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.
Background and purpose
Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end‐stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently ...reported to associate with RLS. We aim to perform a large‐scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world.
Methods
From October 2009 to October 2011, we constitutively recruited 1130 patients with ESRD from 17 hemodialysis centers. Demographic, laboratory data, presence and severity of RLS were collected. Odds ratios (ORs) were estimated by logistic regression models.
Results
We found the prevalence of RLS to be 25.3% in patients with ESRD. Having type 2 diabetes OR = 3.61 (2.27–5.77), P < 0.01, low serum transferrin saturation OR = 1.42 (1.01–2.03), P < 0.05 and duration of dialysis OR = 1.09 (1.03–1.14), P < 0.01 were associated with RLS. In contrast, high serum hemoglobin level was inversely associated with RLS OR = 0.61 (0.40–0.89), P < 0.05. RLS has a significant impact on sleep quality in dialysis patients. Among patients with RLS, history of type 2 diabetes OR = 4.04 (1.65–10.79), P < 0.05, low serum hemoglobin level OR = 5.41 (2.43–13.12), P < 0.01 and duration of dialysis OR = 1.01 (1.01–1.02), P < 0.01 were associated with increased severity of RLS.
Conclusions
Our findings demonstrated that RLS is common in Taiwanese dialysis patients. Clinicians should have a high suspicion for the presence of RLS symptoms in patients with ESRD, especially those with type 2 diabetes, anemia, low serum iron status and long duration of dialysis.
Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ...ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions. Here we demonstrate a trapped-ion quantum network node in the dual-type qubit scheme where two types of qubits are encoded in the S and F hyperfine structure levels of
Yb
ions. We generate ion photon entanglement for the S-qubit in a typical timescale of hundreds of milliseconds, and verify its small crosstalk on a nearby F-qubit with coherence time above seconds. Our work demonstrates an enabling function of the dual-type qubit scheme for scalable quantum networks.
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
To explore the characteristics of Helicobacter pylori resistance in China and the association between antibiotic resistance and several clinical factors.
H. pylori strains were collected from ...patients in 13 provinces or cities in China between 2010 and 2016. Demographic data including type of disease, geographic area, age, gender and isolation year were collected to analyse their association with antibiotic resistance. Antibiotic resistance was detected using the Etest test and the Kirby-Bauer disc diffusion method.
H. pylori were successfully cultured from 1117 patients. The prevalence of metronidazole, clarithromycin (CLA), azithromycin, levofloxacin (LEV), moxifloxacin, amoxicillin (AMO), tetracycline and rifampicin resistance was 78.2, 22.1, 23.3, 19.2, 17.2, 3.4, 1.9 and 1.5%, respectively. No resistance to furazolidone was observed. The resistance rates to LEV and moxifloxacin were higher in strains isolated from patients with gastritis compared to those with duodenal ulcer and among women. Compared to patients ≥40 years old, younger patients exhibited lower resistance rates to CLA, azithromycin, LEV and moxifloxacin. The resistance rates to CLA and AMO were higher in strains isolated more recently, and we also found that the prevalence of resistance to metronidazole, CLA, azithromycin and AMO were significantly different among different regions of China.
The resistance rates to metronidazole, CLA and LEV were high in China. Patient age, gender, disease and location were associated with the resistance of H. pylori to some antibiotics. Furazolidone, AMO and tetracycline are better choices for H. pylori treatment in China.
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.
Aims
Ansamycins are a family of macrolactams that are synthesized by type I polyketide synthase (PKS) using 3‐amino‐5‐hydroxybenzoic acid (AHBA) as the starter unit. Most members of the family have ...strong antimicrobial, antifungal, anticancer and/or antiviral activities. We aimed to discover new ansamycins and/or other AHBA‐containing natural products from actinobacteria.
Methods and Results
Through PCR screening of AHBA synthase gene, we identified 26 AHBA synthase gene–positive strains from 206 plant‐associated actinomycetes (five positives) and 688 marine‐derived actinomycetes (21 positives), representing a positive ratio of 2·4–3·1%. Twenty‐five ansamycins, including eight new compounds, were isolated from six AHBA synthase gene–positive strains through TLC‐guided fractionations followed by repeated column chromatography. To gain information about those potential ansamycin gene clusters whose products were unknown, seven strains with phylogenetically divergent AHBA synthase genes were subjected to fosmid library construction. Of the seven gene clusters we obtained, three show characteristics for typical ansamycin gene clusters, and other four, from Micromonospora spp., appear to lack the amide synthase gene, which is unusual for ansamycin biosynthesis. The gene composition of these four gene clusters suggests that they are involved in the biosynthesis of a new family of hybrid PK‐NRP compounds containing AHBA substructure.
Conclusions
PCR screening of AHBA synthase is an efficient approach to discover novel ansamycins and other AHBA‐containing natural products.
Significance and Impact of the Study
This work demonstrates that the AHBA‐based screening method is a useful approach for discovering novel ansamycins and other AHBA‐containing natural products from new microbial resources.
Paxillin (PXN) is required for receptor tyrosine kinase-mediated ERK activation, and the activation of the Raf/MEK/ERK cascade has been linked with Bcl-2 expression. We hypothesized that ...phosphorylation of PXN by the EGFR/Src pathway might contribute to cisplatin resistance via increased Bcl-2 expression. We show that cisplatin resistance was dependent on PXN expression, as evidenced by PXN overexpression in TL-13 and TL-10 cells and PXN knockdown in H23 and CL1-5 cells. Specific inhibitors of signaling pathways indicated that the phosphorylation of PXN at Y118 and Y31 via the Src pathway was responsible for cisplatin resistance. We further demonstrated that ERK activation was also dependent on this PXN phosphorylation. Bcl-2 transcription was upregulated by phosphorylated PXN-mediated ERK activation via increased binding of phosphorylated CREB to the Bcl-2 promoter. A subsequent increase in Bcl-2 levels by a PXN/ERK axis was responsible for the resistance to cisplatin. Animal models further confirmed the findings of in vitro cells indicating that xenograft tumors induced by TL-13-overexpressing cells were successfully suppressed by cisplatin combined with Src or ERK inhibitor compared with treatment of cisplatin, Src inhibitor or ERK inhibitor alone. A positive correlation of phosphorylated PXN with phosphorylated ERK and Bcl-2 was observed in lung tumors from NSCLC patients. Patients with tumors positive for PXN, phosphorylated PXN, phosphorylated ERK and Bcl-2 more commonly showed a poorer response to cisplatin-based chemotherapy than did patients with negative tumors. Collectively, PXN phosphorylation might contribute to cisplatin resistance via activating ERK-mediated Bcl-2 transcription. Therefore, we suggest that Src or ERK inhibitor might be helpful to improve the sensitivity for cisplatin-based chemotherapy in NSCLC patients with PXN-positive tumors.
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