191 research outputs found

    Investigation of LGALS2 expression in the TCGA database reveals its clinical relevance in breast cancer immunotherapy and drug resistance

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    Abstract Breast cancer (BRCA) is known as the leading cause of death in women worldwide and has a poor prognosis. Traditional therapeutic strategies such as surgical resection, radiotherapy and chemotherapy can cause adverse reactions such as drug resistance. Immunotherapy, a new treatment approach with fewer side effects and stronger universality, can prolong the survival of BRCA patients and even achieve clinical cure. However, due to population heterogeneity and other reasons, there are still certain factors that limit the efficacy of immunotherapy. Therefore, the importance of finding new tumor immune biomarker cannot be emphasized enough. Studies have reported that LGALS2 was closely related to immunotherapy efficacy, however, it is unclear whether it can act as an immune checkpoint for BRCA immunotherapy. In the current study, changes in LGALS2 expression were analyzed in public datasets such as TCGA-BRCA. We found that LGALS2 expression was associated with immune infiltration, drug resistance and other characteristics of BRCA. Moreover, high LGALS2 expression was closely related to immunotherapy response, and was associated with methylation modifications and clinical resistance for the first time. These findings may help to elucidate the role of LGALS2 in BRCA for the development and clinical application of future immunotherapy strategies against BRCA

    Exploring retinal ganglion cells encoding to multi-modal stimulation using 3D microelectrodes arrays

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    Microelectrode arrays (MEA) are extensively utilized in encoding studies of retinal ganglion cells (RGCs) due to their capacity for simultaneous recording of neural activity across multiple channels. However, conventional planar MEAs face limitations in studying RGCs due to poor coupling between electrodes and RGCs, resulting in low signal-to-noise ratio (SNR) and limited recording sensitivity. To overcome these challenges, we employed photolithography, electroplating, and other processes to fabricate a 3D MEA based on the planar MEA platform. The 3D MEA exhibited several improvements compared to planar MEA, including lower impedance (8.73 ± 1.66 kΩ) and phase delay (−15.11° ± 1.27°), as well as higher charge storage capacity (CSC = 10.16 ± 0.81 mC/cm2), cathodic charge storage capacity (CSCc = 7.10 ± 0.55 mC/cm2), and SNR (SNR = 8.91 ± 0.57). Leveraging the advanced 3D MEA, we investigated the encoding characteristics of RGCs under multi-modal stimulation. Optical, electrical, and chemical stimulation were applied as sensory inputs, and distinct response patterns and response times of RGCs were detected, as well as variations in rate encoding and temporal encoding. Specifically, electrical stimulation elicited more effective RGC firing, while optical stimulation enhanced RGC synchrony. These findings hold promise for advancing the field of neural encoding

    How does digital finance accelerate low-carbon development: evidence from the Yellow River Basin, China

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    Digital finance has become one of the most important factors that drives the transformation toward a low-carbon economy. Although some researchers have examined the association between digital finance and low-carbon development, the indirect effect and asymmetric effect of digital finance on low-carbon development still needs to receive more attention. Taking 71 cities in the Yellow River Basin as an empirical area, this study analyzed how digital finance accelerates low-carbon development, proving that digital finance can directly boost low-carbon development. Moreover, technological innovation and industrial upgrading driven by digital finance can also reduce carbon emission intensity and accelerate low-carbon development. Furthermore, the results of the asymmetric test indicate that cities with higher carbon emission intensity have a more substantial positive influence. The recommendations presented in this study are beneficial for accelerating the progress of low-carbon development in the Yellow River Basin.</p

    The triggering process of an X-class solar flare on a small quadrupolar active region

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    The occurrence of X-class solar flares and their potential impact on the space weather often receive great attention than other flares. But predicting when and where an X-class flare will occur is still a challenge. With the multi-wavelength observation from the Solar Dynamics Observatory and FengYun- 3E satellite, we investigate the triggering of a GOES X1.0 flare occurring in the NOAA active region (AR) 12887. Our results show that this unique X-class flare is bred in a relatively small but complex quadrupolar AR. Before the X-class flare, two filaments (F1 and F2) exist below a null-point topology of the quadrupolar AR. Magnetic field extrapolation and observation reveal that F1 and F2 correspond to two magnetic flux ropes with the same chirality and their adjacent feet rooted at nonconjugated opposite polarities, respectively. Interestingly, these two polarities collide rapidly, accompanied by photospheric magnetic flux emergence, cancellation and shear motion in the AR center. Above this site, F1 and F2 subsequently intersect and merge to a longer filament (F3) via a tether-cutting-like reconnection process. As a result, the F3 rises and erupts, involving the large-scale arcades overlying filament and the quadrupolar magnetic field above the AR, and eventually leads to the eruption of the X-class flare with a quasi-X-shaped flare ribbon and a coronal mass ejection. It suggests that the rapid collision of nonconjugated opposite polarities provides a key condition for the triggering of this X-class flare, and also provides a featured case for flare trigger mechanism and space weather forecasting.Comment: 24 pages, 7 figures, accepted for publication in Ap

    Effects of the CYP3A inhibitors, voriconazole, itraconazole, and fluconazole on the pharmacokinetics of osimertinib in rats

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    Background Osimertinib, as third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line treatment approved to treat advanced T790M mutation-positive tumors. Triazole antifungals are therapeutic drugs for cancer patients to reduce the risk of opportunistic fungal infections. Our objective was to investigate whether three triazole antifungals (voriconazole, itraconazole, and fluconazole) could change the pharmacokinetics of osimertinib in rats. Methods The adult male Sprague-Dawley rats were randomly divided into four groups (n = 6): control (0.3% CMC-Na), and voriconazole (20 mg/kg), itraconazole (20 mg/kg), or fluconazole (20 mg/kg) combined with osimertinib (10 mg/kg) group. Tail vein blood samples were collected into heparin tubes at various time points within 0–48 h after osimertinib administration. Osimrtinib’s plasma concentration was detected using HPLC-MS/MS system equipped with a Waters XBridge C18 column, with the mobile phase consisting of acetonitrile and 0.2% formic acid water at a flow rate of 0.5 mL/min. Results Co-administration with voriconazole or fluconazole increased the Cmax of osimertinib by 58.04% and 53.45%, respectively; the AUC0–t increased by 62.56% and 100.98%, respectively. However, when co-administered with itraconazole, the Cmax and AUC0–t of osimertinib only increased by 13.91% and 34.80%, respectively. Conclusions Our results revealed that the pharmacokinetics of osimertinib were significantly changed by voriconazole and fluconazole in rats, whereas it was slightly affected by itraconazole. This work will contribute to a more comprehensive understanding of the pharmacokinetic properties of osimertinib when co-administered with triazole antifungals

    In vivo corneal elastography: A topical review of challenges and opportunities

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    Clinical measurement of corneal biomechanics can aid in the early diagnosis, progression tracking, and treatment evaluation of ocular diseases. Over the past two decades, interdisciplinary collaborations between investigators in optical engineering, analytical biomechanical modeling, and clinical research has expanded our knowledge of corneal biomechanics. These advances have led to innovations in testing methods (ex vivo, and recently, in vivo) across multiple spatial and strain scales. However, in vivo measurement of corneal biomechanics remains a long-standing challenge and is currently an active area of research. Here, we review the existing and emerging approaches for in vivo corneal biomechanics evaluation, which include corneal applanation methods, such as ocular response analyzer (ORA) and corneal visualization Scheimpflug technology (Corvis ST), Brillouin microscopy, and elastography methods, and the emerging field of optical coherence elastography (OCE). We describe the fundamental concepts, analytical methods, and current clinical status for each of these methods. Finally, we discuss open questions for the current state of in vivo biomechanics assessment techniques and requirements for wider use that will further broaden our understanding of corneal biomechanics for the detection and management of ocular diseases, and improve the safety and efficacy of future clinical practice

    Aptamer modified Zr-based porphyrinic nanoscale metal-organic frameworks for active-targeted chemo-photodynamic therapy of tumors

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    Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells

    A new post-hoc flat field measurement method for the Solar X-ray and Extreme Ultraviolet Imager onboard the Fengyun-3E satellite

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    The extreme ultraviolet (EUV) observations are widely used in solar activity research and space weather forecasting since they can observe both the solar eruptions and the source regions of the solar wind. Flat field processing is indispensable to remove the instrumental non-uniformity of a solar EUV imager in producing high-quality scientific data from original observed data. Fengyun-3E (FY-3E) is a meteorological satellite operated in Sun-synchronous orbit, and the routine EUV imaging data from the Solar X-ray and Extreme Ultraviolet Imager (X-EUVI) onboard FY-3E has the characteristics of concentric rotation. Taking advantage of the concentric rotation, we propose a post-hoc flat field measurement method for its EUV 195 channel in this paper. This method removes small-scale and time-varying component of the coronal activities by taking the median value for each pixel along the time axis of a concentric rotation data cube, and then derives large-scale and invariable component of the quiet coronal radiation, and finally generates a flat field image. Analysis shows that our method is able to measure the instrumental spot-like non-uniformity possibly caused by contamination on the detector, which mostly disappears after the in-orbit self-cleaning process. It can also measure the quasi-periodic grid-like non-uniformity, possibly from the obscuration of the support mesh on the rear filter. After flat field correction, these instrumental non-uniformities from the original data are effectively removed. X-EUVI 195 data after dark and flat field corrections are consistent with the 193 channel data from SDO/AIA, verifying the suitability of the method. Our method is not only suitable for FY-3E/X-EUVI but also a candidate method for the flat field measurement of future solar EUV telescopes.Comment: 14 pages, 6 figures, Accepted for publication in RAA (Research in Astronomy and Astrophysics
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