MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR‐98 has been reported to be ...involved in various diseases. However, little is known about the role of miR‐98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR‐98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR‐98 was downregulated in CCI rat models. Overexpression of miR‐9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR‐98 and the direct correlation was confirmed. Then, miR‐98 was overexpressed in CCI rats and it was found that miR‐98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL‐6), IL‐1β, and tumor necrosis factor‐α (TNF‐α) expression was obviously induced in CCI rats, while miR‐98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR‐98 on neuropathic pain development. Taken these together, we reported that overexpression of miR‐98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.
Our study indicated a significant role of miR‐98/STAT3 axis in neuropathic pain. We reported that miR‐98 was able to alleviate neuropathic pain development via targeting STAT3.
Among various flat optical devices, metasurfaces have presented their great ability in efficient manipulation of light fields and have been proposed for variety of devices with specific ...functionalities. However, due to the high phase dispersion of their building blocks, metasurfaces significantly suffer from large chromatic aberration. Here we propose a design principle to realize achromatic metasurface devices which successfully eliminate the chromatic aberration over a continuous wavelength region from 1200 to 1680 nm for circularly-polarized incidences in a reflection scheme. For this proof-of-concept, we demonstrate broadband achromatic metalenses (with the efficiency on the order of ∼12%) which are capable of focusing light with arbitrary wavelength at the same focal plane. A broadband achromatic gradient metasurface is also implemented, which is able to deflect wide-band light by the same angle. Through this approach, various flat achromatic devices that were previously impossible can be realized, which will allow innovation in full-color detection and imaging.Metasurfaces suffer from large chromatic aberration due to the high phase dispersion of their building blocks, limiting their applications. Here, Wang et al. design achromatic metasurface devices which eliminate the chromatic aberration over a continuous region from 1200 to 1680 nm in a reflection schleme.
mutations occur in approximately 40% of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The PI3Kα-specific inhibitor alpelisib ...has shown antitumor activity in early studies.
In a randomized, phase 3 trial, we compared alpelisib (at a dose of 300 mg per day) plus fulvestrant (at a dose of 500 mg every 28 days and once on day 15) with placebo plus fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously. Patients were enrolled into two cohorts on the basis of tumor-tissue
mutation status. The primary end point was progression-free survival, as assessed by the investigator, in the cohort with
-mutated cancer; progression-free survival was also analyzed in the cohort without
-mutated cancer. Secondary end points included overall response and safety.
A total of 572 patients underwent randomization, including 341 patients with confirmed tumor-tissue
mutations. In the cohort of patients with
-mutated cancer, progression-free survival at a median follow-up of 20 months was 11.0 months (95% confidence interval CI, 7.5 to 14.5) in the alpelisib-fulvestrant group, as compared with 5.7 months (95% CI, 3.7 to 7.4) in the placebo-fulvestrant group (hazard ratio for progression or death, 0.65; 95% CI, 0.50 to 0.85; P<0.001); in the cohort without
-mutated cancer, the hazard ratio was 0.85 (95% CI, 0.58 to 1.25; posterior probability of hazard ratio <1.00, 79.4%). Overall response among all the patients in the cohort without
-mutated cancer was greater with alpelisib-fulvestrant than with placebo-fulvestrant (26.6% vs. 12.8%); among patients with measurable disease in this cohort, the percentages were 35.7% and 16.2%, respectively. In the overall population, the most frequent adverse events of grade 3 or 4 were hyperglycemia (36.6% in the alpelisib-fulvestrant group vs. 0.7% in the placebo-fulvestrant group) and rash (9.9% vs. 0.3%). Diarrhea of grade 3 occurred in 6.7% of patients in the alpelisib-fulvestrant group, as compared with 0.3% of those in the placebo-fulvestrant group; no diarrhea of grade 4 was reported. The percentages of patients who discontinued alpelisib and placebo owing to adverse events were 25.0% and 4.2%, respectively.
Treatment with alpelisib-fulvestrant prolonged progression-free survival among patients with
-mutated, HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously. (Funded by Novartis Pharmaceuticals; SOLAR-1 ClinicalTrials.gov number, NCT02437318.).
This work was to analyze and discuss the propagation mechanism of compressive shear initiation of complex fractured rock mass with seepage stress. The dense marble of Daye Iron mine with bulk density ...of 26.6 kN/m3 and uniaxial compressive strength of 52.4 MPa was selected as the material, and the upper and lower fracture surfaces were polished smoothly. The crack initiation criterion under compressive shear stress state is analyzed by taking the theory of fracture mechanics and classical mechanics. The coupling equation in the extended finite element simulation is established. The influence of lateral pressure on the crack propagation law, the relationship between lateral pressure and fracture, the initial expansion angle and pressure change law, and the effect of working face length on the crack expansion are analyzed. Results. The initial expansion angle of cracks increases with the increase of lateral pressure, and that of a single crack decreases with the increase of pressure. When other conditions are constant, the crack angle of the crevice also shows a trend of increasing with the increase of lateral pressure. When the lateral pressure becomes smaller, the initial expansion angle is relatively small. With the progress of the step size, the expansion angle shows a gradually decreasing trend, that is, the initial expansion angle gradually decreases with the increase of water pressure. The smaller the working face length, the smaller the expansion length of the floor crack. Conclusion. The expansion of the floor cracks is mainly formed by the tensile shear failure, and the fracture water pressure will reduce the initiation stress, which makes the rock mass more prone to the fracture failure.
Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-electron ...microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.
Defects on product surfaces affect quality of the product. Machine vision provides an efficient tool for the surface defect detection. Threshold is commonly used to separate objects from the image ...background in the vision-based inspection method. The Otsu method is one of the most used approaches to decide the threshold for a satisfied result when the image histogram is bimodal, but it fails when the histogram of an image is unimodal or close to unimodal. Defects in product surfaces can range from small to large sizes, which results in distributions of the image histogram change from unimodal to bimodal. An improved Otsu method, named the weighted object variance (WOV), is proposed in this research to detect defects on product surfaces. A parameter that equals the cumulative probability of defects occurrence is weighted on the object variance of between-class variance. The weight ensures that the threshold always be a value that locates at the valley of two peaks or at the left bottom rim of a single peak histogram. It is essential to have a high detection rate and low false alarm rate for the defect detection. Experimental results demonstrate the effectiveness of the improved Otsu method in the defect detection of various surfaces. Compared to other thresholding methods such as maximum entropy, Otsu, valley-emphasis, and modified valley-emphasis methods, the WOV method provides better segmentation results.
Observations of surface ozone available from ∼1,000 sites across China for the past 5 years (2013–2017) show severe summertime pollution and regionally variable trends. We resolve the effect of ...meteorological variability on the ozone trends by using a multiple linear regression model. The residual of this regression shows increasing ozone trends of 1–3 ppbv a−1 in megacity clusters of eastern China thatwe attribute to changes in anthropogenic emissions. By contrast, ozone decreased in some areas of southern China. Anthropogenic NOₓ emissions in China are estimated to have decreased by 21% during 2013–2017, whereas volatile organic compounds (VOCs) emissions changed little. Decreasing NOₓ would increase ozone under the VOC-limited conditions thought to prevail in urban China while decreasing ozone under rural NOₓ-limited conditions. However, simulations with the Goddard Earth Observing System Chemical Transport Model (GEOS-Chem) indicate that a more important factor for ozone trends in the North China Plain is the ∼40% decrease of fine particulate matter (PM2.5) over the 2013–2017 period, slowing down the aerosol sink of hydroperoxy (HO₂) radicals and thus stimulating ozone production.
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•Cationic modifiers decorated Ti3C2 ultra-thin nanosheets were prepared.•TPU/modified Ti3C2 nanocomposites were fabricated via solution blending.•TPU/modified Ti3C2 nanocomposites ...showed excellent fire safety properties.
Thermoplastic polyurethane (TPU) has broad applications as lightweight materials due to its multiple advantages and unique properties. Nevertheless, toxicity emission under fire conditions remains a major concern, particularly in building fire scenarios. To circumvent the problem, it is imperative that an effective flame retardant is sought to suppress the flame and release of combustion/smoke products whilst maintaining the favorable material properties of TPU. In the current work, a simple method is proposed for the preparation and utilization of cetyltrimethyl ammonium bromide (CTAB) and tetrabutyl phosphine chloride (TBPC) modified Ti3C2 (MXene) ultra-thin nanosheets. During the cone calorimeter tests, significant reduction in peak heat release rate (51.2% and 52.2%), peak smoke production rate (57.1% and 57.4%), peak CO production (39.4% and 41.6%) and peak CO2 production (49.7% and 51.7%) were recorded by the mere introduction of 2 wt.% CTAB-Ti3C2 and TBPC-Ti3C2 to TPU. These superior fire safety properties resulting from the significant reduction of the fire, smoke and toxicity hazards are attributed to the excellent dispersion, catalytic and barrier effect of Ti3C2 ultra-thin nanosheets in TPU. Future applications of exfoliated MXene nanosheets as flame retardant appear to be very promising.
Taxonomic and phylogenetic studies on the brown-rot fungi,
Fomitopsis
and its related genera, are carried out. On the basis of morphological characters and phylogenetic evidence of DNA sequences of ...multiple loci including the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), the small subunit nuclear ribosomal RNA gene (nSSU), the small subunit mitochondrial rRNA gene sequences (mtSSU), the translation elongation factor 1-α gene (
tef1
) and the second subunit of RNA polymerase II (
rpb2
), six new genera,
Fragifomes
,
Niveoporofomes
,
Piptoporellus
,
Rhodofomitopsis
,
Rubellofomes
and
Ungulidaedalea
are established. Four new species,
Buglossoporus eucalypticola
,
Daedalea allantoidea
,
Piptoporellus hainanensis
and
P. triqueter
are descibed from China. Illustrated descriptions of the novel species are provided. Identification keys to
Fomitopsis
and its related genera, as well as keys to the species of each genus are provided.
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