Search

The RAS gene family holds a central position in controlling key cellular activities such as migration, survival, metabolism, and other vital biological processes. The activation of RAS signaling cascades is instrumental in the development of various cancers. Although several RAS inhibitors have gained approval from the US Food and Drug Administration for their substantial antitumor effects, their widespread and severe adverse reactions significantly curtail their practical usage in the clinic. Thus, there exists a pressing need for a comprehensive understanding of these adverse events, ensuring the clinical safety of RAS inhibitors through the establishment of precise management guidelines, suitable intermittent dosing schedules, and innovative combination regimens. This review centers on the evolution of RAS inhibitors in cancer therapy, delving into the common adverse effects associated with these inhibitors, their underlying mechanisms, and the potential strategies for mitigation. [ABSTRACT FROM AUTHOR]

Oases play a crucial role in arid regions within the human–environmental system, holding significant ecological and biological importance. The Oasis Cold Island Effect (OCIE) represents a distinct climatic feature of oases and serves as a vital metric for assessing oasis ecosystems. Previous studies have overlooked the spatial extent of the Oasis Cold Island Effect (OCIE), specifically the boundary delineating areas influenced and unaffected by oases. This boundary is defined as the Oasis Cold Island Footprint (OCI FP). Utilizing Logistic modeling and MODIS data products, OCI FPs were calculated for the Ejina Oasis from 2000 to 2019. The assessment results underscore the accuracy and feasibility of the methodology, indicating its potential applicability to other oases. Spatial and temporal distributions of OCI FPs and the intensity of the Oasis Cold Island Effect Intensity (OCIEI) in the Ejina Oasis were analyzed, yielding the following findings: (1) OCI FP area and complexity were smallest in summer and largest in autumn. (2) Over the period 2000–2019, OCI FPs exhibited a pattern of increase, decrease, and subsequent increase. (3) OCIEI peaks in summer and reaches its lowest point in winter. Lastly, the study addresses current limitations and outlines future research objectives. [ABSTRACT FROM AUTHOR]

This exploration primarily aims to jointly apply the local FCN (fully convolution neural network) and YOLO-v5 (You Only Look Once-v5) to the detection of small targets in remote sensing images. Firstly, the application effects of R-CNN (Region-Convolutional Neural Network), FRCN (Fast Region-Convolutional Neural Network), and R-FCN (Region-Based-Fully Convolutional Network) in image feature extraction are analyzed after introducing the relevant region proposal network. Secondly, YOLO-v5 algorithm is established on the basis of YOLO algorithm. Besides, the multi-scale anchor mechanism of Faster R-CNN is utilized to improve the detection ability of YOLO-v5 algorithm for small targets in the image in the process of image detection, and realize the high adaptability of YOLO-v5 algorithm to different sizes of images. Finally, the proposed detection method YOLO-v5 algorithm + R-FCN is compared with other algorithms in NWPU VHR-10 data set and Vaihingen data set. The experimental results show that the YOLO-v5 + R-FCN detection method has the optimal detection ability among many algorithms, especially for small targets in remote sensing images such as tennis courts, vehicles, and storage tanks. Moreover, the YOLO-v5 + R-FCN detection method can achieve high recall rates for different types of small targets. Furthermore, due to the deeper network architecture, the YOL v5 + R-FCN detection method has a stronger ability to extract the characteristics of image targets in the detection of remote sensing images. Meanwhile, it can achieve more accurate feature recognition and detection performance for the densely arranged target images in remote sensing images. This research can provide reference for the application of remote sensing technology in China, and promote the application of satellites for target detection tasks in related fields. [ABSTRACT FROM AUTHOR]

The alkaline water electrolyzer (AWE) is the earliest and most mature water‐splitting technology. However, the conventional Raney Ni electrocatalysts dominantly used in AWEs are struggling to meet current demands for higher energy efficiency and cost‐effectiveness in green hydrogen production. Although many promising electrocatalytic materials have been developed using facile preparation methods in the laboratory, they have not received much attention in commercial AWE applications. It is due to the academic negligence on specific operational conditions, critical performance metrics, and material costs associated with industrial AWEs, as well as disregarding the impact of large‐scale electrode manufacturing processes on catalytic performance. Therefore, a timely review to bridge laboratory focus with industrial requirements is essential to guide the future development of water‐splitting electrocatalysts. Here, starting from the differences of operating and testing conditions between laboratory and industrial systems, the gaps in electrocatalytic equipment, evaluation methods, and preparation principles of electrodes are outlined. To narrow these gaps, some academic efforts in advancing industrially relevant electrocatalysts are highlighted and personal perspectives on future opportunities, research focus, and challenges in this field are provided. [ABSTRACT FROM AUTHOR]

In view of the limitation that the transport of intensity equation method can only be used at a single wavelength, we propose a binocular phase retrieval algorithm based on multiwavelength illumination. First, we solve for the corresponding single-phase results at different wavelengths and then calculate the surface height of the object by combining the obtained synthetic wavelengths and synthetic phases, in order to reconstruct the initial phase results at different wavelengths. To solve the problem of amplification of traditional noise and surface profile noise in the phase diagram in the phase synthesis step, we introduce a step-by-step noise reduction method that can reduce the noise in the initial phase results to the level for a single wavelength and finally obtain the corresponding high-precision phase results at different wavelengths. The intensity images collected by the proposed dual-microscope system verify the correctness and effectiveness of the algorithm. [ABSTRACT FROM AUTHOR]

Regorafenib, an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases, has been approved for the treatment of metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma by the US Food and Drug Administration and European Medicines Agency. However, regorafenib-induced cardiotoxicity increases the risk of mortality. Despite reports that regorafenib can cause mitochondrial dysfunction in cardiomyocytes, the molecular mechanism of regorafenib-induced cardiotoxicity is much less known and there is an urgent need for intervention strategies. Here, we treated mice with vehicle or 200 mg/kg regorafenib daily for 42 d by gavage or treated cardiomyocyte lines with 8, 16, or 32 μM regorafenib, and we found that regorafenib could cause apoptosis, mitochondrial injury, and DNA damage in cardiomyocytes. Mechanistically, regorafenib can reduce the expression of EPHA2, which inhibits AKT signaling, leading to cardiomyocyte apoptosis and cardiotoxicity. In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] The tumor suppressor protein p53 participates in the control of key biological functions such as cell death, metabolic homeostasis and immune function, which are closely related to various diseases such as tumors, metabolic disorders, infection and neurodegeneration. The p53 gene is also mutated in approximately 50% of human cancer cells. Mutant p53 proteins escape from the ubiquitination-dependent degradation, gain oncogenic function and promote the carcinogenesis, malignant progression, metastasis and chemoresistance. Therefore, the stability of both wild type and mutant p53 needs to be precisely regulated to maintain normal functions and targeting the p53 stability is one of the therapeutic strategies against cancer. Here, we focus on compound-induced degradation of p53 by both the ubiquitination-dependent proteasome and autophagy-lysosome degradation pathways. We also review other posttranslational modifications which control the stability of p53 and the biological functions involved in these processes. This review provides the current theoretical basis for the regulation of p53 abundance and its possible applications in different diseases. [ABSTRACT FROM AUTHOR]

The article titled "Bridging Laboratory Electrocatalysts with Industrially Relevant Alkaline Water Electrolyzers" discusses the challenges faced by conventional RaneyNi electrocatalysts in meeting the technical demands of producing green hydrogen through alkaline water electrolyzers. The authors, Zhanfeng Deng, Cheng Tang, and their colleagues, highlight the disparities in electrocatalytic equipment, evaluation metrics, and synthesis principles of electrodes between laboratory research and industrial requirements. They also discuss recent academic efforts and future opportunities in critical aspects for industrially relevant alkaline water electrocatalysis electrodes. This article provides valuable insights for researchers and industry professionals interested in this field. [Extracted from the article]

Porous ceramics with high open porosity and good mechanical properties were successfully prepared from fly ash rich in CaO. An addition of 30–50wt.% dolomite decreased the average pore diameter from ∼11.79 μm to ∼2.82μm due to the decrease of viscosity with high dolomite addition, while there is an increase in open porosity from 48.63% to 53.23%. SEM results suggested that pores were firstly surrounded by glassy phase. With the addition of more than 30 wt.% of dolomite, pores were covered by loose structure. XRD results showed the changes in crystal phases of sintered ceramics, from anorthite sodian to alkaline basalt and then to calcium magnesium silicate. CaO and MgO from decomposed dolomite were proposed to be the main reason on modification closed pores to open ones. Except this, CO2 emission and crystalline water emission during sintering were also contributed to the formation of open pores in porous ceramics. [ABSTRACT FROM AUTHOR]

As an emerging contaminant in water, antibiotic resistant bacteria are threatening the public health gravely. In this study, sulfidated ZVI was used to activate persulfate, for antibiotic resistant E. coli and antibiotic resistant genes removal. Impressively, 7 log of antibiotic resistant E. coli was inactivated within 30 min, in sulfidated ZVI activated persulfate system (S/Fe = 0.05). Electron paramagnetic resonance and free radical quenching experiments suggested that sulfidation treatment did not change the specie of radicals. SO 4 • − and HO• were the main reactive oxygen species for the removal of antibiotic resistant E. coli and genes. Investigation on the activation mechanism of persulfate indicated that persulfate decomposition was mainly attributed to heterogeneous activation. More importantly, in-situ characterization (ATR-FTIR) indicated that the main charge transfer complex was formed on the surface of sulfidated ZVI, which would predominantly mediate the generation of SO 4 • − and HO•. Finally, the proposed system was evaluated in modeling water and secondary effluent. Results revealed that only 2.86 log and 0.84 log of antibiotic resistant E. coli were inactivated in the presence of NOM (10 mg/L) and HCO 3 – (84 mg/L), respectively. Besides, sulfidated ZVI activated persulfate system could be pH-dependent in actual wastewater treatment. ga1 • AR E. coli and ARGs can be effectively removed in S-ZVI activated PDS system. • Homogenous and heterogeneous are both involved in the activation of persulfate. • Heterogeneous activation played a major role in S-ZVI activated persulfate system. • SZP system is pH-dependent for AR E. coli inactivation in actual wastewater. [ABSTRACT FROM AUTHOR]

• S-mZVI prepared by physical milling was firstly proposed to activate persulfate. • AR E. coli was completely inactivated within 30 min under S-mZVI activated persulfate system. • Oxidative damage of AR E. coli was systematically studied in SO 4 · - and HO· based AOP. • The role of SO 4 · - and HO· on lipid peroxidation and total ARG removal were firstly identified. Antibiotic resistant bacteria and genes, as emerging pollutants, are threatening public health. In this study, sulfidated micron zero-valent iron (S-mZVI) activated persulfate (SMP) system was used to eliminate antibiotic resistant E. coli (AR E. coli) and antibiotic resistant gene (ARG). S-mZVI exhibited excellent activation of persulfate, which could completely remove AR E. coli within 30 min. The oxidative damage of AR E. coli cell was systemically studied by transmission electron microscopy, fluorescence microscopy, flow cytometry and malondialdehyde analysis. Concentrations of TN and TOC in SMP system were conducted to evaluate the oxidation and mineralization ability for cellular substances in AR E. coli cell. Moreover, removal efficiencies of cell-associated ARG (TetB) and 16S rRNA in SMP system were 2.9 and 2.2 log, respectively. Study on the presence and role of main reactive oxygen species (SO 4 · - and HO ·) in SMP system suggested that SO 4 · - and HO· are key factors when considering membrane lipid oxidation and removal of 16S rRNA and ARG. This study provided a promising treatment method to inhibit antibiotic resistance and revealed the oxidative damage of AR E. coli and gene under SO 4 · - involved system. [ABSTRACT FROM AUTHOR]