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• Extracting complex feature information of TIS using multiple encodings. • Capturing hierarchical relationships between features using capsule network. • Improvements are made to the capsule network to enhance performance. • The proposed model improves the prediction performance compared to other models. Genes are the basic units of protein synthesis in organisms, and accurately identifying the translation initiation site (TIS) of genes is crucial for understanding the regulation, transcription, and translation processes of genes. However, the existing models cannot adequately extract the feature information in TIS sequences, and they also inadequately capture the complex hierarchical relationships among features. Therefore, a novel predictor named CapsNet-TIS is proposed in this paper. CapsNet-TIS first fully extracts the TIS sequence information using four encoding methods, including One-hot encoding, physical structure property (PSP) encoding, nucleotide chemical property (NCP) encoding, and nucleotide density (ND) encoding. Next, multi-scale convolutional neural networks are used to perform feature fusion of the encoded features to enhance the comprehensiveness of the feature representation. Finally, the fused features are classified using capsule network as the main network of the classification model to capture the complex hierarchical relationships among the features. Moreover, we improve the capsule network by introducing residual block, channel attention, and BiLSTM to enhance the model's feature extraction and sequence data modeling capabilities. In this paper, the performance of CapsNet-TIS is evaluated using TIS datasets from four species: human, mouse, bovine, and fruit fly, and the effectiveness of each part is demonstrated by performing ablation experiments. By comparing the experimental results with models proposed by other researchers, the results demonstrate the superior performance of CapsNet-TIS. [ABSTRACT FROM AUTHOR]

• This paper reviews the research progress of peanut evolution and genetic breeding. • Point out the main problems and challenges of molecular genetic breeding in peanut research. • Clarify the future research directions of peanut. Peanut is an important cash crop used in oil, food and feed in our country. The rapid development of sequencing technology has promoted the research on the related aspects of peanut genetic breeding. This paper reviews the research progress of peanut origin and evolution, genetic breeding, molecular markers and their applications, genomics, QTL mapping and genome selection techniques. The main problems of molecular genetic breeding in peanut research worldwide include: the narrow genetic resources of cultivated species, unstable genetic transformation and unclear molecular mechanism of important agronomic traits. Considering the severe challenges regarding the supply of edible oil, and the main problems in peanut production, the urgent research directions of peanut are put forward: The de novo domestication and the exploitation of excellent genes from wild resources to improve modern cultivars; Integration of multi-omics data to enhance the importance of big data in peanut genetics and breeding; Cloning the important genes related to peanut agronomic traits and analyzing their fine regulation mechanisms; Precision molecular design breeding and using gene editing technology to accurately improve the key traits of peanut. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 significantly impacts the UPS, a key cellular regulatory mechanism. • SARS-CoV-2 encoded proteinsinteract with host UPS, influencing immune signaling and apoptosis. • Stability of ORF3a and ORF8 may or may not be influenced by host proteasome. • Unlike previous studies, recent studies do not show ORF3a as an ion channel. • SARS-CoV-2 PLpro alters host immune responses via interfering withUPS. • Proteomic studies reveal changes in ubiquitination in SARS-CoV-2 infected cells. • Promising treatment include targeting PLpro with zinc-ejector drugs, targeting viral nsp12 via heat treatment. The Ubiquitin proteasome system (UPS), an essential eukaryotic/host/cellular post-translational modification (PTM), plays a critical role in the regulation of diverse cellular functions including regulation of protein stability, immune signaling, antiviral activity, as well as virus replication. Although UPS regulation of viral proteins may be utilized by the host as a defense mechanism to invade viruses, viruses may have adapted to take advantage of the host UPS. This system can be manipulated by viruses such as the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to stimulate various steps of the viral replication cycle and facilitate pathogenesis, thereby causing the respiratory disease COVID-19. Many SARS-CoV-2 encoded proteins including open reading frame 3a (ORF3a), ORF6, ORF7a, ORF9b, and ORF10 interact with the host's UPS machinery, influencing host immune signaling and apoptosis. Moreover, SARS-CoV-2 encoded papain-like protease (PLpro) interferes with the host UPS to facilitate viral replication and to evade the host's immune system. These alterations in SARS-CoV-2 infected cells have been revealed by various proteomic studies, suggesting potential targets for clinical treatment. To provide insight into the underlying causes of COVID-19 and suggest possible directions for therapeutic interventions, this paper reviews the intricate relationship between SARS-CoV-2 and UPS. Promising treatment strategies are also investigated in this paper including targeting PLpro with zinc-ejector drugs, as well as targeting viral non-structural protein (nsp12) via heat treatment associated ubiquitin-mediated proteasomal degradation to reduce viral pathogenesis. [ABSTRACT FROM AUTHOR]

• IMF deposition is crucial for beef quality and economic value. • Epigenetic mechanisms transform beef-cattle IMF research globally. • Our paper synthesizes epigenetic-IMF associations in cattle. • We explore environmental factors impacting IMF. • This paper emphasizes DNA methylation, histone modifications, and non-coding RNAs in IMF regulation. Intramuscular fat (IMF) deposition profoundly influences meat quality and economic value in beef cattle production. Meanwhile, contemporary developments in epigenetics have opened new outlooks for understanding the molecular basics of IMF regulation, and it has become a key area of research for world scholars. Therefore, the aim of this paper was to provide insight and synthesis into the intricate relationship between epigenetic mechanisms and IMF deposition in beef cattle. The methodology involves a thorough analysis of existing literature, including pertinent books, academic journals, and online resources, to provide a comprehensive overview of the role of epigenetic studies in IMF deposition in beef cattle. This review summarizes the contemporary studies in epigenetic mechanisms in IMF regulation, high-resolution epigenomic mapping, single-cell epigenomics, multi-omics integration, epigenome editing approaches, longitudinal studies in cattle growth, environmental epigenetics, machine learning in epigenetics, ethical and regulatory considerations, and translation to industry practices from perspectives of IMF deposition in beef cattle. Moreover, this paper highlights DNA methylation, histone modifications, acetylation, phosphorylation, ubiquitylation, non-coding RNAs, DNA hydroxymethylation, epigenetic readers, writers, and erasers, chromatin immunoprecipitation followed by sequencing, whole genome bisulfite sequencing, epigenome-wide association studies, and their profound impact on the expression of crucial genes governing adipogenesis and lipid metabolism. Nutrition and stress also have significant influences on epigenetic modifications and IMF deposition. The key findings underscore the pivotal role of epigenetic studies in understanding and enhancing IMF deposition in beef cattle, with implications for precision livestock farming and ethical livestock management. In conclusion, this review highlights the crucial significance of epigenetic pathways and environmental factors in affecting IMF deposition in beef cattle, providing insightful information for improving the economics and meat quality of cattle production. [ABSTRACT FROM AUTHOR]

• Release of Tumor-derived Exosomes (TDEs) is involved in intercellular information exchange. • Tumor-derived Exosomes (TDEs) can negatively regulate the tumor microenvironment. • Tumor-derived Exosomes (TDEs) inhibit peritumour immune cells and create an immunosuppressive environment. Tumor-derived exosomes (TDEs), as topologies of tumor cells, not only carry biological information from the mother, but also act as messengers for cellular communication. It has been demonstrated that TDEs play a key role in inducing an immunosuppressive tumor microenvironment (TME). They can reprogram immune cells indirectly or directly by delivering inhibitory proteins, cytokines, RNA and other substances. They not only inhibit the maturation and function of dendritic cells (DCs) and natural killer (NK) cells, but also remodel M2 macrophages and inhibit T cell infiltration to promote immunosuppression and create a favorable ecological niche for tumor growth, invasion and metastasis. Based on the specificity of TDEs, targeting TDEs has become a new strategy to monitor tumor progression and enhance treatment efficacy. This paper reviews the intricate molecular mechanisms underlying the immunosuppressive effects induced by TDEs to establish a theoretical foundation for cancer therapy. Additionally, the challenges of TDEs as a novel approach to tumor treatment are discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • PTEN gene expression is epigenetically controlled by circular RNAs from transcription to post-translation. • Most regulatory circRNAs exert their function through sponging miRNAs that target PTEN. • CircPTENs directly derived from PTEN mRNA negatively affect cancer progression. • CircPTENs suppress tumors by regulating PTEN function or affecting TGF-β and AKT pathways. Epigenetic regulation of gene expression, without altering the DNA sequence, is involved in many normal cellular growth and division events, as well as diseases such as cancer. Epigenetics is no longer limited to DNA methylation, and histone modification, but regulatory non-coding RNAs (ncRNAs) also play an important role in epigenetics. Circular RNAs (circRNAs), single-stranded RNAs without 3′ and 5′ ends, have recently emerged as a class of ncRNAs that regulate gene expression. CircRNAs regulate phosphatase and tensin homolog (PTEN) expression at various levels of transcription, post-transcription, translation, and post-translation under their own regulation. Given the importance of PTEN as a tumor suppressor in cancer that inhibits one of the most important cancer pathways PI3K/AKT involved in tumor cell proliferation and survival, significant studies have been conducted on the regulatory role of circRNAs in relation to PTEN. These studies will be reviewed in this paper to better understand the function of this protein in cancer and explore new therapeutic approaches. [ABSTRACT FROM AUTHOR]

[Display omitted] • ELF3 controls photoperiodic flowering and circadian rhythms for proper plant growth and development. • ELF3 enhances plant resilience and adaptability to diverse environmental conditions. • ELF3 interacts with other transcription factors in the EC-independent pathways. • ELF3 provides a strategy to optimize crop cultivation in different geographical regions. The gene encoding EARLY FLOWERING3 (ELF3) is necessary for photoperiodic flowering and the normal regulation of circadian rhythms. It provides important information at the cellular level to uncover the biological mechanisms that improve plant growth and development. ELF3 interactions with transcription factors such as BROTHER OF LUX ARRHYTHMO (BOA), LIGHT-REGULATED WD1 (LWD1), PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), PHYTOCHROME-INTERACTING FACTOR 7 (PIF7), and LUX ARRHYTHMO (LUX) suggest a role in evening complex (EC) independent pathways, demanding further investigation to elucidate the EC-dependent versus EC-independent mechanisms. The ELF3 regulation of flowering time about photoperiod and temperature variations can also optimize crop cultivation across diverse latitudes. In this review paper, we summarize how ELF3′s role in the circadian clock and light-responsive flowering control in crops offers substantial potential for scientific advancement and practical applications in biotechnology and agriculture. Despite its essential role in crop adaptation, very little is known in many important crops. Consequently, comprehensive and targeted research is essential for extrapolating ELF3-related insights from Arabidopsis to other crops, utilizing both computational and experimental methodologies. This research should prioritize investigations into ELF3′s protein–protein interactions, post-translational modifications, and genomic targets to elucidate its contribution to accurate circadian clock regulation. [ABSTRACT FROM AUTHOR]

• Multimodal strategies and interventions, e.g. healthy lifestyle (dietary and physical activity), can be recommended for treatment of Alzheimer's disease (AD). • Gene study and gene-based therapy with a critical role in the detection and cure of AD will have a fundamental role. • Attempts to enhance clinical results are focused on several main areas including design and detection of more effective carrier molecules, selection of the best gene delivery methods, and detection of novel therapeutic targets. Neurodegenerative diseases such as Alzheimer's disease (AD) are still an important issue for scientists because it is difficult to cure with the available molecular medications and conventional treatments. Due to the complex nature of the brain structures and heterogeneous morphological and physiological properties of neuronal cells, interventions for cerebral-related disorders using surgical approaches, and classical and ongoing treatments remain hard for physicians. Furthermore, the development of newly designed medications attempts to target AD are not successful in improving AD, because abnormalities of tau protein, aggregation of amyloid β (Aβ) peptide, inflammatory responses, etc lead to advanced neurodegeneration processes that conventional treatments cannot stop them. In recent years, novel diagnostic strategies and therapeutic approaches have been developed to identify and cure early pathological events of AD. Accordingly, many gene-based therapies have been developed and introduce the therapeutic potential to prevent and cure AD. On the other hand, genetic investigations and postmortem assessments have detected a large number of factors associated with AD pathology. Also, genetically diverse animal models of AD help us to detect and prioritize novel resilience mechanisms. Hence, gene therapy can be considered an effective and powerful tool to identify and treat human diseases. Ultimately, gene study and gene-based therapy with a critical role in the detection and cure of various human disorders will have a fundamental role in our lives forever. This scientific review paper discusses the present status of different therapeutic strategies, particularly gene-based therapy in treating AD, along with its challenges. [ABSTRACT FROM AUTHOR]

• A reference-based, specialized lossless two-level compression technique is proposed for genomic sequences. • The technique employs optimized k -mer indexing with randomization, hashing data structures, and ASCII coding. • Parallel sequence compression is performed with Java multithreading on Amazon Web Services (AWS) Linux platform. • Use of IUPAC codes enables compression of genomic sequences in the FAST-ALL (FASTA) format. • The COVID-19 virus (SARS-CoV-2) and the human genome were used as sources of sequence data. Next Generation Sequencing (NGS) technology generates massive amounts of genome sequence that increases rapidly over time. As a result, there is a growing need for efficient compression algorithms to facilitate the processing, storage, transmission, and analysis of large-scale genome sequences. Over the past 31 years, numerous state-of-the-art compression algorithms have been developed. The performance of any compression algorithm is measured by three main compression metrics: compression ratio, time, and memory usage. Existing k -mer hash indexing systems take more time, due to the decision-making process based on compression results. In this paper, we propose a two-phase reference genome compression algorithm using optimal k -mer length (RGCOK). Reference-based compression takes advantage of the inter-similarity between chromosomes of the same species. RGCOK achieves this by finding the optimal k -mer length for matching, using a randomization method and hashing. The performance of RGCOK was evaluated on three different benchmark data sets: novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Homo sapiens, and other species sequences using an Amazon AWS virtual cloud machine. Experiments showed that the optimal k -mer finding time by RGCOK is around 45.28 min, whereas the time for existing state-of-the-art algorithms HiRGC, SCCG, and HRCM ranges from 58 min to 8.97 h. [ABSTRACT FROM AUTHOR]

• Gene therapy has advanced rapidly into the 21st century with the promise of a cure for SCD, and gene editing strategies based on the cluster-based regularly interspaced short palindromic repeat sequence (CRISPR)/Crispr associates protein 9 (Cas9) system have revolutionized the field of gene therapy by precisely targeting genes. • CRISPR-Cas9 systems can be delivered into cells and generally come in three types: the delivery of plasmid DNA, the delivery of messenger RNA (mRNA) capable of expressing the Cas9 protein and sgRNA, and delivering the Cas9 protein and sgRNA to form ribonucleoprotein (RNP). • Delivery technologies can be divided into three main categories: physical delivery, viral vectors, and nonviral vectors. • CRISPR-Cas9 can be used for gene correction of SCD, promoter mutation of γ-globins, CRISPR-Cas9 for partial deletion of the β-globin gene, use of CRISPR-Cas9 for editing transcriptional repressors. Sickle cell disease (SCD) is the most common monogenic hematologic disorder and is essentially congenital hemolytic anemia caused by an inherited point mutation in the β-globin on chromosome 11. Although the genetic basis of SCD was revealed as early as 1957, treatment options for SCD have been very limited to date. Hematopoietic stem cell transplantation (HSCT) was thought to hold promise as a cure for SCD, but the available donors were still only 15% useful. Gene therapy has advanced rapidly into the 21st century with the promise of a cure for SCD, and gene editing strategies based on the cluster-based regularly interspaced short palindromic repeat sequence (CRISPR)/Cas9 system have revolutionized the field of gene therapy by precisely targeting genes. In this paper, we review the pathogenesis and therapeutic approaches of SCD, briefly summarize the delivery strategies of CRISPR/Cas9, and finally discuss in depth the current status, application barriers, and solution directions of CRISPR/Cas9 in SCD. Through the review in this paper, we hope to provide some references for gene therapy in SCD. [ABSTRACT FROM AUTHOR]

[Display omitted] • The study addresses different biotechnological and nanotechnological approaches in improving steviol glycoside (SG) content. • Biosynthesis of SG production in Stevia rebaudiana under the cell culture system highlighting the use of different plant growth regulators. • Stress application, polyploidy induction, genetic engineering, and transcriptomic approaches are discussed in enhancing SG content. • It also discusses the identification and cloning of crucial genes involved in metabolic engineering and SG biosynthesis pathways. Stevia rebaudiana Bertoni is a natural sweetener plant that is progressively used not only for its sweetening properties but also for its medicinal properties. The plant contains steviol glycoside (SG) which is reported to be up to 300 times sweeter than sucrose. The plant is said to have no side effects on human health and has been approved by FDA. On the basis of previous studies and available databases, this review discusses the extensive understanding of the different approaches for enhancements of SG in S. rebaudiana. To improve the SG biosynthesis, application of different stress, elicitors, induction of polyploidy, cell culture, genetic engineering, and transcriptomic approaches have been addressed. A brief discussion about the cloning and characterization of important genes of the metabolic pathway of SG biosynthesis is also discussed along with various metabolic engineering pathways viz. methylerythritol 4- phosphate (MEP) and mevalonate (MVA) pathways. This review paper also discusses the different aspects as well as the effects of various nanoparticles on S. rebaudiana growth and development, as well as SG biosynthesis. [ABSTRACT FROM AUTHOR]

There is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta -analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609 , rs8050136 and rs17817449) and T2DM in a larger combined population worldwide. A comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609 , rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta -analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed. Of 234 695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I2 = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I2 = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I2 = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I2 = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I2 = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM. The present meta -analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association. [ABSTRACT FROM AUTHOR]

• We have organized the relationship between lncRNA and drug resistance in common tumors and briefly elucidated its mechanism of action. • We screened lncRNAs that exert drug resistance through exosomes and briefly summarized their mechanisms of action. This provides a good reference for researchers interested in tumor exosomes. • We look forward to the important significance and future application prospects of lncRNA in tumor drug resistance research, providing a strong theoretical basis for the current "personalized medicine". Drug resistance is one of the main challenges in cancer treatment. Long non coding RNAs (lncRNAs) play a complex and precise regulatory role in regulating drug resistance of cancer. The common ways of lncRNA regulating drug resistance of cancer involve ATP binding transporter overexpression, abnormal DNA damage response, tumor cell apoptosis, accumulation of epithelial mesenchymal transformation and cancer stem cell formation. Moreover, studies on exosomal lncRNAs regulating cancer drug resistance are developed in recent years. Further study on the role and mechanism of lncRNAs drug resistance in cancer will help clinical cancer treatment program and explore new treatment methods. This paper reviews recent advances in lncRNAs regulating drug resistance of cancer, especially the role of exosomal lncRNAs. [ABSTRACT FROM AUTHOR]

[Display omitted] • A high-density (HD) SNP array for goats (Axiom_Cahi) was designed comprising of 626,975 SNPs. • The average coverage of SNPs in the array is one SNP per four kilobase (kb). • Performance of the array was validated by genotyping 443 samples from 26 indigenous goat breeds/populations. • 95.83% markers were highly informative and polymorphic in Indian goats. • No sampling bias and an improved discriminatory power was demonstrated by the goat HD array designed. Goats are the supporting pillars of rural economy contributing significantly to meat and milk production in India. It is a species targeted for fulfilling the interdependent goals of poverty reduction and creation of employment for supporting the rural income. The increased demand for goat products necessitates their genetic characterization and improvement to augment the production of native breeds. Bi-allelic, genome wide, densely placed single nucleotide polymorphism (SNP) markers are most suitable for this purpose. This paper describes the design and validation of an Affymetrix Axiom-based high-density (HD) SNP chip for goats. The array was designed using a panel of 225 samples from 15 diverse goat breeds of India. In total, more than 38 million high quality SNPs were subjected to stringent filtering and 626,975 SNPs were finally tiled on the array. The average coverage of SNPs in our chip is one SNP per four kilobase (kb), providing a denser coverage of the goat genome than previously available arrays. The HD chip (Axiom_Cahi) was validated by genotyping 443 samples from 26 indigenous goat breeds/populations. The results revealed 95.83% markers to be highly informative and polymorphic in Indian goats. Multivariate analysis indicated population structuring, as 15 breeds could be segregated using the designed array. Phylogenetic analysis suggested stratification of breeds by geographic proximity. This HD SNP chip for goats is a valuable resource for genomic selection, genome wide association as well as population genetic studies in goats. [ABSTRACT FROM AUTHOR]

Although seen as a revolution in modern science, gene therapy has been plagued by failed clinical trials and controversial ethics in the last thirty years. Moreover, there is no comprehensive, in-depth, high-quality analysis of global gene therapy patents. This paper proposes a method to correctly retrieve patents to address the issue and use it for the patent landscape. The results show the global patent landscape of gene therapy, with the United States dominating the field, while China has emerged as a leader in recent years. For various reasons, the EU, Korea, and Japan lag in the development of patented technologies. China has edged closer to the US in both live and indefinite patents, with the Chinese Academy of Military Medical Sciences and the Chinese Academy of Sciences leading the way, surpassing primary applicants such as the US Department of Health and Human Services, the University of California, and the University of Pennsylvania. The study also reveals four broad categories of technologies that have been extensively studied in gene therapy: basic biology of the gene and diseases, diseases being treated, gene delivery methods, and potential adverse events. What is more, Adeno-Associated Virus, Retrovirus, and Lentivirus are the most prevalent gene therapy delivery vectors after 2014. The industrial development trend revealed in this paper can provide an evidence-based basis for scientific research management and decision-making. [ABSTRACT FROM AUTHOR]

• Using F-MSAP measured DNA methylation levels in cartilage (CA) and reserve mesenchyme (RM) cells and tissues. • DNA methylation plays an important role in the fast cartilage of deer antler. • Identified 20 methylated fragments specific to RMCs or the CA. This paper explored using of deer antlers as a model for studying rapid growth and cartilage formation in mammals. The genes and regulatory mechanisms involved in antler chondrogenesis are poorly understood, however, previous research has suggested that DNA methylation played a key role in antler regeneration. By using fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP), this study measured DNA methylation levels in cartilage (CA) and reserve mesenchyme (RM) cells and tissues. Results showed that RM cells (RMCs) DNA methylation levels were significantly lower than those of CA, suggesting that DNA demethylation may be involved in antler fast cartilage differentiation. The study also identified 20 methylated fragments specific to RMCs or CA using the methylation-sensitive amplified polymorphism (MSAP) technique and confirmed these findings using southern blot analysis. The data provide the first experimental evidence of a link between epigenetic regulation and rapid cartilage differentiation in antlers. [ABSTRACT FROM AUTHOR]

• Recurrent Miscarriage is an unpleasant reproductive condition in females. • miRNAs are short sequences of non-coding RNAs with regulatory properties. • Finding suggests the possible correlation between miRNAs levels and miscarriage. • Using different mechanism miRNAs can affect the occurrence of miscarriage. Recurrent miscarriage (RM) is a complex reproductive medicine disease that affects many families. The cause of RM is unclear at this time; however, lifestyle and genetic variables may influence the process. The slight alteration in miRNA expression has enormous consequences for a variety of difficulties, one of which may be RM. The target of this systematic study was to provide a framework of the dysregulated miRNAs in RM. The Prisma guidelines were applied to perform current systematic review pertaining to articles in the seven databases. Thirty-nine papers out of 245 received fulfilled all inclusion requirements. From all the mentioned miRNAs, 40 were up-regulated (65.57 %), whereas 21 were down-regulated (34.43 %). These dysregulated miRNAs contributed to the pathophysiology of RM by influencing key pathways and processes such as apoptosis, angiogenesis, epithelial-mesenchymal transition, and the immune system. Understanding the dysregulation of miRNAs, as well as the pathways and processes that engage these miRNAs and impact disease pathogenesis, may aid in clarifying the unknown underlying mechanisms of RM and the development of novel molecular therapeutic targets and medical domains. [ABSTRACT FROM AUTHOR]

• Significant association of six coding variants across five genes have been identified in familial cases of Schizophrenia. • Glycosylation processes has been found to be involved using pathway analysis. • Novel association of ADAMTS9 gene has been demonstrated with Schizophrenia. • MD simulation study on ADAMTS9 variant revealed a damaging effect on structural stability of the protein. Schizophrenia is a complex neuropsychiatric disorder and heritability is as high as 80 % making it the most heritable mental disorder. Although GWAS has identified numerous variants, the pathophysiology is still elusive. Here, an attempt was made to identify genetic risk factors in familial cases of schizophrenia that are associated with a common causative pathway. To achieve this objective, exome sequencing was done in 4 familial cases and identified six unique coding variants in five genes. Among these genes, PIGQ gene has two pathogenic variants, one nonsense and in-frame deletion. One missense variant in GALNT16 and one in GALNT5 have variable damaging score, however, the other variants, in ADAMTS9 and in LTBP4 have the highest damaging score. Further analysis showed that the variant of LTBP4 was not present in the functional domain. The other missense variant in the ADAMTS9 gene was found to be significant and was present in the thrombospondin repeat motif, one of the important motifs. Detailed molecular dynamics simulation study on this variant showed a damaging effect on structural stability. Since, all these genes culminated into the glycosylation process, it was evident that an aberrant glycosylation process may be one of the risk factors. Although, extracellular matrix formation through glycosylation have been shown to be associated, the involvement of ADAMTS9 and PIGQ gene mediated glycosylation has not been reported. In this paper, a novel link between ADAMTS9 and PIGQ gene with schizophrenia have been reported. Therefore, this novel observation has contributed immensely to the existing knowledge on risk factor of Schizophrenia. [ABSTRACT FROM AUTHOR]

• This paper describes a 24-year-old patient diagnosed with PFBC harboring a novel homozygous MYORG variant. • It is the second Brazilian case due to MYORG PFBC-causative gene. • Our manuscript highlights the early age and onset of symptoms of the proband. Primary familial brain calcifications (PFBC) is characterized by bilateral and symmetrical deposition of inorganic phosphate, mainly in the basal ganglia, thalamus, cerebellum, and dentate nucleus. The symptoms resemble other neuropsychiatric conditions, such as Parkinsonism, dementia, migraine, and mood disorders. Pathogenic variants in six genes have been associated with this disorder, four linked to the autosomal dominant mode (SLC20A2, PDGFRB, PDGFB, and XPR1) and two linked to the recessive fashion (MYORG and JAM2). Herein, we report a young 24-year-old patient with a medical history of bilateral and symmetrical brain calcification and neuropsychiatric symptoms that include movement disturbances (chorea and dystonia), chronic migraine, unexplained tinnitus, and mood swings. After whole-exome sequencing, she was diagnosed with a novel homozygous MYORG variant (c.912_914del; p.(Ser305del)). In silico analysis showed that the variant is located on the extracellular domain of MYORG protein and is predicted to be disease-causing (likely pathogenic), implying that protein features might be affected. This study describes the second Brazilian case of MYORG PFBC-causative gene. Furthermore, it highlights the early age and onset of symptoms of the proband, especially in regard to movement disorders. [ABSTRACT FROM AUTHOR]

• Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer and has an increasing rate of global incidence making it one of the 10 most commonly diagnosed cancer in both men and women. Several subtypes has been characterized being renal clear cell carcinoma (KIRC), renal papillary cell carcinoma (KIRP), chromophobe (KICH) and collecting duct carcinoma. The lack of knowledge on KIRP makes studies aiming to understand its pathogenesis valuable. In this paper our detailed analysis revealed that peroxiredoxin family is crucial for KIRP progression. In particular the oncogenic nature of PRDX4 is evident. My analysis showed that. • PRDX4 levels are upregulated in KIRP tumors compared to healthy tissue. • PRDX4 expression was shown to be elevated in KIRPs with more aggressive clinicopathological features. • PRDX4 levels are under the control of PRDX4 of hypoxia and oxidative stress machinery. • Higher PRDX4 levels were associated with poor prognosis in KIRP patients. • PRDX4 serves as a better prognostic marker for Type 2 KIRPs possibly because of their significantly disturbed redox and protein homeostasis. PRDX4 may activate pro-survival signals under stress conditions thus promoting tumor progression. Alterations in the tumor microenvironment leads to the accumulation of reactive oxygen species (ROS). When in low levels, ROS act as a signaling molecule and contribute to tumor cell proliferation whereas its elevation results in oxidative stress and eventually cell death. It is known that antioxidant systems regulate the ROS levels and thus cell fate. Among these systems, peroxiredoxins (PRDXs) were found to be upregulated in various cancers. However their exact contribution to carcinogenesis is not yet clear. Herein, the expression pattern and prognostic value of PRDXs were explored in cancer setting by using in silico analysis tools and publicly available datasets. Pan-cancer analysis revealed that PRDXs are differentially expressed in normal and tumor tissues. Further analysis showed that higher PRDX4 levels was associated with poor prognosis and clinicopathological and histological features associated with a more aggressive renal papillary cell carcinoma (KIRP) profile. Hypoxia, ER stress and protein folding were shown to be pathways positively correlated with PRDX4 levels. Furthermore, PRDX4 was found to be strong regulator of protein homeostasis. Kaplan-Meier analysis revealed that PRDX4 is a potent prognostic marker in Type 2 KIRP and this might be due to increased ER stress and oxidative stress levels in this subtype. The data suggest that PRDX4 can be used as a prognostic marker for KIRP patients. Its association with more aggressive tumor characteristics also underlines that it might be used for targeted therapy. [ABSTRACT FROM AUTHOR]

• Circular RNAs are differentially expressed in endometrial cancer. • The overall circRNA abundance is lower in cancer compering to control. • Identified circRNAs may serve as biomarkers for obesity-related endometrial cancer. The present study has investigated the circular RNA (circRNA) transcriptome of twenty obese and postmenopausal women, recruited in Australia, with endometrial cancer (EC). This paper expands on previous findings which evaluated the circRNA transcriptome of a similar cohort of six women recruited in the United States of America. EC is the most common gynaecological malignancy and the fifth most common cancer in women worldwide with obesity as one of its major risk factors. CircRNAs, a class of non-coding RNAs, are involved in many human diseases including cancer. As such the objective of this study was to investigate the circRNA transcriptome of these twenty women and identify circRNAs of interest. We obtained paired samples (EC and adjacent normal tissue) from the cohort of twenty women. Samples were subjected to ribosomal RNA depletion and sequencing performed using Illumina sequencing technology. CircRNAs were identified through CIRI2 and CIRCexplorer2 and common circRNAs extracted for differential expression with edgeR which met the criteria of counts per million > 0.1 and expressed in ≥ 10. We found that the overall abundance of circRNAs was lower in EC compared to adjacent non-cancerous endometrial tissue. We also identified hotspot genes, genes expressing over 10 distinct circRNA isoforms. There were 82 hotspot genes in normal tissue and 23 hotspot genes in EC. There were 174 significantly differentially expressed circRNAs, of which 172 were down-regulated and 2 were up-regulated in EC. The circRNAs identified from this study may act as diagnostic or prognostic biomarkers for EC in obese women. While the circRNA transcriptome of obesity-related EC has been investigated further work is required to determine their functional significance. [ABSTRACT FROM AUTHOR]

• A new tool to predict microbial pS, pT, and pY sites. • Extracts structural & evolutionary features and feeds to Rotation Forest classifier. • An effective tool for screening microbial phosphorylation sites. Post-translational modification (PTM) is a biological process involving a protein's enzymatic changes after its translation by the ribosome. Phosphorylation is one of the most critical PTMs that occurs when a phosphate group interacts with an amino acid residue along protein sequence. It contributes to cell communication, DNA repair, and gene regulation. Predicting microbial phosphorylation sites can provide better understanding of host-pathogen interaction and the development of anti-microbial agents. Experimental methods such as mass spectrometry are time-consuming, laborious, and expensive. This paper proposes a new approach, called RotPhoPred, for predicting phospho-serine (pS), phospho-threonine (pT), and phospho-tyrosine (pY) sites in the microbial organism by integrating evolutionary bigram profile with structural information and using Rotation Forest as the classification technique. To the best of our knowledge, our extracted features and employed classifier have never been utilized for this task. Comparative results demonstrate that the RotPhoPred surpasses its peers in terms of different metrics such as sensitivity (90.0%, 75.4% and 78.2%), specificity (92.1%, 97.2% and 94.7%), accuracy (91.0%, 86.3%, 86.4%), and MCC (0.82, 0.74 and 0.74) for pS, pT, and pY sites predictions, respectively. RotPhoPred as a standalone predictor and all its source codes are publicly available at: https://github.com/faisalahm3d/RotPredPho. [ABSTRACT FROM AUTHOR]

• Fifty-three LysM gene family members were found in banana (Musa L.) genomes, and there were more members in Musa acuminata than in both Musa balbisiana and Musa itinerans. • Banana LysMs were expressed under low-temperature stresses, high-temperature stresses and root infestation by pathogens. • LysMs were highly conserved in the evolution of bananas, but they also show some differences among the genomes of three banana species. LysM (Lysin motif), in response to pathogenic molecular stresses, is a crucial signal recognition gene. To understand the molecular characteristics of banana LysM gene family members, we used a series of bioinformatics methods. Based on the genomic databases of Musa acuminata , Musa balbisiana and Musa itinerans , a total of 53 genes and 55 proteins were identified, with 21 genes and 23 proteins in the M.acuminata , 16 genes and 16 proteins in each of M.balbisiana and M.itinerans , respectively. According to the conserved structural domains, LysM can be divided into five classes, namely LysM&MltD , LYK , LYP , LysMn , and LysMe. The LysM gene was relatively highly conserved in the evolution of the three genomes of banana, and some differences occurred. Expression analysis revealed that MaLysM4-5 was relatively highly expressed under high-temperature stress, low-temperature stress and pathogen infection; at the same time, about one-third of the members were down-regulated under low-temperature stress and high-temperature stress, while the expression of MaLysM10-1 and MaLysM4-5 were up-regulated. After the banana wilt fungus Foc TR4 infected the banana roots, MaLysM1 was down-regulated and MaLysM11-1 was up-regulated. In conclusion, our study suggests that MaLysMs may be necessary in the response to high- and low-temperature stresses, as well as the banana wilt fungus infestation. Overall, this paper found that LysM genes may be involved in biotic and abiotic stresses in banana, and provided helpful information about LysM 's evolution, expression and properties, which will provide theoretical references for further studies on the functions of LysM genes and resistance breeding in the future. [ABSTRACT FROM AUTHOR]

• The review covers livestock genomics of South Asian cattle, buffalo, sheep, goat, pig, camel, horse, yak, mithun, and poultry. • Advancements in next-generation sequencing (NGS) technologies led to the discovery of numerous SNP arrays for different livestock species. • The application of genomics in animal breeding has had the biggest economic impact on livestock production. Livestock plays a central role in sustaining human livelihood in South Asia. There are numerous and distinct livestock species in South Asian countries. Several of them have experienced genetic development in recent years due to the application of genomic technologies and effective breeding programs. This review discusses genomic studies on cattle, buffalo, sheep, goat, pig, horse, camel, yak, mithun, and poultry. The frontiers covered in this review are genetic diversity, admixture studies, selection signature research, QTL discovery, genome-wide association studies (GWAS), and genomic selection. The review concludes with recommendations for South Asian livestock systems to increasingly leverage genomic technologies, based on the lessons learned from the numerous case studies. This paper aims to present a comprehensive analysis of the dichotomy in the South Asian livestock sector and argues that a realistic approach to genomics in livestock can ensure long-term genetic advancements. [ABSTRACT FROM AUTHOR]

[Display omitted] • Expression of 'Taxi', a transcription factor/co-activator, is required in neurons for Drosophila flight function. • Jumper and taxi1 are hypermorphic and hypomorphic alleles of taxi, with an I-element insertion in the 5′-UTR and disparate residues in C-terminus, respectively. • Taxi is a negative regulator of Adar, a protein required for post-transcriptional modifications, including RNA editing and alternative splicing. Extensive studies in Drosophila have led to the elucidation of the roles of many molecular players involved in the sensorimotor coordination of flight. However, the identification and characterisation of new players can add novel perspectives to the process. In this paper, we show that the extant mutant, jumper, is a hypermorphic allele of the taxi / delilah gene, which encodes a transcription factor. The defective flight of jumper flies results from the insertion of an I-element in the 5′-UTR of taxi gene, leading to an over-expression of the taxi. We also show that the molecular lesion responsible for the taxi1 allele results from a 25 bp deletion leading to a shift in the reading frame at the C-terminus of the taxi coding sequence. Thus, the last 20 residues are replaced by 32 disparate residues in taxi1. Both taxi1 , a hypomorphic allele, and the CRISPR-Cas9 knock-out (taxiKO) null allele, show a defective flight phenotype. Electrophysiological studies show taxi hypermorphs, hypomorphs, and knock out flies show abnormal neuronal firing. We further show that neuronal-specific knock-down or over-expression of taxi cause a defect in the brain's inputs to the flight muscles, leading to reduced flight ability. Through transcriptomic analysis of the taxiKO fly head, we have identified several putative targets of Taxi that may play important roles in flight. In conclusion, from molecularly characterising jumper to establishing Taxi's role during Drosophila flight, our work shows that the forward genetics approach still can lead to the identification of novel molecular players required for neuronal transmission. [ABSTRACT FROM AUTHOR]

• ZEN can cause genome toxicity, including DNA damage, and epigenetic modification. • Increased ROS is an important pathway that ZEN exposure can lead to genome toxicity. • Strategies to counteract ZEN effects are proposed. Zearalenone (ZEN), a common non-steroidal estrogenic mycotoxin of the Fusarium genus , is one of the most frequent and powerful contaminant of grains and cereal products representing a serious threat for people and livestock health. In fact, ZEN causes cytotoxicity and genotoxicity in a variety of cell types at least in part through binding to estrogen receptors (ERs). The main pathways through which ZEN induces such effects remain, however, elusive. In particular, how the mycotoxin causes DNA damage, dysregulates DNA repair mechanisms, changes epigenome of targeted cells and, not least, affects chromatin conformation and non-coding RNA (ncRNA), is unclear. In the present paper, following extensive review of the literature about such ZEN effects and our own experience in studying the effects of this compound on reproductive processes, we propose that increased production of reactive oxygen species (ROS) and consequently oxidative stress (OS) are central in ZEN genotoxicity. Besides to shed light on the action mechanisms of the mycotoxin, this notion might help to develop effective strategies to counteract its deleterious biological effects. [ABSTRACT FROM AUTHOR]

• Overexpression of EXP1 affects the synthesis of cellulose in plant. • Overexpressed HEX4 affects the synthesis of cellulose in plant. • Overexpression of EXP1 affects the height, number of roots, and root length of plant. • Overexpressed HEX4 affects the height, number of roots, and root length of plant. Eucalyptus (including Eucalyptus grandis) is an excellent wood forest tree species that provides a large number of plant fiber raw materials for the paper and timber industries. Cellulose, an essential structural component in plant cell walls, is a renewable biomass resource that plays a very important role in nature. There is still a lack of research on the role of gene regulation in cellulose synthesis. To study the genes of cellulose synthesis, the wood chemical indexes of Eucalyptus grandis were analyzed by taking three different parts from the main stem of Eucalyptus grandis as raw materials. The results showed that the cellulose content in the middle of the trunk was significantly higher than that at the chest diameter and at the upper part of the trunk. A total of 296 differentially expressed genes (DEGs) were obtained from the three site by transcriptome, and 19 key candidate genes were related to the synthesis of cellulose in Eucalyptus grandis. EgrEXP1 and EgrHEX4 were overexpressed in 84 K poplar, the content of cellulose and lignin in genetically modified plants was significantly higher than that of wild type 84 K poplar. Also, the average plant height and average root count were significantly higher than those of control plants, and the average diameter of the middle and stem bases were significantly larger than those of control plants. In this study, the genes related to cellulose synthesis in Eucalyptus grandis are studied, which serve as a strong foundation for understanding the molecular regulation of cellulose synthesis in plants. [ABSTRACT FROM AUTHOR]

• The clinical and genetic manifestations of SMA are diverse and heterogeneous. • In this paper, we report on the final mutation profiles of the SMN1 and SMN2 genes in terms of exonic deletions. • This is significant because the exact copy number of the SMN2 gene seems to be the determiner in our patients with SMA. • Furthermore, the chaotic manner of the SMN1 and SMN2 gene structures within their respective exonic regions resulted in different inheritance patterns in a family that was segregated in this study. • We also produced an " MLPA - SMA signature " which can be helpful in the initial preparation of patient reports. SMA is a neuromuscular disease and occurs primarily through autosomal recessive inheritance. Identification of deletions in the SMN1 gene especially in the exon 7 and exon 8 regions (hot spot), are used in carrier testing. The exact copy numbers of those exons in the SMN1 and SMN2 genes in 113 patients who presented with a pre-diagnosis of SMA were determined using MLPA method. We aimed to reveal both the most common copy number profiles of different SMA types. It was found that the frequency of homozygous deletions in SMN1 was 15.9%, while heterozygous deletions was 16.9%. The most common SMN-MLPA profile was 0–0-3–3. In the cases with homozygous deletion, SMA type III diagnosis was observed most frequently (44%), and the rate of consanguineous marriage was found 33%. Two cases with the same exonic copy number profile but with different clinical subtypes were identified in a family. We also detected distinct exonic deletion and duplication MLPA profiles for the first time. We created "the SMA signature" that can be added to patient reports. Furthermore, our data are important for revealing potential local profiles of SMA and describing the disease in genetic reports in a way that is clear and comprehensive. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 demonstrates a continuous tendency for new variants emergence. • Differences in those variants regarding their mutations/deletions/insertions in spike genomic sequence leads to altered transmissibility/infectivity/re-infection/morbidity/mortality rates. • Omicron variant is characterized by an ''exotic" genomic profile due to the increased number of host mutations and the combination of deletions/insertion in S1-RBD/S2 domains. • Delta to Omicron transition is the next step for SARS-CoV-2 adjustment regarding its effort to survive in human affected cells. Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) affected negatively the national health systems' endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Spike (S) glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on virion's surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism. On Nov 26th 2021, WHO designated the new SARS-CoV-2 strain – named Omicron, from letter '' όμικρον" in the Greek alphabet - as a variant of concern (B.1.1529 variant). Potentially this new variant is associated with high transmissibility leading to elevated infectivity and probably increased re-infection rates. Its impact on morbidity/mortality remains under investigation. In the current paper, analyzing and comparing the alterations of SARS-CoV-2 S RNA sequences in the defined variants (Alpha to Omicron), we observed some interesting findings regarding the S1-RBD/S2 mutation/deletion equilibrium that maybe affect and modify its activity. [ABSTRACT FROM AUTHOR]

• VE regulates tumor cell physiological activity through MAPK pathway. • VE regulate ERK inducing apoptosis, differentiation, cell cycle arrest. • VE regulates JNK inducing apoptosis and inhibiting the expression of AR. • VE regulates p38MAPK inducing apoptosis and autophagy. In tumour cells, vitamin E and its derivatives play a critical role in the regulation of multiple signalling pathways through their oxidative and nonoxidative functions. To date, there are 8 known natural vitamin E forms and many kinds of derivatives, among which VES and α-TEA have excellent anticancer activities. The MAPK pathway consists of a complex cascade of proteins that control the proliferation, differentiation and apoptosis of tumour cells. The MAPK pathway includes four subfamilies, ERK1/2, JNK1/2, p38 MAPK, and ERK5. Most of the proteins in these subfamilies interact with each other in a complex manner. The anticancer function of vitamin E and its derivatives is closely related to the MAPK cascade. Studies have shown that in tumour cells, α-T/γ-T/γ-T3/δ-T3/VES/α-TEA regulated ERK1/2, prevent tumorigenesis, inhibit tumour cell growth and metastasis and induce cell differentiation, apoptosis, and cell cycle arrest; γ-T3/δ-T3/VES/α-TEA regulates JNK1/2, induce apoptosis, reduce ceramide synthesis and inhibit proliferation; and γ-T3/δ-T3/VES regulate p38 MAPK and induce apoptosis. This paper reviews the role of vitamin E and its derivatives in the MAPK cascade, and tumour cells are used as a model in an attempt to explore the mechanism of their interactions. [ABSTRACT FROM AUTHOR]

This paper reviews theory of DNB (Dynamical Network Biomarkers) and its applications including both modern medicine and traditional medicine. We show that omics data such as gene/protein expression profiles can be effectively used to detect pre-disease states before critical transitions from healthy states to disease states by using the DNB theory. The DNB theory with big biological data is expected to lead to ultra-early precision and preventive medicine. [ABSTRACT FROM AUTHOR]

• PGAM1 is dominantly expressed in post-pubescent sheep testis and epididymis. • PGAM1 is mainly located in Sertoli cells. • PGAM1 promotes the glycolytic metabolic pathway of Tibetan sheep SCs and increases the secretion of lactic acid. This study was to explore the regulation effect of PGAM1 on the proliferation, apoptosis and glycolysis pathway of Tibetan sheep Sertoli cells. In this paper, the reproductive organs of male Tibetan sheep before pre-puberty (3 months old), sexual maturity (1 year old) and adult (3 years old) were used as experimental materials. The complete CDS region sequence of PGAM1 gene was cloned for bioinformatics analysis, and had the closest relationship with Tibetan antelope. QRT-PCR, Western blot and immunohistochemical staining were used to detect the expression and localization of PGAM1 in the testis and epididymis tissues of Tibetan sheep at different growth and development stages at the transcription and translation levels. Then the Tibetan sheep primary Sertoli cells (SCs) were isolated to construct PGAM1 gene overexpression and interference vectors, and to transfect primary SCs so as to promote and inhibit PGAM1 gene expression; CCK-8 and flow cytometry were used to detect the proliferation effect of SCs;qRT-PCR technology was employed to detect the changes in the expression of genes related to cell proliferation and apoptosis. Different kits were used to detect pyruvate, lactic acid, ATP production and LDH activity during glycolysis, and to detect the changes in the expression of downstream genes in the glycolysis pathway. The results showed that the CDS region of Tibetan sheep PGAM1 gene was 765 bp in length, which can encode 254 amino acids; and the expression of PGAM1 protein in the testis and epididymis increased at 1Y group and 3Ygroup compared with 3 M group, and that the PGAM1 protein mainly existed in SCs and Leydig cells at different developmental stages. CCK-8 and flow cytometry test results found that compared with the empty vector group (pcDNA3.1(+)), the proliferation rate of the PGAM1 gene overexpression group (pcDNA3.1(+)-PGAM1) decreased. The mRNA expression of the cell proliferation related genes PCNA and Bcl2 was significantly decreased (P < 0.05), and the expression of apoptosis-related genes Bax and caspase3 was significantly increased (P < 0.05). The expression of downstream genes in the glycolysis pathway was significant increased (P < 0.05), pyruvate content, ATP content, lactic acid production and LDH activity increased significantly (P < 0.05). Compared with the interference control group (NC), the proliferation rate of the PGAM1 gene interference group (si-PGAM1) was weakened. The mRNA expression of the cell proliferation-related genes PCNA and Bcl2 was significantly increased (P < 0.05), and the expression of cell apoptosis related genes Bax and caspase3 was significantly decreased (P < 0.05). The expression of downstream genes in the glycolysis pathway was significantly reduced (P < 0.05), and the pyruvate content, ATP content, lactic acid production and LDH activity were significantly decreased (P < 0.05). The PGAM1 gene might regulate the glycolytic metabolism pathway and regulate the sperm formation and maturation process by affecting the proliferation and apoptosis of SCs. This result provides basic data for the study of the function of PGAM1 in sheep testicular development. [ABSTRACT FROM AUTHOR]

• Saffron and crocetin suppressed the decrease of climbing ability in the fly PD model. • Saffron and crocetin extended the life span in the fly PD model. • Saffron suppressed the rough-eyed phenotype inthe fly PD model. • Saffron attenuated α-synuclein-induced cytotoxicity on a human neuronal cell line. • Saffron and crocetin can be useful for the treatment of Parkinson's disease. Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in the eye of A30P fly PD model. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD. [ABSTRACT FROM AUTHOR]

Earthworm, P. excavatus, is an ideal model organism for studying regeneration. Due to its prodigious regeneration capability, the amputated head part of the earthworm can regenerate completely within 22 days. MicroRNAs (miRNAs) regulate specific genes and are involved in essential biological processes, including regeneration. In this study, we conducted a comprehensive analysis of miRNA profiling of the earthworm, P. excavatus, during the process of anterior regeneration. Our investigation involved in the identification of 55 miRNAs from 30 distinct miRNA families that exhibit significant relevance to wound healing and regeneration. Notably, we have identified 50 novel miRNAs and predicted their pre-miRNA secondary structures using MIREAP. Both Known and Novel miRNAs are validated using qPCR. In addition, we employed the miRanda algorithm to predict the interactions between these miRNAs and their target mRNA transcripts. Based on the miRanda target prediction results, we identified the target genes such as Wnt, Myc, MAPK, SoxB, IHH, Hox, and Notch. These findings indicate that the potential targets of these miRNAs might play crucial roles in various functions related to wound healing, tissue restoration, and regeneration. Furthermore, the acquisition of these findings provides a unique perspective on understanding the molecular mechanisms driving epimorphosis regeneration in connection with miRNAs for the development of miRNA-based therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Topping, an important tree shaping and pruning technique, can promote the outgrowth of citrus axillary buds. However, the underlying molecular mechanism is still unclear. In this study, spring shoots of Citrus reticulata 'Huagan No.2' were topped and transcriptome was compared between axillary buds of topped and untopped shoots at 6 and 11 days after topping (DAT). 1944 and 2394 differentially expressed genes (DEGs) were found at 6 and 11 DAT, respectively. KEGG analysis revealed that many DEGs were related to starch and sucrose metabolism, signal transduction of auxin, cytokinin and abscisic acid. Specially, transcript levels of auxin synthesis, transport, and signaling-related genes (SAURs and ARF5), cytokinin signal transduction related genes (CRE1, AHP and Type-A ARRs), ABA signal responsive genes (PYL and ABF) were up-regulated by topping; while transcript levels of auxin receptor TIR1, auxin responsive genes AUX/IAAs, ABA signal transduction related gene PP2Cs and synthesis related genes NCED3 were down-regulated. On the other hand, the contents of sucrose and fructose in axillary buds of topped shoots were significantly higher than those in untopped shoots; transcript levels of 16 genes related to sucrose synthase, hexokinase, sucrose phosphate synthase, endoglucanase and glucosidase, were up-regulated in axillary buds after topping. In addition, transcript levels of genes related to trehalose 6-phosphate metabolism and glycolysis/tricarboxylic acid (TCA) cycle, as well to some transcription factors including Pkinase, Pkinase&#95;Tyr, Kinesin, AP2/ERF, P450, MYB, NAC and Cyclin&#95;c, significantly responded to topping. Taken together, the present results suggested that topping promoted citrus axillary bud outgrowth through comprehensively regulating plant hormone and carbohydrate metabolism, as well as signal transduction. These results deepened our understanding of citrus axillary bud outgrowth by topping and laid a foundation for further research on the molecular mechanisms of citrus axillary bud outgrowth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The non-coding regions of the mitochondrial DNAs (mtDNAs) of hares, rabbits, and pikas (Lagomorpha) contain short (∼20 bp) and long (130-160 bp) tandem repeats, absent in related mammalian orders. In the presented study, we provide in-depth analysis for mountain hare (Lepus timidus) and brown hare (L. europaeus) mtDNA non-coding regions, together with a species- and population-level analysis of tandem repeat variation. Mountain hare short tandem repeats (SRs) as well as other analyzed hare species consist of two conserved 10 bp motifs, with only brown hares exhibiting a single, more variable motif. Long tandem repeats (LRs) also differ in sequence and copy number between species. Mountain hares have four to seven LRs, median value five, while brown hares exhibit five to nine LRs, median value six. Interestingly, introgressed mountain hare mtDNA in brown hares obtained an intermediate LR length distribution, with median copy number being the same as with conspecific brown hare mtDNA. In contrast, transfer of brown hare mtDNA into cultured mtDNA-less mountain hare cells maintained the original LR number, whereas the reciprocal transfer caused copy number instability, suggesting that cellular environment rather than the nuclear genomic background plays a role in the LR maintenance. Due to their dynamic nature and separation from other known conserved sequence elements on the non-coding region of hare mitochondrial genomes, the tandem repeat elements likely to represent signatures of ancient genetic rearrangements. clarifying the nature and dynamics of these rearrangements may shed light on the possible role of NCR repeated elements in mitochondria and in species evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Potassium ion (K + ) is one of the most essential nutrients for the growth and development of tobacco (Nicotiana tabacum L.), however, the molecular regulation of K + concentration in tobacco remains unclear. In this study, a two-pore K (TPK) channel gene NtTPKa was cloned from tobacco, and NtTPKa protein contains the unique K + selection motif GYGD and its transmembrane region primarily locates in the tonoplast membrane. The expression of NtTPKa gene was significantly increased under low-potassium stress conditions. The concentrations of K + in tobacco were significantly increased in the NtTPKa RNA interference lines and CRISPR/Cas9 knockout mutants. In addition, the transport of K + by NtTPKa was validated using patch clamp technique, and the results showed that NtTPKa channel protein exclusively transported K + in a concentration-dependent manner. Together, our results strongly suggested that NtTPKa is a key gene in maintaining K + homeostasis in tobacco, and it could provide a new genetic resource for increasing the concentration of K + in tobacco., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)