Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
A Geographic Information System (GIS)-based quantitative risk assessment methodology was adopted to evaluate the risks of loose deposits formed by the 2008 Wenchuan earthquake along a highway near ...the epicenter. A total of 305 loose deposits with a total volume of 4.0 × 107 m3 has been identified. A physical model was used to determine the failure probability of these loose deposits under six rainfall scenarios, assuming the loose deposits as infinite slopes. The calculated probability of rain-induced slope failures is verified by the recorded landslides at the same site during a storm in 2010. Seventy-nine out of the 112 rain-induced loose deposit failures are predicted by the reliability analysis, with an accuracy of 71%. The results of reliability analysis and information on the consequence of these rain-induced landslides enable the estimation of the annual societal and individual risks of the loose deposits. Under the rainfall scenarios of 30 mm/12 h and 70 mm/12 h, the estimated annual societal risks reach 8.8 and 7.5, respectively, and the individual risks reach 0.05 and 0.04, respectively, which are very high compared with present risk acceptance criteria. The preliminary assessment provides a benchmark for studying the long-term risks of these loose deposits and engineering decision.
This EAACI position paper aims at providing a state‐of‐the‐art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic ...noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug‐induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called “entopy” or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.
Particle size, composition and optical properties were measured at a regional atmosphere background station in the Yangtze River Delta (YRD) to understand the formation and evolution of haze-fog ...episodes in Jan. 2013. The peak of particle number size distribution was in the size range of 80–100 nm during the measurements. PM1 mass concentration contributed 84% to the total particle mass (PM10). Based on visibility and ambient relative humidity, three types of weather conditions (i.e., clear, haze and fog) were classified in this study. The extinction coefficients of PM1 and PM10 under dry conditions were simulated by the Mie model. Under dry conditions, PM1 was found to contribute approximately 91% to the light extinction coefficient of PM10. However, the PM1 with the assumption of dry state was found to contribute approximately 85% to the ambient extinction coefficient of PM10 during clear conditions, 58% during haze conditions and approximately 41% during fog conditions. The variation of the dry PM1 contribution was related to the water uptake of particles under different relative humidity conditions.
A severe haze-fog event on Jan. 14–17 was discussed in more detail as a case study. Two episodes were chosen to show that nitrate and organics dominated the aerosol component during the severe haze-fog episode and were related to secondary aerosol formation and air mass origin. Nitrate played a more dominant role than sulfate in heavy haze formation in the YRD region, which was different from the North China Plain region.
•Particle number size distribution characteristic during haze-fog episode.•Submicron aerosol influence on light extinction coefficient is evaluated.•Secondary aerosol formation controlling haze-fog episode.•The effect of air mass origin on haze-fog formation episode.
Elevated peripheral inflammation is common in psychosis. Impairments in general cognition were linked to elevated C-reactive protein (CRP) and other inflammatory markers in patients with psychotic ...disorders. Whether there is a subgroup of persons with elevated peripheral inflammation demonstrating deficits in specific cognitive domains remains unclear. While molecular underpinnings of altered inflammation in psychosis are hypothesized, genetic contributions to relationships of psychosis, inflammation, and cognition have not been clarified. Thirteen peripheral inflammatory markers and 17 neurobehavioral tasks were quantified in a subset of participants (129 psychosis, 55 healthy controls-HCs) from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium. Principal component analysis resulted in 5 inflammation factors across inflammatory markers. Three latent cognitive domains (Visual Sensorimotor, General Cognitive Ability, and Inhibitory Control) were characterized based on the neurobehavioral battery. Hierarchical clustering identified a psychosis subgroup with elevated inflammation and worse cognitive performance. Genetic predispositions to schizophrenia and cognition were explored in relation to inflammation. Among persons with psychosis, higher inflammation indices were associated with impairments of Inhibitory Control and Visual Sensorimotor function. Greater deficits in Inhibitory Control were observed in a high inflammation patient subgroup. Consistent with previous studies, global genetic correlations of schizophrenia, CRP, and cognition were observed. Significant bivariate local genetic correlations of CRP with schizophrenia or cognition across 22 loci with several genes in 1 locus on chromosome 3 suggested pleiotropic mechanisms for inflammatory relationships with cognition and psychosis. Specific neurobehavioral domains may be more sensitive to inflammation dysregulation in psychosis as compared to general cognitive function, particularly performance on tasks requiring ongoing behavioral monitoring and control. These, along with evidence of genetic correlations of CRP, psychosis, and cognition, provide further supporting evidence that inflammation dysregulation is an important underlying mechanistic contributor to the disruption of cognition in psychosis. Targeting this dysregulation may be an avenue for novel therapeutics to improve cognitive outcomes in these patients.Disclosure of InterestNone Declared
Scattering of solar radiation by aerosol particles is highly dependent on relative humidity (RH) as hygroscopic particles take up water with increasing RH. To achieve a better understanding of the ...effect of aerosol hygroscopic growth on light scattering properties and radiative forcing, the aerosol scattering coefficients at RH in the range of 40 to ~ 90 % were measured using a humidified nephelometer system in the Yangtze River Delta of China in March 2013. In addition, the aerosol size distribution and chemical composition were measured. During the observation period, the mean and standard deviation (SD) of enhancement factors at RH = 85 % for the scattering coefficient (f(85 %)), backscattering coefficient (fb(85 %)), and hemispheric backscatter fraction (f beta (85 %)) were 1.58 plus or minus 0.12, 1.25 plus or minus 0.07, and 0.79 plus or minus 0.04, respectively, i.e., aerosol scattering coefficient and backscattering coefficient increased by 58 and 25 % as the RH increased from 40 to 85 %. Concurrently, the aerosol hemispheric backscatter fraction decreased by 21 %. The relative amount of organic matter (OM) or inorganics in PM1 was found to be a main factor determining the magnitude of f(RH). The highest values of f(RH) corresponded to the aerosols with a small fraction of OM, and vice versa. The relative amount of NO3- in fine particles was strongly correlated with f(85 %), which suggests that NO3- played a vital role in aerosol hygroscopic growth during this study. The mass fraction of nitrate also had a close relationship to the curvature of the humidograms; higher mass fractions of nitrate were associated with humidograms that had the least curvature. Aerosol hygroscopic growth caused a 47 % increase in the calculated aerosol direct radiative forcing at 85 % RH, compared to the forcing at 40 % RH.
Although regional haze adversely affects human health and possibly counteracts global warming from increasing levels of greenhouse gases, the formation and radiative forcing of regional haze on ...climate remain uncertain. By combining field measurements, laboratory experiments, and model simulations, we show a remarkable role of black carbon (BC) particles in driving the formation and trend of regional haze. Our analysis of long-term measurements in China indicates declined frequency of heavy haze events along with significantly reduced SO₂, but negligibly alleviated haze severity. Also, no improving trend exists for moderate haze events. Our complementary laboratory experiments demonstrate that SO₂ oxidation is efficiently catalyzed on BC particles in the presence of NO₂ and NH₃, even at low SO₂ and intermediate relative humidity levels. Inclusion of the BC reaction accounts for about 90–100% and 30–50%of the sulfate production during moderate and heavy haze events, respectively. Calculations using a radiative transfer model and accounting for the sulfate formation on BC yield an invariant radiative forcing of nearly zero W m−2 on the top of the atmosphere throughout haze development, indicating small net climatic cooling/warming but large surface cooling, atmospheric heating, and air stagnation. This BC catalytic chemistry facilitates haze development and explains the observed trends of regional haze in China. Our results imply that reduction of SO₂ alone is insufficient in mitigating haze occurrence and highlight the necessity of accurate representation of the BC chemical and radiative properties in predicting the formation and assessing the impacts of regional haze.
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
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.
Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant ...advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections. PD-1/PD-L1 overexpression was found to be significantly associated with p-STAT3 in human and mouse HNSCC. Targeting STAT3 by a small molecule effectively inhibited the expression of PD-L1 in the CAL27 cell line. Furthermore, we found that blockade of STAT3 signaling downregulated PD-1/PD-L1 in a Tgfbr1/Pten 2cKO HNSCC mouse model. These findings suggest that STAT3 signaling plays an important role in PD-1/PD-L1 regulation and the antitumor immune response of HNSCC.
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