Multidrug resistance (MDR) is usually correlated with the poor prognosis of gastric cancer. In this study, we revealed a total of 11 microRNAs (miRNA) that regulated MDR of gastric cancer via ...high-throughput functional screening, and miR-508-5p reversed MDR most efficiently among these candidate miRNAs. The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1. These findings suggest that a miR-508-5p/ZNRD1/ABCB1 regulatory loop has a critical role in MDR in gastric cancer. In addition, miR-508-5p could be used as a prognostic factor for overall survival in gastric cancer. These data reveal an important role for miR-508-5p in the regulation of MDR in gastric cancer, and suggest the potential application of miR-508-5p in drug resistance prediction and treatment.
ABSTRACT
Spider pulsars continue to provide promising candidates for neutron star mass measurements. Here we present the discovery of PSR J1910−5320, a new millisecond pulsar discovered in a MeerKAT ...observation of an unidentified Fermi-LAT gamma-ray source. This pulsar is coincident with a recently identified candidate redback binary, independently discovered through its periodic optical flux and radial velocity. New multicolour optical light curves obtained with ULTRACAM/New Technology Telescope in combination with MeerKAT timing and updated SOAR/Goodman spectroscopic radial velocity measurements allow a mass constraint for PSR J1910−5320. icarus optical light curve modelling, with streamlined radial velocity fitting, constrains the orbital inclination and companion velocity, unlocking the binary mass function given the precise radio ephemeris. Our modelling aims to unite the photometric and spectroscopic measurements available by fitting each simultaneously to the same underlying physical model, ensuring self-consistency. This targets centre-of-light radial velocity corrections necessitated by the irradiation endemic to spider systems. Depending on the gravity darkening prescription used, we find a moderate neutron star mass of either 1.6 ± 0.2 or 1.4 ± 0.2 M⊙. The companion mass of either 0.45 ± 0.04 or $0.43^{+0.04}_{-0.03}$M⊙ also further confirms PSR J1910−5320 as an irradiated redback spider pulsar.
This systematic review aimed to assess the current evidence on the directional and non‐directional associations of periodontitis with chronic kidney disease (CKD). Electronic search for observational ...studies on the association of periodontitis with CKD was performed in MEDLINE, EMBASE, PubMed, Open GREY and Cochrane library up to June 5, 2017. Two reviewers conducted study selection, data collection and assessment of methodological quality using the original and modified Newcastle‐Ottawa Scale. Cohort, case‐control and cross‐sectional studies were included, which clearly defined periodontitis and CKD or reported acceptable clinical parameters of these 2 diseases in adults. Meta‐analysis was employed to estimate the pooled odds ratio on the non‐directional association and the incidence rate ratio (IRR) for the directional association. Among 2530 potential eligible articles, 47 were finally included. Most of them investigated a non‐directional association of periodontitis with CKD, including 7 case‐control studies and 38 cross‐sectional studies; 24 studies had statistical analysis on the non‐directional association and 75% of them reported significant results, which were supported further by the meta‐analysis (random: odds ratio = 2.12, P < .001; χ2 = 25.74, I2 = 88.3%). None of the studies focused on the directional association of CKD (as the exposure) with periodontitis (as the outcome), whereas 2 retrospective cohort studies explored a directional association of periodontitis (as the exposure) with CKD (as the outcome) (random: IRR=2.10, P > .05; fixed: IRR=1.76, P < .05; χ2 = 4.65, I2 = 78.3%). Overall, the high heterogeneity of studies limits the significance of these results. There is substantial evidence on the non‐directional association of periodontitis with CKD, while there are limited studies on the directional association. Well‐designed prospective studies with longer follow‐ups in representative communities are needed to clarify the directional association and enhance the quality of the evidence on this topic.
The advent of direct-acting antivirals (DAAs) has brought about a sudden renaissance in the treatment of chronic hepatitis C virus (HCV) infection with SVR rates now routinely >90%. However, due to ...the error-prone nature of the HCV RNA polymerase, resistance-associated substitutions (RASs) to DAAs may be present at baseline and can result in a significant effect on treatment outcomes and hamper the achievement of sustained virologic response. By further understanding the patterns and nature of these RASs, it is anticipated that the incidence of treatment failure will continue to decrease in frequency with the development of drug regimens with increasing potency, barrier to resistance, and genotypic efficacy. This review summarizes our current knowledge of RASs associated with HCV infection as well as the clinical effect of RASs on treatment with currently available DAA regimens.
High-efficiency and high-accuracy deformation analysis using digital image correlation (DIC) has become increasingly important in recent years, considering the ongoing trend of using higher ...resolution digital cameras and common requirement of processing a large sequence of images recorded in a dynamic testing. In this work, to eliminate the redundant computations involved in conventional DIC method using forward additive matching strategy and classic Newton–Raphson (FA-NR) algorithm without sacrificing its sub-pixel registration accuracy, we proposed an equivalent but more efficient DIC method by combining inverse compositional matching strategy and Gauss-Newton (IC-GN) algorithm for fast, robust and accurate full-field displacement measurement. To this purpose, first, an efficient IC-GN algorithm, without the need of re-evaluating and inverting Hessian matrix in each iteration, is introduced to optimize the robust zero-mean normalized sum of squared difference (ZNSSD) criterion to determine the desired deformation parameters of each interrogated subset. Then, an improved reliability-guided displacement tracking strategy is employed to achieve further speed advantage by automatically providing accurate and complete initial guess of deformation for the IC-GN algorithm implemented on each calculation point. Finally, an easy-to-implement interpolation coefficient look-up table approach is employed to avoid the repeated calculation of bicubic interpolation at sub-pixel locations. With the above improvements, redundant calculations involved in various procedures (i.e. initial guess of deformation, sub-pixel displacement registration and sub-pixel intensity interpolation) of conventional DIC method are entirely eliminated. The registration accuracy and computational efficiency of the proposed DIC method are carefully tested using numerical experiments and real experimental images. Experimental results verify that the proposed DIC method using IC-GN algorithm and the existing DIC method using classic FA-NR algorithm generate similar results, but the former is about three to five times faster. The proposed reliability-guided IC-GN algorithm is expected to be a new standard full-field displacement tracking algorithm in DIC.
Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given ...the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo.
FeFETs with 5-nm-thick Hf 0.5 Zr 0.5 O 2 (HZO) have been demonstrated in memory operations for the ON/OFF current ratio >10 4 at zero gate voltage and a memory window (MW) of 0.6-0.7 V. A gradual ...transition of the ferroelectricity with an increasing crystallization temperature for the gate-last process was presented. The excellent data retention are the <inline-formula> <tex-math notation="LaTeX">{\sim }\textsf {2}\times \textsf {10}^{\textsf {4}} </tex-math></inline-formula> ON/OFF ratio and 0.67 V extrapolated to ten years with V P/E = ±4.8 V. The MW remains >0.2 V after 10 6 cycles for read and vanishes with cycles of 10 3 −10 4 for write, which is the bottleneck for ferroelectric (FE)-type memories. The mechanism of retention and endurance is discussed. The characteristic of this letter is an unaffected coercive-field (~1 MV/cm) with scaling FE-HZO down to 5-nm thickness, which is beneficial for reducing the operation voltage. A comparable performance with thick HZO (>5 nm) on high data retention and endurance with low voltage for read is achieved. The ultrathin FE layer proposes a realistic emerging memory for 1T architecture.
Goethite/hematite ratios in soils are widely used to reconstruct past climatic changes, but their accurate measurements have remained challenging due to the matrix effect. Here we present a new ...method for measuring soil goethite/hematite ratios by characterizing the band position of electron pair transition (EPT) based on the diffuse reflectance spectra processed by continuum removal. We introduce a “half‐band‐area wavelength”, λ1/2, to characterize the EPT band position and validate the method using synthetic standards made from mixing pure goethite and hematite and four sets of goethite‐ and hematite‐free matrices derived from arid aeolian deposits and tropical saprolite. A consistent λ1/2‐goethite/hematite relation across four matrices demonstrates that our method eliminates the matrix effect. We further validate our method by applying it to quantify goethite/hematite ratios in 180‐Kyr loess‐paleosol sequences and comparing the results to the reported paleoclimatic records. Our new method is promising for improving the measurement of goethite/hematite ratios in sediments.
Plain Language Summary
Hematite (α‐Fe2O3) and goethite (α‐FeOOH) are common iron oxides in soils and sediments. Their formation processes are sensitive to climatic conditions such as soil humidity. Thus, goethite/hematite ratios in terrestrial and marine deposits have been widely used to infer past climatic changes. However, their use relies on the accurate quantification of goethite/hematite ratios, which has been challenging using existing methods. Conventional X‐ray diffraction methods have high detection limits, whereas rock magnetic methods are limited by the weak magnetization of these minerals and the difficulty in converting magnetic moments to moles. Instead, methods based on diffuse reflectance spectra (DRS) have been frequently used to directly quantify goethite/hematite ratios given the high sensitivity, but major uncertainties exist due to the interference from the sample matrix. We developed a new DRS‐based method to quantify goethite/hematite ratios by characterizing the band position of electron pair transition (EPT). We find consistent statistically significant correlations between a proxy derived from the EPT band positions and goethite/hematite ratios across synthetic standards of different soil matrices, supporting that our method eliminates the matrix effect. Overall, we provided a promising method for precisely quantifying goethite/hematite ratios in soil and sediments.
Key Points
We present a new method for measuring goethite/hematite ratios using the band positions of electron pair transition
The electron pair transition band position characterized by λ1/2 is determined solely by the goethite/hematite ratios, not their contents
The new method is independent of soil matrices and is validated by synthetic and geological samples
PDF
