Background: DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B and HER2-positive Breast Cancer (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). Methods: To decipher its function, DSCAM-AS1 expression was measured by qRT-PCR in tissue samples from 93 BC patients in addition to a meta-analysis of 30 gene expression datasets, together with the evaluation of its association with clinical data. By computational analyses of our RNA-Seq in MCF-7 cells, we investigated the DSCAM-AS1 knock-down effects at both gene and isoform levels. Results: We confirmed DSCAM-AS1 overexpression in high grade Luminal A, B and HER2+ BCs and found a significant correlation with disease relapse. 908 genes were regulated by DSCAM-AS1-silencing, primarily involved in cell cycle and inflammatory response. Noteworthy, the analysis of alternative splicing and isoform regulation revealed 2,085 splicing events regulated by DSCAM-AS1, enriched in differential polyadenylation sites and 3’UTR shortening events. Finally, the DSCAM-AS1-interacting splicing factor hnRNPL was predicted as the most enriched RBP for exon skipping and 3’UTR events. Conclusion: The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer.

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, Wuhan coronavirus (COVID-19), plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms were stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission and cure RNA virus infection were proposed, implying that FIR radiation might be a cheap, convenient, and efficient method in clinic to treat RNA virus.

Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) is one of many severe diseases that threaten bread wheat (Triticum aestivum L.) yield and quality worldwide. The discovery and deployment of powdery mildew resistance genes (Pm) can prevent this disease epidemic in wheat. In a previous study, we transferred the powdery mildew resistance gene Pm57 from Aegilops searsii into common wheat and cytogenetically mapped the gene in a chromosome region with the fraction length (FL) 0.75-0.87, which represents 12% of 2Ss#1 segment on the long arm of chromosome 2Ss#1. In this study, we performed RNA-Seq on three infected and mock-infected wheat-Ae. searsii 2Ss#1 introgression lines with Bgt-isolates inoculation at 0, 12, 24, and 48 hours after inoculation. Then we designed 79 molecular markers based on transcriptome sequences and physically mapped them to Ae. searsii chromosome 2Ss#1- in seven intervals. We used these markers to identify 46 wheat-Ae. searsii 2Ss#1 recombinants induced by ph1b, a deletion mutant of pairing homoelogous (Ph) genes. Analysis of the 46 ph1b-induced 2Ss#1L recombinants with different Bgt-responses using 28 2Ss#1L-specific molecular markers in the interval FL0.72-0.87 where Pm57 is located, and the flanking intervals, we physically mapped Pm57 gene on the long arm of 2Ss#1 in a 5.13 Mb genomic region, which was flanked by markers X67593 (773.72 Mb) and X62492 (778.85 Mb). By comparative synteny analysis of the corresponding region on chromosome 2B in Chinese spring (T. aestivum L.) with other model species we identified ten genes that are putative plant defense-related (R) genes which includes six coiled-coil nucleotide-binding site-leucine-rich repeat (CNL), three nucleotide-binding site-leucine-rich repeat (NL) and a leucine-rich receptor-like repeat (RLP) encoding proteins. This study will lay a foundation for further cloning of Pm57, and benefit the understanding of interactions between resistance genes of wheat and powdery mildew pathogens.

Although there is a several array of diagnostic and therapeutic choices for pancreatic cancer in recent years, a crucial medical approach for the refractory disease is still needed. Oligonucleotide therapeutics, such as those based on antisense RNAs, RNA interference, aptamers and decoys, are promising agents against pancreatic cancer because they identify a specific nucleotide sequence or protein and interfere with gene expression as molecular-targeted agents. Within just the past quarter-century, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Actually, there have been several clinical and preclinical studies of oligonucleotides for patients with pancreatic cancer so far. To support the discovery of effective diagnostic or therapeutic options by using oligonucleotide-based strategies in the absence of satisfactory therapies for long-term survival and the rising trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients with underlying preclinical or scientific data and focus on the possibility of oligonucleotides to target pancreatic cancer in clinical implications.

A dogma is normally considered as a principle or a belief accepted as an indisputable truth by some individuals and/or groups. Theoretically there can be no dogmas in science, but it has been demonstrated that scientific thought operates by conceptual changes. A dogma therefore can be understood as a concept present at the heart of some contemporary research programmes that need to be altered to overcome paradigms. Here we argue that two ideas relating to emergence of the biological system research need to be re-evaluated. First, is the idea that research programmes about the emergence of the biological system are the same as those of the origin of cells. Cells are strikingly important biological entities, hard core concepts for the entire field of biology. The emergence of the biological system happened much earlier than the origin of cells and thus the First Universal Common Ancestor (FUCA) should be viewed as a great-grandfather to the Last Universal Cellular Ancestor (LUCA); i.e. the latter is the first cellular life form. Second, RNA-world theories are the focus of mainstream research programmes for the origin of life stricto sensu. In the RNA-world view, self-replication of nucleic acids is seen as one of the most relevant events in the pre-biotic world. Without denying the relevance of self-replication, we argue here that the most germane event which occurred in the pre-biotic world was the crosstalk between nucleic acids and peptides. When these two macromolecules started to interact, the singularity that aggregated the complexity required to produce life emerged. Thus, comprehension of the early origins of the translation machinery and the assembly of the genetic code is key. Therefore, the relevance of cell theory and self-replication should be re-evaluated as well as the concept of life itself.

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long-term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyse the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in germination rate and RNA integrity number (RIN) after long-term storage, or CDT. The RIN value was obtained by electrophoresis of total RNA extracted from seed embryos. Seeds of ‘Vandaran (Indica)’, ‘Tupa 729 (Japonica)’, and ‘Badari Dhan (Indica)’ consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions, regardless of the harvest year. A strong correlation (R2 = 0.93) was observed between germination rates and RIN values of the seeds after long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials, including both Japonica and Indica cultivars, for improving rice seed longevity.

The augmenting commitment in the entrepreneurial learning process, both at academic and industry level, has led to new mechanisms and methodologies. Entrepreneurship literature has shown evidence of raising interest in the problem-based learning (PBL) methodology with regard to upcoming events from the surrounding learning context. This paper presents a Systematic Bibliographic Literature Review (SBLR) with respect to the application of PBL throughout distinct entrepreneurial processes either in higher education, or in industry. It aimed to identify relevant entrepreneurial opportunities for PBL. Bibliographic databases were searched for documents published between 2002 and May 2024 to categorize key topics discussed in the literature on PBL and entrepreneurship. The review process identified 142 empirical and non-empirical papers on entrepreneurship related PBL. Data analysis revealed diverse subthemes for PBL uses in entrepreneurship in both higher education institutions and industry. The research questions “What is the interplay of problem-based learning methodology with entrepreneurship?” guided the study. The central output of the research is the discovery of the varying uses of PBL to cope with diverse events arising within entrepreneurship context. Future research directions are suggested.

Herein we report the expansion of the chemical space available from the chitin, accessible via the biogenic N-platforms 3A5AF, M4A2C and di-HAF. The biologically active heteroaromatics furo[3,2-d]pyrimidin-4-one and furo[3,2-d]pyrimidin-4-amine can be selectively accessed from 3A5AF and M4A2C, respectively. The chiral pool synthon di-HAF is a viable substrate for the Achmatowicz rearrangement, providing streamlined access to 2-aminosugars possessing a versatile hydroxymethyl group at C5.

Human induced climate change led to the recognition of Community-Based Adaptation (CBA) as one of the remedies in building adaptive capacity and resilience of communities. It recognizes the agency of communities in shaping the optimal strategy. CBA interventions are vital in addressing community needs and contextual specificities, enable participatory and inclusive engagement and thereby facilitate more profound adaptation impacts. Agent-based modelling (ABM) has the potential to be an invaluable approach in developing tailored adaptation strategies considering capacities, resources, skills, priorities, needs and the cultural context of local communities. ABM allows to capture the complex relationships among various components within community decision making on CBA actions, the CBA actions themselves and the environment, however available tools provide for various degrees of freedom in agent definition, sensitivity analysis, scalability, experiment design and output analysis to name a few. This article assesses all available ABM modelling and simulation tools for its application in the context of CBA. NetLogo emerges as the most suitable tool for incorporating and handling the special features of CBA. It is closely followed by GAMA and Envision. The article provides insights and guidance to researchers and practitioners in selecting ABM tools aligned with the specific requirements of their CBA simulations and projects.

Due to the rapid growth of the Internet of Things (IoT), securing communications between a huge number of devices has become very difficult. Access controls and authentication secure the connection between IoT devices and protect sensitive data from unauthorized users or malicious attackers. In this paper, we provide a comprehensive review to emphasize the critical role of authentication and access control in securing IoT environments. This paper explores different types of access controls, like Attribute-Based Access Control and Role-Based Access Control. Furthermore, it demonstrates different authentication techniques, like passwords and biometrics. Based on the previous mechanisms, we discuss different IoT security challenges regarding authentication and access control mechanisms and highlight future directions. In addition, this paper investigates the integration between access control and authentication to safeguard IoT communications.

The evolution of photovoltaic cells is intrinsically linked to advancements in the materials from which they are fabricated. This review paper provides an in-depth analysis of the latest developments in silicon-based, organic, and perovskite solar cells, which are at the forefront of photovoltaic research. We scrutinize the unique characteristics, advantages, and limitations of each material class, emphasizing their contributions to efficiency, stability, and commercial viability. Silicon-based cells are explored for their enduring relevance and recent innovations in crystalline structures. Organic photovoltaic cells are examined for their flexibility and potential for low-cost production, while perovskites are highlighted for their remarkable efficiency gains and ease of fabrication. The paper also addresses the challenges of material stability, scalability, and environmental impact, offering a balanced perspective on the current state and future potential of these material technologies.

The aim of this study was to investigate the impact of Process Oriented Guided Inquiry Learning (POGIL)-based instruction versus lecture-based instruction on Grade 12 students’ performance in circular motion unit. A quasi-experimental, pretest-posttest design, the impact of POGIL-based instruction versus lecture-based instruction on students’ performance as measured by three types of cognitive outcomes: Knowing, Applying and Reasoning (KAR). The total number of participants was approximately 110 students (N=110); 54 were assigned to treatment groups (25 girls and 29 boys) and 56 were assigned to control groups (27 girls and 29 boys). The treatment group was taught a unit of circular motion in physics using POGIL-based instruction while the control group was taught the unit using lecture-based instruction. The findings of the study showed statistically significant differences between students of the control group and the treatment group in favor of the later regarding their circular motion performance, suggesting the superiority of the POGIL in enhancing student understanding of the circular motion.

This article investigates the prospect of implementing multidisciplinary and multicultural student teamwork (MMT) involving Case-based Learning (CBL) and Problem-based Learning (PBL) as a sustainable teaching practice. Based on a mixed methods approach, which includes direct observation (both physical and virtual), questionnaire distribution and focus-group interviews the study reveals that MMT through CBL and PBL can both facilitate and hinder sustainable learning. Our findings show that while MMT enhances knowledge sharing, it also poses a wide range of challenges, raising questions about its social significance as a sustainable teaching practice. The study suggests the implementation of certain mechanisms, such as ‘Teamwork Training’ and ‘Pedagogical Mentors’, aiming to strengthen the sustainable orientation of MMT through CBL and PBL.

In MBSE there is yet no converged terminology. The term ’system model’ is used in different contexts in literature. In this study we elaborated the definitions and usages of the term ’system model’, to find a common definition. 104 publications have been analyzed in depth for their usage and definition as well as their meta-data e.g., the publication year and publication background to find some common patterns. While the term is gaining more interest in recent years it is used in a broad range of contexts for both analytical and synthetic use cases. Based on this three categories of system models have been defined and integrated into a more precise definition.

This article discusses the use of game design as a method for interdisciplinary project-based teaching in secondary school education to convey informatics and society topics. There is a lot of knowledge about learning games but little background on project-based teaching using game design as a method. We present the results of an analysis of student-created games and an evaluation of a student-authored database on learning contents found in commercial off-the-shelf games. We further contextualise these findings using a group discussion with teachers. Results underline the effectiveness of project-based teaching to raise awareness for informatics and society topics. We further outline informatics and society topics that are particularly interesting to students, genre preferences and potentially engaging game mechanics stemming from our analyses.

The ubiquity of mobile sensors (such as GPS, accelerometer and gyroscope) together with increasing computational power have enabled an easier access to contextual information, which proved its value in next generation of the recommender applications. The importance of contextual information has been recognized by researchers in many disciplines, such as ubiquitous and mobile computing, to filter the query results and provide recommendations based on different user status. A context-aware recommendation system (CoARS) provides a personalized service to each individual user, driven by his or her particular needs and interests at any location and anytime. Therefore, a contextual recommendation system changes in real time as a user’s circumstances changes. CoARS is one of the major applications that has been refined over the years due to the evolving geospatial techniques and big data management practices. In this paper, a CoARS is designed and implemented to combine the context information from smartphones’ sensors and user preferences to improve efficiency and usability of the recommendation. The proposed approach combines user’s context information (such as location, time, and transportation mode), personalized preferences (using individuals past behavior), and item-based recommendations (such as item’s ranking and type) to personally filter the item list. The context-aware methodology is based on preprocessing and filtering of raw data, context extraction and context reasoning. This study examined the application of such a system in recommending a suitable restaurant using both web-based and android platforms. The implemented system uses CoARS techniques to provide beneficial and accurate recommendations to the users. The capabilities of the system is evaluated successfully with recommendation experiment and usability test.

Translation of the genetic code into proteins is the main process across all life and ribosomes are ancient cellular machines uniquely enabling this information transformation. We provide a brief overview of the recent advances in linking the ribosomal structure and evolution. Based on these insights into ribosomal organisation across time, we propose that early replication and protein biosynthesis functions were inseparable and in fact were performed by the same ancient RNA molecule, the riboreplisome. Riboreplisome hypothesis helps to address issues of non-Darwinian evolution and complicated starting point that are characteristic to the RNA world, protein world and RNA:protein mixed co-development theories. We suggest that the riboreplisome is the missing link and a molecular machine connecting chemical and biological evolution paths, by being capable of basic genetic and feature selection functions in a cell- or cell-free setting. The riboreplisome hypothesis allows ease of sequential, genetically uninterrupted emergence and sophistication of the genetic code and its decoding machinery, and provides plausible explanations to the origins of the three main RNA types involved in the decoding: the ribosomal, transfer and messenger RNA. Furthermore, riboreplisome can help explaining the co-evolution of aminoacylation machinery, the driving force behind selective gene transcription and expression, and the cell-like compartmentalisation. While we may never find the original riboreplisome again, we might continue to discover different molecular remnants of its prior existence across the existing biological RNA, which, once identified or resurrected, can be useful in synthetic biology applications.

Exploring new approaches to innovating higher vocational education is a worldwide pursuit driven by the increasing demand for graduates equipped with competencies. This study investigated how Outcomes-Based Education (OBE) influences the attainment of graduate competence (AGC) in China’s higher vocational education, using the theory of Constructive Alignment (CA) as its foundation. The OBE framework incorporates intended learning outcomes (ILOs), project-based learning (PjBL), assessment strategies (ASs), and AGC. The study tested the model by assessing the impact of ILOs, PjBL, and ASs on AGC, respectively and sequentially. Surveys were administered to 320 CBEC learners in April 2024, resulting in 301 usable responses. Data were analyzed using structural equation modeling (SEM) with SPSS 23.0 and AMOS 24.0. Results indicated that PjBL and ASs were directly and positively related to graduate competency attainment, while ILOs were indirectly associated with graduate competence through the mediating roles of PjBL and ASs. The most substantial mediating effect between ILOs and graduate competence was ASs, followed by PjBL, and then, the chain mediating effect of PjBL and ASs. These findings enhance the theoretical understanding of OBE and provide detailed procedures for tracking and enhancing sustainability in higher vocational education. Beneficiaries include educators, policymakers, and accreditation bodies.

Modern fighter aircraft increasingly need to conjugate aerodynamic performance and low observability. In this paper we showcase a methodology for a gradient-based bidisciplinary aero-stealth optimization. The shape of the aircraft is parametrized with the help of a CAD modeler, and we optimize with the SLSQP algorithm. The drag, computed with the help of a RANS method, is used as the aerodynamic criterion. The stealth criterion, a function is derived from the radar cross section in a given cone of directions, weighed with a function whose goal is to cancel the electromagnetic intensity in a given direction. Stealth is achieved passively by scattering back the electromagnetic energy away from the radar antenna and no energy is absorbed by the aircraft, which is considered as a perfect conductor. A Pareto front is identified by varying the weights of the aerodynamic and stealth criteria. The Pareto front allows for an easy identification of the CAD model corresponding to a chosen aero-stealth trade-off.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

The correlations of seismic noise, recorded during 1997-2022 at 229 stations around the world are investigated. The property of waveforms, known as the Donoho-Johnston threshold, is analyzed, which separates the absolute values of the orthogonal wavelet coefficients into "small" and "large". Network of 50 reference points is considered. For each reference point, a time series with a time step of 1 day is calculated as the median of the values of the DJ index from the 5 nearest stations. For each reference point, the correlations between the values of the DJ index at other reference points are calculated in a sliding time window of 365 days. Average values of the DJ index decrease, which is interpreted as indicators of global seismic hazard increasing. The maximum distances between reference points with strong correlations show an explosive increase after 2011. Bursts in the mean coherences between the length of day (LOD) and the values of the DJ index at the reference points precede the release of seismic energy with a delay of about 530 days. High amplitude of the DJ index response to LOD for the times 2020-2022 was identified, which may forecast a strong earthquake in the second half of 2023.

Noise in requirements has been known to be a defect in software requirements specifications (SRS). Detecting defects at an early stage is crucial in the process of software development. Noise can be in the form of irrelevant requirements that are included within a SRS. A previous study had attempted to detect noise in SRS, in which noise was considered as an outlier. However, the resulting method only demonstrated a moderate reliability due to the overshadowing of unique actor words by unique action words in the topic-word distribution. In this study, we propose a framework to identify irrelevant requirements based on the MultiPhiLDA method. The proposed framework distinguishes the topic-word distribution of actor words and action words as two separate topic-word distributions with two multinomial probability functions. Weights are used to maintain a proportional contribution of actor and action words. We also explore the use of two outlier detection methods, namely Percentile-based Outlier Detection (PBOD) and Angle-based Outlier Detection (ABOD), to distinguish irrelevant requirements from relevant requirements. The experimental results show that the proposed framework was able to exhibit better performance than previous methods. Furthermore, the use of the combination of ABOD as the outlier detection method and topic coherence as the estimation approach to determine the optimal number of topics and iterations in the proposed framework outperformed the other combinations and obtained sensitivity, specificity, F1-score, and G-mean values of 0.59, 0.65, 0.62, and 0.62, respectively.

Animal-based measures are the measure of choice in animal welfare assessment protocols as they can often be applied completely independently to the housing or production system employed. Although there has been a small body of work on potential animal-based measures for farmed crocodilians [1-3], they have not been studied in the context of an animal welfare assessment protocol. Potential animal-based measures, that could be used to reflect the welfare state of farmed crocodilians, were identified and aligned with the Welfare Quality® principles of good housing, good health, good feeding and appropriate behaviour. A consultation process with a panel of experts was used to evaluate and score the potential measures in terms of validity and feasibility. This resulted in a toolbox of measures being identified for further development and integration into animal welfare assessment on the farm. Animal-based measures related to ‘good feeding’ and ‘good health’ received the highest scores for validity and feasibility by the experts. There was less agreement on the animal-based measures that could be used to reflect ‘appropriate behaviour’. Where no animal-based measures were deemed to reliably reflect a welfare criterion nor be useful as a measure on the farm, additional measures of resources or management were suggested as alternatives. Future work in this area should focus on the reliability of the proposed measures and involve further evaluation of their validity and feasibility as they relate to different species of crocodilian and farming system.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

Given the increase in consumers’ preferences for coffee, it is becoming important to understand their decision-making processes in the coffee chain context. To deepen the understanding of sustainable outcomes in this context, this study investigates the role of dedication- and constraint-based mechanisms in forming consumers’ repurchase and positive word-of-mouth (WOM) intentions, two critical sustainable outcomes. We examined the effects of coffee quality, the quality of the physical environment, and service quality in accelerating the formation of dedication-based factors. Moreover, this study offers an in-depth understanding of the enablers of perceived switching costs. Data collected from 238 university students that frequently visit coffee chains are empirically tested against the proposed theoretical framework by using structural equation modeling. The results confirm that both dedication- and constraint-based factors substantially predict consumers’ sustainable outcomes in the coffee chain context. Brand image and perceived switching costs play an important role in enhancing consumers’ repurchase and positive WOM intentions compared with customer satisfaction. Coffee quality is significantly associated with both customer satisfaction and brand image, whereas the quality of the physical environment and service quality are only significantly associated with brand image. Habit is found to be the key enabler of perceived switching costs, while loyalty programs have no significant impact on perceived switching costs.

Effectively mapping and monitoring rubber plantation is still changing. Previous studies have explored the potential of phenology features for rubber plantation mapping through a pixel-based approach (pixel-based phenology approach). However, in fragmented mountainous Xishuangbanna, it could lead to noises and low accuracy of resultant maps. In this study, we investigated the capability of an integrated approach by combining phenology information with an object-based approach (object-based phenology approach) to map rubber plantations in Xishuangbanna. Moderate Resolution Imaging Spectroradiometer (MODIS) data were firstly used to acquire the temporal profile and phenological features of rubber plantations and natural forests, which delineates the time windows of defoliation and foliation phases. Landsat images were then used to extract a phenology algorithm comparing three different approaches: pixel-based phenology, object-based phenology, and extended object-based phenology to separate rubber plantations and natural forests. The results showed that the two object-based approaches achieved higher accuracy than the pixel-based approach, having overall accuracies of 96.4%, 97.4%, and 95.5%, respectively. This study proved the reliability of a phenology-based rubber mapping in fragmented landscapes with a distinct dry/cool season using Landsat images. This study indicated that the object-based phenology approaches can effectively improve the accuracy of the resultant maps in fragmented landscapes.

Cotton seeds as the main by-product of cotton are not only an important raw material for edible oil and feed but also a source of biofuel. The quality of cotton seeds directly affects cotton planting and is closely related to the yield and fiber quality. However, the molecular mechanism governing cotton seed size remains largely unexplored. This study investigates the regulatory mechanisms of cotton seed size by focusing on two cotton genotypes, N10 and N12, which exhibit notable phenotypic variations across multiple environments. Developing seeds were sampled at various stages (5, 20, 30, and 35 DAP) and subjected to RNA-seq. The temporal pattern clustering and WGCNA on differentially expressed genes identified 413 candidate genes, including these related to sugar metabolism that were significantly enriched in transcriptional regulation. A genetic transformation experiment indicated that the overexpression of the GhUXS5 gene encoding UDP-glucuronate decarboxylase 5 significantly increased seed size, suggesting an important role of GhUXS5 in regulating cotton seed size. This discovery provides crucial insights into the molecular mechanisms controlling cotton seed size, helping to unravel the complex regulatory network and offering new strategies and targets for cotton breeding to enhance the economic value of cotton seeds and overall cotton yield.

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.

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.

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.

Cytochrome P450 monooxygenases (P450s) and UDP-glycosyltransferases (UGTs) are involved in the evolution of insecticide resistance. Leptinotarsa decemlineata (Say), Colorado potato beetle (CPB), is the notorious insect that has developed resistance to various of insecticides including neonicotinoids. This study investigated whether the differentially expressed P450 genes CYP9Z140 and CYP9AY1 and UGT gene UGT321AP1, found from our transcriptome results conferred resistance to thiamethoxam in L. decemlineata. Resistance monitoring showed that sampled field populations of L. decemlineata adults collected from Urumqi City, Qapqal, Jimsar and Mulei County of Xinjiang in 2021-2023 developed low levels to thiamethoxam with resistance ratios ranging from 6.66- to 9.52-fold. Expression analyses indicated that CYP9Z140, CYP9AY1, and UGT321AP1 were significantly upregulated in thiamethoxam-resistant populations compared with susceptible population. The expression of all three genes also increased significantly after thiamethoxam treatment compared with control. Spatiotemporal expression patterns showed that the highest expression of CYP9Z140 and CYP9AY1 occurred in pupae and midgut, whereas UGT321AP1 was highly expressed in adults and Malpighian tubules. Knocking down all three genes individually or simultaneously using RNA interference increased the sensitivity of adult L. decemlineata to thiamethoxam. These results suggest that overexpression of CYP9Z140, CYP9AY1, and UGT321AP1 contribute to the development of thiamethoxam resistance in L. decemlineata and provide scientific basis for improving new resistance management of CPB.

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletic has become a concern. However, there is still room for improvement in gene doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9 including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

The addition of 50% vitreous humor to the media bathing lens explants results in the induction of both fiber cell differentiation and a significant immune/inflammatory response. Although Fgfr loss blocks differentiation in lens epithelial explants, this loss is partially rescued by deleting Pten. To investigate the functions of the Fgfrs and Pten during lens fiber cell differentiation, we utilized a lens epithelial explant system and conducted RNA sequencing on vitreous humor-exposed explants lacking Fgfrs, or Pten or both Fgfrs and Pten. We found that Fgfr loss impairs both vitreous-induced differentiation and inflammation while the additional loss of Pten restores these responses. Furthermore, transcriptomic analysis suggested that PDGFR-signaling in FGFR-deficient explants is required to mediate the rescue of vitreous-induced fiber differentiation in explants lacking both Fgfrs and Pten. The blockage of β-crystallin induction in explants lacking both Fgfrs and Pten in the presence of a PDGFR-inhibitor supports this hypothesis. Our findings demonstrate that a wide array of genes associated with fiber cell differentiation are downstream of FGFR-signaling and that the vitreous-induced immune responses also depend on FGFR-signaling. Our data also demonstrates that many of the vitreous-induced gene expression changes Fgfr-deficient explants are rescued in explants lacking both Fgfrs and Pten.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella Sativa, has been extensively researched for its anti-cancer properties across various human cancers. Yet, its specific anticancer mechanisms and pathways in glioblastoma remain to be elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 µM and 5 µM TQ concentrations. However, at 25 µM and 50 µM, TQ significantly reduced cell viability in a dose-dependent manner. We identified 1548 DEGs at 25 µM TQ (684 upregulated, 864 downregulated) and 2797 DEGs at 50 µM TQ (1528 upregulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5), while modulating Wnt signaling and upregulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anticancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.

Background: RNA helicase DHX15 plays a significant role in vasculature development and lung metastasis in vertebrates. In addition, several studies have demonstrated the overexpression of DHX15 in the context of hepatocellular carcinoma. Therefore, we hypothesized that this helicase may play a significant role in liver regeneration, physiology and pathology. Methods: Dhx15 gene deficiency was generated by CRISPR/Cas9 in zebrafish and by TALEN-RNA in mice. FANA Antisense-Oligonucleotides were used to silence Dhx15 in wild-type mice. The hepatocellular carcinoma tumor induction model was generated by subcutaneous injection of Hepa 1-6 cells. Results: Homozygous Dhx15 gene deficiency was lethal in zebrafish and mouse embryos. Dhx15 gene deficiency impaired liver organogenesis in zebrafish embryos and liver regeneration after partial hepatectomy in mice. Also, heterozygous mice presented decreased number and size of liver metastasis after Hepa 1-6 cells injection compared to wild-type mice. Dhx15 gene silencing with FANA Antisense-Oligonucleotides in wild-type mice resulted in 80% reduced expression in the liver and a significant reduction in other major organs. In addition, Dhx15 gene silencing significantly hindered primary tumor growth in the hepatocellular carcinoma experimental model. Regarding the potential use of DHX15 as a diagnostic marker for liver disease, patients with hepatocellular carcinoma showed increased levels of DHX15 in blood samples compared with subjects without hepatic affectation. Conclusion: Dhx15 is a key regulator of liver physiology and organogenesis, is increased in the blood of cirrhotic and hepatocellular carcinoma patients and has a key role in controlling hepatocellular carcinoma tumor growth and expansion in experimental models.

Sugarcane mosaic virus (SCMV) is a (genus, Potyvirus; family, Potyviridae) is a widespread, deleterious, and the most damaging pathogen of sugarcane ((Saccharum officinarum L. and Saccharum spp.) which causes a substantial barrier to producing high sugarcane earning. Sugarcane mosaic disease (SCMD) is caused by, single or compound infection of SCMV, disseminated by the several aphid vectors in a non-persistent manner. SCMV has flexuous filamentous particle of 700-750 nm long, which encapsidated a positive-sense, single-stranded RNA molecule of 9575 nucleotides. RNA interference (RNAi)-mediated antiviral innate immunity is an evolutionary conserved, key biological process in eukaryotes and has evolved as an antiviral defence system to interfere with viral genomes for controlling infections in plants. The current study aims to analyze sugarcane (Saccharum officinarum L. and Saccharum spp.) locus-derived microRNAs (sof-miRNAs/ssp-miRNAs) with predicted potential for targeting the SCMV +ssRNA-encoded mRNAs, using a predictive approach that involves five algorithms. The ultimate goal of this research is to mobilize the in silico- predicted endogenous sof-miRNAs/ssp-miRNAs to experimentally trigger the catalytic RNAi pathway and generate sugarcane cultivars to evaluate the potential antiviral resistance surveillance ability and capacity for SCMV. Experimentally validated mature sugarcane (S. officinarum, 2n = 8X = 80) and (S. spp., 2n = 100-120) sof-miRNA/ssp-miRNA sequences (n = 28) were downloaded from the miRBase database and aligned with the SCMV genome (KY548506). Among the 28 targeting mature locus-derived sof-miRNAs/ssp-miRNAs evaluated, one sugarcane miRNA homolog, sof-miR159c, was identified to have a predicted miRNA binding site, at nucleotide position 3847 of the SCMV genome targeting CI ORF. To verify the accuracy of the target prediction accuracy and to determine, whether the sugarcane sof-miRNA/ssp-miRNA could bind the predicted SCMV mRNA target(s), we constructed an integrated Circos plot. A genome-wide in-silico-predicted miRNA-mediated target gene regulatory network has implicated to validate interactions necessary to warrant in vivo analysis. The current work provides valuable computational evidence for the generation of SCMV-resistant sugarcane cultivars.

Trichothecene mycotoxin T-2 toxin is an important environmental pollutant and poses a global threat to human and animal health. T-2 toxin could induce nephrotoxicity, however, the precise molecular mechanism remains unclear. In this study, the mice were intraperitoneally administrated with a single dose of 2 mg/kg T-2 toxin. The kidney function and ultrastructural observation were also assessed and found T-2 toxin exposure could cause kidney damage. Transmission electron microscopy showed a significant swelling and vacuolization of the mitochondria of renal cell. A total of 1122, 58, and 391 differential expression genes (DEGs) that were predominantly expressed in kidney tissues at 1 d, 3 d, and 7 d after T-2 toxin exposure, respectively. Early transcriptomic changes at 1 d after exposure were down-regulation of DEGs involved in the cell cycle, p53 signaling pathway, and cellular senescence, while up-regulation of DEGs referred to the ribosome pathway. The temporal variations in gene expression pattern in T-2 toxin exposure in mice kidney were presented and cellular metabolism was disturbed at the exposure recovery period with 7 d. In conclusion, this study, for the first time, provided a comprehensive comparative transcriptomic analysis of gene regulation in T-2 toxin exposure-induced nephrotoxicity at different temporal periods and explored the nephrotoxicity mechanism of T-2 toxin at the mRNA level.

The shoot apical meristem (SAM) gives rise to the aerial structure of plants by producing lateral organs and secondary meristems. The SAM is responsible for plant developmental patterns, thus determining plant morphology and, consequently, many agronomic traits such as the number and size of fruits and flowers and kernel yield. Our current understanding of SAM morphology and regulation is based on studies conducted mainly on some angiosperms, including economically important crops such as maize (Zea mays) and rice (Oryza sativa), and the model species Arabidopsis (Arabidopsis thaliana). However, studies in other plant species from the gymnosperm class are scant, making difficult comparative analyses that help us understand SAM regulation in diverse plant species. This limitation prevents deciphering the mechanisms by which evolution gave rise to the multiple plant structures within the plant kingdom, and determined the conserved mechanisms involved in SAM maintenance and operation. This review aims to integrate and analyze the current knowledge of SAM evolution by combining the morphological and molecular information recently reported from the plant kingdom.

Mycoviruses are widespread across the major taxa of fungi including yeasts. Mycoviruses in the yeast fungus Geotrichum candidum are not well studied with three G. candidum-associated viral species characterized to date, all of which belong to the Totiviridae genus Totivirus. In this study, we report the molecular characteristics of another two totiviruses co-infecting isolate Gc6 of G. candidum. The two totiviruses were tentatively named Geotrichum candidum totivirus 2 (GcTV2-Gc6) and GcTV4-Gc6). Both viruses have typical genome organization of totiviruses comprising two ORFs encoding capsid protein (CP) and RNA-dependent RNA polymerase (RdRp) at the N and C termini, respectively. Genomes of GcTV2-Gc6 and GcTV4-Gc6 are 4592 and 4530 bp long, respectively. Both viruses contain the -1 frameshifting elements and their proteins could be expressed as a single fusion protein. GcTV2-Gc6 is closely related to a totivirus isolated from the same host whereas GcTV4-Gc6 is related to insect-associated totiviruses. The phylogenetic analysis indicated that GcTV2-Gc6 and GcTV4-Gc6 belong to two different sister clades, I-A and I-B, respectively. It is interesting that all viruses identified from G. candidum belong to the genus Totivirus. It is possible that the RNA interference (RNAi) mechanism is not active to suppress totivirus accumulation in isolate Gc6.

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.

The development of biosensors for target detection plays a crucial role in advancing various fields of bioscience. This work presents the development of a genosensor that exploits the colorimetric phenol-sulfuric acid sugar reaction for the detection of DNA, and RNA as specific targets, and DNA intercalator molecules. The biosensor combines simplicity and reliability to create a novel bio-assay for accurate and rapid analysis. A 96-well microplate based on polystyrene polymer was used as the platform for an unmodified capture DNA immobilization via a silanization process and with (3-Aminopropyl) triethoxysilane (APTES). After that, a hybridization step was carried out to catch the target molecule, followed by adding phenol and sulfuric acid to quantify the amount of DNA or RNA sugar backbone. This reaction generates a yellow-orange color on the wells measured at 490 nm that was proportional to the target concentration. Under the optimum conditions, a calibration curve was obtained for each target. The developed biosensor demonstrated high sensitivity, good selectivity, and linear response over a wide concentration range for DNA and RNA targets. Additionally, the biosensor was successfully employed for the detection of DNA intercalator agents that inhibit the hybridization of DNA complementary to the immobilized capture DNA. The developed biosensor offers a potential tool for sensitive and selective detection in various applications, including virus diagnosis, genetic analysis, pathogenic bacteria monitoring, and drug discovery.

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU including identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-Transgenic (HIV-Tg) animal model, to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). RNA-Seq analysis on the striatum - a brain region that is primarily targeted by both HIV and drugs of abuse - identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptor, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND.

Sugarcane mosaic virus (SCMV) is a deleterious pathogen which causes widespread Sugarcane mosaic disease (SCMD) and is classified in the genus Potyvirus (Potyviridae), disseminated by the aphid vector. RNA interference (RNAi)-mediated antiviral innate immunity is a key biological process and antiviral defence system to interfere with viral genomes for controlling plant pathogens. The current study aims to analyze sugarcane (Saccharum officinarum L. and Saccharum spp.) locus-derived microRNAs (sof-miRNAs/ssp-miRNAs) with predicted potential for targeting the SCMV +ssRNA-encoded mRNAs, using ‘five algorithms’ approach. The ultimate goal in this research is to mobilize the in silico endogenous predicted sof-miRNAs/ssp-miRNAs to trigger RNAi catalytic pathway experimentally and generate sugarcane cultivars for evaluating potential antiviral resistance monitoring capability and capacity for SCMV. Experimentally validated mature sugarcane (S. officinarum, 2n = 8X = 80) and (S. spp., 2n = 100-120) sof-miRNAs/ssp-miRNAs (n = 28) were acquired for alignment with the SCMV genome. Of the 28 targeting mature locus-derived sof-miRNAs/ssp-miRNAs investigated, one sugarcane miRNA homolog, sof-miR159c, was concluded to localize potential binding site at genomic nucleotide site 3847 targeting CI ORF of SCMV. In order to validate target prediction accuracy, whether the sugarcane sof-miRNA/ssp-miRNA might bind predicted SCMV mRNA target(s), we created an integrated Circos plot. Genome-wide in-silico-predicted miRNA-mediated target gene regulatory network validated interactions that warrant in vivo analysis. The current work provides valuable evidence and biological material for generating SCMV-resistant sugarcane varieties.

Because rice is native to tropical and subtropical regions, it is generally more sensitive to cold stress compared to other cereals. Low temperature stress has become one of the most important conditions that affects the growth, development, and yield of rice. Plant NAC (NAM, ATAF1/2, and CUC) transcription factors are known to play significant regulatory roles in the stress response. In our research, we found that OsNAC050 (LOC_Os03g60080） is mainly expressed in leaves, and low temperature can further up-regulate its expression. OsNAC050 mutants created using CRISPR-Cas9 gene editing technology showed significantly enhanced tolerance to low temperature treatment. Detection of enzyme activities related to the redox pathway also showed that the mutants had stronger viability under low temperature stress. Comparative transcriptome analysis showed that photosynthesis and soluble sugar metabolism were significantly affected in the osnac050 mutant lines, suggesting that OsNAC050 may participate in the above molecular pathways in the response to low temperature stress. The results will enhance our understanding of molecular mechanisms underlying the responses to cold stress in rice and can provide new strategies for engineering cold-tolerance in high-yielding rice varieties.

Olfaction plays a crucial role in many important behavioral activities of insects, such as finding sexual partners, locating hosts, and selecting oviposition sites. Ionotropic receptors (IRs) play a central role in detecting chemosensory information from the environment and guiding insect behaviors and are potential target genes for pest control. Empoasca onukii Matsuda is a major pest of the tea plant Camellia sinensis (L.) O. Ktze, and seriously influences tea yields and quality. In this study, the ionotropic receptor gene EnouIR25a in E. onukii was cloned, and the expression pattern of EnouIR25a was detected in various tissues. Behavioral responses of E. onukii to volatile compounds emitted by tea plants were determined by the olfactometer bioassay and field trials. To further explore the function of EnouIR25a in olfactory recognition of compounds, RNAi (RNA interference) of EnouIR25a was carried out by ingestion of in vitro synthesized dsRNAs. The CDS length of EnouIR25a was 1266 bp and it encoded a 48.87 kD protein. EnouIR25a was enriched in the antennae of E. onukii. E. onukii were more significantly attracted by 1-phenylethanol at concentration of 100 µl/ml. Feeding with dsRNA-IR25a significantly downregulated the expression level of EonuIR25a, after 3 h of treatment, which disturbed the behavioral responses of E. onukii to 1-phenylethanol at concentration of 100µl/ml. The response rate of E. onukii to 1-phenylethanol was significantly decreased after dsRNA-IR25a treatment for 12 h. In summary, the ionotropic receptor gene EnouIR25a was highly expressed in the antennae of E. onukii and was involved in olfactory recognition of the tea plant volatile 1-phenylethanol. The present study may help us to use the ionotropic receptor gene as a target for the behavioral manipulation of E. onukii in the future.

The emergence of drug resistant pathogenic bacteria is increasingly challenging conventional antibiotics. Plant derived flavonoids are considered as potential alternatives to antibiotics due to their antimicrobial properties. However, the mechanisms by which flavonoids modulate pathogenic microorganisms’ growth are not fully understood. In our previous studies we found that Rutin, a kind of flavonoids showed inhibition against Klebsiella pneumoniae strains. In order to better understand its inhibitory mechanism on strain growth, we used both Rutin and Luteolin as treatments to incubate K. pneumoniae ATCC700603 strain. After incubation for 4 hours, the homogenous and differential effects of two different flavonoids on the growth of K. pneumoniae were evaluated. The integrated metabolomic and transcriptomic analysis was performed. The expression levels of 5,483 genes and the contents of 882 metabolites were measured. The differentially expressed genes (DEGs) and metabolites (DEMs) were screened and analyzed. The correlation between DEGs and DEMs were also studied. Our results showed that Rutin could inhibit the strain growth by changing metabolic pathways and ABC transporters pathways. Our study also revealed FU841_RS17580 and FU841_RS19145 as functional genes that played vital roles in the strain growth.

The innate immune system is the first line of host defense sensing viral infection. Manganese (Mn) has recently been found to be involved in the activation of innate immune DNA sensing cGAS-STING pathway and subsequent anti-DNA virus function. However, whether Mn2+ mediates host defense against RNA viruses is still unclear. In the current study, we demonstrated that Mn2+ exhibited antiviral effects against various animal and human viruses including RNA viruses such as PRRSVs and the VSV as well as a DNA virus such as the HSV1 in a dose-dependent manner. Moreover, cGAS and STING were both investigated in the Mn2+ mediated antiviral roles using the knockout cells made by CRISPR-Cas9 approach. Unexpectedly, the results revealed that neither cGAS knockout nor STING knockout had any effect on Mn2+ mediated antiviral functions. Nevertheless, we verified that Mn2+ promoted the activation of cGAS-STING signaling pathway. These findings suggest that Mn2+ has broad spectrum antiviral activities in a cGAS-STING pathway independent manner. This study also provides significant insights into redundant mechanisms participating in the Mn2+ antiviral functions and also indicates new target for Mn2+ antiviral therapeutics.

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Hearth where key biomolecules such as amino acids, polypeptides, purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. We describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus.

The pandemic of COVID-19 ravaged most countries and made the healthcare system go for a toss. The impact of the disease is different in each patient and it progresses differently. Based on the severity, the COVID-19 infection is stratified into three main categories- mild, moderate, and severe. In this study, we performed a transcriptomic study of different stages and studied the progression of the disease. The study was based on an Indian population of 28 COVID-19 patients, which were classified into different groups. Our analysis has shown that as the disease progresses, the genes involved in the degranulation of the neutrophils and galactose metabolism increase. Furthermore, we identified the hub proteins in each stage. TB is one of the comorbidities of COVID-19 and a comparative study was done to identify the preserved module of genes in both. Enrichment analysis showed that the members of this module are significantly involved in translation and ribosome synthesis.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Single-cell RNA sequencing data facilitates investigation of cell heterogeneity and subpopulations as well as differentially abundant states however modern single-cell RNA sequencing datasets are growing in size and complexity requiring advances in the bioinformatic methods that analyze them. Many methods exist for each step of analysis including read alignment, normalization, quality control, batch effect correction, imputation and dimensionality reduction. With so many options to choose from at each step of the analysis, benchmarking and a synthesis of the literature on the methods available is necessary to inform biological researchers on the most optimal workflow for their data. Here, recent key methods of analysis are highlighted with a focus on methods that facilitate identification of cell subpopulations and differentially abundant cell states. With a constantly expanding toolset for each step in single-cell RNA sequencing dataset analysis, biological researchers should stay informed to utilize the most applicable methods for their own analyses.

Mosquitoes are widespread arthropods that serve as vectors for a broad spectrum of viruses, many of which pose a substantial threat to humans. Conversely, some viruses may seemingly present with beneficial implications for the health of man whilst impinging on other domains of life, such as the fungi-infecting mycoviruses. This study is only the second one so far to describe the exceptionally scarcely identified Xanthi chryso-like virus (XCLV), member of the mycopathogenic Chrysoviridae family, in a new geographical area and a novel potential arthropod vector, the Culex pipiens mosquito. Interestingly, the XCLV was initially fortuitously detected by West Nile virus-specific primers directed at a conserved part of the NS5 gene, possibly indicative of a genetic resemblance and shared ancestry reflected in the NS5 evolutionary heritage. Detection and characterization of the virus and insect alike was done via PCR and Sanger sequencing. This investigation draws attention to our knowledge of viral pervasiveness – be it topographical or vectorial – and how humble it truly is. Additionally, we would propose that more attention be given to arthropod-borne viral pathogens that might prove advantageous to human health.

Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.

Intratumoral heterogeneity associates with more aggressive disease progression and worse patient outcomes. Understanding the reasons enabling the emergence of such heterogeneity remains incomplete, which restricts our ability to manage it from a therapeutic perspective. Technological advancements such as high-throughput molecular imaging, single-cell omics and spatial transcriptomics now allow recording the patterns of spatiotemporal heterogeneity in a longitudinal manner, thus offering insights into the multi-scale dynamics of its evolution. Here, we review latest technological trends and biological insights from molecular diagnostics as well as spatial transcriptomics, both of which have witnessed a burgeoning growth in recent past in terms of mapping heterogeneity within tumor cell types as well as stromal constitution. We also discuss ongoing challenges, indicating possible ways to integrate insights across these methods to have a systems-level spatiotemporal map of heterogeneity in each tumor, and a more systematic investigation of implications of heterogeneity for the patient outcomes.

Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses confirmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically significantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was significantly enhanced in fish by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 significantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.

In this paper we establish a topological framework of τ-structures to quantify the evolutionary transitions between two RNA sequence-structure pairs. τ-structures developed here consist of a pair of RNA secondary structures together with a non-crossing partial matching between the two backbones. The loop complex of a τ-structure captures the intersections of loops in both secondary structures. We compute the loop homology of τ-structures. We show that only the zeroth, first and second homology groups are free. In particular, we prove that the rank of the second homology group equals the number γ of certain arc-components in a τ-structure, and the rank of the first homology is given by γ−χ+1, where χ is the Euler characteristic of the loop complex.

Pratylenchus loosi is an important root-lesion nematode that cause damage to tea plantations in Iran and all over the world. The present study reports on the characterization and evolution of three ß-1,4-engoglucanase genes Pl-eng-2, Pl-eng-3 and Pl-eng-4. The gene structure of Pl-eng-2 was fully determined with the predicted signal peptide and devoid of the linker domain and carbohydrate-binding domain, while Pl-eng-3 and Pl-eng-4 were only partially sequenced. The transcription of Pl-eng-2 was localized in the secretory esophageal glands of all life stages, but it was upregulated in male and females stages. Exon/intron structures of Pl-eng-2, Pl-eng-3 and Pl-eng-4 confirmed that they resulted from gene duplication followed by sequence and gene structure diversification with loss of linker domain and carbohydrate-binding domain during evolution. Phylogenetic analysis further confirmed that nematode endoglucanases resulted from horizontal gene transfer of a bacterial gene as Pl-eng-3 showed sister relationships with CelB cellulase of Bacillus subtilis. Silencing Pl-eng-2 by in vitro RNA interference, produced a 60% decrease of the transcript level. The reproductive ability of silenced P. loosi showed a 35% reduction of eggs and larval stages compared to untreated nematodes suggesting that this gene is involved in the early steps of invasion.

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.

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.

As a major infectious disease in chickens, Newcastle disease causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 dpi after infection at day21 with a lentogenic Newcastle disease virus in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV challenged and nonchallenged groups, 526 differentially expressed genes (DEGs) (FDR &lt; 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, IPA analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis and angiogenesis. Upregulation of Interferon Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK Signaling Antagonist 1 (SPRY1), a DEG in the current study is located in a significant QTL associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.

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.

The biosynthesis of DNA inherently competes with RNA synthesis because it depends on the reduction of ribonucleotides (RNA precursors) to 2’-deoxyribonucleotides by ribonucleotide reductase (RNR). Hence, RNA viruses can increase viral RNA production in cells by partially blocking the synthesis of DNA, e.g. by downregulating the mammalian selenoprotein thioredoxin reductase (TR), which normally acts to sustain DNA synthesis by regenerating reduced thioredoxin, a hydrogen donor for RNR. Computational and preliminary experimental evidence supports the hypothesis that a number of pathogenic RNA viruses, including HIV-1, Ebola, Zika, some flu viruses, and SARS-CoV-2, target TR isoforms by antisense. TR knockdown would create a host antioxidant defect that could be partially rectified by increased selenium intake, or be exacerbated by selenium deficiency, contributing to viral pathogenesis. There are several non-selenium-dependent means that viruses might also exploit to slow DNA synthesis, such as targeting RNR itself, or components of the glutaredoxin system, which serves as a backup redox system for RNR. HIV-1 substantially downregulates glutathione synthesis, so it interferes with both the thioredoxin and glutaredoxin systems. Computational results suggest that, like Ebola, SARS-CoV-2 targets TR3 by antisense. TR3 is the only TR isoform that includes an N-terminal glutaredoxin domain, so antisense knockdown of TR3 may also affect both redox systems, favoring RNA synthesis. In contrast, some DNA viruses encode their own glutaredoxins, thioredoxin-like proteins and even RNR homologues – so they are doing just the opposite, favoring DNA synthesis. This is clear evidence that viruses can benefit from shifting the RNA:DNA balance to their advantage.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) has claimed nearly 180,000 lives and continues to spread. There are currently no approved medications or vaccines for this new coronavirus. Studies have shown that the positive RNA genome of SARS-CoV-2 contains unique features, including a 12-base sequence inserted between the two subunits of viral receptor protein Spike. This inserted sequence facilitates the cleavage of Spike by the cellular proteases Furin and TMPRSS2, leading to the fusion of virus and host cell membranes. Current studies are mostly focused on the SARS-CoV-2 Spike protein and its interacting cellular proteins ACE2, Furin, and TMPRSS2. RNA structural studies are limited and little is known about the potential impact of the 12-base sequence insert on the secondary structure of SARS-CoV-2 genomic RNA and/or its transcripts. Here, by using local and global RNA secondary structure predictions, we show that the novel 12-base insert of SARS-CoV-2 genome likely induces a major RNA secondary structure change.

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 outbreak of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused severe damage to the world. With the support of classic evolutionary theories and population genetics principles, many studies on the origin of SARS-CoV-2 have revealed encouraging results but meanwhile are still under debate. We are concerned with the validity of applying classic evolutionary theories and formula to the evolution of RNA viruses. We have raised several factors like the RNA replication feature and the RNA modification systems of the hosts, which might jeopardize the validity of the application of classic methods to analyze the SARS-CoV-2 data.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in China towards the end of 2019, and has spread rapidly ever since. Previous studies showed that some virus could affect the reproductive system and cause long-term complications. Recent studies exploring the source of SARS-CoV-2 using genomic sequencing have revealed that SARS-CoV-2 enters the host cells via the angiotensin-converting enzyme II (ACE2), the receptor that recognizes SARS-CoV. To investigate the expression of ACE2 and to explore the potential risk of infection in the reproductive system, we performed a thorough bioinformatic analysis on data from public databases involving RNA expression, protein expression, and single-cell RNA expression studies. The analyzed data showed high levels of ACE2 mRNA and protein expression in the testis and spermatids and equal levels of ACE2 expression in the uterus and lung. Comprehensive single-cell analysis identified ACE2 expression in the lung, testis, spermatids, and uterus. In conclusion, this study revealed the potential risk associated with the SARS-CoV-2 infection in the reproductive system and predicted that long-term complications might have a significant impact on the prevention and management of COVID-19, the disease caused upon infection with SARS-CoV-2.

Autophagy is an evolutionarily conserved central process in host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention.

The circulating transcriptome is a valuable source of cancer biomarkers, which with the exception of miRNAs, remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients of healthy individuals, we used next generation sequencing (NGS) and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (P < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (P<0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA, 5´-fragments, were enriched for the angiopoietin, PAK and EIF2 pathways. Levels of ATM1, AMFR, SOS1 and CD109 gene fragments were up-regulated (P < 0.001) in melanoma samples (n=144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1 and RNY4P25 were significantly higher in patients with stage 0 disease, than either healthy controls or more advanced stage disease (P < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which most importantly we validated in multi-centre retrospective and prospective cohorts suggesting potential diagnostic use of these RNA species.

Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA-Sequencing analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

Currently there is little doubt left on the symbiogenetic nature of eukaryotes - genomes of archaeon and bacterium participated in shaping a genome of last eukaryotic common ancestor in equal albeit asymmetric manner, while a merger event itself indicated the advent of a new domain of life. The “symbiogenetic” framework of interaction of two partners is proposed, outlining similar steps essential for three major advents: the origin of life, the origin of complex life and the origin of humans. Given the immense importance of proper energy source for the evolution of life it seems plausible that for any principal increase in complexity, a partnership with a novel energy donor is required. Moreover, a “language” elaborated in the course of communication of partners might have been a prerequisite for a subsequent increase in complexity. Transitions, which led to RNA-protein world, eukaryotes and human brain, resulted in advent of complex languages via communication onsets between two entities in close partnership. Accordingly this further facilitated formation of first cells, multicellular organisms and human society.

Scientific knowledge evolves in small steps, with occasional backsteps to correct inaccuracies, all occurring within a competitive environment. This perspective for the first time looks at the history of latency-related RNA (LR-RNA) that was later renamed latency-associated transcript (LAT). At the 1986 International Herpesvirus Workshop (IHW) meeting in Leeds, England, Daniel L Rock and Anthony B Nesburn first reported the discovery of human herpes virus 1 (HSV-1) latency-related (LR)-RNA that is antisense to ICP0. Less than a month after the IHW meeting a paper was submitted to Science magazine and 8 months later appeared in print thanking “D. Rock for suggesting RNA complementary to the ICP0 message may be present in latently infected cells”. This perspective is not a review of LAT literature but intends to clarify the timeline of LAT discovery and subsequent breakthroughs such as reactivation, apoptosis, CD8+ T cell exhaustion, and LAT expression in different cell types detected during latency. While many review articles have been written about LAT since 1987, the most comprehensive and balanced review about LAT was written by Dr. David Bloom’s group (1). In this overview, I will discuss our original collaboration with Dr. Dan Rock and subsequent work that our group performed, which is still ongoing. Finally, I will discuss the controversies associated with LAT from its inception to current times.

Saudi Arabia is an oil-reliant nation as a large percentage of its GDP comes from oil resources. Oil dependency leaves a county at the mercy of the international crude market, and a decrease in the price of crude can seriously destabilize the economy of such nations. An example is the case of Venezuela whose dependence on oil caused a national disaster (McCarthy, 2017). As such, the nation’s exports, GDP, and government revenue are primarily dependent on oil revenue, and the recent decrease in the oil prices has decreased Venezuela’s national revenue resulting in economic collapse as well as inflation. A shift from a resource based economy to a knowledge based economy will help Saudi Arabia become less reliant on its oil revenues for its economic stability and growth (Nurunnabi, 2017).

The ASEAN Community-based Tourism (CBT) Standard has been adopted by 10 ASEAN member states in 2016 in order to collectively promote ASEAN as a competitive community-based tourism destination. Among the ASEAN member states, Lao PDR (Laos), has a unique CBT development experience through collaboration with various international development agencies. Such history has brought about issues when ASEAN CBT Standard was implemented at to provincial and district levels in Laos, including concerns of related communities on the Standard being not easily applicable considering the state of tourism development. While the application of the regional standard is a significant issue to the tourism industries in the Member States, however, there has been a lack of studies regarding the dynamics of implementation of regional tourism standards at the national level. In order to fill the research gap, this study utilized in-depth interviews with seven executives with significant experiences from the government, international development agency, international organization, and the private sector. Interviewees projected a diversity of perspectives on enabling factors and challenges in implementing ASEAN Community-based Tourism Standard at the national level focusing on Laos, which showed the complexity of CBT dynamics. The results also revealed how regional standards can be further recognized and promoted to the key stakeholders of Laos, better accepted and utilized by end users, and possibly better customized according to the local circumstances. Findings of this study evidence that collaboration among key stakeholders and the expected role of these stakeholders are critical when implementing ASEAN CBT Standard.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improve the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical-dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

In this study, graphite, the most stable form of carbon, was examined for its hexagonal crystalline structure with specific dimensions (ao=2.46 Ǻ; co=6.70 Ǻ). Its framework comprises parallel carbon atom planes forming regular hexagons (side length 1.415 Ǻ) and 120° angles between adjacent atoms. Two structural variations exist: hexagonal symmetry (1-2-1-2-1-2 planes) and rhomboidal symmetry (1-2-3-1-2-3 planes). The research aimed to produce high-density graphite utilizing carbonaceous raw materials. Graphite-based materials often exhibit high porosity, necessitating additional treatments. The study successfully obtained mesophase tar pitch (yield: 45%), a pivotal raw material, and high-density graphite. The resulting graphite underwent characterization for physical properties (apparent and real density, porosity and compression strength), demonstrating conformity with existing literature data.

After the great success of Mobile wallet, the Internet of Things (IoT) leaves the door wide open for consumers to use their connected devices to access their bank accounts and perform routine banking activities from anywhere, anytime and with any device. However, consumers need to feel safe when interacting with IoT-based payment systems, and their personal information should be protected as much as possible. Unlike as usually done in the literature, in this paper, we introduce two lightweight and secure IoT-based payment protocols based on an identity-based signature scheme. We adopt a server-aided verification technique to construct the first scheme. This technique allows to outsource the heavy computation overhead on the sensor node to a cloud server while maintaining the user's privacy. The second scheme is built upon a pairing-free ECC-based security protocol to avoid the heavy computational complexity of bilinear pairing operations. The security reduction results of both schemes are held in the Random Oracle Model (ROM) under the discrete logarithm and computational Diffie-Hellman assumptions. Finally, we experimentally compare the proposed schemes against each other and against the original scheme on the most commonly used IoT devices: a smartphone, a smartwatch and the embedded device Raspberry Pi. Compared with existing schemes, our proposed schemes achieve significant efficiency in the term of communication and computational overheads

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

Acute myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation, leading to continual proliferation of myeloid progenitor cells. These alterations can include a well-documented chromosomal translocation that leads to the synthesis of the PML-retinoic acid receptor fusion protein that leads to a block in differentiation and the ability to induce differentiation with all-trans retinoic acid and other small molecules. In essence, in large part, the disease is due to stem cell-like cells that are blocked in their ability to undergo terminal differentiation to more mature, non-proliferative cell types. We discovered a long non-coding RNA (lncRNA), lncRNAp53int1, encoded from the first intron of the p53 tumor suppressor gene. Interestingly, lncRNAp53int1 appears to play an important regulatory role in maintaining the undifferentiated and proliferative state in a manner independent from p53 gene expression. lncRNAp53int1 is expressed at high levels in proliferating, undifferentiated promyelocytes and its levels fall significantly during their terminal differentiation to non-proliferating granulocytes or macrophages. Furthermore, forced overexpression of lncRNAp53int1 blocks terminal differentiation. The observation that the expression of this lncRNA is repressed during terminal differentiation of human leukemic cells and its expression blocks differentiation of leukemic myeloid progenitor cells, is likely to have clinical implications with regards to differentiation therapy for myeloid leukemia. Ongoing research aims to identify the molecular partners that it associates with and the signaling pathways that this lncRNA participates in with the long-term goal of identifying molecules that inhibit lncRNAp53int1 activity and serve as potential therapeutic drugs. The goal of this mini-review is to disseminate these novel and interesting findings to readers and to describe where we think this research is headed and the impact it can have on myeloid leukemias.

The SARS-CoV-2 nucleocapsid protein (N protein) is critical to viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex to drive viral genomic RNA (gRNA) translation and in also suppressing both stress granules and processing bodies which is postulated to increase uncoated gRNA availability. The N protein can also form biomolecular condensates with a broad range of host endogenous proteins including RNA binding proteins (RBPs). Amongst these RBPs are proteins that are associated with pathological neuronal and glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, including TAR DNA binding protein 43 kDa (TDP-43) which forms pathological inclusions in over 95% of amyotrophic lateral sclerosis cases. In this study, we demonstrate that the N protein can form biomolecular condensates with TDP-43 and that this is dependant on the N protein C-terminus domain (N-CTD) and the intrinsically disordered C-terminus domain of TDP-43. This process is markedly accelerated in the presence of RNA. In silico modelling suggests that the biomolecular condensate that formed in the presence of RNA is composed of a N protein quadriplex in which the intrinsically disordered TDP-43 C terminus domain is incorporated.

PARK7, also known as DJ-1, plays a critical role in protecting cells by functioning as a sensitive oxidation sensor and modulator of antioxidants. DJ-1 acts to maintain mitochondrial function and regulate transcription in response to different stressors. In this study, we showed that cell lines vary based on their antioxidation potential at basal conditions. The transcriptome of HEK293 cells was tested following knockdown (KD) of DJ-1 using siRNAs which reduced the DJ-1 transcripts to only 12% of the original level. We compared the expression levels of 14k protein-coding transcripts, and 4.2k non-coding RNAs relative to control cells treated with non-specific siRNAs. Among the coding genes, ~200 upregulated differentially expressed genes (DEGs) signified a coordinated antiviral innate immune response. Most genes were associated with regulation of type 1 interferons (IFN) and induction of inflammatory cytokines. About a quarter of these genes were also induced in cells treated by non-specific siRNAs that were used as a negative control. Beyond the antiviral response, 114 genes were specific to KD of DJ-1 with enrichment in RNA metabolism and mitochondrial functions. A smaller set of downregulated genes (58 genes) were associated with dysregulation in membrane structure, cell viability, and mitophagy. We propose that KD of DJ-1 diminish its protective potency against oxidative stress, rendering the cells labile and responsive to dsRNA signal by activation of a large number of genes, many of which drive apoptosis, cell death, and inflammatory signatures. The KD of DJ-1 highlights its crucial role in regulating genes associated with antiviral responses, RNA metabolism, and mitochondrial functions, apparently through alteration in STAT activity and downstream signaling. Given that DJ-1 is highly expressed in metastatic cancers, targeting DJ-1 could be a promising therapeutic strategy where manipulation of DJ-1 levels may reduce cancer cell viability and enhance the efficacy of cancer treatments.

The interaction between native and invasive plant species plays a crucial role in understanding invasion mechanisms and developing control strategies. This study investigated the differences in photosynthetic and fluorescence parameters, gene expression profiles, and rhizosphere soil microbial composition between the native species Ficus tikoua Bur. and the invasive species Alternanthera philoxeroides. For the first time, it was demonstrated that that F. tikoua Bur. may enhance photoinhibition ability and the expression of genes involved in carbon metabolism, protein processing in the endoplasmic reticulum, and plant-pathogen interactions to maintain growth. Additionally, it recruits beneficial microbes, e.g. Actinomarina (Bacteria), Nitrosotenuis (Archaea) and Laccaria (fungi), to suppress pathogens, thereby preserving soil DMSP and carbon cycling pathways to resist invasion by A. philoxeroides. These findings provide novel insights into the mechanisms underlying plant invasion and suggest potential strategies for invasive plant management. Further research is needed to investigate this relationship and determine the mechanisms underlying the potential resistance of F. tikoua Bur. to plant invasion.

Transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in root and shoot of Populus euphratica (salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba ‘717-1B4’ (P. × canescens) increased salt sensitivity, which was reflected in plant growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich target mRNAs that physically interact with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in transgenic poplar. Particularly, PeGRP2 negatively affected the stability of target mRNAs encoding photosynthetic proteins (PETC and RBCMT), antioxidant enzymes (SOD[Mn], CDSP32 and CYB1-2), ATPases (AHA11, ACA8 and ACA9), and Na+/H+ antiporter (NHA1). This resulted in (i) a greater reduction in Fv/Fm, YII, ETR and Pn, (ii) a less pronounced salt activation of antioxidative enzymes, and (iii) a reduced ability to maintain Na+ homeostasis in transgenic poplars during long-term salt stress, leading to a lowered ability to tolerate salinity stress.

Tomato (Solanum lycopersicum L.) is one of the most commercially essential vegetable crops cultivated worldwide. In addition to the nutritional value, tomato is an excellent model for studying climacteric fruits' ripening process. Despite this, the available natural pool of genes that allows expanding phenotypic diversity is limited, and the difficulties of crossing using classical selection methods when stacking traits increase proportionally with each additional feature. Genetic engineering makes it possible to introduce changes in genes of interest without changing the allelic combinations characteristic of successful commercial varieties, to enhance the expression of existing genes, to create and transfer artificial and heterologous genes, and much more. However, this requires understanding the fundamental principles of the molecular interaction. Although the leading candidate genes for these components have been identified, a complete picture of their relationship has yet to be formed. The review summarizes the latest (2017-2023) achievements related to studying the ripening processes of tomato fruits. In this work, an attempt is made to systematize the results of various research and display the interaction pattern of genes regulating the process of tomato fruit ripening.

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.

Wool quality and yield are important economic traits of livestock. In this study, the skin tissues of the upper scapula of Super Merino sheep (SM) and Small-Tailed Han sheep (STH) during the growing period were studied. Differentially expressed (DE) long non-coding RNAs (lncRNAs) and messenger RNAs (mRNA) were identified via histopathological observation and high-throughput RNA sequencing. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze differentially expressed genes. Reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify nine selected DE lncRNAs and five DE mRNAs. Significant differences were found in the expression levels of LOC114113396 (KRTAP15-1), CRABP1, KRT10, KRTAP1-3, KRTAP4.3, KRT2, FGF1, IGF-1, and KIT in SM and STH skin tissues. These results indicate that these mRNAs may play an important role in the growth and development of hair follicles and the regulation of hair fiber traits. Differentially expressed lncRNA target genes and mRNAs were mainly enriched in biological processes and pathways related to skin development and fiber traits, which is consistent with previous studies. LncRNA MSTRG.9225.1, MSTRG.124320.1, MSTRG.96951.1, MSTRG.91685.1, MSTRG.122229.1, MSTRG.89255.1, MSTRG.98769.1, and MSTRG.84658.1 may indirectly participate in the growth and development of sheep hair follicles and the regulation of hair fiber diameter by regulating the expression of their respective target genes. These candidate lncRNAs and mRNAs may provide a basis for the study of sheep hair follicle growth and development and hair fiber traits.

Aluminum (Al) toxicity is the most common factor limiting the growth of alfalfa in acidic soil conditions. Melatonin (MT), a significant pleiotropic molecule present in both plants and animals, has shown promise in mitigating Al toxicity in various plant species. This study aims to elucidate the underlying mechanism by which melatonin alleviates Al toxicity in alfalfa through a combined physiological and transcriptomic analysis. The results reveal that 5 μM MT significantly alleviates Al-induced growth inhibition and preserves the morphology of root tip cells. Moreover, MT application reduces Al accumulation in alfalfa roots and shoots by 28.6% and 27.6%, respectively. Additionally, MT plays a crucial role in scavenging Al-induced excess H2O2 by enhancing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), consequently reducing malondialdehyde (MDA) levels. The RNA-seq results reveal that MT application significantly upregulates the expression of xyloglucan endotransglucosylase/hydrolase (XTH) and carbon metabolism-related genes, including those involved in the glycolysis process, as well as sucrose and starch metabolism, suggesting that MT application may mitigate Al toxicity by facilitating the binding of Al to the cell walls, thereby reducing intracellular Al accumulation, and by improving respiration and the content of sucrose and trehalose. Taken together, our study demonstrates that MT alleviates Al toxicity in alfalfa by restoring redox homeostasis, enhancing Al binding to the cell wall, and modulating carbon metabolism. This research advances our understanding of the mechanisms underlying MT's effectiveness in mitigating Al toxicity, offering potential strategies for reducing Al accumulation in alfalfa.

This paper describes new horizons in the diversity and taxonomy of negev-like viruses encoding the membrane-embedded SP24 protein. First, our data extend the known host range of SP24-encoding negev-like viruses to include brown algae, fungi, green plants, the phylum Entoprocta, the phylum Mollusca, and vertebrates. Second, our phylogenetic analysis suggests that the evolution of the SP24 gene family may have involved frequent events of inter-order virus genome shuffling. Third, the identification of 2-3 copies of SP24 protein genes in some virus RNAs shows that virus genomes may have acquired additional SP24 genes during the evolutionary process due to duplications or new acquisition steps. Forth, the broad host specificity of some SP24-encoded viruses may be related to an important adaptive role of SP24. Fifth, insect and nematode genomes may acquire viral SP24 genes by putative horizontal transfer from negev-like viruses known to infect species of both taxa.

Intramuscular fat content (IFC) and meat color are vital indicators affecting pork quality. A significant positive correlation between IFC and redness meat color (a* value) indicates that these two traits are likely to be regulated by shared molecular pathways. To identify candidate genes, hub genes, and signaling pathways that regulate these two traits, we measured the IFC and a* value in 147 hybrid pigs and selected individuls with extreme phenotypes for transcriptome analysis. The results revealed 485 and 394 overlapping differentially expressed genes (DEGs) using DESeq2, limma, and edgeR packages affecting IFC and a* value, respectively. Weighted gene co-expression network analysis (WGCNA) identified four modules significantly correlated with IFC and a* value. Moreover, we integrated functional enrichment analysis results based on DEGs, GSEA, and WGCNA conditions to identify candidate genes, and identified 47 and 53 candidate genes affecting IFC and a* value, respectively. The protein-protein interaction (PPI) network analysis of candidate genes showed that 6 and 14 hub genes affecting IFC and a* value, respectively. These genes mainly participated in various pathways related to lipid metabolism and redox reactions. Notably, four crucial hub genes (MYC, SOX9, CEBPB, and PPAGRC1A) were shared for these two traits. After functional annotation of these four hub genes, we hypothesized that the SOX9/CEBPB/PPARGC1A axis could co-regulate lipid metabolism and myoglobin redox response. Further research on these hub genes, especially the SOX9/CEBPB/PPARGC1A axis, will help to understand the molecular mechanism of the co-regulation of IFC and a* value, which will provide the theoretical basis for improving pork quality.

The chitin synthase B gene is a key enzyme in the chitin synthesis of insect peritrophic matrix (PM), affecting insects' feeding behavior. The chitin synthase B gene has been cloned from the transcription library of Heortia vitessoides Moore. RT-qPCR showed that HvChsb was highly expressed in the larval stage of H. vitessoides, especially on the first day of the prepupal stage, and in the midgut of larvae and the abdomen of adults. After starvation treatment, HvChsb was found to be significantly inhibited with time. After 48 h of starvation, the feeding experiment showed that HvChsb increased with the prolongation of the refeeding time. The experimental data showed that feeding affected the expression of HvChsb. HvChsb was effectively silenced by RNA interference, so its function was lost, significantly decreasing the survival rate of H. vitessoides. The survival rate from larval-to-pupal stages was only 43.33%, accompanied by abnormal phenotypes. It can be seen that HvChsb plays a key role in the average growth and development of H. vitessoides.

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of the heterogeneity of programmed cell death. The purpose of this work is to investigate and develop a cuproptosis-associated lncRNA-based LUAD prediction marker. We firstly performed bioinformatic analysis of the Cuprotosis database and The Cancer Genome Atlas (TCGA) database to obtain 19 cuprotosis-related gene datasets and transcriptional data for LUAD. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were utilized to construct cuproptosis-associated lncRNA modes. LUAD patients were thus classified into high-risk and low-risk categories based on prognostic risk values, with a median of It acted as a boundary. Risk models were evaluated and validated using Kaplan-Meier analysis, principal component analysis (PCA), gene set enrichment analysis (GSEA) and nomograms. Utilizing the TCGA-LUAD dataset, we identified seven predicted cuproptosis-associated lncRNAs in tumor microenvironment to create the risk model. 95.54% (214/224) of high-risk category tumor samples included cuproptosis-associated gene alterations, compared to 85.65% (203/237) of low-risk category tumor samples, with TP53 accounting for the bulk of occurrences. According to these findings, risk value was superior to other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival (OS). The predictive validity of the cuproptosis-associated lncRNA-based risk model for LUAD is high, and this may have implications for how lung cancer patients are treated individually.

Injury to the central nervous system (CNS), in most vertebrate animals, results in permanent damage and lack of function, due to their limited regenerative capacities. In contrast, echinoderms can fully regenerate their radial nerve cord (RNC) following transection, with little or no scarring. Investigators have associated the regenerative capacity of some organisms with the stress response and inflammation produced by the injury. Here we explore the gene activation profile of the stressed holothurian CNS. To do this, we performed RNA sequencing on isolated RNC explants submitted to the stress of transection and enzyme dissection and compared them to explants kept in culture for 3 days following dissection. We describe stress-associated genes, including members of heat-shock families, ubiquitin-related pathways, transposons, and apoptosis that were differentially expressed. Surprisingly, the stress response does not induce apoptosis in this system. Other genes associated with stress in other animal models, such as hero proteins and those associated with the integrated stress response, were not found to be differentially expressed either. Our results provide a new viewpoint on the stress response in the nervous system of an organism with an amazing regenerative capacity. This is the first step to deciphering the molecular processes that allow echinoderms to undergo fully functional CNS regeneration while also providing a comparative view for students of the stress response in other organisms.

Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs) involved in the regulation of 60% of human gene activity remains poorly explored. Similar to what we have previously done with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 hours post-infection, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h while at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. By RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17 and FURIN), in renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2.

Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. They arrest in the G0 phase and generate non-CSC progeny by self-renewing and pluripotency activity, resulting in tumor recurrence, metastasis, and chemoresistance. One CSC can stimulate tumor relapse and can re-grow a metastatic tumor. So, CSC is a promising target for eradicating tumors, and developing an anti-CSC method has become a top priority in cancer therapy. In recent years competing endogenous RNA (ceRNA) have emerged as an important class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. To overcome therapeutic resistance due to CSCs, we need to improve our existing understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed in order to discuss the role of ceRNAs in CSCs function. We reviewed the role of ceRNAs in acquiring CSCs characteristics in the form of different pathways including Rho GTPase/F-actin_ Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) (Hippo), Wnt/β-catenin pathway, transforming growth factor (TGF)-b–urothelial carcinoma-associated 1 (UCA1)–Slug pathway, etc. Finally, considering the comprehensive impacts of the ceRNA network on different pathways, a treatment strategy driving the ceRNA network might be effective. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research.

Here, our data provide the first evidence for the existence of a previously unknown receptive system formed by novel DNA- and RNA-based receptors in eukaryotes. This system, named the TR-system, is capable of recognizing and generating a response to different environmental factors and has been shown to orchestrate major vital functions of fungi, mammalian cells, and plants.Recently, we discovered the existence of a similar regulatory system in prokaryotes. These DNA- and RNA-based receptors are localized outside of the membrane forming a type of a network around cells that respond to a variety of chemical, biological, and physical factors and enabled the TR-system to regulate major aspects of eukaryotic cell life as follows: growth, including reproduction and development of multicellular structures; sensitivity to temperature, geomagnetic field, UV, light, and hormones; interaction with viruses; gene expression, recognition and utilization of nutrients. The TR-system was also implicated in cell memory formation and was determined to be responsible for its maintenance and the forgetting of preceding events. This system is the most distant receptive and regulatory system of the cell that regulates interactions with the outer environment and governs the functions of other receptor-mediated signaling pathways.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.