Regulatory Factors Research Articles

The effect of miR-205a with RUNX2 towards proliferation and differentiation of chicken chondrocytes in thiram-induced tibial dyschondroplasia

Tibial dyschondroplasia (TD) is a kind of metabolic bone disease in fast-growing broilers, which seriously restricts the development of poultry industry. Our previous studies have revealed a significant upregulation of miR-205a in TD cartilage tissue, suggesting its potential role as a regulatory factor in the pathogenesis of TD. However, the precise function implications and underlying regulatory mechanism remain elusive. Therefore, this study aims to elucidate the biological functions and regulatory mechanisms of miR-205a in the progression of TD by employing mehtodologies such as qRT-PCR, CCK-8 assay, EdU assays, and flow cytometry. The findings demonstrated that the transfection of miR-205a overexpression plasmid reduced chondrocytes growth and development in TD while enhancing apoptosis; conversely, blocking miR-205a had opposite effects. RUNX2 was identified as a target gene of miR-205a through biosynthesis and dual luciferase assays, and its overexpression helps chondrocytes in TD grow and develop. However, when both miR-205a and RUNX2 were overexpressed, the regulatory effect of RUNX2 was significantly suppressed. In conclusion, miR-205a plays a role in slowing the growth and development of chondrocytes in TD by targeting and reducing RUNX2 expression, which helps to initiate and progress TD.

Esculetin improves inflammation of the kidney via gene expression against doxorubicin-induced nephrotoxicity in rats: In vivo and in silico studies

Examining the preventive potential and underlying mechanisms of Esculetin (E) in mitigating kidney damage induced by doxorubicin (DOX) in rats, this study also assessed the nephrotoxic effects when DOX was administered in combination with E. The experimental protocol involved a two-week treatment period with cumulative DOX doses (5 mg/kg), daily administration of E (50 mg/kg and 100 mg/kg), and the combined treatment of DOX with E50 and E100. The study delved into the gene expression levels of key regulatory factors associated with inflammation and apoptosis. Molecular analyses revealed that E effectively ameliorated the dysregulations induced by DOX at gene levels in the kidneys. Notably, the concurrent administration of E was observed to counteract the alterations in gene expressions induced by DOX significantly. E treatment decreased serum creatinine, albumin, and urea nitrogen levels in DOX-induced kidney damage. Furthermore, the docking analysis revealed that pi–cation, pi–pi stacking, and hydrogen bond interactions were the predominant molecular interactions within the binding pockets of these genes. This suggests that the nephroprotection provided by E involves the remodeling of inflammation and apoptosis pathways affected by DOX.

AmTPS6 promotes trehalose biosynthesis to enhance the Cd tolerance in mangrove Avicennia marina

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd2+ influx from the root to reduce the Cd2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands.

Comprehensive identification of PIN and PILS in crape myrtle genomes reveals their putative functions in bud-to-branch development and callus generation

Polar auxin transport in plants is facilitated by influx and efflux transporters encoded by PIN-FORMED (PIN) and PIN-like (PILS) genes, respectively. While the auxin transporter gene families have been extensively studied in various monocot and dicot species, a comprehensive genome-wide analysis of PIN and PILS gene families in Lagerstroemia indica is currently lacking. In this study, we identified 22 LiPIN and LiPILS genes in L. indica genome, distributed across 17 chromosomes. Gene structure and conserved motif analyses revealed relative conservation within the same group. Additionally, we identified 16 syntenic gene pairs in LiPIN and LiPILS genes, with Ka/Ks values below 1 indicating purifying selection during evolutionary processes. Expression profiling indicated that several genes, notably LiPIN3a and LiPILS5b/6a/6b/6c, responded to salt stress. LiPIN1d, LiPIN5, and LiPILS3a were potentially linked to bud-to-branch development in L. indica. Moreover, the expression levels of LiPILS3a and LiPILS5a exhibited significant differences during the callus formation process, indicating their potential as key regulatory factors in this developmental stage. These findings offered new insights into auxin transporter genes in L. indica and enhanced our understanding of their roles in stress tolerance, growth, and development.

IRF4: A potential prognostic biomarker for immunotherapy in NSCLC

BackgroundImmunotherapy is revolutionizing the management of advanced non-small cell lung cancer (NSCLC). However, sustained responses are observed in only a minority of patients. Reliable biomarkers are required to identify potential beneficiaries. Interferon regulatory factor 4 (IRF4) plays a crucial role in immune regulation, suggesting its potential as a prognostic biomarker in NSCLC immunotherapy. This study aimed to investigate the predictive role of IRF4 expression in patients with NSCLC receiving immunotherapy. MethodsData from three NSCLC cohorts treated with immune checkpoint inhibitors were collected from the Gene Expression Omnibus (GEO) database. The prognostic significance of IRF4 was assessed across these cohorts, and gene set enrichment analysis (GSEA) was performed. IRF4-based nomograms were developed to predict the outcomes of immunotherapy. Correlations among IRF4 expression, immune cell infiltration, and immunotherapy prognosis were evaluated in our cohort. ResultsElevated IRF4 expression was associated with improved prognosis in patients with NSCLC undergoing immunotherapy, consistent with both GEO dataset and our cohort. IRF4 emerged as an independent predictor for progression-free survival (PFS) and overall survival (OS) in multivariable Cox regression analysis. GSEA analysis highlighted links between IRF4 expression and immune activation pathways such as Chemokine_Signaling_Pathway, Natural_Killer_Cell_Mediated_Cytotoxicity, B_Cell_Receptor_Signaling_Pathway, and T_Cell_Receptor_Signaling_Pathway. In our cohort, immunohistochemistry demonstrated correlations between IRF4 expression and the infiltration of CD8+ T cells, CD20+ B cells, and PD-L1 expression in the tumor microenvironment. ConclusionHigh IRF4 expression in baseline tumor tissue could serve as a favorable predictor of NSCLC immunotherapy outcomes, aiding in personalized treatment strategies.

AhGSNOR1 negatively regulates Al-induced programmed cell death by regulating intracellular NO and redox levels

The toxicity of aluminum (Al) in acidic soil inhibits plant development and reduces crop yields. Programmed cell death (PCD) is one of the important mechanisms in the plant response to Al toxicity. However, it is yet unknown if S-nitrosoglutathione reductase (GSNOR) provides Al-PCD. Here, transcription and protein expression of AhGSNOR1 were both induced by Al stress. AhGSNOR1-overexpressing transgenic tobacco plants reduced Al-induced nitric oxide (NO) and S-nitrosothiol accumulation, the inhibitory effect of Al stress on root elongation and the degree of cell death, and enhanced antioxidant enzyme activity to effectively remove hydrogen peroxide. In addition, AhGSNOR1 directly interacted with AhTRXh in vivo. Expression of Trxh3 in AhGSNOR1-overexpressing transgenic plants was significantly upregulated, indicating that AhGSNOR1 positively regulated the transcriptional level of Trxh3. Together, these results suggested that AhGSNOR1 was a negative regulatory factor of Al-induced PCD and improved plant Al-tolerance by modulating intracellular NO and redox homeostasis.

Vibrio cholerae CsrA controls ToxR levels by increasing the stability and translation of toxR mRNA

ABSTRACT Intestinal colonization and virulence factor production in response to environmental cues is mediated through several regulatory factors in Vibrio cholerae , including the highly conserved RNA-binding global regulatory protein CsrA. We have shown previously that CsrA increases synthesis of the virulence-associated transcription factor ToxR in response to specific amino acids (NRES) and is required for the virulence of V. cholerae in the infant mouse model of cholera. In this study, we mapped the 5′ untranslated region (5′ UTR) of toxR and showed that CsrA can bind directly to an RNA sequence encompassing the 5′ UTR, indicating that the regulation of ToxR levels by CsrA is direct. Consistent with this observation, the 5′ UTR of toxR contains multiple putative CsrA binding sequences (GGA motifs), and mutating these motifs disrupted the CsrA-mediated increase in ToxR. Optimal binding of CsrA to a defined RNA oligonucleotide required the bridging of two GGA motifs within a single RNA strand. To determine the mechanism of regulation by CsrA, we assayed toxR transcript levels, stability, and efficiency of translation. Both the amount of toxR mRNA in NRES and the stability of the toxR transcript were increased by CsrA. Using an in vitro translation assay, we further showed that synthesis of ToxR was greatly enhanced in the presence of purified CsrA, suggesting a direct role for CsrA in the translation of toxR mRNA. We propose a model in which CsrA binding to the 5′ UTR of the toxR transcript promotes ribosomal access while precluding interactions with RNA-degrading enzymes. IMPORTANCE Vibrio cholerae is uniquely adapted to marine environments as well as the human intestinal tract. Global regulators, such as CsrA, which help translate environmental cues into an appropriate cellular response, are critical for switching between these distinct environments. Understanding the pathways involved in relaying environmental signals is essential for understanding both the environmental persistence and the intestinal pathogenesis of this devastating human pathogen. In this study, we demonstrate that CsrA directly regulates the synthesis of ToxR, a key virulence factor of V. cholerae . Under conditions favoring high levels of active CsrA in the cell, such as in the presence of particular amino acids, CsrA increases ToxR protein levels by binding to the toxR transcript and enhancing both its stability and translation. By responding to nutrient availability, CsrA is perfectly poised to activate the virulence gene regulatory cascade at the preferred site of colonization in the human host, the nutrient-rich small intestinal mucosa.

Abstract A004: E2F5 conditional knockout in mammary epithelium drives organotropic metastasis in breast cancer

Abstract Breast cancer ranks as the most commonly diagnosed cancer in women with 90% of associated deaths caused by distant metastasis. The metastatic lesions in brain, lung, liver, bone and lymph nodes in human breast cancer are not arbitrary, but rather are a complex mechanism of extrinsic and intrinsic regulatory factors controlling organ-specific colonization. Specialized mechanisms driving bone, brain and lung cancer have been described. However, the studies of liver and lymph node metastatic drivers are limited despite the prevalence of metastases in these organs. A significant limitation is the lack of genetically engineered mouse models that develop mammary tumors that spontaneously metastasize to liver and lymph nodes. Our previous research identified the role for E2F5 in both mammary gland development and breast cancer. Loss of E2F5 resulted in tumorigenesis after a latency of one year and 70% of mice showed metastatic lesions in lung, lymph node and liver. Transplantation of these spontaneous tumors into FVB MMTV Cre mice recapitulated the metastatic pattern observed in the primary tumors. We propose that E2F5 regulates drivers of metastasis and potentiates organ tropism to lymph nodes and the liver. To address this hypothesis, we conducted serial transplantations of tumors originating from the lymph nodes and liver back into the mammary gland. This enrichment study led to a significant increase in organ-specific metastasis, with 60% and 77% of penetrance observed in two distinct mouse lineages with liver (LVM) and lymph node tropism (LNM). Immunohistochemical studies confirmed a complete epithelial-mesenchymal transition (EMT) phenotype in LVM that is conserved in the cell lines generated. LNM showed a partial EMT with a more epithelial phenotype in cell lines. We observed the presence of an immune enriched environment in primary and metastatic tumors in both lineages. Bulk-RNA sequencing studies uncovered the presence of unique organotropic pathways associated with liver and lymph node metastasis. We observed enriched pathways from the primary tumor as major component of our organotropic drivers with a clear distinction between liver and lymph node enriched lineages. Additionally, a gradual acquisition of distant organ-specific markers and signaling pathways suggests that phenotypic mimicry and tumor plasticity are key for successful events of colonization to liver and lymph nodes in our model. With these results, we unravel potential mechanisms responsible for the organotropic metastases in breast cancer under the absence of the transcription factor E2F5. Citation Format: Jesus A. Garcia Lerena, Briana To, Jing-Ru Jhan, Eran Andrechek. E2F5 conditional knockout in mammary epithelium drives organotropic metastasis in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A004.

The effects of PstR, a PadR family transcriptional regulatory factor, in Plesiomonas shigelloides are revealed by transcriptomics.

Plesiomonas shigelloides is a gram-negative opportunistic pathogen associated with gastrointestinal and extraintestinal diseases in humans. There have been reports of specific functional genes in the study of P. shigelloides, but there are also many unknown genes that may play a role in P. shigelloides pathogenesis as global regulatory proteins or virulence factors. In this study, we found a transcriptional regulator of the PadR family in P. shigelloides and named it PstR (GenBank accession number: EON87311.1), which is present in various pathogenic bacteria but whose function has rarely been reported. RNA sequencing (RNA-Seq) was used to analyze the effects of PstR on P. shigelloides, and the results indicated that PstR regulates approximately 9.83% of the transcriptome, which includes impacts on motility, virulence, and physiological metabolism. RNA-seq results showed that PstR positively regulated the expression of the flagella gene cluster, which was also confirmed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Luminescence screening assay. Meanwhile, the ΔpstR mutant strains lacked flagella and were non-motile, as confirmed by motility assays and transmission electron microscopy (TEM). Additionally, PstR also positively regulates T3SS expression, which aids in P. shigelloides' capacity to infect Caco-2 cells. Meanwhile, we also revealed that PstR negatively regulates fatty acid degradation and metabolism, as well as the regulatory relationship between PsrA, a regulator of fatty acid degradation and metabolism, and its downstream genes in P. shigelloides. Overall, we revealed the effects of PstR on motility, virulence, and physiological metabolism in P. shigelloides, which will serve as a foundation for future research into the intricate regulatory network of PstR in bacteria.

Analysis of single-cell RNA sequencing in human oocytes with diminished ovarian reserve uncovers mitochondrial dysregulation and translation deficiency.

Diminished ovarian reserve (DOR) is clinically characterized by a decrease in the number of available ovarian follicles and a decline in the quality of oocytes, accompanied by hormonal changes. Low quality of DOR oocyte leads to impaired embryo development, an increased risk of aneuploid pregnancies and miscarriages. However, the specific pathogenic mechanism remains unclear, posing a significant challenge for assisted reproductive technology. For the first time, our study employed single-cell RNA sequencing to reveal the altered transcriptomic landscape of DOR oocytes at GV stage after ovarian stimulation. Differentially expressed genes analysis (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interactions network analysis were performed. We found 132 up-regulated genes and 466 down-regulated genes in DOR oocytes, with the down-regulated genes primarily enriched in mitochondrial function and translation. Hub genes, identified through integrated analysis of WGCNA and DEGs, were further validated in DOR and control oocytes using RT-qPCR. By utilizing hub genes and employing transcription factor enrichment tools, it had been predicted that pleomorphic adenoma gene 1 (PLAG1) played a crucial role as a transcriptional regulatory factor in DOR oocytes. Additionally, we conformed the PLAG1-IGF2 axis was dysregulated in DOR oocytes. Transcriptome analysis revealed that DOR oocytes exhibited mitochondrial dysfunction and translational defects, and the PLAG1-IGF2 axis might be a potential contributor for the low quality of DOR oocytes.

Spore-Forming Clostridia in Raw Cow Milk from Northern Italy: A Trend Analysis over the Past 20 Years

Clostridium species are known for their impact on animal and human health, but also for the spoilage of foodstuffs. Their spores contaminate milk and result in germination and gas production, the latter being particularly evident in the cheeses that suffer severe depreciation. To address this issue, the Primary Production Department of the IZSLER institute in Brescia, Italy conducts the Most Probable Number (MPN) method on bovine milk samples collected from Northern Italian dairies between 2004 and 2023. This approach leverages two semi-quantitative protocols, S2 and S3, to detect Clostridium species spore forms upon customer request. Here, we would like to present an a-posteriori analysis on the results of the S2 and S3 protocols. The goal of this study is to highlight the differences between these two methods and provide evidence of the actual decrease in Clostridium species in raw cow milk over a 20-year period. Our analysis shows that client demand for S2 has progressively decreased, while S3’s has remained constant, and both protocols reveal a significant reduction in positives; furthermore, S3’s greater sensitivity made it more responsive to environmental changes. This highlights the necessity of choosing the appropriate testing protocol that accounts for both regulatory standards and environmental factors. Overall, our findings underscore the importance of continued monitoring to manage Clostridium species contamination and ensure milk quality.

The role of the Polybromo-associated BAF complex in development.

Chromatin is dynamically regulated during development, where structural changes affect the transcription of genes required to promote different cell types. One of the chromatin regulatory factors responsible for transcriptional regulation during development is the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, an ATP-dependent chromatin remodeling factor conserved throughout eukaryotes. The catalytic subunit of this complex, BRG1, is shared in all three SWI/SNF complexes subfamilies and is essential for developing most cell lineages. Interestingly, many human developmental diseases have correlative or causative mutations in different SWI/SNF subunits. Many polybromo-associated BAF (pBAF) complex-specific subunit genetic alterations result in developmental failures in tissue-specific ways. This observation suggests that the pBAF complex plays a vital role in development and differentiation, and studying the pBAF complex may provide an opportunity to better understand gene regulation during development. In this mini-view, we will focus on the functions of pBAF-specific subunits and their influence on the development of various cell and tissue types by regulating developmental gene expression.

Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation.

Porcine reproductive and respiratory syndrome virus (PRRSV) has led to significant economic losses in the global swine industry. Type I interferon (IFN-I) plays a crucial role in the host's resistance to PRRSV infection. Despite extensive research showing that PRRSV employs multiple strategies to antagonise IFN-I induction, the underlying mechanisms remain to be fully elucidated. In this study, we have discovered that PRRSV inhibits the production of IFN-I by degrading TANK-binding kinase 1 (TBK1) through chaperon-mediated autophagy (CMA). From a mechanistic standpoint, PRRSV nonstructural protein 2 (Nsp2) increases the interaction between the heat shock protein member 8 (HSPA8) and TBK1. This interaction leads to the translocation of TBK1 into lysosomes for degradation, mediated by lysosomal-associated membrane protein 2A (LAMP2A). As a result, the downstream activation of IFN regulatory factor 3 (IRF3) and the production of IFN-I are hindered. Together, these results reveal a new mechanism by which PRRSV suppresses host innate immunity and contribute to the development of new antiviral strategies against the virus.

Variations in DNA methylation and the role of regulatory factors in rice (Oryza sativa) response to lunar orbit stressors

Variations in DNA methylation and the role of regulatory factors in rice (Oryza sativa) response to lunar orbit stressors

Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.

HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1's involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal.

Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression.

The tumor microenvironment (TME) influences cancer progression and metastasis. Integrin β8 (ITGβ8), a member of the integrin family, is upregulated in various cancers. In this study, it is determined as a key factor that mediates the interaction between lung adenocarcinoma (LUAD) cells and macrophages. Increased expression levels of ITGβ8 are associated with increased numbers of CD163+ macrophages and poor prognosis in LUAD patients. The overexpression of ITGβ8 in LUAD cells promotes the polarization of THP-1 macrophages toward the M2 phenotype. In contrast, TCM (conditioned medium from the co-culture system) from THP-1 macrophages and ITGβ8-overexpressing A549 cells promoted the proliferation and invasion of A549 cells. Mechanistically, chemokine (C-C motif) ligand 5 (CCL5) plays an important role in mediating ITGβ8-induced macrophage polarization, and the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/interferon regulatory factor 9 (IRF9) pathway is involved in this process. Moreover, interleukin 8 (IL8) and interleukin 10 (IL10) produced by M2-like macrophages regulate the expression of ITGβ8 in LUAD cells through the spi-1 proto-oncogene (SPI1). This study elucidates the feedback mechanism of ITGβ8 between LUAD cells and macrophages.

Single-cell transcriptomic analysis reveals the developmental trajectory and transcriptional regulatory networks of quinoa salt bladders.

Salt bladders, specialized structures on the surface of quinoa leaves, secrete Na+ to mitigate the effects of the plant from abiotic stresses, particularly salt exposure. Understanding the development of these structures is crucial for elucidating quinoa's salt tolerance mechanisms. In this study, we employed transmission electron microscopy to detail cellular differentiation across the developmental stages of quinoa salt bladders. To further explore the developmental trajectory and underlying molecular mechanisms, we conducted single-cell RNA sequencing on quinoa protoplasts derived from young leaves. This allowed us to construct a cellular atlas, identifying 13 distinct cell clusters. Through pseudotime analysis, we mapped the developmental pathways of salt bladders and identified regulatory factors involved in cell fate decisions. GO and KEGG enrichment analyses, as well as experimental results, revealed the impacts of salt stress and the deprivation of sulfur and nitrogen on the development of quinoa salt bladders. Analysis of the transcription factor interaction network in pre-stalk cells (pre-SC), stalk cells (SC), and epidermal bladder cells (EBCs) indicated that TCP5, YAB5, NAC078, SCL8, GT-3B, and T1P17.40 play crucial roles in EBC development. Based on our findings, we developed an informative model elucidating salt bladder formation. This study provides a vital resource for mapping quinoa leaf cells and contributes to our understanding of its salt tolerance mechanisms.

Identifying and validating the key regulatory transcription factor YY1 in the aging process of pancreatic beta cells based on bioinformatics.

The aging of pancreatic beta cells is closely associated with various diseases, such as impaired glucose tolerance, yet the underlying regulatory mechanisms remain unclear. In this study, we screened young and aged mouse pancreatic beta cells' high-throughput sequencing data from the GEO public database. Utilizing bioinformatics techniques, we identified the key regulatory factor YY1 in the aging process of pancreatic islets. We observed a significant decrease in the expression of YY1 in a D-gal-induced mouse model of pancreatic aging and an H2O2-induced MIN6 cell model of aging. Moreover, both vivo and vitro models, we found that the YY1 agonist eudesmin (EDN) improved glucose intolerance in mice, alleviated aging of pancreatic beta cells, and downregulated the expression of cell cycle protein P21. Mechanistically, we discovered that EDN inhibited the P38/JNK MAPK pathway in aging cells. In summary, our study confirms the regulatory role of the transcription factor YY1 in the aging process of pancreatic beta cells. This finding may provide a new approach for the clinical treatment of pancreatic aging-related diseases such as impaired glucose tolerance or diabetes.

The Mediator complex subunit MoMed15 plays an important role in conferring sensitivity to isoprothiolane by modulating xenobiotic metabolism in M. oryzae.

Rice blast caused by Magnaporthe oryzae is one of the most economically important rice diseases. Fungicides such as isoprothiolane (IPT) have been used extensively for rice blast control, but resistance to IPT in M. oryzae is an emerging threat. In this study, molecular mechanisms of resistance in IPT-resistant mutants were identified. Through whole-genome sequencing and genetic transformation, we identified the gene MoMed15, encoding a transcriptional glutamine-rich co-activator Mediator complex subunit, in which mutations or deletion resulted in moderate IPT resistance. Further research found that MoMed15 physically interacted with the IPT resistance regulatory factor MoIRR to simultaneously regulate both MoIRR expression and the expression of multiple xenobiotic-metabolizing enzymes in response to IPT stress. We hypothesize that some xenobiotic-metabolizing enzymes enhance IPT toxicity by modifying the IPT structure. Variation of MoMed15 affected the recruitment of the transcriptional Mediator complex and decreased the expression of these xenobiotic-metabolizing enzymes, resulting in moderate IPT resistance. We also found that MoPGR1, encoding a protein that activates cytochrome P450 enzymes, was essential to confer IPT sensitivity, and its expression was directly regulated by MoIRR.IMPORTANCEIsoprothiolane (IPT) has been used extensively for the management of rice blast disease and IPT-resistant subpopulations have emerged in Chinese rice fields. The emergence of resistant pathogen populations has led to a steep increase in fungicide use, increasing pesticide risk for the applicator and the environment. The molecular mechanisms of IPT resistance in M. oryzae remain elusive. In this study, we demonstrated that transcriptional co-activator MoMed15 interacts with IPT resistance regulator MoIRR to recruit the Mediator complex, which promotes the expression of xenobiotic-metabolizing enzymes, leading to exacerbated IPT toxicity. The MoMed15 could be used for IPT resistance detection in rice fields.

The role of ethylene in the regulation of plant response mechanisms to waterlogging stress.

Waterlogging stands as a common environmental challenge, significantly affecting plant growth, yield, and, in severe cases, survival. In response to waterlogging stress, plants exhibit a series of intricate physiologic, metabolic, and morphologic adaptations. Notably, the gaseous phytohormone ethylene is rapidly accumulated in the plant submerged tissues, assuming an important regulatory factor in plant-waterlogging tolerance. In this review, we summarize recent advances in research on the mechanisms of ethylene in the regulation of plant responses to waterlogging stress. Recent advances found that both ethylene biosynthesis and signal transduction make indispensable contributions to modulating plant adaptation mechanisms to waterlogged condition. Ethylene was also discovered to play an important role in plant physiologic metabolic responses to waterlogging stress, including the energy mechanism, morphologic adaptation, ROS regulation and interactions with other phytohormones. The comprehensive exploration of ethylene and its associated genes provides valuable insights into the precise strategies to leverage ethylene metabolism for enhancing plant resistance to waterlogging stress.