Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.

The present work investigates primarily the morphology evolution of the body-centered-cubic (BCC)/B2 phases in AlxNiCoFeCr high-entropy alloys (HEAs) with increasing Al content, which has been neglected so far. There exist two types of microscopic morphologies of BCC and B2 phases in this HEA series: one is the weave-like morphology induced by the spinodal decomposition, and the other is the microstructure of a spherical disordered BCC precipitation on the ordered B2 matrix that appears in HEAs with a much higher Al content. The shape of coherent precipitates is found to be closely related to the lattice misfit between BCC and B2 phases, which is sensitive to Al. The mechanical properties, including the compressive yielding strength and microhardness of the AlxNiCoFeCr HEAs, are also discussed in light of the concept of the valence electron concentration (VEC).

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.

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.

The collapsible loess will rapidly soften and lose its bearing capacity when soaked in water. Under a mild condition (20°C), the biomimetic inorganic agent, Diammonium phosphate (DAP), reacts with calcite in the collapsible loess, producing a stronger bonding material, hydroxyapatite (HAP), to modify and stabilize the soil. Uniaxial compression, permeability tests and morphological analysis using XRD and SEM/EDX microscopy were carried out to assess the effectiveness of DAP stabilization on the collapsible loess. The results indicated that HAP improved the inter-particle bonding within loess, filled the pores within particles, reduced the permeability, and consequently mitigated collapsibility of loess. The compressive strength of DAP-treated loess increased as DAP concentration increased. Following 28-days curing, the compressive strength of the loess treated with a 3.0 mol/L DAP solution was six times greater than that of the untreated group. DAP's reinforcement effect on loess was superior to that of cement. The compressive strength of DAP-treated loess was about double that of cement-treated loess and the permeability coefficient was reduced by more than 50% at equivalent solid content. Furthermore, DAP generated 68% fewer carbon emissions compared to Portland cement. Considering eco-friendly and sustainable development, DAP offers a more competitive alternative for modification and stabilization of loess.

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.

Mammalian species possess sophisticated innate immune mechanisms that collectively combat a wide array of viral pathogens. Among these, the well-characterized interferon (IFN) response has been extensively researched; however, the role of antiviral RNA interference (RNAi) in mammals is emerging as an area of significant interest. Previous research has noted that Dicer, an enzyme crucial for processing double-stranded RNA (dsRNA), exhibits reduced activity in vitro, and that the IFN response may overshadow or inhibit the antiviral functions of RNAi in mammalian cells. Consequently, the functional relevance of RNAi in antiviral defense within mammalian somatic cells remains an open question. The evolution of antiviral systems in human populations reflects their substantial advantages, paralleling the evolutionary pressure on genomes encoding such defense mechanisms. While the well-studied protein-guided immune responses in mammals are essential for survival in viral environments, small RNA-mediated antiviral systems, which utilize complementary base pairing to silence non self-genetic material, also play a crucial role. In mammals, evidence suggests that microRNAs (miRNAs) regulate genes integral to antiviral responses, and emerging data indicate that small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) can directly target virus-derived nucleic acids. This review aims to highlight some of the recent progress in understanding mammalian antiviral RNAi mechanisms.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

The morphological and compositional complexities of keratinized components make feathers ingenious skin appendages adapted to diverse ecological needs. Frizzling feathers, characterized by their distinct curling phenotypes, offer a unique model to explore the intricate morphogenesis in developing a keratin-based bioarchitecture over a wide range of morphospace. Here, we investigated the heterogeneous allocation of α- and β-keratins in flight feather shafts of homozygous and heterozygous frizzle chickens by analyzing the medulla-cortex integrations using quantitative morphology characterizations across scales. Our results reveal intriguing construction of frizzling feather shaft through modified medulla development, leading to a perturbed balance of the internal biomechanics and, therefore, introducing the inherent natural frizzling compared to those from wild-type chickens. We elucidate how the localized developmental suppression of the α-keratin in the medulla interferes with the growth of the hierarchical keratin organization by changing the internal stress in the frizzling feather shaft. This research not only offers insights into the morphogenetic origin of the inherent bending of frizzling feathers but also facilitates our in-depth understanding of the developmental strategies toward the diverse integuments adapted for ecological needs.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Abstract: Due to sever land degradation throughout Ethiopia, the government has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. However, most of the rivers in Ethiopia carry huge amount of sediment in rainy season and streams dried up in the dry period. Planned research was conducted on two paired micro-catchments Mt.Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were collected from 22/11/2020 to 8/11/2022 on both micro-catchments at their outlets and center respectively. Base flow separation was done using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software was employed for data analysis. Flow duration curve (FDC) for both watersheds were developed. The FDC indicated that the base flow from treated micro-catchment ishigher and sustained in the dry season while it is low and un-sustained in untreated micro-catchment. From statistical analysis, there is a significant difference in base flow enhancement between the treated and untreated micro-catchment (P<0.001). Hence, catchment treatment contributed to improve groundwater recharge and sustain base flow in the dry season by reduce surface runoff during rainy season.

Abstract: Severe land degradation is the principal environmental problem in Ethiopian highlands in the form of soil erosion, and soil fertility loss, which is caused by human intervention for food, shelter, and energy demands. Soil erosion contributes to the loss of precious soil and water resources which are the basis of agricultural production and provide numerous other eco-system services. The Ethiopian highlands are one of the most degraded regions in the world. To combat such problems, the government of Ethiopia has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. Mount Yewel is one of the highlands in Northeastern Ethiopia where intensive soil and water conserva-tion has been implemented. Despite the massive investment in soil and water conservation measures, most of the rivers in the highlands of Ethiopia carry huge amounts of sediment with high flood risks in the wet season and streams are dried up in the dry period. Nonetheless, the impact of soil and water conservation measures on flood reduction and dry season flow en-hancement has not yet been quantified and evaluated. This research was then conducted on paired micro-catchments of Mount Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were col-lected from 22/11/2020 to 8/11/2022 on paired micro-catchments of Mount Yewel at their outlets and centers respectively. Base flow separation was done from the stream hydrograph using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software were employed for data analysis. Flow duration curves (FDC) for both watersheds were developed to compare the stream flow patterns between treated and untreated micro-catchments of Mount Yewel. The FDC indi-cated that the base flow from treated micro-catchment is higher and sustained in the dry season while it is low and unsustained in untreated micro-catchment. From statistical analysis, there is a significant (P

In forests, the microbial populations living in the soil can directly affect the carbon decomposed by the surface plants, and promote carbon storage and stability. In this study, 3 plots of 25.82 m×25.82 m were set up in 5 stand types, respectively. Soil samples were collected from 0~20 cm, 20~40 cm and 40~60 cm layers. Soil microbial composition, organic carbon component, pH, water content, bulk density, nitrogen, phosphorus, potassium and other physicochemical indexes and correlations were determined, and the correlations between soil carbon components and soil microbial functional modules in different mixed modes were analyzed. The results showed that: (1) The SOC of the same soil layer varied significantly, which also showed significant differences on the composition of soil bacteria and fungal microbial communities. Moreover, the bacterial community was more sensitive to the vegetation change environment, and the fungal community structure was more resistant to the influence of soil environment changes. (2) Fun_mod 1,6 and Bac_mod 7 were the microbial functional modules that played a decisive role in the process of soil carbon pool change, and the diversity and composition of bacterial community had more positive effects on soil organic carbon than that of fungal community. (3) Linear fitting and RDA results showed that POC in soil had the strongest correlation with SOC content, indicating that soil microorganisms affected the storage and stability of soil carbon mainly by regulating the conversion of surface plants (carbon sources) into POC. The soil environment of different mixed modes has different effects on soil carbon accumulation. Soil microorganisms affect soil carbon storage and stability mainly by regulating the conversion of surface plants (carbon sources) into POC forms.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

RNA sequencing techniques, like bulk RNA-seq and Single Cell (sc) RNA-seq, are critical tools for the biologist looking to analyze the genetic activity/transcriptome of a tissue or cell during an experimental procedure. Platforms like Illumina's next-generation sequencing (NGS) are used to produce the raw data for this experimental procedure. This raw FASTQ data must then be prepared via a complex series of data manipulations by bioinformaticians. This process currently takes place on an unwieldy textual user interface like a terminal/command line that requires the user to install and import multiple program packages, preventing the untrained biologist from initiating data analysis. Open-source platforms like Galaxy have produced a more user-friendly pipeline, yet the visual interface remains cluttered and highly technical, remaining uninviting for the natural scientist. To address this, SeqMate is a user-friendly tool that allows for one-click analytics by utilizing the power of a large language model (LLM) to automate both data preparation and analysis (differential expression, trajectory analysis, etc). Furthermore, by utilizing the power of generative AI, SeqMate is also capable of analyzing such findings and producing written reports of upregulated/downregulated/user-prompted genes with sources cited from known repositories like PubMed, PDB, and Uniprot.

The movement of liquid droplets on the energy gradient surface has attracted extensive attention. Inspired by biological features in nature, such as the periodic spindle-shaped nodes in spider silks and conical-like barbs of cacti, the structure-property-function relationship of multifunctional gradient surfaces. In this study, a series of specific patterns are fabricated by 3D printing technology, followed by modification via the atmospheric pressure plasma treatment and liquid phase chemical deposition, resulting in enhancing the ability of water droplets of 5μL to travel 18.47mm on a horizontal plane and 22.75mm against gravity up to 20° tilting angle. Additionally, analysis techniques have been employed including contact angle analyzer, ESCA and laser confocal microscope to evaluate the sample performance. This work could further be applied to many applications related to microfluidic devices, drug delivery and water/fog collection.

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.

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.

Microplastics (MPs) are a critical environmental issue, with impacts ranging from ecosystem contamination to health risks through bioaccumulation. This review addresses the inefficacy of traditional water treatments in removing MPs and proposes photodegradation, particularly via nanomaterial-enhanced photocatalysts, as a solution. Utilizing their unique properties like large surface area and tunable bandgap, nanomaterials significantly improve degradation efficiency. Different strategies for photocatalysts modification to improve photocatalytic performance are thoroughly summarized, with the particular emphasis on element doping and heterojunction construction. Furthermore, this review thoroughly summarizes the possible fundamental mechanisms driving photodegradation of microplastics facilitated by nanomaterials, with a focus on processes like free radical formation and singlet oxygen oxidation. By clearly elucidating these strategies and mechanisms, this review aims to provide valuable insights and inspire further progress in microplastic photodegradation.

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.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

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.

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.

The purpose of the review is to provide new insight into the potential of surface modification of carbon fibers for enhancing the application of the carbon fibers many a fold. To this end a total of 429 papers on the subject of surface modication of carbon fibers by a variety of chemical and electrochemical methods published during the period from 2010-2022 have been reviewed. Astounding results of surface funcationalization of carbon fibers by a variety of state of the art methods resulting in the unconventional applications of the resulting modified carbon fibers are summarized in a nut-shell in schemes from 1-6 towards the end of the review. Surface modifica-tion induces functionality to carbon fibers (CFs). The vitality of CF surface modification reac-tions could only be compared to the life process of respiration that sustains the multi functional-ity of living cells. Applicability of CFs can be drastically enhanced in incomprehensible ways by surface modification. Upon surface modification, inert and non-reactive CF surface becomes chemically active and functional with utility in diverse fields, namely, health, energy, environ-ment, defense, catalysis, smart materials and many others. Surface modification methods can be broadly classified into chemical, electrochemical and physical methods. By these surface modi-fication methods, the inert FC surface becomes polar. Surface properties like roughness, wetta-bility and energy are enhanced. Modification processes like sizing, oxidation, amination, si-lanization, polymerization, nanoarchitecture induces multifunctionality on CF surface. Modi-fied CFs when used as reinforcing material in carbon fiber reinforced plastics (CFRPs), im-proved bonding at the interface with resin matrices is observed with enhanced and outstanding mechanical properties (flexural strength, flexural modulus, IFSS, ILSS, hardness, elastic modulus, bending strength and compression strength).

Wind tunnels are devices that enable researchers to study the flow over objects of interest, the forces acting on them and their interaction with the flow, which is nowadays playing an increasingly important role due to noise pollution. Since the first closed circuit wind tunnel with variable cross-section was built in G¨ottingen, its Prandtl configuration has little change. The wind tunnel with Prandtl configuration has four corners and vanes, more than 50% of the total pressure loss are caused by the corners and vanes. How to reduce the total pressure loss is a world class problem in the wind tunnel design. This study attempts to propose a novel configuration of wind tunnel, where the corners have been replaced by semi-circular tunnel. Sun wind tunnel 2 has only two corners and vanes, while Sun wind tunnel 1 has no corners and vanes at all. It is expected the new wind tunnel can reduce the total pressure loss from 50% to 10%.

The rheological properties of a polyamide (PA) resin with low crystallinity were modified by melt-mixing it with a small amount of an alternative a-olefin–maleic anhydride copolymer as a reactive compound. Because PA has a low melting point, rheological characterization was performed over a wide temperature range. Owing to the reaction between PA and the alternative a-olefin–maleic anhydride copolymer, the blend sample behaved as a long-chain branched polymer in the molten state. The thermo-rheological complexity was obvious owing to large flow activation energy values in the low modulus region. The primary normal stress difference under steady shear was greatly increased in the wide shear rate range, leading to a large swell ratio at capillary extrusion. Furthermore, strain hardening in the transient elongational viscosity, which is responsible for favorable processability, was clear. Because this is a simple modification method, it will be widely employed to modify the rheological properties of various polyamide resins.

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.

The use of biomass as a source of energy has been identified to be energy intensive which involves high cost of handling. However, pelletization reduces the bulk density of biomass, thereby reducing the cost of handling and enhancing ease of use. This study modified and evaluated an existing hand operated fish feed pelleting machine. The parts of the machine that were redesigned are hopper and power transmission unit. Corncob was used to evaluate the modified machine using die hole diameter (5,6 and 7 mm) and binder quantity (0, 2.5 and 5 wt%) as factors. The average results obtained for machine efficiency, throughput, pellet length and bulk density were 58.83%, 4.24 kg/h, 15.51 mm and 0.160 g/cm3. Die hole diameter had significant effect on pellet length only. Binder quantity had significant effect on machine efficiency, throughput and pellet length. Machine efficiency and throughput reduces as the quantity of binder increases and pellet length increases with increasing quantity of binder.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

The ethics of invertebrate research have largely been ignored compared to the consideration of higher order animals, but more recent focus has questioned this trend. Using biohybrid robotic jellyfish as a case study, we examine the ethical considerations of invertebrate work and provide recommendations for future guidelines. This paper starts with an overview of philosophical views of animal ethics, the current state of knowledge for invertebrate pain and nociception, and current ethical guidelines. Next, we delve into the case study and analogous precedents. Specifically, in prior studies, we developed biohybrid robotic jellyfish, which modified live moon jellyfish with microelectronic swim controllers for future applications in ocean monitoring. Although jellyfish possess no central nervous system, pain receptors, or nociceptors, we closely monitored their stress responses, using the precautionary and minimization principles in consideration of the 4Rs: reduction, replacement, refinement, and reproducibility. We also discuss ethical considerations related to our studies and suggest that public opinion of invertebrate research relies heavily on repugnance, including fears of ‘playing God’ or limiting the ‘free will’ of animals. These issues are also examined for prior bioethics cases, such as the RoboRoach, cyborg beetle, ‘microslavery’ of microbes, biohybrid robots incorporating tissues from sea slugs (which are known to possess nociceptors), and other tissue cutting experiments involving soft-bodied invertebrates. However, biohybrid robotic jellyfish pose further ethical questions of potential ecological consequences as ocean monitoring tools, such as the impact of electronic waste in the ocean. To conclude these evaluations, we recommend that publishers require brief ethical statements for invertebrate research, which can include the following: a scientific justification for the research, discussion of the 4Rs, and cost-benefit analysis. We also delineate the need for more research on pain and nociception in invertebrates, which can then be used to revise or validate current research standards. These actions provide a stronger basis for the ethical study of invertebrate species, with implications for individual, species-wide, and ecological impacts on animals, as well as for interdisciplinary studies in science, engineering, and philosophy.

Graphene-oxide (G) was prepared by the Hummers’ method. A G-COOH layer was synthesised using chloroacetic acid and G. To fabricate carboxylated graphene-RuO2 (G-COORu) nano¬¬-composites, RuO2 nano particles were grown on graphene layers using a one-step thermal method, -COOH(G-COOH), and RuCl3. All materials were characterised using X-ray diffraction, transmission electron microscopy, scanning electron microscopy, 13C-nuclear magnetic resonance as well as X-ray photoelectron, Fourier-transform infrared spectroscopy, and Raman. The electrochemical characteristics of the G-COORu supercapacitors were analysed using electrochemical impedance spectroscopy, cyclic voltammetry, constant current charge–discharge tests, and Nyquist impedance plots. The supercapacitors exhibit a specific capacitance of ~125 F g-1 at 100 mA cm-2 within the potential range of 0–1.0 V. The method used here provides a simple approach for the deposition of RuO2 nano particles on graphene layers and can be widened to the fabrication of other classes of hybrids based on G layers for specific technical applications.

With the increasingly stringent airworthiness standards, the noise generated during the rotorcraft flight is gradually attracting people’s attention. It widely operated helicopters at low altitudes because of their maneuverability. The way to reduce the noise caused by the complex airflow of the helicopter rotor system has progressively become a hot topic for researchers. Using a hybrid acoustic analysis method, this paper investigates the improvement of the noise and thrust of the helicopter’s tail rotor through the tail rotor structural parameters. For the basic model, the turbulence simulation is performed using an incompressible detached eddy simulation (DES) method, and the Lighthill acoustic analog equation is calculated using the finite element method (FEM). We verified the accuracy of the method through wind tunnel tests. We chose a series of structural parameters for sound simulation and fluid simulation calculations. The results indicate that the modified tail rotor noise reduced by 16.5 dBA and the total thrust increased by 19.9% from the prototype model. This work can enhance the duct tail rotor design to improve aerodynamic and aeroacoustic performance.

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.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

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.

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.

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.

Paper presents proposition of possible extension of The Standard Model Classification of Particles and Fields in way to include gravitation into it.

Basic mechanisms of laser interaction with synthetic diamond are reviewed. The features of the major regimes of diamond surface etching are considered. Besides well-known graphitization and ablation processes, the nanoablation and accumulative graphitization, which attracted the attention relatively recently, are described in detail. The focus is placed on femtosecond (fs) laser exposure which provides a formation of dense cold electron-hole plasma in focal zone and a minimum overheating in surrounding area. This potentially opens the way to develop unique laser-based technologies combining physical and chemical processes for precise surface treatment and functionalization. The physical limitations determining how precisely the diamond surface can be treated by short-pulsed laser radiation and possible pathways to overcome them with the end to remove ultra-thin layers of the material are discussed. Particular attention is devoted to the novel possibility to induce local formation of point active defects - nitrogen vacancy (NV) complexes in the laser-irradiated zone. Both the regimes of NV centers generation with and without graphitization of diamond lattice are reviewed. It is thus shown that intensive pulse laser radiation is a perfect tool for processing of synthetic diamonds on the micro, nano and even on an atomic level that can be well controlled and managed.

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.

The research that we are referring to examines the morphological, structural, and optical characteristics of kesterite (Cu1-xAgx)2ZnSnS4 (CAZTS) thin films, which are produced using a process known as thermal evaporation (TE). The study's main goal was to determine how different Ag contents affect the characteristics of CAZTS systems. X-ray diffraction (XRD) and Raman Spectroscopy: were used to confirm the crystal structure of the CAZTS thin films. Using a mathematical model of spectroscopic ellipsometry, the refractive index (n) represented the part of the complex refractive index, the extinction coefficient (k) portrayed the imaginary one, and also the energy band gap of the fabricated films were all calculated. The energy band gap of the thin films was also calculated. This is a crucial parameter for solar cell applications, as it determines the wavelength of light that the material can absorb. The energy band gap was found to decrease from 1.74 eV to 1.55 eV with increasing Ag content. The ITO/n-CdS/p-CAZTS/Mo heterojunction was well constructed, and the primary photovoltaic characteristics of the n-CdS/p-CAZTS junctions were examined for use in solar cells. Different Ag contents of the CAZTS layers were used to determine the dark and illumination (current-voltage) characteristics of the heterojunctions. The study's findings collectively point to CAZTS thin layers as potential absorber materials for solar cell applications.

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.

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.

This study investigates the impact of plasma gradient modification and gradient illumination on the optoelectronic properties of buckypaper (BP), a flexible and large-scale material composed of multi-walled carbon nanotubes (MWCNTs). The BP samples were subjected to argon ion plasma treatment at varying power levels and durations, thereby creating different carrier concentration gradients on the surface. The photovoltage and photocurrent responses of the samples were then measured under uniform full illumination and gradient illumination conditions. The findings revealed that both plasma gradient modification and gradient illumination significantly enhanced the optoelectronic performance of BP. Notably, the combined application of these two methods yielded superior results compared to the application of either method alone. Specifically, the optimal plasma power for improving BP was found to be 20W. Under conditions of plasma gradient modification and gradient illumination, a photovoltage of 267.76 μV was generated, which represents a 21.44 times increase, and a photocurrent of 15.69 μA, reflecting a 32.69 times enhancement. The mechanism underlying this optoelectronic effect can be attributed to the presence of π-bonds in the carbon atoms. These π-bonds are excited by photons, resulting in the generation of small voltages and currents. This study underscores the potential of BP as an optoelectronic material and introduces a novel approach to enhance its optoelectronic properties through plasma gradient modification and gradient illumination.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020; we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients and their families. Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels are varying by changes in RNA/DNA structure during development, thereby creating transcription alteration. Behavioral tests were conducted on the offspring of Cc2d1a +/- mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells by standard TRIzol extraction: total RNA and fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice in RNA fractions, particularly in colonies of Cc2d1a +/- mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.

Atrial fibrillation (AF), a complex cardiac arrhythmia, necessitates a shift in management paradigms, emphasizing an integrative approach that incorporates lifestyle modifications. Investigations into the role of interleukins and inflammatory mediators are underway, exploring their potential as diagnostic markers and predictors of cardiovascular events in AF. Despite the identification of biomarkers related to cardiac remodeling, their predictive ability for post-cardioversion outcomes remains controversial. Computational models are being developed to understand proarrhythmic contributions and identify anti-AF targets. Addressing the rising global incidence of AF, linked to stroke and heart failure, presents a critical health challenge. As risk factors like obesity prevail, AF becomes a pervasive public health concern, expected to double in prevalence over the next 50 years. The impact on mortality and morbidity, especially through hospitalizations, underscores the need for early detection and effective clinical management. Identifying individuals at increased AF risk becomes crucial for screening and prevention strategies. Lifestyle modifications, including weight management and physical activity, emerge as influential factors in AF management, offering the potential to alleviate symptoms and modify disease progression. The paper concludes by emphasizing the need for safer antiarrhythmic therapies based on AF mechanisms, promising improvement in global AF management. The multifaceted nature of AF etiology requires a broader perspective beyond traditional medical interventions, acknowledging the importance of integrated care to address this significant public health challenge.

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.

Chikungunya virus (CHIKV) is a mosquito borne RNA virus that poses an emerging threat to humans. As other RNA viruses, CHIKV encodes an error-prone RNA polymerase which, in addition to full-length genomes, gives rise to truncated, non-functional genomes coined defective viral genomes (DVGs). DVGs have been intensively studied in the context of therapy, as they can inhibit viral replication and dissemination in their hosts. In this work, we interrogate the influence of viral RNA secondary structures on the production of CHIKV DVGs. We experimentally map RNA secondary structures of CHIKV genome using selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), which couples chemical labelling with next-generation sequencing. We correlate the inferred secondary structure with preferred deletion sites of CHIKV DVGs. We document an increased probability of DVG generation with truncations at unpaired nucleotides within the secondary structure. We then generated a CHIKV mutant bearing synonymous changes at the nucleotide level to disrupt existing RNA secondary structure (CHIKV-D2S). We show that CHIKV-D2S presents altered DVG generation compared to wild-type virus, correlating with its change in RNA secondary structure obtained by SHAPE-MaP. Our work thus demonstrates that RNA secondary structure impacts CHIKV DVG production during replication.

Nowadays there is a growing interest in membrane modification processes, to improve their characteristics, the effectiveness of their treatments and reduce the possible fouling. In this sense, in this work a modification of an ultrafiltration membrane with tree different materials has been carried out: reduced graphene oxide (rGO), chitosan and MgCl2. For both the native and the modified membranes, a study has been carried out to remove the emerging contaminant sul-fomethoxazole. SEM and SEM-EDX analyses have been performed to confirm membrane surface modifications. In the characterization of the membranes, it is noteworthy that the values of the permeability coefficient, Aw, have been lower in the modified membranes, which is unexpected. Regarding the pollutant removal tests, the influence of pressure and initial concentration on permeate flows and rejections has been studied. Native membrane shows the highest permeate flow values. Comparing the modified membranes, the highest rejection values are obtained with the rGO-modified membrane, which can be explained by its greater hydrophilic character. Finally, a fouling study has been carried out, verifying that in almost all cases such fouling occurs after the passage of the pollutant, due to the blockage of the membrane pores.

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.

N6-methyladenosine (m6A) is an RNA modification wherein N6-position of adenosine is methylated. It is one of the most prevalent internal modifications on RNA and regulates various aspects of RNA metabolism. M6A is deposited by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which modulate splicing, export, translation and stability of the modified mRNA. Recently evidence suggests that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), circular RNAs (circRNAs), and long con-coding RNAs (lncRNAs) are also targeted by this modification. Depending on the ncRNA species, m6A may affect processing, stability, or localization of these molecules. The m6A modified ncRNAs are implicated in a number of diseases including cancer. In this review, I summarize the role of m6A modification in the regulation and function of ncRNAs in tumor development. Moreover, the potential applications in cancer prognosis and therapeutics is discussed.

Various methods of polymer surface tailoring have been studied to control the changes in wetting behavior. Polymers having precisely controlled wetting behavior in a specific environment are blessed with a wealth of opportunities and potential applications exploitable in biomaterial engineering. The controlled wetting behavior can be obtained by combining surface chemistry and morphology. Plasma assisted polymer surface modification technique have played a significant part to control surface chemistry and morphology. This review focuses on plasma polymerization and investigations regarding surface chemistry, surface wettability, coating kinetics, as well as coating stability. We begin with brief overview of plasma polymerization; these include growth mechanisms of plasma polymerization and influence of plasma parameters. Next, surface wettability and theoretical background structures and chemistry of superhydrophobic and superhydrophilic surfaces. In this review, overview of recent work on tunable wettability by tailoring surface chemistry and physical appearance (i.e. substrate texture) is also described. The formation of smart polymer coatings, which adjust their surface wettability by according to outside environment, including, pH, light, electric field and temperature. Finally, the applications of tunable wettability and pH responsiveness of polymer coatings in real life are addressed. This review should be of interest to plasma surface science communality specifically focused controlled wettability of smart polymer surfaces.

Clustered regularly interspaced short palindromic repeats (CRISPR) based gene-editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single guide RNA (sgRNA)-based gene-editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, instructive, and inspiring for future advances. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent beta thalassemia has renewed hope for treating other hematologic diseases, including patients with germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-based gene therapies. The purpose of this manuscript is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy; and third, the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with germline predisposition to hematologic malignancies.

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.

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.

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.

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.

Modification of Scots pine sapwood (Pinus sylvestris L.) with heterocyclic compounds, imidazole and succinimide, was investigated. Pressure-impregnation with aqueous solutions containing imidazole, imidazole + citric acid, succinimide, succinimide + citric acid, and citric acid + sorbitol (CIOL®) at 5%, 10%, and 15% solid content was followed by oven-curing at 220 °C for 1 hour. Mass changes during treatment steps, bending properties, and anti-swelling efficiency (ASE) were examined. Results indicate that solid concentrations within the range of 5% to 10% were optimal. Results seem to show there are two differing mechanisms in the modification of imidazole and succinimide, respectively. Mass loss due to the heat treatment was highest in imidazole-treated specimens, whereas it remained low and concentration-independent in succinimide-treated specimens. ASE after three cycles reached 31% for imidazole-treated specimens and improved to 38% with the addition of citric acid. For succinimide, ASE increased from 17% to 41%. Bending properties generally showed improvement, except for succinimide + citric acid and CIOL®, which displayed a reduced modulus of rupture. Chemical analyses are warranted to fully understand the reaction mechanisms of the treatments. Imidazole treatment's positive effects are suggested to stem from a thermal reaction between the chemical and wood, indicated by substantial mass loss during leaching and specimen darkening. Succinimide and citric acid might exhibit polymerization with each other and wood components, akin to the CIOL® process. Further research should delve into reaction mechanisms and the impact of imidazole and succinimide on biological durability.

Biosensors are analytical devices that utilize biological interactions to detect and quantify clinical biomarkers, contaminants, allergens, and microorganisms. They combine different disciplines including analytical chemistry, molecular biology, and electrical engineering. Biosensors operate by coupling a bioreceptor, such as nucleic acid or proteins, with a transducer that converts the biological interaction into an electrical signal. Electrochemical and optical transduction are commonly used approaches due to their high detection capability and compatibility with miniaturization. Biosensors provide both high specificity and sensitivity and can be integrated into low-cost microfluidic platforms for rapid and point-of-care applications. These attributes make these devices valuable tools in analytical chemistry, particularly for early diagnostic applications. However, conventional biosensors face challenges related to the immobilization of biorecognition elements on the transducer surface, leading to issues like lost of sensitivity and selectivity. To address these problems, the introduction of nanomaterials, particularly magnetic nanoparticles (MNPs) and magnetic beads (MBs), has been implemented. MNPs combine their magnetic properties with other interesting characteristics such as small size, high surface-to-volume ratio, and excellent biocompatibility. They can be tailored for specific applications and have been extensively used in various fields, including biosensing and clinical diagnosis. Furthermore, MNPs simplify sample preparation by isolating target analytes through magnetic separation, thus improving sensitivity, and reducing analysis time and interference phenomena. The synthesis and modification of MNPs play a crucial role in adjusting their properties for different applications. This review presents an overview of the synthesis and surface modifications of magnetic nanoparticles, their role in the development of biosensors and bioassays, and their applications across various scientific areas.

Hypoxia contributes to tumor progression and metastasis, and hypoxically dysregulated RNA molecules may thus be implicated in poor outcomes. Canine oral melanoma (COM) has a par-ticularly poor prognosis, and some hypoxia-mediated miRNAs are known to exist in this cancer; however, equivalent data on hypoxically dysregulated other non-coding RNAs (ncRNAs) are lacking. Accordingly, we aimed to elucidate non-miRNA ncRNAs that may be mediated by hy-poxia, targeting primary-site and metastatic COM cell lines and clinical COM tissue samples in next generation sequencing (NGS), with subsequent qPCR validation and quantification in COM primary and metastatic cells, plasma and extracellular vesicles (EVs) for any identified ncRNA of interest. Findings suggested that a number of non-miRNA ncRNA species are hypoxically up- or downregulated in COM. We identified one ncRNA, the long ncRNA fragment EN-SCAFT00000084705.1, as a molecule of interest due to its consistent downregulation in COM tissues, hypoxically and normoxically cultured primary and metastatic cell lines, when compared to the oral tissues from healthy dogs. However, this molecule was undetectable in plasma and plasma EVs, suggesting that its expression may be tumor tissue-specific and it has little potential as a biomarker. Here, we provide evidence of hypoxic transcriptional dysregulation for ncRNAs other than miRNA in COM for the first time, and suggest that ncRNA ENSCAFT00000084705.1 is a molecule of interest for future research on the role of the transcriptome in hypoxia-mediated progression of this aggressive cancer.

The use of sustainable energy sources is a feasible alternative for fossil fuel products, which can represent a positive factor to alleviate many current environmental issues. In that sense, not only the sustainable industrial development is important, but also sustainable practices at local level, including households. Specifically, heating and cooking are one of the most important activities that require energy in households, where the role of biomass could be interesting, as it can provide an energy source with lower environmental impact. However, there is room for improvement in biomass stoves, whose adaptability to specific wastes, as well as their improvement in efficiency, should be accomplished. The aim of this work was to assess the improvement of combustion performance of a domestic stove by the implementation of a programmable logic converter for a better adaptation to different biomass samples (holm oak, pear tree, poplar and sugarcane bagasse pellets). Thus, the working regime of the stove was controlled, especially concerning the screw conveyor (to regulate pellet feeding) and flue gas fan (to change oxygen supply). As a result, better combustion performances were obtained, heat capacities from 5.66 to 8.67 kW for the selected samples. On the other hand, different improvements of the combustion stove to avoid blockages, for instance, are proposed as further steps.

Proso millet starch (PMS) as an unconventional and underutilized cereal starch is becoming increasingly popular worldwide due to its health-promoting properties. This review summarizes research progress in the isolation, characterization, modification, and applications of PMS. PMS can be isolated from proso millet grains by acidic, alkaline, or enzymatic extraction. PMS exhibits typical A-type polymorphic diffraction patterns and shows polygonal and spherical granular structures with a granule size of 0.3-17 µm. PMS is modified by chemical, physical, and biological methods. The native and modified PMS are analyzed for swelling power, solubility, pasting properties, thermal properties, retrogradation, freeze-thaw stability, and in vitro digestibility. The improved physicochemical, structural, and functional properties and digestibility of modified PMS are discussed in terms of their suitability for specific applications. The potential applications of native and modified PMS in food and non-food products are presented. Future prospects for research and commercial use of PMS in the food industry are also highlighted.

Biochirality is evident in the hierarchical relation of molecular and cellular physiology during organism development and aging. Chirality influences the higher levels of biological processes, such as perception, memory and cognition, through intermolecular interactions between DNA, proteins, and lipids. At the molecular level, an organism's aging is the accumulation of macro-molecules with the aberrant composition, chirality, and folding. Cellular aging is driven by the non-physiological phase transitions (PhTs) withing membrane-bound and membrane-less compartments. Genomic instability and protein aging, as the interconnected root-causes of cell and organism aging, share two essential feature – spontaneous nature and accumulation over a lifetime. Consequently, we will analyze the interaction between the enzymatic (Enz) and spontaneous (Sp) post-translational modifications (PTMs^Enz and PTMs ^Sp). Both forms of PTMs significantly contribute to the balance of L- and D-amino acids (L/D-AAs) in organisms, modulating the functions of nervous and immune systems. The most abundant form of PTM - enzymatic phosphorylation is bio-chemically associated with the spontaneous racemization (Rz^Sp). The crass talk of enzymatic phosphorylation and spontaneous racemization, as an essential determinant of protein aging and aggregation, associated with the aberrant autophagy, apoptosis, and cell signaling, is discussed in this review.

The compatibility of graphene or graphene oxide with its dispersion medium (polymer) plays a critical role in the formation nanocomposite materials with significant property improvements. Environmentally friendly miniemulsion polymerization, which allows a formation of nanoencapsulation in an aqueous phase and high molecular weight polymer/composite production is one promising method. In this study, we screened a series of amphiphilic modifiers and found that the quaternary ammonium (ar-vinyl benzyl) trimethyl ammonium chloride (VBTAC) pending carbon double bonds could effectively modify the graphene oxide (GO) to be compatible with the organophilic monomer. After that, free radical miniemulsion polymerization could successfully synthesize stable latex of exfoliated poly (methyl methacrylate) (PMMA)/ GO nanocomposite. The final latex had an extended storage life and a relatively uniform particle size distribution. X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) analysis of this latex and its films indicated successful encapsulation of exfoliated nano-dimensional graphene oxide inside a polymer matrix.

Carbon-based nanomaterials, such as carbon nanomaterials, play an important role in many promising nanomaterials in the field of biomedicine. Among them, carbon nanomaterials are a new kind of porous carbon nanomaterials with great application potential. Therefore, based on carbon nanomaterials, the interaction between biomaterials and cells and surface modification were analyzed. Studies have shown that the interaction between the surface of biological materials and cells is mainly the mutual molecular recognition between the surface receptors of cell membranes and the ligands on the surface of biomaterials. Therefore, biomimetic modification of the surface of biomaterials is used to enhance cell affinity and specific recognition. The carbon nanomaterial has a large specific surface area and pore volume, can provide high drug-loading capacity, has an adjustable pore structure and pores, can control the release of the drug molecules, and has a good application prospect in the field of drug delivery systems.

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.

During HIV-1 virus assembly the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag-Psi interactions, there is almost no information on kinetic aspects of this interaction. We have investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3’ two of the three Psi stem-loops than with monomeric RNA containing the 5’ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.

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.

Adulteration of food products, including honey, is a serious problem in today’s economy. Honey has become the third most counterfeited food product in the world, which requires effective authentication methods. This article presents considerations regarding the development of meteorology to test the quality of honey based on the analysis of bee pollen. The justification for conducting such analyses is the relatively high need for the authentication of honey and its derivatives. It turns out that the honey market and honey itself are the third products in the world in which undesirable, inappropriate, and quality-reducing components may appear, affecting the final quality of a product such as honey. The analyses mentioned above thus come down to issues related to the analysis and processing of images. A certain novelty of the approach to this analysis is an attempt to parameterize them using the so-called Hjorth descriptors, which have been a tool known for almost 50 years from the analysis of electroencephalographic (EEG) signals. In this paper, after an introduction to the issues related to testing honey, the issues related to the method of obtaining bee pollen images, improving their quality by applying appropriate filtration, performing normalization, and finally calculating Hjorth distributors such as: Activity, Mobility, and Complexity will be discussed. In the next stage described in this article, the authors perform a detailed statistical analysis leading to the initial construction of a simple classifier that distinguishes defined gropus of bee pollen images.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

Modification the biodegradable matrix was carried by graft-copolymerization polylactide with methacrylic acid of various concentrations. Ultraviolet irradiation with different exposure times to the samples was chosen as the initiator of copolymerization. In the experiment the effect of ultraviolet light on polylactide and graft copolymerization was investigated: the resulting samples were studied by viscosimetry, gravimetry, FTIR, static cation- exchange capacity analysis . The conditions for obtaining grafted copolymers and the dependence of the characteristics on the reaction conditions are established.

This paper presents a novel statistical model i.e. the Laplace-Rician distribution, for the characterisation of synthetic aperture radar (SAR) images. Since accurate statistical models lead to better results in applications such as target tracking, classification, or despeckling, characterising SAR images of various scenes including urban, sea surface, or agricultural, is essential. The proposed Laplace-Rician model is investigated for SAR images of several frequency bands and various scenes in comparison to state-of-the-art statistical models that include K, Weibull, and Lognormal. The results demonstrate the superior performance and flexibility of the proposed model for all frequency bands and scenes.

We present an improved algorithm for fast calculation of the inverse square root for single-precision floating-point numbers. The algorithm is much more accurate than the famous fast inverse square root algorithm and has a similar computational cost. The presented modification concern Newton-Raphson corrections and can be applied when the distribution of these corrections is not symmetric (for instance, in our case they are always negative).

We describe our investigations of the surface physicochemical and biological properties of polylactic acid modified by silver, argon and carbon ion implantation to doses of 1 × 10¹⁴, 1 × 10¹⁵ and 1 × 10¹⁶ ion/cm² at energies of 20 keV (for C and Ar) and 40 keV (for Ag). X-ray analysis shows enhancement of coherent scattering regions and lattice constant increase after ion implantation. Secondary electron mass-spectrometry indicates that Ag concentration in the subsurface layer is less than 80%, but at a depth of 500 nm does not exceed 1–2%. The silver forms metal particles in the subsurface layer rather than making additional chemical bonds with polymer atoms. Atomic force microscopy reveals that the higher the irradiation dose the larger the surface roughness of the samples. Ag-irradiated samples implanted to a dose of 1 × 10¹⁶ ions/cm² have the highest roughness, 190 nm. Our investigation of the cytotoxicity of two individual donor macrophages shows that Ag-implanted polylactic acid has no negative impact on immune system cells and could be a promising material for biomedical application.

Titanium membranes are used for guided bone regeneration in implant therapy. However, as a bioinert material, titanium does not have the ability to accelerate bone formation. Various titanium surface treatments to confer bioactivity have been demonstrated; however, there are concerns about the influence of chemical treatments on the corrosion of thin titanium membranes. This study investigated the influence of surface modifications on the structure of thin titanium membranes. Titanium membranes of 20 µm thickness were treated with acid or alkali solutions, and we evaluated their surface structure, wettability, corrosion depth, and mechanical strength compared to non-treated membranes. Alkali-treated thin titanium membranes displayed the formation of nanoscale pore structures on their surfaces, enhanced hydrophilicity, and less corrosion depth compared with acid-treated membranes. Furthermore, the tensile strength of alkali-treated membranes was comparable to non-treated membranes. These results suggest that alkali treatment is an appropriate surface modification method for thin titanium membranes.

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.

Why do the eyes remain comparatively large whereas the cornea is reduced in most troglobiont mysids? Are there any important organ size-dependent functions served by non-visual eye rudiments? This issue was approached by measuring eye structures in five troglobiont species of Mysida and two Stygiomysida compared with 14 troglophile and 49 trogloxene Mysida species. The Organ of Bellonci (OB) was found in all Mysida and as first records also in Stygiomysida. The length of OBs increased with individual body length and eye length in four examined species: from postnauplioid larvae to adult stage in a troglophile and a trogloxene mysid species examined; and from juveniles to adults in a troglobiont mysid and a troglobiont stygiomysid. At the interspecific level, eye length was on average 26% shorter at a given body length while the OB was 40% longer at a given body length and 54% longer at a given eye length, respectively, in adult troglobionts compared with trogloxene mysids. The OB is clearly proliferating while the cornea is reduced in troglobionts. This points to sensory functions (possibly together with other functions). The sensory pore organ was found in all 15 Mysida species whose eyes were mounted on slides, and a first record of this organ was also found in Stygiomysida.

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.

Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m6A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m6A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m6A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m6A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze current literature on m6A modification of HIV-1 RNA, the multifaceted functions of m6A in regulating HIV-1 replication, and the role of viral RNA m6A modification in evading the innate immune responses to infection. Furthermore, we briefly discuss future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications.

Adopting banana peel as raw material, the adsorption properties of banana peel hydrothermal carbon modified with KOH solution for lead ions in aqueous solution were studied. The surface structure and functional groups of the modified hydrothermal carbon were analyzed by XRD and SEM. The results showed that the banana peel hydrothermal carbon prepared from 0.5 mol/L KOH solution had large pores, and its adsorption capacity reached 42.92 mg/g at a pH value of 6; When the concentration of KOH solution is 0.5 mol/L, the solid liquid ratio is 2 g/L, the adsorption capacity reaches 21.39 mg/g, and the adsorption rate reaches 82.74%; When the concentration of lead solution increased to 100 mg/L, the adsorption capacity of modified hydrothermal carbon for lead ions decreased to 78.26%; The equilibrium adsorption time of lead ion in solution on phosphoric acid modified hydrothermal carbon from banana peel was 250 minutes, and the adsorption process met the quasi second order kinetic model and Freundlich isotherm equation, with an equilibrium adsorption rate of 88.62%. The adsorption of lead ions in solution by KOH modified hydrothermal carbon is mainly chemical physical adsorption.

The aim of this study was to evaluate the emulsification properties of garlic water-soluble compounds (GWSC) after heat treatment (10 min at 95 °C) or pH adjustments (2.5, 3.5 and 7.8). After the various treatments, the extracts were used as such or filtrated (0.45 µm) and 10% soybean oil-in-water emulsions were prepared using low (0.48%) or high (6.55% wt/wt) extract concentrations. Whereas at low GWSC concentration, both heating or acidifying resulted in the formation of bigger oil droplet sizes (i.e. from d32=0.36 µm using unmodified extract, to d32=7–22 µm µm at pH 2.5 with or without extract filtration), the effects were opposite at the highest GWSC concentration. In the latter, heat treatment clearly reduced the droplet size as observed from the micrographs as well as the degree of creaming, though the occurrence of depletion and/or bridging flocculation was still strong. The acidification of the extract at this high GWSC concentration, significantly reduced the droplet size as observed from the micrographs but a strong flocculation was observed. Removal of protein aggregates, and possibly also saponin micelles from the extract, resulted in an obvious increase in emulsion droplet size. This research brings valuable insights on the study and utilisation of novel natural food emulsifiers from plant sources.

Advancements in genomics, bioinformatics and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts have been directed towards investigating this process in heart development and failure. However, few studies have shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports have shown the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has not been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs’ roles in heart development and CHDs and discuss the impacts of perinatal splicing transition and its dysregulation in CHDs. We further summarize discoveries made of causal splicing variants in key transcription factors that have been implicated in CHDs. Improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.

A new approach to fabricate TiNi surfaces combining the advantages of both monolithic and porous materials for implants is used in this work. New materials were obtained by depositing a porous TiNi powder onto monolithic TiNi plates followed by sintering at 1200°C. Then, further modification of the material surface with a high-current-pulsed electron beam (HCPEB) was carried out. Three materials obtained (one after sintering and two after subsequent beam treatment by 20 and 30 pulses, respectively) were studied by XRD, SEM, EDX, EIS methods, profilometry and OCP measurements. Structural and compositional changes caused by HCPEB treatment were investigated. Surface properties of the samples during their storage in saline for 10 days were studied and a model experiment with cell growth (MCF-7) was carried out for the sample unmodified with electron beam to detect cell appearance on different surface locations.

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.

Canine influenza virus (CIV) H3N2 causes a highly contagious respiratory disease in dogs and has been the source of outbreaks across North America since 2015. An injectable RNA Particle (RP)-CIV H3N2 vaccine has been developed to protect dogs against this disease. To demonstrate efficacy, dogs were randomized into two treatment groups, then vaccinated subcutaneously twice, 21 days apart, with a placebo vaccine (n = 20) or a RP-CIV H3N2 vaccine (n = 20). Three weeks later, dogs were challenged intranasally with virulent CIV H3N2 and observed daily for 10 days for clinical signs of disease. Nasal swabs were also collected daily to evaluate shedding of the challenge virus. Ten days post-challenge, dogs were euthanized, and the lungs were examined for consolidation. RP-CIV H3N2 vaccination demonstrated a significant reduction in duration of clinical signs, duration and amount of virus shed, lung consolidation, and the incidence of suppurative pneumonia. To evaluate safety, dogs from multiple geographic regions were vaccinated subcutaneously, 3-4 weeks apart, with a RP-CIV H3N2 vaccine and observed for adverse events for 14 days after each administration. The RP-CIV H3N2 vaccine was deemed safe, with lethargy being the most reported adverse event at a rate of 1.6%.

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.