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Panax quinquefolius L. is an important medicinal plant, and flavonoids are among its main secondary metabolites. The R2R3-MYB transcription factor plays an irreplaceable role in plant growth, development, and secondary metabolism. In our study, we identified 159 R2R3-MYBs and analyzed their physical and chemical properties in P. quinquefolius. The protein length of 159 PqMYBs varied from 107 to 1050 amino acids. The molecular weight ranged from 12.21 to 116.44 kDa. The isoelectric point was between 4.57 and 10.34. We constructed a phylogenetic tree of P. quinquefolius and Arabidopsis thaliana R2R3-MYB family members, and PqMYB members were divided into 33 subgroups. Transcriptome data analysis showed that the expression patterns of PqMYBs in root, leaf, and flower were significantly different. Following the MeJA treatment of seedlings, five candidate PqMYB genes demonstrated a response. A correlation analysis of PqMYBs and candidate flavonoid pathway genes showed that PqMYB2, PqMYB46, and PqMYB72 had correlation coefficients that were higher than 0.8 with PqCHS, PqANS4, and PqCCoAMT10, respectively. Furthermore, a transient expression assay confirmed that the three PqMYBs were localized in the nucleus. We speculated that these three PqMYBs were related to flavonoid biosynthesis in P. quinquefolius. These results provided a theoretical basis and a new perspective for further understanding the R2R3-MYB gene family and the biosynthesis mechanism of secondary metabolites in P. quinquefolius. [ABSTRACT FROM AUTHOR]

The gaseous phytohormone ethylene plays a crucial role in plant growth, development, and stress responses. In the ethylene signal transduction cascade, the F-box proteins EIN3-BINDING F-BOX 1 (EBF1) and EBF2 are identified as key negative regulators governing ethylene sensitivity. The translation and processing of EBF1/2 mRNAs are tightly controlled, and their 3′ untranslated regions (UTRs) are critical in these regulations. However, despite their significance, the exact mechanisms modulating the processing of EBF1/2 mRNAs remain poorly understood. In this work, we identified the gene DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1), which encodes an endoribonuclease and is induced by ethylene treatment, as a positive regulator of ethylene response. The loss of function mutant dne1-2 showed mild ethylene insensitivity, highlighting the importance of DNE1 in ethylene signaling. We also found that DNE1 colocalizes with ETHYLENE INSENSITIVE 2 (EIN2), the core factor manipulating the translation of EBF1/2, and targets the P-body in response to ethylene. Further analysis revealed that DNE1 negatively regulates the abundance of EBF1/2 mRNAs by recognizing and cleaving their 3′UTRs, and it also represses their translation. Moreover, the dne1 mutant displays hypersensitivity to 1,4-dithiothreitol (DTT)-induced ER stress and oxidative stress, indicating the function of DNE1 in stress responses. This study sheds light on the essential role of DNE1 as a modulator of ethylene signaling through regulation of EBF1/2 mRNA processing. Our findings contribute to the understanding of the intricate regulatory process of ethylene signaling and provide insights into the significance of ribonuclease in stress responses. [ABSTRACT FROM AUTHOR]

MutS homolog 1 (MSH1) is involved in the recombining and repairing of organelle genomes and is essential for maintaining their stability. Previous studies indicated that the length of the gene varied greatly among species and detected species-specific partial gene duplications in Physcomitrella patens. However, there are critical gaps in the understanding of the gene size expansion, and the extent of the partial gene duplication of MSH1 remains unclear. Here, we screened MSH1 genes in 85 selected species with genome sequences representing the main clades of green plants (Viridiplantae). We identified the MSH1 gene in all lineages of green plants, except for nine incomplete species, for bioinformatics analysis. The gene is a singleton gene in most of the selected species with conserved amino acids and protein domains. Gene length varies greatly among the species, ranging from 3234 bp in Ostreococcus tauri to 805,861 bp in Cycas panzhihuaensis. The expansion of MSH1 repeatedly occurred in multiple clades, especially in Gymnosperms, Orchidaceae, and Chloranthus spicatus. MSH1 has exceptionally long introns in certain species due to the gene length expansion, and the longest intron even reaches 101,025 bp. And the gene length is positively correlated with the proportion of the transposable elements (TEs) in the introns. In addition, gene structure analysis indicated that the MSH1 of green plants had undergone parallel intron gains and losses in all major lineages. However, the intron number of seed plants (gymnosperm and angiosperm) is relatively stable. All the selected gymnosperms contain 22 introns except for Gnetum montanum and Welwitschia mirabilis, while all the selected angiosperm species preserve 21 introns except for the ANA grade. Notably, the coding region of MSH1 in algae presents an exceptionally high GC content (47.7% to 75.5%). Moreover, over one-third of the selected species contain species-specific partial gene duplications of MSH1, except for the conserved mosses-specific partial gene duplication. Additionally, we found conserved alternatively spliced MSH1 transcripts in five species. The study of MSH1 sheds light on the evolution of the long genes of green plants. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) functions as a polypeptide hormone to regulate glucose and lipid metabolism, and its expression is regulated by cellular metabolic stress. Pyruvate is an important intermediate metabolite that acts as a key hub for cellular fuel metabolism. However, the effect of pyruvate on hepatic FGF21 expression and secretion remains unknown. Herein, we examined the gene expression and protein levels of FGF21 in human hepatoma HepG2 cells and mouse AML12 hepatocytes in vitro, as well as in mice in vivo. In HepG2 and AML12 cells, pyruvate at concentrations above 0.1 mM significantly increased FGF21 expression and secretion. The increase in cellular cAMP levels by adenylyl cyclase activation, phosphodiesterase (PDE) inhibition and 8-Bromo-cAMP administration significantly restrained pyruvate-stimulated FGF21 expression. Pyruvate significantly increased PDE activities, reduced cAMP levels and decreased CREB phosphorylation. The inhibition of exchange protein directed activated by cAMP (Epac) and cAMP response element binding protein (CREB) upregulated FGF21 expression, upon which pyruvate no longer increased FGF21 expression. The increase in plasma pyruvate levels in mice induced by the intraperitoneal injection of pyruvate significantly increased FGF21 gene expression and PDE activity with a reduction in cAMP levels and CREB phosphorylation in the mouse liver compared with the control. In conclusion, pyruvate activates PDEs to reduce cAMP and then inhibits the cAMP–Epac–CREB signaling pathway to upregulate FGF21 expression in hepatocytes. [ABSTRACT FROM AUTHOR]

Early-life stress during critical periods of brain development can have long-term effects on physical and mental health. Oxytocin is a critical social regulator and anti-inflammatory hormone that modulates stress-related functions and social behaviors and alleviates diseases. Oxytocin-related neural systems show high plasticity in early postpartum and adolescent periods. Early-life stress can influence the oxytocin system long term by altering the expression and signaling of oxytocin receptors. Deficits in social behavior, emotional control, and stress responses may result, thus increasing the risk of anxiety, depression, and other stress-related neuropsychiatric diseases. Oxytocin is regarded as an important target for the treatment of stress-related neuropsychiatric disorders. Here, we describe the history of oxytocin and its role in neural circuits and related behaviors. We then review abnormalities in the oxytocin system in early-life stress and the functions of oxytocin in treating stress-related neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Uveitis, defined as inflammation of the uveal tract, may cause blindness in both young and middle-aged people. Approximately 10–15% of blindness in the West is caused by uveitis. Therefore, a comprehensive investigation to determine the disease pathogenesis is urgent, as it will thus be possible to design effective treatments. Identification of the disease genes that cause uveitis is an important requirement to achieve this goal. To begin to answer this question, in this study, a computational method was proposed to identify novel uveitis-related genes. This method was executed on a large protein–protein interaction network and employed a popular ranking algorithm, the RandomWalk with Restart (RWR) algorithm. To improve the utility of the method, a permutation test and a procedure for selecting core genes were added, which helped to exclude false discoveries and select the most important candidate genes. The five-fold cross-validation was adopted to evaluate the method, yielding the average F1-measure of 0.189. In addition, we compared our method with a classic GBA-based method to further indicate its utility. Based on our method, 56 putative genes were chosen for further assessment. We have determined that several of these genes (e.g., CCL4, Jun, and MMP9) are likely to be important for the pathogenesis of uveitis. [ABSTRACT FROM AUTHOR]

For crop seed production, the development of anthers and male fertility are the main agronomic traits and key biological processes for flowering plants. Active DNA demethylation regulates many plant developmental processes and is ensured by 5-meC DNA glycosylase enzymes. To find out the role of OsROS1a, OsROS1a gene editing mutants were generated using the CRISPR/Cas9 system. The osros1a mutants had shrink spikelets, smaller anthers and pollen grains, and were not stained by iodine staining showing a significant reduction in total soluble sugar and starch contents as compared to wildtype (WT), which caused complete male sterility. Similarly, the expression of genes involved in pollen and anther development was decreased in osros1a mutants as compared to WT. Furthermore, bisulfite sequencing showed that the CG and CHG methylation of the OsPKS2 gene promoter was significantly increased in the osros1a mutant, which caused a reduced expression of OsPKS2 in osros1a mutants. DNA methylation of the TDR gene promoter was similar between WT and osros1a mutants, indicating that the DNA methylation effect by OsROS1a was gene specific. The expression of OsROS1a in the mutants was not changed, but it produced a frame-shift mutation to truncate the Pem-CXXC and RRMF domains. Combined with previous studies, our findings suggested that the RRMF domain in OsROS1a is the functional domain and loss of RRMF for OsROS1a causes sterility in rice. [ABSTRACT FROM AUTHOR]

The (--)-gallocatechin-3-gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM) on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent. [ABSTRACT FROM AUTHOR]

CXCL14 is not only involved in the immune process but is also closely related to neurodevelopment according to its molecular evolution. However, what role it plays in neurodevelopment remains unclear. In the present research, we found that, by crossbreeding CXCL14+/− and CXCL14−/− mice, the number of CXCL14−/− mice in their offspring was lower than the Mendelian frequency; CXCL14−/− mice had significantly fewer neurons in the external pyramidal layer of cortex than CXCL14+/− mice; and CXCL14 may be involved in synaptic plasticity, neuron projection, and chemical synaptic transmission based on analysis of human clinical transcriptome data. The expression of CXCL14 was highest at day 14.5 in the embryonic phase and after birth in the mRNA and protein levels. Therefore, we hypothesized that CXCL14 promotes the development of neurons in the somatic layer of the pyramidal cells of mice cortex on embryonic day 14.5. In order to further explore its mechanism, CXCR4 and CXCR7 were suggested as receptors by Membrane-Anchored Ligand and Receptor Yeast Two-Hybrid technology. Through metabolomic techniques, we inferred that CXCL14 promotes the development of neurons by regulating fatty acid anabolism and glycerophospholipid anabolism. [ABSTRACT FROM AUTHOR]

The hippocampal formation, particularly the CA2 subregion, is critical for social memory formation and memory processing, relying on synaptic plasticity—a fundamental mechanism by which synapses strengthen. Given the role of the ubiquitin–proteasome system (UPS) in various nervous system processes, including learning and memory, we were particularly interested in exploring the involvement of RING-type ubiquitin E3 ligases, such as UHRF2 (NIRF), in social behavior and synaptic plasticity. Our results revealed altered social behavior in mice with systemic Uhrf2 knockout, including changes in nest building, tube dominance, and the three-chamber social novelty test. In Uhrf2 knockout mice, the entorhinal cortex-CA2 circuit showed significant reductions in synaptic plasticity during paired-pulse facilitation and long-term potentiation, while the inability to evoke synaptic plasticity in the Schaffer-collateral CA2 synapses remained unaffected. These changes in synaptic plasticity correlated with significant changes in gene expression including genes related to vesicle trafficking and transcriptional regulation. The effects of Uhrf2 knockout on synaptic plasticity and the observed gene expression changes highlight UHRF2 as a regulator of learning and memory processes at both the cellular and systemic levels. Targeting E3 ubiquitin ligases, such as UHRF2, may hold therapeutic potential for memory-related disorders, warranting further investigation. [ABSTRACT FROM AUTHOR]

In this study, we hypothesized that different strains of Lactobacillus can alleviate hyperlipidemia and liver steatosis via activation of 5′ adenosine monophosphate-activated protein kinase (AMPK), an enzyme that is involved in cellular energy homeostasis, in aged rats. Male rats were fed with a high-fat diet (HFD) and injected with D-galactose daily over 12 weeks to induce aging. Treatments included (n = 6) (i) normal diet (ND), (ii) HFD, (iii) HFD-statin (lovastatin 2 mg/kg/day), (iv) HFD-Lactobacillus fermentum DR9 (10 log CFU/day), (v) HFD-Lactobacillus plantarum DR7 (10 log CFU/day), and (vi) HFD-Lactobacillus reuteri 8513d (10 log CFU/day). Rats administered with statin, DR9, and 8513d reduced serum total cholesterol levels after eight weeks (p < 0.05), while the administration of DR7 reduced serum triglycerides level after 12 weeks (p < 0.05) as compared to the HFD control. A more prominent effect was observed from the administration of DR7, where positive effects were observed, ranging from hepatic gene expressions to liver histology as compared to the control (p < 0.05); downregulation of hepatic lipid synthesis and β-oxidation gene stearoyl-CoA desaturase 1 (SCD1), upregulation of hepatic sterol excretion genes of ATP-binding cassette subfamily G member 5 and 8 (ABCG5 and ABCG8), lesser degree of liver steatosis, and upregulation of hepatic energy metabolisms genes AMPKα1 and AMPKα2. Taken altogether, this study illustrated that the administration of selected Lactobacillus strains led to improved lipid profiles via activation of energy and lipid metabolisms, suggesting the potentials of Lactobacillus as a promising natural intervention for alleviation of cardiovascular and liver diseases. [ABSTRACT FROM AUTHOR]

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details of the interaction mechanisms between inhibitors and SIRT6 at the atomic level. The nature of small molecules from herbs have many advantages as inhibitors. Based on the conformational characteristics of the inhibitor Compound 9 (Asinex ID: BAS13555470), we explored the natural molecule Scutellarin, one compound of Huang Qin, which is an effective herb for curing cancer that has been described in the Traditional Chinese Medicine (TCMS) library. We investigated the interactions between SIRT6 and the inhibitors using molecular dynamics (MD) simulations. We illustrated that the structurally similar inhibitors have a similar binding mode to SIRT6 with residues—Leu9, Phe64, Val115, His133 and Trp188. Hydrophobic and π-stacking interactions play important roles in the interactions between SIRT6 and inhibitors. In summary, our results reveal the interactive mechanism of SIRT6 and the inhibitors and we also provide Scutellarin as a new potential inhibitor of SIRT6. Our study provides a new potential way to explore potential inhibitors from TCMS. [ABSTRACT FROM AUTHOR]

Plant R2R3-MYB transcription factors (TFs) have been suggested to play crucial roles in the response to diverse abiotic and biotic stress factors but there is little molecular evidence of this role in soybean plants. In this work, we identified and functionally characterized an R2R3-MYB TF, namely, GsMYB15, from the wild soybean ED059. Protein and promoter sequence analysis indicated that GsMYB15 is a typical R2R3-MYB TF and contains multiple stress-related cis-elements in the promoter region. GsMYB15 is located in the nucleus and exhibits transcriptional activation activity. QPCR assays suggested that the expression of GsMYB15 could be induced by NaCl, insect attacks and defense-related hormones (MeJA and SA). Furthermore, GsMYB15 exhibited highest expression in pods compared to other tissues. Functional analysis of GsMYB15 demonstrated that overexpression of GsMYB15 could increase salt tolerance and enhance the resistance to H. armigera larvae in transgenic Arabidopsis plants. Moreover, overexpression of GsMYB15 also affected the expression levels of salt stress- and defense-related genes in the transgenic plants. Feeding with transgenic Arabidopsis plant leaves could significantly suppress the expression levels of immunity-related genes in H. armigera larvae. Overexpression of GsMYB15 also increased mesophyll cell levels in transgenic plants. Taken together, these results provide evidence that GsMYB15 is a positive regulator of salt stress tolerance and insect resistance in transformed Arabidopsis plants. [ABSTRACT FROM AUTHOR]

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric αβγ complex that functions as a central regulator of energy homeostasis. Energy stress manifests as a drop in the ratio of adenosine triphosphate (ATP) to AMP/ADP, which activates AMPK's kinase activity, allowing it to upregulate ATP-generating catabolic pathways and to reduce energy-consuming catabolic pathways and cellular programs. AMPK senses the cellular energy state by competitive binding of the three adenine nucleotides AMP, ADP, and ATP to three sites in its γ subunit, each, which in turn modulates the activity of AMPK's kinase domain in its α subunit. Our current understanding of adenine nucleotide binding and the mechanisms by which differential adenine nucleotide occupancies activate or inhibit AMPK activity has been largely informed by crystal structures of AMPK in different activity states. Here we provide an overview of AMPK structures, and how these structures, in combination with biochemical, biophysical, and mutational analyses provide insights into the mechanisms of adenine nucleotide binding and AMPK activity modulation. [ABSTRACT FROM AUTHOR]

5-aminolevulinic acid (ALA) increases plant tolerance to low-temperature stress, but the physiological and biochemical mechanisms that underlie its effects are not fully understood. To investigate them, cucumber seedlings were treated with different ALA concentrations (0, 15, 30 and 45 mg/L ALA) and subjected to low temperatures (12/8 °C day/night temperature). The another group (RT; regular temperature) was exposed to normal temperature (28/18 °C day/night temperature). Low-temperature stress decreased plant height, root length, leaf area, dry mass accumulation and the strong seedling index (SSI), chlorophyll contents, photosynthesis, leaf and root nutrient contents, antioxidant enzymatic activities, and hormone accumulation. Exogenous ALA application significantly alleviated the inhibition of seedling growth and increased plant height, root length, hypocotyl diameter, leaf area, and dry mass accumulation under low-temperature stress. Moreover, ALA increased chlorophyll content (Chl a, Chl b, Chl a+b, and Carotenoids) and photosynthetic capacity, net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr), as well as the activities of superoxide dismutase (SOD), peroxidase (POD, catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) enzymes, while decreasing hydrogen peroxide (H2O2), superoxide (O2•−), and malondialdehyde (MDA) contents under low-temperature stress. In addition, nutrient contents (N, P, K, Mg, Ca, Cu, Fe, Mn, and Zn) and endogenous hormones (JA, IAA, BR, iPA, and ZR) were enhanced in roots and leaves, and GA4 and ABA were decreased. Our results suggest the up-regulation of antioxidant enzyme activities, nutrient contents, and hormone accumulation with the application of ALA increases tolerance to low-temperature stress, leading to improved cucumber seedling performance. [ABSTRACT FROM AUTHOR]

Sipunculus nudus, an old marine species, has great potential for use as functional seafood due to its various bioactivities. Its potential antithrombotic activity pushed us to isolate the bio-active components bio-guided by tracking fibrinolytic activity. As a result, a novel protease named as SK (the kinase obtained from S. nudus) was obtained, which possessed a molecular weight of 28,003.67 Da and 15 N-terminal amino acid sequences of PFPVPDPFVWDTSFQ. SK exerted inhibitory effects on thrombus formation through improving the coagulation system with dose-effect relationship within a certain range. Furthermore, in most cases SK got obviously better effect than that of urokinase. With the help of untargeted mass spectrometry-based metabolomics profiling, arachidonic acid, sphingolipid, and nicotinate and nicotinamide mechanism pathways were found to be important pathways. They revealed that the effect mechanism of SK on common carotid arterial thrombosis induced by FeCl3 was achieved by inhibiting vessel contraction, platelet aggregation, adhesion, and release, correcting endothelial cell dysfunction and retarding process of thrombus formation. This study demonstrated SK was a promising thrombolytic agent on the basis of its comprehensive activities on thrombosis, and it should get further exploitation and utilization. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NACT) has been established as being an effective treatment for advanced gastric cancer (GC), while the predictive biomarker of NACT efficacy remains under investigation. Aspartate β-hydroxylase (ASPH) represents an attractive target which is a highly conserved transmembrane enzyme overexpressed in human GC, and participates in the malignant transformation by promoting tumor cell motility. Here, we evaluated the expression of ASPH by immunohistochemistry in 350 GC tissues (including samples for NACT) and found that ASPH expression was higher in patients undergoing NACT compared with patients without NACT pre-operation. The OS and PFS time of ASPH-intensely positive patients was significantly shorter than that of the negative patients in the NACT group, while the difference was not significant in patients without NACT. We showed that ASPH knockout enhanced the inhibitory effects of chemotherapeutic drugs on the cell proliferation, migration, and invasion in vitro and suppressed tumor progression in vivo. Co-immunoprecipitation revealed that ASPH might interact with LAPTM4B to perform chemotherapeutic drug resistance. Our results suggested that ASPH might serve as a candidate biomarker to predict prognosis and a novel therapeutic target for gastric cancer patients treated with neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Orchidaceae is one of the largest families of angiosperms. Considering the large number of species in this family and its symbiotic relationship with fungi, Orchidaceae provide an ideal model to study the evolution of plant mitogenomes. However, to date, there is only one draft mitochondrial genome of this family available. Here, we present a fully assembled and annotated sequence of the mitochondrial genome (mitogenome) of Paphiopedilum micranthum, a species with high economic and ornamental value. The mitogenome of P. micranthum was 447,368 bp in length and comprised 26 circular subgenomes ranging in size from 5973 bp to 32,281 bp. The genome encoded for 39 mitochondrial-origin, protein-coding genes; 16 tRNAs (three of plastome origin); three rRNAs; and 16 ORFs, while rpl10 and sdh3 were lost from the mitogenome. Moreover, interorganellar DNA transfer was identified in 14 of the 26 chromosomes. These plastid-derived DNA fragments represented 28.32% (46,273 bp) of the P. micranthum plastome, including 12 intact plastome origin genes. Remarkably, the mitogenome of P. micranthum and Gastrodia elata shared 18% (about 81 kb) of their mitochondrial DNA sequences. Additionally, we found a positive correlation between repeat length and recombination frequency. The mitogenome of P. micranthum had more compact and fragmented chromosomes compared to other species with multichromosomal structures. We suggest that repeat-mediated homologous recombination enables the dynamic structure of mitochondrial genomes in Orchidaceae. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease characterized by pulmonary vascular remodeling and right heart enlargement the pathogenesis of PAH is complicated; no biologic-based therapy is available for the treatment of PAH, but recent studies suggest that inflammatory response and abnormal proliferation of pulmonary artery smooth muscle cells are the main pathogenic mechanism, while the role of immune-related long non-coding RNAs (lncRNAs) remains unclear. The aim of this study was to systematically analyze immune-related lncRNAs in PAH. Here, we downloaded a publicly available microarray data from PAH and control patients (GSE113439). A total of 243 up-regulated and 203 down-regulated differentially expressed genes (DEGs) were screened, and immune-related DEGs were further obtained from ImmPort. The immune-related lncRNAs were obtained by co-expression analysis of immune-related mRNAs. Then, immune-related lncRNAs-mRNAs network including 2 lncRNAs and 6 mRNAs was constructed which share regulatory miRNAs and have significant correlation. Among the lncRNA-mRNA pairs, one pair (JPX-RABEP1) was verified in the validating dataset GSE53408 and PAH mouse model. Furthermore, the immune cell infiltration analysis of the GSE113439 dataset revealed that the JPX-RABEP1 pair may participate in the occurrence and development of PAH through immune cell infiltration. Together, our findings reveal that the lncRNA-mRNA pair JPX-RABEP1 may be a novel biomarker and therapeutic target for PAH. [ABSTRACT FROM AUTHOR]

Demethyleneberberine (DMB) is an essential metabolite of Berberine (BBR) in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA)-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs) and induce cell apoptosis through the nuclear factor-κB (NF-κB) cascade. Immunohistochemical (IHC) and quantitative polymerase chain reaction (qPCR) analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor β 1 (TGF-β1)-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs). These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation. [ABSTRACT FROM AUTHOR]

The endosperm is the main nutrient source in cereals for humans, as it is a highly specialized storage organ for starch, lipids, and proteins, and plays an essential role in seed growth and development. Active DNA demethylation regulates plant developmental processes and is ensured by cytosine methylation (5-meC) DNA glycosylase enzymes. To find out the role of OsROS1a in seed development, the null mutant of OsROS1a was generated using the CRISPR/Cas9 system. The null mutant of OsROS1a was stable and heritable, which affects the major agronomic traits, particularly in rice seeds. The null mutant of OsROS1a showed longer and narrower grains, and seeds were deformed containing an underdeveloped and less-starch-producing endosperm with slightly irregularly shaped embryos. In contrast to the transparent grains of the wild type, the grains of the null mutant of OsROS1a were slightly opaque and rounded starch granules, with uneven shapes, sizes, and surfaces. A total of 723 differential expression genes (DEGs) were detected in the null mutant of OsROS1a by RNA-Seq, of which 290 were downregulated and 433 were upregulated. The gene ontology (GO) terms with the top 20 enrichment factors were visualized for cellular components, biological processes, and molecular functions. The key genes that are enriched for these GO terms include starch synthesis genes (OsSSIIa and OsSSIIIa) and cellulose synthesis genes (CESA2, CESA3, CESA6, and CESA8). Genes encoding polysaccharides and glutelin were found to be downregulated in the mutant endosperm. The glutelins were further verified by SDS-PAGE, suggesting that glutelin genes could be involved in the null mutant of OsROS1a seed phenotype and OsROS1a could have the key role in the regulation of glutelins. Furthermore, 378 differentially alternative splicing (AS) genes were identified in the null mutant of OsROS1a, suggesting that the OsROS1a gene has an impact on AS events. Our findings indicated that the function on rice endosperm development in the null mutant of OsROS1a could be influenced through regulating gene expression and AS, which could provide the base to properly understand the molecular mechanism related to the OsROS1a gene in the regulation of rice seed development. [ABSTRACT FROM AUTHOR]

Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification. [ABSTRACT FROM AUTHOR]

Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opioids, which are frequently prescribed post-operatively. In light of the opioid crisis, understanding the interactions between opioid use and the development of sepsis has become extremely relevant, as opioid use is associated with increased risk of infection. Given that the intestinal tract is a major site of origin of sepsis-causing microbes, there has been an increasing focus on how alterations in the gut microbiome may predispose towards sepsis and mediate immune dysregulation. MicroRNAs, in particular, have emerged as key modulators of the inflammatory response during sepsis by tempering the immune response, thereby mediating the interaction between host and microbiome. In this review, we elucidate contributing roles of microRNA 146 in modulating sepsis pathogenesis and end with a discussion of therapeutic targeting of the gut microbiome in controlling immune dysregulation in sepsis. [ABSTRACT FROM AUTHOR]

In a previous paper, we reported that triptolide (TP), a commonly used immunomodulator, could attenuate cardiac hypertrophy. This present study aimed to further explore the inhibition of cardiac fibrosis by TP and the possible mechanism from the perspective of the NOD-like receptor protein 3 (NLRP3) inflammasome. Hematoxylin-eosin and Masson's staining, immunohistochemistry, and immunofluorescence were performed to observe cardiac fibrotic changes in mice and mouse cardiac fibroblasts (CFs). The Western blot, colocalization, and immunoprecipitation were applied to detect protein expression and interactions. Results suggested that TP dose-dependently inhibited cardiac fibrosis induced by isoproterenol and collagen production of CFs induced by angiotensin II. TP exhibited an antifibrotic effect via inhibiting activation of the NLRP3 inflammasome, which sequentially decreased IL-1β maturation, myeloid differentiation factor 88 (MyD88)-related phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase 1/2 (ERK1/2), and TGF-β1/Smad signaling, and ultimately resulted in less collagen production. Moreover, TP showed no antifibrotic effect in Nlrp3-knockout CFs. Notably, TP inhibited the expression of NLRP3 and apoptosis-associated speck-like proteins containing a caspase recruitment domain (ASC) as well as inflammasome assembly, by interrupting the NLRP3-ASC interaction to inhibit inflammasome activation. Finally, TP indeed inhibited the NLRP3-TGFβ1-Smad pathway in vivo. Conclusively, TP was found to play a dual role in interrupting the activation of the NLRP3 inflammasome to attenuate cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs) function to selectively control the flow of water and other small molecules through biological membranes, playing crucial roles in various biological processes. However, little information is available on the AQP gene family in bananas. In this study, we identified 47 banana AQP genes based on the banana genome sequence. Evolutionary analysis of AQPs from banana, Arabidopsis, poplar, and rice indicated that banana AQPs (MaAQPs) were clustered into four subfamilies. Conserved motif analysis showed that all banana AQPs contained the typical AQP-like or major intrinsic protein (MIP) domain. Gene structure analysis suggested the majority of MaAQPs had two to four introns with a highly specific number and length for each subfamily. Expression analysis of MaAQP genes during fruit development and postharvest ripening showed that some MaAQP genes exhibited high expression levels during these stages, indicating the involvement of MaAQP genes in banana fruit development and ripening. Additionally, some MaAQP genes showed strong induction after stress treatment and therefore, may represent potential candidates for improving banana resistance to abiotic stress. Taken together, this study identified some excellent tissue-specific, fruit development- and ripening-dependent, and abiotic stress-responsive candidate MaAQP genes, which could lay a solid foundation for genetic improvement of banana cultivars. [ABSTRACT FROM AUTHOR]

BASIC PENTACYSTEINE (BPC) is a small transcription factor family that functions in diverse growth and development processes in plants. However, the roles of BPCs in plants, especially cucumber (Cucumis sativus L.), in response to abiotic stress and exogenous phytohormones are still unclear. Here, we identified four BPC genes in the cucumber genome, and classified them into two groups according to phylogenetic analysis. We also investigated the gene structures and detected five conserved motifs in these CsBPCs. Tissue expression pattern analysis revealed that the four CsBPCs were expressed ubiquitously in both vegetative and reproductive organs. Additionally, the transcriptional levels of the four CsBPCs were induced by various abiotic stress and hormone treatments. Overexpression of CsBPC2 in tobacco (Nicotiana tabacum) inhibited seed germination under saline, polyethylene glycol, and abscisic acid (ABA) conditions. The results suggest that the CsBPC genes may play crucial roles in cucumber growth and development, as well as responses to abiotic stresses and plant hormones. CsBPC2 overexpression in tobacco negatively affected seed germination under hyperosmotic conditions. Additionally, CsBPC2 functioned in ABA-inhibited seed germination and hypersensitivity to ABA-mediated responses. Our results provide fundamental information for further research on the biological functions of BPCs in development and abiotic stress responses in cucumber and other plant species. [ABSTRACT FROM AUTHOR]

Rootstocks frequently exert detrimental effects on the fruit quality of grafted cucumber (Cucumis sativus L.) plants. To understand and ultimately correct this deficiency, a transcriptomic and metabolomic comparative analysis was performed among cucumber fruits from non-grafted plants (NG), and fruits from plants grafted onto different rootstocks of No.96 and No.45 (Cucurbita moschata. Duch), known to confer a different aroma and taste. We found remarkable changes in the primary metabolites of sugars, organic acids, amino acids, and alcohols in the fruit of the grafted cucumber plants with different rootstocks, compared to the non-grafted ones, especially No.45. We identified 140, 131, and 244 differentially expressed genes (DEGs) in the comparisons of GNo.96 vs. NG, GNo.45 vs. NG, and GNo.45 vs. GNo.96. The identified DEGs have functions involved in many metabolic processes, such as starch and sucrose metabolism; the biosynthesis of diterpenoid, carotenoid, and zeatin compounds; and plant hormone signal transduction. Members of the HSF, AP2/ERF-ERF, HB-HD-ZIP, and MYB transcription factor families were triggered in the grafted cucumbers, especially in the cucumber grafted on No.96. Based on a correlation analysis of the relationships between the metabolites and genes, we screened 10 candidate genes likely to be involved in sugar metabolism (Fructose-6-phosphate and trehalose), linoleic acid, and amino-acid (isoleucine, proline, and valine) biosynthesis in grafted cucumbers, and then confirmed the gene expression patterns of these genes by qRT-PCR. The levels of TPS15 (Csa3G040850) were remarkably increased in cucumber fruit with No.96 rootstock compared with No.45, suggesting changes in the volatile chemical production. Together, the results of this study improve our understanding of flavor changes in grafted cucumbers, and identify the candidate genes involved in this process. [ABSTRACT FROM AUTHOR]

The class III peroxidase (POD) enzymes participate in plant development, hormone signaling, and stress responses. However, little is known about the POD family in cassava. Here, we identified 91 cassava POD genes (MePODs) and classified them into six subgroups using phylogenetic analysis. Conserved motif analysis demonstrated that all MePOD proteins have typical peroxidase domains, and gene structure analysis showed that MePOD genes have between one and nine exons. Duplication pattern analysis suggests that tandem duplication has played a role in MePOD gene expansion. Comprehensive transcriptomic analysis revealed that MePOD genes in cassava are involved in the drought response and postharvest physiological deterioration. Several MePODs underwent transcriptional changes after various stresses and related signaling treatments were applied. In sum, we characterized the POD family in cassava and uncovered the transcriptional control of POD genes in response to various stresses and postharvest physiological deterioration conditions. These results can be used to identify potential target genes for improving the stress tolerance of cassava crops. [ABSTRACT FROM AUTHOR]