We continue our systematic statistical study of various components of gamma-ray burst (GRB) optical light curves. We decompose the early onset bump and the late re-brightening bump with empirical ...fits and analyze their statistical properties. Among the 146 GRBs that have well-sampled optical light curves, the onset and re-brightening bumps are observed in 38 and 26 GRBs, respectively. It is found that the typical rising and decaying slopes for both the onset and re-brightening bumps are ~1.5 and ~ - 1.15, respectively. No early onset bumps in the X-ray band are detected to be associated with the optical onset bumps, while an X-ray re-brightening bump is detected for half of the re-brightening optical bumps. The peak luminosity is anti-correlated with the peak time Lp is proportional to t super(-1.81+ or -0.32)p for the onset bumps and Lp is proportional to t super(-0.83+ or -0.17)p for the re-brightening bumps. Both Lp and the isotropic energy release of the onset bumps are correlated with E sub(Gamma, iso), whereas no similar correlation is found for the re-brightening bumps. These results suggest that the afterglow onset bumps are likely due to the deceleration of the GRB fireballs. Taking the onset bumps as probes for the properties of the fireballs and their ambient medium, we find that the typical power-law index of the relativistic electrons is 2.5 and the medium density profile behaves as nis proportional tor super(-1) within the framework of the synchrotron external shock models. With the medium density profile obtained from our analysis, we also confirm the correlation between the initial Lorentz factor (Gamma sub(0)) and E sub(iso, Gamma) in our previous work. The jet component that produces the re-brightening bump seems to be on-axis and independent of the prompt emission jet component. Its typical kinetic energy budget would be about one order of magnitude larger than the prompt emission component, but with a lower Gamma sub(0), typically several tens.
We have studied two events in which relatively superdense plasma appeared near geosynchronous orbit after the interplanetary magnetic field (IMF) changed from a long period of northward condition to ...southward condition. We used the magnetosphere MHD model Open Geospace General Circulation Model to simulate these two events and compared the simulation results with observations. The observations and the simulation results show that an extended period of northward IMF caused a cold dense plasma sheet (CDPS) to form in the near tail, and a subsequent southward IMF caused a highly stretched near‐tail dipole field, which enhanced the earthward convection and eventually set off reconnection. Some of the cold dense plasma was thus consequently transported to geosynchronous orbit and formed a superdense plasma sheet (SDPS). CDPS is the main source of SDPS in its early stage after the IMF southward turning.
Key Points
An event with both CDPS and SDPS observations is reproduced in an OpenGGCM simulation
CDPS is the main source of SDPS in its early stage
CDPS and a subsequent IMF southward turning causes the formation of SDPS
The Asian citrus psyllid, Diaphorina citri is the principal vector of huanglongbing, which transmits Candidatus Liberibacter asiaticus. Trehalase is a key enzyme involved in trehalose hydrolysis and ...plays an important role in insect growth and development. The specific functions of this enzyme in D. citri have not been determined. In this study, three trehalase genes (DcTre1‐1, DcTre1‐2, and DcTre2) were identified based on the D. citri genome database. Bioinformatic analysis showed that DcTre1‐1 and DcTre1‐2 are related to soluble trehalase, whereas DcTre2 is associated with membrane‐bound trehalase. Spatiotemporal expression analysis indicated that DcTre1‐1 and DcTre1‐2 had the highest expression levels in the head and wing, respectively, and DcTre2 had high expression levels in the fat body. Furthermore, DcTre1‐1 and DcTre1‐2 expression levels were induced by 20‐hydroxyecdysone and juvenile hormone Ⅲ, but DcTre2 was unaffected. The expression levels of DcTre1‐1, DcTre1‐2, and DcTre2 were significantly upregulated, which resulted in high mortality after treatment with validamycin. Trehalase activities and glucose contents were downregulated, but the trehalose content increased after treatment with validamycin. In addition, the expression levels of chitin metabolism‐related genes significantly decreased at 24 and 48 h after treatment with validamycin. Furthermore, silencing of DcTre1‐1, DcTre1‐2, and DcTre2 reduced the expression levels of chitin metabolism‐related genes and led to a malformed phenotype of D. citri. These results indicate that D. citri trehalase plays an essential role in regulating chitin metabolism and provides a new target for control of D. citri.
Major depressive disorder (MDD) is a prevalent and debilitating psychiatric mood disorder that lacks objective laboratory-based tests to support its diagnosis. A class of microRNAs (miRNAs) has been ...found to be centrally involved in regulating many molecular processes fundamental to central nervous system function. Among these miRNAs, miRNA-134 (miR-134) has been reported to be related to neurogenesis and synaptic plasticity. In this study, the hypothesis that plasma miR-134 can be used to diagnose MDD was tested. Perturbation of peripheral and central miR-134 in a depressive-like rat model was also examined. By reverse-transcription quantitative PCR, miR-134 was comparatively measured in a small set of plasma samples from MDD and healthy control (HC) subjects. To determine its diagnostic efficacy, plasma miR-134 levels were assessed in 100 MDD, 50 bipolar disorder (BD), 50 schizophrenic (SCZ), and 100 HC subjects. A chronic unpredictable mild stress (CUMS) rat model was also developed to evaluate miR-134 expression in plasma, hippocampus (HIP), prefrontal cortex (PFC), and olfactory bulb. We found that plasma miR-134 was significantly downregulated in MDD subjects. Diagnostically, plasma miR-134 levels could effectively distinguish MDD from HC with 79% sensitivity and 84% specificity, while distinguishing MDD from HC, BD, and SCZ subjects with 79% sensitivity and 76.5% specificity. Congruent with these clinical findings, CUMS significantly reduced miR-134 levels in the rat plasma, HIP, and PFC. Although limited by the relatively small sample size, these results demonstrated that plasma miR-134 displays potential ability as a biomarker for MDD.
Background
Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High‐dose dual therapy has recently shown encouraging results in H. pylori eradication, but it ...has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first‐line therapy for H. pylori eradication, and factors that affect the curing rate.
Methods
This is a single‐center, prospective, open‐label, randomized‐controlled trial. Naive patients (n=292) were randomly treated with bismuth‐containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13C‐urea breath test.
Results
In per‐protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention‐to‐treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group.
Conclusions
Rabeprazole‐amoxicillin dual therapy is equally effective to the bismuth‐containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non‐smoking condition, which deserves future stratified analysis for refinement and optimization.
Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes, and leads to apoptosis. Apoptosis is very important in regulating the homeostasis of the hepatobiliary system. Endoplasmic ...reticulum (ER) stress is one of the signaling pathways that induce apoptosis. Moreover, the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-induced apoptotic pathway is the main way; but its role in liver injury remains unclear. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that alleviates liver injury and apoptosis, yet its mechanism is unknown. We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice (OJ).
To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein (CHOP)-growth arrest and DNA damage-inducible protein 34 (GADD34) pathway and B cell lymphoma/leukemia-2 related X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) ratio.
For
experiments, 30 rats were divided into three groups: control group, OJ model group, and YCHD-treated group. Blood was collected to detect the indicators of liver function, and liver tissues were used for histological analysis. For
experiments, 30 rats were divided into three groups: G1, G2, and G3. The rats in group G1 had their bile duct exposed without ligation, the rats in group G2 underwent total bile duct ligation, and the rats in group G3 were given a gavage of YCHD. According to the serum pharmacology, serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells. Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) assay was used to detect BRL-3A hepatocyte apoptosis. Alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in the medium were detected. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to detect protein and gene expression levels of PERK, CHOP, GADD34, Bax, and Bcl-2 in the liver tissues and BRL-3A cells.
Biochemical assays and haematoxylin and eosin staining suggested severe liver function injury and liver tissue structure damage in the OJ model group. The TUNEL assay showed that massive BRL-3A rat hepatocyte apoptosis was induced by OJ. Elevated ALT and AST levels in the medium also demonstrated that hepatocytes could be destroyed by OJ. Western blot or qRT-PCR analyses showed that the protein and mRNA expression levels of PERK, CHOP, and GADD34 were significantly increased both in the rat liver tissue and BRL-3A rat hepatocytes by OJ. The Bax and Bcl-2 levels were increased, and the Bax/Bcl-2 ratio was also increased. When YCHD was used, the PERK, CHOP, GADD34, and Bax levels quickly decreased, while the Bcl-2 levels increased, and the Bax/Bcl-2 ratio decreased.
OJ-induced liver injury and hepatocyte apoptosis are associated with the activation of the PERK-CHOP-GADD34 pathway and increased Bax/Bcl-2 ratio. YCHD can attenuate these changes.
Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces ...neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells.
BV-2 cells were treated with resveratrol (25, 50, and 100 µM) and/or LPS (1 µg/ml). Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP-responsive element-binding protein (CREB) were measured by western blot. Resveratrol significantly attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked the effects of resveratrol on LPS-induced microglial activation. In addition, mTOR inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK).
This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes and proinflammatory cytokines via down-regulation phosphorylation of NF-κB, CREB and MAPKs family in a mTOR-dependent manner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol.
Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main ...constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS).
BV-2 cells were pretreated with gastrodin (30, 40, and 60 µM) for 1 h and then stimulated with LPS (1 µg/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-κB (NF-κB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1β and NF-κB. LPS (1 µg/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 µM). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor κB-α (IκB-α) (and hence the activation of NF-κB) and of CREB, respectively.
This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases.
Six new citreoviridins (citreoviridins J-O,
-
) and twenty-two known compounds (
-
) were isolated from the deep-sea-derived
MCCC 3A00169. The structures of the new compounds were determined by ...spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O (
-
) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A (
), terrein (
), and citreoviridin (
) significantly induced apoptosis for HeLa cells with IC
values of 5.4
M, 11.3
M, and 0.7
M, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.
A metal- and base-free 5- endo -trig sulfonylative cyclization between 1,5-dienes, aryldiazonium salts and SO 2 (from SOgen) is presented. This method could successfully produce sulfonylated ...pyrrolin-2-ones in one pot with excellent regioselectivity and good-to-excellent yields. This strategy features mild reaction conditions and broad substrate scope. Moreover, a scale-up reaction and three synthetic applications demonstrate the practicality of this method. Lastly, control experiments indicate that the 5- endo -trig sulfonylative cyclization may proceed in a radical pathway.
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