Highlights of how single-cell analyses are illuminating differentiation and disease in the gastric corpus.

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful technique to identify novel cell markers, developmental trajectories, and transcriptional changes during cell differentiation and disease onset and progression. In this review, we highlight recent scRNA-seq studies of the gastric corpus in both human and murine systems that have provided insight into gastric organogenesis, identified novel markers for the various gastric lineages during development and in adults, and revealed transcriptional changes during regeneration and tumorigenesis. Overall, by elucidating transcriptional states and fluctuations at the cellular level in healthy and disease contexts, scRNA-seq may lead to better, more personalized clinical treatments for disease progression.

Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human-derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation-related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs.

Caffeic Acid O-Methyltransferase Gene Family in Mango (Mangifera indica L.) with Transcriptional Analysis under Biotic and Abiotic Stresses and the Role of MiCOMT1 in Salt Tolerance.

Caffeic acid O-methyltransferase (COMT) participates in various physiological activities in plants, such as positive responses to abiotic stresses and the signal transduction of phytohormones. In this study, 18 COMT genes were identified in the chromosome-level reference genome of mango, named MiCOMTs. A phylogenetic tree containing nine groups (I-IX) was constructed based on the amino acid sequences of the 71 COMT proteins from seven species. The phylogenetic tree indicated that the members of the MiCOMTs could be divided into four groups. Quantitative real-time PCR showed that all MiCOMT genes have particularly high expression levels during flowering. The expression levels of MiCOMTs were different under abiotic and biotic stresses, including salt and stimulated drought stresses, ABA and SA treatment, as well as Xanthomonas campestris pv. mangiferaeindicae and Colletotrichum gloeosporioides infection, respectively. Among them, the expression level of MiCOMT1 was significantly up-regulated at 6-72 h after salt and stimulated drought stresses. The results of gene function analysis via the transient overexpression of the MiCOMT1 gene in Nicotiana benthamiana showed that the MiCOMT1 gene can promote the accumulation of ABA and MeJA, and improve the salt tolerance of mango. These results are beneficial to future researchers aiming to understand the biological functions and molecular mechanisms of MiCOMT genes.

Genome-Wide Characterization and Haplotypic Variation Analysis of the IDD Gene Family in Foxtail Millet (Setaria italica).

The indeterminate domain proteins (IDD proteins) play essential roles in the growth and development of various plant tissues and organs across different developmental stages, but members of this gene family have not yet been characterized in foxtail millet (Setaria italica). To have a comprehensive understanding of the IDD gene family in foxtail millet, we performed a genome-wide characterization and haplotypic variation analysis of the IDD gene family in foxtail millet. In this study, sixteen IDD genes were identified across the reference genome of Yugu1, a foxtail millet cultivar. Phylogenetic analysis revealed that the Setaria italica IDD (SiIDD) proteins were clustered into four groups together with IDD proteins from Arabidopsis thaliana (dicot) and Oryza sativa (monocot). Conserved protein motif and gene structure analyses revealed that the closely clustered SiIDD genes were highly conserved within each subgroup. Furthermore, chromosomal location analysis showed that the SiIDD genes were unevenly distributed on nine chromosomes of foxtail millet and shared collinear relationships with IDD genes of other grass species. Transcriptional analysis revealed that the SiIDD genes differed greatly in their expression patterns, and paralogous genes shared similar expression patterns. In addition, superior haplotypes for two SiIDD genes (SiIDD8 and SiIDD14) were identified to correlate with traits of early heading date, and high thousand seed weight and molecular markers were designed for SiIDD8 and SiIDD14 to distinguish different haplotypes for breeding. Taken together, the results of this study provide useful information for further functional investigation of SiIDD genes, and the superior haplotypes of SiIDD8 and SiIDD14 will be particularly beneficial for improving heading date and yield of foxtail millet in breeding programs.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.

Transcriptomic profiling and differential analysis reveal the renal toxicity mechanisms of mice under cantharidin exposure.

Cantharidin (CTD), extracted from the traditional Chinese medicine mylabris, has shown significant curative effects against a variety of tumors, but its clinical application is limited by its high toxicity. Studies have revealed that CTD can cause toxicity in the kidneys; however, the underlying molecular mechanisms remain unclear. In this study, we investigated the toxic effects in mouse kidneys following CTD treatment by pathological and ultrastructure observations, biochemical index detection, and transcriptomics, and explored the underlying molecular mechanisms by RNA sequencing (RNA-seq). The results showed that after CTD exposure, the kidneys had different degrees of pathological damage, altered uric acid and creatinine levels in serum, and the antioxidant indexes in tissues were significantly increased. These changes were more pronounced at medium and high doses of CTD. RNA-seq analysis revealed 674 differentially expressed genes compared with the control group, of which 131 were upregulated and 543 were downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that many differentially expressed genes were closely related to the stress response, the CIDE protein family, and the transporter superfamily, as well as the MAPK, AMPK, and HIF-1 pathways. The reliability of the RNA-seq results was verified by qRT-PCR of the six target genes. These findings offer insight into the molecular mechanisms of renal toxicity caused by CTD and provide an important theoretical basis for the clinical treatment of CTD-induced nephrotoxicity.

Transcriptomics confirm the establishment of a liver-immune dual-humanized mouse model after transplantation of a single type of human bone marrow mesenchymal stem cell.

BACKGROUND AND AIMS: Human bone marrow mesenchymal stem cells (hBMSCs) are important for developing a dual-humanized mouse model to clarify disease pathogenesis. We aimed to elucidate the characteristics of hBMSC transdifferentiation into liver and immune cells. METHODS: A single type of hBMSCs was transplanted into immunodeficient Fah-/- Rag2-/- IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF). Liver transcriptional data from the hBMSC-transplanted mice were analysed to identify transdifferentiation with traces of liver and immune chimerism. RESULTS: Mice with FHF were rescued by implanted hBMSCs. Human albumin/leukocyte antigen (HLA) and CD45/HLA double-positive hepatocytes and immune cells were observed in the rescued mice during the initial 3 days. The transcriptomics analysis of liver tissues from dual-humanized mice identified two transdifferentiation phases (cellular proliferation at 1-5 days and cellular differentiation/maturation at 5-14 days) and ten cell lineages transdifferentiated from hBMSCs: human hepatocytes, cholangiocytes, stellate cells, myofibroblasts, endothelial cells and immune cells (T/B/NK/NKT/Kupffer cells). Two biological processes, hepatic metabolism and liver regeneration, were characterized in the first phase, and two additional biological processes, immune cell growth and extracellular matrix (ECM) regulation, were observed in the second phase. Immunohistochemistry verified that the ten hBMSC-derived liver and immune cells were present in the livers of dual-humanized mice. CONCLUSIONS: A syngeneic liver-immune dual-humanized mouse model was developed by transplanting a single type of hBMSC. Four biological processes linked to the transdifferentiation and biological functions of ten human liver and immune cell lineages were identified, which may help to elucidate the molecular basis of this dual-humanized mouse model for further clarifying disease pathogenesis.

Comparative Transcriptomic Analysis of MAPK-Mediated Regulation of Pathogenicity, Stress Responses, and Development in Cytospora chrysosperma.

Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction pathways that mediate cellular responses to various biotic and abiotic signals in plant-pathogenic fungi. Generally, there are three MAPKs in filamentous pathogenic fungi: Pmk1/Fus3/Kss1, Hog1, and Stl2. Our previous studies have shown that CcPmk1 is a core regulator of fungal pathogenicity in Cytospora chrysosperma, the causal agent of canker disease in a wide range of woody plants. Here, we identified and functionally characterized the other two MAPK genes (CcHog1 and CcSlt2) and then compared the transcriptional differences among these three MAPKs in C. chrysosperma. We found that the MAPKs shared convergent and distinct roles in fungal development, stress responses, and virulence. For example, CcHog1, CcSlt2, and CcPmk1 were all involved in conidiation and response to stresses, including hyperosmotic pressure, cell wall inhibition agents, and H2O2, but only CcPmk1 and CcSlt2 were required for hyphal growth and fungal pathogenicity. Transcriptomic analysis showed that numerous hyperosmosis- and cell wall-related genes significantly reduced their expression levels in ΔCcHog1 and ΔCcSlt2, respectively. Interestingly, RNA- and ribosome-related processes were significantly enriched in the upregulated genes of ΔCcSlt2, whereas they were significantly enriched in the downregulated genes of ΔCcPmk1. Moreover, two secondary metabolite gene clusters were significantly downregulated in ΔCcPmk1, ΔCcSlt2, and/or ΔCcHog1. Importantly, some virulence-associated genes were significantly downregulated in ΔCcPmk1 and/or ΔCcSlt2, such as candidate effector genes. Collectively, these results suggest that the similar and distinct phenotypes of each MAPK deletion mutant may result from the transcriptional regulation of a series of common or specific downstream genes, which provides a better understanding of the regulation network of MAPKs in C. chrysosperma.

Genome-Wide Identification and Transcriptional Analysis of the MYB Gene Family in Pearl Millet (Pennisetum glaucum).

The MYB gene family widely exists in the plant kingdom and participates in the regulation of plant development and stress response. Pearl millet (Pennisetum glaucum (L.) R. Br.), as one of the most important cereals, is not only considered a good source of protein and nutrients but also has excellent tolerances to various abiotic stresses (e.g., salinity, water deficit, etc.). Although the genome sequence of pearl millet was recently published, bioinformatics and expression pattern analysis of the MYB gene family are limited. Here, we identified 208 PgMYB genes in the pearl millet genome and employed 193 high-confidence candidates for downstream analysis. Phylogenetic and structural analysis classified these PgMYBs into four subgroups. Eighteen pairs of segmental duplications of the PgMYB gene were found using synteny analysis. Collinear analysis revealed pearl millet had the closest evolutionary relationship with foxtail millet. Nucleotide substitution analysis (Ka/Ks) revealed PgMYB genes were under purifying positive selection pressure. Reverse transcription-quantitative PCR analysis of eleven R2R3-type PgMYB genes revealed they were preferentially expressed in shoots and seeds and actively responded to various environment stimuli. Current results provide insightful information regarding the molecular features of the MYB family in pearl millet to support further functional characterizations.

Histaminergic System and Inflammation-Related Genes in Normal Large Intestine and Adenocarcinoma Tissues: Transcriptional Profiles and Relations.

Transcriptional analyses such as microarray data have contributed to the progress in the diagnostics and therapy of colorectal cancer (CRC). The need for such research is still present because of the disease being common in both men and women with a high second position in cancer rankings. Little is known about the relations between the histaminergic system and inflammation in the large intestine and CRC. Therefore, the aim of this study was to evaluate the expression of genes related to the histaminergic system and inflammation in the CRC tissues at three cancer development designs: all tested CRC samples, low (LCS) and high (HCS) clinical stage, and four clinical stages (CSI-CSIV), to the control. The research was carried out at the transcriptomic level, analysing hundreds of mRNAs from microarrays, as well as carrying out RT-PCR analysis of histaminergic receptors. The following histaminergic mRNAs: GNA15, MAOA, WASF2A, and inflammation-related: AEBP1, CXCL1, CXCL2, CXCL3, CXCL8, SPHK1, TNFAIP6, were distinguished. Among all analysed transcripts, AEBP1 can be considered the most promising diagnostic marker in the early stage of CRC. The results showed 59 correlations between differentiating genes of the histaminergic system and inflammation in the control, control and CRC, and CRC. The tests confirmed the presence of all histamine receptor transcripts in both the control and colorectal adenocarcinoma. Significant differences in expression were stated for HRH2 and HRH3 in the advanced stages of CRC adenocarcinoma. The relations between the histaminergic system and inflammation-linked genes in both the control and the CRC have been observed.

Physiological, Epigenetic, and Transcriptome Analyses Provide Insights into the Responses of Wheat Seedling Leaves to Different Water Depths under Flooding Conditions.

Flooding stress, including waterlogging and submergence, is one of the major abiotic stresses that seriously affects the growth and development of plants. In the present study, physiological, epigenetic, and transcriptomic analyses were performed in wheat seedling leaves under waterlogging (WL), half submergence (HS), and full submergence (FS) treatments. The results demonstrate that FS increased the leaves' hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and reduced their chlorophyll contents (SPAD), photosynthetic efficiency (Fv/Fm), and shoot dry weight more than HS and WL. In addition, FS increased catalase (CAT) and peroxidase (POD) activities more than HS and WL. However, there were no significant differences in the contents of H2O2, MDA, SPAD, and Fv/Fm, and the activities of superoxide dismutase (SOD) and POD between the HS and WL treatments. The changes in DNA methylation were related to stress types, increasing under the WL and HS treatments and decreasing under the FS treatment. Additionally, a total of 9996, 10,619, and 24,949 genes were differentially expressed under the WL, HS, and FS treatments, respectively, among which the 'photosynthesis', 'phenylpropanoid biosynthesis', and 'plant hormone signal transduction' pathways were extensively enriched under the three flooding treatments. The genes involved in these pathways showed flooding-type-specific expression. Moreover, flooding-type-specific responses were observed in the three conditions, including the enrichment of specific TFs and response pathways. These results will contribute to a better understanding of the molecular mechanisms underlying the responses of wheat seedling leaves to flooding stress and provide valuable genetic and epigenetic information for breeding flood-tolerant varieties of wheat.

[Transcriptional Analysis of the Gene Encoding the Putative Myristoylated Membrane Protein (ORF458R) of Invertebrate Iridescent Virus 6 (IIV6)].

Invertebrate iridescent virus 6 (IIV6) is a member of the genus Iridovirus and belongs to the Iridoviridae family. The entirely sequenced dsDNA genome, composed of 212.482 bp, encodes 215 putative open reading frames (ORFs). ORF458R encodes a putative myristoylated membrane protein. RT-PCR analysis of ORF458R expression in the presence of DNA replication and protein synthesis inhibitors showed that this gene is transcribed in the late phase of the virus infection. Time course analysis showed that transcription of ORF458R initiates between 12 and 24 h p.i. and starts to decrease after this point. Transcription of ORF458R initiated 53 nucleotides upstream of the translation start site and ended 40 nucleotides after the stop codon. Dual luciferase reporter gene assay showed that sequences between -61st and +18th nucleotides are essential for promoter activity. Interestingly, a remarkable decrease in promoter activity, in the presence of sequences between -299th and -143rd nucleotides, suggested a repressor activity between these regions. Our results showed that ORF458R is transcriptionally active, and separately located sequences at its upstream region with promoter and repressor activities regulating its expression. This information on the transcriptional analysis of ORF458R will contribute to our understanding of the molecular mechanisms of IIV6 replication.

Identification of potential lncRNA-miRNA-mRNA regulatory network contributing to aldosterone-producing adenoma.

Aldosterone-producing adenoma (APA) is a common cause of secondary hypertension. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network to uncover molecular mechanism underlying APA. The mRNA and lncRNA expression data of APA and adjacent adrenal gland (AAG) from GSE60044, GSE64957 and GSE101894 were obtained from the Gene Expression Omnibus (GEO) database to analyse differentially expressed genes (DEGs) and lncRNAs (DElncs). Hub genes were identified by robust rank aggregation (RRA) and protein-protein interaction (PPI) network analysis. The miRcode and miRWalk network tools were used to construct the ceRNA network. 1526 upregulated and 1512 downregulated DEGs were identified, which are mainly enriched in extracellular matrix and Ca2 + -related GO terms. In the KEGG pathway analysis, Ca2+ signalling and the aldosterone synthesis and secretion pathways were enriched. ceRNA network included 2 lncRNAs, 9 miRNAs, and 13 mRNAs. The lncRNAs are MEG3 and LINC00115. The mRNAs included CCND1, TP53, GPRC5B, BMI1, COMMD3-BMI1, ADAMTS15, STAT3, MMP2, SCN2B, CXCL12, HGF, FOS, and THBS1. Overall, this study conducted a ceRNA regulatory network analysis and identified that 2 lncRNAs and 13 mRNAs may contribute to the development of APA. These findings may provide novel diagnostic and intervention targets for APA.

Blastemal progenitors modulate immune signaling during early limb regeneration.

Blastema formation, a hallmark of limb regeneration, requires proliferation and migration of progenitors to the amputation plane. Although blastema formation has been well described, the transcriptional programs that drive blastemal progenitors remain unknown. We transcriptionally profiled dividing and non-dividing cells in regenerating stump tissues, as well as the wound epidermis, during early axolotl limb regeneration. Our analysis revealed unique transcriptional signatures of early dividing cells and, unexpectedly, repression of several core developmental signaling pathways in early regenerating stump tissues. We further identify an immunomodulatory role for blastemal progenitors through interleukin 8 (IL-8), a highly expressed cytokine in subpopulations of early blastemal progenitors. Ectopic il-8 expression in non-regenerating limbs induced myeloid cell recruitment, while IL-8 knockdown resulted in defective myeloid cell retention during late wound healing, delaying regeneration. Furthermore, the il-8 receptor cxcr-1/2 was expressed in myeloid cells, and inhibition of CXCR-1/2 signaling during early stages of limb regeneration prevented regeneration. Altogether, our findings suggest that blastemal progenitors are active early mediators of immune support, and identify CXCR-1/2 signaling as an important immunomodulatory pathway during the initiation of regeneration.

Transcriptome and Metabolome Analysis Revealing the Improved ε-Poly-l-Lysine Production Induced by a Microbial Call from Botrytis cinerea.

ε-Poly-l-lysine (ε-PL) is a wide-spectrum antimicrobial agent, while its biosynthesis-inducing signals are rarely reported. This study found that Botrytis cinerea extracts could act as a microbial call to induce a physiological modification of Streptomyces albulus for ε-PL efficient biosynthesis and thereby resulted in ε-PL production (34.2 g/liter) 1.34-fold higher than control. The elicitors could be primary isolated by ethanol and butanol extraction, which resulted in more vibrant, aggregate and stronger mycelia. The elicitor-derived physiological changes focused on three aspects: ε-PL synthase, energy metabolism, and lysine biosynthesis. After elicitor addition, upregulated sigma factor hrdD and improved transcription and expression of pls directly contributed to the high ε-PL productivity; upregulated genes in tricarboxylic acid (TCA) cycle and energy metabolism promoted activities of citrate synthase and the electron transport system; in addition, pool enlargements of ATP, ADP, and NADH guaranteed the ATP provision for ε-PL assembly. Lysine biosynthesis was also increased based on enhancements of gene transcription, key enzyme activities, and intracellular metabolite pools related to carbon source utilization, the Embden-Meyerhof pathway (EMP), the diaminopimelic acid pathway (DAP), and the replenishment pathway. Interestingly, the elicitors stimulated the gene transcription for the quorum-sensing system and resulted in upregulation of genes for other antibiotic production. These results indicated that the Botrytis cinerea could produce inducing signals to change the Streptomyces mycelial physiology and accelerate the ε-PL biosynthesis. IMPORTANCE This work identified the role of microbial elicitors on ε-PL production and disclosed the underlying mechanism through analysis of gene transcription, key enzyme activities, and intracellular metabolite pools, including transcriptome and metabolome analysis. It was the first report for the inducing effects of the "microbial call" to Streptomyces albulus and ε-PL biosynthesis, and these elicitors could be potentially obtained from decayed fruits infected by Botrytis cinerea; hence, this may be a way of turning a biohazard into bioproduct wealth. This study provided a reference for application of microbial signals in secondary metabolite production, which is of theoretical and practical significance in industrial antibiotic production.

Metabolic Profiling and Transcriptional Analysis of Carotenoid Accumulation in a Red-Fleshed Mutant of Pummelo (Citrus grandis).

Citrus grandis 'Tomentosa', commonly known as 'Huajuhong' pummelo (HJH), is used in traditional Chinese medicine and can moisten the lungs, resolve phlegm, and relieve coughs. A spontaneous bud mutant, named R-HJH, had a visually attractive phenotype with red albedo tissue and red juice sacs. In this study, the content and composition of carotenoids were investigated and compared between R-HJH and wild-type HJH using HPLC-MS analysis. The total carotenoids in the albedo tissue and juice sacs of R-HJH were 4.03- and 2.89-fold greater than those in HJH, respectively. The massive accumulation of carotenoids, including lycopene, ß-carotene and phytoene, led to the attractive red color of R-HJH. However, the contents of flavones, coumarins and most volatile components (mainly D-limonene and γ-terpinene) were clearly reduced in R-HJH compared with wild-type HJH. To identify the molecular basis of carotenoid accumulation in R-HJH, RNA-Seq transcriptome sequencing was performed. Among 3948 differentially expressed genes (DEGs), the increased upstream synthesis genes (phytoene synthase gene, PSY) and decreased downstream genes (ß-carotene hydroxylase gene, CHYB and carotenoid cleavage dioxygenase gene, CCD7) might be the key factors that account for the high level of carotenoids in R-HJH. These results will be beneficial for determining the molecular mechanism of carotenoid accumulation and metabolism in pummelo.

Profiling biotoxicities of hexafluoropropylene oxide trimer acid with human embryonic stem cell-based assays.

Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging replacement of perfluorooctanoic acid (PFOA), has recently been reported to be a potential environmental contaminant. Due to the similar structure to PFOA, HFPO-TA may cause comparable adverse effects on human health. Therefore, evaluating the toxic profiles of HFPO-TA has become an urgent task. In this study, we investigated the cytotoxicity and hepatoxicity of HFPO-TA using human embryonic stem cell (hESC)-based assays. Results showed that HFPO-TA reduced hESCs' viability in a dose dependent manner, and the calculated IC50 for 24, 48 and 72 hr were 222.8, 167.4, and 80.6 µmol/L, respectively. Significant intracellular ROS accumulation and mitochondrion membrane potential reduction were detected with HFPO-TA exposure, and increased apoptotic/necrotic cells were also observed in high dose of HFPO-TA treated group. Moreover, HFPO-TA at noncytotoxic concentrations also significantly impaired the functions of induced hepatocytes by diminishing cell glycogen storage ability and deregulating specific functional genes. Transcriptome sequencing analysis identified a set of hepatic associated biological processes responding to HFPO-TA exposure. PPAR was the most significantly enriched pathway. Genes including FGA, FGB, FGG, AHSG, HRG, ITIH2, ALB were characterized as hub genes by cytoHubba plug-in. These data indicated that HFPO-TA is a potential hepatotoxicant, and may not be a safe replacement for PFOA.

Transcriptome analysis of the influence of high plant protein based diet on Trachinotus ovatus liver.

Seeking out fish meal (FM) alternatives is an important requirement for aquaculture all over the world. And most practitioners believe that the plant protein is most potential for FM surrenal. While high plant protein feed caused some common problems in aquatic livestock: the absorption rate and growth rate are decreased, and even caused digestive tract inflammation. In present study, the inflence of high plant protien feed in Trachinotus ovatus was investigated using illumina HiSeqTM2000 based RNA-Seq. By comparing the two groups of cDNA libraries developed from high plant protien based diet or FM based diet fed T. ovatus livers, 836 unigenes were significantly upregulated, and 345 were significantly down regulated. KEGG analysis indicated that the differentially expressed genes (DEGs) are mainly metabolic-related genes. It was found that more than 28 DGEs beloned to the protein metabolism and absorption, lipid biosynthesis or other metabolic pathways. It indicated that high plant protein based diet had broad effects on metabolism on T. ovatus. There were also more DEGs belong to immune-related signaling pathways, include genes were involved in pathpathogen resistance and genes related to immunity system. These DEGs provided useful clues to explore the mechanisms that high plant protein based diet caused side effects on T. ovatus. These results improved our current understanding of the response of high plant protein based diet in T. ovatus, and outstanding the reasons of the side effect caused by high protein based diet.

Comparative transcriptome analysis of Tilletia horrida infection in resistant and susceptible rice (Oryza sativa L.) male sterile lines reveals potential candidate genes and resistance mechanisms.

Rice kernel smut (RKS), caused by the basidiomycete fungus Tilletia horrida, is one of the most devastating diseases affecting the production of male sterile lines of rice (Oryza sativa) worldwide. However, the molecular mechanisms of resistance to T. horrida have not yet been explored. In the present study, RNA sequencing analysis of rice male sterile lines, that are resistant and susceptible to RKS (Jiangcheng 3A and 9311A, respectively) was conducted after T. horrida infection. Transcriptomic analysis showed that a greater number of differentially expressed gene (DEGs) was observed in Jiangcheng 3A compared with 9311A after T. horrida inoculation. Furthermore, 4, 425 DEGs were uniquely detected in Jiangcheng 3A, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these DEGs revealed that oxidoreductase activity, peroxidase activity, cutin, suberine and wax biosynthesis, and flavonoid biosynthesis were key pathways for T. horrida resistance. In summary and based on transcriptome analysis, we suggest a preliminary regulatory mechanism for Jiangcheng 3A cultivar resistance response to T. horrida inoculation.

The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis.

Despite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological interventions. Recent transcriptional analyses in preclinical SCI studies have provided a snapshot of the local SCI-induced molecular responses in different animal models. However, the variation in the pathogenesis of traumatic SCI across species is yet to be explored. This study aims to identify and characterize the common and inconsistent SCI-induced differentially expressed genes across species to identify potential therapeutic targets of translational relevance. A comprehensive search of open-source transcriptome datasets identified four cross-compatible microarray experiments in rats, mice, and salamanders. We observed consistent expressional changes in extracellular matrix components across the species. Conversely, salamanders showed downregulation of intracellular MAPK signaling compared to rodents. Additionally, sequence conservation and interactome analyses highlighted the well-preserved sequences of Fn1 and Jun with extensive protein-protein interaction networks. Lastly, in vivo immunohistochemical staining for fibronectin was used to validate the observed expressional pattern. These transcriptional changes in extracellular and MAPK pathways present potential therapeutic targets for traumatic SCI with promising translational relevance.