NB-IoT Uplink Synchronization by Change Point Detection of Phase Series in NTNs

Non-Terrestrial Networks (NTNs) are widely recognized as a potential solution to achieve ubiquitous connections of Narrow Bandwidth Internet of Things (NB-IoT). In order to adopt NTNs in NB-IoT, one of the main challenges is the uplink synchronization of Narrowband Physical Random Access procedure which refers to the estimation of time of arrival (ToA) and carrier frequency offset (CFO). Due to the large propagation delay and Doppler shift in NTNs, traditional estimation methods for Terrestrial Networks (TNs) can not be applied in NTNs directly. In this context, we design a two stage ToA and CFO estimation scheme including coarse estimation and fine estimation based on abrupt change point detection (CPD) of phase series with machine learning. Our method achieves high estimation accuracy of ToA and CFO under the low signal-noise ratio (SNR) and large Doppler shift conditions and extends the estimation range without enhancing Random Access preambles

Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis

BackgroundPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.MethodsEligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.ResultsFourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, P = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, P < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, P = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, P = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.ConclusionsThis is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance

The research on FBW7 gene enhances antitumor effect of paclitaxel on pancreatic cancer through GSDME-mediated pyroptosis

Background and purpose: Pancreatic cancer is a highly malignant disease. Most patients are in advanced stage upon diagnosis. Systemic chemotherapy is an important treatment method, but the chemotherapy drug resistance to tumors brings many problems to clinical treatment. As a commonly used chemotherapy drug, paclitaxel can induce apoptosis in tumor cells. The FBW7 gene is a tumor suppressor gene, and the loss of its function can lead to tumor occurrence and progression. Research has shown that it has the effect of promoting tumor cell apoptosis and inhibiting tumor proliferation. In addition, this gene has been proven to promote apoptosis and ferroptosis, which increase the effect of chemotherapy drugs. Pyroptosis is a programmed cell death mode mediated by gasdermin (GSDM) protein, and this cell death is often accompanied by inflammatory reactions. This study aimed to investigate whether FBW7 gene can promote the anti-tumor effect of paclitaxel by increasing pyroptosis. Methods: A PANC-1 cell line overexpressing FBW7 was constructed using lentivirus transfection. The correlation between FBW7 and GSDME gene expressions was detected by immunohistochemistry in clinical samples, and the expression levels of mRNA and protein were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. We observed the morphological changes of cells treated with paclitaxel under light microscopy. Cell counting kit-8 (CCK-8) was used to detect the effect of paclitaxel on cell viability, and flow cytometry and lactate dehydrogenase (LDH) release assay were performed to detect the effect of paclitaxel on cell death. Western blot was used to detect caspase-3 and GSDME activation after paclitaxel treatment. Results: RTFQ-PCR and Western blot experiments showed that overexpression of FBW7 gene increased the expression of GSDME. Immunohistochemical staining of pathological sections of clinical patients also showed that the expressions of FBW7 and GSDME genes was positively correlated in vivo. Flow cytometry and LDH release experiments showed that the level of cell death in pancreatic cancer cell line PANC-1 overexpressing FBW7 was significantly increased compared with its empty vector (EV) cells after being treated with paclitaxel. Under light microscopy, it was observed that the number of cells with pyroptosis was significantly higher in PANC-1 cell lines overexpressing FBW7 than in EV cells. The CCK-8 experiment results showed that the cell viability was significantly lower in FBW7 overexpressed cell lines than in EV cells after paclitaxel treatment. Western blot experiment results showed that after pancreatic cancer cell line PANC-1 was treated with paclitaxel, the protein expressions of active-caspase-3 and GSDME-NT in FBW7 overexpression cell lines increased, which proved that they had more obvious activation, indicating that the FBW7 gene can increase the sensitivity of PANC-1 cells to paclitaxel through caspase-3/GSDME signaling pathway induced cell pyroptosis. Conclusion: FBW7 can increase the sensitivity of pancreatic cancer cells to paclitaxel by increasing the expression of GSDME, which is realized through caspase-3/GSDME pathway

Genetic relationships within Brassica rapa as inferred from AFLP finterprints

Amplified fragment length polymorphism (AFLP) markers were employed to assess the genetic diversity amongst two large collections of Brassica rapa accessions. Collection A consisted of 161 B. rapa accessions representing different morphotypes among the cultivated B. rapa, including traditional and modern cultivars and breeding materials from geographical locations from all over the world and two Brassica napus accessions. Collection B consisted of 96 accessions, representing mainly leafy vegetable types cultivated in China. On the basis of the AFLP data obtained, we constructed phenetic trees using mega 2.1 software. The level of polymorphism was very high, and it was evident that the amount of genetic variation present within the groups was often comparable to the variation between the different cultivar groups. Cluster analysis revealed groups, often with low bootstrap values, which coincided with cultivar groups. The most interesting information revealed by the phenetic trees was that different morphotypes are often more related to other morphotypes from the same region (East Asia vs. Europe) than to similar morphotypes from different regions, suggesting either an independent origin and or a long and separate domestication and breeding history in both region

Lipoxin A4 attenuates MSU-crystal-induced NLRP3 inflammasome activation through suppressing Nrf2 thereby increasing TXNRD2

Gout is a common inflammatory disease. The activation of NLRP3 inflammasome induced by monosodium urate (MSU) crystals has a critical role in gout, and its prevention is beneficial for patients. Lipoxin A4 (LXA4) is an endogenous lipoxygenase-derived eicosanoid mediator with powerful anti-inflammatory properties. However, whether LXA4 can suppress NLRP3 inflammasome activation induced by MSU crystals remains unclear. This study aimed to investigate the protective effect of LXA4 on MSU-crystal-induced NLRP3 inflammasome activation and its underlying molecular mechanisms. We found that LXA4 inhibited MSU-crystal-induced NLRP3 inflammasome activation, interleukin (IL)-1β maturation, and pyroptosis. More specifically, LXA4 suppressed the assembly of the NLRP3 inflammasome, including oligomerization and speck formation of ASC, and ASC-NLRP3 interaction. Furthermore, LXA4 suppressed oxidative stress, the upstream events for NLRP3 inflammasome activation, as evidenced by the fact that LXA4 eliminated total reactive oxygen species (ROS) generation and alleviated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and mitochondrial dysfunction. However, LXA4 also depressed the Nrf2 activation, a critical molecule in the antioxidant pathway, and then exerted an inhibitory impact on Klf9 expression and promotional impact on TXNRD2 expression, two molecules located downstream of Nrf2 in sequence. Knockdown of TXNRD2 reversed the LXA4-induced depression of ROS and NLRP3 inflammasome. Moreover, LXA4 alleviated joint inflammation and decreased the production of cleaved caspase-1 and matured IL-1β in gouty arthritis rats. Taken together, our findings demonstrate that LXA4 can attenuate MSU-crystal-induced NLRP3 inflammasome activation, probably through suppressing Nrf2 activation to increase TXNRD2 expression. The present study highlights the potential of LXA4 as an attractive new gout treatment candidate