In this Letter, we present a spectacular eruptive flare (X8.2) associated with a coronal mass ejection on 2017 September 10 at the west limb of the Sun. A flux rope eruption is followed by the ...inflow, the formation of a current sheet, and a cusp structure, which were simultaneously observed during the occurrence of this flare. The hierarchical layers of the cusp-shaped structure are well observed in 131 observation. The scenario that can be created from these observations is very consistent with the predictions of some eruptive models. Except for the characteristics mentioned above in the process of the flare predicted by classical eruption models, the current sheet separating into several small current sheets is also observed at the final stage of the flux rope eruption. The quantitative calculation of the velocities and accelerations of the inflow, hot cusp structure, and post-flare loops is presented. The width of the current sheet is estimated to be about 3 × 103 km. These observations are very useful in understanding the process of solar eruptions.
Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development ...and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC). Increased expression and nuclear localization of TEAD4 were found in a significant portion of CRC tissues, in association with metastasis and a poor prognosis. In CRC cells, TEAD4 knockdown induced the mesenchymal-epithelial transition and decreased cell mobility in vitro and metastasis in vivo. Microarray analysis revealed that TEAD4 promoted cell adhesion and upregulated the epithelial-mesenchymal transition-related transcriptome in CRC cells. Vimentin was identified as a new direct target gene mediating TEAD4 function in CRC cells, whereby forced vimentin expression markedly reversed TEAD4-knockdown-induced cell morphological changes and decreased mobility. Interestingly, rescued expression of both WT TEAD4 and a Y429H mutant can reverse the mesenchymal-epithelial transition and increase vimentin expression, cell mobility and metastatic potential in TEAD4-knockdown CRC cells. The discrepant expression of YAP and TEAD4 in CRC tissues, the rescue ability of TEAD4 mutant defect in YAP binding and no effect on vimentin expression by YAP knockdown in CRC cells, all implicated a YAP-independent manner of TEAD4 function in CRC. Furthermore, vimentin positively correlated and CDH1 reversely correlated with the level of TEAD4 in CRC tissues and xenograft tumors. Our results suggest that TEAD4 nuclear expression can serve as a biomarker for CRC progression and poor prognosis. The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway.
The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the ...impact of tumour-infiltrating inflammation on survival outcomes.
Ovid MEDLINE and EMBASE were searched to identify studies reporting the prognostic significance of tumour-infiltrating inflammation for patients with CRC. The primary outcome measures were overall survival (OS), cancer-specific survival (CS) and disease-free survival (DFS).
A total of 30 studies involving 2988 patients were identified. Studies were subdivided into those considering the associations between CRC survival and generalised tumour inflammatory infiltrate (n=12) and T lymphocyte subsets (n=18). Pooled analyses revealed that high generalised tumour inflammatory infiltrate was associated with good OS (HR, 0.59; 95% CI, 0.48-0.72), CS (HR, 0.40; 95% CI, 0.27-0.61) and DFS (HR, 0.72; 95% CI, 0.57-0.91). Stratification by location and T lymphocyte subset indicated that in the tumour centre, CD3+, CD8+ and FoxP3+ infiltrates were not statistically significant prognostic markers for OS or CS. In the tumour stroma, high CD8+, but not CD3+ or FoxP3+ cell infiltrates indicated increased OS. Furthermore, high CD3+ cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS; and high CCR7+ infiltrate was also indicated increased OS.
Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses.
Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%–20% of colorectal cancers (CRCs) harbor activating mutations ...in PIK3CA, making it one of the most frequently mutated genes in CRC. We thus carried out a systematic review and meta-analysis investigating the prognostic significance of PIK3CA mutations in CRC.
Electronic databases were searched from inception through May 2015. We extracted the study characteristics and prognostic data of each eligible study. The hazard ratio (HR) and 95% confidence interval (CI) were derived and pooled using the random-effects Mantel–Haenszel model.
Twenty-eight studies enrolling 12 747 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 19 and 10 studies, respectively. Comparing PIK3CA-mutated CRC patients with PIK3CA-wild-type CRC patients, the summary HRs for OS and PFS were 0.96 (95% CI 0.83–1.12) and 1.20 (95% CI 0.98–1.46), respectively. The trim-and-fill, Copas model and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Five studies reported the CRC prognosis for PIK3CA mutations in exons 9 and 20 separately; neither exon 9 mutation nor exon 20 mutation in PIK3CA was significantly associated with patient survival.
Our findings suggest that PIK3CA mutation has the neutral prognostic effects on CRC OS and PFS. Evidence was accumulating for the establishment of CRC survival between PIK3CA mutations and patient-specific clinical or molecular profiles.
Using the projector-augmented wave method within the generalized gradient approximation, a systematic first-principles calculation for energy vs. volume (
E–V) equations of state (EOS’s) and single ...crystal elastic stiffness constants (
c
ij
’s) has been performed for 76 pure elemental solids with face-centered-cubic (fcc), body-centered-cubic (bcc), and hexagonal-close-packed (hcp) crystal structures, wherein the
c
ij
’s are determined by an efficient strain–stress method, and the EOS’s are fitted by a 4-parameter Birch–Murnaghan equation upon the first-principles
E–V data points. Based on the predicted EOS’s and
c
ij
’s, the phase transition pressures between bcc, fcc, and hcp structures, as well as the structural stabilities and the polycrystalline aggregate properties including bulk modulus (
B), shear modulus (
G),
B/
G ratio, and anisotropy ratio have been analyzed for pure elements and compared with available experimental data. The present systematic studies of pure elements provide not only the EOS’s and
c
ij
’s but also the benchmarks of first-principles calculations.
Sleep is an evolutionarily conserved state that supports brain functions, including synaptic plasticity, in species across the animal kingdom. Here, we examine the neuroanatomical and cell-type ...distribution of presynaptic scaling in the fly brain after sleep loss. We previously found that sleep loss drives accumulation of the active zone scaffolding protein Bruchpilot (BRP) within cholinergic Kenyon cells of the
mushroom body (MB), but not in other classes of MB neurons. To test whether similar cell type-specific trends in plasticity occur broadly across the brain, we used a flp-based genetic reporter to label presynaptic BRP in cholinergic, dopaminergic, GABAergic, or glutamatergic neurons. We then collected whole-brain confocal image stacks of BRP intensity to systematically quantify BRP, a marker of presynapse abundance, across 37 neuropil regions of the central fly brain. Our results indicate that sleep loss, either by overnight (12-h) mechanical stimulation or chronic sleep disruption in
mutants, broadly elevates cholinergic synapse abundance across the brain, while synapse abundance in neurons that produce other neurotransmitters undergoes weaker, if any, changes. Extending sleep deprivation to 24 h drives brain-wide upscaling in glutamatergic, but not other, synapses. Finally, overnight male-male social pairings induce increased BRP in excitatory synapses despite male-female pairings eliciting more waking activity, suggesting experience-specific plasticity. Within neurotransmitter class and waking context, BRP changes are similar across the 37 neuropil domains, indicating that similar synaptic scaling rules may apply across the brain during acute sleep loss and that sleep need may broadly alter excitatory-inhibitory balance in the central brain.
Bedaquiline treatment significantly improves multidrug-resistant tuberculosis (MDR-TB) patient treatment outcomes. However, safety and efficacy data are lacking for bedaquiline used with background ...regimens to treat Chinese TB patients. Here, we describe our initial clinical experience for bedaquiline treatment of a large multicentre cohort of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patients in China.
Patients (177) received 24-week bedaquiline treatment combined with personalized anti-TB drug background regimens. As primary efficacy endpoints, times to initial sputum culture conversion were measured.
Of 177 MDR-TB patients completing the 24-week treatment course, sputum culture conversion occurred for 151/177 (85.3%), while 26 had unfavourable outcomes, including 3/177 (1.7%) deaths and 23/177 (13.0%) non-responders at treatment completion. The median time to sputum culture conversion was 4 (interquartile range 2–8) weeks. Conversion rates were 33/39 (84.6%, 95% confidence interval (CI) 73.3–95.9) for MDR-TB patients, 47/56 (83.9%, 95% CI 74.3–93.6) for pre-XDR-TB patients and 71/82 (86.6%, 95% CI 79.2–94.0) for XDR-TB patients. Multivariate analysis demonstrated that patients with low body mass index (odds ratio 7.356; 95% CI 2.652–20.401) were at significantly high risk of unfavourable outcomes, with serious adverse events noted in 15 (8.5%) patients, including six with corrected QT interval (QTc) prolongation times (>500 ms).
Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.
Aims. We perform a three-dimensional (3D) high resolution numerical simulation in isothermal magnetohydrodynamics to study the magnetic reconnection process in a current sheet (CS) formed during an ...eruption of a twisted magnetic flux rope (MFR). Because the twist distribution violates the Kruskal-Shafranov condition, the kink instability occurs, and the MFR is distorted. The centre part of the MFR loses its equilibrium and erupts upward, which leads to the formation of a 3D CS underneath it. Methods. In order to study the magnetic reconnection inside the CS in detail, mesh refinement has been used to reduce the numerical diffusion and we estimate a Lundquist number S = 104 in the vicinity of the CS. Results. The refined mesh allows us to resolve fine structures inside the 3D CS: a bifurcating sheet structure signaling the 3D generalization of Petschek slow shocks, some distorted-cylindrical substructures due to the tearing mode instabilities, and two turbulence regions near the upper and the lower tips of the CS. The topological characteristics of the MFR depend sensitively on the observer’s viewing angle: it presents as a sigmoid structure, an outwardly expanding MFR with helical distortion, or a flare-CS-coronal mass ejection symbiosis as in 2D flux-rope models when observed from the top, the front, or the side.
Aims
To reveal the microbial communities from Qinghai–Tibetan Plateau wetland soils that have the potential to be used in the utilization of cellulosic and chitinous biomass at low temperatures ...(≤25°C).
Methods and Results
Soil samples collected from six wetlands on Qinghai–Tibetan Plateau were supplemented with or without cellulose and chitin flakes, and anaerobically incubated at 25 and 15°C; high‐throughput 16S rRNA gene sequencing was used to access the composition and localization (in the slurry and on the surface) of enriched microbial communities; a hypothetical model was constructed to demonstrate the functional roles of involved microbes mainly at genus level. Overall, microbial communities from Qinghai–Tibetan Plateau wetlands showed significant potential to convert both cellulose and chitin to methane at low temperatures; Clostridium III, Clostridium XIVa, Paludibacter, Parcubacteria, Saccharofermentans, Pelotomaculum, Methanosaeta, Methanobrevibacter, Methanoregula, Methanospirillum and Methanosarcina participated in methanogenic degradation of both cellulose and chitin through the roles of hydrolytic, saccharolytic and secondary fermenters and methanogens respectively. Acetotrophic methanogens were mainly enriched in the slurries, while hydrogenotrophic methanogens could be both in the slurries and on the surface.
Conclusions
The composition and localization of microbial communities that could effectively convert cellulose and chitin to methane at low temperatures have been revealed by high‐throughput 16S rRNA gene sequencing methods, and reviewing the literatures on the microbial pure culture helped to elucidate functional roles of significantly enriched microbes.
Significance and Impact of the Study
This study will contribute to the understanding of carbon and nitrogen cycling of cellulose and chitin in cold‐area wetlands and provide fundamental information to obtain microbial resources for the utilization of biomass wastes at low temperatures.
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