Phosphatidylinositol Signaling Research Articles

Silencing CaPIP5K4-1 leads to decreased male fertility in Capsicum annuum L.

Phosphatidylinositol 4-phosphate 5-kinase gene CaPIP5K4-1 is highly expressed in the pepper anthers. Virus-induced gene silencing of CaPIP5K4-1 leads to reduced male fertility in pepper. The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) is a pivotal enzyme in the phosphatidylinositol signaling pathway, and its crucial involvement in both plant development and stress response has been established. Here, we found that the expression of CaPIP5K4-1 in pepper was significantly higher in the fertile flower buds compared to sterile flower buds. Furthermore, its expression was validated in anthers and pollens by qRT-PCR and RNA-ISH assays, respectively. Its GFP fusion protein was mainly located on the plasma membrane. Silencing CaPIP5K4-1 in fertile pepper accessions resulted in wrinkled pollen grain cell walls, decreased pollen germination efficiency, and inhibited pollen tube growth. The transcription levels of multiple genes in the phosphatidylinositol signaling pathway were also assessed. Five phospholipase C (PLC) genes were downregulated in silenced plants. On the contrary, inositol phosphatase SAC and phosphatase and tensin homolog (PTEN) were upregulated. This study reported the role of CaPIP5K4-1 in pepper male fertility and provided insights into the regulatory mechanisms of PI signaling in pepper.

Exploring the role of miR-125b-5p as a pro-inflammatory factor in Alzheimer's disease pathology.

Alzheimer's disease (AD) is a common neurodegenerative disease, where neuroinflammation significantly influences its pathophysiology by driving the disease's pathological cascade. As a pro-inflammatory regulator, miR-125b-5p contributes to AD progression, though its precise role and mechanisms remain unclear. We aims to identify mRNAs significantly regulated by pro-inflammatory miR-125b-5p in AD and uncover key neuroinflammatory pathways. Target mRNAs regulated by miR-125b-5p were predicted using online databases and analyzed with two mRNA datasets to identify differentially expressed mRNAs (DEmRNAs). Enrichment analysis was conducted to explore their biological functions and pathways. The significance of DEmRNAs expression in AD-related inflammatory pathways was verified by the Wilcoxon test, predictive accuracy was assessed via area under the curves (AUCs), and novel mRNAs were identified through positive control analysis. A total of 613 miR-125b-5p target mRNAs were identified, and 44 DEmRNAs were detected to be regulated by miR-125b-5p in two datasets. The 44 target DEmRNAs associated with AD include three key pathways: insulin signaling (EXOC7, FLOT2, MKNK2), phosphatidylinositol signaling (IP6K1, MTMR3), and phospholipase D signaling (CYTH1, GAB2). Correlation analysis indicated strong correlations among 7 mRNAs, all showing significant differential expression, with AUCs above 0.5, confirming their predictive value. Three mRNAs (EXOC7, IP6K1, CYTH1) were identified as novel AD-related genes. MiR-125b-5p binding sites in the 3'-UTRs of these 7 mRNAs suggest their potential roles in AD-related inflammation and signaling pathways. This study investigates the pro-inflammatory miR-125b-5p's role in the pathological processes of AD, highlighting its regulation of key target mRNAs and critical pathways.

Screening of SNP Loci Related to Leg Length Trait in Leizhou Goats Based on Whole-Genome Resequencing.

Leizhou goats can be classified into tall and short types based on their size and habits. The tall Leizhou goats are well-suited for grazing management due to their robust physique, while the dwarf types are smaller, grow rapidly, and are more appropriate for feeding management systems. In this study, whole-genome resequencing was conducted to identify genomic variants in 15 Tall-legged (TL) and 15 Short-legged (SL) Leizhou goats, yielding 8,641,229 high-quality SNPs in the Leizhou goat genome. Phylogenetic tree and principal component analyses revealed obvious genetic differentiation between the two groups. Fst and θπ analyses identified 420 genes in the TL group and 804 genes in the SL group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the phosphatidylinositol signaling system is associated with growth and development. Additionally, Genome-Wide Association Study (GWAS) analysis identified eight genes linked to leg length, including B4GALT7 and NR1D1. Notably, the NC_030818.1 (g.53666634T > C) variant was significantly associated with leg length traits, where the CC genotype was linked to shorter legs and the TT genotype to longer legs. This study identifies candidate genes and molecular markers, serving as a reference point for breeding and genetic improvement efforts in Leizhou goats and other goat breeds.

Analyzing immune cell infiltrates in skeletal muscle of infantile-onset Pompe disease using bioinformatics and machine learning

Pompe disease, a severe lysosomal storage disorder, is marked by heart problems, muscle weakness, and respiratory difficulties. This study aimed to identify novel markers for infantile-onset Pompe disease by analyzing key genes and immune cells infiltrating affected skeletal muscles, building on existing research linking its progression to the immune cell infiltration. The datasets GSE38680 and GSE159062 were downloaded and differential expression genes (DEGs) were identified. Potential markers were screened using support vector machine recursive feature elimination (SVM-RFE) analysis and least absolute shrinkage and selection operator (LASSO) regression models. To analyze DEGs and immune processes, 22 immune cell types in affected tissues were examined using CIBERSORT. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment in the calcium signaling pathway, phosphatidylinositol signaling system, ubiquitin-mediated proteolysis and JAK-STAT signaling pathway. Machine learning identified GPNMB, CALML6 and TRIM7 as key genes. Immune cell infiltration analysis showed that the expression levels of the above three genes were closely related to immune cells in our target population under study, including T cells regulatory (Tregs), monocytes, macrophages M0, resting and activated dendritic cells, naive and memory B cells. Overall, our study results may provide new clues for exploring markers related to Pompe disease by highlighting key genes and their relationship with immune infiltration, offering insights into the disease’s development. However, previous studies have shown limited evidence of significant immune cell infiltration in muscle biopsies from Pompe patients, and this lack of direct evidence necessitates further investigation and experimental validation in laboratory settings to confirm these associations.

OsPIPK-FAB, A Negative Regulator in Rice Immunity Unveiled by OsMBL1 Inhibition

Phosphatidylinositol signaling system plays a crucial role in plant physiology and development, phosphatidylinositol phosphate kinases (PIPKs) are one of the essential enzymes responsible for catalyzing the synthesis of phosphatidylinositol bisphosphate (PIP2) within this signaling pathway. However, its mechanism of signal transduction remains poorly exploited in plants. OsMBL1, a jacalin-related mannose-binding lectin in rice, plays a crucial role in plant defense mechanisms, acting as a key component of the pattern-triggered immunity (PTI) pathway. Here, a rice phosphatidylinositol-phosphate kinase FAB (OsPIPK-FAB), a member of the rice PIPKs family, as an interacting protein of OsMBL1 through yeast-two-hybrid (Y2H) screening assay. And this interaction was confirmed by using co-immunoprecipitation (Co-IP) and pull-down assay techniques. Furthermore, we demonstrated that the deletion of OsPIPK-FAB gene in plant enhanced resistance against rice blast while overexpression of OsPIPK-FAB increases sensitivity to the fungal infection. Additionally, through determination and measurement of the plant inositol 1,4,5-trisphosphate (IP3) contents and the plant phosphatidylinositol 4-phosphate 5-kinase (PIP5K) activity, we revealed that OsMBL1 inhibits the PIP5K kinase activity of OsPIPK-FAB as well as the plant IP3 contents in rice. Conclusively, these findings indicated that OsPIPK-FAB serves as a novel and critical component that is negatively involved in PTI activation and was inhibited by OsMBL1.

Lipid metabolism improves salt tolerance of Salicornia europaea.

Salicornia europaea L., a succulent euhalophyte plant, has been found to exhibit optimal reproductive capabilities under appropriate salinity concentrations. However, the underlying metabolic changes are not yet fully understood. This study conducted a comprehensive analysis combining transcriptomic and lipidomic techniques to investigate the molecular mechanisms of lipid metabolism in response to different NaCl concentrations (0 and 200mM). Transcriptomic data demonstrated that salt treatment mainly affected processes including lipid biosynthesis, phosphatidylinositol signaling, and glycerophospholipid metabolism. The expression levels of several key genes involved in salt tolerance, namely SeSOS1, SeNHX1, SeVHA-A, SeVP1, and SePSS, were found to be upregulated upon NaCl treatment. A total of 485 lipid compounds were identified, of which 27 changed in abundance under salt treatment, including the enrichment of phospholipids and sphingolipids. Moreover, the increase in the double-bond index (DBI) was mainly due to phospholipids and sphingolipids. Comparing the acyl chain length (ACL) showed that the ACL coefficient of S1P significantly decreased under 200mM NaCl. This study suggests that S. europaea adapt to saline environments through altering phospholipids and sphingolipids to improve salt tolerance. The salinity response of S. europaea can provide important insights into the action of lipids and their salt adaptation mechanisms.

Brain-Region-Specific Differences in Protein Citrullination/Deimination in a Pre-Motor Parkinson's Disease Rat Model.

The detection of early molecular mechanisms and potential biomarkers in Parkinson's disease (PD) remains a challenge. Recent research has pointed to novel roles for post-translational citrullination/deimination caused by peptidylarginine deiminases (PADs), a family of calcium-activated enzymes, in the early stages of the disease. The current study assessed brain-region-specific citrullinated protein targets and their associated protein-protein interaction networks alongside PAD isozymes in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Six brain regions (cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb) were compared between controls/shams and the pre-motor PD model. For all brain regions, there was a significant difference in citrullinated protein IDs between the PD model and the controls. Citrullinated protein hits were most abundant in cortex and hippocampus, followed by cerebellum, midbrain, olfactory bulb and striatum. Citrullinome-associated pathway enrichment analysis showed correspondingly considerable differences between the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways identified in PD brains only were associated with neurological, metabolic, immune and hormonal functions and included the following: "Axon guidance"; "Spinocerebellar ataxia"; "Hippo signalling pathway"; "NOD-like receptor signalling pathway"; "Phosphatidylinositol signalling system"; "Rap1 signalling pathway"; "Platelet activation"; "Yersinia infection"; "Fc gamma R-mediated phagocytosis"; "Human cytomegalovirus infection"; "Inositol phosphate metabolism"; "Thyroid hormone signalling pathway"; "Progesterone-mediated oocyte maturation"; "Oocyte meiosis"; and "Choline metabolism in cancer". Some brain-region-specific differences were furthermore observed for the five PAD isozymes (PADs 1, 2, 3, 4 and 6), with most changes in PAD 2, 3 and 4 when comparing control and PD brain regions. Our findings indicate that PAD-mediated protein citrullination plays roles in metabolic, immune, cell signalling and neurodegenerative disease-related pathways across brain regions in early pre-motor stages of PD, highlighting PADs as targets for future therapeutic avenues.

Comparative Analyses of Dynamic Transcriptome Profile of Heart Highlight the Key Response Genes for Heat Stress in Zhikong Scallop Chlamys farreri.

Heat stress resulting from global climate change has been demonstrated to adversely affect growth, development, and reproduction of marine organisms. The Zhikong scallop (Chlamys farreri), an important economical mollusk in China, faces increasing risks of summer mortality due to the prolonged heat waves. The heart, responsible for transporting gas and nutrients, is vital in maintaining homeostasis and physiological status in response to environmental changes. In this study, the effect of heat stress on the cardiac function of C. farreri was investigated during the continuous 30-day heat stress at 27 °C. The results showed the heart rate of scallops increased due to stress in the initial phase of high temperature exposure, peaking at 12 h, and then gradually recovered, indicating an acclimatization at the end of the experiment. In addition, the levels of catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) exhibited an initial increase followed by recovery in response to heat stress. Furthermore, transcriptome analysis of the heart identified 3541 differentially expressed genes (DEGs) in response to heat stress. Subsequent GO and KEGG enrichment analysis showed that these genes were primarily related to signal transduction and oxidative stress, such as the phosphatidylinositol signaling system, regulation of actin cytoskeleton, MAPK signaling pathway, FoxO signaling pathway, etc. In addition, two modules were identified as significant responsive modules according to the weighted gene co-expression network analysis (WGCNA). The upregulation of key enzymes within the base excision repair and gap junction pathways indicated that the heart of C. farreri under heat stress enhanced DNA repair and maintained cellular integrity. In addition, the variable expression of essential signaling molecules and cytoskeletal regulators suggested that the heart of C. farreri modulated cardiomyocyte contraction, intracellular signaling, and heart rate through complex regulation of phosphorylation and calcium dynamics in response to heat stress. Collectively, this study enhances our understanding of cardiac function and provides novel evidence for unraveling the mechanism underlying the thermal response in mollusks.

Identification of growth-related genes based on BSA in Pacific white shrimp Litopenaeus vannamei

The development of SNP genotyping techniques has facilitated the application of genome-wide association studies (GWAS) and genomic selection (GS) in plants and animals. However, the cost of high-throughput SNP genotyping is particularly high in the case of aquaculture animals which can produce a large number of offspring. Consequently, a cost effective method for trait-associated SNP identification and application was urgently needed in aquaculture breeding. In this study, a Bulk Segregation Analysis sequencing (BSA-seq) method was employed to identify growth-related single nucleotide polymorphisms (SNPs) and genes in the Pacific white shrimp Litopenaeus vannamei. Two independent families were used for this analysis to reduce the false positive. The DNA of individuals with the highest and lowest body weights was pooled separately. Two methods including the ED (Euclidean distance) method and the chi-square test were applied to calculate the allele differences between high and low growth rate individuals. A total of 24,325,437 SNPs were identified and consequently 1,299 SNPs and 163 genes were identified to be associated with growth traits. KEGG enrichment analysis showed that these genes were significantly enriched in phosphatidylinositol signaling system and phospholipase D signaling pathway. The diacylglycerol kinase genes, phosphatidylinositol 3-kinase genes, inositol polyphosphate 5-phosphatase genes, mitogen-activated protein kinase genes, myotubularin-related protein genes and epidermal growth factor receptor genes in these pathways were considered as candidate growth genes. This study demonstrated that the BSA-seq based on whole genome resequencing is cost-effective and useful in aquaculture. The results not only provide useful information for understanding the genetic basis of growth traits, but also offer a source of SNPs for marker-assisted selection (MAS) and genomic selection (GS) in shrimp.

Elucidating the downstream pathways triggered by H2S signaling in Arabidopsis thaliana under drought stress via transcriptome analysis

ABSTRACT Hydrogen sulfide (H2S) is a crucial signaling molecule in plants. Recent studies have shown that H2S plays an equally important role as nitric oxide (NO) and hydrogen peroxide (H2O2) in plant signaling. Previous studies have demonstrated the involvement of H2S in regulating drought and other stressful environmental conditions, but the exact downstream molecular mechanisms activated by the H2S signaling molecule remain unclear. In this study, we conducted a comprehensive genome-wide transcriptomic analysis of both wild type (WT) and double mutant (lcd/des1). Arabidopsis thaliana plants were exposed to 40% polyethylene glycol (PEG) to induce drought stress and 20 µM sodium hydrosulfide (NaHS). The resulting transcriptome data were analyzed for differentially significant genes and their statistical enrichments in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results indicated significant upregulation of genes related to photosynthesis, carbon fixation, plant secondary metabolite biosynthesis, inositol and phosphatidylinositol signaling pathways, and stress-responsive pathways in mutant plants under drought stress. Mutant plants with impaired H2S signaling mechanisms displayed greater susceptibility to drought stress compared to wild-type plants. In summary, all findings highlight the pivotal role of H2S signaling in stimulating other drought-responsive signaling pathways.

The influence and mechanism of fish collagen peptide and egg yolk lecithin on proliferation and lipid composition in feline adipocytes.

The influences of fish collagen peptide (FCP) and egg yolk lecithin (EYL) on the proliferation, fat accumulation and triglyceride content in feline adipocytes were investigated in this work, aiming at unveiling the mechanism of fat accumulation for cheek of feline animals. The lipogenic changes of adipocytes in the presence of FCP and EYL were determined by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results demonstrated that FCP of 10mg/mL had the strongest cell activity, with a relative increment rate of 156 ± 0.23%, and the triglyceride content reached 215.9 ± 3.86 mmol/L. By comparison, it was observed that an EYL concentration of 5mg/mL elicited the highest cell activity, exhibiting a relative increment rate of 152 ± 0.60%, and the level of triglyceride content was noted to reached 256.56 ± 25.68 mmol/L. After the feline adipocytes were treated with different concentrations of two active substances, fat formation and lipid droplets were found by oil red O staining. Liposome analyses confirmed that the formation of lipid compounds was regulated by FCP and EYL through pathways involved in lipid metabolism, notably including inositol phosphate insulin resistance, and phosphatidylinositol signaling pathways. This regulation was found to enhance cell vitality and facilitate fat accumulation. These findings provide a new strategy for the development of nutritional and healthy products or foods that promote feline cheek.

High-throughput Approaches to Detect Cytokines and Chemokines Secretion by Both Autophagy and Endosome Vesicle Fusion of HBMEC by Knocking Down the NLRP2 Gene

Background: Given the rapid increase in serious infectious and inflammatory diseases in the general population worldwide, it is vital to advance our understanding of the process of infection and inflammation. Objective: These illnesses can be treated by diverse cytokines, chemokines, and chemical compounds, but how to find and identify effective protein drugs is unknown. In this study, large–scale analytical approaches, such as high–throughput chips with RNA-Seq that construct the protein regulatory networks, were established. Methods: NLRP2:shRNA (1–3) and GFP: Control lentivirus were fabricated to infect Human Brain Microvascular Endothelial Cells (HBMEC) to knock down NLRP2 gene that not only possesses biochemical activity but also bio-mechanical properties. Once HBMEC was loaded on the 18mmX18mm circular soft cover slip, by knocking down NLRP2 gene processing and adding puromycin, a large number of cytokines were secreted to activate both autophagy and endosome vesicle signaling by KEGG pathway analysis, which was successfully detected by both ELISA approach and QAH-Neu-1 chip. However, no secretion from GFP: Control was reported. Results: It was demonstrated that the NLRP2 gene was highly responsive to cytokines. The protein regulatory network from RNA–Seq platform demonstrated that the secretion by knocking down the NLRP2 gene was highly correlated with autophagy, endosome, multivesicular body, phosphatidylinositol, and necrosis signalling pathway. Furthermore, most of the cytokines expressed were found to be specific for intracellular vesicle–dependent secretion, leading to obvious cell swelling and shedding, membrane protein dotting to nucleation, and actin dynamics. Interestingly, it was also found that autophagy, together with endosome signalling, was collectively activated to boost the secretion to cause a “cytokine storm”, which led to lipid phase separation. Conclusion: This study proposed high throughput approaches centered on the NLRP2 gene network for many severe diseases, providing novel insight into biological pathways influencing infection and inflammation (e.g., COVID-19/E.coli). They can be modulated as potential therapeutic targets and used as biomarkers in the diagnosis and treatment of many diseases to promote human health. This increases our interest in developing new leadless-peptides at the genomics and proteomics levels to obtain cytokines and chemokines for micro-array constructions (VirD‒cytokines, VirD‒enzymes), antibody and vaccine development for infections, diabetes, cardiovascular disease, atherosclerosis, non–alcoholic fatty liver, auto-immune, neurodegenerative disorder, and even cancer-related disease therapy. They have the most valuable applications in molecular diagnosis, protein marker discovery, and bio-therapy.

Transcriptomic profiling reveals potential regulatory genes and molecular mechanisms of residual feed intake in Jian carp (Cyprinus carpio var. Jian)

Feed efficiency is one of the most important economic traits in animal production. Improving feed efficiency through genetic selection or other approaches will reduce production costs and mitigate environmental impacts. Residual feed intake (RFI) has some advantages over traditional feed efficiency metrics as a selection criterion for improving feed efficiency, because it is not a ratio and unrelated to growth. In this study, high RFI (HRFI) and low RFI (LRFI) Jian carp (Cyprinus carpio var. Jian) were tested for feed efficiency traits and serum biochemical indices. No significant differences were observed in the growth rates between HRFI and LRFI group, but daily feed intake of LRFI was significantly lower than that of the HRFI group. The results indicated that significantly higher content of triglyceride (TG) and total cholesterol (T-CHO) in the LRFI group was significantly correlated with RFI. We also selected HRFI and LRFI carp for transcriptomic analysis to determine differentially expressed genes (DEGs) in the liver tissues of 12 individuals. A total of 830 DEGs were identified between HRFI and LRFI group, of which 486 genes were up-regulated and 344 genes were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that DEGs were mainly enriched in fatty acid metabolism, ErbB signaling pathway, phosphatidylinositol signaling system, and autophagy. Lipid metabolism and autophagy-related genes, were considered candidate genes that played a crucial role in regulating feed efficiency. Taken together, these results indicated that differences in RFI affect Jian carp metabolism and cell fate, and that alterations in fatty acid metabolism and autophagy are key physiological modes of regulation in low RFI Jian carp. Our data provide valuable candidate genes and candidate pathways, which will help to study the molecular mechanisms of feed efficiency in carp.

A cause-effect relationship between uterine diseases and breast cancer: A bidirectional Mendelian randomization study

ObjectiveTo explore the cause-effect relationship between uterine diseases (UDs) and breast cancer (BC) and underlying mechanism of the cause-effect relationship, enhance understanding of the association between BC and UDs. MethodsA two-sample bidirectional Mendelian randomization (MR) analysis was conducted. We obtained summary statistics data from GWAS for BC, endometriosis, endometrial cancer (EC), uterine leiomyoma (UL), uterine polyps (UP), and cervical cancer (CC). Independent SNPs were selected as instrumental variables (IVs) for each disease. The inverse variance weighted (IVW) method was primary used for estimating the causal association between UDs and BC. To further evaluate the consistency and dependability of the results, we also utilized the weighted median, weighted mode, simple mode, and MR-Egger methods, along with sensitivity analyses. Furthermore, a supplementary analysis focusing on the variants linked to BC and UDs was conducted. This involved identifying corresponding genes and subsequently performing KEGG/GO analyses to investigate potential molecular mechanisms. ResultsThe results indicated significant associations between genetic susceptibility to endometriosis, EC, and UL with BC risk. The odds ratios (ORs) were as follows: endometriosis at 0.963 (95 % CI, 0.942–0.984; p = 7.11e-5), EC at 1.056 (95 % CI, 1.033–1.081; p = 2.39e-6), and UL at 1.027 (95 % CI, 1.006–1.048; p = 0.010). Conversely, the predisposition to BC inferred from genetic factors was markedly correlated with an elevated risk of EC indicated by an OR of 1.066 (95 % CI, 1.019–1.116; p = 0.006), and was correlated with UP risk (OR, 1.001,95 % CI, 1.000–1.002; p = 0.001).Sensitivity analyses provided weak evidence for these effects, suggesting that the study's outcomes are consistent and trustworthy. Further analysis of the genetic variants associated with BC, and these related genes are enriched in Cellular senescence, GnRH secretion, Phosphatidylinositol signaling system, and so on. ConclusionThis study corroborates the existence of a reciprocal causal relationship between BC and EC, as well as highlighting the substantial correlations between a genetic susceptibility to UL and endometriosis with BC. BC may exert their influence on EC and UP through Cellular senescence, GnRH secretion, and other pathways. These discoveries offer fresh perspectives on the genetic pathogenesis of BC and UDs, and can guide future experimental studies. Additionally, they lay down a groundwork for the development of tailored preventative and therapeutic strategies moving forward.

Longitudinal multiomics analysis of aggressive pituitary neuroendocrine tumors: comparing primary and recurrent tumors from the same patient, reveals genomic stability and heterogeneous transcriptomic profiles with alterations in metabolic pathways

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET.

Using Transcriptomics to Determine the Mechanism for the Resistance to Fusarium Head Blight of a Wheat-Th. elongatum Translocation Line.

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, is a destructive disease in wheat worldwide. The lack of FHB-resistant germplasm is a barrier in wheat breeding for resistance to FHB. Thinopyrum elongatum is an important relative that has been successfully used for the genetic improvement of wheat. In this study, a translocation line, YNM158, with the YM158 genetic background carrying a fragment of diploid Th. elongatum 7EL chromosome created using 60Co-γ radiation, showed high resistance to FHB under both field and greenhouse conditions. Transcriptome analysis confirmed that the horizontal transfer gene, encoding glutathione S-transferase (GST), is an important contributor to FHB resistance in the pathogen infection stage, whereas the 7EL chromosome fragment carries other genes regulated by F. graminearum during the colonization stage. Introgression of the 7EL fragment affected the expression of wheat genes that were enriched in resistance pathways, including the phosphatidylinositol signaling system, protein processing in the endoplasmic reticulum, plant-pathogen interaction, and the mitogen-activated protein kinase (MAPK) signaling pathway at different stages after F. graminearium infection. This study provides a novel germplasm for wheat resistance to FHB and new insights into the molecular mechanisms of wheat resistance to FHB.

ITRAQ proteome analysis reveals the underling mechanisms of foliage zinc-spraying to improve photosynthetic capacity and seed yields of Peaonia ostii ‘Fengdan’

Zinc (Zn) deficiency is a significant nutritional limitation to crop yield globally, particularly in calcareous soil environments. Tree peony of Peaonia ostii ‘Fengdan’ is regarded as an oil crop due to its seeds rich in alpha-linolenic acid, a beneficial compound for health promotion. However, low seed yield remains a primary challenge in attaining sufficient seed oil from tree peony. In this study, Zn fertilization was applied to soil or foliage of P. ostii ‘Fengdan’ in the growth period before fruit development. Our findings reveal that foliar Zn-spraying, as opposed to soil application, proves to be a more effective method for augmenting seed yield, Zn accumulation and photosynthetic capacity in ‘Fengdan’. Comparative analyses of the leaf proteome of ‘Fengdan’ using iTRAQ profiling under foliar Zn-spraying identified 115 differentially expressed proteins (DEPs), including 36 upregulated proteins, which likely contribute to the observed increase in seed yields of ‘Fengdan’ caused by foliage Zn-spraying. Specifically, Zn2+ stimulation of phosphatidylinositol signaling initiates a cascade of metabolic regulations. Firstly, ATP synthesis promotes leaf photosynthetic capacity, facilitated by improved sucrose metabolism through upregulated pullulanase and 1,4-alpha-glucan-branching enzyme. Furthermore, lipid synthesis and transport are facilitated by upregulated lipoyl synthase and plastid lipid-associated proteins. Additionally, DEPs involved in secondary metabolism are upregulated in the production of various metabolites conducive to ‘Fengdan’ growth. Overall, our results demonstrate that foliage Zn-spraying enhances seed yield in P. ostii ‘Fengdan’ by elevating Zn content and secondary metabolite synthesis in leaves, thereby augmenting leaf photosynthetic capacity and lipid synthesis. This study provides an effective way to increase seed yield of tree peony by exogenous Zn application.

A Potential Neurotoxic Mechanism: Bisphenol S-Induced Inhibition of Glucose Transporter 1 Leads to ATP Excitotoxicity in the Zebrafish Brain.

Many environmental pollutants have neurotoxic effects, but the initial molecular events involved in these effects are unclear. Here, zebrafish were exposed to the neurotoxicant bisphenol S (BPS, 1, 10, or 100 μg/L) from the embryonic stage to the larval stage to explore the ability of BPS to interfere with energy metabolism in the brain. BPS, which is similar to a glucose transporter 1 (GLUT1) inhibitor, inhibited GLUT1 function but increased mitochondrial activity in the brains of larval zebrafish. Interestingly, GLUT1 inhibitor treatment and BPS exposure did not reduce energy production in the brain; instead, they increased ATP production by inducing the preferential use of ketone bodies. Moreover, BPS promoted the protein expression of the purinergic 2X receptor but inhibited the purinergic 2Y-mediated phosphatidylinositol signaling pathway, indicating that excess ATP acts as a neurotransmitter to activate the purinergic 2X receptor under the BPS-induced restriction of GLUT1 function. BPS-induced inhibition of GLUT1 increased the number of neurons but promoted apoptosis by activating ATP-purinergic 2X receptors in the brain, causing ATP excitatory neurotoxicity. Our data reveal a potential neurotoxic mechanism induced by BPS that may represent a new adverse outcome pathway.

Exploring the anti-inflammatory and immunomodulatory potential of licochalcone B against psoralidin-induced liver injury

Ethnopharmacological relevanceHerb-induced liver injury (HILI) represents an exacerbated inflammatory response, with Psoraleae fructus (PF) and its preparations recently associated with hepatotoxicity. Licorice, historically recognized as a detoxifying herbal remedy, is considered to possess hepatoprotective properties. Our previous research identified bavachin, bakuchiol, and psoralidin (PSO) as potential toxic constituents in PF, while licochalcone B (LCB) and echinatin were identified as bioactive components in licorice. However, evidence regarding the interactions of active compounds in herbs and their underlying mechanisms remains limited. Aim of the studyThe objective of this study is to assess the potential mechanisms through which LCB modulates immunological and anti-inflammatory responses to treat PSO-induced liver injury by using human hepatocyte cells (L02) and LPS-primed mice. MethodsThe ameliorative effects of LCB and echinatin on bavachin, bakuchiol, and PSO-induced liver injury were demonstrated in L02 cells. Subsequently, the efficacy of LCB on PSO-induced idiosyncratic liver injury was further validated in C57BL/6 mice under moderate inflammatory stress induced by LPS priming. The mechanisms were preliminarily explored with an integrated strategy of molecular docking, RT-PCR verification, and untargeted metabolomics. ResultsThe study shows that LCB significantly reduced cell injury induced by the three chemicals in PF and provided substantial protection against PSO-induced hepatic damage, as indicated by the levels of ALT, AST, and LDH. LCB normalized liver function and remarkedly alleviated hepatic lesions and inflammation caused by PSO in mice under moderate inflammatory stress. The mRNA profiles of both L02 cells and mice liver tissue revealed that LCB mitigated PSO-induced hepatotoxicity by regulating the gene expression of pro-inflammatory cytokines IL1B and TNF, as well as immunoinflammatory genes PIK3CA, AKT1, NFKB1, and NLRP3. Furthermore, untargeted metabolomics of liver tissue indicated that LCB could reverse the abnormal expression of 11 discriminatory metabolites, with the interrelationship between differential metabolites and target genes primarily clustering in glycerophospholipid metabolism, arachidonic acid metabolism, and phosphatidylinositol signaling system. ConclusionLCB demonstrated a superior anti-inflammatory and immunomodulatory effect on PSO-induced hepatotoxicity by modulating the inflammatory response and metabolic signaling system. Key interactive targets included phosphatidylcholine, phosphatidic acid, and subunit isoforms of PI3K.

Effects of Refrigerated Storage on Restarted Morphological Development of Dictyophora indusiata Fruiting Bodies

Mature Dictyophora indusiata fruiting bodies are brittle and broken easily during storage. Peach-shaped Dictyophora indusiata before maturity respond well to refrigerated maintenance, but some cannot resume their development after storage. This study analyzed the effects of refrigerated storage and transportation on the restarted development of Dictyophora indusiata fruiting bodies using quantitative transcriptome analysis. The refrigerated (4 °C, 3 d) peach-shaped Dictyophora indusiata (CK) was used as the control. After induction treatment for 3 d (26 ± 2 °C, 95 ± 3% RH), 81.25% of CK could achieve restarted development and mature (D-M), whereas 18.75% failed (D-P) to restart. Quantitative transcriptome analysis revealed that 1389 and 4451 differentially expressed genes (DEGs) were identified in the D-P and D-M groups when compared with the results for the CK group, respectively. DEG annotation and functional analysis revealed that D-P did not initiate energy and nutrient metabolism. Most DEGs involving the phosphatidylinositol signaling pathway and the MAPK signaling pathway were significantly downregulated or unchanged in the D-P and significantly upregulated in the D-M groups. These results suggested that the phosphatidylinositol signaling pathway may play a crucial role in transmitting environmental signals and initiating the morphogenesis of CK, and that the downstream MAPK signaling pathway may be responsible for signal transmission, thereby regulating cellular activities. This study provides a theoretical basis for regulating the growth and development of postharvest Dictyophora indusiata fruiting bodies.