon, this benign condition presents consistent clinical and histological findings. We present a new case of PPH in an 81-year-old male and review the existing literature. The persistence over time and the need to distinguish PPH from more significant lesions underscore the importance of its clinical and pathological recognition.

The natural product elaiophylin is a macrodiolide with broad biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein-protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here we elaborate that elaiophylin likewise disrupts the Hsp90/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similar to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1⍺, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 3D spheroid formation. Finally, a strong inhibition of the same cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90/ Cdc37 interface as a target site.

Cancer is the second leading cause of death worldwide. Key to cancer initiation and progression is the crosstalk between cancer cells and their microenvironment. The extracellular matrix (ECM) is a major component of the tumour microenvironment and integrins, main cell-ECM adhesion receptors, are involved in every step of cancer progression. However, accumulating evidence has shown that integrins can act as tumour promoter but also as tumour suppressor factors, revealing that the biological roles of integrins in cancer are complex. This incites a better understating of integrin function in cancer progression. To achieve this goal, simple model organisms, such as Drosophila, offer a great potential to unravel underlying conceptual principles. Here, we find that in the Drosophila wing disc epithelium the PS integrins act as suppressors of tumours induced by a gain of function of the oncogenic form of Ras, RasV12. We show that PS integrin depletion enhances the growth, delamination and invasive behaviour of RasV12 tumour cells, as well as their ability to affect the tumour microenvironment. These results strongly suggest that integrin function as tumour suppressors might be evolutionary conserved. Drosophila can be used to understand the complex tumour modulating activities conferred by integrins, thus facilitating drug development.

In this study, a new type of temperature sensor device was developed. The circular electrode of the thermal sensitive sensor was modified with TMT and O₂ plasma to enhance the conductivity by forming a thin SnOxCy layer on the electrode surface. The Nano-Au particles were subjected to O₂ plasma pretreatment to form peroxide groups on the surface. The thermally sensitive sensor was made by mixing the above-treated Nano-Au particles with N-isopropylacrylamide (NIPAAm) to form solution and then UV-induced grafting polymerization of the NIPAAm-containing solution onto the electrode substrate. The composite hydrogels on the electrode introduce thermo-sensitive polymeric surface films for temperature sensing. Using ambient environment resistance test to measure the resistance, the LCST (lower critical solution temperature) of Nano-Au (MUA) mixed with NIPAAm hydrogel was found to be 32 °C. At ambient temperatures higher than LCST, the electrode resistance decreases linearly.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Abstract: Kiwifruit, a perennial horticultural crop known for its nutritional value, faces significant challenges due to biotic and abiotic stresses, affecting its yield and quality. Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we investigated the expression patterns of kiwifruit LRR-RLPs under various stress conditions, including pathogen stress, heat stress, waterlogging stress, and copper stress. Through genome and transcriptome analyses, we identified a total of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5' kiwifruit, respectively, classified into 9 subgroups based on phylogenetic relationships. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Using RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP genes in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

In this paper, we consider the formation of quantum black holes (QBHs) through a genuine quantum process. We treat particles at the Planck energy as QBHs. The Hawking temperature and entropy of QBHs are estimated. We also show that a QBH has a discrete energy spectrum. By analogy with supersymmetric theory, the mass of the superpartner of a QBH is estimated.

Background: Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcome, which opens up new avenues for using them in personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in preoperative diagnosis of aggressive variants of papillary thyroid cancer. Methods: The molecular genetic profile (expression levels of 34 different markers and BRAF mutation) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Results: Statistically significant differences with adjustment for multiple comparisons (p &lt; 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, FN1, and CDKN2A. Weak statistical correlation (0.0015&lt; р&lt;0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. Conclusions: The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, the fibronectin and cyclin-dependent kinase inhibitor 2A genes.

This paper delves into the challenge of controlling the multiple synchronizations in mechatronic vibration machines featuring a duo of unbalanced rotors. Its primary aim is to not only attain specific rotation speeds but also to ensure the desired phase shift between these rotors. To tackle this issue, the paper employs a control law integrating cross-couplings. It conducts an analysis of the dynamics of a simplified linearized system, showcasing the robustness of the control system across varying plant parameters. Additionally, the paper outlines experimental findings from a multi-resonance vibrational laboratory setup. These findings effectively demonstrate the effectiveness of the proposed approach and highlight its potential applications. Crucially, the paper provides experimental evidence illustrating the capability to control vibration fields on the operational platform, a vital aspect pertinent to vibration transportation and bulk material mixing processes.

To date, viruses closely related to SARS-CoV-2 have been reported in four bat species: Rhinolophus acuminatus, Rhinolophus affinis, Rhinolophus malayanus, and Rhinolophus shameli. Here, we analysed 343 sequences of the mitochondrial cytochrome c oxidase subunit 1 gene (CO1) from georeferenced bats of the four Rhinolophus species identified as reservoirs of SARS-CoV-2-like viruses. Haplotype networks were constructed in order to investigate patterns of genetic diversity among bat populations of Southeast Asia. No strong geographic structure was found for the four Rhinolophus species, suggesting high dispersal capacity. The ecological niche of SARS-CoV-2 like viruses was predicted using the four localities of bat SARS-CoV-2-like viruses and the localities where bats showed identical or very similar CO1 haplotypes than virus-positive bats. The ecological niche of SARS-CoV-like viruses was deduced from the localities where bat SARS-CoV-like viruses were previously detected. The results show that the ecological niche of SARS-CoV2-like viruses includes several regions of mainland Southeast Asia whereas that of SARS-CoV-like viruses is mainly restricted to China. In agreement with these results, human populations in Laos, Vietnam, Cambodia, and Thailand appear to be much less affected by the Covid-19 pandemic than other countries of Southeast Asia. In the climatic transitional zone between the two ecological niches (southern Yunnan, northern Laos, northern Vietnam, and possibly Hainan and Taiwan), genomic recombination between highly divergent viruses is more likely to occur. Since recombinant viruses can threaten the benefit of vaccination campaigns, these regions should be under surveillance.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis is due to the absence of specific biomarkers, aggressiveness and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that cause cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory property. Regarding CBG anticancer ef-fect, up to now there are only few evidence in human cancers. We investigated CBG effects on PDAC cell lines, PANC-1 and MIAPaCa-2. It was investigated CBG activity on cell viability, cell death and its effect of EGFR-RAS-associated signalling. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate CBG effect on PDAC cell lines viability. Annexin-V and Acridine Orange staining followed by cytofluorimetric analysis and Western blot were used to evaluate CBG effect on cell death. Modulation of EGFR-RAS-associated pathways was determined by Western Blot analysis and Milliplex multiplex assay. Moreover, by MTT data and Synergy finder software analysis the effect of the combination of CBG and chemotherapeutic drugs, was determined.

Oncogenic mutations in the small GTPase Ras contributes to ~30% of human cancers. However, tissue growth induced by oncogenic Ras is restrained by induction of cellular senescence and additional mutations are required to induce tumor progression. Therefore, it is paramount to identify cooperating cancer genes. Recently, the tensin family of focal adhesion proteins, TNS1-4, have emerged as regulators of carcinogenesis, yet their role in cancer appears somewhat controversial. Around 90% of human cancers are of epithelial origin. We have used the Drosophila wing imaginal disc epithelium as model system to gain insight into the roles of two orthologs of human TNS2 and 4, blistery (by) and PVRAP, in epithelial cancer progression. We have generated null mutations in PVRAP and found that, as it is the case for by and mammalian tensins, PVRAP mutants are viable. We have also found that elimination of either PVRAP or by potentiates RasV12-mediated wing disc hyperplasia. Furthermore, our results have unravelled a mechanism by which tensins may limit Ras oncogenic capacity, the regulation of cell shape and growth. These results demonstrate that Drosophila tensins behave as suppressors of Ras-driven tissue hyperplasia, suggesting that the roles of tensins as modulators of cancer progression might be evolutionary conserved.

We propose a method for creating parallel Bessel-like vortical optical needles with an arbitrary axial intensity distribution via superposition of different cone-angle Bessel vortices. We analyze the interplay between the separation of individual optical vortical needles and their respective lengths and introduce a super-Gaussian function as their axial profile. We also analyze the physical limitations to observe well-separated optic needles, as they are influenced by mutual interference of the individual beams. To verify our theoretical and numerical results, we generate controllable spatial arrays of individual Bessel beams with various numbers and spatial separations by altering the spectrum of the incoming laser beam via the spatial light modulator. We demonstrate experimentally how to implement such beams using a diffractive mask. The presented method facilitates the creation of diverse spatial intensity distributions in three dimensions, potentially finding applications in specific microfabrication tasks or other contexts. These beams may have benefits in laser material processing applications such as nanochannel machining, glass via production, modification of glass refractive indices, and glass dicing.

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

The urban population in developing countries, especially sub-Saharan Africa, is rapidly increas-ing. As towns and cities grow, so does the demand for fish protein. While flow-through aqua-culture can provide fresh, healthy and nutritious fish protein, it is plagued by extensive land re-quirement as well as effluent discharge, thus, unsuitable for city regions. Alternatively, small-scale Recirculating Aquaculture System (RAS) could improve food and nutritional security (FNS), livelihoods as well as reduce environmental degradation in urban areas despite land and water constraints. The question however remains - what are the key technical, business and managerial issues, surrounding small-scale RAS in urban farming? This study reviews the RAS prototype of the Sustainable Aquaponics for Nutritional and Food Security in Urban Sub-Saharan Africa (SANFU) II project based on mass balance and stock density, relevant for fish survival and/or availability as well as net cash-flow analyses. The results suggest that small-scale RAS are technically and financially viable only with family labor having proper aquaculture monitoring and management skills. Furthermore, access to adequate equipment and inputs as well as electricity for the recirculating system are crucial. Urban innovation actors will adopt RAS if operations are profitable given that family labor is employed.

Time is a component quantity of various measurements and is also used on its own to sequence events, to compare the duration of events or the intervals between them, and to quantify rates of change of quantities in material reality or in the conscious experience [1]. The measuring equipment well might happen to be a clock. By making a presupposition that clock is Time, it is perceived experimentally that “Time exhibits wave-like properties”

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.

Factors affecting the host-virus interaction must be understood for the effective application of bacteriophages to combat bacterial pathogens. Two novel E. coli phages, the T1-like siphophage LL5 and the rV5-like myophage LL12, were subjected to forward genetic screens against the Keio collection, a library of single non-essential gene deletions in E.coli str. BW25113. These genome-wide screens and subsequent experiments identified eight genes required for efficient propagation of phage LL5 and six genes required for propagation of LL12. The majority of the genes identified were involved in production of the phage receptors. E. coli mutants deficient in heptose II and the phosphoryl substituent of heptose I of the inner core lipopolysaccharide (LPS) were unable to propagate phage LL5, as were mutants deficient in the outer membrane protein TolC. Mutants lacking glucose I of the LPS outer core failed to propagate LL12. Two cytoplasmic chaperones, PpiB and SecB, were found to be required for efficient propagation of phage LL5 but not LL12. This approach may be useful for identifying phage receptors and required host factors in other phages, which would provide valuable information for their potential use as therapeutics and for phage engineering.

This is a short introductory review on quantum-like modeling of cognition with applications to decision making and rationality. The aim of the review is twofold: a) to present briefly the apparatus of quantum information and probability theory useful for such modeling; b) to motivate applications of this apparatus in cognitive studies and artifical intelligence, psychology, decision making, social and political sciences. We define quantum rationality as decision making that is based on quantum information processing. Quantumly and classically rational agents behaves differently. A quantum-like agent can violate the Savage Sure Thing Principle, the Aumann theorem on impossibility of agreeing to disagree.Such an agent violates the basic laws of classical probability, e.g., the law of total probability and the Bayesian probability inference. In some contexts, ``irrational behavior'' (from the viewpoint of classical theory of rationality) can be profitable, especially for agents who are overloaded by a variety of information flows. Quantumly rational agents can save a lot of information processing resources. At the same time, this sort of rationality is the basis for quantum-like socio-political engineering, e.g., social laser. This rationality plays the important role in the process of decision making not only by biosystems, but even by AI-systems. The latter equipped with quantum(-like) information processors would behave irrationally, from the classical viewpoint. As for biosystems, quantum rational behavior of AI-systems has its advantages and disadvantages. Finally, we point out that quantum-like information processing in AI-systems can be based on classical physical devices, e.g., classical digital or analog computers.

Rhes is one of the most interesting proteins regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. It is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D2 and adenosine A2A receptors. Rhes is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes-dependent regulation of dopaminergic transmission, several data showed that lack of Rhes enhanced cocaine and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces Rhes mRNA levels in rodents, non-human primates and Parkinson’s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.

This study deals with vibrational and crystallographic aspects of the thermally induced transformation of serpentine-like garnierite into quartz, forsterite, and enstatite occurring at about 620 °C. Powder specimens of garnierite have been annealed in static air between room temperature and 1000 °C. The resulting products from the transformations detected based on thermogravimetric and differential thermal analysis, have been extensively characterized via microRaman spectroscopy, and X-ray diffraction. Our study shows that serpentine-like garnierite consists of a mixture of different mineral species. Furthermore, these garnierites and their composition can provide details based on the mineralogy and the crystalline phases resulting from the thermal treatment.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

In this paper, we study the third order semilocal convergence of the Newton-like method for finding the approximate solution of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis under ω-continuity condition, which is weaker than the Lipschitz and Hölder continuity conditions. Second, we apply our approach to solve Fredholm integral equations, where the first derivative of involved operator not necessarily satisfy the Hölder and Lipschitz continuity conditions. Finally, we also prove that the R-order of the method is 2p + 1 for any p $\in$ (0,1].

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Phar-maceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with associated drug trends and characteristics. Our findings indicate that similar to　Parkinson’s disease, age-related differences affect the onset of these events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, side effects can vary depending on the site of action. These insights underline the importance of swift identification of the drugs suspected of causing these events and implementation of measures to reduce their side effects.

Diamond-like carbon (DLC) films have a promising tribological application in green precision manufacturing, but their toughness represents a serious issue in the way of their application perspective. The film thickness is on the micrometer scale and makes conventional methods unsuitable for its toughness characterization. The absence of an accepted method for characterizing the DLC toughness has hindered the related research on the development of toughening methods and understanding the mechanism. This work intends to explore a relatively simple and acceptable characterization method to measure the film toughness. Moreover, toughening mechanisms of DLC films are proposed during the characterization to reveal the toughening mechanism. The toughness can be fully characterized through combining impact toughness and scratch toughness. The impact toughness can be obtained by observing the size of the indentation and the crack state around the indentation in the impact experiment. The scratch toughness could be assessed by combining the scratch morphology and Crack Propagation Resistance (CPRS). The improvement of film toughness should be carried out from two aspects: preventing microcrack initiation and suppressing crack propagation. Appropriate doping of non-carbide metal particles can effectively improve the toughness of the film, and there are seven main factors affecting the toughening of the film. Five toughening mechanisms of non-carbide metals from film preparation to test stage are revealed during the investigation of the change patterns.

Methodologies for the synthesis and purification of metabolites, which have been developed following their discovery, analysis and structural identification, have been involved in numerous life science milestones. The renewed focus on the small molecule domain of biological cells has also created an increasing awareness of the rising gap between the metabolites identified and the metabolites which have been prepared as pure compounds. Due to the large number and molecular diversity of metabolites the design and engineering of resource-efficient and straightforward synthetic methodologies for their production have attracted much interest. The variety of metabolic pathways in biological cells provide a wonderful blueprint for designing simplified and resource-efficient synthetic routes to desired metabolites. Therefore, biocatalytic systems have become key enabling tools for the synthesis of an increasing number of metabolites, which can then be utilized as standards, enzyme substrates, inhibitors or products, or for the discovery of novel biological functions.

Spacetime torsion is known to be highly suppressed at the end of inflation, called preheating. Of course this fact does not avoid that metric could affect the cosmic dynamos at preheating phase as was showed by Bassett et al, in the general relativity (GR) case. In this paper, is to show that a torsionful magnetogenesis in QED effective lagrangean, drives either a torsion damping or an amplification mechanism or dynamo effect, depending upon torsion chirality. The present extension of Basset et al theory yields a new magnetic field expression $B\sim{a^{(1\pm{\beta})}}$, obtained from dynamo equation in QED. Here a cosmic factor ${\beta}=g_{T}{\eta}k$ is present. In a second example we find Higgs inlationary fields in Einstein-Cartan gravity thick domain walls (DWs). Recently a moodified Einstein-Cartan gravity was given by M Shaposhnikov et al [PRL (2020)] to obtain higgs like inflatons as a portal to dark energy.

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Because of the toxicity of cyanides, many are working on the development of cyanide-free baths, which are promising but not satisfactory to replace the classic methods. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized by their morphology, chemical composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structures observed were fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at.% copper and exhibited relatively strong corrosion resistance. High improvement of corrosion properties was found in the case of copper and brass coatings with an olive-like structure.

Several optimization models of irreversible reverse cycle machines have been developed based on different optimization criteria in the literature, most of them using linear heat transfer laws at the source and sink. This raises the issue how close to actual operation conditions they are, since the heat transfer law on the phase-change processes is dependent on ΔT3. This paper addresses this issue by proposing a general model for study and optimization of thermal machines with two heat reservoirs applied to a Carnot-like refrigerator, with non-linear heat transfer laws and internal and external irreversibility. The optimization was performed using First and Second Law of Thermodynamics and Lagrange multipliers method. Thus, several constraints were imposed to the system, also different objective functions were considered, allowing finding the optimum operating conditions, as well as the limited variation ranges of the system parameters. Results show that the nature of the heat transfer laws affects the optimum values of system parameters for obtaining maximum performances and also their magnitude. Sensitivity studies with respect to system several parameters are presented. The results contribute to the understanding of the system limits in operation under different constraints and allow choosing the most convenient variables in given circumstances.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

This paper examines radially infalling worldlines in both Schwarzschild and Kruskal-Szekeres coordinates. A new Schwarzschild coordinate chart is presented which emphasizes the curvature of both the time and space coordinates and makes clear not only the mechanism by which the inertial observer is accelerated relative to the rest observers, but also clearly shows the light-like nature of the inertial worldline at the event horizon. The light-like nature of the falling frame is then supported by examining the falling worldlines in Kruskal-Szekeres coordinates. The effect of length contraction in the falling frame is also analyzed in both Schwarzschild and Kruskal-Szekeres coordinates.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

In the last decade, the objectives outlined by the needs of personal robotics have led to the rise of new biologically-inspired techniques for arm motion planning. This paper presents a literature review of the most recent research on the generation of human-like arm movements in humanoid and manipulation robotic systems. Search methods and inclusion criteria are described. The studies are analysed taking into consideration the sources of publication, the experimental settings, the type of movements, the technical approach, and the human motor principles that have been used to inspire and assess human-likeness. Results show that there is a strong focus on the generation of single-arm reaching movements and biomimetic-based methods. However, there has been poor attention to manipulation, obstacle-avoidance mechanisms, and dual-arm motion generation. For these reasons, human-like arm motion generation may not fully respect human behavioural and neurological key features and may result restricted to specific tasks of human-robot interaction. Limitations and challenges are discussed to provide meaningful directions for future investigations.

Vaccination has been one of the most successful and the most significant scientific advances in human health and life expectancy all around the globe. The World Health Organization considers that immunization should be recognized as the main component of human health right, due to the fact that vaccination prevents 2.5 million deaths annually (World Health Organization, 2011). The most successful vaccines have been developed using conventional methods that follow the paradigm established by Pasteur: "to isolate, inactivate and inject" the pathogen microorganism and mimic a natural infection. Recently, metagenomics have played an important role in the discovery of new immunogens for vaccine design and the selection of antigens based on genomic information. The main approach that has used this strategy has been called "reverse vaccinology". This promising and arising field allows the screening of the entire potential antigenic repertoire of an organism using predictive bioinformatic tools. Once the antigenic protein or proteins have been selected, they are expressed and purified using molecular cloning and in vitro expression techniques. Following the in vitro production step, they are probed in animal models to evaluate the in vivo protective strength of the immune response. The main aim of this in vivo approach is to evaluate the ability of the immune response to eliminate or neutralize the pathogen at the time of infection. Those antigens capable of generate a specific immune response with neutralizing activity for natural infections are the best candidate vaccines. In this review we summarize the evolution of vaccinology since its inception, with special emphasis on the development of VLPs as vaccine platforms and their future in preventive medicine and we introduce a new recombinant platform for antigen presentation based on Junin virus VLPs (JUNV-VLPs).

The formal transfer of GNSS under water is not possible. It probably makes sense to talk only about the transformation of GPS into LPS, that is, in the Local Position System. However, the basic methods that are used to solve the problem of Spoofing Detection above water can be used under water. It should be understood that engineering problems are significantly different, since the nature of the propagation of acoustic waves in water and electromagnetic waves in the atmosphere are fundamentally different. In this article, we will limit the navigation with acoustically passive receiver. The receiver “listens” to the buoys and solves the problem of finding its own position based on the coordinates of the buoys (such systems are called GNSS-like Underwater Positioning Systems or GNSS-like UPS). Depending on the scale of system service areas, GNSS-like UPS are divided into global, regional, zonal and local system. In this article, we will limit ourselves to considering only local GNSS-like UPS. The acoustic signal generator transmits a signal simulation of several satellites. If the level of the simulated signal exceeds the signal strength of real satellites, the receiver of UPS will “capture” the fake signal and calculate the false position based on it.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles: spins interactions with in each sub-ensemble are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors, and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents (, , , ) gives way to the non-classical form (, , , ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions, but only shifts their critical points, allowing for control of the system’s parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau, and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model.

Paraffin wax stores energy in the form of latent heat at a nearly constant temperature during melting and releases this energy during solidification. This effect is used in industrial energy storage. An unusual change in the shape of a melted droplet of paraffin wax placed on a relatively cold glass plate is studied. As the droplet solidifies, its upper surface becomes nearly flat and a dimple is formed in the center of this surface, making the droplet look like a fruit (pumpkins are more commonly shaped like this, but the authors prefer apples). A series of experiments, as well as physical and numerical modeling of the droplet's thermal state, taking into account the formation of a mushy zone between liquidus and solidus, made it possible to understand the role of gravity and gradual increase in viscosity and density of paraffin wax on changing the droplet shape and, in particular, to clarify the mechanism of formation of the dimple on its upper.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

Tubulin superfamily (TSF) proteins are widespread and known for multifaceted roles as cytoskeletal proteins underpinning many basic cellular functions including morphogenesis, division, and motility. In eukaryotes, tubulin assembles into microtubules, a major component of the dynamic cytoskeletal network of fibres, whereas the bacterial homolog FtsZ assembles the division ring at midcell. Functions of the lesser-known archaeal TSF proteins are beginning to be identified, and show surprising diversity, including homologs of tubulin and FtsZ, and a third archaea-specific family, CetZ, implicated in the regulation of cell shape and possibly other unknown functions. In this study, we defined sequence and structural characteristics of the CetZ family and CetZ1 and CetZ2 subfamilies, identified CetZ groups and diversity amongst archaea, and identified potential functional relationships through analysis of the genomic neighbourhoods of cetZ genes. At least three subfamilies of orthologous CetZ proteins were identified in the archaeal class Halobacteria, including CetZ1 and CetZ2 and a novel uncharacterized subfamily. CetZ1 and CetZ2 were correlated to one another and to cell shape and motility phenotypes across diverse Halobacteria. Amongst other known CetZ clusters in orders Archaeoglobales, Methanomicrobiales, Methanosarcinales, and Thermococcales, an additional uncharacterized group from Archaeoglobales and Methanomicrobiales affiliated strongly with Halobacteria CetZs, suggesting they originated via horizontal transfer. Subgroups of Halobacteria CetZ2 and Thermococcales CetZ genes were found adjacent to different type IV pili regulons, suggesting a potential utilization of CetZs by type IV systems. More broadly conserved cetZ gene neighbourhoods included nucleotide and cofactor biosynthesis (e.g., F420) and predicted cell surface sugar epimerase genes. The findings imply that CetZ subfamilies are involved in multiple functions linked to the cell surface, biosynthesis and motility.

The cuttlebone-like structure is a complex porous bionic structure with asymmetric sinusoidal S-shaped wall structure connecting laminar septa, and studies have shown that the cuttlebone-like structure has light weight, high strength and excellent energy absorption capability. It has become an important research to investigate the mechanical mechanism of cuttlebone-like structure and to design a bionic structure beyond nature structure based on it. In order to investigate the mechanical properties of the static compression and shearing processes of the cuttlebone-like structure, this paper establishes theoretical formulas and analyzes the influence of dimensionless parameters such as height-to-thickness ratio $\lambda$, period-to-thickness ratio $\xi$ and amplitude to period ratio $\eta$ on the compression and shearing processes with the help of ABAQUS finite element software.The parameter sensitivity analysis method was used to compare the important influence degree of each dimensionless parameter on the mechanical properties of the structure and to determine the relative optimal parameters of the structural mechanical properties under compression and shearing. Based on the relatively optimal parameter of the cuttlebone-like structure, the cross-sectional geometry of the structure is improved to build a new cuttlebone-like structure.The experimental results showed that the new cuttlebone-like structure with revised cross-section improved the mechanical properties of the cuttlebone-like structure.The study results are of theoretical guidance to enhance the mechanical properties and geometric design of cuttlebone-like structures.

The increasing detection of infections of Trypanosoma cruzi, the etiological agent of Chagas disease, in non-endemic regions beyond Latin America has risen to be a major public health issue. With an impact in the millions of people, current treatments rely on antiquated drugs that produce severe side effects and are considered nearly ineffective for the chronic phase. The minimal progress in the development of new drugs highlights the need for advances in basic research on crucial biochemical pathways in T. cruzi to identify new targets. Here, we report on the T. cruzi presenilin-like transmembrane aspartyl enzyme, a protease of the aspartic class in a unique phylogenetic subgroup with T. vivax separate from protozoans. Computational analyses suggests it contains 9 transmembrane domains and an active site with the characteristic PALP motif of the A22 family. Multiple linear B-cell epitopes were identified by SPOT synthesis analysis with Chagasic patient sera. Two were chosen to generate rabbit antisera, whose signal was primarily localized to the flagellar pocket, intracellular vesicles and endoplasmic reticulum in parasites by whole cell immunofluorescence. The results suggest that the parasitic presenilin-like enzyme could have a role in the secretory pathway and serve as a biomarker for infections.

1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. 2) Methods: Here, we report the effects of long-term treatment with a SPM, maresin like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. 3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced astrogliosis and microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in an-ti-inflammatory Iba1+Arg-1+-M2 microglia, reduced astrogliosis-associated level of neuroin-flammatory TNF-α, inhibited phenotype switching of pro-inflammatory neurotoxic A1 astrocytes and N1 neutrophils, promoted polarization of inflammation-resolving neuroprotective A2 as-trocytes, promoted the blood–brain-barrier-associated tight-junction protein claudin-5 and de-creased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. 4) Conclusion: Long-term administration of MarL1 mit-igates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegen-eration. These findings provided the preclinical leads and mechanistic insights for the develop-ment of MarL1 into an effective modality to ameliorate AD pathogenesis.

The extended cleavage specificity of catfish granzyme-like II has been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated by using a panel of recombinant substrates. This serine protease, which has previously been isolated as cDNA from a catfish natural killer-like cell line showed a preference for alanine in the P1 position of the substrate, and for multiple basic amino acids N-terminally of the cleavage site. Using a set of recombinant substrates revealed the enzyme was most active on substrates with an alanine preceded by 3 or 4 basic amino acids in a row, but also showed activity against substrates with two basic amino acids, as well as with two basic amino acids separated by one amino acid just N-terminally of the Ala. The characteristics of this separating amino acid seemed less important, as many different amino acids were accepted in this position, except for proline. The amino acids following the basic amino acids and the P1 Ala residue also appeared to be of major importance for efficient cleavage. The most preferred P1 residue was Ala, and replacing Ala with Gly or Leu resulted in a clear reduction in the cleavage rate. A closely-related zebrafish serine protease (Zebrafish esterase-like) showed a very similar cleavage specificity, indicating an evolutionary conservation of this protease specificity among various fish species. Two catfish serine proteases, originating from NK-like cells, have now been isolated and characterized. One of them is highly specific met-ase with similar characteristics as the mammalian granzyme M. This enzyme may be involved in the induction of apoptosis in virus infected cells, with a potential target in (catfish) caspase 6. In contrast to catfish granzyme -like I, the second enzyme analysed here, doesn’t seem to have a direct counterpart in mammalian NK-cells, and its role in the immune function of catfish NK cells is therefore still not known. However, this enzyme seems to be able to cleave a number of cytoskeletal proteins indicating a separate strategy to induce apoptosis in target cells. Both of these enzymes are very interesting targets for further studies of their roles in catfish immunity, as enzymes with similar specificities have been identified also in zebrafish.

Fibroepithelial lesions (FL) of the breast, in particular Phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT, and FA. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions and EGFR amplifications may inform therapeutic decision-making.

Chitinase 3-like 1 （also known as CHI3L1 or YKL-40）is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce CHI3L1 to protect the body from exogenous pathogen as well as hostile environments, and it was thought that it has a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pro-inflammatory role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we will summarize the expression of CHI3L1 under the chronic inflammatory conditions in various disorders and would like to discuss the potential roles of CHI3L1 in those disorders on various cell types.

Teachability has been extensively studied under the context of making industrial robots to be programmable and reprogrammable. However, it is only recently that the artificial intelligence (AI) research community is accelerating the research works with the objective of making humanoid robots and many other robots to be teachable under the context of using natural languages. We human beings spend many years to learn knowledge and skills despite our extraordinary mental capabilities of being teachable with the use of natural languages. Therefore, if we would like to develop human-like robots such as humanoid robots, it is inevitable for us to face the issue of making future humanoid robots to be teachable with the use of natural languages as well. In this paper, we present the key details of a top-down design for achieving a teachable mind which consists of two major processes: the first one is the process which enables humanoid robots to gain innate mental capabilities of transforming incoming signals into meaningful crisp data, and the second one is the process which enables humanoid robots to gain innate mental capabilities of undertaking incremental and deep learning with the main focus of associating conceptual labels in a natural language to meaningful crisp data. These two processes consist of the two necessary and sufficient conditions for future humanoid robots to be teachable with the use of natural languages. In addition, this paper outlines a very likely new finding underlying human brain’s neural systems as well as the obvious mathematics underlying artificial deep neural networks. These outlines provide us the strong reason to separate the study of mind from the study of brain. Hopefully, the content discussed in this paper will help the AI research community to venture into the right direction which is to make future humanoid robots, non-humanoid robots, and many other systems to achieve human-like self-intelligence at cognitive level with the use of natural languages.