Double neutron star (DNS) merger events are promising candidates of short gamma-ray burst (sGRB) progenitors as well as high-frequency gravitational wave (GW) emitters. On August 17, 2017, such a ...coinciding event was detected by both the LIGO-Virgo gravitational wave detector network as GW170817 and Gamma-Ray Monitor on board NASA's Fermi Space Telescope as GRB 170817A. Here, we show that the fluence and spectral peak energy of this sGRB fall into the lower portion of the distributions of known sGRBs. Its peak isotropic luminosity is abnormally low. The estimated event rate density above this luminosity is at least Formula: see text Gpc
yr
, which is close to but still below the DNS merger event rate density. This event likely originates from a structured jet viewed from a large viewing angle. There are similar faint soft GRBs in the Fermi archival data, a small fraction of which might belong to this new population of nearby, low-luminosity sGRBs.
Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment ...remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial.
Twenty-eight patients ...with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1-T2) and then every 2 months throughout treatment (T3-T10) and posttreatment periods (T11-T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC).
Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had -1.88 for GMFM (p = 0.11), -0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function.
Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia.
This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.
Natural deep eutectic solvents (NADESs) are efficient in extracting natural products. However, traditional organic solvents are toxic in the extraction of anthraquinones from
Rheum palmatum
L. To ...solve this problem, we applied natural deep eutectic solvent ultrasound-assisted extraction in this study for the extraction of total anthraquinones from
R. palmatum
L. Principal component analysis revealed that the selected NADES which consisted of lactic acid, glucose and water (LGH), was highly efficient in extracting anthraquinones from
R. palmatum
L. The ratio of lactic acid/glucose and the addition of water in LGH were investigated
via
a single-factor experiment. With a lactic acid/glucose ratio of 5 : 1 (mol/mol), and 10% of water (v/v), LGH had a high extraction yield to anthraquinones. Optimized by response surface methodology (RSM), the optimized extraction conditions of extraction time, extraction temperature and solvent-to-solid ratio of 1.5 h, 82 °C and 26 mL g
−1
, respectively. Under optimum conditions, the extraction yields of aloe-emodin, rhein, emodin, chrysophanol, physcion and total anthraquinones were 2.60 ± 0.01, 5.78 ± 0.02, 2.21 ± 0.02, 5.87 ± 0.02, 8.81 ± 0.01 and 25.27 ± 0.07 mg g
−1
, respectively. The enrichment and separation of five anthraquinones in LGH extraction solution were efficiently achieved using DM130 macroporous resin, with purities of 90.98%, 96.67%, 92.37%, 95.80% and 91.61% as indicated by HPLC, and recovery yields of 84.08%, 79.51%, 84.96%, 81.83% and 78.35%, respectively. LGH was environmentally friendly and highly efficient in extracting anthraquinones from
R. palmatum
L., and NADESs showed potential for the extraction of effective components from natural products.
Natural deep eutectic solvents ultrasound-assisted extraction (NADES-UAE) was applied to extract total anthraquinones from
Rheum palmatum
L.
Migmatite gneisses are widespread in the Dabie orogen, but their formation ages are poorly constrained. Eight samples of migmatite, including leucosome, melanosome, and banded gneiss, were selected ...for U–Pb dating and Hf isotope analysis. Most metamorphic zircon occurs as overgrowths around inherited igneous cores or as newly grown grains. Morphological and internal structure features suggest that their growth is associated with partial melting. According to the Hf isotope ratio relationships between metamorphic zircon and inherited cores, three formation mechanisms for metamorphic zircon can be determined, which are dissolution–reprecipitation of pre‐existing zircon, breakdown of Zr‐bearing phase other than zircon in a closed system and crystallization from externally derived Zr‐bearing melt. Four samples contain magmatic zircon cores, yielding upper intercept U–Pb ages of 807 ± 35–768 ± 12 Ma suggesting that the protoliths of the migmatites are Neoproterozoic in age. The migmatite zircon yields weighted mean two‐stage Hf model ages of 2513 ± 97–894 ± 54 Ma, indicating reworking of both juvenile and ancient crustal materials at the time of their protolith formation. The metamorphic zircons give U–Pb ages of 145 ± 2–120 ± 2 Ma. The oldest age indicates that partial melting commenced prior to 145 Ma, which also constrains the onset of extensional tectonism in this region to pre‐145 Ma. The youngest age of 120 Ma was obtained from an undeformed granitic vein, indicating that deformation in this area was complete at this time. Two major episodes of partial melting were dated at 139 ± 1 and 123 ± 1Ma. The first episode of partial melting is obviously older than the timing of post‐collision magmatism, corresponding to regional extension. The second episode of partial melting is coeval with the widespread post‐collision magmatism, indicating the gravitational collapse and delamination of the orogenic lithospheric keel of the Dabie orogen, which were possibly triggered by the uprising of the Cretaceous mid‐Pacific superplume.
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
One of the main functions of the piwi‐interacting RNA pathway is the post‐transcriptional silencing of transposable elements in the germline of many species. In insects, proteins belonging to the ...Tudor superfamily proteins belonging to the Tudor superfamily play an important role in to play an important role in this mechanism. In this study, we identified the tudor gene in the oriental fruit fly, Bactrocera dorsalis, investigated the spatiotemporal expressional profile of the gene, and performed a functional analysis using RNA interference. We identified one transcript for a tudor homologue in the B. dorsalis transcriptome, which encodes a protein containing the typical 10 Tudor domains and an Adenosine triphosphate (ATP) synthase delta subunit signature. Phylogenetic analysis confirmed the identity of this transcript as a tudor homologue in this species. The expression profile indicated a much higher expression in the adult and pupal stages compared to the larval stages (up to a 60‐fold increase), and that the gene was mostly expressed in the ovaries, Malpighian tubules and fat body. Finally, gene knockdown of tudor in B. dorsalis led to clearly underdeveloped ovaries in the female adult and reductions in copulation rate and amount of oviposition, indicating its important role in reproduction. The results of this study shed more light on the role of tudor in ovary development and reproduction.
Summary
Background
IL‐21 is a key cytokine for regulating B cell immunity, which is involved in several inflammatory conditions. This study sought to define a role for IL‐21 in activated B ...lymphocytes and enhanced tissue eosinophilia in NP tissues during the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).
Methods
NP and uncinate process tissues were collected from 64 CRSwNP patients, 25 CRSsNP patients, and 29 control subjects. IL‐21 expression was examined using IHC staining, qRT‐PCR, flow cytometry, and ELISA, and its clinical implication was evaluated. Moreover, the effects of IL‐21 on B cell differentiation and Ig production in cultured NP cells were examined in vitro.
Results
The mRNA and protein levels of IL‐21 were significantly increased in polyp tissues compared with control tissues (P < 0.05). Polyp IL‐21 level was significantly associated with polyp size, tissue eosinophilia and asthma comorbidity, and recurrence after surgery (P < 0.05). Both Th1 and Th17 cells were the main cellular sources of IL‐21 in polyp tissues. The percentage of IL‐21+CD4+ cells was significantly higher in polyp tissues compared with control tissues and matched PBMCs (P < 0.01). Accordingly, the percentage of CD19+CD20+/− CD38high cells was significantly higher in polyp tissues compared with control tissues (P < 0.01). Moreover, recombinant IL‐21 significantly increased the percentage of CD19+CD20+/− CD38high cells (plasmablasts) and IgG and IgA production in cultured NP cells in vitro (P < 0.05).
Conclusion and Clinical Relevance
Increased IL‐21 level in polyp tissues was associated with disease severity, local B cell activation, and immunoglobulin production, suggesting that IL‐21 might play an important role in promoting persistent mucosal inflammation in CRSwNP patients.
We present an empirical stellar spectra library created using spectra from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) DR5. This library represents a uniform data set ...ranging from 3750 through 8500 K in effective temperature (Teff), from −2.5 through +1.0 dex in metallicity (Fe/H), and from 0 to 5.0 dex in gravity (log g). The spectra in the library have resolutions R ∼ 1800, with well-calibrated fluxes and rest-framed wavelengths. Using a large number of red stars observed by LAMOST, we generated denser K-type templates to fill in data missing from current empirical spectral libraries, particularly the late K type. For K giants, we calibrated the spectroscopic surface gravities against the asteroseismic surface gravities. To verify the reliability of the parameters labeled for this library, we performed an internal cross-validation using a χ2 minimization method to interpolate the parameters of each individual spectrum using the remaining spectra in the library. We obtained precisions of 41 K, 0.11 dex, and 0.05 dex for Teff, log g, and Fe/H, respectively, which means the templates are labeled with correct stellar parameters. Through external comparisons, we confirmed that measurements of the stellar parameters through this library can achieve accuracies of approximately 125 K in Teff, 0.1 dex in Fe/H and 0.20 dex in log g without systematic offset. This empirical library is useful for stellar parameter measurements because it has large parameter coverage and full wavelength coverage from 3800 to 8900 .
PDF
