Pancreatic cancer is one of the most malignant tumors. However, radiotherapy can lead to tumor recurrence, which is caused by the residual surviving cells repopulation stimulated by some molecular ...released from dying cells. Exosomes may mediate cell-cell communication and transfer kinds of signals from the dying cells to the surviving cells for stimulating tumor repopulation. Circular RNAs (circRNAs) may be one vital kind of exosomal cargos involving in modulating cancer cell repopulation.
Next generation sequencing (NGS) and bioinformatics were performed to analyze and annotate the expression and function of exosome-derived circRNAs in pancreatic cancer cells after radiation. Four circRNAs were chosen for qRT-PCR analysis to validate the sequencing results.
In this study, 3580 circRNAs were annotated in literatures and circBase among 12,572 identified circRNAs. There were 196 filtered differentially expressed circRNAs (the up-regulation and down-regulation respectively is 182 and 14, fold change > 2, p-value < 0.05). Regulation of metabolic process and lysine degradation were the main enriched biological processes and pathway according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.
The hsa_circ_0002130-hsa_miR_4482-3p-NBN interaction network suggested potential sponging miRNA and target mRNA. Our results provided potential functions of circRNAs to explore molecular mechanisms and therapeutic targets in pancreatic cancer cell repopulation upon irradiation.
A raw electron backscatter diffraction (EBSD) signal can be empirically decomposed into a Kikuchi diffraction pattern and a smooth background. For pattern indexing, the latter is generally ...undesirable but can reveal topographical, compositional, or diffraction contrast. In this study, we proposed a new background correction method using polynomial fitting (PF) algorithm to obtain clear Kikuchi diffraction patterns for some applications in nonconductive materials due to coating problems, at low accelerated voltage and at rough sample surfaces and for the requirement of high pattern quality in HR-EBSD. To evaluate the quality metrics of the Kikuchi patterns, we initially used three indices, namely, pattern quality, Tenengrad variance, and spatial-spectral entropy-based quality to detect the clarity, contrast, and noise of Kikuchi patterns obtained at 5 and 15 kV. Then, we examined the performance of PF method by comparing it with pattern averaging and Fourier transform-based methods. Finally, this PF background correction is demonstrated to extract the background images from the blurred diffraction patterns of EBSD measurements at low kV accelerating voltage and with coating layer, and to provide clear Kikuchi patterns successfully.
Overweight and obesity are important risk factors of gestational diabetes mellitus (GDM). Clustering of metabolic risk factors in early pregnancy may be a potential pathogenesis between the link of ...overweight/obesity and GDM. Since it remains unexplored, we investigated if overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM in this cohort study.
Total 527 women who visited National Taiwan University Hospital for prenatal care in between November 2013 to April 2018 were enrolled. Risk factors of GDM in the first prenatal visit (FPV) were recorded. Overweight/obesity was defined if body mass index ≥24 kg/m2. GDM was diagnosed from the result of a 75g oral glucose tolerance test in 24-28 gestational weeks.
Overweight/obesity was associated with clustering of metabolic risk factors of GDM, including high fasting plasma glucose, high HbA1c, insulin resistance, high plasma triglyceride and elevated blood pressure in FPV (p<0.05). There was a positive relationship between the number of metabolic risk factors and the incidence of GDM (p <0.05). The odds ratios of HbA1c and diastolic blood pressure were higher in overweight/obese women, compared with those in normal-weight women.
Overweight/obesity is associated with clustering of metabolic risk factors in early pregnancy, which is correlated with higher risk of GDM. Our findings suggest that metabolic risk factors during early pregnancy should be evaluated in overweight/obese women.
Influenza virus is one of the most important human pathogens, causing substantial seasonal and pandemic morbidity and mortality. Houttuynia cordata is a traditionally used medicinal plant for the ...treatment of pneumonia. Flavonoids are one of the major bioactive constituents of Houttuynia cordata.
This study was designed to investigate the therapeutic effect and mechanism of flavonoid glycosides from H. cordata on influenza A virus (IAV)-induced acute lung injury (ALI) in mice.
Flavonoids from H. cordata (HCF) were extracted from H. cordata and identified by high-performance liquid chromatography. Mice were infected intranasally with influenza virus H1N1 (A/FM/1/47). HCF (50, 100, or 200 mg/kg) or Ribavirin (100 mg/kg, the positive control) were administered intragastrically. Survival rates, life spans, weight losses, lung indexes, histological changes, inflammatory infiltration, and inflammatory markers in the lungs were measured. Lung virus titers and neuraminidase (NA) activities were detected. The expression of Toll-like receptors (TLRs) and levels of NF-κB p65 phosphorylation (NF-κB p65(p)) in the lungs were analysed. The effects of HCF on viral replication and TLR signalling were further evaluated in cells.
HCF contained 78.5% flavonoid glycosides. The contents of rutin, hyperin, isoquercitrin, and quercitrin in HCF were 8.8%, 26.7%, 9.9% and 31.7%. HCF (50, 100 and 200 mg/kg) increased the survival rate and life span of mice infected with the lethal H1N1 virus. In H1N1-induced ALI, mice treated with HCF (50, 100 and 200 mg/kg) showed lesser weight loss and lower lung index than the model group. The lungs of HCF-treated ALI mice presented more intact lung microstructural morphology, milder inflammatory infiltration, and lower levels of monocyte chemotactic protein 1 (MCP-1), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) than in the model group. Further investigation revealed that HCF exerted antiviral and TLR-inhibitory effects in vivo and in vitro. HCF (50, 100 and 200 mg/kg) reduced lung H1N1 virus titers and inhibited viral NA activity in mice. HCF (100 and 200 mg/kg) elevated the levels of interferon-β in lungs. HCF also decreased the expression of TLR3/4/7 and level of NF-κB p65(p) in lung tissues. In vitro experiments showed that HCF (50, 100 and 200 μg/ml) significantly inhibited viral proliferation and suppressed NA activity. In RAW 264.7 cells, TLR3, TLR4, and TLR7 agonist-stimulated cytokine secretion, NF-κB p65 phosphorylation, and nuclear translocation were constrained by HCF treatment. Furthermore, among the four major flavonoid glycosides in HCF, hyperin and quercitrin inhibited both viral replication and TLR signalling in cells.
HCF significantly alleviated H1N1-induced ALI in mice, which were associated with its dual antiviral and anti-inflammatory effects via inhibiting influenzal NA activity and TLR signalling. among the four major flavonoid glycosides in HCF, hyperin and quercitrin played key roles in the therapeutic effect of HCF.
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The protective effect of statins in cirrhosis and its decompensation in chronic hepatitis B (CHB) patients remains unknown.
We conducted a population-based cohort study using data from the Taiwanese ...National Health Insurance Research Database from 1997 to 2009. A total of 298,761 CHB patients were identified. CHB patients using statins (n=6,543; defined as ≥28 cumulative defined daily doses (cDDD)) and a 1:1 ratio propensity score and inception point (the date of first use of statins)-matched non-statins (<28 cDDD) were followed up from the inception point until the development of cirrhosis or its decompensation or until withdrawal from insurance or December 2009.
After adjustment for competing mortality, CHB patients using statins had a significantly lower cumulative incidence of cirrhosis (relative risk)=0.433; 95% confidence interval (CI)=0.344-0.515; modified log-rank test, P<0.001) and decompensated cirrhosis (relative risk=0.468; 95% CI=0.344-0.637; P<0.001) compared with patients not using statins. After adjustment for age, gender, comorbidity index, hypertension, diabetes, hyperlipidemia, hepatocellular carcinoma, obesity, non-alcoholic fatty liver disease, aspirin use, diabetes medication, CHB treatment, non-statin lipid-lowering drugs, and triglyceride lipid-lowering drugs using the Cox proportional hazard model, statins were still an independent protector against cirrhosis (adjusted hazard ratio (AHR)=0.512; 95% CI=0.413-0.634; P<0.001) and its decompensation (AHR=0.534; 95% CI=0.433-0.659; P<0.001). The AHRs for cirrhosis were 0.467 and 0.200, and the AHRs for decompensated cirrhosis were 0.611 and 0.231 with 91-365 and >365 cDDD of statins, respectively.
CHB patients who receive statin therapy have a dose-dependent reduction in the risk of cirrhosis and its decompensation.
Fruit ripening is a complex, genetically programmed process involving the action of critical transcription factors (TFs). Despite the established significance of dehydration-responsive element ...binding (DREB) TFs in plant abiotic stress responses, the involvement of DREBs in fruit ripening is yet to be determined.
Here, we identified four genes encoding ripening-regulated DREB TFs in banana (Musa acuminata), MaDREB1, MaDREB2, MaDREB3, and MaDREB4, and demonstrated that they play regulatory roles in fruit ripening.
We showed that MaDREB1–MaDREB4 are nucleus-localized, induced by ethylene and encompass transcriptional activation activities. We performed a genome-wide chromatin immunoprecipitation and high-throughput sequencing (ChIP-Seq) experiment for MaDREB2 and identified 697 genomic regions as potential targets of MaDREB2. MaDREB2 binds to hundreds of loci with diverse functions and its binding sites are distributed in the promoter regions proximal to the transcriptional start site (TSS). Most of the MaDREB2-binding targets contain the conserved (A/G)CC(G/C)AC motif and MaDREB2 appears to directly regulate the expression of a number of genes involved in fruit ripening. In combination with transcriptome profiling (RNA sequencing) data, our results indicate that MaDREB2 may serve as both transcriptional activator and repressor during banana fruit ripening.
In conclusion, our study suggests a hierarchical regulatory model of fruit ripening in banana and that the MaDREB TFs may act as transcriptional regulators in the regulatory network.
•ECT was the most efficacious, but least tolerated.•R-rTMS was the best tolerated treatment for MDD.•B-rTMS appears to have the most favorable balance between efficacy and acceptability.
The effects ...of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD.
The literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates.
Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non −significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate.
ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability.
Complex oxide heterostructures have fascinating emergent properties that originate from the properties of the bulk constituents as well as from dimensional confinement. The conductive behavior of the ...polar/nonpolar LaAlO3/SrTiO3 interface can be reversibly switched using conductive atomic force microscopy (c‐AFM) lithography, enabling a wide range of devices and physics to be explored. Here, extreme nanoscale control over the CaZrO3/SrTiO3 (CZO/STO) interface, which is formed from two materials that are both nonpolar, is reported. Nanowires with measured widths as narrow as 1.2 nm are realized at the CZO/STO interface at room temperature by c‐AFM lithography. These ultrathin nanostructures have spatial dimensions at room temperature that are comparable to single‐walled carbon nanotubes, and hold great promise for alternative oxide‐based nanoelectronics, as well as offer new opportunities to investigate the electronic structure of the complex oxide interfaces. The cryogenic properties of devices constructed from quasi‐1D channels, tunnel barriers, and planar gates exhibit gate‐tunable superconductivity, quantum oscillations, electron pairing outside of the superconducting regime, and quasi‐ballistic transport. This newly demonstrated ability to control the metal–insulator transition at nonpolar oxide interface greatly expands the class of materials whose behavior can be patterned and reconfigured at extreme nanoscale dimensions.
Ultrathin (1–3 nm wide) nanostructures can be realized at the nonpolar CaZrO3/SrTiO3 interface using conductive atomic force microscopy lithography, enabling the observation of tunable superconductivity, quantum oscillations, electron paring without superconductivity, and quasi‐ballistic transport. Such extreme nanoscale control over a nonpolar complex oxide interface offers new ways to investigate fundamental physics in other correlated systems and develop future oxide‐based nanoelectronics.
Global warming and increasing extreme weather have become a severe problem in recent years, posing a significant threat to human health worldwide. Research exploring the link between injury as one of ...the leading causes of death globally and ambient temperature was lacking. Based on the hourly injury emergency ambulance dispatch (IEAD) records from 2019-2021 in the main urban area of Chongqing, this study explored the role of temperature extremes on the pathogenesis of injury by different mechanisms and identified sensitive populations for different mechanisms of injury.
In this study, we collected hourly injury emergency ambulance dispatch (IEAD) records from Chongqing Emergency Dispatch Center in the main urban area of Chongqing from 2019 to 2021, and used a distributed lagged nonlinear model (DLNM) with quasi-Poisson distribution to evaluate the association between ambient temperature and IEADs. And the stratified analysis was performed by gender, age and different injury mechanisms to identify susceptible groups. Finally, the attributable burden of ambient extreme temperatures was also investigated.
The risk for total IEADs increased significantly at high temperature (32 °C) compared with optimal temperature (9 °C) (CRR: 1.210; 95%CI1.127,1.300). The risks of traffic accident injury (CRR: 1.346; 95%CI1.167,1.552), beating injury (CRR: 1.508; 95%CI1.165,1.952), fall-height injury (CRR: 1.871; 95%CI1.196-2.926) and injury of sharp penetration (CRR: 2.112; 95%CI1.388-3.213) were significantly increased. At low temperature (7 °C), the risk of fall injury (CRR: 1.220; 95% CI 1.063,1.400) increased significantly. Lag for 24 hours at extreme low temperature (5 °C), the risk of 18-45 years (RR: 1.016; 95%CI1.009,1.024) and over 60 years of age (RR: 1.019; 95%CI1.011,1.025) increased significantly. The effect of 0 h delay in extreme high temperature (36 °C) on males aged 18-45 years (RR: 1.115; 95%CI1.071,1.162) and 46-59 years (RR: 1.069; 95%CI1.023,1.115) had significant impact on injury risk.
This study showed that ambient temperature was significantly related to the risk of injury, and different mechanisms of injury were affected differently by extreme temperature. The increasing risk of traffic accident injury, beating injury, fall-height injury and sharp penetrating injury was associated with extreme heat, while fall injury was associated with extreme cold. The risk of injury in high temperature environment was mainly concentrated in males and young adults. The results of this study can help to identify the sensitive population with different injury mechanisms in extreme temperature environment, and provide reference for public health emergency departments to respond to relevant strategies in extreme temperature environment to minimize the potential risk to the public.
As a leading cause of death, second only to heart disease, cancer has always been one of the burning topics in medical research. When targeting multiple signal pathways in tumorigenesis ...chemoprevention, using natural or synthetic anti-cancer drugs is a vital strategy to reduce cancer damage. However, toxic effects, multidrug resistance (MDR) as well as cancer stem cells (CSCs) all prominently limited the clinical application of conventional anticancer drugs. With low side effects, strong biological activity, unique mechanism, and wide range of targets, natural products derived from plants are considered significant sources for new drug development. Nobiletin is one of the most attractive compounds, a unique flavonoid primarily isolated from the peel of citrus fruits. Numerous studies in vitro and in vivo have suggested that nobiletin and its derivatives possess the eminent potential to become effective cancer chemoprevention agents through various cellular and molecular levels. This article aims to comprehensively review the anticancer efficacy and specific mechanisms of nobiletin, enhancing our understanding of its chemoprevention properties and providing the latest research findings. At the end of this review, we also give some discussion and future perspectives regarding the challenges and opportunities in nobiletin efficient exploitation.
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