Background
Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the ...pathogenesis of CRS with nasal polyps (CRSwNP).
Methods
The expression of autophagic proteins microtubule‐associated protein 1 light chain 3B (LC3B)‐II, autophagy‐related proteins (Atg), and Beclin 1, substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules cysteine‐aspartic protease‐3 and cysteine‐aspartic protease‐8, and poly‐ADP‐ribose polymerase in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS‐2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.
Results
Although autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up‐regulation of substrate proteins and apoptotic signaling molecules. IFN‐γ, but not IL‐4, IL‐13, or IL‐17A, simultaneously enhanced LC3B‐II and p62 levels as well as cell apoptosis in BEAS‐2B cells and/or normal NECs. Bafilomycin A1 up‐regulated the levels of LC3B‐II and p62 in polyp NECs and IFN‐γ‐treated normal NECs. IFN‐γ‐induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN‐γ‐treated NECs. IFN‐γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP.
Conclusions
IFN‐γ induces activated but insufficient autophagy and thus contributes to a degree to p62‐dependent apoptosis of NECs in CRSwNP.
The egg-laying interval (LI) directly reflects the laying performance of breeding pigeons, influenced by reproductive hormones. This study aimed to assess reproductive hormone levels in serum and the ...expression of related genes and their receptors in the hypothalamus and pituitary gland in 4 stages: first (LI1), third (LI3), fifth (LI5), and seventh (LI7) days. The results showed that serum gonadotropin-releasing hormone (GnRH) level decreased from LI1 to LI7 (P < 0.01) and peaked in LI1. The serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels stayed at high levels from LI1 to LI5. The FSH level decreased slightly from LI5 to LI7 (P > 0.05), but the LH level decreased rapidly (P < 0.01). The prolactin (PRL) levels significantly increased in LI5 (P < 0.01) compared with LI1 and then stayed at a high level. The GnRH1 expression in the hypothalamus had no significant change in LI (P > 0.05). However, the GnRHR first decreased from LI1 to LI3 (P < 0.05) and then increased. The FSH mRNA level in the pituitary gland decreased from LI1 to LI3 and slightly increased in LI5 (P > 0.05). The change pattern of FSHR was similar to that of FSH and peaked in LI5 (P < 0.05). The LH expression level was the highest in LI5 and significantly higher than that in LI3 and LI7 (P < 0.05). However, the LHR mRNA level decreased in LI (P < 0.05). The expression patterns of PRL and PRLR were similar; they were upregulated in LI and peaked in LI7 (P < 0.01). The expression pattern of GnRHR was similar to that of FSH, LH, and FSHR, suggesting the critical role of GnRHR in LI. Furthermore, the expression levels of these genes peaked in LI5, closely correlating with the maturation of the first largest follicle in pigeons. PRL–PRLR signaling inhibited GnRH activity to promote ovulation. This study provided a basis for further investigating the molecular mechanisms underlying the regulation of reproduction in pigeons.
This study aims to investigate the expression status of miRNA-216b in familial hepatocellular carcinoma (HCC) and the correlation between miRNA-216b expression and pathogenesis, as well as the ...progression of HCC. The expression profile of miRNAs in plasma of peripheral blood between HCC patients with HCC family history and healthy volunteers without HCC family history was determined by microarray. Using real-time quantitative PCR to detect the expression in paired tissues from 150 patients with HCC, miR-216b was selected as its expression value in HCC patients was significantly lower compared with healthy volunteers. Next, miR-216b expression and the clinicopathological features of HCC were evaluated. The effect of miR-216b expression on tumor cells was investigated by regulating miR-216b expression in SMMC-7721 and HepG2 in vitro and in vivo. Finally, we explored mRNA targets of miR-216b. In 150 HCC, 37 (75%) tumors showed reduced miR-216b expression comparing with their adjacent liver tissues. The decreased expression of miR-216b was significantly correlated with tumor volume (P=0.044), HBV infection (P=0.026), HBV DNA quantitative (P=0.001) and vascular invasion (P=0.032). The 5-year disease-free survival and overall rates after liver resection in low expression and high expression groups of miR-216b are 62% and 54%, 25% and 20%, respectively. MiR-216b overexpression inhibited cell proliferation, migration and invasion, and miR-216b inhibition did the opposite. The expression of hepatitis B virus x protein (HBx) has tight correlation with downregulation of miR-216b. Furthermore, miR-216b downregulated the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and exerted its tumor-suppressor function through inhibition of protein kinase B and extracellular signal-regulated kinase signaling downstream of IGF2. MiR-216b inhibits cell proliferation, migration and invasion of HCC by regulating IGF2BP2 and it is regulated by HBx.
Our goal in this work was to illustrate the Epstein-Barr virus (EBV)-modulated global biochemical profile and provide a novel metabolism-related target to improve the therapeutic regimen of ...nasopharyngeal carcinoma (NPC). We used a metabolomics approach to investigate EBV-modulated metabolic changes, and found that the exogenous overexpression of the EBV-encoded latent membrane protein 1 (LMP1) significantly increased glycolysis. The deregulation of several glycolytic genes, including hexokinase 2 (HK2), was determined to be responsible for the reprogramming of LMP1-mediated glucose metabolism in NPC cells. The upregulation of HK2 elevated aerobic glycolysis and facilitated proliferation by blocking apoptosis. More importantly, HK2 was positively correlated with LMP1 in NPC biopsies, and high HK2 levels were significantly associated with poor overall survival of NPC patients following radiation therapy. Knockdown of HK2 effectively enhanced the sensitivity of LMP1-overexpressing NPC cells to irradiation. Finally, c-Myc was demonstrated to be required for LMP1-induced upregulation of HK2. The LMP1-mediated attenuation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis resulted in the stabilization of c-Myc. These findings indicate a close relationship between EBV and glycolysis in NPC. Notably, LMP1 is the key regulator of the reprogramming of EBV-mediated glycolysis in NPC cells. Given the importance of EBV-mediated deregulation of glycolysis, anti-glycolytic therapy might represent a worthwhile avenue of exploration in the treatment of EBV-related cancers.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
Aim
Perineal wound complications after abdominoperineal resection (APR) have become a major clinical challenge. Myocutaneous flap closure has been proposed in place of primary closure to improve ...wound healing. We conducted this comprehensive meta‐analysis to evaluate the current scientific evidence of primary closure vs myocutaneous flap closure of perineal defects following APR for colorectal disease.
Methods
We systematically searched the MEDLINE, Embase, PubMed, Web of Science and Cochrane Library databases to identify all relevant studies. After data extraction from the included studies, meta‐analysis was performed to compare perioperative outcomes of primary closure and myocutaneous flap closure.
Results
Eighteen studies with a total of 17 913 patients (16 346 primary closure vs 1567 myocutaneous flap closure) were included. We found that primary closure was significantly associated with higher total perineal wound complications (P = 0.007), major perineal wound complications (P < 0.001) and perineal wound infection (P = 0.001). On the other hand, myocutaneous flap closure takes more operation time (P < 0.001) and increases the risk of perineal wound dehiscence (P = 0.01), deep surgical site infection (P < 0.001), enterocutaneous fistulas (P = 0.03) and return to the operating room (P = 0.0005). There were no significant differences between the two groups for other outcomes.
Conclusions
This is the first systematic review with meta‐analysis comparing primary closure with myocutaneous flap closure of perineal defects after APR for colorectal disease. Although taking more operation time and an increased risk of specific complications, the pooled results have validated the use of myocutaneous flaps for reducing total/major perineal wound complications. More investigations are needed to draw definitive conclusions on this dilemma.
By using a database of 4,634 cold patches (high density and low electron temperature) and 4,700 hot patches (high density and high electron temperature) from Defense Meteorological Satellite Program ...F16 in 2005–2018 winter months (October–March), we present a statistical survey of the distributions of polar cap patches for different interplanetary magnetic field (IMF) orientations and ionospheric convection geometries. We investigate the dependence of cold and hot patches on local plasma transport and soft‐electron precipitation. Our results indicate that: in winter, (a) more cold and hot patches occur in the stronger anti‐sunward flow organized by different IMF orientations. (b) cold patches are frequent near the central polar cap, while hot patches are closer to the auroral oval. (c) enhanced anti‐sunward flow (E × B drift) mainly contributes to cold patch occurrence under Bz < 0, and soft‐electron precipitation contributes to hot patch occurrence both under southward and northward IMF.
Plain Language Summary
Polar cap patches are common phenomena in the polar ionosphere and consist of high‐density plasma. We use 4,634 cold patches and 4,700 hot patches observed by the Defense Meteorological Satellite Program to investigate the distributions of polar cap patches for different interplanetary magnetic field (IMF) orientations and ionospheric convection geometries. We find that more cold and hot patches are distributed in areas of stronger anti‐sunward flow in winter. The hot patches are more frequent at lower magnetic latitudes, and located closer to the auroral oval than cold patches. Furthermore, in winter months, higher anti‐sunward flow velocity mainly contributes to a higher occurrence of cold patches under southward IMF, and stronger soft‐electron precipitation mainly contributes to a higher occurrence of hot patches both under southward and northward IMF.
Key Points
The spatial distributions of cold and hot patches respond well to the convection pattern for different interplanetary magnetic field orientations
The hot patches are more frequent at lower magnetic latitudes than cold patches, and located closer to the auroral oval
Enhanced anti‐sunward flow promotes cold patch occurrence under Bz < 0, and soft‐electron precipitation promotes hot patch occurrence
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