Models of quantum measurements are presented, including observers subject to the laws of quantum mechanics. Observers perform multiple measurements in an attempt to disprove the collapse hypothesis. It is shown that under reasonable assumptions the effort cannot succeed. Under a unitary evolution the end state is a correlation between the result of the first measurement and the result(s) of the others, consistent with the observer's collapse hypothesis. The observer may conclude that the laws of nature include a non-unitary collapse mechanism, even if one does not actually exist. Discard of information is the crucial factor which distinguishes entanglement from measurement.

10% copper substituted (BiCUVOX/Bi₂V_0.9Cu_0.1O_5.5−δ) and 5% copper/titanium double-substituted bismuth vanadate (BiCUTIVOX/Bi₂V_0.9(Cu_0.05Ti_0.05)O_5.5−δ) platelets were formed by molten salt synthesis (MSS) using a eutectic KCl/NaCl salt mixture. The product was phase pure within the limits of X-ray diffraction. The size and form of the platelets could be controlled by changing the heating temperature and time. The crystallite growth rate at a synthesis temperature of 650 °C, and activation energy for grain growth were determined for BICUTIVOX, which experienced inhibited growth compared to BICUVOX. Quasi-equilibrium, multi-foil shapes consisting of lobes around the perimeter of the platelets were observed and explained in the context of relative two-dimensional nucleation and edge growth rates.

Microelectromechanical System (MEMS) vibrating gyroscope design considerations are always intriguing due to their microscale mechanical, electrical, and material behavior. MEMS vibrating ring gyroscopes have become important inertial sensors in inertial measurement units (IMU) for navigation and sensing applications. The design of a MEMS vibrating ring gyroscope incorporates an oscillating ring structure as a proof mass, reflecting unique design challenges and possibilities. This paper presents a comprehensive design analysis of the MEMS vibrating ring gyroscope from the mechanical, electrical, and damping perspectives. The mechanical design of the MEMS vibrating ring gyroscope investigates the various frame designs of the vibrating ring structure, as well as the various beam structures, including curved, rectangular, and semicircular beam structures, which are analyzed using mathematical models and finite element analysis (FEA) simulations that provide an in-depth analysis of the stiffness and deflection of the vibrating structures. The electrical designs of the MEMS vibrating ring gyroscope were analyzed using various electrode configurations, electrostatic actuation, and capacitive detection mechanisms, respectively. The design analysis of various forms of damping, including viscous, structural, thermoelastic, and anchor damping, has been discussed. The variety of design structures investigated for MEMS vibrating ring gyroscopes' mechanical, electrical, and damping performance.

The current state-of-the-art does not provide a universal and rapid method of determining the state of health (SOH) of a battery or a supercapacitor without carefully examining the degradation of hundreds of full charge/discharge cycles. Lithium-ion batteries, sodium-ion batteries and supercapacitors of different cell chemistries were studied by impedance spectroscopy during lifetime tests. Faradaic and capacitive charge storage are distinguished by the relationships between stored electric charge and capacitance. For batteries, impedance spectroscopy is best applicable in the flat region of the voltage-charge curve. An approximately linear correlation between pseudocapacitance and Ah capacity is observed as long as overcharge and deep discharge are avoided. The correct calculation of quantities related to complex impedance and differential capacitance is outlined – which may also be useful as an introductory text and tutorial for newcomers to the field. Novel diagram types are proposed for the purpose of instant performance and failure diagnosis of batteries and supercapacitors.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

In recent decades, with the ever-growing scale of video data, near-duplicate videos continue to emerge. Data quality issue caused by near-duplicate videos is becoming more and more prominent, which has affected the application of normal videos. Although current studies on near-duplicate video detection can be helpful to uncover data quality issues for videos, they still lack a process of automatic merging for the video data represented by high-dimensional features, which are difficult to automatically clean the near-duplicate videos to improve data quality for video datasets. At present, there are few studies on near-duplicate video data cleaning. The existing studies have the sensitive problems of video data orderliness and clustering initial center under a condition that prior distribution is unknown, which seriously affect the accuracy of near-duplicate video data cleaning. To address the above issues, an automatic near-duplicate video data cleaning method based on a consistent feature hash ring is proposed in this paper. First, a residual network with convolutional block attention modules, a long short-term memory deep network, and an attention model are integrated to construct an RCLA deep network with the multi-headed attention mechanism to extract spatiotemporal features of video data. Then, a consistent feature hash ring is constructed, which can effectively alleviate the sensitivity of video data orderliness while providing a condition of near-duplicate video merging. To reduce the sensitivity of the initial cluster centers to results of near-duplicate video cleansing, an optimized feature distance-means clustering algorithm is constructed by utilizing a mountain peak function on a consistent feature hash ring, which can implement automatic cleaning of near-duplicate video data. Finally, experiments are conducted based on a commonly used dataset named CC_WEB_VIDEO and a coal mining video dataset. Compared with some existing works, simulation results demonstrate that the performance of the proposed method.

An easy to implement and cost-effective Fiber Bragg Grating (FBG) sensor interrogation technique based on a ring Erbium-Doped Fiber Laser (EDFL) topology is proposed and experimentally assessed. The FBG sensor is part of the EDFL cavity and must have a central wavelength located within the linear region of the EDF’s amplified spontaneous emission (ASE) spectrum which occurs between 1530 and 1540nm. In this manner, the wavelength-encoded response of the FBG under strain is converted to a linear variation of the laser output power, removing the need for spectrum analysis as well as any limitations from the use of external edge-filtering components. In addition, the laser linewidth is significantly reduced with respect to the FBG bandwidth thus improving the resolution of the system, whereas its sensitivity can be controlled through the pumping power. The performance of the system has been characterized by modeling and experiments for EDF's with different lengths, doping concentrations and pumping power levels. The influence of mode-hopping in the laser cavity on the resolution and accuracy of the system has also been investigated.

(1) Background: A simple approach to map irrigated landcover has been introduced by using measures derived from optical spectral range as an alternative to thermal range. It has been demonstrated that substituting surface temperature (Ts, ‘thermal approach’) with SWIR transformed reflectance (STR, ‘optical approach’) to detect surface moisture is feasible with comparable results. (2) Methods: Using an iterative thresholding procedure to minimize within-class variance, the bilevel segmentation of variables derived from Landsat-8 representing surface moisture and vegetation cover was achieved for the 2020-21 summer for a key irrigation district in Australia. (3) Results: The results of irrigated landcover by optical approach found to be comparable with those by thermal approach. The classification accuracy was assessed using water delivery records at farm level. Though the overall accuracy is high in both cases, the optical approach (97.6%) performed slightly better than the thermal approach (93.9%). (4) Conclusions: The feasibility of using STR to map irrigated landcover has been confirmed by a high-level overall accuracy assessment. This has broader implications in terms of irrigated landcover assessment, as the use of satellite imagery in these applications may not necessarily be limited to microwave or thermal sensors.

The interface of a structural system in the soil is usually unsaturated. A decrease in the shear strength of the soil-structure interface can degrade the structure, especially under humid conditions. Studying the shear characteristics of the silt-concrete interface using a shear apparatus. Suction-controlled ring shear tests were carried out on the silt-concrete interface for three interface roughness values. The influence of the matric suction (s) and interface roughness (R) on the shear strength index of the silt-concrete interface was analyzed. The test results showed that high values of s and R improved the shear strength of the interface, but the result was affected by the net normal stress (NNS). High values of NNS and R improved the strain-hardening characteristics. NNS, s, and R significantly affected the interface shear shrinkage. The internal friction angle of the saturated interface was smaller than that of saturated silt, whereas the opposite occurred in the unsaturated state. The cohesion and internal friction angle of the interface rose with an increase in R, and they were larger than that of silt. A shear strength model of the silt and interface was established.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

Buckling defect will appear on the outer surface of the deformed ring during constrained ring rolling (CRR) of aluminum alloy thin wall conical ring with inner high ribs (AATWCRIHR), if the geometrical dimension of the ribs doesn't match the wall thickness. To avoid the buckling defect, a quantitative method for characterizing the degree of the buckling defect is proposed using the area of buckling profile. Then an orthogonal experimental scheme was designed taking the width of the middle rib, thickness of wall, and height of the middle rib as design variables and defining the area of buckling profile as optimization objective. Subsequently, a quadratic polynomial response surface model was established by combining the optimization algorithm with the finite element method (FEM), and the geometrical dimension of the middle ribs of the deformed AATWCRIHR is optimized. Also the optimal parameter combination to minimize the area of buckling profile is obtained and verified using FE simulation. Results show that the AATWCRIHR after optimization doesn’t generate the buckling defect during constrained ring rolling, and it is proved that the quantitative buckling defect representation method and the optimization design method based on the response surface model and the finite element simulation results are feasible for the constrained ring rolling process of the AATWCRIHR.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the chemical components on eggshell deserve further exploration. In two representative Coleopterans, a Coccinellid Henosepilachna vigintioctopunctata and a Chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and declined CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two Coleopteran species. Moreover, our findings propose the deposition of a CLS on the chorions.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

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

Transcription is carried out in most eukaryotes by three multimeric complexes (RNA polymerases I, II and III). However, plants contain two additional RNA polymerases (IV and V), which have evolved from RNA polymerase II. RNA polymerases II, IV and V contain both common and specific subunits that may specialize some of their functions. In this study, we conducted a search for the genes that putatively code for the specific subunits of RNA polymerases IV and V, as well as the corresponding of RNA polymerase II in olive. Based on the homology with the genes of Arabidopsis thaliana, we identified 13 genes that putatively code for the specific subunits of polymerases IV and V, and 16 genes that code for the corresponding specific subunits of polymerase II in olive. The transcriptomic analysis by RNA-Seq revealed that the expression of the RNA polymerases IV and V genes was induced during the initial stages of fruit development. Given that RNA polymerases IV and V are involved in the transcription of long non-coding RNAs, we investigated their expression and observed relevant changes in the expression of this type of RNAs. Particularly, the expression of the intergenic and intronic long non-coding RNAs tended to increase in the early steps of fruit development, suggesting their potential role in this process. The positive correlation between the expression of RNA polymerases IV and V subunits and the expression of non-coding RNAs supports the hypothesis that RNA polymerases IV and V may play a role in fruit development throughout the synthesis of this type of RNAs.

In this paper we study the normal bases for Galois ring extension ${{R}} / {Z}_{p^r}$ where ${R}$ = ${GR}$(p^r, n). We present a criterion on normal basis for ${{R}} / {Z}_{p^r}$ and reduce this problem to one of finite field extension $\overline{R} / \overline{Z}_{p^r}=F_{q} / F_{p} (q=p^n)$ by Theorem 1. We determine all optimal normal bases for Galois ring extension.

Mode locked pulse generation has been reported using both active and passive mode locking schemes. Active mode locking technique has been proven to be an effective way to generate high-repetition-rate pulses by incorporating a modulator inside the laser cavity. Compared to actively mode locked lasers, passively mode locked lasers can generate pulse train at ultrashort pulse width but with relatively lower repetition rate. Thus, it is a brilliant idea to build a hybrid mode locked system combining both active and passive mode lockers. In this review, several hybrid mode locked fiber ring laser systems are discussed and summarized. Hybrid mode locking is a promising method to generate high speed ultrashort optical pulses for fiber-optic telecommunication system.

The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the “Central Dogma of Molecular Biology”, has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesisfound to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundanceof a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer’s disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a Two-Tier Paradox and RNA Dark Matter. RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.

A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) is the Leishmania parasites carrying a viral endosymbiont Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable clinical outcomes. LRV1 has been observed in cultured strains of five L. (Viannia) species, and host specificity was suggested when studying LRV1 from L. braziliensis and L. guyanensis strains. The coevolution hypothesis of LRV1 and Leishmania was based on phylogenetic analyses, implying an association between LRV1 genotypes, Leishmania species, and their geographic origins. This study aimed to investigate LRV1 specificity to Leishmania (Viannia) species hosts by analyzing LRV1 from L. (Viannia) species. To this end, LRV1 was screened in L. (Viannia) species other than L. braziliensis or L. guyanensis, and it was detected in 11 out of 15 L. naiffi and in 2 out of 4 L. shawi. Phylogenetic analyses based on partial LRV1 genomic sequencing supported the hypothesis of host specificity, as LRV1 clustered according to their respective Leishmania species hosts. These findings underscore the importance of investigating Leishmania and LRV1 coevolution and its impact on Leishmania (Viannia) species dispersion and pathogenesis in the American Continent.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers. This manuscript gives an overview of the strategies employed in protamine-based RNA delivery, including the optimization of the nucleic acid’s stability and translational efficiency, as well as the regulation of its immunostimulatory properties from early studies to recent developments.

This review explores the unique structural and functional characteristics of natural products featuring highly oxygenated cyclobutane rings, with a specific focus on oxetane and 1,2-dioxetane motifs. It presents the structures and biological activities of compounds containing these rings, highlighting their contribution to molecular stability and pharmacological potency. Through detailed case studies and recent research findings, it has been demonstrated that these oxygen-rich rings enhance the molecular diversity and biological efficacy of natural products, potentially offering new avenues for drug development. Notably, these compounds are predominantly synthesized by microorganisms and can also be found in extracts from fungi, plants, and certain marine invertebrates. Compounds with oxetane and 1,2-dioxetane rings are primarily noted for their strong antineoplastic properties, among other biological activities. In contrast, most 1,2-dioxetanes exhibit potent antiprotozoal effects. It is important to note that 1,2-dioxetanes often serve as intermediate products in oxidation reactions, characterized by their instability and propensity to decompose into new compounds.

This paper describes developing and analyzing an analytical model of Microelectromechanical Systems (MEMS) internal vibrating ring gyroscope. The internal ring structure consists of eight semicircular beams attached to the externally placed anchors. The paper analyses the vibrating ring gyroscope inplane displacement behavior and the resulting elliptical vibrational modes. The elliptical vibrational modes appear as pairs with the same resonance frequency due to the symmetric nature of the design. The analysis commences by conceptualizing the ring as a geometric structure with a circular shape, possessing specific dimensions such as thickness, height, and radius. We construct a linear model that characterizes the vibrational dynamics of the internal vibrating ring. The analysis encompasses comprehensive mathematical formulations for the radial and tangential displacements in local polar coordinates, considering the inextensional displacement of the ring structure. By utilizing the derived equations, we highlight the underlying relationships driving the vibrational characteristics of the MEMS vibrating ring gyroscope. These dynamic vibrational relationships are essential in enabling the vibrating ring gyroscope's future utilization in accurate navigation and motion sensing technologies.

COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.

Abstract Background Context Pelvic ring fractures are becoming more common in the aging population and can prove to be fatal, having mortality rates between 10% and 16%. Stabilization of these fractures is challenging and often require immediate internal fixation. Therefore, it is necessary to have a biomechanical understanding of the different fixation techniques for pelvic ring fractures. Methods A previously validated three-dimensional finite element model of the lumbar spine, pelvis, and femur was used for this study. A unilateral pelvic ring fracture was simulated by resecting the left side of the sacrum and pelvis. Five different fixation techniques were used to stabilize the fracture. A compressive follower load and pure moment was applied to compare different biomechanical parameters including range of motion (contralateral sacroiliac joint, L1-S1 segment, L5-S1 segment), and stresses (L5-S1 nucleus stresses, instrument stresses) between different fixation techniques. Results Transiliac -trans sacral screw fixation at S1 and S2 showed the highest stabilization for horizontal and vertical displacement at the sacral fracture site and reduction of contralateral sacroiliac joint for bending and flexion range of motion by 165% and 121%, respectively. DTSF (Double transiliac rod and screw fixation) model showed highest stabilization in horizontal displacement at the pubic rami fracture site, while the L5_PF_W_CC (L5-Ilium posterior screw fixation with cross connectors) and L5_PF_WO_CC ( L5-Ilium posterior screw fixation without cross connectors) showed higher rod stresses, reduced L1-S1 (approximately 28%), and L5-S1 (approximately 90%) range of motion. Conclusions Longer sacral screw fixations were superior in stabilizing sacral and contralateral sacroiliac joint range of motion. Lumbopelvic fixations displayed a higher degree of stabilization in the horizontal displacement compared to vertical displacement of pubic rami fracture, while also indicating the highest rod stresses. When determining the surgical approach for pelvic ring fractures, patient-specific factors should be accounted for to weigh the advantages and disadvantages for each technique.

The utilization and engineering of thermo-optic effects have found broad applications in integrated photonic devices, facilitating efficient light manipulation to achieve various functionalities. Here, we perform both an experimental characterization and theoretical analysis of these effects in integrated micro-ring resonators in high index doped silica (HIDS), which has had many applications in integrated photonics and nonlinear optics. By fitting the experimental results with theory, we obtain fundamental parameters that characterize their thermo-optic performance, including the thermo-optic coefficient, the efficiency for the optically induced thermo-optic process, and the thermal conductivity. The characteristics of these parameters are compared to those of other materials commonly used for integrated photonic platforms, such as silicon, silicon nitride, and silica. These results offer a comprehensive insight into the thermo-optic properties of HIDS based devices. Understanding these properties is essential for efficiently controlling and engineering them in many practical applications.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

In this note we consolidate and give a brief description of several recently published results in ring theory having disproof. These results have been published during 2016 to 2021 in the so called non-predatory reputed mathematical journals indexed in the well known database like Scopus. We have considered results on rings in which each element is a sum of two idempotents appeared in Canad. Math. Bull. (2016), weakly tripotent rings appeared in Bull. Korean Math. Soc. (2018) and Rendiconti Sem. Mat. Univ. Pol. Torino (2021), involution t-clean rings appeared in Eur. J. Pure Appl. Math (2022) and strongly 2-nil clean rings with units of order two appeared in Eur. J. Pure Appl. Math (2023).

Six Half-ring with varying linewidth from 120nm to 370nm were connected in series on five corners. The magnetization reversal processes were investigated by the measurement of anisotropic magnetoresistances (AMR). The number of switching jumps in the AMR loops, from zero to five, varied with the longitudinal applied field. These discrete jumps result from domain wall nucleating and depinning on the corners. The larger external field applied the fewer number of jumps in the MR curve. This reproducible and particular-respondence of domain wall device in pattern of half-ring wire might be the new promising magnetoelectronic devices.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

A novel coronavirus (SARS-CoV-2) that is initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has killed 2,718 people in China by February 26, 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 38 countries around the world. However, the drug has not yet been officially licensed or approved to treat SARS-Cov-2 infection. NSP12-NSP7-NSP8 complex of SARS-CoV-2, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7-NSP8 complex (PDB ID: 6NUR) structure of SARS, two homologous models were established for virtual screening in the present study, namely NSP12-NSP7 interface model and NSP12-NSP8 interface model. Seven compounds (Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All seven compounds can combine well with NSP12-NSP7-NSP8 in the homologous model, providing drug candidates for the treatment and prevention of SARS-CoV-2.

Collision tumors, even uncommon, characterized by two distinctive (morphological, as well immunohistochemical) and spatially independent tumor components in the same location, are always puzzling for clinicians, pathologists and patients because they don’t fit in usual approaching schemes, neither diagnostic, nor therapeutic. Reviewing the specialized literature, until now, collision tumors have been reported in multiple locations such as the skin, esophagus, stomach, liver, kidney, bladder, adrenal gland or thyroid. We report a case of coexistence on the same site of a malignant tumor of ascending colon and a benign one emerging from peritoneal lining, thought initially by the surgeon to be right sided serosal carcinomatosis. But the histopatological examination reveals that those multiple serosal nodules were benign granular cell tumors collided with highly aggressive transparietal signet-ring colon carcinoma. These results put the patient's prognosis and therapeutic strategy in a different light than the clinical-imaging and intraoperative assessment.

Cutaneous Melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors (PD-1 and CTLA4) constituted a main breakthrough in the treatment of metastatic CM, particularly in the long-term benefit. However, several molecular pathways are responsible for the failure of this strategy in about 50-70% of CM patients. Some Long Non-coding RNAs (lncRNAs), and circular RNAs (circRNA) are implicated in triggering pro- and antitumorigenic responses to various cancer treatments. The relationship between lncRNA, circRNA and Immune Checkpoint Blockade (ICB) immunotherapy is not extensively explored in cutaneous metastatic melanoma (CMM). The aim of this study is to evaluate the potential role of both circRNA and lncRNA as a predictive immunotherapy biomarker in CMM. RNA-seq from 12 FFPE samples from the metastatic biopsy of metastatic melanoma patients treated with Nivolumab were analyzed. Our findings indicate that specific lncRNA and circRNA are involved in regulatory networks of the immune response against metastatic melanoma under treatment with nivolumab. Moreover, we have established a risk score that allows the prediction of Overall survival (OS) and Progression-free survival (PFS) of CMM patients with high accuracy. This proof of principle work provides a possible insight on the function of ceRNA, contributing to decipher the complex molecular mechanism of ICB cancer treatment response.

As an outstanding information carrier, skyrmion is increasingly widely used in devices based on complex geometries. To achieve the skyrmion-based spintronic devices, a reasonable and feasible nanotrack is essential. In this paper, we conducted a study on the current-driven skyrmion movement in a circular-ring-shaped nanotrack. Our results suggest that the asymmetry of the inside and outside boundary of the circular ring changed the stable position of the skyrmion, causing it to move like the skyrmion Hall effect when driven by currents. Moreover, the asymmetric boundaries have advantages in enhancing or weakening the skyrmion Hall effect. Additionally, we also compared the skyrmion Hall effect from the asymmetric boundary of circular ring nanotracks with that from inhomogeneous DMI. It is found that the skyrmion Hall effect caused by the circular ring is significantly greater than that caused by the inhomogeneous DMI. These results contribute to our understanding of the skyrmion dynamics in confined geometries and offer an alternative method for controlling the skyrmion Hall effect of skyrmion-based devices.

This work communicates cavity ring-down spectroscopy (CRDS) of methylidyne (CH) in a chemiluminescent plasma that is produced in a microwave cavity. Of interest are the rotational lines of the 0-0 vibrational transition for the A-X band and the 1-0 vibrational transition for the B-X band. The reported investigations originate from CH-radical research in 1996 that constituted the first case of applying CRDS to the CH radical. The report also includes recent analysis that shows excellent agreement of measured and computed data, and it communicates CH line strength data.

Solanesol is a noncyclic terpene alcohol composed of nine isoprene units and it mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). Here, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify solanesol biosynthesis genes. Six 1-deoxy-d-xylulose 5-phosphate synthase, two 1-deoxy-d-xylulose 5-phosphate reductoisomerase, two 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase, four 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase, two 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, four 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, two 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase, six isopentenyl diphosphate isomerase, and two solanesyl diphosphate synthase (SPS) genes were identified to be involved in solanesol biosynthesis. Furthermore, the two N. tabacum SPS (NtSPS1 and NtSPS2), which had two conserved aspartate-rich DDxxD domains, were highly homologous with SPS enzymes from other solanaceous plant species. In addition, the solanesol contents of three organs, and leaves from four growing stages, corresponded with the distribution of chlorophyll. Our findings provide a comprehensive evaluation of the correlation between the expression of different biosynthetic genes and the accumulation of solanesol in tobacco.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predict small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of Cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV-1 and MERS-CoV. Indeed, two of these drugs- emetine and homoharringtonine- were independently shown to inhibit SARS-CoV-2 as this article was in preparation. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy" nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA metabolism, showcasing the power of our approach. We investigate (i) mRNA translation in prokaryotes and eukaryotes, (ii) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (iii) miRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (iv) the identification of disrupted sequences that could lead to potential illnesses. To achieve this, we employ (a) infinite (finitely generated) groups fp, with generators representing the r+1 distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the miRNA seed in item (iii)], (b) aperiodicity theory, which connects “healthy groups" fp to free groups Fr of rank r and their profinite completion F^r, and (c) the representation theory of groups fp over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

Transcription factors (TFs) and microRNAs (miRNAs) are co-actors in genome-scale decoding and regulatory networks, often targeting common genes. In this paper, we describe the algebraic geometry of both TFs and miRNAs thanks to group theory. In TFs, the generator of the group is a DNA-binding domain while, in miRNAs, the generator is the seed of the sequence. For such a generated (infinite) group $\pi$, we compute the $SL(2,\mathbb{C})$ character variety, where $SL(2,\mathbb{C})$ is simultaneously a \lq space-time' (a Lorentz group) and a \lq quantum' (a spin) group. A noteworthy result of our approach is to recognize that optimal regulation occurs when $\pi$ looks like a free group $F_r$ ($r =1$ to $3$) in the cardinality sequence of its subgroups, a result obtained in our previous papers. A non free group structure features a potential disease. A second noteworthy result is about the structure of the Groebner basis $\mathcal{G}$ of the variety. A surface with simple singularities (like the well known Cayley cubic) within $\mathcal{G}$ is a signature of a potential disease even when $G$ looks like a free group $F_r$ in its structure of subgroups. Our methods apply to groups with a generating sequence made of two to four distinct DNA/RNA bases in $\{A,T/U,G,C\}$. Several human TFs and miRNAs are investigated in detail thanks to our approach.

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

Large aluminum alloy ring forgings are the core components of heavy-duty rocket fuel storage tanks, and the large residual stress inside the rings leads to poor shape accuracy of large thin-walled parts. The initial stress of the 2219 aluminum alloy ring blank was tested using the drilling method, and the creep constitutive coefficient of the 2219 aluminum alloy was determined through stress relaxation tests. The numerical simulation processes of thermal stress relief (TSR), vibration stress relief (VSR), and thermal-vibration stress relief (TVSR) were compared and established. Through the correlation analysis between the actual measurement results of residual stress and the simulation results, it can be seen that the strong correlation in three directions at each measurement point accounts for over 37.5%, and the moderate correlation accounts for over 62.5%. This indicates that the numerical simulation model of 2219 aluminum alloy ring containing initial residual stress can accurately reflect the size and distribution of residual stress inside the actual ring. The simulation results show that the derived constitutive model can describe the stress relaxation process of TVSR by combining a single thermal time effect stress relaxation constitutive theory with a VSR plastic deformation material model. The simulation models established above were used to calculate the residual stress homogenization ability of three types of aging. The results showed that VSR, TSR, and TVSR can homogenize and reduce the residual stress field inside the ring, improve the distribution of residual stress inside the ring, and have a better overall homogenization ability of TVSR. The VSR control has a certain effect on reducing and homogenizing residual stress, but compared with TSR and TVSR, the reduction and homogenization ability of residual stress control is limited. The homogenization control effect TVSR>TSR>VSR, and the maximum equivalent stress homogenization rates of VSR, TSR, and TVSR are 52.8%, 80.6%, and 82.2%, respectively. Then, numerical simulation technology is used to study how the initial residual stress in the blank will cause the deformation of the ring during the thin-walled machining process. The roundness error theory of the minimum containment area method is applied to evaluate the deformation degree during the thin-walled numerical machining process, and the TVSR method is used for stress regulation. The deformation law of the thin-walled machining of the ring under different aging parameters is studied.

Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from GISAID database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p<0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group. The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group. We concluded that RdRp P323L and spike protein D614G mutations predominate in severely affected COVID-19 patients. Further studies will be required to explore whether these mutations have any impact on the severity of COVID-19.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

Karst aquifers show dissolution/precipitation processes of the minerals present in the carbonate rocks. The Ring of Cenotes (RC) extends along the edge of the Chicxulub crater, in the limestone platform of the Yucatan Peninsula (YP), where groundwater shows preferential flow paths toward the coast near Celestun and Dzilam Bravo towns. This study aimed to describe the regional hydrogeochemical evolution of groundwater of the RC, and its association with the dissolution/precipitation of the minerals present along its path to the ocean. To achieve this aim, we: a) characterized groundwater's hydrogeochemistry; b) determined the calcite, dolomite, and gypsum saturation indexes (reaction phases with the groundwater) in the study area; c) proposed a hydrogeochemical model developed through PHREEQC using an inverse modelling approach. The model predictions confirmed that there are two evolution pathways of the groundwater consistent with the preferential flow paths suggested in a previous regionalization of the RC. On the western path, where groundwater flows towards Celestun, an important marine intrusion influences the hydrogeochemical processes and represents a risk for the prevalence of freshwater. On the eastern path, where groundwater flows toward Dzilam Bravo, the hydrogeochemistry in the sinkholes correlates well with rainfall, suggesting a higher vulnerability during droughts than during rainy periods.

Recent developments in optical biosensors based on integrated photonic devices are reviewed with a special emphasis on silicon-on-insulator ring resonator. The review is mainly devoted to the following aspects: (1) Principles of sensing mechanism, (2) sensor design, (3) biofunctionalization procedures for specific molecule detection and (4) measurement set-ups and advances in chip-integration. The inherent challenges of implementing photonics-based biosensors to meet specific requirements of applications in medicine, food analysis, and environmental monitoring are discussed.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

During the last few years, advancement in the area of biochemistry, science of the material world, engineering and computer-aided testing has directed towards advancement of high-throughput tools for the sake of profiling information encoded in a gene. Single-cell RNA-sequencing (scRNA-seq) tools capable to examine the sequence data from each individual cells and it shows within population variety and permit exploring of cell conditions and transformation by extreme resolution, possibly give out cell sub-types or gene expression fluctuations that are shaded in mass sequencing processes, which shows population-averaged evaluations. Yet, the major disadvantage for this tool is the lack of success to pick out location related details of the RNA transcriptome, as this needs tissue detachment and cell isolation. Location based transcript determination is among the advancements in the area of medical biotechnology as this can find out the molecules like RNA dataset in their intact physical placement in tissue segment with spatial context at the scale of a single-cell, which is very advantageous as compare to single-cell sequencing techniques. These approaches give key observation in the areas of biomedical field sub-disciplines like neurology, embryology, carcinoma study, immune cell investigation and histological activities. Generally, this review mainly focused towards single-cell sequencing methods, technology development, its challenges observed, different expression data analysis mechanisms and their applications in different areas, such as in cancer research, microbes, central nervous system, sex organs and immune-biology, intensifying the essentiality of sequencing tools at single-cell level for the characterization of extremely dynamic individual cells.

The transition from the Peptide/RNA world to the Protein/RNA world in the hydrothermal vent environment was a major event in the history of life. The advent of proteins utterly changed the conditions of emerging life, representing a watershed in its development. During subsequent translation various protein enzymes emerged driving protocells into a more complex and interconnected system. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Four major events followed after availability of various kinds of protein molecules during prebiotic synthesis. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) the beginnings of the virus world; and (4) the advent of DNA. The first innovation mediated by proteins was the improvement of the cell membrane. The phospholipid membrane was initially evolved in a vent environment from the gradual modification of a fatty acid membrane via an intermediate phosphatidate acid by non-enzymatic reactions. The phospholipid is then synthesized from phosphatidate acid by a series of enzymes. To make the phospholipid membrane more permeable, various protein molecules interacted with the cell membrane. Proteins not only stabilized the wall membrane, but also acted as pumps, preventing some molecules from the protocells from crossing the membrane barriers, while permitting other selected molecules and ions to enter and leave the protocell. The second modification led by proteins is the gradual conversion of the interior of the protocell from a water-like medium into a gel-like cytoplasm, which became the storehouse of a wide range of biomolecules including amino acids, proteins, nucleic acids, ribosomes, as well as salt and water. The third innovation utilizing the newly synthesized proteins was the emergence of the ancient virus world. In the milieu of different kinds of mRNAs in the prebiotic soup, jelly-roll capsid genes originated de novo within genomes of nonviral mRNAs by overprinting. These fragile capsid genes were possibly coated by proteins on the mineral substrate for stability and durability, transforming them into ancient viral particles. These protein coats were random and were not encoded by encased genes. Some protocells might have engulfed these viral particles, when the capsid genes utilized the ribosomes of the host to translate into the appropriate capsid proteins. These capsid proteins then coated the viral genes to make new copies of primordial viruses inside the protocell. Since then, viruses became capsid-encoding organisms. These primordial mRNA viruses parasitized RNA-based protocells, manipulating them to make new copies of themselves. This was the beginning of a relentless war between viruses and their protocellular hosts. The next stage in viral evolution was the emergence of a primitive retrovirus (pre-retrovirus) with a new kind of replicative strategy in a sense that it could turn its RNA into DNA using its own reverse transcriptase enzyme. This is the beginning of the Retro world that facilitated the transition from RNA to DNA genomes. The infection of RNA protocells with pre-retroviruses progressively transferred the RNA genome to a viral DNA genome by retro-transcription. The advent of DNA by the pre-retrovirus marks the fourth innovation, when a number of enzymes had already developed and were utilized by pre-retroviruses. With continued infection, DNA viruses slowly transferred not only their core replication enzymes, such as helicase, primase, and DNA polymerase, to RNA protocells, but also to their DNAs as well. Thus, began the DNA world, when DNA replaced RNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. The new protocell with the DNA genome will diversify into large populations of DNA protocells that will outcompete populations of RNA protocells. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. It was carried out by a set of enzymes that formed a Z-ring at the site of replication. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification. These primordial hyperthermophiles, presumably the first life, obtained food and energy directly from the vent environment. However, such a situation was self-limiting, so the early cells evolved their own mechanisms for generating metabolic energy and synthesizing the molecules necessary for their reproduction. The earliest fossil record (≥ 3.5 Ga) of biotic activity is preserved in the Archean hydrothermal and sedimentary rocks of the Nuvvuagittuq Craton of Canada, the Isua Craton of Greenland, the Pilbara Craton of Australia, the Kaapvaal Craton of South Africa, and the Singhbhum Craton of India in the form of the carbonaceous remains of microbial cells, cellular microfossils, and stromatolites. These microscopic fossils provide crucial evidence of the origin and early evolution of prokaryotic cells, beginning with hyperthermophiles. Molecular phylogenetic analysis suggests that both domains of life ¬– Bacteria and Archaea probably split from the last universal common ancestor (LUCA), a hyperthermophilic organism. In the younger sequences of these Archean cratons, two kinds of photosynthetic bacteria, anoxygenic green sulfur bacteria, and oxygenic cyanobacteria, appeared in quick succession from the thermophilic ancestor, indicating a shift of niche from a benthic to a planktonic, with reduced thermotolerance. The development of anoxygenic and oxygenic photosynthesis would have allowed life to escape the hydrothermal setting and invade a newly evolved habitat—broad continental shelves to tap solar energy. Cyanobacteria invaded the global ocean, turned it into blue and green, produced oxygen for the first time, and left their signatures in the carbonates and stromatolites.

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25^o C beclabuvir, a non-nucleoside inhibitor of the RdRp_HCV can efficiently bind to RdRp _SARS-CoV-2 (ΔG_AutoDock = -9.95 kcal mol^-1) with an inhibition constant of 51.03 nM. Both the ΔG_London and ΔG_{GBVI / WSA} values were - 9.06 and - 6.67 kcal mol^-1, respectively for binding of beclabuvir to RdRp_SARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRp_SARS-CoV-2 (ΔG_vina = -8.0 kcal mol^-1) than that observed with the Thumb 1 domain of RdRp_HCV (ΔG_vina = -7.1 kcal mol^-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549^th to 776^th amino acid residues of RdRp_SARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp_SARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

Abstract: (1) Background: Cancer immune escape is associated with the metabolic reprogramming of TME, and combining metabolic targets with immunotherapy has great potential to improve clinical outcomes. Among all metabolic processes, lipid metabolism, especially fatty acid (FA) metabolism, has a huge role in cancer cell survival, migration, and proliferation, but its mechanism and role in the tumor immune microenvironment remain to be investigated. (2) Methods: We comprehensively analyzed 309 fatty acid-related genes, screened 121 different genes, and used one-way COX regression to select 15 genes with prognostic impact. Systematically evaluated the correlation between FMGs modification patterns and Tumor Microenvironment Infiltration, prognosis, and Immunotherapy. The FMGs-Score was constructed to quantify the FMGs modification patterns using principal component analysis. (3) Results: Three clusters based on FMGs-related genes were demonstrated in breast cancer, with three patterns of distinct immune cell infiltration and biological behavior. An FMGsScore signature was constructed to reveal that patients with a low FMGsScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, better survival advantage, and were more sensitive to immunotherapy than those with a high FMGsScore. Finally, the expression and function of the signature key gene NDUFAB1 were examined by in vitro experiments. (4) Conclusions: This study significantly demonstrates the non-negligible role of FMGs in the immune microenvironment of breast cancer, and that FMGsScores can be used to guide the prediction of immunotherapy in breast cancer patients. In in vitro experiments, knockdown of the NDUFAB1 gene resulted in reduced proliferation and migration of MCF-7 cell lines.

Zika virus (ZIKV) has been characterized as one of the potential pathogens and placed under future epidemic outbreaks by the WHO. However, lack of potential therapeutics can result in uncontrolled pandemic like other human pandemic viruses; therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted the strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the ZIKVpro and ZIKVRdRp proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of top four common bioflavonoids, viz. rutin, nicotiflorin, isoquercitrin, and hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (His51, Asp74, and Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals the stability of respective docked complexes contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp for further experimental assessment.

Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first reagent that was used suc-cessfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from their activity in neurons, chlorpromazine have also been reported to display anticancer and antibacterial properties. In these studies, we present the synthesis and research on the activ-ity against A549, MDA, MiaPaCa, PC3 and HCT116 cancer cell lines and against S. aureus, S. epi-dermidis, E. coli and P. aeruginosa bacterial strains a series of new tetracyclic chlorpromazine ana-logues containing a quinoline scafford in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been deter-mined by 1H NMR, 13C NMR and HRMS spectral techniques. The seven most active of the twen-ty-four new chlorpromazine analogues tested were selected for study of the mechanism of cyto-toxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected com-pounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, Mi-aPaCa-2 and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis.

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m⁶A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m⁶A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.

This research focuses on deriving the equation of motion for fermions on a ring. The paper proposes an alternative equation for fermions on the ring, incorporating a self-rotation angle denoted as $\Delta$, and explores its relationship with the original equation.

Cytokinesis, as the last stage of the cell division cycle, is a tightly controlled process amongst all eukaryotes, and defective division can lead to severe cellular consequences, and is implicated in serious human diseases and conditions such as cancer. Both mammalian cells and the fission yeast Schizosaccharomyces pombe use binary fission to divide into two equal sized daughter cells. In S. pombe such cytokinetic division is driven by the assembly of an actin-myosin contractile ring (ACR) at the cell equator between the two cell tips. The ACR is composed of a complex network of membrane scaffold proteins, actin filaments, myosin motors, and other cytokinesis regulators. Contraction of the ACR leads to the formation of a cleavage furrow which is severed leading to the final cell separation during the last stage of cytokinesis, abscission. This review describes recent findings defining the three phases to establish cytokinesis in S. pombe: ACR assembly, ACR constriction, and its coordination with septation. Collectively, we provide an overview of current understanding of the mechanisms regulating the ACR-mediated cytokinesis in S. pombe.

A closed chain of oscillators can be considered as a model of ring-shaped ecosystems, such as atolls or coastal zones of inland reservoirs. As an oscillator model, we use the logistic map that often referred to as an archetypical example of how complex dynamics can arise from very simple nonlinear equations. We investigate the influence of the model parameters both on the nature of oscillations in the oscillator ring and on the spatial structures that arise in this case. Namely, we demonstrate a variety of emerging spatial structures depending on the initial conditions.

This work presents first time successfully fabricated silica few-mode microstructured optical fiber (MOF) with hollow GeO2-doped ring core and strongly induced twisting up to 790 revolutions per meter. Some technological issues for manufacturing of GeO2-doped supporting elements for large hollow cores as well as described above complicated spun MOFs are discussed. We introduce some results of tests, performed for pilot samples of designed and manufactured described above untwisted and twisted MOFs with outer diameter 65 µm and hollow ring core inner diameter 30.5 µm under wall thickness 1.7 µm and refractive index difference n=0.030, including their geometrical parameters, basic transmission characteristics and measurements of far-field laser beam profile patterns.

We demonstrate a compact 4x4 wavelength selective switch with 50 % fewer electrical pads as compared with our previous generation. We report loss and crosstalk for different paths of the switch. We measure median loss of 5.32 dB and worst case crosstalk of -35 dB. The microring resonators tune by more than one free spectral range, which is an improvement over our previous generation of switches. This switch can support 8 channels at 400 GHz spacing. We conclude that it is not possible to drive both microring resonators with the same voltage and separate control is required because of fabrication variation of the current technology.

Floral meristems are dynamic systems that generate floral organ primordia at their flanks and, in most species, terminate while giving rise to the gynoecium primordia. However, we find species with floral meristems that generate additional ring meristems repeatedly throughout angiosperm history. Ring meristems produce only stamen primordia, resulting in polystemous flowers (having stamen numbers more than double that of petals or sepals), and act independently of the floral meristem activity. Most of our knowledge on floral meristem regulation is derived from molecular genetic studies of Arabidopsis thaliana, a species with a fixed number of floral organs and as such of only limited value to understand ring meristem function, regulation, and ecological value. This review provides an overview of the main molecular players regulating floral meristem activity in A. thaliana, and summarizes our knowledge of ring primordia morphology and occurrence in dicots. Our work provides a first step towards understanding the significance and molecular genetics of ring meristem regulation and evolution.

We investigate a notable class of states peculiar to a bosonic binary mixture featuring repulsive intraspecies and attractive interspecies couplings. We evidence that, for small values of the hopping amplitudes, one can access particular regimes marked by the fact that the interwell boson transfer occurs in a jerky fashion. This property is shown to be responsible for the emergence of a staircase-like structure in the phase diagram and to strongly resemble the mechanism of the superfluid-Mott insulator transition. Under certain conditions, in fact, we show that it is possible to interpret the interspecies attraction as an effective chemical potential and the supermixed soliton as an effective particle reservoir. Our investigation is developed both within a fully quantum approach based on the analysis of several quantum indicators and by means of a simple analytical approximation scheme capable of capturing the essential features of this ultraquantum effect.

A modified free-wake vortex ring model is proposed to compute the dynamics of a floating horizontal-axis wind turbine. The model is divided into two parts. The near wake model uses a blade bound vortex model and trailed vortex model, which is developed based on vortex filament method. By contrast, the far wake model is based on the vortex ring method. The proposed model is a good compromise between accuracy and computational cost, for example when compared with more complex vortex methods. The present model is used to assess the influence of floating platform motions on the performance of a horizontal-axis wind turbine rotor. The results are validated on the 5MW NREL rotor and compared with other aerodynamic models for the same rotor subjected to different platform motions. It was found that the results from the proposed method are more reliable than the results from BEM theory especially at small angles of attack in the region of low wind speeds, on the one hand, and high wind speeds with blade pitch motions, on the other hand. And also the proposed method is less time consuming and has similar accuracy when comparing with more advanced vortex based methods.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

The Ro60 autoantigen is an RNA-binding protein, and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates quality control and cellular dis-tribution of YRNAs, retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal TLRs and cytoplasmic RNA sensors, which typically sense patho-gen-associated molecular patterns (PAMPs) and mount the first line of defence against invading pathogens. However, recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases including Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for an-ti-drug antibody response among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mecha-nisms of autoimmune conditions.

The COVID-19 pandemic stimulated attention to the medicinal applications of messenger RNA (mRNA). mRNA is expected to be applied not only to vaccines but also to regenerative medicines. The purity of mRNA is important for its medicinal application. However, the current mRNA synthesis techniques have problems, e.g., contamination of undesired 5’-uncapped mRNA and double-stranded RNAs. Recently, our group developed a completely capped mRNA synthesis technology that contributed to the progress of mRNA research. The introduction of chemically modified nucleosides, e.g., N1-methylpseudouridine and 5-methylcytidine, have been demonstrated by Dr. Karikó and Dr. Weissman which opened the practical application of mRNA for vaccines and regenerative medicines. Dr. Yamanaka reported the production of Induced Pluripotent Stem Cells (iPSCs) by the introduction of 4 types of genes using a retrovirus vector. iPSCs are widely used for research about regenerative medicines and the preparation of disease models to screen new drug candidates. Of the Yamanaka factors, Klf4 and c-Myc are oncogenes, and there is a tumor development risk if these are integrated into genomic DNA. Therefore, regenerative medicines using mRNA, which has no risk of genome insertion, have attracted attention. In this review, we summarized the synthesis of mRNA and its application for regenerative medicine.

X-ray diffraction (XRD) analysis of complex poly-atomic systems, especially of biomolecules, using ultra-short laser pulses (USP), is currently one of the most important fields of modern physics. The basis for interpreting and "deciphering" experimental data is the well-known theory of X-ray scattering, where the main parameter of USPs - its duration - is not taken into account. In the present work it is shown that for scattering of attosecond USPs on DNA and RNA trinucleotides the pulse length is the most important scattering parameter. In this case the diffraction pattern significantly changes with respect to the previously known scattering theory. The results obtained are extremely important in XRD when using attosecond pulses to study trinucleotides of DNA and RNA because using the previously known scattering theory which does not take into account the duration of USPs one can not correctly interpret and therefore "decode" DNA and RNA structures.

Our perspective article covers major findings concerning Feline Infectious Peritonitis (FIP) - a fatal coronaviral disease of cats. In the context of FIP pathogenesis, we outline disease signalment and focus on the challenges and promises of FIP invoking coronavirus RNA detection. In particular, we outline critical aspects of coronavirus RNA replication and biogenesis. We infer the replicative intermediates of feline coronavirus may constitute an underappreciated factor triggering the progression of the maladaptive immune response underlying FIP pathogenesis.

The role of innate immunity in neutralization of viral infections (including COVID-19) and forming long-lasting and specific immune memory is considered. It is assumed that antiviral protection is generated by the mechanism of RNA interference (RNAi) and is based on the presence of specific viral patterns in the DNA library of the host cells.

Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. After the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“Oral Turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.

To understand the evolution of the human norovirus GII.P6-GII.6 and GII.P7-GII.6 strains, we analyzed both the RdRp region and VP1 gene in globally collected strains using authentic bioinformatics technologies. A common ancestor of the P6- and P7-type RdRp region emerged approximately 50 years ago and a common ancestor of the P6- and P7-type VP1 gene emerged approximately 110 years ago. Subsequently, the RdRp region and VP1 gene evolved. Moreover, the evolutionary rates were significantly faster for the P6-type RdRp region and VP1 gene than the P7-type RdRp region and VP1 genes. Large genetic divergence was observed in the P7-type RdRp region and VP1 gene compared with the P6-type RdRp region and VP1 gene. The phylodynamics of the RdRp region and VP1 gene fluctuated after the year 2000. Positive selection sites in VP1 proteins were located in the antigenicity-related protruding 2 domain, and these sites overlapped with conformational epitopes. These results suggest that the GII.6 VP1 gene and VP1 proteins evolved uniquely due to recombination between the P6- and P7-type RdRp regions in the HuNoV GII.P6-GII.6 and GII.P7-GII.6 virus strains.

Grinding processes’ stochastic nature poses a challenge in predicting the quality of the resulting surfaces. Post-production measurements for form, surface roughness, and circumferential waviness are commonly performed due to infeasibility in measuring all quality parameters during the grinding operation. Therefore, it is challenging to diagnose the root cause of quality deviations in real-time resulting from variations in the machine’s operating condition. This paper introduces a novel approach to predicting the overall quality of the individual parts. The grinder is equipped with sensors to implement condition-based maintenance and is induced with five frequently occurring failure conditions for the experimental test runs. The crucial quality parameters are measured for the produced parts. Fuzzy c-means (FCM) and Hotelling’s T-squared (T2) have been evaluated to generate quality labels from the multi-variate quality data. Benchmarked random forest regression models are trained using fault diagnosis feature set and quality labels. Quality labels from the T2 statistic of quality parameters are preferred over FCM approach for their repeatability. The model, trained from T2 labels achieves more than 94% accuracy when compared to the measured ring disposition. The predicted overall quality using the sensors’ feature set is compared against the threshold to reach a trustworthy maintenance decision.

A progressive FEA fatigue degradation model for composites was developed and implemented using a UMAT user material subroutine in Abaqus. Numerical results were compared to experimental strain field data from high frequency Digital Image Correlation (DIC) of split disk fatigue testing of pressure vessel cut outs with holes. The model correctly predicted the onset and evolution of damage in the matrix as well as the onset of fiber failure. The model use progressive failure analysis based on the maximum strain failure criterion, the cycle jump method and Miner sum damage accumulation rule. A parameter study on matrix properties was needed to capture the scatter in strain fields observed experimentally by DIC. S-N curve for the matrix material had to be lowered by 0% to 60% to capture the experimental scatter. The onset of local fiber failure had to be described by local S-N curves measured by DIC having 2.5 times greater strain than that of S-N curves found from standard coupon testing.

Height assignment is an important problem for satellite measurements of Atmospheric Motion Vectors (AMVs) that are interpreted as winds by forecast and assimilation systems. Stereo methods assign heights to AMVs from the parallax observed between observations from different vantage points in orbit while tracking cloud or moisture features. In this paper, we fully develop the stereo method to jointly retrieve wind vectors with their geometric heights from geostationary satellite pairs. Synchronization of observations between observing systems is not required. NASA and NOAA stereo-winds codes have implemented this method and we have processed large datasets from GOES-16, -17, and Himawari-8. Our retrievals are validated against rawinsonde observations and demonstrate the potential to improve forecast skill. Stereo winds also offer an important mitigation for the loop heat pipe anomaly on GOES-17 during times when warm focal plane temperatures cause infra-red channels that are needed for operational height assignments to fail. We also examine several application areas, including deep convection in tropical cyclones, planetary boundary layer dynamics, and fire smoke plumes, where stereo methods provide insights into atmospheric processes. The stereo method is broadly applicable across the geostationary ring where systems offering similar Image Navigation and Registration (INR) performance as GOES-R are deployed.

Layered two-dimensional (2D) graphene oxide (GO) films are integrated with micro-ring resonators (MRRs) to experimentally demonstrate enhanced nonlinear optics in the form of four-wave mixing (FWM). Both uniformly coated and patterned GO films are integrated on CMOS-compatible doped silica MRRs using a large-area, transfer-free, layer-by-layer GO coating method together with photolithography and lift-off processes, yielding precise control of the film thickness, placement, and coating length. The high Kerr nonlinearity and low loss of the GO films combined with the strong light-matter interaction within the MRRs results in a significant improvement in the FWM efficiency in the hybrid MRRs. Detailed FWM measurements are performed at different pump powers and resonant wavelengths for the uniformly coated MRRs with 1−5 layers of GO as well as the patterned devices with 10−50 layers of GO. The experimental results show good agreement with theory, achieving up to ~7.6-dB enhancement in the FWM conversion efficiency (CE) for an MRR uniformly coated with 1 layer of GO and ~10.3-dB for a patterned device with 50 layers of GO. By fitting the measured CE as a function of pump power for devices with different numbers of GO layers, we also extract the dependence of GO’s third-order nonlinearity on layer number and pump power, revealing interesting physical insights about the evolution of the layered GO films from 2D monolayers to quasi bulk-like behavior. These results confirm the high nonlinear optical performance of integrated photonic resonators incorporated with 2D layered GO films.

RNA pol II assembly occurs in the cytoplasm before the translocation of the enzyme to the nucleus. Affecting assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In this work, we show that impairment of RNA pol II assembly leads to a decrease in cryptic non-coding RNAs (preferentially CUTs and SUTs). This alteration is partially restored upon overcoming the assembly defect. Notably, this drop in ncRNAs is only partially dependent on the nuclear exosome, which suggests a major specific effect of enzyme assembly. Our data also point out a defect in transcription termination and lead as to proposes that CTD phosphatase Rtr1 could be involved in this process.

SARS-CoV-2 infection remains a global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of genomic RNA (gRNA), sub-genomic RNA (sgRNA) and replication centers/organelles (ROs). We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA, immunofluorescence to detect nsp3 protein, a marker for the formation RO, and carried out a time course analysis. We found that single molecules of gRNA are visible within the cytoplasm at 30 minutes post-infection (p.i.). Starting from 2 hr. p.i., most of the viral RNA existed in clusters/speckles, some of which were surrounded by single molecules of sgRNA. These speckles associated with nsp3 protein starting at 3 hr. p.i., indicating that these were precursors to ROs. Furthermore, RNA replication was asynchronous as cells with RNA at all stages of replication were found at any given time point. Our probes detected the SARS-COV-2 variants of concern, and BA.1 strain exhibited slower rate of replication kinetics than the WA1 strain. Our results provide insights into the kinetics of SARS-CoV-2 early post-entry events, which will facilitate identification of new therapeutic targets to early stage replication to combat COVID-19.

Influenza virus transcription is catalyzed by the viral RNA-polymerase (FluPol) through a cap-snatching activity. The snatching of the cap of cellular mRNA by FluPol is preceded by its binding to the flexible C-terminal domain (CTD) of the RPB1 subunit of RNA-polymerase II (Pol II). To better understand how FluPol brings the 3’-end of the genomic RNAs in close proximity to the host-derived primer, we hypothesized that FluPol may recognize additional Pol II subunits/domains to ensure cap-snatching. Using binary complementation assays between the Pol II and FluPol subunits and their structural domains, we revealed an interaction between the N-third domain of PB2 and RPB4. This interaction was confirmed by a co-immunoprecipitation assay and found to occur with the homologous domains of influenza B and C FluPols. Residues [1-72] of RPB4 were found critical in this interaction. Numerous punctual mutants generated at conserved positions between influenza A, B and C FluPols in the N-third domain of PB2 exhibited strong transcriptional activity defect. These results suggest that FluPol interacts with several domains/subunits of Pol II, the CTD to bind Pol II initiating host transcription and a second on RPB4 to locate FluPol at the proximity of the 5’-end of nascent host mRNA.

Background: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. Methods: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations at one side of the mandible and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, the xenograft block was adapted to the defect and fixed with an implant (inlay group). Results: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close at the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ±9.3%) compared to the onlay (10.4 ±7.4%) groups (p=0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ±1.05% at the onlay group and 0.78 ±0.71% at the inlay group (p=0.603). Conclusion: The inlay grafts exhibited a higher new bone percentage than the onlay grafts possibly due to the defect conformation that presented more sources for bone formation. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in growth of bone on the graft trabeculae toward the most superior regions in both groups, and in the closure of the coronal entrance of the defects in the inlay group.

The aim of this work is to propose two different and complementary sensors for the structural health monitoring of concrete beams. In particular, a diffused sensing element and a split ring resonator network are presented. The first sensor is able to detect the variation of the dielectric properties of the concrete along the whole beam length, for a diffuse monitoring both during the important concrete curing phase and also for the entire life cycle of the concrete beams. The resonators instead work punctually, in their surroundings, allowing an accurate evaluation of the permittivity both during the drying phase and after. This allows the continuous monitoring of any presence of water both inside the concrete beam and in points that can be critical, in the case of beams in dams, bridges or in any case subject to a strong presence of water which could lead to deterioration, or worse, cause serious accidents. Moreover, the punctual sensors are able to detect the presence of cracks in the structure and to localize them.

This study investigates the vertical structure of the dynamical properties of a warm-core ring in the Gulf of Mexico (Loop Current ring) using glider observations. We introduce a new method to correct the glider’s along-track coordinate which is, in general, biased by the unsteady relative movements of the glider and the eddy, yielding large errors on horizontal derivatives. Here, we take advantage of the synopticity of satellite along-track altimetry to apply corrections on the glider’s position, by matching in situ steric height with satellite-measured sea surface height. This relocation method allows to recover the eddy’s azimuthal symmetry, to precisely estimate the rotation axis position, and to compute reliable horizontal derivatives. It is shown to be particularly appropriate to compute the eddy’s cyclo-geostrophic velocity, relative vorticity, and shear strain, which are otherwise out of reach when using the glider’s raw traveled distance as an horizontal coordinate. The Ertel potential vorticity (PV) structure of the warm core ring is studied in details, and we show that the PV anomaly is entirely controlled by vortex stretching. Sign reversal of the PV gradient across the water column suggests that the ring might be baroclinically unstable. The PV gradient is also largely controlled by gradients of the vortex stretching term. We also show that the ring’s total energy partition is strongly skewed, with available potential energy being 3 times larger than kinetic energy. The possible impact of this energy distribution on the Loop Current rings longevity is also discussed.

N6-methyladenosine (M6A) modification is the most abundant internal chemical modification on RNA molecules in eukaryotes and can affect mRNA metabolism and regulate RNA transcription, nuclear export, splicing, degradation, translation, ets, and has a significant impact on various aspects of physiology or pathobiology. Radiotherapy is the most common measure of tumor treatment, variety of cellular intrinsic mechanisms affect the responses of cells to ionizing radiation (IR) and effectiveness of cancer radiotherapy. In this review, we summarize and discuss the recent advances about the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage response, and outcomes of cancer radiotherapy. Insights into the RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy as well as radioprotection on normal tissues.

Non-alcoholic steatohepatitis (NASH) is a clinically serious stage of non-alcoholic fatty liver disease (NAFLD). Histologically characterized by hepatocyte ballooning, immune cell infiltration and fibrosis, NASH at a molecular level involves lipid induced hepatocyte death and cytokine production. Currently, there are very few diagnostic biomarkers available to screen NASH, and no pharmacological intervention is available for its treatment. In this study, we show that hepatocyte damage by lipotoxicity results in the release of extracellular RNAs (eRNAs) which serve as damage-associated molecular patterns (DAMPs) that stimulate the expression of pro-apoptotic and pro-inflammatory cytokines, aggravating inflammation, and cell death in HepG2 cells. Furthermore, the inhibition of eRNA activity by RNase 1 significantly increased cellular viability and reduced NF-kB mediated cytokine production. Similarly, RNase 1 administration significantly improved hepatic steatosis, inflammatory and injury markers in a murine NASH model. This study, therefore, for the first time, underscores the therapeutic potential of inhibiting eRNA action as a novel strategy for NASH treatment.

For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies into shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extra ordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease (Mpro), Nsp12 RNA-dependent-RNA-polymerase (RdRp) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 outbreak.

Malaria, leishmaniasis, and African trypanosomiasis are protozoan diseases that constitute a major global health problem, especially in developing countries; however the development of drug resistance coupled with the toxicity of current treatments have hindered their management. The implication of certain enzymes (dihydrofolate reductase, DHFR) or proteins (potassium channels) in the pathogenesis of these protozoan diseases is undeniable. In this study, a series of three DHFR inhibitors (6-5 fused heterocyclic derivatives X, Y and Z) and one K+ channel blocker (E4031) were screened for their inhibitory effect on Leishmania donovani, Plasmodium falciparum, and Trypanosoma brucei. Resazurin assay was used to assess antitrypanosomal and antileishmanial activities of test compounds, whereas the antimalarial activity was appraised through SYBR Green I test. Moreover, cytotoxicity of test compounds was evaluated on Vero, Raw 264.7 and HepG-2 cells using the resazurin-based test, whilst their pharmacokinetic properties were predicted using the online tool pkCSM. As a result, compound Y revealed a selective (selectivity index range: 2.69 - &gt;61.4; Vero, Raw 264.7 and HepG-2 cells) and broad-spectrum antiprotozoal activity against L. donovani promastigotes (IC50: 12.4 µM) and amastigotes (IC50: 4.28 µM), P. falciparum (IC50: 0.028 µM), and T. brucei brucei (IC50: 0.81 µM). In addition, compound X inhibited the growth P. falciparum (IC50: 0.0052 µM) and T. brucei brucei (IC50: 6.49 µM). In silico screening of the active antiprotozoal compounds revealed positive drug-likeness scores as none of Lipinski's rule of five’s criteria was violated by these compounds. However, in-depth pharmacokinetic and mechanistic studies are warranted to support discovery of novel antiprotozoal agents against malaria, leishmaniasis, and African trypanosomiasis by repurposing K+ channel blocker and DHFR inhibitors.

Background: The lymph nodes staging system can predict the prognosis of gastric signet ring cell carcinoma (SRCC), but the optimal system for early and advanced SRCC remains unknown. Methods: This study retrospectively analyzed 693 SRCC patients who underwent radical resection in the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital. The predicted performance of three lymph node staging systems, including pN staging, lymph node metastasis rate (LNR), and log odds of positive lymph nodes (LODDS), was compared using the receiver characteristic operating curve (ROC). The kaplan⁃meier method and the log⁃rank test analyze the overall survival of patients. The Cox risk regression model identifies independent risk factors associated with patient outcomes. The nomogram was made by R studio. Results: The 693 SRCC included 165 early SRCC and 528 advanced SRCC. ROC showed that LODDS had better predictive performance than pN and LNR in predicting prognosis regardless of early or advanced SRCC. LODDS can be used to predict the prognosis of early and advanced SRCC and was an independent risk factor associated with patient outcomes (P=0.002, P<0.001). Furthermore, the nomogram constructed by LODDS and clinicopathological features had good predictive performance. Conclusion: LODDS showed a clear prognostic superiority over both pN and LNR in early and advanced SRCC.

Background: Redo mitral valve surgery is the standard of care for failed mitral bioprostheses or recurrence of mitral regurgitation after repair. Nonetheless, catheterbased valve-in-valve (ViV) or valve-in-ring (ViR)-procedures increasingly become viable alternatives in high risk subpopula-tions. Despite reported good initial results, only little is known about longer-term outcomes. The present series report long-term outcomes of transcatheter mitral ViV- and ViR-procedures. Methods: All consecutive patients (n=54) undergoing transcatheter mitral ViV- or ViR-procedures for failed bioprostheses or recurring regurgitation after mitral repair were retrospectively en-rolled in the time period between 2011 and 2021. The mean age was 76.5 ± 6.5 years, and 30 (55.6%) of the patients were male. The procedures were done using a commercially available balloon-expandable transcatheter heart valve. Clinical and echocardiographic follow-up data were obtained out of the hospital’s database and analyzed. Follow-up reached up to 9.9 years with a total of 164.3 patient-years. Results: A total 25 patients received a ViV- and 29 patients a ViR-procedure. Both groups were at high surgical risk with an STS-PROM of 5.9 ± 3.7 % in ViV- and 8.7 ± 9.0% in ViR-patients, respectively (p<0.01). The procedures itself were mainly unevent-ful with no intraoperative deaths and a low conversion rate (n=2/54; 3.7%). VARC-2 procedural success was low (ViV 20.0% and ViR 10.3%; p=0.45), which was either driven by high rates of transvalvular pressure gradients “>5mmHg” (ViV 92.0% and ViR 27.6%; p<0.01) or residual regurgitation “>trace” (ViV 28.0% and ViR 82.7%; p<0.01). ICU-stay was prolonged in both groups (ViV 3.8 ± 6.8 days and ViR 4.3 ± 6.3 days; p=0.96) with acceptable hospital stay (ViV 9.9 ± 5.9 days and ViR 13.5 ± 8.0 days; p=0.13). Despite 30-days mortality was acceptable (ViV 4.0% and ViR 6.9%; p=1.00), the mean posthospital survival time was disappointingly low (ViV 3.9 ± 2.6 years and ViR 2.3 ± 2.7 years; p<0.01). Overall survival I the entire group was 33.3%.Cardiac reasons for death were frequent in both groups (ViV 38.5% and ViR 52.2%). Cox-regression analysis identified ViR-procedures as a predictor of mortality (HR 2.36, CI 1.19 - 4.67, p=0.01). Conclusions: Despite acceptable immediate outcomes in this high-risk subpopulation, long-terms results are discouraging. Transvalvular pressure gradients as well as residual regurgitations remained drawbacks in this real-world population. The indication for catheterbased mitral ViV- or ViR-procedures thoughtfully must be made in consideration of conventional redo-surgery or conservative treatment.

We review recent work on narrowband orthogonally polarized optical RF single sideband generators as well as dual-channel equalization, both based on high-Q integrated ring resonators. The devices operate in the optical telecommunications C-band and enable RF operation over a range of either fixed or thermally tuneable frequencies. They operate via TE/TM mode birefringence in the resonator. We achieve a very large dynamic tuning range of over 55 dB for both the optical carrier-to-sideband ratio and the dual-channel RF equalization for both the fixed and tunable devices.

Graphene as a new two-dimensional material can be utilized to design tunable optical devices owing to its exceptional physical properties such as high mobility and tunable conductivity. In this paper, we present the design and analysis of a tunable broadband terahertz absorber based on periodic graphene ring arrays. Due to plasmon hybridization modes excited in the graphene ring, the proposed structure achieves a broad absorption bandwidth with more than 90% absorption in the frequency range of 0.88-2.10THz under normal incidence and its relative absorption bandwidth is about 81.88%. Meanwhile, it exhibits polarization-insensitive behavior and maintains high absorption over 80% when incident angle is up to 45º for both TE and TM polarizations. Additionally, the peak absorption rate of the absorber can be tuned from 21% to nearly 100% by increasing the graphene’s chemical potential from 0eV to 0.9eV. Such a design can have some potential applications in various terahertz devices, such as modulators, detectors, spatial filters.

Tree decline resulting from climate change results in physiological weaknesses, attack by harmful pests and pathogen, and threatens forest ecosystem stability. In the work described here, the effects of drought on wood density, tree ring width, and variations in vessel morphology were investigated in Persian oak (Quercus brantii) in the forests of the Zagros Mountains, Ilam province, western Iran. Radial discs were cut from trunks of declined and healthy trees and wood blocks cut radially from the sapwood, heartwood, and juvenile core. Observations were made on transverse sections from the blocks using microscopy. In trees with decline symptoms, wood density was greater than the healthy trees. Furthermore, declining trees had the narrowest ring width, reduced vessel diameter, vessel area, and highest number of vessels and tylose in pith towards bark. It was concluded that changes in anatomical features are associated with the weakening of the trees and are components in declining tree health.

RNA-seq faces persistent challenges due to the ongoing expanding array of data processing workflows, none of which have yet achieved standardization to date. It is imperative to determine which method most effectively preserves biological facts. Shannon entropy serves as a tool for depicting the biological status of a system. Thus, we assessed the measurement of Shannon entropy by several RNA-seq workflow approaches, employing RPKM and median normalization on paired samples of 475 TCGA RNA-seq datasets spanning eight different cancer types with 5-year overall survival rates ranging from 30% to 98%. Our analysis revealed that the RPKM normalization coupled with a threshold of log2 fold change ≥1 for indentifying differentially expressed genes, yielded the best results with a correlation coefficient of 0.91. We propose that Shannon entropy can serve as an objective metric for refining the optimization of RNA-seq workflows.

In the last decades, technological advances related to RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle employed. Among the systems, yeasts emerge as a new approach to a natural delivery platform. The presence of β-glucans and mannans in its wall is responsible for the adjuvant action of this system. Yeasts are already employed to deliver protein antigens, with success and efficacy demonstrated through pre-clinical and clinical trials. Yeast β-glucan capsules, microparticles, and nanoparticles are capable of modulating host immune responses and have a high capacity to carry RNA and small molecules, with bioavailability upon oral immunization and with targeting to receptors present in anti-gen-presenting cells (APCs). Besides, yeasts are interesting vehicles for the protection and specific delivery of therapeutic vaccines based on shRNA or dsRNA. In this review, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing their current challenges and prospects for using this promising strategy.

MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dog is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MicroRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor microRNAs (miRNAs), we report 30 oncogenic miRNAs in COM. Expression of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had significant negative co-relation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors in respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA’s profile in COM which will be a useful resource for developing therapeutic interventions in both species.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

Advancements in genomics and molecular biology have propelled our understanding of genetic information far beyond the iconic double helix structure of DNA. This comprehensive review delves into the intricate world of DNA and RNA networks, exploring the complexities that extend beyond the classical model. We investigate the dynamic interactions, regulatory mechanisms, and functional implications of the broader genetic landscape, encompassing both coding and non-coding elements. From chromatin architecture to the diverse array of non-coding RNAs, this exploration seeks to provide a holistic perspective on the multifaceted roles played by DNA and RNA in cellular processes. The three-dimensional organization of genetic material within the cell has emerged as a crucial determinant of cellular function. Chromatin architecture, comprising DNA, histones, and other associated proteins, plays a dynamic role in regulating gene expression. We delve into the intricate choreography of chromatin remodeling, deciphering the interplay between transcription factors, epigenetic modifications, and higher-order structures that modulate gene activity. The exploration of chromatin dynamics unveils a nuanced understanding of how the genome responds to environmental cues, cellular signals, and developmental processes. Moreover, the once-dismissed non-coding portion of the genome has emerged as a key regulator of cellular function. Various classes of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in diverse cellular processes, ranging from fine-tuning gene expression to modulating chromatin structure. The review critically examines the functional roles of these non-coding RNAs, shedding light on their involvement in cellular homeostasis, development, and disease. As I traverse this landscape beyond the double helix, our review synthesizes current knowledge on the intricacies of DNA and RNA networks. By exploring the regulatory mechanisms, functional implications, and emerging paradigms, we aim to inspire a deeper appreciation for the molecular choreography that underlies the cellular symphony of life. Furthermore, we discuss the implications of these findings in the context of disease, highlighting potential diagnostic and therapeutic avenues that arise from a comprehensive understanding of DNA and RNA networks. In doing so, this exploration not only broadens our theoretical understanding but also opens new frontiers for translational research in genetics and molecular medicine.