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Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways. [ABSTRACT FROM AUTHOR]

Fruit ripening represents a multifaceted biological process intricately controlled by an array of plant hormones, transcription factors, and epigenetic modifications. These regulatory mechanisms are crucial in determining fruit quality and post-harvest shelf life. Recent advancements in proteomics have shifted the focus toward understanding protein post-translational modifications (PTMs), which play a crucial role in modulating protein function. PTMs enhance protein activity and stability by altering their properties after biosynthesis, thereby adding an additional layer of regulation to the ripening process. This paper provides a comprehensive review of the roles of PTMs, including ubiquitination, phosphorylation, redox modifications, and glycosylation in regulating fruit ripening. Emphasis is placed on the intricate interplay between these PTMs and key regulator factors such as plant hormones, transcriptional mechanisms, and epigenetic modifications. By exploring these interactions, this review seeks to enhance our understanding of the complex regulatory network underlying fruit ripening and to offer novel perspectives on strategies for fruit preservation. [ABSTRACT FROM AUTHOR]

Clubroot disease, caused by the pathogen Plasmodiophora brassicae, is a serious disease that poses a critical threat to cabbage production. However, the molecular mechanism of the microRNAs (miRNAs) involved in the cabbage's response to P. brassicae infection remains to be elucidated. Here, the mRNA and miRNA expression profiles of cabbage in response to a P. brassicae infection were analyzed. In the transcriptome analysis, 2217 and 5552 differentially expressed genes (DEGs) were identified at 7d and 21d after inoculation, which were enriched in MAPK signaling, plant–pathogen interaction, plant hormone signal transduction, and phenylpropanoid biosynthesis pathways. BolC02g057640.2J, BolC09g006890.2J, BolC02g013230.2J, BolC06g006490.2J, BolC03g052660.2J, BolC07g052580.2J, and BolC04g044910.2J were predicted to be significantly involved in the defense response or plant–pathogen interaction through co-expression network analysis. Small RNA data analysis identified 164 miRNAs belonging to 51 families. miR1515, miR166, miR159, and miR9563 had the greatest number of members among the miRNA families. Integrated analysis revealed 23 miRNA–mRNA interactions related to a P. brassicae infection. The target genes of differentially expressed miRNAs (DEMs) revealed the NAC, ARF, TCP, and SPL transcription factor members that probably participate in the defense response. This study provided new insights into the miRNA-involved regulatory system during the process of disease infection with P. brassicae in cabbage. [ABSTRACT FROM AUTHOR]

The formation of seedless traits is regulated by multiple factors. AGLs, which belong to the MADS-box family, were reported to be important regulators in this process; however, the underlying mechanism remains elusive. Here, we identified the VvAGL sub-family genes during the seed abortion process in seedless grapevine cv. 'JingkeJing' and found 40 differentially expressed VvAGL members and 1069 interacting proteins in this process. Interestingly, almost all members and their interacting proteins involved in the tryptophan metabolic pathway (K14486) and participated in the phytohormone signalling (KO04075) pathway, including the growth hormone (IAA), salicylic acid (SA), abscisic acid (ABA), cytokinin (CTK), and ethylene signalling pathways. The promoters of AGL sub-family genes contain cis-elements in response to hormones such as IAA, ABA, CTK, SA, and ETH, implying that they might respond to multi-hormone signals and involve in hormone signal transductions. Further expression analysis revealed VvAGL6-2, VvAGL11, VvAGL62-11, and VvAGL15 had the highest expression at the critical period of seed abortion, and there were positive correlations between ETH-VvAGL15-VvAGL6-2, ABA-VvAGL80, and SA-VvAGL62 in promoting seed abortion but negative feedback between IAA-VvAGL15-VvAGL6-2 and CTK-VvAGL11. Furthermore, many genes in the IAA, ABA, SA, CTK, and ETH pathways had a special expressional pattern in the seed, whereby we developed a regulatory network mediated by VvAGLs by responding to multihormonal crosstalk during grape seed abortion. Our findings provide new insights into the regulatory network of VvAGLs in multi-hormone signalling to regulate grape seed abortion, which could be helpful in the molecular breeding of high-quality seedless grapes. [ABSTRACT FROM AUTHOR]

The aquatic γ-proteobacterium Shewanella oneidensis is able to form two types of biofilms: a floating biofilm at the air–liquid interface (pellicle) and a solid surface-associated biofilm (SSA-biofilm). S. oneidensis possesses the Bpf system, which is orthologous to the Lap system first described in Pseudomonas fluorescens. In the Lap systems, the retention of a large adhesin (LapA) at the cell surface is controlled by LapD, a c-di-GMP effector protein, and LapG, a periplasmic protease targeting LapA. Here, we showed that the Bpf system is mandatory for pellicle biogenesis, but not for SSA-biofilm formation, indicating that the role of Bpf is somewhat different from that of Lap. The BpfD protein was then proved to bind c-di-GMP via its degenerated EAL domain, thus acting as a c-di-GMP effector protein like its counterpart LapD. In accordance with its key role in pellicle formation, BpfD was found to interact with two diguanylate cyclases, PdgA and PdgB, previously identified as involved in pellicle formation. Finally, BpfD was shown to interact with CheY3, the response regulator controlling both chemotaxis and biofilm formation. Altogether, these results indicate that biofilm formation in S. oneidensis is under the control of a large c-di-GMP network. [ABSTRACT FROM AUTHOR]

Abstract Background Plant A/T-rich protein and zinc-binding protein (PLATZ) transcription factors are pivotal regulators in various aspects of plant biology, including growth, development, and responses to environmental stresses. While PLATZ genes have been extensively studied and functionally characterized in various plants, limited information is available for these genes in barley. Results Here, we discovered a total of 11 PLATZ genes distributed across seven chromosomes in barley. Based on phylogenetic and conserved motif analysis, we classified PLATZ into five subfamilies, comprising 3, 1, 2, 1 and 4 genes, respectively. Analysis of gene structure demonstrated that these 11 HvPLATZ genes typically possessed two to four exons. Most HvPLATZ genes were found to possess at least one ABRE cis-element in their promoter regions, and a few of them also contained LTR, CAT-box, MRE, and DRE cis-elements. Then, we conducted an exploration of the expression patterns of HvPLATZs, which displayed notable differences across various tissues and in response to abiotic stresses. Functional analysis of HvPLATZ6 and HvPLATZ8 in yeast cells showed that they may be involved in drought tolerance. Additionally, we constructed a regulatory network including miRNA-targeted gene predictions and identified two miRNAs targeting two HvPLATZs, such as hvu-miR5053 and hvu-miR6184 targeting HvPLATZ2, hvu-miR6184 targeting HvPLATZ10. Conclusion In summary, these findings provide valuable insights for future functional verification of HvPLATZs and contribute to a deeper understanding of the role of HvPLATZs in response to stress conditions in barley.

Objective The objective of this study was to identify the N6-methyladenosine (m6A)-circHECA molecule in secondary hair follicles (SHFs) of cashmere goats, and generate its potential regulatory network, as well as explore the potential relationship between transcriptional pattern of m6A-circHECA and promoter methylation of its host gene (HECA). Methods The validation of circHECA m6A sites was performed using methylation immunoprecipitation (Me-RIP) along with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technique. The nucleus and cytoplasm localizations of m6A-circHECA were performed using SHF stem cells of cashmere goats with RT-qPCR analysis. Based on in-silico analysis, the regulatory networks of m6A-circHECA were generated with related signal pathway enrichment. The methylation level of promoter region of m6A-circHECA host gene (HECA) was assessed by the bisulfite sequencing PCR (BSP-PCR) technique. Results The m6A-circHECA was confirmed to contain four m6A modification sites including m6A-213, m6A-297, m6A-780, and m6A-927, and it was detected mainly in cytoplasm of the SHF stem cells of cashmere goats. The integrated regulatory network analysis showed directly or indirectly complex regulatory relationships between m6A-circHECA of cashmere goats and its potential target molecules: miRNAs, mRNAs, and proteins. The regulatory network and pathway enrichment indicated that m6A-circHECA might play multiple roles in the SHF physiology process of cashmere goats through directly or indirectly interacting or regulating its potential target molecules. A higher methylation level of promoter region of HECA gene in SHFs of cashmere goats might cause the lower expression of m6A-circHECA. Conclusion The m6A-circHECA might play multiple roles in SHF physiology process of cashmere goats through miRNA mediated pathways along with directly or indirectly interaction with its target proteins. The promoter methylation of m6A-circHECA host gene (HECA) most likely was implicated in its expression inhibition in SHFs of cashmere goats.

BACKGROUND: Osteoblasts are the main cell types responsible for bone formation and remodeling, and the normal performance of their function is precisely regulated by various signaling pathways. Among them, the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE: To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS: The Chinese and English search terms “BMP signaling pathway, Wnt signaling pathway, and osteogenesis” were searched in CNKI, Wanfang, and PubMed databases for original researches published from the inception to June 2023. Totally 61 articles were finally selected for analysis and summary. Using the method of the literature review, the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION: (1) Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation, proliferation, and maturation of osteoblasts. Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein. Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis. Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects. (2) The regulatory effect of bone morphogenetic protein/ Wnt signaling pathway will be affected by many factors in different physiological and pathological states. Growth factors, hormones, and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent. (3) Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis, and they together constitute a complex regulatory network. (4) Chinese medicine and natural compounds can promote bone health by regulating signaling pathways, providing new possibilities for treating bone diseases. (5) Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions, resolve the key nodes and regulation mechanism in the complex network, to provide more precise targets for the treatment of bonerelated diseases, and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify the N6-methyladenosine (m6A)- circHECA molecule in secondary hair follicles (SHFs) of cashmere goats, and generate its potential regulatory network, as well as explore the potential relationship between transcriptional pattern of m6A-circHECA and promoter methylation of its host gene (HECA). Methods: The validation of circHECA m6A sites was performed using methylation immunoprecipitation (Me-RIP) along with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technique. The nucleus and cytoplasm localizations of m6A- circHECA were performed using SHF stem cells of cashmere goats with RT-qPCR analysis. Based on in-silico analysis, the regulatory networks of m6A-circHECA were generated with related signal pathway enrichment. The methylation level of promoter region of m6A-circHECA host gene (HECA) was assessed by the bisulfite sequencing PCR (BSPPCR) technique. Results: The m6A-circHECA was confirmed to contain four m6A modification sites including m6A-213, m6A-297, m6 A-780, and m6A-927, and it was detected mainly in cytoplasm of the SHF stem cells of cashmere goats. The integrated regulatory network analysis showed directly or indirectly complex regulatory relationships between m6A-circHECA of cashmere goats and its potential target molecules: miRNAs, mRNAs, and proteins. The regulatory network and pathway enrichment indicated that m6A-circHECA might play multiple roles in the SHF physiology process of cashmere goats through directly or indirectly interacting or regulating its potential target molecules. A higher methylation level of promoter region of HECA gene in SHFs of cashmere goats might cause the lower expression of m6A-circHECA. Conclusion: The m6A-circHECA might play multiple roles in SHF physiology process of cashmere goats through miRNA mediated pathways along with directly or indirectly interaction with its target proteins. The promoter methylation of m6A-circHECA host gene (HECA) most likely was implicated in its expression inhibition in SHFs of cashmere goats. [ABSTRACT FROM AUTHOR]

Abstract Climate deterioration, water shortages, and abiotic stress are the main threats worldwide that seriously affect cotton growth, yield, and fiber quality. Therefore, research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance. The NAC proteins are crucial and plant-specific transcription factors (TFs) that are involved in cotton growth, development, and stress responses. The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible. Based on cotton genomic data, genome-wide identification and analyses have revealed potential functions of cotton NAC genes. Here, we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought, salt, and Verticillium wilt-related stresses, as well as leaf senescence and the development of fibers, xylem, and glands. The detailed regulatory network of NAC proteins in cotton is also elucidated. Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation, participate in several biological processes by interacting with related proteins, and regulate the expression of downstream genes. Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance. This review elucidates the latest findings on the functions and regulation of cotton NAC proteins, broadens our understanding of cotton NAC TFs, and lays a fundamental foundation for further molecular breeding research in cotton.

Abstract Background Abnormal endometrial blood flow causes a decrease in endometrial receptivity and is considered a relatively independent risk factor for recurrent implantation failure (RIF). This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in RIF, and further explore its mechanism. Methods Datasets were downloaded from the GEO database to identify differentially expressed circRNAs, miRNAs and mRNAs. The circRNA–miRNA–mRNA and PPI networks were constructed using Cytoscape 3.6.0 and the STRING database, the hub genes were identified with the cytoHubba plug-in, and a circRNA–miRNA–hub mRNA regulatory sub-network was constructed. Then, GO and KEGG pathway enrichment analyses of the hub genes were performed to comprehensively analyze the mechanism of hub mRNAs in RIF. Due to the results of circRNAs-miRNAs-hub mRNAs regulatory network, we verified the expression of circRNA_0001721, circRNA_0000714, miR-17-5p, miR-29b-3p, HIF1A and VEGFA in the RIF mouse model by qRT‒PCR and western blotting. Results We initially identified 175 DEmRNAs, 48 DEmiRNAs and 56 DEcircRNAs in RIF associated with angiogenesis and constructed a circRNA-miRNA‒mRNA network and PPI network. We further identified six hub genes in the acquired network. Based on these genes, functional enrichment analysis revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. In addition, the interaction networks of circRNA_0001721/miR-17-5p/HIF1A and the circRNA_0000714/miR-29b-3p/VEGFA axis were predicted. In the RIF mouse model, circRNA_0001721, circRNA_0000714, HIF1A and VEGFA were down-regulated, whereas miR-17-5p and miR-29b-3p were up-regulated according to qRT‒PCR and western blotting. Conclusion This study revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. The circRNA_0001721/miR-17-5p/HIF1A and circRNA_0000714/miR-29b-3p/VEGFA axes might play a role in the pathogenesis of endometrial angiogenesis in RIF.

Abstract With global warming, high temperature (HT) has become one of the most common abiotic stresses resulting in significant crop yield losses, especially for jujube (Ziziphus jujuba Mill.), an important temperate economic crop cultivated worldwide. This study aims to explore the coping mechanism of jujube to HT stress at the transcriptional and post-transcriptional levels, including identifying differentially expressed miRNAs and mRNAs as well as elucidating the critical pathways involved. High-throughput sequencing analyses of miRNA and mRNA were performed on jujube leaves, which were collected from “Fucumi” (heat-tolerant) and “Junzao” (heat-sensitive) cultivars subjected to HT stress (42 °C) for 0, 1, 3, 5, and 7 days, respectively. The results showed that 45 known miRNAs, 482 novel miRNAs, and 13,884 differentially expressed mRNAs (DEMs) were identified. Among them, integrated analysis of miRNA target genes prediction and mRNA-seq obtained 1306 differentially expressed miRNAs-mRNAs pairs, including 484, 769, and 865 DEMIs-DEMs pairs discovered in “Fucuimi”, “Junzao” and two genotypes comparative groups, respectively. Furthermore, functional enrichment analysis of 1306 DEMs revealed that plant-pathogen interaction, starch and sucrose metabolism, spliceosome, and plant hormone signal transduction were crucial pathways in jujube leaves response to HT stress. The constructed miRNA-mRNA network, composed of 20 DEMIs and 33 DEMs, displayed significant differently expressions between these two genotypes. This study further proved the regulatory role of miRNAs in the response to HT stress in plants and will provide a theoretical foundation for the innovation and cultivation of heat-tolerant varieties.

Seed plumules comprise multiple developing tissues and are key sites for above-ground plant organ morphogenesis. Here, the spatial expression of genes in developing rice seed plumules was characterized by single-cell transcriptome sequencing in Zhongjiazao 17, a popular Chinese indica rice cultivar. Of 15 cell clusters, 13 were assigned to cell types using marker genes and cluster-specific genes. Marker genes of multiple cell types were expressed in several clusters, suggesting a complex developmental system. Some genes for signaling by phytohormones such as abscisic acid were highly expressed in specific clusters. Various cis-elements in the promoters of genes specifically expressed in cell clusters were calculated, and some key hormone-related motifs were frequent in certain clusters. Spatial expression patterns of genes involved in rapid seed germination, seedling growth, and development were identified. These findings enhanced our understanding of cellular diversity and specialization within plumules of rice, a monocotyledonous model crop.

Abstract Micro RNAs (miRNAs, miRs) and relevant networks might exert crucial functions during differential host cell infection by the different Leishmania species. Thus, a bioinformatic analysis of microarray datasets was developed to identify pivotal shared biomarkers and miRNA-based regulatory networks for Leishmaniasis. A transcriptomic analysis by employing a comprehensive set of gene expression profiling microarrays was conducted to identify the key genes and miRNAs relevant for Leishmania spp. infections. Accordingly, the gene expression profiles of healthy human controls were compared with those of individuals infected with Leishmania mexicana, L. major, L. donovani, and L. braziliensis. The enrichment analysis for datasets was conducted by utilizing EnrichR database, and Protein–Protein Interaction (PPI) network to identify the hub genes. The prognostic value of hub genes was assessed by using receiver operating characteristic (ROC) curves. Finally, the miRNAs that interact with the hub genes were identified using miRTarBase, miRWalk, TargetScan, and miRNet. Differentially expressed genes were identified between the groups compared in this study. These genes were significantly enriched in inflammatory responses, cytokine-mediated signaling pathways and granulocyte and neutrophil chemotaxis responses. The identification of hub genes of recruited datasets suggested that TNF, SOCS3, JUN, TNFAIP3, and CXCL9 may serve as potential infection biomarkers and could deserve value as prognostic biomarkers for leishmaniasis. Additionally, inferred data from miRWalk revealed a significant degree of interaction of a number of miRNAs (hsa-miR-8085, hsa-miR-4673, hsa-miR-4743-3p, hsa-miR-892c-3p, hsa-miR-4644, hsa-miR-671-5p, hsa-miR-7106-5p, hsa-miR-4267, hsa-miR-5196-5p, and hsa-miR-4252) with the majority of the hub genes, suggesting such miRNAs play a crucial role afterwards parasite infection. The hub genes and hub miRNAs identified in this study could be potentially suggested as therapeutic targets or biomarkers for the management of leishmaniasis.

Background: Intracranial aneurysms (IAs) represent protrusions in the vascular wall, with their growth and wall thinning influenced by various factors. These processes can culminate in the rupture of the aneurysm, leading to subarachnoid hemorrhage (SAH). Unfortunately, over half of the patients prove unable to withstand SAH, succumbing to adverse outcomes despite intensive therapeutic interventions, even in premier medical facilities. This study seeks to discern the pivotal microRNAs (miRNAs) and genes associated with the formation and progression of IAs. Methods: The investigation gathered expression data of miRNAs (from GSE66240) and mRNAs (from GSE158558) within human aneurysm tissue and superficial temporal artery (STA) samples, categorizing them into IA and normal groups. This classification was based on the Gene Expression Omnibus (GEO) database. Results: A total of 70 differentially expressed microRNAs (DEMs) and 815 differentially expressed mRNAs (DEGs) were pinpointed concerning IA. Subsequently, a miRNA-mRNA network was constructed, incorporating 9 significantly upregulated DEMs and 211 significantly downregulated DEGs. Simultaneously, functional enrichment and pathway analyses were conducted on both DEMs and DEGs. Through protein-protein interaction (PPI) network analysis and functional enrichment, 9 significantly upregulated DEMs (hsa-miR-188-5p, hsa-miR-590-5p, hsa-miR-320b, hsa-miR-423-5p, hsa-miR-140-5p, hsa-miR-486-5p, hsa-miR-320a, hsa-miR-342-3p, and hsa-miR-532-5p) and 50 key genes (such as ATP6V1G1, KBTBD6, VIM, PA2G4, DYNLL1, METTL21A, MDH2, etc.) were identified, suggesting their potential significant role in IA. Among these genes, ten were notably negatively regulated by at least two key miRNAs. Conclusions: The findings of this study provide valuable insights into the potential pathogenic mechanisms underlying IA by elucidating a miRNA-mRNA network. This comprehensive approach sheds light on the intricate interplay between miRNAs and genes, offering a deeper understanding of the molecular dynamics involved in IA development and progression.

Ralstonia solanacearum species complex (RSSC) includes soilborne bacterial plant pathogens with worldwide distribution and wide host ranges. Virulence factors are regulated via four hierarchically organized cell–cell contact independent quorum‐sensing (QS) signalling systems: the Phc, which uses as signals (R)‐methyl 3‐hydroxypalmitate [(R)‐3‐OH PAME] or (R)‐methyl 3‐hydroxymyristate [(R)‐3‐OH MAME], the N‐acyl homoserine lactone (AHL)‐dependent RasI/R and SolI/R systems, and the recently identified anthranilic acid‐dependent system. The unique Phc QS system has been extensively studied; however, the role of the two AHL QS systems has only recently been addressed. In this microreview, we present and discuss current data of the SolI/R and RasI/R QS systems in the RSSC. We also present the distribution and frequency of these AHL QS systems in the RSSC, discuss possible ecological roles and evolutive implications. The complex QS hierarchical networks emphasizes the crucial role of cell–cell signalling in the virulence of the RSSC. [ABSTRACT FROM AUTHOR]

The fluctuation in temperature poses a significant challenge for poikilothermic organisms, notably insects, particularly in the context of changing climatic conditions. In insects, temperature adaptation has been driven by polygenes. In addition to genes that directly affect traits (core genes), other genes (peripheral genes) may also play a role in insect temperature adaptation. This study focuses on two peripheral genes, the GRIP and coiled‐coil domain containing 2 (GCC2) and karyopherin subunit beta 1 (KPNB1). These genes are differentially expressed at different temperatures in the cosmopolitan pest, Plutella xylostella. GCC2 and KPNB1 in P. xylostella were cloned, and their relative expression patterns were identified. Reduced capacity for thermal adaptation (development, reproduction and response to temperature extremes) in the GCC2‐deficient and KPNB1‐deficient P. xylostella strains, which were constructed by CRISPR/Cas9 technique. Deletion of the PxGCC2 or PxKPNB1 genes in P. xylostella also had a differential effect on gene expression for many traits including stress resistance, resistance to pesticides, involved in immunity, trehalose metabolism, fatty acid metabolism and so forth. The ability of the moth to adapt to temperature via different pathways is likely to be key to its ability to remain an important pest species under predicted climate change conditions. [ABSTRACT FROM AUTHOR]

Climate deterioration, water shortages, and abiotic stress are the main threats worldwide that seriously affect cotton growth, yield, and fiber quality. Therefore, research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance. The NAC proteins are crucial and plant-specific transcription factors (TFs) that are involved in cotton growth, development, and stress responses. The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible. Based on cotton genomic data, genome-wide identification and analyses have revealed potential functions of cotton NAC genes. Here, we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought, salt, and Verticillium wilt-related stresses, as well as leaf senescence and the development of fibers, xylem, and glands. The detailed regulatory network of NAC proteins in cotton is also elucidated. Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation, participate in several biological processes by interacting with related proteins, and regulate the expression of downstream genes. Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance. This review elucidates the latest findings on the functions and regulation of cotton NAC proteins, broadens our understanding of cotton NAC TFs, and lays a fundamental foundation for further molecular breeding research in cotton. [ABSTRACT FROM AUTHOR]

Background: Abnormal endometrial blood flow causes a decrease in endometrial receptivity and is considered a relatively independent risk factor for recurrent implantation failure (RIF). This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in RIF, and further explore its mechanism. Methods: Datasets were downloaded from the GEO database to identify differentially expressed circRNAs, miRNAs and mRNAs. The circRNA–miRNA–mRNA and PPI networks were constructed using Cytoscape 3.6.0 and the STRING database, the hub genes were identified with the cytoHubba plug-in, and a circRNA–miRNA–hub mRNA regulatory sub-network was constructed. Then, GO and KEGG pathway enrichment analyses of the hub genes were performed to comprehensively analyze the mechanism of hub mRNAs in RIF. Due to the results of circRNAs-miRNAs-hub mRNAs regulatory network, we verified the expression of circRNA_0001721, circRNA_0000714, miR-17-5p, miR-29b-3p, HIF1A and VEGFA in the RIF mouse model by qRT‒PCR and western blotting. Results: We initially identified 175 DEmRNAs, 48 DEmiRNAs and 56 DEcircRNAs in RIF associated with angiogenesis and constructed a circRNA-miRNA‒mRNA network and PPI network. We further identified six hub genes in the acquired network. Based on these genes, functional enrichment analysis revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. In addition, the interaction networks of circRNA_0001721/miR-17-5p/HIF1A and the circRNA_0000714/miR-29b-3p/VEGFA axis were predicted. In the RIF mouse model, circRNA_0001721, circRNA_0000714, HIF1A and VEGFA were down-regulated, whereas miR-17-5p and miR-29b-3p were up-regulated according to qRT‒PCR and western blotting. Conclusion: This study revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. The circRNA_0001721/miR-17-5p/HIF1A and circRNA_0000714/miR-29b-3p/VEGFA axes might play a role in the pathogenesis of endometrial angiogenesis in RIF. [ABSTRACT FROM AUTHOR]

In China, the Liaodong Peninsula is an important growing area for blueberries because of the high organic matter content in the soil, the abundance of light, and the large temperature difference between day and night. However, the low temperature and relative humidity of the air during the winter and early spring in the Liaodong Peninsula are the main reasons for the damage to blueberry plants. Here, we documented the transcriptome and proteome dynamics in response to cold stress in three blueberry cultivars ('Northland', 'Bluecrop', and 'Berkeley'). Functional enrichment analysis indicated that many differentially expressed genes (DEGs) and differentially abundant proteins (DAPs) were mainly involved in the pathways of protein processing in the endoplasmic reticulum, the glutathione metabolism pathway, and ribosomes. We identified 12,747 transcription factors (TFs) distributed in 20 families. Based on our findings, we speculated that cold tolerance development was caused by the expression of calcium-related genes (CDPKs and CMLs), glutathione proteins, and TFs (NAC, WRKY, and ERF). Our investigation found that three cultivars experienced cold damage when exposed to temperatures between −9 °C and −15 °C in the field. Therefore, the cold resistance of blueberries during overwintering should not only resist the influence of low temperatures but also complex environmental factors such as strong winds and low relative humidity in the air. The order of cold resistance strength in the three blueberry cultivars was 'Berkeley', 'Bluecrop', and 'Northland'. These results provide a comprehensive profile of the response to cold stress, which has the potential to be used as a selection marker for programs to improve cold tolerance in blueberries. [ABSTRACT FROM AUTHOR]

In plant hormone signaling, transcription factor regulatory networks (TFRNs), which link the master transcription factors to the biological processes under their control, remain insufficiently characterized despite their crucial function. Here, we identify a TFRN involved in the response to the key plant hormone auxin and define its impact on auxin-driven biological processes. To reconstruct the TFRN, we developed a three-step procedure, which is based on the integrated analysis of differentially expressed gene lists and a representative collection of transcription factor binding profiles. Its implementation is available as a part of the CisCross web server. With the new method, we distinguished two transcription factor subnetworks. The first operates before auxin treatment and is switched off upon hormone application, the second is switched on by the hormone. Moreover, we characterized the functioning of the auxin-regulated TFRN in control of chlorophyll and lignin biosynthesis, abscisic acid signaling, and ribosome biogenesis. [ABSTRACT FROM AUTHOR]

Growth-regulating factors (GRFs) are transcription factors that play a pivotal role in plant growth and development. This study identifies 12 Solanum tuberosum GRF transcription factors (StGRFs) and analyzes their physicochemical properties, phylogenetic relationships, gene structures and gene expression patterns using bioinformatics. The StGRFs exhibit a length range of 266 to 599 amino acids, with a molecular weight of 26.02 to 64.52 kDa. The majority of StGRFs possess three introns. The promoter regions contain a plethora of cis-acting elements related to plant growth and development, as well as environmental stress and hormone response. All the members of the StGRF family contain conserved WRC and QLQ domains, with the sequences of these two conserved domain modules exhibiting high levels of conservation. Transcriptomic data indicates that StGRFs play a significant role in the growth and development of stamens, roots, young tubers, and other tissues or organs in potatoes. Furthermore, a few StGRFs exhibit differential expression patterns in response to Phytophthora infestans, chemical elicitors, heat, salt, and drought stresses, as well as multiple hormone treatments. The results of the expression analysis indicate that StGRF1, StGRF2, StGRF5, StGRF7, StGRF10 and StGRF12 are involved in the process of tuber sprouting, while StGRF4 and StGRF9 may play a role in tuber dormancy. These findings offer valuable insights that can be used to investigate the roles of StGRFs during potato tuber dormancy and sprouting. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is considered one of the most severe complications of diabetes mellitus, but its pathogenesis is still unclear. We hypothesize that certain genes exert a pivotal influence on the progression of DR. This study explored biomarkers for the diagnosis and treatment of DR through bioinformatics analysis. Methods: Within the GSE221521 and GSE189005 datasets, candidate genes were acquired from intersections of genes obtained using WGCNA and DESeq2 packages. Mendelian randomization (MR) analysis selected candidate biomarkers exhibiting causal relationships with DR. Receiver Operating Characteristic (ROC) analysis determined the diagnostic efficacy of biomarkers, the expression levels of biomarkers were verified in the GSE221521 and GSE189005 datasets, and a nomogram for diagnosing DR was constructed. Enrichment analysis delineated the roles and pathways associated with the biomarkers. Immune infiltration analysis analyzed the differences in immune cells between DR and control groups. The miRNet and networkanalyst databases were then used to predict the transcription factors (TFs) and miRNAs, respectively, of biomarkers. Finally, RT-qPCR was used to verify the expression of the biomarkers in vitro. Results: MR analysis identified 13 candidate biomarkers that had causal relationships with DR. The ROC curve demonstrated favorable diagnostic performance of three biomarkers (OSER1, HIPK2, and DDRGK1) for DR, and their expression trends were consistent across GSE221521 and GSE189005 datasets. The calibration curves and ROC curves indicated good predictive performance of the nomogram. The biomarkers were enriched in pathways of immune, cancer, amino acid metabolism, and oxidative phosphorylation. Ten immune cell lines showed notable disparities between the DR and control groups. Among them, effector memory CD8+ T cells, plasmacytoid dendritic cells, and activated CD4+ T cells exhibited good correlation with biomarker expression. The TF-mRNA-miRNA network suggested that hsa-mir-92a-3p, GATA2, and RELA play important roles in biomarker targeting for DR. RT-qPCR results also demonstrated a notably high expression of HIPK2 in patients with DR, whereas notably low expression of OSER1. Conclusion: OSER1, HIPK2, and DDRGK1 were identified as biomarkers for DR. The study findings provide novel insights into the pathogenesis of DR. [ABSTRACT FROM AUTHOR]

Introduction: The unique dormancy of Mycobacterium tuberculosis plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate. Methods: To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites. Results and discussion: The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.7% of the binding sites were located inside the target genes. The functions of 288 potential MtrA target genes predicted according to 294 confirmed binding sites were highly diverse, and DNA replication and damage repair, lipid metabolism, cell wall component biosynthesis, cell wall assembly, and cell division were the predominant pathways. Among the 53 pathways shared between dormancy/resuscitation and persistence, which accounted for 81.5% and 93.0% of the total number of pathways, respectively, MtrA regulatory genes were identified not only in 73.6% of their mutual pathways, but also in 75.4% of the pathways related to dormancy/resuscitation and persistence respectively. These results suggested the pivotal roles of MtrA in regulating dormancy/resuscitation and the apparent relationship between dormancy/resuscitation and persistence. Furthermore, the finding that 32.6% of the MtrA regulons were essential in vivo and/or in vitro for M. tuberculosis provided new insight into its indispensability. The findings mentioned above indicated that MtrA is a novel promising therapeutic target for tuberculosis treatment since the crucial function of MtrA may be a point of weakness for M. tuberculosis. [ABSTRACT FROM AUTHOR]

With global warming, high temperature (HT) has become one of the most common abiotic stresses resulting in significant crop yield losses, especially for jujube (Ziziphus jujuba Mill.), an important temperate economic crop cultivated worldwide. This study aims to explore the coping mechanism of jujube to HT stress at the transcriptional and post-transcriptional levels, including identifying differentially expressed miRNAs and mRNAs as well as elucidating the critical pathways involved. High-throughput sequencing analyses of miRNA and mRNA were performed on jujube leaves, which were collected from "Fucumi" (heat-tolerant) and "Junzao" (heat-sensitive) cultivars subjected to HT stress (42 °C) for 0, 1, 3, 5, and 7 days, respectively. The results showed that 45 known miRNAs, 482 novel miRNAs, and 13,884 differentially expressed mRNAs (DEMs) were identified. Among them, integrated analysis of miRNA target genes prediction and mRNA-seq obtained 1306 differentially expressed miRNAs-mRNAs pairs, including 484, 769, and 865 DEMIs-DEMs pairs discovered in "Fucuimi", "Junzao" and two genotypes comparative groups, respectively. Furthermore, functional enrichment analysis of 1306 DEMs revealed that plant-pathogen interaction, starch and sucrose metabolism, spliceosome, and plant hormone signal transduction were crucial pathways in jujube leaves response to HT stress. The constructed miRNA-mRNA network, composed of 20 DEMIs and 33 DEMs, displayed significant differently expressions between these two genotypes. This study further proved the regulatory role of miRNAs in the response to HT stress in plants and will provide a theoretical foundation for the innovation and cultivation of heat-tolerant varieties. [ABSTRACT FROM AUTHOR]

Fracture healing is a complex process that involves multiple molecular events, and the regulation mechanism is not fully understood. We acquired miRNA and mRNA transcriptomes of mouse fractures from the Gene Expression Omnibus database (GSE76197 and GSE192542) and integrated the miRNAs and genes that were differentially expressed in the control and fracture groups to construct regulatory networks. There were 130 differentially expressed miRNAs and 4,819 differentially expressed genes, including 72 upregulated and 58 downregulated miRNAs, along with 2,855 upregulated and 1964 downregulated genes during early fracture healing. Gene ontology analysis revealed that most of the differentially expressed genes were enriched in the extracellular matrix (ECM) structure and the ECM organization. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested cell cycle, DNA replication, and mismatch repair were involved in the progression of fracture healing. Furthermore, we constructed a molecular network of miRNAs and mRNAs with inverse expression patterns to elucidate the molecular basis of miRNA–mRNA regulation in fractures. The regulatory network highlighted the potential targets, which may help to provide a mechanistic basis for therapies to improve fracture patient outcomes. [ABSTRACT FROM AUTHOR]

Herba Epimedii’s leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant’s therapeutic properties. This study investigated the metabolomic, transcriptomic and proteomic profiles of leaves from two Herba Epimedii cultivars, Epipremnum sagittatum (J) and Epipremnum pubescens (R), at three different developmental stages. Metabolite identification and analysis revealed a total of 1,412 and 1,421 metabolites with known structures were found. Flavonoids made up of 33%, including 10 significant accumulated icariin analogues. Transcriptomic analysis unveiled totally 41,644 differentially expressed genes (DEGs) containing five encoded genes participated in icariin biosynthesis pathways. Totally, 9,745 differentially expressed proteins (DEPs) were found, including Cluster-47248.2.p1 (UDP-glucuronosy/UDP-glucosyltransferase), Cluster-30441.2.p1 (O-glucosyltransferase), and Cluster-28344.9.p1 (anthocyanidin 3-O-glucoside 2 “-O-glucosyltransferase-like) through proteomics analysis which are involved to icariin biosynthesis. Protein-protein interaction (PPI) assay exhibited, totally 12 proteins showing a strong relationship of false discovery rate (FDR) <0.05 with these three proteins containing 2 leucine-rich repeat receptor kinase-like protein SRF7, and 5 methyl jasmonate esterase 1. Multi-omics connection networks uncovered 237 DEGs and 72 DEPs exhibited significant associations with the 10 icariin analogues. Overall, our integrated omics approach provides comprehensive insights into the regulatory network underlying icariin synthesis in Herba Epimedii, offering valuable resources for further research and development in medicinal plant cultivation and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Seed quality traits of oilseed rape, Brassica napus (B. napus), exhibit quantitative inheritance determined by its genetic makeup and the environment via the mediation of a complex genetic architecture of hundreds to thousands of genes. Thus, instead of single gene analysis, network-based systems genomics and genetics approaches that combine genotype, phenotype, and molecular phenotypes offer a promising alternative to uncover this complex genetic architecture. In the current study, systems genetics approaches were used to explore the genetic regulation of lignin traits in B. napus seeds. Four QTL (qLignin_A09_1, qLignin_A09_2, qLignin_A09_3, and qLignin_C08) distributed on two chromosomes were identified for lignin content. The qLignin_A09_2 and qLignin_C08 loci were homologous QTL from the A and C subgenomes, respectively. Genome-wide gene regulatory network analysis identified eightythree subnetworks (or modules); and three modules with 910 genes in total, were associated with lignin content, which was confirmed by network QTL analysis. eQTL (expression quantitative trait loci) analysis revealed four cis-eQTL genes including lignin and flavonoid pathway genes, cinnamoyl-CoA-reductase (CCR1), and TRANSPARENT TESTA genes TT4, TT6, TT8, as causal genes. The findings validated the power of systems genetics to identify causal regulatory networks and genes underlying complex traits. Moreover, this information may enable the research community to explore new breeding strategies, such as network selection or gene engineering, to rewire networks to develop climate resilience crops with better seed quality. [ABSTRACT FROM AUTHOR]

Flavonoids are the most abundant medicinal ingredients in Ginkgo biloba L. leaf extract (GBE), which is an important industrial raw material for the treatment of cardiovascular and cerebrovascular diseases. Our previous study found significantly higher flavonoid content in G. biloba leaves treated with UV-B for 7 days. However, the molecular mechanisms by which the miRNA-mRNA network responds to UV-B irradiation and regulates flavonoid biosynthesis remain unclear. Here, we identified 1348 differentially expressed genes (DEGs) by transcriptome sequencing of G.biloba leaves from UV-B treatment at 0 (CK) and 7 days, and 89.76% of DEG were induced by UV-B irradiation. Analysis of the flavonoid biosynthesis pathway revealed 16 differentially expressed structural genes (SGs), all of which were upregulated after UV-B treatment. Twelve DEGs were identified by analyzing transcription factors (TFs), including MYB, bHLH, and WD40, which regulate flavonoid biosynthesis, 11 of which were upregulated. Furthermore, small RNA sequencing of ginkgo leaves from control and UV-B-treated groups on days 0 and 7 revealed 58 differentially expressed miRNAs (DEMs). KEGG enrichment analysis showed that the target genes of the DEMs were significantly enriched in the flavonoid biosynthesis pathway. Finally, combined analysis of transcriptome and miRNA data identified 32 DEMs targeting 43 SGs involved in flavonoid biosynthesis, and 42 DEMs targeting 68 TFs that regulate flavonoid biosynthesis. Taken together, our findings revealed that multiple miRNA-SG and miRNA-TF networks may regulate G. biloba flavonoid biosynthesis in response to UV-B irradiation, providing new insights into the miRNA regulation of G. biloba flavonoid biosynthesis. [ABSTRACT FROM AUTHOR]

Objective: Analyzing the gene expression microarray of patients experiencing acute asthma by bioinformatics methods, in order to explore the mechanism of acute asthma and to identify early indicator of acute asthma attacks. Methods: The GSE103166 microarray dataset was retrieved from the GEO database, and after cleaning and organizing the data, differential expression analysis was conducted between children experiencing acute asthma attacks and non-asthmatic children. Enrichment analysis was performed using R language to annotate the functions of the differentially expressed genes (DEGs). Using gene interaction information, a network of interactions among these genes was constructed, and the network structure was deconstructed to identify key genes and regulatory sub-networks. Results: GSE103166 data set contained 87 nasal swab specimens from children (56 cases of acute asthma, 31 cases of control). Compared with control group, the acute asthma group had 63 differentially expressed genes (39 upregulated and 24 downregulated). The results of enrichment analysis showed that the DEGs were primarily enriched in endocytic vesicle and endocytic vesicle membrane. Among these, CD163 was the only gene significantly upregulated in both cellular components. The network dismantling analysis demonstrated four different sub-networks. CD163 was involved in sub-network Ⅰ, which was composed of CD163, ARG2, CAT, GSTA2, SCNN1G and MT2A. Among them, ARG2 and CAT were at the regulatory center of the network. Conclusion: CD163 and regulatory networks based on CD163, ARG2, CAT, GSTA2, SCNN1G and MT2A are possible the crucial factors contributing to acute asthma. This study provides research ideas for the precise and early identification of biomarkers and therapeutic targets for acute asthma attacks. [ABSTRACT FROM AUTHOR]

Myasthenia Gravis (MG) is a chronic autoimmune disease that primarily affects the neuromuscular junction, leading to muscle weakness in patients with this condition. Previous studies have identified several dysfunctions in thymus and peripheral blood mononuclear cells (PBMCs), such as the formation of ectopic germinal centers in the thymus and an imbalance of peripheral T helper cells and regulatory T cells, that contribute to the initiation and development of MG. Recent evidences suggest that noncoding RNA, including miRNA, lncRNA and circRNA may play a significant role in MG progression. Additionally, the network between these noncoding RNAs, such as the competing endogenous RNA regulatory network, has been found to be involved in MG progression. In this review, we summarized the roles of miRNA, lncRNA, and circRNA, highlighted their potential application as biomarkers in diagnosing MG, and discussed their potential regulatory networks in the abnormal thymus and PBMCs during MG development.

Abstract Background Autism spectrum disorder (ASD) is a complex neurological disability with multifactorial etiology. ASD is described by behavior, speech, language, and communication defects. CircRNA is a type of ceRNA that plays an important role in modulating microRNAs (miRNA) in several disorders. However, the potential role of the circRNA/miRNA/mRNA regulatory network in the pathogenesis of ASD is not fully understood. Therefore, this study aimed to create a circRNA/miRNA/mRNA network associated with ASD to cast light on the pathogenesis of ASD. Methods CircRNA expression profile data were recruited from Gene Expression Omnibus datasets, and the differentially expressed circRNAs (DEcircRNAs) were identified. Then, miRNAs modulated by these circRNAs were predicted and overlapped with differentially expressed miRNAs. Next, the potentially involved genes were identified by overlapping predicted targets, and differentially expressed genes. The enrichment analysis was performed, and a PPI network was projected. Subsequently, ten key genes were selected from the network. Furthermore, a circRNA/miRNA/mRNA regulatory network was constructed, and probable molecules and drugs with potential anti-ASD effects were predicted. Results 11 DEcircRNAs and 8 miRNAs regulated by 4 circRNAs were identified as being significantly involved. Subsequently, gene enrichment analysis of 71 overlapped mRNA regulated by these miRNAs showed that they are mostly associated with hippocampal synaptogenesis, neurogenesis, and axon guidance. Additionally, two high-score compounds, GSK3β inhibitor (SB216763) and dexamethasone, and three drugs (haloperidol, nystatin, paroxetine) were confirmed as potential therapeutic options for ASD. Conclusion The results of this study may help gain deeper insight into the pathogenesis of the circRNA/miRNA/mRNA regulatory network in ASD, providing potential therapeutic management options.

Liangwen Chen,1,2,&ast; Ziqiao Tang,1,&ast; Liangliang Fu,1 Yang Xie,1 Junyi Xu,1 Haibin Xia,1,3 Ting Xia,3 Min Wang1,3 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 2Center for Prosthodontics and Implant Dentistry, Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 3Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Xia; Min Wang, Department of Dental Implantology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, Hubei Province, 430079, People’s Republic of China, Email tingzi90s@whu.edu.cn; 83wangmin@whu.edu.cnBackground: Peri-implantitis (PI) is a prevalent complication of implant treatment. Pyroptosis, a distinctive inflammatory programmed cell death, is crucial to the pathophysiology of PI. Despite its importance, the pyroptosis-related genes (PRGs) influencing PI’s progression remain largely unexplored.Methods: This study conducted histological staining and transcriptome analyze from three datasets. The intersection of differentially expressed genes (DEGs) and PRGs was identified as pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment analyses were conducted to shed light on potential underlying mechanisms. Weighted Gene Co-expression Network Analysis (WGCNA) and a pyroptotic macrophage model were utilized to identify and validate hub PRDEGs. Immune cell infiltration in PI and its relationship with hub PRDEGs were also examined. Furthermore, consensus clustering was performed to identify new PI subtypes. Protein-protein interaction (PPI) network, competing endogenous RNA (ceRNA) network, mRNA-mRNA binding protein regulatory (RBP) network, and mRNA-drugs regulatory network of hub PRDEGs were also analyzed.Results: Eight hub PRDEGs were identified: PGF, DPEP1, IL36B, IFIH1, TCEA3, RIPK3, NET7, and TLR3, which are instrumental in the PI’s progression. Two PI subtypes were distinguished, with Cluster 1 exhibiting higher immune cell activation. The exploration of regulatory networks provided novel mechanisms and therapeutic targets in PI.Conclusion: Our research highlights the critical role of pyroptosis and identifies eight hub PRDEGs in PI’s progression, offering insights into novel immunotherapy targets and laying the foundation for advanced diagnostic and treatment strategies. This contributes to our understanding of PI and underscores the potential for personalized clinical management.Keywords: peri-implantitis, pyroptosis, consensus clustering, immune cell infiltration, regulatory network

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb), which threatens human health and safety all over the world. Hundreds of thousands of people die from TB every year. Timely early diagnosis and treatment of patients is the most important measure to control the source of infection and curb the epidemic of tuberculosis. The existing diagnostic methods have the disadvantages of poor sensitivity and long culture time. Competitive endogenous RNAs (ceRNAs) can regulate the expression of corresponding target genes by competing for the same microRNA (miRNA) response elements (MREs) as mRNA. Recent studies have found that circRNA has the advantages of long half-life, good stability and tissue specificity, and can be used as a biomarker for predicting, diagnosing and treating various diseases, and is an ideal candidate for biomarkers in body fluid biopsy. In this study, transcriptome sequencing was performed on whole blood samples to screen out TB-related mirna and mRNA differential expression, and to construct the ceRNA regulatory network. Through the analysis of ceRNA regulatory network, it was found that circRNA could competitively bind has-miR-607 and induce down-regulation of has-miR-607, thereby inhibiting the expression of IFNG. The hsa_circ_0000566, hsa_circ_0001844, hsa_circ_0005408, hsa_circ_0007587, hsa_circ_0086710, IFNG and has-miR-607 couble be used as new diagnostic targets for TB. The results of this study not only provide a new perspective for studying the potential role of ceRNA regulatory network in tuberculosis, but also provide a new target and method for the diagnosis of tuberculosis.

There is a growing demand for wood as a sustainable energy source and an essential carbon sink for ecosystems. Wood formation is a dynamic process involving plant radial growth in various stages, including vascular cambial cell proliferation, xylem mother cell differentiation and expansion, secondary cell wall thickening, and programmed cell death. Wood formation is controlled by highly complex molecular regulatory networks. Identifying and analyzing the molecular mechanisms regulating key target genes is crucial for further characterizing how wood is formed. This article summarizes the current knowledge regarding wood formation and the underlying molecular regulatory mechanisms.

In this study, oxidative stress-related genes (OSRGs) were used to discover membranous nephropathy (MN) genes, evaluate their biological activities and molecular pathways, and develop regulatory networks for drugs, miRNAs and transcription factors. All 862 differentially expressed genes (DEGs) in the GSE108113 dataset were evaluated using the gene expression matrix. Cross-testing of 437 OSRg in the gene cards revealed 28 DE-OSRG genes. We performed the KEGG and gene ontology enrichment studies. Response to reactive oxygen species, chemical stress, oxidative stress, bound globin-hemoglobin complex, endocytic vesicle lumen, blood microparticles, conjugated globin binding, peroxidase activity and heme binding are the major GO-enriched active DE-OSRGs. As in the KEGG pathway study. After excluding the disconnected genes, 19 DE-OSRGs were introduced into the PPI network, and the top five CDE-OSRGs were found: G6PD, HBB, TP 53, KEAP 1, and PXDN. The ROC curve study shows the CDE-OS.

Genotype-fitness maps of evolution have been well characterized for biological components, such as RNA and proteins, but remain less clear for systems-level properties, such as those of metabolic and transcriptional regulatory networks. Here, we take multi-omics measurements of 6 different E. coli strains throughout adaptive laboratory evolution (ALE) to maximal growth fitness. The results show the following: (i) convergence in most overall phenotypic measures across all strains, with the notable exception of divergence in NADPH production mechanisms; (ii) conserved transcriptomic adaptations, describing increased expression of growth promoting genes but decreased expression of stress response and structural components; (iii) four groups of regulatory trade-offs underlying the adjustment of transcriptome composition; and (iv) correlates that link causal mutations to systems-level adaptations, including mutation-pathway flux correlates and mutation-transcriptome composition correlates. We thus show that fitness landscapes for ALE can be described with two layers of causation: one based on system-level properties (continuous variables) and the other based on mutations (discrete variables). IMPORTANCE Understanding the mechanisms of microbial adaptation will help combat the evolution of drug-resistant microbes and enable predictive genome design. Although experimental evolution allows us to identify the causal mutations underlying microbial adaptation, it remains unclear how causal mutations enable increased fitness and is often explained in terms of individual components (i.e., enzyme rate) as opposed to biological systems (i.e., pathways). Here, we find that causal mutations in E. coli are linked to systems-level changes in NADPH balance and expression of stress response genes. These systems-level adaptation patterns are conserved across diverse E. coli strains and thus identify cofactor balance and proteome reallocation as dominant constraints governing microbial adaptation.

Nitrogen is one of the important factors restricting the development of sesame planting and industry in China. Cultivating sesame varieties tolerant to low nitrogen is an effective way to solve the problem of crop nitrogen deficiency. To date, the mechanism of low nitrogen tolerance in sesame has not been elucidated at the transcriptional level. In this study, two sesame varieties Zhengzhi HL05 (ZZ, nitrogen efficient) and Burmese prolific (MD, nitrogen inefficient) in low nitrogen were used for RNA-sequencing. A total of 3964 DEGs (differentially expressed genes) and 221 DELs (differentially expressed lncRNAs) were identified in two sesame varieties at 3d and 9d after low nitrogen stress. Among them, 1227 genes related to low nitrogen tolerance are mainly located in amino acid metabolism, starch and sucrose metabolism and secondary metabolism, and participate in the process of transporter activity and antioxidant activity. In addition, a total of 209 pairs of lncRNA-mRNA were detected, including 21 pairs of trans and 188 cis. WGCNA (weighted gene co-expression network analysis) analysis divided the obtained genes into 29 modules; phenotypic association analysis identified three low-nitrogen response modules; through lncRNA-mRNA co-expression network, a number of hub genes and cis/trans-regulatory factors were identified in response to low-nitrogen stress including GS1-2 (glutamine synthetase 1–2), PAL (phenylalanine ammonia-lyase), CHS (chalcone synthase, CHS), CAB21 (chlorophyll a-b binding protein 21) and transcription factors MYB54, MYB88 and NAC75 and so on. As a trans regulator, lncRNA MSTRG.13854.1 affects the expression of some genes related to low nitrogen response by regulating the expression of MYB54, thus responding to low nitrogen stress. Our research is the first to provide a more comprehensive understanding of DEGs involved in the low nitrogen stress of sesame at the transcriptome level. These results may reveal insights into the molecular mechanisms of low nitrogen tolerance in sesame and provide diverse genetic resources involved in low nitrogen tolerance research. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a complex neurological disability with multifactorial etiology. ASD is described by behavior, speech, language, and communication defects. CircRNA is a type of ceRNA that plays an important role in modulating microRNAs (miRNA) in several disorders. However, the potential role of the circRNA/miRNA/mRNA regulatory network in the pathogenesis of ASD is not fully understood. Therefore, this study aimed to create a circRNA/miRNA/mRNA network associated with ASD to cast light on the pathogenesis of ASD. Methods: CircRNA expression profile data were recruited from Gene Expression Omnibus datasets, and the differentially expressed circRNAs (DEcircRNAs) were identified. Then, miRNAs modulated by these circRNAs were predicted and overlapped with differentially expressed miRNAs. Next, the potentially involved genes were identified by overlapping predicted targets, and differentially expressed genes. The enrichment analysis was performed, and a PPI network was projected. Subsequently, ten key genes were selected from the network. Furthermore, a circRNA/miRNA/mRNA regulatory network was constructed, and probable molecules and drugs with potential anti-ASD effects were predicted. Results: 11 DEcircRNAs and 8 miRNAs regulated by 4 circRNAs were identified as being significantly involved. Subsequently, gene enrichment analysis of 71 overlapped mRNA regulated by these miRNAs showed that they are mostly associated with hippocampal synaptogenesis, neurogenesis, and axon guidance. Additionally, two high-score compounds, GSK3β inhibitor (SB216763) and dexamethasone, and three drugs (haloperidol, nystatin, paroxetine) were confirmed as potential therapeutic options for ASD. Conclusion: The results of this study may help gain deeper insight into the pathogenesis of the circRNA/miRNA/mRNA regulatory network in ASD, providing potential therapeutic management options. [ABSTRACT FROM AUTHOR]

Main conclusion: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron. [ABSTRACT FROM AUTHOR]

This article is an editorial discussing the importance of transcriptomic analysis in understanding fruit growth, development, and ripening. It provides examples of transcriptomic studies conducted on various plant species, highlighting the diversity of fruits in terms of form, size, texture, color, flavor, and aroma. The document also includes a research topic with nine articles that delve into different aspects of fruit transcriptomics, such as gene expression during different stages of development and ripening, the effects of domestication on gene expression, and the analysis of specific gene families. Additionally, there are lists of scientific research articles and references related to transcriptome analysis and the molecular mechanisms underlying fruit development and ripening in various fruit species. These resources can be valuable for researchers studying fruit biology and agriculture. [Extracted from the article]

Background: This study investigated the molecular mechanisms of long non-coding RNAs (lncRNAs) in RSA using the lncRNA–miRNA–mRNA regulatory network. Methods: The present study obtained expression datasets of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) from blood samples of individuals with unexplained recurrent spontaneous abortion (RSA) and healthy controls. Differentially expressed lncRNAs (DELs), mRNAs (DEMs), and miRNAs (DEmiRs) were identified. A regulatory network comprising lncRNA, miRNA, and mRNA was constructed, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEM. Also, a protein–protein interaction (PPI) network was made and key genes were identified. Results: A total of 57 DELs, 212 DEmiRs, and 301 DEMs regarding RSA were identified. Later analysis revealed a lncRNA–miRNA–mRNA network comprising nine lncRNAs, 14 miRNAs, and 65 mRNAs. Then, the ceRNA network genes were subjected to functional enrichment and pathway analysis, which showed their association with various processes, such as cortisol and thyroid hormone synthesis and secretion, human cytomegalovirus infection, and parathyroid hormone synthesis. In addition, ten hub genes (ITGB3, GNAI2, GNAS, SRC, PLEC, CDC42, RHOA, RAC1, CTNND1, and FN1) were identified based on the PPI network results. Conclusion: In summary, the outcomes of our study provided some data regarding the alteration genes involved in RSA pathogenic mechanism via the lncRNA–miRNA–mRNA network and reveal the possibility of identifying new lncRNAs and miRNAs as promising molecular biomarkers. [ABSTRACT FROM AUTHOR]

Members of the abscisic acid (ABA)-responsive element (ABRE) binding factor (ABF) and ABA-responsive element binding protein (AREB) families play essential roles in the regulation of ABA signaling pathway activity and shape the ability of plants to adapt to a range of stressful environmental conditions. To date, however, systematic genome-wide analyses focused on the ABF/AREB gene family in wheat are lacking. Here, we identified 35 ABF/AREB genes in the wheat genome, designated TaABF1–TaABF35 according to their chromosomal distribution. These genes were further classified, based on their phylogenetic relationships, into three groups (A–C), with the TaABF genes in a given group exhibiting similar motifs and similar numbers of introns/exons. Cis-element analyses of the promoter regions upstream of these TaABFs revealed large numbers of ABREs, with the other predominant elements that were identified differing across these three groups. Patterns of TaABF gene expansion were primarily characterized by allopolyploidization and fragment duplication, with purifying selection having played a significant role in the evolution of this gene family. Further expression profiling indicated that the majority of the TaABF genes from groups A and B were highly expressed in various tissues and upregulated following abiotic stress exposure such as drought, low temperature, low nitrogen, etc., while some of the TaABF genes in group C were specifically expressed in grain tissues. Regulatory network analyses revealed that four of the group A TaABFs (TaABF2, TaABF7, TaABF13, and TaABF19) were centrally located in protein–protein interaction networks, with 13 of these TaABF genes being regulated by 11 known miRNAs, which play important roles in abiotic stress resistance such as drought and salt stress. The two primary upstream transcription factor types found to regulate TaABF gene expression were BBR/BPC and ERF, which have previously been reported to be important in the context of plant abiotic stress responses. Together, these results offer insight into the role that the ABF/AREB genes play in the responses of wheat to abiotic stressors, providing a robust foundation for future functional studies of these genes. [ABSTRACT FROM AUTHOR]

Aims: The aim of this review is to systematically summarize and analyze the noncoding RNAs (ncRNAs), especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the cell apoptosis among Alzheimer's disease (AD) in recent years to demonstrate their value in the diagnosis and treatment of AD. Methods: We systematically summarized in vitro and in vivo studies focusing on the ncRNAs in the regulation of cell apoptosis among AD in PubMed, ScienceDirect, and Google Scholar. Results: We discover three patterns of ncRNAs (including 'miRNA‐mRNA', 'lncRNA‐miRNA‐mRNA', and 'circRNA‐miRNA‐mRNA') form the ncRNA‐based regulatory networks in regulating cell apoptosis in AD. Conclusions: This review provides a future diagnosis and treatment strategy for AD patients based on ncRNAs. [ABSTRACT FROM AUTHOR]

Non-coding RNA (ncRNA) plays a vital part in the regulation of immune responses, growth, and development in plants and animals. Here, the identification, characteristic analysis, and molecular verification of circRNAs in Apis cerana cerana worker larval guts were conducted, followed by in-depth investigation of the expression pattern of larval circRNAs during Ascosphaera apis infection and exploration of the potential regulatory part of differentially expressed circRNAs (DEcircRNAs) in host immune responses. A total of 3178 circRNAs in the larval guts of A. c. cerana were identified, with a length distribution ranging from 15 to 96,007 nt. Additionally, 155, 95, and 86 DEcircRNAs were identified in the in the 4-, 5-, and 6-day-old larval guts following A. apis infection. These DEcircRNAs were predicted to target 29, 25, and 18 parental genes relevant to 12, 20, and 17 GO terms as well as 144, 114, and 61 KEGG pathways, including 5 cellular and 4 humoral immune pathways. Complex competing endogenous RNA (ceRNA) regulatory networks were detected as being formed among DEcircRNAs, DEmiRNAs, and DEmRNAs. The target DEmRNAs were engaged in 36, 47, and 47 GO terms as well as 331, 332, and 331 pathways, including 6 cellular and 6 humoral immune pathways. Further, 19 DEcircRNAs, 5 DEmiRNAs, and 3 mRNAs were included in the sub-networks relative to 3 antioxidant enzymes. Finally, back-splicing sites within 15 circRNAs and the difference in the 15 DEcircRNAs' expression between uninoculated and A. apis–inoculated larval guts were confirmed based on molecular methods. These findings not only enrich our understanding of bee host–fungal pathogen interactions but also lay a foundation for illuminating the mechanism underlying the DEcircRNA-mediated immune defense of A. c. cerana larvae against A. apis invasion. Key points: • The expression pattern of circRNAs was altered in the A. cerana worker larval guts following A. apis infection. • Back-splicing sites within 15 A. cerana circRNAs were verified using molecular approaches. DEcircRNAs potentially modulated immune responses and antioxidant enzymes in A. apis–challenged host guts. [ABSTRACT FROM AUTHOR]

Iron is an essential trace element in the human body. However, excess iron is harmful and may cause ferroptosis. The expression and role of microRNAs (miRNAs) in ferroptosis remain largely unknown. A model of ferroptosis induced by ferric ammonium citrate in HT-1080 cells was established in this study. The miRNAs expression profiles of the control and iron groups were obtained using small RNA sequencing and verified using qRT-PCR. A total of 1346 known miRNAs and 80 novel miRNAs were identified, including 12 up-regulated differentially expressed miRNAs (DE-miRNAs) and 16 down-regulated DE-miRNAs. SP1 was the most important upstream transcription factor regulating DE-miRNAs. The downstream target genes of DE-miRNAs were predicted based on miRDB, TargetScan, and miRBase databases, and 403 common target genes were screened. GO annotation and KEGG analysis revealed that the target genes were mainly involved in various biological processes and regulatory pathways, especially the MAPK signaling pathway and PI3K-Akt signaling pathway. Afterwards, a target genes network was constructed using STRING and Cytoscape, and the hub genes were compared with the ferroptosis database (FerrDb V2) to discover the hub genes related to ferroptosis. EGFR, GSK3B, PARP1, VCP, and SNCA were screened out. Furthermore, a DE-miRNAs-target genes network was constructed to explore key DE-miRNAs. hsa-miR-200c-3p, hsa-miR-26b-5p, and hsa-miR-7-5p were filtered out. Comprehensive bioinformatics analysis of miRNAs and its upstream and downstream regulation in ferroptosis in HT-1080 cells using small RNA sequencing is helpful for understanding the role of miRNAs in iron overload-related diseases and ferroptosis-targeted therapy for cancer. [ABSTRACT FROM AUTHOR]

Symbiotic nitrogen fixation (SNF) by rhizobia is not only the main natural bionitrogen-source for organisms but also a green process leveraged to increase the fertility of soil for agricultural production. However, an insufficient understanding of the regulatory mechanism of SNF hinders its practical application. During SNF, nifA -fixA signaling is essential for the biosynthesis of nitrogenases and electron transfer chain proteins. In the present study, the TetR regulator NffT, whose mutation increased fixA expression, was discovered through a fixA-promoter-β-glucuronidase fusion assay performed with Rhizobium johnstonii. Real-time quantitative PCR analysis showed that nffT deletion increased the expression of symbiotic genes including nifA and fixA in nifA-fixA signaling, and fixL, fixK, fnrN, and fixN9 in fixL-fixN signaling. nffT overexpression resulted in disordered nodules and reduced nitrogen-fixing efficiency. Electrophoretic mobility shift assays revealed that NffT directly regulated the transcription of RL0091–93, which encode an ATP-binding ABC transporter predicted to be involved in carbohydrate transport. Purified His-tagged NffT bound to a 68 bp DNA sequence located −32 to −99 bp upstream of RL0091–93 and NffT deletion significantly increased the expression of RL0091–93. nffT-promoter-β-glucuronidase fusion assay indicated that nffT expression was regulated by the cobNTS genes and cobalamin. Mutations in cobNTS significantly decreased the expression of nffT, and cobalamin restored its expression. These results revealed that NffT affects nodule development and nitrogen-fixing reaction by participating in a complex regulatory network of symbiotic and carbohydrate metabolic genes and, thus, plays a pivotal regulatory role during symbiosis of R. johnstonii-Pisum sativum. IMPORTANCE Symbiotic nitrogen fixation (SNF) by rhizobia is a green way to maintain soil fertility without causing environmental pollution or consuming chemical energy. A detailed understanding of the regulatory mechanism of this complex process is essential for promoting sustainable agriculture. In this study, we discovered the TetR-type regulator NffT, which suppressed the expression of fixA in Rhizobium johnstonii. Furthermore, NffT was confirmed to play pleiotropic roles in R. johnstonii-Pisum sativum symbiosis; specifically, it inhibited rhizobial growth, nodule differentiation, and nitrogen-fixing reactions. We revealed that NffT indirectly affected R. johnstonii-P. sativum symbiosis by participating in a complex regulatory network of symbiotic and carbohydrate metabolic genes. Furthermore, cobalamin, a chemical molecule, was reported for the first time to be involved in TetR-type protein transcription during symbiosis. Thus, NffT identification connects SNF regulation with genetic, metabolic, and chemical signals and provides new insights into the complex regulation of SNF, laying an experimental basis for the targeted construction of rhizobial strains with highly efficient nitrogen-fixing capacity. [ABSTRACT FROM AUTHOR]