Pomolic acid inhibits proliferation of human lung carcinoma cells via induction of apoptosis and suppression of cell migration and invasion

Purpose: To investigate the anti-proliferative effect of pomolic acid on lung cancer cells (A549), and theunderlying mechanism.Methods: The viability of pomolic acid-treated A549 cells was determined by MTT and colony formation assays. Cell colony formation was monitored with acridine orange/ethidium bromide (AO/EB) staining. Protein expressions of Bax and Bcl-2 were assayed by western blotting.Results: Pomolic acid suppressed the growth of A549 cells, with an half-maximal inhibitory concentration of (IC50) of 10 μM (p < 0.05). However, the IC50 of pomolic acid for normal BEAS-2B cells was 80 μM. Pomolic acid also decreased colony formation of A549 cells. At 20 μM, the percentage of A549 colonies decreased to 14 % of control. The dose-dependent cytotoxicity of pomolic acid against A549 cells was mediated via induction of apoptosis and oxidative stress. Pomolic acid treatment enhanced the expression of Bax and decreased the expression of Bcl-2 in A549 cells. Moreover, pomolic acid inhibited the migration and invasion in A549 cells in a dose-dependent manner (p < 0.05).Conclusion: These results indicate the potent anticancer effect of pomolic acid against human lung cancer cells. Thus, pomolic acid has promising potential as a lead molecule for the development of chemotherapy

ABI4 Mediates Antagonistic Effects of Abscisic Acid and Gibberellins at Transcript and Protein Levels

Abscisic acid (ABA) and gibberellins (GA) are plant hormones which antagonistically mediate numerous physiological processes, and their optimal balance is essential for normal plant development. However, the molecular mechanism underlying ABA and GA antagonism still needs to be determined. Here, we report that ABA- INSENSITIVE 4 (ABI4) is a central factor for GA/ABA homeostasis and antagonism in post-germination stages. ABI4 over-expression in Arabidopsis (OE-ABI4) leads to developmental defects including a decrease in plant height and poor seed production. The transcription of a key ABA biosynthetic gene, NCED6, and of a key GA catabolic gene, GA2ox7, is significantly enhanced by ABI4 over-expression. ABI4 activates NCED6 and GA2ox7 transcription by directly binding to the promoters, and genetic analysis revealed that mutation in these two genes partially rescues the dwarf phenotype of ABI4 overexpressing plants. Consistently, ABI4 overexpressing seedlings have a lower GA/ABA ratio compared to the wild type. We further show that ABA induces GA2ox7 transcription while GA represses NCED6 expression in an ABI4-dependent manner; and that ABA stabilizes the ABI4 protein, whereas GA promotes its degradation. Taken together, these results propose that ABA and GA antagonize each other by oppositely acting on ABI4 transcript and protein levels

Transcriptional Profiling of Protein Expression Related Genes of Pichia pastoris under Simulated Microgravity

The physiological responses and transcription profiling of Pichia pastoris GS115 to simulated microgravity (SMG) were substantially changed compared with normal gravity (NG) control. We previously reported that the recombinant P. pastoris grew faster under SMG than NG during methanol induction phase and the efficiencies of recombinant enzyme production and secretion were enhanced under SMG, which was considered as the consequence of changed transcriptional levels of some key genes. In this work, transcriptiome profiling of P. pastoris cultured under SMG and NG conditions at exponential and stationary phases were determined using next-generation sequencing (NGS) technologies. Four categories of 141 genes function as methanol utilization, protein chaperone, RNA polymerase and protein transportation or secretion classified according to Gene Ontology (GO) were chosen to be analyzed on the basis of NGS results. And 80 significantly changed genes were weighted and estimated by Cluster 3.0. It was found that most genes of methanol metabolism (85% of 20 genes) and protein transportation or secretion (82.2% of 45 genes) were significantly up-regulated under SMG. Furthermore the quantity and fold change of up-regulated genes in exponential phase of each category were higher than those of stationary phase. The results indicate that the up-regulated genes of methanol metabolism and protein transportation or secretion mainly contribute to enhanced production and secretion of the recombinant protein under SMG

Electroshock treatment dependent microstructural evolution and mechanical properties of near-β titanium alloy manufactured by directed energy deposition

Effects of electroshock treatment (EST) on the microstructural evolution and mechanical properties of near-β titanium alloy (Ti-55531) formed by directed energy deposition (DED) was studied in this work. With the increase in EST time, the average hardness of specimen decreased from 426 HV to 316 HV, and the fracture strain increased significantly, which was attributed to the uniform dispersion of α phase along grain boundaries and inside the β grains. After EST, the texture intensity decreased in terms of the orientation distribution function (ODF), which was ascribed to the redistribution of α phase. Moreover, more atomic vacancies and lattice distortion were formed near the α/β interfaces, which were verified by transmission electron microscopy (TEM) observation and ascribed to the migration of atoms near the interface under EST. External loadings facilitated the dislocation motion and lattice distortions near the interfaces, which resulted in the reduction in hardness and the improvement in ductility. The above results indicated that EST can quickly alter the microstructure and mechanical properties of DED titanium alloys as a simple and energy-saving method

A SURVEY OF LUMINOUS HIGH-REDSHIFT QUASARS WITH SDSS AND WISE. II. THE BRIGHT END OF THE QUASAR LUMINOSITY FUNCTION AT z similar to 5

This is the second paper in a series on a new luminous z ~ 5 quasar survey using optical and near-infrared colors. Here we present a new determination of the bright end of the quasar luminosity function (QLF) at z ~ 5. Combining our 45 new quasars with previously known quasars that satisfy our selections, we construct the largest uniform luminous z ~ 5 quasar sample to date, with 99 quasars in the range of 4.7 ≤ z < 5.4 and −29 < M 1450 ≤ −26.8, within the Sloan Digital Sky Survey (SDSS) footprint. We use a modified 1/V a method including flux limit correction to derive a binned QLF, and we model the parametric QLF using maximum likelihood estimation. With the faint-end slope of the QLF fixed as α = −2.03 from previous deeper samples, the best fit of our QLF gives a flatter bright end slope β = −3.58 ± 0.24 and a fainter break magnitude ${M}_{1450}^{* }$ = −26.98 ± 0.23 than previous studies at similar redshift. Combined with previous work at lower and higher redshifts, our result is consistent with a luminosity evolution and density evolution model. Using the best-fit QLF, the contribution of quasars to the ionizing background at z ~ 5 is found to be 18%–45% with a clumping factor C of 2–5. Our sample suggests an evolution of radio loud fraction with optical luminosity but no obvious evolution with redshift

SDSS J013127.34−-032100.1: A newly discovered radio-loud quasar at z=5.18z=5.18 with extremely high luminosity

Only very few z>5 quasars discovered to date are radio-loud, with a radio-to-optical flux ratio (radio-loudness parameter) higher than 10. Here we report the discovery of an optically luminous radio-loud quasar, SDSS J013127.34-032100.1 (J0131-0321 in short), at z=5.18+-0.01 using the Lijiang 2.4m and Magellan telescopes. J0131-0321 has a spectral energy distribution consistent with that of radio-loud quasars. With an i-band magnitude of 18.47 and radio flux density of 33 mJy, its radio-loudness parameter is ~100. The optical and near-infrared spectra taken by Magellan enable us to estimate its bolometric luminosity to be L_bol ~ 1.1E48 erg/s, approximately 4.5 times greater than that of the most distant quasar known to date. The black hole mass of J0131-0321 is estimated to be 2.7E9 solar masses, with an uncertainty up to 0.4 dex. Detailed physical properties of this high-redshift, radio-loud, potentially super-Eddington quasar can be probed in the future with more dedicated and intensive follow-up observations using multi-wavelength facilities.Comment: 5 pages, 3 figures, accepted to ApJ

RNA methylation pattern and immune microenvironment characteristics mediated by m6A regulator in ischemic stroke

Background: Ischemic stroke (IS) is a highly heterogeneous disease. Recent studies have shown that epigenetic variables affect the immune response. However, only a few studies have examined the relationship between IS and m6A immunoregulation. Therefore, we aim to explore the methylation of RNA mediated by m6A regulatory factor and the immune microenvironment characteristics of IS.Methods: Differentially expressed m6A regulators were detected in IS microarray datasets GSE22255 and GSE58294. We used a series of machine learning algorithms to identify key IS-related m6A regulators and validated them on blood samples of IS patients, oxygen-glucose deprivation/reoxygenation (OGD/R) microglia and GSE198710 independent data sets. Different m6A modification modes were determined and the patients were classified. In addition, we systematically associate these modification patterns with the characteristics of immune microenvironment, including infiltrating immune cells, immune function genes and immune response genes. Then we developed a model of m6A score to quantify the m6A modification in IS samples.Results: Through the analysis of the differences between the control group and IS patients, METTL16, LRPPRC, and RBM15 showed strong diagnostic significance in three independent data sets. In addition, qRT-PCR and Western blotting also confirmed that the expression of METTL16 and LRPPRC was downregulated and the expression of RBM15 was upregulated after ischemia. Two m6A modification modes and two m6A gene modification modes were also identified. m6A gene cluster A (high m6A value group) was positively correlated with acquired immunity, while m6A gene cluster B (low m6A value group) was positively correlated with innate immunity. Similarly, five immune-related hub genes were significantly associated with m6Acore (CD28, IFNG, LTF, LCN2, and MMP9).Conclusion: The modification of m6A is closely related to the immune microenvironment. The evaluation of individual m6A modification pattern may be helpful for future immunomodulatory therapy of anti-ischemic response

Dcf1 Deficiency Attenuates the Role of Activated Microglia During Neuroinflammation

Microglia serve as the principal immune cells and play crucial roles in the central nervous system, responding to neuroinflammation via migration and the execution of phagocytosis. Dendritic cell-derived factor 1 (Dcf1) is known to play an important role in neural stem cell differentiation, glioma apoptosis, dendritic spine formation, and Alzheimer’s disease (AD), nevertheless, the involvement of the Dcf1 gene in the brain immune response has not yet been reported. In the present paper, the RNA-sequencing and function enrichment analysis suggested that the majority of the down-regulated genes in Dcf1-/- (Dcf1-KO) mice are immune-related. In vivo experiments showed that Dcf1 deletion produced profound effects on microglial function, increased the expression of microglial activation markers, such as ionized calcium binding adaptor molecule 1 (Iba1), Cluster of Differentiation 68 (CD68) and translocator protein (TSPO), as well as certain proinflammatory cytokines (Cxcl1, Ccl7, and IL17D), but decreased the migratory and phagocytic abilities of microglial cells, and reduced the expression levels of some other proinflammatory cytokines (Cox-2, IL-1β, IL-6, TNF-α, and Csf1) in the mouse hippocampus. Furthermore, in vitro experiments revealed that in the absence of lipopolysaccharide (LPS), the majority of microglia were ramified and existed in a resting state, with only approximately 10% of cells exhibiting an amoeboid-like morphology, indicative of an activated state. LPS treatment dramatically increased the ratio of activated to resting cells, and Dcf1 downregulation further increased this ratio. These data indicated that Dcf1 deletion mediates neuroinflammation and induces dysfunction of activated microglia, preventing migration and the execution of phagocytosis. These findings support further investigation into the biological mechanisms underlying microglia-related neuroinflammatory diseases, and the role of Dcf1 in the immune response

Endoscopic endonasal transsphenoidal surgery for unusual sellar lesions: eight cases and review of the literature

BackgroundPreoperative imaging for some unusual lesions in the sellar region can pose challenges in establishing a definitive diagnosis, impacting treatment strategies.MethodsThis study is a retrospective analysis of eight cases involving unusual sellar region lesions, all treated with endoscopic endonasal transsphenoidal surgery (EETS). We present the clinical, endocrine, and radiological characteristics, along with the outcomes of these cases.ResultsAmong the eight cases, the lesions were identified as follows: Solitary fibrous tumor (SFT) in one case, Lymphocytic hypophysitis (LYH) in one case, Cavernous sinus hemangiomas (CSH) in one case, Ossifying fibroma (OF) in two cases; Sphenoid sinus mucocele (SSM) in one case, Pituitary abscess (PA) in two cases. All patients underwent successful EETS, and their diagnoses were confirmed through pathological examination. Postoperatively, all patients had uneventful recoveries without occurrences of diabetes insipidus or visual impairment.ConclusionOur study retrospectively analyzed eight unusual lesions of the sellar region. Some lesions exhibit specific imaging characteristics and clinical details that can aid in preoperative diagnosis and inform treatment strategies for these unusual sellar diseases