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The dysregulated NF-κB basal activity is a common feature of human thyroid carcinomas, especially in poorly differentiated or undifferentiated forms that, even if rare, are often resistant to standard therapies, and, therefore, are uncurable. Despite the molecular mechanisms leading to NF-κB activation in thyroid cancer being only partially understood, during the last few years, it has become clear that NF-κB contributes in different ways to the oncogenic potential of thyroid neoplastic cells. Indeed, it enhances their proliferation and viability, promotes their migration to and colonization of distant organs, and fuels their microenvironment. In addition, NF-κB signaling plays an important role in cancer stem cells from more aggressive thyroid carcinomas. Interfering with the different upstream and/or downstream pathways that drive NF-κB activity in thyroid neoplastic cells is an attractive strategy for the development of novel therapeutic drugs capable of overcoming the therapy resistance of advanced thyroid carcinomas. This review focuses on the recent findings about the key functions of NF-κB in thyroid cancer and discusses the potential implications of targeting NF-κB in advanced thyroid carcinomas. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia‐inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel–Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen‐dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses on the functional role of HIF and its target genes during ARDS, as well as how HIF has evolved as a therapeutic target in current medical management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. Methods: In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. Results: In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. Conclusions: Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis. [ABSTRACT FROM AUTHOR]

Aluminum toxicity is a major abiotic stress on acidic soils, leading to restricted root growth and reduced plant yield. Long non-coding RNAs are crucial signaling molecules regulating the expression of downstream genes, particularly under abiotic stress conditions. However, the extent to which lncRNAs participate in the response to aluminum (Al) stress in barley remains largely unknown. Here, we conducted RNA sequencing of root samples under aluminum stress and compared the lncRNA transcriptomes of two Tibetan wild barley genotypes, XZ16 (Al-tolerant) and XZ61 (Al-sensitive), as well as the aluminum-tolerant cultivar Dayton. In total, 268 lncRNAs were identified as aluminum-responsive genes on the basis of their differential expression profiles under aluminum treatment. Through target gene prediction analysis, we identified 938 candidate lncRNA-messenger RNA (mRNA) pairs that function in a cis-acting manner. Subsequently, enrichment analysis showed that the genes targeted by aluminum-responsive lncRNAs were involved in diterpenoid biosynthesis, peroxisome function, and starch/sucrose metabolism. Further analysis of genotype differences in the transcriptome led to the identification of 15 aluminum-responsive lncRNAs specifically altered by aluminum stress in XZ16. The RNA sequencing data were further validated by RT-qPCR. The functional roles of lncRNA-mRNA interactions demonstrated that these lncRNAs are involved in the signal transduction of secondary messengers, and a disease resistance protein, such as RPP13-like protein 4, is probably involved in aluminum tolerance in XZ16. The current findings significantly contribute to our understanding of the regulatory roles of lncRNAs in aluminum tolerance and extend our knowledge of their importance in plant responses to aluminum stress. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer is one of the deadliest malignancies in women worldwide. Zinc finger protein 32 (ZNF32) has been reported to be involved in autophagy and stem cell like properties of breast cancer cells. However, the effects, mechanisms, target genes and pathways of ZNF32 in breast cancer development have not been fully explored. In this study, stable ZNF32 overexpression breast cancer cell line was generated, and we used RNA-seq and RT-qPCR to quantify and verify the changes in transcription levels in breast cancer cells under ZNF32 overexpression. Transcriptome analysis showed that high expression of ZNF32 is accompanied by changes in downstream focal adhesion, ECM-receptor interaction, PI3K-AKT, HIPPO and TNF signaling pathways, which are critical for the occurrence and development of cancer. Multiple differentially expressed genes (DEGs) were significantly involved in cell proliferation, adhesion and migration, including 11 DEGs such as CA9, CRLF1 and ENPP2P with fundamental change of regulation modes. All the 11 DEGs were validated by RT-qPCR, and 9 of them contained potential transcriptional binding sequences of ZNF32 in their promoter region. This study provides a holistic perspective on the role and molecular mechanism of ZNF32 in breast cancer progression.

Abstract Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the genus Alphavirus and is responsible for causing Chikungunya fever, a type of arboviral fever. Despite extensive research, the pathogenic mechanism of CHIKV within host cells remains unclear. In this study, an in-silico approach was used to predict that CHIKV produces micro-RNAs that target host-specific genes associated with host cellular regulatory pathways. Putative micro-RNAs of CHIKV were predicted using the miRNAFold and Vmir RNA structure web servers, and secondary structure prediction was performed using RNAfold. Host-specific target genes were then predicted, and hub genes were identified using CytoHubba and module selection through MCODE. Functional annotations of hub genes revealed their association with various pathways, including osteoclast differentiation, neuroactive ligand-receptor interaction, and mRNA surveillance. We used the freely available dataset GSE49985 to determine the level of expression of host-specific target genes and found that two genes, F-box and leucine-rich repeat protein 16 (FBXL16) and retinoic acid receptor alpha (RARA), were down-regulated, while four genes, RNA binding protein with serine-rich domain 1 (RNPS1), RNA helicase and ATPase (UPF1), neuropeptide S receptor 1 (NPSR1), and vasoactive intestinal peptide receptor 1 (VIPR1), were up-regulated. These findings provide insight into novel miRNAs and hub genes associated with CHIKV infection and suggest potential targets for therapeutic intervention. Further experimental validation of these targets could lead to the development of effective treatments for CHIKV-mediated diseases.

Abstract Salmonella, the prevailing zoonotic pathogen within the Enterobacteriaceae family, holds the foremost position in global bacterial poisoning incidents, thereby signifying its paramount importance in public health. Consequently, the imperative for expeditious and uncomplicated detection techniques for Salmonella in food is underscored. After more than two decades of development, loop-mediated isothermal amplification (LAMP) has emerged as a potent adjunct to the polymerase chain reaction, demonstrating significant advantages in the realm of isothermal amplification. Its growing prominence is evident in the increasing number of reports on its application in the rapid detection of Salmonella. This paper provides a systematic exposition of the technical principles and characteristics of LAMP, along with an overview of the research progress made in the rapid detection of Salmonella using LAMP and its derivatives. Additionally, the target genes reported in various levels, including Salmonella genus, species, serogroup, and serotype, are summarized, aiming to offer a valuable reference for the advancement of LAMP application in Salmonella detection. Finally, we look forward to the development direction of LAMP and expect more competitive methods to provide strong support for food safety applications.

Abstract Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.

Background: Schizophrenia (SZ), a complex and chronic neuropsychiatric disorder affecting approximately 1 % of the general population, presents diagnostic challenges due to the absence of reliable biomarkers, and relying mainly on clinical observations. MicroRNAs (miRNAs) signatures in a wide range of diseases, including psychiatric disorders, hold immense potential for serving as biomarkers. This study aimed to analyze the expression levels of specific microRNAs (miRNAs) namely miR-29b-3p, miR-106b-5p, and miR-199a-3p and explore their diagnostic potential for SZ in Jordanian patients. Methods: Small RNAs (miRNAs) were extracted from plasma samples of 30 SZ patients and 35 healthy controls. RNA was reverse transcribed and quantified by real-time polymerase chain reaction (qRT-PCR). The expression levels of three miRNAs (miR-29b-3p, miR-106b-5p and miR-199a-3p) were analyzed. Receiver operating characteristic (ROC) curves analysis was performed to evaluate diagnostic value of these miRNAs. Target genes prediction, functional enrichment and pathway analyses were done using miRWalk and Metascape. STRING database was used to construct protein-protein network and identify hub genes. Results: Notably, miR-106b-5p and miR-199a-3p were significantly upregulated (p

Objective To explore the expression of miR-451 and target gene PSMB8 in non-small cell lung cancer and their correlation with related cell cycle proteins, so as to provide new targets for the treatment of non-small cell lung cancer. Methods The tissue specimens from six lung cancer patients who underwent radical lung cancer surgery in the thoracic surgery department of the hospital from January 2020 to December 2022 were selected, and divided into two groups based on cancer tissue and adjacent tissue, with six samples in each group. The relative expression levels of miR-451, proteasome subunit beta 8 (PSMB8), Cyclin D1, Cyclin El, cyclin dependent kinase 4(CDK4), and CDK2 proteins between the two groups were compared, and the correlation between miR-451 and related cyclin proteins was analyzed. Results The CT value of miR-451 in the lung cancer tissue group was higher than that in the adjacent tissue group, and the difference was statisti- cally significant (P<0.05). The 2-AACT value of miR-451 in the lung cancer tissue group was 0. 53, and the rel- ative expression level of miR-451 in the adjacent tissue group was 1. 87 times higher than that in the lung cancer tissue group. The relative expression level of PSMB8 in the lung cancer tissue group was(1.55±0.23), significantly higher than that in the adjacent tissue group(0.98±0.15), and the difference was statistically significant(P<0.05). The relative expression levels of Cyclin D1, Cyclin E1, CDK4, and CDK2 proteins in the lung cancer tissue group were significantly higher than those in the adjacent tissue group, with statistical sig- nificance(P<0.05). The relative expression level of miR-451 was negatively correlated with the relative ex- pression levels of Cyclin D1, Cyclin E1, CDK4, and CDK2 proteins(r=-0.93,-0.89,-0.86,-0.84,P<0.05). Conclusion Low expression of miR-451 in lung cancer tissue can reduce the inhibitory effect on the ex- pression of target gene PSMB8, thereby interfering with the expression of cell cycle related proteins, affecting cell proliferation and apoptosis, and indirectly regulating the occurrence and development of non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Salmonella, the prevailing zoonotic pathogen within the Enterobacteriaceae family, holds the foremost position in global bacterial poisoning incidents, thereby signifying its paramount importance in public health. Consequently, the imperative for expeditious and uncomplicated detection techniques for Salmonella in food is underscored. After more than two decades of development, loop-mediated isothermal amplification (LAMP) has emerged as a potent adjunct to the polymerase chain reaction, demonstrating significant advantages in the realm of isothermal amplification. Its growing prominence is evident in the increasing number of reports on its application in the rapid detection of Salmonella. This paper provides a systematic exposition of the technical principles and characteristics of LAMP, along with an overview of the research progress made in the rapid detection of Salmonella using LAMP and its derivatives. Additionally, the target genes reported in various levels, including Salmonella genus, species, serogroup, and serotype, are summarized, aiming to offer a valuable reference for the advancement of LAMP application in Salmonella detection. Finally, we look forward to the development direction of LAMP and expect more competitive methods to provide strong support for food safety applications. [ABSTRACT FROM AUTHOR]

Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research. [ABSTRACT FROM AUTHOR]

Simple Summary: Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is native to tropical and subtropical regions and is a major pest of many important fruit trees and vegetables. In this study, the egg hatching rate, larval/pupal rate, pupal feathering rate, and pre-laying stage of the beta-cypermethrin-medium-resistant strain were found to be markedly lower compared to the sensitive strain. In contrast, the average adult longevity and female longevity of the high resistant strain were significantly longer than those of the sensitive strain, though the fecundity of the resistant strains was lower than that of the sensitive strain. Population growth was suppressed in the medium-resistant strain, while it was enhanced in the high resistant strain populations. In this experiment, the annotation of the Suppression Subtractive Hybridization (SSH) library revealed that the relevant genes mainly pertain to metabolic processes in biological pathways, followed by genes related to cellular processes. Regarding molecular functions, relevant genes mainly pertain to catalytic and binding functions. In terms of cellular-component-related genes, they are mainly associated with cell, organelle, and macromolecule complexes. So, the proportion of the relevant genes in the beta-cypermethrin-resistant strains of Bactrocera dorsalis is the same as the gene expression pattern in the organism, which suggests that the development of resistance in insects does not change the proportion of the genes. Diptera and Lepidoptera species have the highest levels of insecticide resistance, and the mechanism of drug resistance has been studied in detoxification metabolism genes such as P450, GST, EST, and ABC. Since Bactrocera dorsalis are resistant to a variety of chemicals, the pattern and mechanism of resistance in Bactrocera dorsalis have been investigated from a variety of aspects such as detoxification metabolism genes, detoxification enzymes, intestinal symbiotic bacteria, and synergists in the world. In this study, 51 species and 149 detoxification metabolism genes were annotated in the Suppression Subtractive Hybridization (SSH) library, and 12 candidate genes related to beta-cypermethrin resistance were screened and quantitatively expressed in this library. Two genes were found to be upregulated in the egg stage, three genes in the larval stage, one gene in the pupal stage, and five genes in the adult stage, and four genes were found to be upregulated in the midgut and the malacca ducts in the midgut. The expression of cyp6g1, cyp6a22, GST-Epsilon9, and Trypsin-4 genes was upregulated in resistant strains, with the most obvious upregulation occurring in the midgut and the Malpighian tubules. These results provide new insights into the study of pesticide resistance in quarantine insects. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p < 0.05) in Q23 and Q74 cell lines. A majority of the miRNAs were downregulated in the HD cell model. Moreover, we revealed that six DE miRNAs target seven genes (ATN1, GEMIN4, EFNA5, CSMD2, CREBBP, ATXN1, and B3GNT) that play important roles in neurodegenerative disorders and showed significant expression differences in mutant Htt (Q74) when compared to wild-type Htt (Q23) using RT-qPCR (p < 0.05 and 0.01). We demonstrated the most important DE miRNA-mRNA profiles, interaction binding sites, and their related pathways in HD using experimental and bioinformatics methods. This will allow the development of novel diagnostic strategies and provide alternative therapeutic routes for treating HD. [ABSTRACT FROM AUTHOR]

Objective: Curcumin is considered an epigenetic regulator with anticancer effects. The micro-RNA (miRNA) miR-145-5p is a tumor suppressor that shows low expression levels in various cancers, including breast cancer (BC). This study aims to investigate whether curcumin inhibits MCF-7 human BC cell line proliferation and migration by regulating miR-145-5p and its possible target genes. Material and Method: MCF-7 cells were treated with curcumin and its solvent control. Additionally, cells were transfected with an miR-145-5p mimic and a non-targeting miRNA mimic. Cell viability was then evaluated, and the scratch wound assay was used to assess cell migration. The study predicts the miR-145- 5p putative target genes by searching for overlapping genes in the miRNet and miRTarBase v8 databases via the overexpressed genes in the BC tissue samples in the Cancer Genome Atlas (TCGA) datasets. Expression levels of miR-145-5p and the selected genes were detected using the quantitative real-time polymerase chain reaction (qRT-PCR). The 2-ΔΔCt method was used for the quantification analysis, with p<0.05 being considered statistically significant. Result: Curcumin treatment and overexpression of miR-145- 5p via the transfection of an miR-145-5p mimic significantly decreased the proliferation and migration of MCF-7 cells. Moreover, curcumin treatment significantly increased the expression of miR-145-5p. The possible target genes of miR-145- 5p (i.e., MCM2, MMP1, MMP9, EEF1A2) were downregulated in curcumin-treated MCF-7 cells. Additionally, miR-145-5p mimictransfected cells showed low expression levels of the MCM2, MMP1, and MMP9 genes. Conclusion: Curcumin inhibits the proliferation and migration of MCF-7 cells by acting on miR-145-5p and its possible target genes. [ABSTRACT FROM AUTHOR]

As a common foodborne pathogen, infection with L. monocytogenes poses a significant threat to human life and health. The objective of this study was to employ comparative genomics to unveil the biodiversity and evolutionary characteristics of L. monocytogenes strains from different regions, screening for potential target genes and mining novel target genes, thus providing significant reference value for the specific molecular detection and therapeutic targets of L. monocytogenes strains. Pan-genomic analysis revealed that L. monocytogenes from different regions have open genomes, providing a solid genetic basis for adaptation to different environments. These strains contain numerous virulence genes that contribute to their high pathogenicity. They also exhibit relatively high resistance to phosphonic acid, glycopeptide, lincosamide, and peptide antibiotics. The results of mobile genetic elements indicate that, despite being located in different geographical locations, there is a certain degree of similarity in bacterial genome evolution and adaptation to specific environmental pressures. The potential target genes identified through pan-genomics are primarily associated with the fundamental life activities and infection invasion of L. monocytogenes, including known targets such as inlB, which can be utilized for molecular detection and therapeutic purposes. After screening a large number of potential target genes, we further screened them using hub gene selection methods to mining novel target genes. The present study employed eight different hub gene screening methods, ultimately identifying ten highly connected hub genes (bglF_1, davD, menE_1, tilS, dapX, iolC, gshAB, cysG, trpA, and hisC), which play crucial roles in the pathogenesis of L. monocytogenes. The results of pan-genomic analysis showed that L. monocytogenes from different regions exhibit high similarity in bacterial genome evolution. The PCR results demonstrated the excellent specificity of the bglF_1 and davD genes for L. monocytogenes. Therefore, the bglF_1 and davD genes hold promise as specific molecular detection and therapeutic targets for L. monocytogenes strains from different regions. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA. Objectives: This study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms. Materials and methods: A total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays. Results: Significant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells. Conclusions: Increased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells. [ABSTRACT FROM AUTHOR]

As a representative genetic and economic trait, pigmentation has a strong impact on speciation and adaptation. However, information and reports on microRNAs (miRNAs) associated with pigmentation remain limited. The Midas cichlid fish, with three typical distinct stages of body color pattern, "black-gray-gold", is an ideal model system for investigating pigmentation traits. In this study, miRNA libraries from scale tissues with the attached epidermis of Midas cichlids at three distinct stages of color transformation, black (B), transition (T), and gold (G), were sequenced using Illumina sequencing technology. In total, 53 (B vs. G), 88 (B vs. T), and 57 (T vs. G) miRNAs were differentially expressed between the respective groups. Target genes of the identified miRNAs were predicted, and the results showed that multiple target genes were related to pigmentation and pigment–cell differentiation. The miRNA–mRNA regulatory network suggests that miR-183-x and miR-133-x were predicted to be involved in regulating morphological color changes in Midas cichlids. The results advance our understanding of potential functions of miRNAs in skin pigment differentiation and early skin color fading of fishes. [ABSTRACT FROM AUTHOR]

High-temperature stress poses a significant environmental challenge for aquatic organisms, including tsinling lenok trout (Brachymystax lenok tsinlingensis). This study aimed to investigate the role of microRNAs (miRNAs) in inducing liver inflammation in tsinling lenok trout under high-temperature stress. Tsinling lenok trout were exposed to high-temperature conditions (24 °C) for 8 h, and liver samples were collected for analysis. Through small RNA sequencing, we identified differentially expressed miRNAs in the liver of high-temperature-stressed tsinling lenok trout compared to the control group (maintained at 16 °C). Several miRNAs, including novel-m0105-5p and miR-8159-x, showed significant changes in expression levels. Additionally, we conducted bioinformatics analysis to explore the potential target genes of these differentially expressed miRNAs. Our findings revealed that these miRNA target genes are involved in inflammatory response pathways, such as NFKB1 and MAP3K5. The downregulation of novel-m0105-5p and miR-8159-x in the liver of high-temperature-stressed tsinling lenok trout suggests their role in regulating liver inflammatory responses. To validate this, we performed a dual-luciferase reporter assay to confirm the regulatory relationship between miRNAs and target genes. Our results demonstrated that novel-m0105-5p and miR-8159-x enhance the inflammatory response of hepatocytes by promoting the expression of NFKB1 and MAP3K5, respectively. In conclusion, our study provides evidence that high-temperature stress induces liver inflammation in tsinling lenok trout through dysregulation of miRNAs. Understanding the molecular mechanisms underlying the inflammatory response in tsinling lenok trout under high-temperature stress is crucial for developing strategies to mitigate the negative impacts of environmental stressors on fish health and aquaculture production. [ABSTRACT FROM AUTHOR]

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Long non-coding RNAs (lncRNAs) are pivotal regulators of the abiotic stress responses in plants, yet their specific involvement in salt/alkali stress during alfalfa germination remains incompletely understood. Here, we subjected Zhongmu No.1 alfalfa (Medicago sativa L.) seeds to salt stress (20 mM NaCl and 20 mM Na2SO4 solutions) or alkali stress (5 mM NaHCO3 and 5 mM Na2CO3 solutions) treatments for 3 days, followed by total RNA extraction and RNA-seq analysis to delineate stress-responsive alfalfa lncRNAs. We identified 17,473 novel alfalfa lncRNAs, among which 101 and 123 were differentially expressed lncRNAs (DElncRNAs) under salt and alkali stress, respectively, compared to the control. Furthermore, we predicted 16 and 237 differentially expressed target genes regulated by DElncRNAs through cis/trans-regulatory mechanisms under salt or alkali stress, respectively. A functional enrichment analysis of DElncRNA target genes indicated that lncRNAs were implicated in the fatty acid metabolism pathway under salt stress, while they played a significant role in the phenylpropanoid and flavonoid biosynthesis pathway under alkali stress. Notably, lncRNAs were found to participate in the plant hormone signal transduction pathway, a common regulatory mechanism in both salt and alkali stress responses. These findings contribute to a deeper understanding of the mechanisms underlying alfalfa's response to salt and alkali stresses. [ABSTRACT FROM AUTHOR]

Insomnia, affecting the quality of life of millions globally, necessitates urgent and effective treatment strategies. This study conducted a randomized controlled trial to compare traditional and novel treatment methods in a cohort of 60 insomnia patients. Sleep quality and symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS). Additionally, transcranial Doppler (TCD) technology was employed to measure cerebral hemodynamic parameters. We divided the patients into two groups for insomnia treatment: (1) Control group: oral administration of zopiclone tablets; (2) Treatment group: oral administration of WuMei Decoction. The findings revealed that novel treatment approaches significantly improved sleep quality, disturbances, daytime functionality, and cerebral hemodynamic indicators. Furthermore, identifying 220 potential target genes through systems biology approaches offers new insights into the molecular mechanisms of insomnia and opportunities for drug development.

Abstract Background In the context of early sowing of maize as a promising adaptation strategy that could significantly reduce the negative effects of climate change, an in-depth understanding of mechanisms underlying plant response to low-temperature stress is demanded. Although microRNAs (miRNAs) have been recognized as key regulators of plant stress response, research on their role in chilling tolerance of maize during early seedling stages is scarce. Therefore, it is of great significance to explore chilling-responsive miRNAs, reveal their expression patterns and associated target genes, as well as to examine the possible functions of the conserved and novel miRNAs. In this study, the role of miRNAs was examined in 5d-old maize seedlings of one tolerant and one sensitive inbred line exposed to chilling (10/8 °C) stress for 6 h and 24 h, by applying high throughput sequencing. Results A total of 145 annotated known miRNAs belonging to 30 families and 876 potentially novel miRNAs were identified. Differential expression (DE) analysis between control and stress conditions identified 98 common miRNAs for both genotypes at one time point and eight miRNAs at both time points. Target prediction and enrichment analysis showed that the DE zma-miR396, zma-miR156, zma-miR319, and zma-miR159 miRNAs modulate growth and development. Furthermore, it was found that several other DE miRNAs were involved in abiotic stress response: antioxidative mechanisms (zma-miR398), signal transduction (zma-miR156, zma-miR167, zma-miR169) and regulation of water content (zma-miR164, zma-miR394, zma-miR396). The results underline the zma-miRNAs involvement in the modulation of their target genes expression as an important aspect of the plant’s survival strategy and acclimation to chilling stress conditions. Conclusions To our understanding, this is the first study on miRNAs in 5-d old seedlings’ response to chilling stress, providing data on the role of known and novel miRNAs post-transcriptional regulation of expressed genes and contributing a possible platform for further network and functional analysis.

Background: In the context of early sowing of maize as a promising adaptation strategy that could significantly reduce the negative effects of climate change, an in-depth understanding of mechanisms underlying plant response to low-temperature stress is demanded. Although microRNAs (miRNAs) have been recognized as key regulators of plant stress response, research on their role in chilling tolerance of maize during early seedling stages is scarce. Therefore, it is of great significance to explore chilling-responsive miRNAs, reveal their expression patterns and associated target genes, as well as to examine the possible functions of the conserved and novel miRNAs. In this study, the role of miRNAs was examined in 5d-old maize seedlings of one tolerant and one sensitive inbred line exposed to chilling (10/8 °C) stress for 6 h and 24 h, by applying high throughput sequencing. Results: A total of 145 annotated known miRNAs belonging to 30 families and 876 potentially novel miRNAs were identified. Differential expression (DE) analysis between control and stress conditions identified 98 common miRNAs for both genotypes at one time point and eight miRNAs at both time points. Target prediction and enrichment analysis showed that the DE zma-miR396, zma-miR156, zma-miR319, and zma-miR159 miRNAs modulate growth and development. Furthermore, it was found that several other DE miRNAs were involved in abiotic stress response: antioxidative mechanisms (zma-miR398), signal transduction (zma-miR156, zma-miR167, zma-miR169) and regulation of water content (zma-miR164, zma-miR394, zma-miR396). The results underline the zma-miRNAs involvement in the modulation of their target genes expression as an important aspect of the plant's survival strategy and acclimation to chilling stress conditions. Conclusions: To our understanding, this is the first study on miRNAs in 5-d old seedlings' response to chilling stress, providing data on the role of known and novel miRNAs post-transcriptional regulation of expressed genes and contributing a possible platform for further network and functional analysis. [ABSTRACT FROM AUTHOR]

Sericulture, the practice of rearing silkworms for the production of silk, is an essential agro‐based industry in several countries. However, silkworms are susceptible to a variety of diseases caused by viruses, bacteria and parasites, which may have a significant negative impact on global silk production. Traditional methods of pathogen identification, such as microscopy and laboratory culturing, have limitations in terms of accuracy and efficiency. The development of molecular techniques for pathogen identification has revolutionised the field of sericulture over the last decade. Genomic DNA and RNA‐based molecular techniques allow for the rapid and accurate detection of disease‐causing pathogens in silkworms. Molecular diagnosis has several advantages over traditional methods, including increased sensitivity and specificity, shorter turnaround time and the ability to detect pathogens that are difficult to culture or visualise under a microscope. Molecular techniques have been applied to detect several important pathogens of silkworms, including Nosema sp., nucleopolyhedrovirus, cypovirus, iflavirus and bidensovirus. The use of molecular diagnostics in sericulture is immensely important as the demand for high‐quality silk increases globally and the assessment of emerging pathogens associated with crop loss is essential. Major advancements in the improvement and application of molecular methods for diagnosing widespread silkworm pathogens are discussed. [ABSTRACT FROM AUTHOR]

Main conclusion: Differentially expressed microRNAs were found associated with the development of chasmogamous and cleistogamous flowers in Viola prionantha, revealing potential roles of microRNAs in the developmental evolution of dimorphic flowers. In Viola prionantha, chasmogamous (CH) flowers are induced by short daylight, while cleistogamous (CL) flowers are triggered by long daylight. How environmental factors and microRNAs (miRNAs) affect dimorphic flower formation remains unknown. In this study, small RNA sequencing was performed on CH and CL floral buds at different developmental stages in V. prionantha, differentially expressed miRNAs (DEmiRNAs) were identified, and their target genes were predicted. In CL flowers, Viola prionantha miR393 (vpr-miR393a/b) and vpr-miRN3366 were highly expressed, while in CH flowers, vpr-miRN2005, vpr-miR172e-2, vpr-miR166m-3, vpr-miR396f-2, and vpr-miR482d-2 were highly expressed. In the auxin-activated signaling pathway, vpr-miR393a/b and vpr-miRN2005 could target Vpr-TIR1/AFB and Vpr-ARF2, respectively, and other DEmiRNAs could target genes involved in the regulation of transcription, e.g., Vpr-AP2-7. Moreover, Vpr-UFO and Vpr-YAB5, the main regulators in petal and stamen development, were co-expressed with Vpr-TIR1/AFB and Vpr-ARF2 and showed lower expression in CL flowers than in CH flowers. Some V. prionantha genes relating to the stress/defense responses were co-expressed with Vpr-TIR1/AFB, Vpr-ARF2, and Vpr-AP2-7 and highly expressed in CL flowers. Therefore, in V. prionantha, CH–CL flower development may be regulated by the identified DEmiRNAs and their target genes, thus providing the first insight into the formation of dimorphic flowers in Viola. [ABSTRACT FROM AUTHOR]

Grafting is widely used to improve the resistance to abiotic stresses in cucurbit plants, but the effect and molecular mechanism of grafting on cold stress are still unknown in melon. In this study, phenotypic characteristics, physiological indexes, small-RNA sequencing and expression analyses were performed on grafted plants with pumpkin rootstock (PG) and self-grafted plants (SG) to explore the mechanism of changed cold tolerance by grafting in melon. Compared with SG plants, the cold tolerance was obviously enhanced, the malondialdehyde (MDA) content was significantly decreased and the activities of antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD) were significantly increased in PG plants. Depend on differentially expressed miRNA (DEM) identification and expression pattern analyses, cme-miR156b, cme-miR156f and chr07_30026 were thought to play a key role in enhancing low-temperature resistance resulting from grafting. Subsequently, 24, 37 and 17 target genes of cme-miR156b, cme-miR156f and chr07_30026 were respectively predicted, and 21 target genes were co-regulated by cme-miR156b and cme-miR156f. Among these 57 unique target genes, the putative promoter of 13 target genes contained the low-temperature responsive (LTR) cis-acting element. The results of qRT-PCR indicated that six target genes (MELO3C002370, MELO3C009217, MELO3C018972, MELO3C016713, MELO3C012858 and MELO3C000732) displayed the opposite expression pattern to their corresponding miRNAs. Furthermore, MELO3C002370, MELO3C016713 and MELO3C012858 were significantly downregulated in cold-resistant cultivars and upregulated in cold-sensitive varieties after cold stimulus, and they acted as the key negative regulators of low-temperature response in melon. This study revealed three key miRNAs and three putative target genes involved in the cold tolerance of melon and provided a molecular basis underlying how grafting improved the low-temperature resistance of melon plants. [ABSTRACT FROM AUTHOR]

Simple Summary: Epigenetic factor microRNAs may modulate vaccine protective efficacy well, supported by experimental data showing that the expression of some microRNAs drastically differs between well-protected and poorly protected genetic lines of chickens. Marek's disease vaccination and virus challenge trials were conducted in two genetically divergent inbred lines of chickens, and hundreds of microRNAs were identified. However, a small number of miRNAs were observed with significant differential expression per line per vaccination treatment group. One of the vaccines was HVT, which reportedly protects the two lines of birds with a significant difference. The target genes of the differentially expressed miRNAs in response to HVT were reportedly involved with many Gene Ontology terms and pathways, which suggests there is a high complexity of the genetic/epigenetic mechanism modulating vaccine protective efficacy. Epigenetic factors, including microRNAs (miRNAs), play an important role in affecting gene expression and, therefore, are involved in various biological processes including immunity protection against tumors. Marek's disease (MD) is a highly contagious disease of chickens caused by the MD virus (MDV). MD has been primarily controlled by vaccinations. MD vaccine efficacy might, in part, be dependent on modulations of a complex set of factors including host epigenetic factors. This study was designed to identify differentially expressed miRNAs in the primary lymphoid organ, bursae of Fabricius, in response to MD vaccination followed by MDV challenge in two genetically divergent inbred lines of White Leghorns. Small RNA sequencing and bioinformatic analyses of the small RNA sequence reads identified hundreds of miRNAs among all the treatment groups. A small portion of the identified miRNAs was differentially expressed within each of the four treatment groups, which were HVT or CVI988/Rispens vaccinated line 63-resistant birds and line 72-susceptible birds. A direct comparison between the resistant line 63 and susceptible line 72 groups vaccinated with HVT followed by MDV challenge identified five differentially expressed miRNAs. Gene Ontology analysis of the target genes of those five miRNAs revealed that those target genes, in addition to various GO terms, are involved in multiple signaling pathways including MAPK, TGF-β, ErbB, and EGFR1 signaling pathways. The general functions of those pathways reportedly play important roles in oncogenesis, anti-cancer immunity, cancer cell migration, and metastatic progression. Therefore, it is highly likely that those miRNAs may, in part, influence vaccine protection through the pathways. [ABSTRACT FROM AUTHOR]

Huntington’s disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p

The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans.

Abstract Phytobiotic compositions are commercially used in broiler production, mostly to improve general health and the production parameters. Moreover, some of their active substances may change the expression of miRNA in different tissues. Therefore, the purpose of this study was to evaluate the effect of the phytobiotic composition (PBC) containing white mustard, calamus, turmeric, and common ivy on production parameters, oxidative stress markers and expression of selected miRNAs in pectoral muscle of broiler chickens. The experiment was performed on broiler chickens fed the control diet (without PBC), and a diet supplemented with 60 or 100 mg/kg of PBC for 35 days. After the experiment, samples (blood and muscle) were collected for analyses. The analyzed production parameters included: feed conversion ratio, feed intake and body weight. There was no effect on growth performance of broiler chickens but feeding diet supplemented with 60 mg/kg phytobiotics significantly increased the expression of miR-30a-5p, miR-181a-5p, and miR-206, and decreased that of miR-99a-5p, miR-133a-5p, miR-142-5p, and miR-222 in pectoral muscle of chickens. The addition of 100 mg/kg phytobiotics significantly increased miR-99a-5p and miR-181a-5p expression, and caused down-regulation of the expression of miR-26a-5p and miR-30a-5p. Chickens fed diet supplemented with 100 mg/kg PBC had lower level of lipid peroxidation products in blood, while in the muscle tissue it was higher in birds fed a diet with the addition of 60 mg/kg as compared to the control group. The results suggest that this unique composition of phytobiotics does not affect productive traits but can change expression of miRNAs that are crucial for muscle physiology and pathology in broiler chickens. This additive may also protect against the oxidative stress but the effect is dose dependent.

Purpose: To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. Methods: This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. Results: Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. Conclusions: Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

There is a list of limitations for accurate clinical assessment of chronic periodontitis (CP) activity. The search for new mechanisms of pathogenesis leads to the selection of appropriate test substrates and research methods. Today, a number of miRNAs are known, which are involved in maintaining a healthy state or periodontal diseases. The aim of this systematic review was to analyze researches devoted to the role of miRNA in chronic periodontitis and various research methods to clarify the further study. Materials and methods. We followed PRISMA guidelines to conduct this systematic review. To identify the types of miRNAs, and their research methods in CP, PubMed database were systematically screened for medical literature. The articles published from 2019 up to November 27, 2023, were included. The articles were screened by using the search strategy as "chronic periodontitis miRNA". Results. We identified 35 miRNAs whose expression was significantly altered in chronic periodontitis (CP) compared to healthy gingiva. Fifteen of these miRNAs were correlated with the clinical manifestations of CP. The studies differed in the RNA-containing substrates, which included crevicular fluid, saliva, blood plasma, or exosomes from these substrates, as well as gingival biopsies. Real-time reverse transcription-PCR was the final method used for miRNA identification in all the studies. miRNAs are involved in almost all cellular processes and play a crucial role in development, differentiation, and homeostasis. They achieve these functions indirectly by suppressing gene expression, particularly through the inhibition of translation at the initiation stage. Target genes associated with the pathogenesis of chronic periodontitis (CP) have been previously identified for some miRNAs. Conclusion. Among the studied miRNAs, there are promising candidates to become targets for correction to optimize treatment, especially considering their predicted or known target genes involved in the pathogenesis of chronic periodontitis. However, no study has been devoted to pharmacological corrections of altered miRNA expression in chronic periodontitis.

Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. Methods: In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. Results: In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. Conclusions: Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis.

MicroRNAs (miRNAs) are conserved noncoding small RNAs that play essential regulatory roles in gene function by regulating target genes. Pardosa pseudoannulata is an important natural predatory enemy of insect pests and plays a significant role in controlling pests in rice fields, with temperature having a significant impact on their growth and development. To understand the response of miRNAs to temperature stress in P. pseudoannulata, we performed miRNA identification analyses of adult spiders exposed to 10°C and 40°C for 12 h, as low‐temperature and high‐temperature treatment groups, respectively. We obtained 54.74 M clean reads from 69.84 M raw reads after filtering out low‐quality reads, and 78 miRNAs including 13 novel miRNAs were identified from three small RNA libraries (10°C, 25°C and 40°C). At the low temperature and the high temperature, eight (one upregulated and seven downregulated) and ten (nine upregulated and one downregulated) differentially expressed miRNAs were identified, respectively. These differentially expressed miRNAs negatively regulated 43 and 12 target mRNA (the unigenes in our previous transcriptome sequence data) in response to low‐ and high‐temperature stress, respectively. These target genes are mainly involved in translation, ribosome structure and biotransformation, as well as the generation and conversion of energy. This study represents the first report of miRNA identification related to the Araneae spider species in response to temperature stress. These results will greatly facilitate our understanding of the physiological and biochemical mechanisms of spiders in response to temperature stress, which might be beneficial for the conservation and utilization of this species as an important natural insect enemy of pests in rice ecosystems. [ABSTRACT FROM AUTHOR]

A connection between diabetes and an increased risk of epilepsy has been suggested by observational studies. Animal studies have also shown that antihyperglycemic drugs can improve seizures. However, it is unclear whether antihyperglycemic drugs have a causal role in epilepsy in humans. To investigate this potential causal relationship, a Mendelian randomisation study was conducted using International League Against Epilepsy data as the discovery set and FinnGen data as the replication set. It was discovered that three antidiabetic drug target genes, ETFDH, CYP21A2 and CYP2D6, were involved in the occurrence of epilepsy. In particular, ETFDH was identified as a target gene in both the discovery set (inverse variance weighting [IVW], odds ratio [OR] = 1.018, 95% confidence interval [CI], 1.004–1.033, p = 0.009) and replication set (IVW, OR = 1.074, 95% CI, 1.034–1.114, p = 0.00016), and CYP21A2 was identified in the discovery set (IVW, OR = 1.029, 95% CI, 1.005–1.053, p = 0.016) and replication set (IVW, OR = 1.057, 95% CI, 1.001–1.116, p = 0.045) as having a causal association with an increased risk of epilepsy. Conversely, the CYP2D6 gene was found to be a protective factor for epilepsy in both the discovery set (IVW, OR = 0.0984, 95% CI, 0.969–0.998, p = 0.025) and replication set (IVW, OR = 0.977, 95% CI, 0.955–1.000, p = 0.046). A search of DrugBank revealed that metformin, an anti-glucose drug, is an inhibitor of the ETFDH gene and may have a potential therapeutic effect on epilepsy. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a gene-silencing mechanism extensively studied in invertebrates. It involves introducing double-stranded RNA (dsRNA) to silence specific genes and observe phenotypic effects. RNAi has revolutionized insect science research by enabling the investigation of gene function and novel approaches in pest management. With the development of the omics technology, more and more genes have been screened and used for research and production. The target genes are typically those essential for the survival, growth, development, or specific biological processes. This comprehensive review covers advancements in target genes and signaling pathways across various insect orders, providing insights into genetic functions and potential candidates for pest control strategies. [ABSTRACT FROM AUTHOR]

[Objectives]This paper aimed to explore the effect of heat stress on partial miRNA in myoblasts,and analyze by bioinformatics and predict the target genes of miR-23a,miR-24,miR-27a-3p and miR-30a-5p,so as to reveal the mechanism of miRNA regulating the development of skeletal muscle under heat stress. [Methods]The expression of miRNA in myoblasts under heat stress was studied by RT-qPCR. The miRBase was used to obtain the precursor sequences and mature sequences of miR-23a,miR-24,miR-27a-3p and miR-30a-5p in different species,then MEGA X software was used to construct the phylogenetic trees for similarity analysis. The target genes of the above miRNA were predicted by TargetScan,miRDB,RNA22 and miRWalk,and the predicted common targets were analyzed by DAVID for GO function and KEGG pathway enrichment. Ultimately,the correlation among miRNA,common target genes and the KEGG pathway was analyzed. [Results]Heat stress significantly decreased the expression of miRNA in myoblasts at the proliferation and differentiation stages. The miR-23a,miR-24,miR-27a and miR-30a showed high conservation among different species,and except for miR-24 of Bos taurus,the mature sequences of four miRNA were basically the same,and the seed sequences were completely the same. The predicted common target genes were mainly enriched in the GO items,such as cell proliferation,cell differentiation,cell cycle,cell apoptosis and cell migration,as well as mTOR,TGFβ,MAPK,Ras,ErbB,FoxO,and PI3K-Akt and other KEGG pathways. Additionally,the correlation analysis showed that miR-24 and miR-27a-3p may target NLK and TAOK1 to participate in the MAPK and FoxO signaling pathways to regulate skeletal muscle development. [Conclusions]The miR-23a,miR-24,miR-27a and miR-30a were highly conserved in different species and the expression of partial miRNA was down-regulated in myoblasts under heat stress,thereby it might affect the development of skeletal muscle. [ABSTRACT FROM AUTHOR]

To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log 2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play an important role in the response to many diseases. The previous study reported the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, retinopathy of prematurity (ROP) model) by hypoxia-inducible factor (HIF) stabilisation via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarateanalog dimethyloxalylglycine (DMOG). However, there is little understanding of how those genes are regulated. In the present study, 6918 known lncRNAs and 3654 novel lncRNAs were obtained, and a series of differentially expressed lncRNAs (DELncRNAs) were also identified. By cis- and trans-regulation analyses, the target genes of DELncRNAs were predicted. Functional analysis demonstrated that multiple genes were involved in the MAPK signalling pathway, adipocytokine signalling pathway was regulated by the DELncRNAs. By HIF-pathway analysis, two lncRNAs Gm12758 and Gm15283 were found that can regulate the HIF-pathway by targeting the Vegfa, Pgk1, Pfkl, Eno1, Eno1b and Aldoa genes. In conclusion, the present study provided a series of lncRNAs for further understanding and protecting the extremely premature infant from oxygen toxicity. What is already known on this subject? Roxadustat can prevent oxygen-induced retinopathy (OIR) by two pathways: direct retinal hypoxia-inducible factor (HIF) stabilisation and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilisation and increased serum angiokines. However, underlying the long non-coding RNAs (lncRNAs) that may regulate the HIF stabilisation-related genes have not been investigated thoroughly. What do the results of this study add? Six thousand nine hundred and eighteen known lncRNAs and 3654 novel lncRNAs were identified. GO and KEGG enrichment analysis showed that the MAPK signalling pathway and adipocytokine signalling pathway were regulated by the differentially expressed lncRNAs (DELncRNAs). Two lncRNAs Gm12758 and Gm15283 were found that may regulate the HIF-pathway by targeting the Vegfa, Pgk1, Pfkl, Eno1, Eno1b and Aldoa genes. What are the implications of these findings for clinical practice and/or further research? It provides a further rationale for protecting severe premature infants from oxygen poisoning. [ABSTRACT FROM AUTHOR]

Anadequate selenium (Se) intake can enhance human immunity and prevent diseases development. About one billion people in the world have varying degrees of Se deficiency in the world. Organic Se from tea infusion is the most easily absorbed and utilized Se form by the human body. Therefore the production of tea plants rich in Se is an effective way to increase Se dietary intake, but there are few studies on the involvement and functions of miRNAs in the responses of tea plants after Se treatment. MicroRNAs (miRNAs) are endogenous (non-coding) single-stranded RNAs that play crucial roles in regulating plant nutrient element acquisition and accumulation. Physiological analysis discovered that the total Se content in tea plant roots markedly increased under 0.05 mmol·L−1 selenite treatment, with no toxicity symptoms in the leaves and roots. To screen the miRNAs responsive to Se treatment in tea plants, miRNA libraries were constructed from the tea cultivar "Echa 1". Using high-throughput sequencing, 455 known miRNAs and 203 novel miRNAs were identified in this study. In total, 13 miRNAs were selected that were differentially expressed in tea plants' roots under 0.05 mmol·L−1 selenite treatments. Gene Ontology enrichment analysis revealed that the target genes of the differentially expressed miRNAs mainly belonged to the metabolic process, membrane, and catalytic activity ontologies. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis suggested that beta-alanine, taurine, hypotaurine, and sulfur metabolism were the most enriched pathways among the differentially expressed miRNAs, implying their involvement in Se accumulation and tolerance in tea plants. Further characterization of the data revealed that the number of novel miRNAs was comparable to that of known miRNAs, indicating that novel miRNAs significantly contributed to the regulation of Se accumulation in tea plant roots. Thisstudy lays the foundation for further research on the regulatory mechanisms underlying Se accumulation and tolerance in tea plants, providing targets to molecular breeding strategies for improving tea nutritional properties. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains the most prevalent malignancy among women globally, ranking as the second leading cause of cancer-related mortality. Approximately 70%-80% of patients with early-stage, non-metastatic disease are curable. Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Contemporary therapeutic strategies in breast cancer are geared towards the individualization of treatment, including both de-escalation and escalation based on tumor biology and early therapeutic response. This study aims to identify significant miRNAs and genes that are dysregulated in TNBC, contributing to its pathogenesis.Method: The dataset GSE38167 was retrieved from the Gene Expression Omnibus (GEO). Differential expression analysis of miRNAs between control and TNBC patient samples across various stages was conducted using R packages (GEOquery, limma, BiocGenerics, affy, and oligo). The multi-MiR package identified target genes of differentially expressed miRNAs (DEmiRNAs). A protein-protein interaction (PPI) network highlighted vital target genes, followed by gene ontology (GO) and KEGG pathway analyses to elucidate potential gene functions.Results: Differential expression analysis revealed significant miRNAs with |log2FC| > 2 and adjusted P < 0.05. Upregulated miRNAs included hsa-miR-135b, hsa-miR-183, hsa-miR-18b, hsa-miR-96, and hsa-miR-7; downregulated miRNAs comprised hsamiR- 377, hsa-miR-376a, hsa-miR-145, hsa-miR-451, and hsa-miR-376c. Target genes for these DEmiRNAs were identified, with ten hub genes (MYC, HIF1A, JUN, FN1, CD44, ERBB2, MMP2, CCN2, THBS1, AXL) emerging from the PPI network. GO analysis indicated enrichment in positive regulation of DNA-templated transcription, nucleus, and RNA binding. KEGG pathway analysis identified focal adhesion as a significant enrichment pathway.Conclusion: This study provides valuable insights into the regulatory mechanisms of miRNAs and their target genes in TNBC, offering a foundation for further research into the molecular underpinnings of this aggressive cancer subtype.

Abstract Objectives Wilms tumor (WT) is a common renal malignant tumor in children. We aimed to investigate the potential prognostic value of m6A-related genes and their relationship to the immune microenvironment in WT. Methods RNA-seq data and clinical information from 121 WT and 6 normal samples were obtained from the University of California Santa Cruz Xena database. We used various bioinformatics analysis tools to analyze these data and verify the expression level of m6A-related genes by experiments. Results Four m6A-related genes were successfully screened, including ADGRG2, CPD, CTHRC1, and LRTM2. Kaplan–Meier survival curves showed that the four genes were closely related to the prognosis of WT, which was also confirmed by receiver operator characteristic curves. Subsequently, in the immune microenvironment of WT, we discovered that Th1_cells were positively correlated with ADGRG2, CCR was negatively correlated with CPD, CCR was positively correlated with CTHRC1, APC_co_stimulation, CCR, Macrophages, inflammation-promoting cells, Treg, and Type_II_IFN_Reponse were negatively correlated with LRTM2. Finally, qRT-PCR showed that expression levels of the four genes were upregulated in the nephroblastoma cell lines (G-401, SK-NEP-1, and WT-CLS1) compared with the human embryonic kidney cell lines (293T). Conclusions Taken together, our study first time screened the m6A-related genes and revealed that ADGRG2, CPD, CTHRC1, and LRTM2 are the prognostic and immune-associated biomarkers in WT.

Abstract Background Rapeseed (Brassica napus L.) is the third largest source of vegetable oil in the world, and Sclerotinia sclerotiorum (Lib.) is a major soil-borne fungal plant pathogen that infects more than 400 plant species, including B. napus. Sclerotinia stem rot caused an annual loss of 10 − 20% in rapeseed yield. Exploring the molecular mechanisms in response to S. sclerotiorum infection in B. napus is beneficial for breeding and cultivation of resistant varieties. To gain a better understanding of the mechanisms regarding B. napus tolerance to Sclerotinia stem rot, we employed a miRNAome sequencing approach and comprehensively investigated global miRNA expression profile among five relatively resistant lines and five susceptible lines of oilseed at 0, 24, and 48 h post-inoculation. Results In this study, a total of 40 known and 1105 novel miRNAs were differentially expressed after S. sclerotiorum infection, including miR156, miR6028, miR394, miR390, miR395, miR166, miR171, miR167, miR164, and miR172. Furthermore, 8,523 genes were predicted as targets for these differentially expressed miRNAs. These target genes were mainly associated with disease resistance (R) genes, signal transduction, transcription factors, and hormones. Constitutively expressing miR156b (OX156b) plants strengthened Arabidopsis resistance against S. sclerotiorum accompanied by smaller necrotic lesions, whereas blocking miR156 expression in Arabidopsis (MIM156) led to greater susceptibility to S. sclerotiorum disease, associated with extensive cell death of necrotic lesions. Conclusions This study reveals the distinct difference in miRNA profiling between the relatively resistant lines and susceptible lines of B. napus in response to S. sclerotiorum. The identified differentially expressed miRNAs related to sclerotinia stem rot resistance are involved in regulating resistance to S. sclerotiorum in rapeseed by targeting genes related to R genes, signal transduction, transcription factors, and hormones. miR156 positively modulates the resistance to S. sclerotiorum infection by restricting colonization of S. sclerotiorum mycelia. This study provides a broad view of miRNA expression changes after S. sclerotiorum infection in oilseed and is the first to elucidate the function and mechanism underlying the miR156 response to S. sclerotiorum infection in oilseed rape.

Diptera and Lepidoptera species have the highest levels of insecticide resistance, and the mechanism of drug resistance has been studied in detoxification metabolism genes such as P450, GST, EST, and ABC. Since Bactrocera dorsalis are resistant to a variety of chemicals, the pattern and mechanism of resistance in Bactrocera dorsalis have been investigated from a variety of aspects such as detoxification metabolism genes, detoxification enzymes, intestinal symbiotic bacteria, and synergists in the world. In this study, 51 species and 149 detoxification metabolism genes were annotated in the Suppression Subtractive Hybridization (SSH) library, and 12 candidate genes related to beta-cypermethrin resistance were screened and quantitatively expressed in this library. Two genes were found to be upregulated in the egg stage, three genes in the larval stage, one gene in the pupal stage, and five genes in the adult stage, and four genes were found to be upregulated in the midgut and the malacca ducts in the midgut. The expression of cyp6g1, cyp6a22, GST-Epsilon9, and Trypsin-4 genes was upregulated in resistant strains, with the most obvious upregulation occurring in the midgut and the Malpighian tubules. These results provide new insights into the study of pesticide resistance in quarantine insects.

Long non-coding RNAs (lncRNAs) are pivotal regulators of the abiotic stress responses in plants, yet their specific involvement in salt/alkali stress during alfalfa germination remains incompletely understood. Here, we subjected Zhongmu No.1 alfalfa (Medicago sativa L.) seeds to salt stress (20 mM NaCl and 20 mM Na2SO4 solutions) or alkali stress (5 mM NaHCO3 and 5 mM Na2CO3 solutions) treatments for 3 days, followed by total RNA extraction and RNA-seq analysis to delineate stress-responsive alfalfa lncRNAs. We identified 17,473 novel alfalfa lncRNAs, among which 101 and 123 were differentially expressed lncRNAs (DElncRNAs) under salt and alkali stress, respectively, compared to the control. Furthermore, we predicted 16 and 237 differentially expressed target genes regulated by DElncRNAs through cis/trans-regulatory mechanisms under salt or alkali stress, respectively. A functional enrichment analysis of DElncRNA target genes indicated that lncRNAs were implicated in the fatty acid metabolism pathway under salt stress, while they played a significant role in the phenylpropanoid and flavonoid biosynthesis pathway under alkali stress. Notably, lncRNAs were found to participate in the plant hormone signal transduction pathway, a common regulatory mechanism in both salt and alkali stress responses. These findings contribute to a deeper understanding of the mechanisms underlying alfalfa’s response to salt and alkali stresses.