In this study, we investigated, for the first time, the effects of the spatially varying effective mass, asymmetry parameter, and well width on the electronic and optical properties of the quantum well which has an improved Rosen-Morse potential. Calculations are made within the framework of the effective mass and parabolic band approximations. We have used the diagonalization method by choosing a wave function based on the trigonometric orthonormal functions to find eigenvalues and eigenfunctions of the electron confined within the improved Rosen-Morse potential. Our results show that the position-dependence mass, asymmetry, and confinement parameters cause significant changes in the electronic and optical properties of the structure we focus on since these effects create a significant increase in electron energies and a blue shift in the absorption spectrum. The increase in energy levels enables the development of optoelectronic devices that can operate at wider wavelengths and absorb higher energy photons. This offers potential advancements in fields such as optical communication, imaging technology, and solar cells.

In this article, we delve into the intricate behavior of electronic mechanisms underlying NMR magnetic shieldings, σ, in molecules containing heavy atoms such as cadmium, platinum, and mercury. Specifically, we explore PtXn^{−2} (X = F, Cl, Br, I; n = 4, 6) and XCl2 Te2 Y2 H6 (X = Cd, Hg; Y = N, P) molecular systems. It is known that the leading electronic mechanisms responsible for the relativistic effects on σ are well characterized by the linear response with elimination of small components model (LRESC). In this study, we present results obtained from the innovative LRESC-Loc model, which offers the same outcomes as the LRESC model but employs localized molecular orbitals (LMOs) instead of canonical MOs. These LMOs provide a chemist’s representation of atomic core, lone pairs, and bonds. The whole set of electronic mechanisms responsible of the relativistic effects can be expressed in terms of both non-ligand-dependent and ligand-dependent contributions. We elucidate the electronic origins of trends and behaviors exhibited by these di- verse mechanisms in the aforementioned molecular systems. In PtX4^{−2} molecules, the predominant relativistic mechanism is the well-established one-body spin-orbit (σ^SO(1) ) mechanism, while the paramagnetic mass-velocity (σ^Mv ) and Darwin (σ^Dw ) contributing mechanisms also demand con- sideration. However, in PtX6−2 molecules, the σ Mv+ Dw contribution surpasses that of the SO(1) mechanism, thus influencing the overall ligand-dependent contributions. As for complexes con- taining Cd and Hg, the ligand-dependent contributions exhibit similar magnitudes when nitrogen is substituted with phosphorus. The only discrepancy arises from the σ^SO(1) contribution, which changes sign between the two molecules due to the contribution of bond orbitals between the metal and tellurium atoms.

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

River valley bottoms have hydrological, geomorphological, and ecological importance and are buffers for protecting the river from upland nutrient loading coming from agriculture and other sources. They are relatively flat, low-lying areas of the terrain that are adjacent to the river and bound by increasing slopes at the transition to the uplands. These areas have under natural conditions, a groundwater table close to the soil surface. The objective of this paper is to present a stepwise GIS approach for the delineation of river valley bottom within drainage basins and use it to perform a national delineation. We developed a tool that applies a concept called cost distance accumulation with spatial data inputs consisting a river network and slope derived from a digital elevation model. We then used wetlands adjacent to rivers as a guide finding the river valley bottom boundary from the cost distance accumulation. We present results from our tool for the whole country of Denmark carrying out a validation within three selected areas. The results reveal that the tool visually performs well and delineates both confined and unconfined river valleys within the same drainage basin. We use the most common forms of wetlands (meadow and marsh) in Denmark's river valleys known as Groundwater Dependent Ecosystems (GDE) to validate our river valley bottom delineated areas. Our delineation picks about half to two-thirds of these GDE. However, we expected this since farmers have reclaimed Denmark's low-lying areas during the last 200 years before the first map of GDE was created. Our tool can be used as a management tool, since it can delineate an area that has been the focus of management actions to protect waterways from upland nutrient pollution.

Transfusion dependent thalassemia (TDT) patients are treated with continued blood transfusions and show a higher prevalence of depression. TDT with consequent iron overload and inflammation is associated with increased severity of depressive symptoms in TDT children.Aim of the study: To construct a pathway-phenotype which combines iron overload and neuro-immune biomarkers with depressive symptom subdomains in TDT children.Methods: We measured iron status parameters (iron, ferritin, transferrin saturation percentage) and inflammatory (interleukin-1β and tumour necrosis factor-α) biomarkers in TDT (n=111) and healthy (n=53) children and analyzed the results using machine learning.Results: Cluster analysis separated TDT children with depression from those without depression and revealed two depressive subgroups one with low self-esteem and another with increased social-irritability scores. Exploratory factor analysis validated four depressive symptom dimensions as reliable constructs, namely key depressive, physiosomatic, lowered self-esteem and social-irritability dimensions. Partial Least Squares showed that 73.0% of the variance in a latent vector extracted from those four clinical subdomains, immune-inflammatory and iron overload biomarkers was explained by exposure variables including the number of blood transfusions and hospitalizations and use of deferoxamine. The exposure data, iron and immune biomarkers, and symptom subdomains are reflective manifestations of a single latent trait, which shows internal consistency reliability and predictive relevance.Conclusions: The nomological network combining exposure, pathways and behavioral phenome manifestations provides an index of overall severity and disease risk and, therefore, constitutes a new drug target, indicating that iron overload and immune activation should be targeted to treat depression due to TDT.

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer.

Circular RNAs (circRNAs) are covalently closed RNAs that are present in all eukaryotes tested. CircRNAs are less abundantly expressed than mRNAs. Recent RNAseq analyses indicate that more than 800,000 circRNA isoforms exist in humans, which is more than twice the number of currently known mRNA isoforms. CircRNAs are generated through backsplicing that depends on pre-mRNA structures, which are influenced by intronic elements, for example primate-specific Alu elements, leading to species-specific circRNAs. CircRNAs are mostly cytosolic, stable and influence cells by sequestering miRNAs and RNA-binding proteins. We review the increasing evidence that circRNAs are translated into proteins using several cap-independent translational mechanisms, that include internal ribosomal entry sites, N6-methyladenosine RNA modification, adenosine to inosine RNA editing and interaction with the eIF4A3 component of the exon junction complex. CircRNA are translated under conditions that favor cap-independent translation, notably in cancer. CircRNA-encoded proteins are shorter than mRNA-encoded proteins and overall have a high propensity for phase separation. In summary, circRNA encoded proteins are translated under particular cellular conditions and contribute to proteome diversity and pathophysiology.

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the USFDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. The article explores various vaccine candidates, including live attenuated, killed, nucleic-acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines emerge as promising candidates due to their rapid response capabilities and enhanced safety profile. The review underscores the importance of E1 and E2 proteins as immunogens, emphasising their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical study results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates.

The exogenous application of phenolic compounds is increasingly recognized as a valuable strategy for promoting growth and mitigating the adverse effects of abiotic stress. However, the biostimulant effect under optimal conditions have not been thoroughly explored. In this study, we investigated the impact of foliar application of flavonoids, specifically Crop Bio Life (CBL), on tomato plants grown under controlled conditions. Our study focused on determining growth parameters, such as cell size, and assessing the concentration of hormones. Principal component analysis (PCA) from all physiological variables were determined. Additionally, we utilized high-throughput mRNA sequencing technology and bioinformatic methodologies to robustly analyze the transcriptomes of tomato leaves regulated by flavonoids. The findings revealed that CBL primarily influenced cells enlargement, leading to increased growth. Furthermore, CBL-treated plants exhibited higher concentrations of the hormone zeatin but lower concentrations of IAA. Moreover, RNAseq analysis indicated that CBL-treated plants required increased mineral transport and water uptake, as evidenced by gene expression patterns. Genes related to pathways such as fatty acid degradation, phenylpropanoid biosynthesis, and ABC transporters showed regulatory mechanisms governing internal flavonoid biosynthesis, transport, and tissue concentration, ultimately resulting in higher flavonoid concentrations in tomato leaves.

The Arbas cashmere goat is a unique biological resource that plays a vital role in livestock husbandry in China. LCDM is a medium with special small molecules (consisting of human LIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride) for generation pluripotent stem cells (PSCs) with bidirectional developmental potential in mice, humans, pigs, and bovines. However, there is no report on whether LCDM can support for generation of PSCs with the same ability in Arbas cashmere goats. In this study, we applied LCDM to generation goat induced PSCs (giPSCs) from goat fetal fibroblasts (GFFs) by reprogramming. The derived giPSCs exhibited stem cell morphology, expressing pluripotent markers, and could differentiate into three germ layers. Moreover, the giPSCs differentiated into the trophectoderm lineage by spontaneous and directed differentiation in vitro. The giPSCs contributed to embryonic and extraembryonic tissue in preimplantation blastocysts and postimplantation chimeric embryos. RNA-sequencing analysis showed that the giPSCs were very close to goat embryos at the blastocyst stage and giPSCs have similar properties to typical extended PSCs (EPSCs). The establishment of giPSCs with LCDM provides a new way to generate high quality of PSCs from domestic animals and lays the foundation for basic and applied research in biology and agriculture.

The deadliest disease in the world, cancer, kills many people every year. The early detection is the only hope for the survival of malignant cancer patients. As a result, in the preliminary stages of , the diagnosis of cancer biomarkers at the cellular level is critical for improving cancer patient survival rates. For decades, scientists have focused their efforts on the invention of biosensors. Biosensors, in addition to being employed in other practical scenarios, can essentially function as cost effective and highly efficient devices for this purpose. Traditional cancer screening procedures are expensive, time-consuming, and inconvenient for repeat screenings. Biomarker-based cancer diagnosis, on the other hand, is rising as one of the most potential tools for early detection, disease progression monitoring, and eventual cancer treatment. As Biosensor is an analytical device, it allows the selected analyte to bind to the biomolecules being studied (– for example RNA, DNA, tissue, proteins, cells). They can be divided based on the kind of biorecognition or transducer elements on the sensor. Most biosensor analyses necessitate the analyte being labeled with a specific marker. In this review article, the application of distinct variants of biosensors against cancer has been described.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, in culture, in infected mammalian cells and in patients. Among these noncoding RNAs are both small RNAs (sRNAs) between 50-350 nts in length and smaller RNAs (sncRNA) <50 nts. In this review, we provide an up-to-date synopsis of the identification, designation, and function of these Mtb-encoded sRNAs and sncRNAs. The methodological advances including RNA sequencing strategies, small RNA antagonists and locked nucleic acid sequence specific RNA probes advancing the studies on these small RNA are described. Initial insights into the regulation of the small RNA expression and putative processing enzymes required for their synthesis and function are discussed. There are many open questions remaining about the biological and pathogenic roles of these small non-coding RNAs, and potential research directions needed to define the role of these mycobacterial noncoding RNAs summarized.

Despite several decades of research, the physics underlying translation – protein synthesis at the ribosome – remains poorly studied. For instance, the mechanism coordinating various events occurring in distant parts of the ribosome is unknown. Very recently, we have suggested that this allosteric mechanism could be based on the transport of electric charges (electron holes) along RNA molecules and localization of these charges in the functionally important areas; this assumption was justified using tRNA as an example. In this study, we turn to the ribosome and show computationally that holes can also efficiently migrate within the whole ribosomal small subunit (SSU). The potential sites of charge localization in SSU are revealed, and it is shown that most of them are located in the functionally important areas of the ribosome – intersubunit bridges, Fe4S4 cluster and the pivot linking the SSU head to the body. As a result, we suppose that hole localization within the SSU can affect intersubunit rotation (ratcheting) and SSU head swiveling, in agreement with the scenario of electronic coordination of ribosome operation. We anticipate that our findings will improve the understanding of the translation process and advance the molecular biology and medicine.

Alphaviruses are positive-sense RNA arboviruses that are capable of causing severe disease in otherwise healthy individuals. There are many aspects of viral infection that determine pathogenesis and major efforts regarding the identification and characterization of virulence determinants have largely focused on the roles of the nonstructural and structural proteins. Nonetheless, the viral RNAs of the alphaviruses themselves play important roles in regard to virulence and pathogenesis. In particular, many sequences and secondary structures within the viral RNAs play an important part in the development of disease and may be considered important determinants of virulence. In this review article, we summarize the known RNA-based virulence traits and host:RNA interactions that influence alphaviral pathogenesis for each of the viral RNA species produced during infection. Overall, the viral RNAs produced during infection are important contributors to alphaviral pathogenesis and more research is needed to fully understand how each RNA species impacts the host response to infection as well as the development of disease.

Kiwifruit vines are generally sensitive to waterlogging stress. So far, molecular responses of different kiwifruit genotypes for waterlogging stress are less well-explored. In this study, using RNA-sequencing, we examined transcriptional regulation in the roots of a waterlogging-tolerant genotype KR5 (Actinidia valvata), and a sensitive genotype ‘Hayward’ (Actinidia deliciosa) subjected to 0, 12, 24, and 72 h of waterlogging. Compared with 0 h, transcriptional adjustments of these two genotypes occurred as early as 12 h and became notably pronounced 72 h after waterlogging. Waterlogging stress for 72 h promoted the expression of genes involved in ethylene biosynthesis, sucrose and hexose transport, anaerobic fermentation, nitrate reduction, alanine accumulation, and reactive oxygen scavenging in both genotypes. The differential regulation of genes encoding 9-cis-epoxycarotenoid dioxygenase, phosphoglucomutase, alanine-glyoxylate transaminase, and other enzymes pointed to their diverse strategies upon waterlogging in these two genotypes. In addition, more sucrose and trehalose contents, as well as a higher activity of alcohol dehydrogenase and manganese superoxide dismutases were stimulated in KR5 roots after 72h of waterlogging than that in ‘Hayward’. Overall, our results provided more insights into the molecular basis of the waterlogging response in kiwifruit.

The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made on complex multicellular organisms, and then modified to fit a DNA-centric view. In this article, I argue that, based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that: i) natural selection plays a dominant role in evolution, and ii) the probability of mutations is independent of the generated phenotype. I will show that the adaptation of a phenotype to an environment does not correspond to organism fitness but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome, and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype, the phenotype ensuring the stability of the genotype in a cellular and environment physicochemical parameter-depending manner.

A model of the early RNA world is proposed. Nearly self-complementary sequences that could adopt double-stranded, smallhairpin-like (shRNA), structures would be selected for due to their greater hydrolytic stability. These would be phosphorylated attheir 5' ends. We suppose that dehydrating conditions arise (perhaps intermittently) in the early environment allowing amino acidsto condense with these RNA molecules. The resulting phosphate-amino acid anhydrides would play the role of early, charged,tRNAs. A crude genetic code could emerge owing to the greater resistance of some amino acid-shRNA pairings to hydrolysisrelative to others. Early on there is no division of labor between mRNAs and tRNAs; the same molecules perform both functions.But the first systems would have encoded little in the way of protein sequence information. Rather they would have served as catalysts for the random polymerization of amino acids. It is speculated that the selective advantage inhering in such systems lay intheir ability to supply raw materials for the formation of coacervates within which the various molecules essential to proto-lifecould be concentrated. This would greatly facilitate the necessary chemistries. The evolution of homochiral protein and RNA populations is discussed. An appealing feature of this model is its ability to explain the transition from phosphorylated amino acids to the 3' ester-linked aminoacyl-tRNAs employed by modern life.

Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally de-fined coronaviral enhancers, we detected via in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian IBV to the recently emerged SARS-CoV-2. These potential enhancers possess a core duplex-forming region that could transition between closed and open states, as molecular switches directed by viral or host factors. The open state would permit the enhancer to pair with remote sequences in the viral genome and modulate the expression of crucial genes involved in viral replication and host immune evasion. Consistently, variations in the predicted IBV enhancer region or its distant targets coincide with cases of viral attenuation possibly driven by decreased expression of the ORF3a immune evasion protein. The annotated enhancer sequences could inform structural prediction tools and antiviral interventions if validated experimentally.

The present contribution introduces the task dependent comfort zone as a base placement strategy for mobile manipulators using different manipulability measures. Four different manipulability measures depending on end-effector velocities, forces, stiffness, and accelerations are considered. By evaluating a discrete subspace of the manipulator workspace with these manipulability measures and by using image processing algorithms, a suitable goal position for the autonomous mobile manipulator was defined within the comfort zone. This always ensures a certain manipulator manipulablity value with a lower limit in respect to the maximum possible manipulability in the discrete subspace. Results are shown for three different mobile manipulators using the velocity dependent manipulability measure in a simulation.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

The current work reveals the fine tuning between stability zones and randomness of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing D/M/1 system. More specifically, this clearly provides more insights into developing a contemporary PSFFA theory that unifies non-stationary queueing theory with chaos theory and fields in both theoretical physics and chaotic systems. This opens new grounds for stability analysis of non-stationary queueing systems.

In this essay, I revisit Neural Networks (NNs) through the lens of evolutionary dynamics. From the two most important features of NNs, I recover the two most general equations of evolutionary dynamics. These two equations may thus serve as a connection between NNs and a body of knowledge that has been built over multiple centuries and has found application across a vast range of disciplines. This connection may therefore also help explain why NNs with the two features in question are applicable across a much broader range of domains than initially envisioned.

Chromium poisoning strongly influences the performance of solid oxide fuel cell (SOFC) stacks. A three-dimensional, time-dependent, computational fluid dynamics model of a single channel of a F10 SOFC stack in Forschungszentrum Jülich GmbH is developed to investigate chromium poisoning for different stack designs, temperatures and absolute air humidities. The model takes into account both chemical and electrochemical mechanisms of chromium poisoning and is able to predict the spatial distribution of SrCrO4 and Cr2O3. The voltage degradation over 100 kh can be simulated quantitatively. According to the simulation results, chromium poisoning is almost eliminated by the application of the protective coating fabricated by the atmospheric plasma-spraying (APS) technology. Besides, with the help of the APS protective coating, operating a SOFC stack with less dehumidified air at 650 oC is possible according to the simulation.

Many studies on magnetorheological fluid (MRF) have been carried out over last three decades several salient advantages such as fast phase change, easy control of the yield stress and so forth. Especially, several review articles of MRF technology have been reported for last two decades summarizing the development of MRFs and their applications. As specific examples, the review articles including the optimization of the particles and carrier liquid to achieve minimum off-state viscosity and maximum yield stress at on-state, the formulation of many constitutive models in-cluding Casson model and Herschel-Bulkley (H-B) model, the sedimentation enhancement using additives and nanosized particles, many types of dampers for automotive suspension and civil structures, medical and rehabilitation devices, MRF polishing technology, the methods of mag-netic circuit design, and the synthesis of various controllers have been published. More recently, the effect of the temperature and thermal conductivity on the properties of MRFs and application systems are actively being investigated by several works. However, there is no review article on this issue so far despite of that the thermal problem is one of crucial factors to be seriously con-sidered for the development of advanced MRFs and commercial products of application systems. In this work, studies on the thermal conductivity and temperature in MRFs themselves and tem-perature-dependent application systems are reviewed, respectively, and principal results are summarized emphasizing on the followings: how to reduce the temperature effect on the field-dependent properties of MRFs and how to design application system to minimize the thermal effect. It is noted here that the review summary is organized in a chronological format using tables.

In this paper, we examine the mathematical and physical consistencies of the three primary couple stress theories: original Mindlin-Tiersten-Koiter couple stress theory (MTK-CST), modified couple stress theory (M-CST) and consistent couple stress theory (C-CST). As has been known for many years, MTK-CST suffers from some fundamental inconsistencies, such as the indeterminacy of the couple-stress tensor. Therefore, despite the fact that MTK-CST has a fundamental position in the evolution of size-dependent continuum mechanics, it is not a reliable theory within continuum mechanics, for example, in developing new size-dependent multi-physics formulations. We also observe that M-CST not only inherits all inconsistences from the original MTK-CST, but also suffers from new additional inconsistencies, such as the introduction of a new non-physical governing equation. These inconsistencies refute the claim of those who state that the couple-stress tensor may be chosen symmetric. Therefore, the apparent success of MTK-CST and M-CST in describing a size-effect for some problems, such as two-dimensional plate and beam bending, is not enough to justify these theories as suitable for general cases. In fact, the symmetric couple-stresses in M-CST create torsional or anticlastic deformation, not bending. On the other hand, C-CST, with a skew-symmetric couple-stress tensor, is the consistent continuum mechanics suitable for solving different size-dependent solid, fluid and multi-physics problems.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

Brain plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions of genetic and environmental influences, and structure-functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Herein, we review brain plasticity association with non-coding RNAs (ncRNAs). Studies on brain plasticity have important practical implications. Numerous cerebral ncRNAs are linked with neurological disorders, which makes them putative targets for RNA-based diagnostics and therapeutics since molecular characteristics of brain plastic change may reveal disease course and rehabilitative potential of the patient. A new insight into the concept of brain plasticity will provide perspectives on functional recovery following brain damage. The knowledge of this phenomenon will enable physicians to exploit cerebral plastic potential and regulate eloquent networks with timely interventions. Future studies will provide pathophysiologic mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve the quality of life in neurological disorders.

Mulberries is a type of fruit tree that is rich in nutrients and possesses both medicinal and dietary properties, deeply loved by consumers. The fragrance is a significant factor in the sensory quality of mulberries, playing a crucial role in consumer purchasing behavior. 'Baichang' mulberry is a unique variety of mulberry that emits a strong, creamy-like fragrance, which has enormous potential market value. However, the key metabolites and mechanisms responsible for the formation of this fragrance are still unclear. In this study, we utilized GC-MS technology and RNA-seq to examine the Volatile Organic Compounds (VOCs) and gene expression in 'Baichang' (Morus macroura) mulberries and 'Hongchang' (Morus laevigata) mulberries, the latter of which do not have a distinct fragrance. The results showed that 661 volatile metabolites were detected in both mulberry varieties. Most of these were found in higher relative amounts in the 'Baichang' mulberry variety, with 47 types being present only in the 'Baichang' mulberries, suggesting a rich composition of VOCs in the 'Baichang' mulberry. 312 metabolites were identified as differential metabolites; combining the sensory annotation information and relative content of VOCs, 70 candidate VOCs were annotated as related to the formation of 'sweet, waxy, coconut, and oily' sensations. They could potentially be the key metabolites contributing to the unique aroma of 'Baichang' mulberries. The relative odor activity value (rOAV) analysis revealed that 2(3H)-Furanone, 5-hexyldihydro- was the key VOC contributing to the formation of the special aroma of 'Baichang' mulberries. By RNA-seq, 19 key structural genes related to ester synthesis were identified, including AAT , ACX , ALDH, CYP, EHL, FAD, HPL, and LOX. The high expression of these structural genes in the "Baichang" mulberry fruit is the main reason for its unique creamy aroma. This study provides insights into the aroma differences among different kinds of mulberrie.

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and the most common form of head and neck cancer, posing significant challenges for disease management. Single-cell RNA sequencing (sc-RNAseq) has emerged as a valuable tool for addressing these challenges by enabling detailed characterization of the tumor microenvironment (TME) at the cellular level. This review assesses the utility of sc-RNAseq in HNSCC research, compiling current strategies employing single-cell technologies. For HNSCC etiology, sc-RNAseq allows for the construction of cellular atlases, characterization of different cell types, and investigation of key genes and processes involved in cancer initiation, development, and progression within the TME. In terms of HNSCC diagnosis and prognosis, the high resolution offered by sc-RNAseq enables the identification of cell type-specific signatures, enhancing prognostic models and disease stratifiers for more accurate patient outcome assessments. Regarding HNSCC treatment, sc-RNAseq provides insights into cellular responses to various treatments, including radiotherapy, chemotherapy, and immunotherapy, contributing to improved patient stratification and personalized treatment strategies. This review highlights the unique contributions of sc-RNAseq to HNSCC research, addressing its cellular and biological complexity, and emphasizes its potential for advancing research and clinical practice in other cancer types.

In virology, the term reverse genetics refers to a set of methodologies in which changes are introduced into the viral genome and their effects on the generation of infectious viral progeny and their phenotypic features are assessed. Reverse genetics emerged thanks to advances in recombinant DNA technology, which made the isolation, cloning, and modification of genes through mutagenesis possible. Most virus reverse genetics studies depend on our capacity to rescue an infectious wild-type virus progeny from cell cultures transfected with an “infectious clone”. This infectious clone generally consists of a circular DNA plasmid containing a functional copy of the full-length viral genome, under the control of an appropriate polymerase promoter. For most DNA viruses, reverse genetics systems are very straightforward, since DNA virus genomes are relatively easy to handle and modify and are also (with few notable exceptions) infectious per se. This is not true for RNA viruses, whose genomes need to be reverse transcribed into cDNA before any modification can be done. Establishing reverse genetics systems for members of the Caliciviridae has proven exceptionally challenging, due to the low number of members of this family that propagate in cell culture. Despite the early successful rescue of a calicivirus from a genome-length cDNA more than two decades ago, reverse genetics methods are not routine procedures that can be easily extrapolated to other members of the family. Reports of calicivirus reverse genetics systems have been few and far between. In this review, we discuss the main pitfalls, failures, and delays behind the generation of several successful calicivirus infectious clones.

This study explored the effects of pBD114 (porcine β-defensin 114) on inflammatory response. The results in RAW264.7 cells showed that 100 μg/mL of pBD114 significantly increased the concentrations of TNFα and IL-10, and 10 μg/mL of pBD114 significantly decreased the concen-tration of TNFα in LPS-induced RAW264.7 cell cultures at 10 ng/mL. These results suggest that pBD114 can exhibit pro-inflammatory or anti-inflammatory activities under certain conditions. RNA-seq analysis was performed to gain further insight into the effects of pBD114 on the in-flammatory response. Among pBD114 promoting RAW264.7 pro-inflammatory response, pBD114 significantly up-regulated 1170 genes and down-regulated 724 genes. KEGG enrichment found that the DEGs were significantly enriched in immune- and signal-transduction-related signaling pathways. PPI and KDA analyses revealed that Bcl10 and Bcl3 were the key genes. In addition, pBD114 significantly up-regulated 12 genes and down-regulated 38 genes in the an-ti-inflammatory response. KEGG enrichment analysis revealed that the DEGs were mainly en-riched in the "Cytokine-cytokine receptor interaction" signaling pathway, and PPI and KDA analyses showed that Stat1 and Csf2 were the key genes. The results of qRT-PCR verified those of RNA-seq. In vivo mice tests also confirmed the pro- or anti-inflammatory activity of pBD114. Although the inflammatory response is a rapid and complex physiological reaction to noxious stimuli, this study found that pBD114 plays an essential role in the inflammatory response mainly by acting on genes related to immunity, signal transduction, signaling molecules, and interactions.

Cervical cancer presents a significant global health concern with high-risk human papilloma-viruses (HPVs) being identified as the cause of this cancer. Although current treatment methods for cervical cancer can eliminate lesions, preventing metastatic spread and minimizing tissue damage remains a major challenge. Therefore, the development of a safer and innovative thera-peutic approach is of utmost importance. Natural products like Fig latex, derived from the Ficus Carica tree, have demonstrated promising anti-cancer properties when tested on cervical cancer cell lines. However, the specific mechanisms by which Fig latex exerts its effects are still un-known. In this study, we conducted RNA-seq analysis to explore how Fig latex may counteract carcinogenesis in HPV-positive cervical cancer cell lines, namely CaSki (HPV type 16-positive) and HeLa (HPV type 18-positive). Our data from this investigation indicates that Fig latex influ-ences the expression of genes associated with the development and progression of cervical can-cer, including pathways related to " Nonsense-Mediated Decay (NMD) "cell cycle regulation" and Transcriptional Regulation by TP53. This selective impact of Fig latex on cancer-related pathways suggests a potential novel therapeutic approach for HPV-related cervical cancer.

Alternative splicing can produce transcripts that affect cancer development and shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been less systematically studied in cancer biology research. Here, we generated a pan-cancer IR landscape for more than 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). We characterized differentially retained introns between tumor and normal samples and identified retained introns associated with survival. We discovered 988 differentially retained introns in 14 cancers, some of which demonstrated diagnostic potential in multiple cancer types. We also inferred a large number of prognosis-related introns in 33 cancer types, and the associated genes included well-known cancer hallmarks such as angiogenesis, metastasis, and DNA mutations. Notably, we discovered a novel intron retention event inside 5′UTR of STN1 that is associated with the survival of lung cancer patients. The retained intron reduces translation efficiency by producing upstream open reading frames (uORFs) and thereby inhibits colony formation and cell migration of lung cancer cells. Besides, the IR-based prognostic model achieved good stratification on certain cancers, as illustrated in acute myeloid leukemia. Taken together, we performed a comprehensive IR survey at a pan-cancer level, and the results implied that IR has the potential to be diagnostic and prognostic cancer biomarkers, as well as new drug targets.

Henipaviruses are single-stranded RNA viruses that have been shown to be virulent in several species including humans, pigs, horses, and rodents. Isolated nearly 30 years ago, these viruses have been shown to be of particular concern to public health, as at least two members (Nipah and Hendra viruses) are highly virulent, as well as zoonotic, and are thus classified as BSL4 pathogens. Although only 5 members of this genus have been isolated and characterized, metagenomics analysis using animal fluids and tissues has demonstrated the existence of other novel henipaviruses, suggesting a far greater degree of phylogenetic diversity than currently known. Using a variety of molecular biology techniques, it has been shown that these viruses exhibit varying degrees of tropism, on a species, organ/tissue, and cellular level. This review will attempt to provide a general overview of our current understanding of henipaviruses, with particular emphasis on viral tropism.

The transcriptomic analysis of the dehydration rate of mature rice seeds was conducted to explore candidate genes related to the dehydration rate and provide a theoretical basis for breeding and utilization. In this study, we selected Baghlani Nangarhar, an extremely fast dehydration material, and Saturn, a slow dehydration material, based on the results of the previous studies of screening of 165 germplasm materials for dehydration rate phenotypes. Fast dehydration experiment on these two types of seeds was conducted. Four comparative groups were set up under control and dehydration conditions. The differentially expressed genes (DEGs) were quantified by transcriptome sequencing and quantitative real-time PCR (qRT-PCR). GO and KEGG analyses were carried out. The results showed that in Baghlani Nangarhar, 53 DEGs were screened, of which 33 were up-regulated and 20 were down-regulated. Similarly, in Saturn, 25 DEGs were screened, of which 19 were up-regulated and 6 down-regulated. The results of the GO analysis showed that the sites of action of the differentially expressed genes enriched in the fast dehydration modes were concentrated in the cytoplasm, internal components of the membrane and nucleosomes. They play regulatory roles in catalysis, binding, translocation, transcription, protein folding, degradation and replication. They are involved in adaptive responses to adverse external environments such as reactive oxygen species and high temperature. The KEGG analysis showed that the main metabolic pathways enriched are protein processing in the endoplasmic reticulum, amino acid biosynthesis, and oxidative phosphorylation. The key differentially expressed genes and the most important metabolic pathways in the rapidly and slowly dehydrated materials obtained in this study were protein processing in the endoplasmic reticulum and oxidative phosphorylation metabolism, which are presumed to have important regulatory roles in stress/defense, energy metabolism, protein synthesis/folding, and signal transduction during dehydration and drying of mature seeds. The results of this study could potentially provide a valuable reference for further research on the genes and metabolic pathways related to the dehydration rate of mature rice seeds and provide theoretical guidance for the selection and breeding of new rice germplasm that can be rapidly dehydrated at the mature stage.

Caseous lymphadenitis (CL) is a chronic contagious disease that affects small ruminants and is characterized by the formation of pyogranulomas in lymph nodes and other organs. However, the pathogenesis of this disease and the response of the host genome to infection are not yet fully understood. This study aimed to investigate the whole blood transcriptome and evaluate differential gene expression during the later stages of CL in naturally infected ewes. The study included diseased, serologically positive (EP), exposed, serologically negative (EN) ewes from the same infected flock and healthy ewes (CN) from a different flock. RNA sequencing was performed using the Illumina NextSeq system, and differential gene expression was estimated using DESeq2 and Edge R approaches. The analysis identified 191 annotated differentially expressed genes (DEGs) in the EP group (102 upregulated and 89 downregulated) and 256 DEGs in the EN group (106 upregulated and 150 downregulated). Infection influenced numerous immunoregulatory interactions between lymphoid and nonlymphoid cells in both EP and EN ewes. Immune DEGs were preferentially assigned to antigen presentation through the MHC complex, T-lymphocyte mediated immunity, and extracellular matrix interactions. Furthermore, the EP group showed altered regulation of cytokine and chemokine signalling and activation and recombination of B-cell receptors. Conversely, NF-kappa B signalling, apoptosis, and stress response were the main processes influenced in the EN group. In addition, statistically significant enrichment of the essential immune pathways of Binding and Uptake of Ligands by Scavenger Receptors in EP and p53 signalling in the EN group was found. In conclusion, this study provides new insights into the disease course and host‒pathogen interaction in naturally CL-infected sheep by investigating the blood transcriptome.

Brown-marbled grouper is one of the most important mariculture species in China, which is used as an important crossbreeding parent in grouper industry. Enhancing growth rates is a key target in fish breeding, and gaining insight into the underlying mechanisms responsible for growth differences among individuals can aid in the improvement of grouper growth rates. However, the mechanism behind this difference in growth in this fish is unclear. The difference of transcriptome profiles of muscle tissue between fast- and slow-growing brown-marbled grouper was analyzed by RNA-Seq. 77 significantly up-regulated genes and 92 significantly down-regulated genes were identified in the growth extreme groups. The up-regulated of ghr and tnni2 and the down-regulated of stc2 led to the growth advantages of brown-marbled grouper. The differently expressed genes (DEGs) were used for GO and KEGG enrichment analysis. The results of GO enrichments indicated that the significantly upregulated genes in the fast-growing group were involved in protein folding, actin cytoskeleton, myosin complex, etc. The results of KEGG enrichments indicated that the significantly upregulated genes in the fast-growing group were involved in glycolysis/ gluconeogenesis, adipocytokine signaling pathway, MAPK signaling pathway, carbon metabolism, PI3K-Akt signaling pathway, etc. To analysis the difference gene sets between fast- and slow-growing group, the RNA-seq data were used by gene set enrichment analysis (GSEA). The results showed that the PI3K/AKT/mTOR pathway was up-regulated in the fast-growing group. The up-regulated of this pathway could lead to higher nutrient absorption efficiency and lead to muscle growth in the fast-growing group. These results contribute to understanding of the molecular mechanisms of fast growth and regulative pathways regulating growth in brown-marbled grouper.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. Dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA Binding Motif Single Stranded Interacting Protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. The RBMS1 polymorphism has been shown to be associated with obesity and Type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.

Research Highlights: This study identified the cell cycle genes in birch that likely play important roles during plant growth and development. This analysis provides a basis for understanding the regulatory mechanism of various cell cycles in Betula pendula. Background and Objectives: The cell cycle factors not only influence cell cycle progression together, but also regulate accretion, division and differentiation of cells, and then regulate growth and development of plant. In this study, we identified the putative cell cycle genes in B. pendula genome, based on the annotated cell cycle genes in A. thaliana. It could serve as a foundation for further functional studies. Materials and Methods: The transcript abundance was determined for all the cell cycle genes in xylem, root, leaf and flower tissues using RNA-seq technology. Results: We identified 59 cell cycle gene models in the genome of B. pendula, 17 highly expression genes among them. These genes were BpCDKA.1, BpCDKB1.1, BpCDKB2.1, BpCKS1.2, BpCYCB1.1, BpCYCB1.2, BpCYCB2.1, BpCYCD3.1, BpCYCD3.5, BpDEL1, BpDpa2, BpE2Fa, BpE2Fb, BpKRP1, BpKRP2, BpRb1 and BpWEE1. Conclusions: We identified 17 core cell cycle genes in the genome of birch by combining phylogenetic analysis and tissue specific expression data.

The physics–biology continuum relies on the fact that life emerged from prebiotic molecules. Here, I argue that life emerged from the physical coupling between the synthesis of nucleic acids and the synthesis of amino acid polymers. Owing to this physical coupling, amino acid polymers (or proto-phenotypes) maintained the physicochemical parameter equilibria (proto-homeostasis) in the immediate environment of their encoding nucleic acids (or proto-genomes). This protected the proto-genome physicochemical integrity (i.e., atomic composition) from environmental physicochemical stresses, and therefore increased the probability of reproducing the proto-genome without variation. From there, genomes evolved depending on the biological activities they generated in response to environmental fluctuations. Thus, a genome generating an internal environment whose physicochemical parameters guarantee homeostasis and genome integrity has a higher probability to be reproduced without variation and therefore to reproduce the same phenotype in offspring. Otherwise, the genome is modified by the imbalances of the internal physicochemical parameters it generates, until new emerging biological activities maintain homeostasis. In sum, evolution depends on feedforward and feedback loops between genome and phenotype, since the internal physicochemical conditions that a genome generates in response to environmental fluctuations in turn either guarantee the stability or direct the variation of the genome.

More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m⁷G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m⁷G modification occurs at position 46 in the variable region and is a product of tRNA (m⁷G46) methyltransferase. The m⁷G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. Recently, we have proposed a reaction mechanism for eubacterial tRNA m⁷G methyltransferase (TrmB) based on the results of biochemical studies and previous biochemical, bioinformatic, and structural studies by others. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m⁷G46 in tRNA have started to be determined over the past decade. To be able to better respond to diseases and infections in which the m⁷G modification is considered to be involved, it is still necessary to further understand the catalytic mechanism of AdoMet and/or the tRNA bound form of m⁷G methyltransferases. In this review, information of tRNA m⁷G modifications and tRNA m⁷G methyltransferases are summarized and the differences in reaction mechanism between tRNA m⁷G methyltransferase and rRNA or mRNA m⁷G methylation enzyme are discussed.

Alfalfa, an important legume forage, is an ideal crop for sustainable agriculture and a potential bioenergy plant. Drought, one of the most common environmental stresses, substantially affects plants’ growth, development and productivity. MicroRNAs (miRNAs) are newly discovered gene expression regulators that have been linked to several plant stress responses. To elucidate the role of miRNAs in drought stress regulation of alfalfa, a high-throughput sequencing approach was used to analyze 12 small RNA libraries comprising of 4 samples, each with 3 biological replicates. We identified 348 known miRNAs, belonging to 80 miRNA families, from the 12 libraries and 281 novel miRNAs using Mireap software. 18 known miRNAs in roots and 12 known miRNAs in leaves were screened out as drought-responsive miRNAs. Except for miR319d and miR157a which were upregulated under drought stress, the expression pattern of drought-responsive miRNAs were different between roots and leaves in alfalfa. This is the first study discovering miR157a, miR1507, miR3512, miR3630, miR5213, miR5294, miR5368 and miR6173 are drought-responsive miRNAs. Target transcripts of drought-responsive miRNAs were computationally predicted. All 447 target genes for the known miRNAs were predicted using an online tool. This study provides a significant insight on understanding drought-responsive mechanisms of alfalfa.

According to the International Agency for Research on Cancer (IARC) of the World Health Organization (data of year 2020), Breast Cancer (BC) is one of the most common cancer types worldwide, with large geographical variations occurring between countries and world regions and highest incidence rates in countries that have undergone economic transition. The risk factors for BC include women ageing, genetic mutations, reproductive history, dense breast tissues, personal history of BC or specific non-cancerous breast diseases, family history of breast or ovarian cancer, previous treatment using radiation therapy, and exposure to hormone-like drugs such as diethylstilbestrol (DES). Additional risk factors include being overweight or having obesity after menopause, and taking hormones. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. In the last years, the knowledge about miRNAs role in BC has significantly improved, and complex interactions among coding and non-coding RNA has been elucidated. In this context, an increasing number of papers had been published regarding the role of miR-125 in BC. In this review, we summarize the state-of-the-art about this research topic in addition to elaborating on the need to set novel ethical and legal standards for the governance of such innovations in healthcare.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

A difficult open problem that has never been fully resolved in the literature to date is the behaviour of the (TDCDP) third approximation. As a giant step towards modern control theory, this cutting-edge paper will advance control theory and other relevant inter-disciplinary subjects. Because control theory is important in industry and engineering, this study will be especially beneficial to anyone working in these disciplines who wish to understand more about recent advances in control theory settings. In contrast, the wealth of applications of Fokker Planck Kolmogorov (FPK) equations numerous disciplines As a result, the study instantly gains more taste and credibility. At the end of the paper, there are several challenging open problems, some concluding remarks, and recommendations for further investigation.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

An exposition is undertaken to reveal the significant impact of the time-dependent root parameter, on the stability of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing system. This opens new grounds to stability analysis of non-stationary queueing systems. Potential PSFFA applications of IoT are highlighted.

Drought stress imposes substantial constraints on the growth and production of wheat (Triticum aestivum L.), a globally important cereal crop that is essential for food security. To mitigate these adverse effects, researchers are intensifying their efforts to comprehend how different genotypes respond to drought stress, aiding in the development of sustainable breeding and management strategies. This review summarized past and recent research on genotype-dependent responses of wheat to drought stress, encompassing morphological, physiological, biochemical, molecular, genetic, and epigenetic reactions in plants. Screening of drought-affected features at early developmental stages can provide valuable insights into the adult growth stages that are closely linked to plant productivity. The review underscores the importance of identifying key traits associated with drought resistance, and the potential of leveraging wheat diversity to select cultivars with desirable agronomic characteristics. It also highlights recent advancements in investigating Bulgarian wheat genotypes with varying levels of drought tolerance, specifically in detecting essential features contributing to drought tolerance. Cultivating drought-resistant wheat genotypes and understanding stress stability determinants could markedly contribute to enhancing wheat production and ensuring stable yields under changing climate conditions.

The dynamic response of a Bell-and-Bloom magnetometer to a parallel (to the bias field) time-dependent field is modelled beyond the commonly assumed quasi-static regime. The results unveil features that are related to the parametric nature of the considered system. It is shown that a for low-amplitude time-dependent field different operating conditions are possible and that, beside the commonly reported low-pass-filter behaviour, a band-pass response emerges. Moreover, we numerically show that for larger field amplitude the system, due to its parametric nature, has a kind of ``non-linear'' response.

Natural gas hydrate has gained significant attention in recent years. To safely and sustainably exploit the natural gas from gas hydrate-bearing sediments, it is crucial to understand the long-term mechanical characteristics of the hydrate reservoir. In this study, the influence of hydrate and fine particles on the strain rate dependence of hydrate-bearing sediments under plane strain conditions has been studied. The experimental results show that the strain rate dependency of the mechanical properties of hydrate-bearing sediments is positively correlated with hydrate saturation instead of the morphology of hydrate in sediments. The residual strength of hydrate-bearing sediments is primarily controlled by the hydrate saturation and is independent of the strain rate. Changes in hydrate saturation, and fines content, can affect the relationship between the strain rate and shear band angle. Finally, the local volumetric expansion effect of hydrate-bearing sediments without fines content is more significant and shows a strong strain rate dependence characteristic. Overall, this study provides valuable insights into the long-term mechanical characteristics of hydrate reservoirs. These insights can contribute to the development of a constitutive model of hydrate-bearing sediments with time-dependence in the future, and which is meaningful to the exploitation of natural gas hydrate.

Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have more effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple combination therapy of TMZ, Simvastatin (Simva), and Acetylshikonin (ASH) and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that TMZ/Simva/ASH combination therapy significantly induced more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and induced caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to partial inhibition of autophagy flux (accumulation of LC3β-II and decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for more effective treatment of GBM but further investigations are required for better identification of the mechanisms.

The lateral pressure generated by liquefied soil on pile is a critical parameter in the analysis of soil-pile interaction in liquefaction-susceptible sites. Previous studies have shown that liquefied sand behaves like a non-Newton fluid, and its effect on piles has rate-dependent properties. In this study, a simplified pseudo-static method for liquefiable soil-pile interaction analysis is proposed by treating the liquefied soil as a thixotropic fluid, which considers the rate-dependent behavior. The viscous shear force generated by the relative movement between the viscous fluid (whose viscosity coefficient varies with excess pore pressure and shear strain rate) and the pile was assumed to be the lateral load on the pile. The results from the simplified analysis show that the distribution of bending moment is in good agreement with experiments data. Besides, the effects of various parameters, including relative density, thickness ratio of non-liquefiable layer to liquefiable layer, and frequency of input ground motion, on the pile-soil rate-dependent interaction were discussed in detail.

In this paper, we address the energy eigenvalues of two-dimensional Dirac oscillator perturbed by dynamical noncommutative space. We derived the relativistic Hamiltonian of Dirac oscillator in dynamical noncommutative space ($\tau$-space), in which the space-space Heisenberg–like commutation relations and noncommutative parameter are position-dependent. Then used this Hamiltonian to calculate the first-order correction to the eigenvalues and eigenvectors, based on the second quantization and using the perturbation theory. It is shown that the energy shift depends on the dynamical noncommutative parameter $\tau$. Knowing that with a set of two-dimensional Bopp-shift transformation, we mapped the noncommutative problem to the standard commutative one.

Objective: To investigate the protein expression levels of cyclin‑dependent kinase subunit 2 (CKS2) and cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significances. Methods: A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumor, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analyzed the clinical significance of the expression of the two factors. Results: (1) The positivity rates for CKS2 in benign gastric tumor tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, i.e., 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumor diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=0.625, P=0.000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the overall survival rate for patients in the CKS2 (+) group was significantly worse (25.0% vs 64.0%, 2=15.67, P=0.000) and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse overall survival (30.1% vs 60.5%, 2=15.67, P=0.000). (4) The overall survival rates of CKS2(+)CD47(+) group, CKS2(+)CD47(-) group, CKS2(-)CD47(+) group, and CKS2 (-)CD47 (-) group were 20.0%(13/65), 58.3%(7/12), 57.1%(8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2(+)CD47(+) group was significantly poor. Conclusion: High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

In recent years, the photophysical properties of crystalline metal-organic frameworks (MOFs) have become increasingly relevant for their potential application in light-emitting devices, photovoltaics, nonlinear optics and sensing. The availability of high-quality experimental data for such systems makes them ideally suited for a validation of quantum mechanical simulations, aiming at an in-depth atomistic understanding of photophysical phenomena. Here we present a computational DFT study of the absorption and emission characteristics of a Zn-based surface-anchored metal-organic framework (Zn-SURMOF-2) containing anthracenedibenzoic acid (ADB) as linker. Combining band-structure and cluster-based simulations on ADB chromophores in various conformations and aggregation states, we are able to provide a detailed explanation of the experimentally observed photophysical properties of Zn-ADB SURMOF-2: The unexpected (weak) red-shift of the absorption maxima upon incorporating ADB chromophores into SURMOF-2 can be explained by a combination of excitonic coupling effects with conformational changes of the chromophores already in their ground state. As far as the unusually large red-shift of the emission of Zn-ADB SURMOF-2 is concerned, based on our simulations, we attribute it to a modification of the exciton coupling compared to conventional H-aggregates, which results from a relative slip of the centers of neighboring chromophores upon incorporation in Zn-ADB SURMOF-2.

Evolutionary, sequence and structural analyses of tRNA variable (V) loops provides a new understanding. Type I tRNA V loops have a primordial length of 5 nt, and type II tRNA V loops have a primordial length of 14 nt. Sequence-based alignments of type I and type II V loops gave deceptive results. Type II V loops are characterized by the trajectory of the V arm, the size and sequence of the loop and the first and last V loop nucleotides and their known contacts. Depending on the V arm trajectory, type II V stems and loops can be interaction sites for aminoacyl-tRNA synthetases. So, type II V arms for tRNALeu, tRNASer and tRNATyr (found in Bacteria) were coevolved and selected to distinguish determinants to support cognate tRNA charging. The alignment of type I and type II V loops was adjusted based on tRNA evolution. Results are consistent with Archaea being an older and simpler life form than Bacteria. TRNAome sequences were derived from radiation of an ordered tRNAPri (Pri for primordial) sequence comprised of known RNA repeats and inverted repeats. V loop and tRNA sequences, therefore, convey a history of the primary successful pathway in the origin of life.

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and a several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in-vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.

A spike-timing-dependent-plasticity (STDP) device with a Ga-Sn-O (GTO) conductance change layer deposited by a mist-CVD method has been developed. First, the memristive characteristic is analyzed. Next, based on it, spike waveforms are determined. Finally, the STDP characteristic is successfully confirmed. This is the first report on the realization of a STDP characteristic using a thin film deposited by the mist-CVD method, which is achieved by the GTO properties and a well-designed clear methodology to realize a STDP characteristic from a memristive characteristic.

This study investigates the impact of Government Consumption (GC) on Saudi Arabia’s GDP during major economic crises from 1969 to 2022, with a focus on periods marked by fluctuations in oil and non-oil revenues. By integrating these revenue streams, the research provides a more comprehensive analysis of fiscal policy effectiveness during economic downturns. Using an Autoregressive Distributed Lag (ARDL) model, the study reveals the complex role of Government Consumption (GC) in stabilizing and stimulating the Saudi economy amidst revenue volatility.Key findings indicate that while GC does not significantly influence GDP in the short term, its long-term effectiveness varies across different crises. Specifically, GC has acted as a buffer against immediate economic shocks during certain crises while providing a stimulus for economic recovery in others. For instance, during the 2020 COVID-19 pandemic, timely fiscal measures significantly boosted GDP, underscoring the importance of adaptive and proactive fiscal policies. Conversely, the 2014-2016 oil price collapse demonstrated that GC alone was insufficient to counteract economic downturns, emphasizing the need for diversified revenue strategies.These findings underscore the dual role of GC in economic stabilization and recovery. During the COVID-19 pandemic, GC played a crucial role in both mitigating negative economic impacts and supporting recovery efforts, showcasing its effectiveness in times of global disruptions. This demonstrates GC's capability as an immediate buffer against economic shocks and a stimulus for economic recovery. In contrast, during the 2014-2016 oil price collapse, GC was less effective, indicating the limitations of relying solely on government spending without broader economic diversification. This highlights the necessity of diversified revenue strategies to complement fiscal measures for long-term economic resilience.The robustness of the findings was ensured through various diagnostic tests, including checks for autocorrelation, heteroskedasticity, and stationarity of residuals. The absence of significant autocorrelation and heteroskedasticity, along with the stationarity of differenced variables, confirms the validity of the econometric models used.The study contributes to the discourse on fiscal policy in oil-dependent economies by illustrating the critical role of diversified revenue strategies and adaptive fiscal measures in enhancing economic resilience. Recommendations are offered for policymakers to optimize fiscal strategies, ensuring robust economic recovery and long-term stability in volatile markets. This research highlights the necessity for Saudi Arabia to refine its fiscal policies towards greater economic diversification and stability.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

A two-qubit Hamiltonian model exhibiting an SU(2) symmetry is considered. The related dynamical problem results to be then exactly solvable both in the time-independent and in the time-dependent case. Basing on the formal, general form of the related time evolution operator, the time-dependence of the level of entanglement of some initial conditions is studied within both the Rabi and the Landau-Majorana-Stückelber-Zener scenarios.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

This article deals with a finite-source stock-dependent stochastic inventory system with heterogeneous servers and retrial facility. The system can store up to S number of items, and the lifetime of each item follows an exponential distribution. The primary customers arrive in a finite waiting hall from a finite source and get service from the multi-channel (c-heterogeneous servers). The customer’s arrival rate depends on the present stock level. Those customers who arrive while the waiting hall is full enter into the finite orbit. Also, customers in the waiting hall can become impatient and enter the orbit. The (s,Q) ordering policy is adopted for the replenishment of stocks. In the steady state, the joint probability distribution of a number of items in the inventory, busy servers, customers in the waiting hall, and orbit is computed. The comparative numerical analysis of heterogeneous and homogeneous servers on the expected total cost, the average number of customers in the waiting hall and orbit, the fraction of successful retrial rate, and the average impatient customer rate are also carried out.

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordination of cell cycle, transcription and replication. Inhibition of WEE1 and PKMYT1 kinases, which prevent unscheduled mitosis entry, leads to fragility of under-replicated sites. Recent evi-dence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets – ATR, CHK1, PARP and their inhibitors.

Two-dimensional (2D) materials show advantages as surface enhanced Raman scattering (SERS) substrate over traditional noble metals, such as chemically inert flat surface and uniform SERS signals. However, due to the low density of free electrons of 2D materials, the enhancement mechanism is mainly restricted to chemical enhancement instead of electromagnetic enhancement, resulting a relatively low enhancement factor. In this work, we reported a sensitive 2D SERS substrate based on chemical vapor deposited MoN nanosheets with electromagnetic enhanced mechanism. The maximum enhancement factor can be 3×105 with a limit of detected concentration of 4×10-8 M, which is comparable to those noble metal SERS substrates without hot spots. The MoN nanosheets show strong surface plasmon resonance in the visible range as evidenced by the UV-vis absorption spectroscopy and first principle calculation. The MoN nanosheets SERS substrates exhibit excellent Raman signal uniformity within the nanosheets. Meanwhile, Distinct thickness dependent sensitivity was observed in the MoN nanosheets, higher sensitivity can be achieved by decreasing the thickness of the nanosheets. Furthermore, the MoN nanosheets SERS substrate also show high thermal stability, which can be annealed in air for more than 300℃ and maintain its SERS activity. The high stability of MoN nanosheets allows it to be reused for 20 cycles without obvious signal decay. The high sensitivity, stability, reusability and Raman signal uniformity, makes MoN nanosheets an ideal 2D SERS substrate for practical applications.

Creep is a fundamental property naturally exists in some types of rock, which is significant for the long-term stability of roadways during the mining process. In this paper, the long-term strength of coal and rock were obtained via laboratory experiments, and a Cvisc elasto-viscoplastic model was adopted and introduced in FLAC3D, based on the 3101 transport roadway in Hongqinghe Coal Mine, to investigate the influence of creep on the stability of deep-high stress roadway. The test results show that the long-term strength of 3-1 coal and sandy mudstone, respectively, is 18.65 MPa, 39.95 MPa. The plastic zone, the deformation, and the damage of roadway surrounding rock behave an obvious increase after being excavated for 720d as the creep model was chosen. The plastic zone failure with models shear-p (1090.7 m3), shear-n (381.7 m3), tension-n (98.4 m3), and tension-p (30.8 m3), the damage value has an obvious increment of increased 21.2% (0.053), the deformation increases in the order is two-sidewalls (1978 mm), roof (907 mm), floor (101 mm). The creep of the roadway can be divided into three stages: the accelerating stage, the decaying stage, and the stable stage. The creep speed of each stage is greatly affected by the presence or absence of anchor spray support: the creep speed of the bare roadway roof, roadway side, and floor stability, respectively, is 1.01, 1.02, and 0.12 mm/d; After anchor spray support, the creep velocity, correspondingly, decreased to 0.69, 0.37, and 0.12 mm/d, and the amount of surrounding rock damage decreased from 0.302 to 0.243. This indicates that the anchor spray support can significantly reduce the creep effect of the roadway. The Cvisc creep model was verified reliable and can provide guidance for deep high-stress coal roadway support.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.

Potential dependent special relativity and Gauss's law for the electric field have been used for gravity by assuming vacuum energy to be generated when the energy is a minimum useful expression for vacuum energy has been found. This expression shows that elementary particles are generated by gravity vacuum filling their hollow balls; using Schrödinger equation for spherically symmetric particles vacuum energy is quantized. Treating mass as vibrating spheres thus solving Schrödinger, coordinate harmonic oscillator energy relation has been found.

Regression models are mostly used in all fields of sciences for modelling the relationship between a dependent variable and independent variable(s). The least square method is often used to estimate the parameters in a linear model because it is the best linear unbiased estimator. These estimates can only be reliable if the assumption of normality is satisfied. In some cases the dependent variable might be bimodal and shows a non-linear relationship with the independent variable(s). In this case, a non-linear model should be used. In non-linear model, the standard errors are often obtained by linearizing the nonlinear function around the parameter, assuming central limit theorem. After the linearization, the least square parameter estimates are obtained. It should be noted that the error of the non-linear model is different from that of the transformed linear model. Thus, there is a need to transform back to the original non-linear model. In this note, a novel non-linear function was developed into a non-linear regression model, called Normal-Power model. The least square method was used to estimate the parameter of the transformed model. Its usefulness in regression model was demonstrated using real data of Nigeria Economy-Tourism model.

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: i) primary dengue infection, ii) secondary dengue infection with the same (homologous) dengue virus and iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production, and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights on the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

Real-time evolution of the electron densities under excitations in La₂CuO₄ was calculated by the time-dependent density functional theory (TDDFT). The author found, for the first time, under excitations, the electron cloud of Cu²⁺ changes obviously and the characteristic frequencies are 83 meV and 36 meV, respectively, for two different modes. The results are unexpected and close to that of lattice vibrations. The results show that the electron cloud of Cu²⁺ (just like the lattice) can be the electron-pairing medium in high temperature copper oxide superconductors.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

As the natural resources are getting exhausted, the concept of sustainable development of region has received increasing attentions, especially for resource-dependent cities. In this paper an innovative method that emergy analysis and IPAT (Human Impact Population Affluence Technology) model were combined in order to analyze the quantitative relationship of economic growth and energy consumption and further to evaluate its overall sustainability level. Taiyuan, a traditional, resource-dependent city in China, is selected as the case study region. The main results show that total emergy of Taiyuan increased from 9.023× 1023 sej in 2007 to 9.116× 1023sej in 2014, with 38% reduction on non-renewable emergy and 125% growth on imported emergy. Regional emergy money ratio (RMB) was reduced by 48% from 5.31× 1013sej/$ in 2007 to 2.74× 1013sej/$ in 2014, indicating that the increasing speed of consuming resources and energy was faster than the increase of GDP, and that Taiyuan’s money purchasing power declined. The lower emergy sustainability index (ESI) indicates that Taiyuan was explored and produced large quantities of mineral resources, which puts more stress on the environment as a consequence, and that this is not sustainable in the long run. The IPAT analysis demonstrates that Taiyuan sticks to the efforts of energy conservation and environmental protection, in order to promote regional sustainable development, it is necessary to take an integrated effort. Policy insights suggest that resourceful regions should improve include energy and resource efficiency, optimizing energy and resourceful structure.

Abstract: RNase Y is an endoribonuclease that governs global mRNA turnover/processing in Ba-cillus subtilis and likely many other bacteria. The enzyme is anchored at the cell membrane, a pseudo-compartmentalization that appears coherent with its task to initiate decay of mRNAs translated predominantly at the cell periphery. However, the reason and consequence for RNase Y attachment to the membrane are largely unknown. We have studied a strain expressing wild-type levels of a cytoplasmic form of RNase Y from the chromosomal locus. This strain exhibits a slow growth phenotype similar to an RNase Y null mutant. Genome-wide data show a significant effect on the expression of hundreds of genes. Certain RNA substrates clearly require RNase Y membrane attachment but others do not. We found no correlation between mRNA stabilization and the cellular location or function of encoded proteins. The Y-complex, an RNase Y specificity factor, appears to also recognize the cytoplasmic form of the enzyme which is able to restore wild-type levels of the corresponding transcripts. We propose that membrane attachment of RNase Y is required for the functional interaction with many coding and non-coding RNAs, for limiting the cleavage of certain substrates and potentially to avoid unfavorable competition between RNase Y and other ribonucleases like RNase J that have a similar evolutionarily conserved cleavage speci-ficity.

Comparative metatranscriptomics of bacterial and yeast communities of two milk kefir beverages (MKAA1 and MKAA2) obtained by fermentation with two different frozen stocks of the kefir grain CIDCA AGK1, and differing in rheological features and organic acid amounts production was carried out to figure out the relation between differences in physicochemical and rheological properties of kefir and the microbial active profile associated with each product. The dominance of lactic acid bacteria and yeast and a marginal amount of acetic acid bacteria marked the microbiome. The bacterial families Lactobacillaceae and Streptococcaceae account for almost all bacterial gene transcripts, with Lactobacillus helveticus, L. kefiranofaciens, L. gallinarum and Lactococcus lactis being most frequent in the microbiome of MKAA1 beverage, and L. kefiranofaciens, Lc. lactis and Leuconostoc mesenteroides being most prevalent in the MKAA2. Dipodascaceae and Saccharomycetaceae were the leading yeast families represented by Yarrowia lipolytica, Saccharomyces unisporus, and Kluyveromyces marxianus. The MKAA1 and MKAA2 shared >75% KEGG Ortologs (KO) in bacteria and yeast libraries. Considerable decreases in total expressed genes (KEGG Ortolog) assigned to Lactobacillus helveticus and L. gallinarum might be related to the variations in rheological features of the beverages, probably by compromising the interrelations with L. kefiranofaciens which might explain the variations in rheological features of the beverages.

Equine herpesvirus-1 (EHV-1) causes respiratory diseases, abortion, and encephalomyelitis in horses. EHV-1 immediate-early (IE) protein, essential for viral replication, is transactivated by the binding of a multiprotein complex including the open reading frame 12 (ORF12) and some host factors to the IE promoter region. Promoter-associated non-coding RNAs (pancRNAs), which are transcribed from bidirectional promoters, regulate the transcription of neighboring genes in mammals and pathogens. In this study, we identified a novel pancRNA transcribed from across the areas of the 5’-untranslated region and promoter of EHV-1 IE and named it IE pancRNA. IE pancRNA and mRNA were simultaneously expressed in EHV-1-infected RN33B-A68B2M cells. This pancRNA was also transcribed in RK13 and E. Derm cells, which are highly susceptible to EHV-1 infection. Furthermore, IE pancRNA upregulated IE gene expression in the presence of ORF12, and stable expression of IE pancRNA increased the number of EHV-1-infected RN33B-A68B2M cells. These results suggest that IE pancRNAs facilitate EHV-1 proliferation by promoting IE gene expression.

The incidence of hepatocellular carcinoma (HCC) is increasing and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinical available treatments have dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients showing a durable treatment benefit over time, and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with non-viral etiologies, such non-alcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers informative of the best treatment approach are required actions to improve patient survival. Numerous evidence indicated non-coding RNAs (ncRNAs) as pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.

The Jeryak, a hybrid offspring of Gannan yak and Jersey cattle, exhibits evident hybrid advantages over the Gannan yak in terms of production performance and other various aspects. The small non-coding RNAs known as miRNAs exert a significant regulatory influence on gene expression post-transcriptionally. However, the regulatory mechanism of miRNA associated with muscle development in Jeryak remains elusive. To elucidate the regulatory role of miRNAs in orches-trating the skeletal muscle development in Jeryak, we selected dorsal longissimus muscle tissues from Gannan yak and Jeryak for transcriptome sequencing analysis. A total of 230 (DE)miRNAs and 1819 differentially expressed mRNAs (DEMs) were identified in the longest dorsal muscle of Gannan yak and Jeryak. The functional enrichment analysis revealed a significantly enrichment of target genes from differentially expressed (DE)miRNAs and DEMs in signaling pathways associ-ated with muscle growth, such as the Ras signaling pathway and the MAPK signaling pathway. The network of interactions between miRNA and mRNA suggested that some differentially ex-pressed miRNAs, including miR-2478-z, miR-339-x, novel-m0036-3p and novel-m0037-3p, played a pivotal role in facilitating muscle development. These findings help us to deepen our under-standing of the hybrid dominance of Jeryaks and provide a theoretical basis for further research on the regulatory mechanisms of miRNAs associated with Jeryak muscle growth and development.

Epitranscriptomics refers to post-transcriptional regulation of gene expression via RNA modifications and editing that affect RNA functions. Many kinds of modifications of mRNA have been described, among which N6-Methyladenosine (m6A), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (Ψ), 5-methylcytidine (m5C). They alter mRNA structure and consequently stability, localization and translation efficiency. Perturbation of the epitranscriptome is associated with human diseases, thus opening the opportunity for potential manipulations as therapeutic approach. In this review, we overview the functional roles of epitranscriptomic marks in the skeletal muscle system, in particular in embryonic myogenesis, muscle cell differentiation and muscle homeostasis processes. Further, we explored high throughput epitranscriptome sequencing data to identify RNA chemical modifications in muscle-specific genes and we discuss the possible functional role and the potential therapeutic applications.

Abstract: Autophagy has a dual role in gliomagenesis in a microRNA-modulated environment. We investigated the potential relevance of autophagy in glioma development and survival by exploring the association of autophagy-associated genes and microRNAs in low- and high-grade gliomas. Real-time PCR (qPCR) was used to determine the expression of genes and microRNAs in 50 fresh glioma tissues while Formalin-fixed paraf-fin-embedded tissues of the same patients were used for immunohistochemistry. The Mann-Whitney U-test test, Spearman correlation test, and Kaplan-Meier survival analysis were performed to evaluate the expression, association, and overall survival in patients respectively. The expression of LC3, AKT, and miR-21 was increased in high-grade glioma compared to low-grade glioma while ULK2 expression was decreased in high-grade glioma. A strong positive correlation was observed for ULK2 with UVRAG, PTEN, miR-7, and miR-100, while the moderate correlation with mTOR, Beclin1, miR-30, miR-204, miR-374, miR-21 and miR-126 in low-grade glioma, while a moderate positive correlation between ULK2 and PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, AKT and miR-374, and between AKT and ULK1, VPS34, UVRAG, and miR-7 in high-grade gliomas. The low ULK2 and LC3 expression group was significantly associated with better overall survival in gliomas while miR-21 overexpression showed a poor prognosis in glioma patients. Therefore, miR-21, ULK2, and LC3 may serve as prognostic biomarkers for survival outcomes in glioblastoma.

Inflammatory activation within the brain was linked to a decrease in cognitive abilities, however the molecular mechanisms implicated in the development of inflammatory-related cognitive dysfunction and its prevention are poorly understood. This study compared responses of hippocampal transcriptomes 3 months after the striatal infusion of lipopolysaccharide, alone (LPS; 30 µg) resulting in memory loss, or with dexamethasone (DEX; 5 mg/kg intraperitoneal) pretreatment, which abolished the long-term LPS-induced memory impairment. After LPS alone, a significant elevation in the expression of immunity/inflammatory-linked genes, including chemokine (Cxcl13), cytokines (Il1b, Tnfsf13b), and major histocompatibility complex (MHC) class II members (Cd74, RT1-Ba, RT1-Bb, RT1-Da, RT1-Db1) was revealed. DEX pretreatment did not change expression of these genes, but significantly affected expression of genes encoding ion channels, primarily calcium and potassium channels, regulators of glutamate (Slc1a2, Grm5, Grin2a) and GABA (Gabrr2, Gabrb2) neurotransmission which enriched in such GO biological processes as “Regulation of transmembrane transport”, “Cognition”, “Learning”, “Neurogenesis”, and “Nervous system development”. Taken together, the data suggest that: (1) pretreatment with DEX did not markedly affect LPS-induced prolonged inflammatory response; (2) DEX pretreatment can affect processes associated with glutamatergic signaling and nervous system development, possibly involved by that in the recovery of memory impairment induced by LPS

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

The formation and development of potato tissues and organs is a complex process regulated by a variety of genes and environmental factors. However, the regulatory mechanisms underlying the growth and development are still unclear. In this study, we used autotetraploid potato JC14 as experimental subject to analyze the transcriptome of root, stem and leaf at seedling, tuber formation and tuber expansion stages to explore the spatio-temporal expression pattern of genes and genetic development characteristics. The results identified thousands of differentially expressed genes and KEGG pathway enrichment analysis showed that these genes were mainly involved in defense response and carbohydrate metabolism pathways. A total of 12 co-expressed Gene modules were identified by Weighted Gene Co-expression Network Analysis (WGCNA), and 4 modules were screened out with the highest correlation with potato stem developmental traits. Core genes in the network were further investigated and functionally annotated by computing the connectivity of genes within the module. The results unveiled number of hub genes in stems at different developmental stages, including carbohydrate metabolism related genes, the defense response related genes, and transcription factors. These findings provide important leads for further understanding of the molecular regulation and genetic mechanisms of potato tissue development.

Iron is the most abundant micronutrient in plant mitochondria and it has a crucial role in biochemical reactions involving electron transfer. It has been described in Oryza sativa that Mitochondrial Iron Transporter (MIT) is an essential gene and that knockdown mutant rice plants have a decreased amount of iron in mitochondria, strongly suggesting that OsMIT is involved in mitochondrial iron uptake. In Arabidopsis thaliana, two genes encode MIT homologues. In this study, we analyzed different AtMIT1 and AtMIT2 mutant alleles, confirming that individually AtMIT1 nor AtMIT2 genes are essential. When we generated crosses between Atmit1 and Atmit2 alleles we were able to isolate homozygous double mutant plants. Interestingly, homozygous double mutant plants were obtained only when mutant alleles of Atmit2 with the T-DNA insertion in the intron region were used for crossings, and in these cases a correctly spliced AtMIT2 mRNA was generated, although at a low level. Atmit1 Atmit2 double homozygous mutant plants, which were knockout for AtMIT1 and knockdown for AtMIT2, were grown and chacterised in iron sufficient conditions. Pleiotropic developmental defects were observed including abnormal seeds, increased number of cotyledons, slow growth rate, pinoid stems, defects in flower structures and reduced seed set. We observed a possible phenomenon of T-DNA suppression in the next generation of Atmit1 Atmit2 double homozygous mutant plants, correlating with an increased splicing of the AtMIT2 intron containing the T-DNA. Molecular analysis of gene expression markers for mitochondrial and oxidative stress showed that Atmit1 Atmit2 double homozygous mutant plants express a degree of mitochondrial perturbation. A RNA-Seq study was performed and we could identify more than 760 genes differentially expressed in Atmit1 Atmit2, including genes involved in iron transport, coumarin metabolism, and hormones metabolism, transport and signaling. Our data suggest that some of the phenotypes observed in Atmit1 Atmit2 double homozygous mutant plants are mediated by defects in auxin homeostasis.

Multisubunit RNA polymerases (RNAP) carry out transcription in all domains of life; during vi-rus infection, RNAPs are targeted by transcription factors encoded by either the cell or the virus, resulting in the global repression of transcription with distinct outcomes for different host-virus combinations. These repressors serve as versatile molecular probes to study RNAP mechanisms, as well as they aid the exploration of druggable sites for the development of new antibiotics. Here, we review the mechanisms and structural basis of RNAP inhibition by the viral repressor RIP and the crenarchaeal negative regulator TFS4, which follow distinct strategies. RIP operates by occluding the DNA-binding channel and mimicking the initiation factor TFB/TFIIB. RIP binds tightly to the clamp and locks it into one fixed position, thereby preventing conformational oscil-lations that are critical for RNAP function as it progresses through the transcription cycle. TFS4 engages with RNAP in a similar manner to transcript cleavage factors such as TFS/TFIIS through the NTP-entry channel; TFS4 interferes with the trigger loop and bridge helix within the active site by occlusion and allosteric mechanisms, respectively. The conformational changes of RNAP described above are universally conserved and are also seen in inactive dimers of eukaryotic RNAPI and several inhibited RNAP complexes of both bacterial and eukaryotic RNA polymer-ases, including inactive states that precede transcription termination. A comparison of target sites and inhibitory mechanisms reveals that proteinaceous repressors and RNAP-specific antibiotics use surprisingly common ways to inhibit RNAP function.

The mosaic disease in maize is caused by Sugarcane mosaic virus (SCMV), a member of the Potyviridae family. The best strategy to cope with viral infections is the use of disease-resistant maize lines. To better understand the resistance response to SCMV, we analyzed differentially expressed genes among a resistant line (CI-RL1), a susceptible line (B73), and the F1 progeny from a cross between both lines using RNA-Seq data. We also analyzed transcript expression pattern clustering to allocate previously reported resistance candidate genes. GO enrichment analysis of biological processes highlighted a strong regulation in ROS detoxification in both the susceptible and resistant lines. The enrichment of cellular components led to the identification of an integral component of the plasma membrane in the RL line. Transcript expression patterns provide evidence of the importance of host translation in virus response, showing the diverse and complex behavior of eIF4E homologs and the presence of eleven eEF1α factors in maize. In addition, we identified two genes putatively implied in long-distance movement: ZmPiezo and ZmPVIP1. Finally, we propose an ABC transporter to be associated with viral resistance.

The provenance of the aminoacyl-tRNA synthetases (aaRS) poses challenging questions because of their role in the emergence and evolution of genetic coding. We investigate evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—residue-by-residue conservation, its variance, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from distinct, successive genetic sources. These data are especially significant in light of: (i) experimental fragmentations of the Class I scaffold into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that two of these partitions arose from an ancestral Class I aaRS gene encoding a Class II ancestor in frame on the opposite strand. Phylogenetic metrics of different modules vary in accordance with their presumed functionality. A 46-residue Class I “protozyme” roots the Class I molecular tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting is consistent with near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved long after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

The major threats to the sustainable supply of forest tree products are adverse climate, pests and diseases. Climate change, exemplified by increased drought, poses a unique threat to global forest health. This is attributed to the unpredictable behavior of forest pathosystems, which can favor fungal pathogens over the host under persistent drought stress conditions in the future. Currently, the effects of drought on tree resistance against pathogens are hypothetical, thus research is needed to identify these correlations. Norway spruce (Picea abies) is one of the most economically important tree species in Europe, and is considered highly vulnerable to changes in climate. Dedicated experiments to investigate how disturbances will affect the Norway spruce - Heterobasidion sp. pathosystem are important, in order to develop different strategies to limit the spread of H. annosum s.l. under the predicted climate change. Here, we report a transcriptional study to compare Norway spruce gene expressions to evaluate the effects of water availability and the infection of Heterobasidion parviporum. We performed inoculation studies of three-year-old saplings in a greenhouse (purchased from a nursery). Norway spruce saplings were treated in either high (+) or low (-) water groups: high water group received double the water amount than the low water group. RNA was extracted and sequenced. Similarly, we quantified gene expression levels of candidate genes in biotic stress and jasmonic acid (JA) signaling pathways using qRT-PCR, through which we discovered a unique preferential defense response of H. parviporum-infected Norway spruce under drought stress at the molecular level. Disturbances related to water availability, especially low water conditions can have negative effects on the tree host and benefit the infection ability of the pathogens in the host. From our RNA-seq analysis, 114 differentially expressed gene regions were identified between high (+) and low (-) water groups under pathogen attack. None of these gene pathways were identified to be differentially expressed from both non-treated and mock-control treatments between high (+) and low (-) water groups. Finally, only four genes were found to be associated with drought in all treatments.

In this letter we investigate if SARS-CoV-2 RNA is involved in the increased ageing of alveolar cells. Our in silico study is explorative. With the results we are able to outline experiments with AEC2 repair of bleomycin damaged alveolar cells. If AEC2 repair capability is diminished by spike RNA then perhaps this result provides a first step on a route to treat immortal lung cancer cells.

Muscle is one of the most critical organs for mammals, which governs multiple movement and physiological functions. Circular RNA (circRNA) is a kind of novel endogenous RNA without 5'-Caps and 3'-poly(A) structures formed by pre-mRNA's back-splicing. RNA binding proteins (RBPs) control the production and degradation of circRNA, help nucleus-cytoplasm transport and locate circRNA, and regulate circRNA translation. Therefore, circRNAs and the chaperoned RBPs play critical roles in muscle growth, development, and disease progression. In this review, we systematically characterize the possible molecular mechanism of circRNA-protein interactions. Also, we summarize the latest researches on circRNA-protein interactions in muscle development and diseases. Besides, we provide several valid prediction methods and experimental verification approaches. Our review reveals the importance of circRNAs and their protein chaperones and provides a reference for further study in this field.

Streptococcus suis is a zoonotic pathogen causing serious infections in both swine and humans. Although metals are essential for life, excess amounts of metals they are toxic to bacteria. when accumulated in excess amounts. Except for zinc, Transcriptome-level data of the mechanisms for resistance to metal-induced toxicity in S. suis are available for no metals other than zinc. have not been investigated from the transcriptome level in S. suis. Herein, we explored the transcriptome-level changes of in S. suis in response to ferrous iron and cobalt toxicity by RNA sequencing. Many A lot of genes were differentially expressed in the presence of excess ferrous iron and cobalt. Most of the genes in response to cobalt toxicity showed the same expression trends as those were expressed in the same trend in response to ferrous iron toxicity. qRT-PCR analysis of the selected genes confirmed the accuracy of RNA sequencing results. Bioinformatics analysis of the differentially expressed genes indicated that ferrous iron and cobalt have similar impacts effects on the cellular processes of S. suis. Treatment with ferrous Ferrous iron treatment resulted in down-regulation of several oxidative stress tolerance-related genes involved in oxidative stress tolerance and up-regulation of the genes in an amino acid ABC transporter operon. Expression of the several genes in the arginine deiminase system was down-regulated in the presence of after ferrous iron and cobalt treatment. Collectively, our results suggested that S. suis alters the expression of a lot of multiple genes to respond to ferrous iron and cobalt toxicity.

The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. Despite the close pet-human contact, little is known about the predisposition of pets to SARS-CoV-2. Among these, felines are the most susceptible. In this study, a domestic cat with clear symptoms of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. This is the first Italian study reporting on the request of the scientific community to focus attention on the possible role of pets as a SARS-CoV-2 reservoir. An important question remains unanswered: did the cat die from SARS-CoV-2 infection?

This study aimed to rank cancers by the strength of relationship between comprehensive mRNA expression of the most harmful or protective genes and patient survival. Using TCGA dataset including RNA-SEQ and clinical data, we investigated not only gene specific prognostic availability, but also comprehensive prognostic availability of prognostic genes filtered by cox coefficient, and ranked cancers by specially designed prognostic indicator. Through Kaplan-Meier plots, we checked that cancers vary in the strength of influence of prognostic genes, and they follow as the rank. Developing treatment with method to reduce or increase expression of biomarkers for specific cancer which ranked bottom, it would be not efficient in high probability. The results of this study can be a scientific evidence for that.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Removal of the proliferation component of gene expression by PCNA adjustment has been addressed in numerous survival prediction studies for breast cancer and all cancers in the TCGA. These studies indicate that widespread co-regulation of proliferation upwardly biases survival prediction when gene selection is performed on a genome-wide basis. In addition, removal of the correlative effects of proliferation does not reduce the random bias associated with survival prediction using random gene selection. Since most cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we pursued an investigation to remove the proliferation component of expression in DNA repair genes to determine survival prediction. This translational hypothesis-driven focus on DNA repair genes is directly amenable to finding new sets of DNA repair genes that could potentially be studied for inhibition therapy. Overall survival (OS) prediction was evaluated in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene expression were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Interestingly, PARP1 was not a significant predictor of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic cancers for inhibition therapy may be AML, colorectal, and renal papillary, because of potentially less confounding due to lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer for inhibition therapy is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications in DNA repair genes. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.

Peanut (Arachis hypogaea) is a crop plant with high economic value, but the epigenetic regulation of its growth and development has only rarely been studied. The peanut histone deacetylase 1 gene (AhHDA1) has been isolated and is known to be ABA- and drought-responsive. In this paper, we investigate the role of AhHDA1 in more detail, focussing on the effect of altered AhHDA1 expression in hairy roots at both the phenotypic and transcriptional levels. Agrobacterium rhizogenes-mediated transformation of A. hypogaea hairy roots was used to analyse how overexpression or RNA interference of AhHDA1 affects this tissue. In both types of transgenic hairy root, RNA sequencing was adopted to identify genes that were differentially expressed, and these genes were assigned to specific metabolic pathways. AhHDA1-overexpressing hairy roots were growth-retarded after 20 d in vitro cultivation, and superoxide anions and hydrogen peroxide accumulated to a greater extent than in control or RNAi groups. Overexpression of AhHDA1 is likely to accelerate flux through various secondary synthetic metabolic pathways in hairy roots, as well as reduce photosynthesis and oxidative phosphorylation. Genes encoding the critical enzymes caffeoyl-CoA O-methyltransferase (Araip.XGB85) and caffeic acid 3-O-methyltransferase (Araip.Z3XZX) in the phenylpropanoid biosynthesis pathway, chalcone synthase (Araip.B8TJ0) and polyketide reductase (Araip.MKZ27) in the flavonoid biosynthesis pathway, and hydroxyisoflavanone synthase (Araip.0P3RJ) and isoflavone 2'-hydroxylase (Araip.S5EJ7) in the isoflavonoid biosynthesis pathway were significantly upregulated by AhHDA1 overexpression, while their expression in AhHDA1-RNAi and control hairy roots remained at a lower level or was unchanged. Our results suggest that alteration of secondary metabolism activities is related to overexpression of AhHDA1, which is mainly reflected in phenylpropanoid, flavonoid and flavonoid biosynthesis. Future studies will focus on the function of AhHDA1 interacting proteins and their action on cell growth and stress responses.