The proto-oncogenic protein, c-KIT, plays a crucial role in regulating cellular transformation and differentiation processes, such as proliferation, survival, adhesion, and chemotaxis. The ...overexpression of, and mutations, in c-KIT can lead to its dysregulation and promote various human cancers, particularly gastrointestinal stromal tumors (GISTs); approximately 80-85% of cases are associated with oncogenic mutations in the
gene. Inhibition of c-KIT has emerged as a promising therapeutic target for GISTs. However, the currently approved drugs are associated with resistance and significant side effects, highlighting the urgent need to develop highly selective c-KIT inhibitors that are not affected by these mutations for GISTs. Herein, the recent research efforts in medicinal chemistry aimed at developing potent small-molecule c-KIT inhibitors with high kinase selectivity for GISTs are discussed from a structure-activity relationship perspective. Moreover, the synthetic pathways, pharmacokinetic properties, and binding patterns of the inhibitors are also discussed to facilitate future development of more potent and pharmacokinetically stable small-molecule c-KIT inhibitors.
Regional changes in the flow velocity of Antarctic glaciers can affect the ice sheet mass balance and formation of surface crevasses. The velocity anomaly of a glacier can be detected using the ...Double-Differential Interferometric Synthetic Aperture Radar (DDInSAR) technique that removes the constant displacement in two Differential Interferometric SAR (DInSAR) images at different times and shows only the temporally variable displacement. In this study, two circular-shaped ice-velocity anomalies in Campbell Glacier, East Antarctica, were analyzed by using 13 DDInSAR images generated from COSMO-SkyMED one-day tandem DInSAR images in 2010–2011. The topography of the ice surface and ice bed were obtained from the helicopter-borne Ice Penetrating Radar (IPR) surveys in 2016–2017. Denoted as A and B, the velocity anomalies were in circular shapes with radii of ~800 m, located 14.7 km (A) and 11.3 km (B) upstream from the grounding line of the Campbell Glacier. Velocity anomalies were up to ~1 cm/day for A and ~5 cm/day for B. To investigate the cause of the two velocity anomalies, the ice surface and bed profiles derived from the IPR survey crossing the anomalies were analyzed. The two anomalies lay over a bed hill along the glacial valley where stick-slip and pressure melting can occur, resulting in temporal variation of ice velocity. The bright radar reflection and flat hydraulic head at the ice bed of A observed in the IPR-derived radargram strongly suggested the existence of basal water in a form of reservoir or film, which caused smaller friction and the reduced variation of stick-slip motion compared to B. Crevasses began to appear at B due to tensile stress at the top of the hill and the fast flow downstream. The sporadic shift of the location of anomalies suggests complex pressure melting and transportation of the basal water over the bed hill.
Annually, millions of new cancer cases are reported, leading to millions of deaths worldwide. Among the newly reported cases, breast and colon cancers prevail as the most frequently detected ...variations. To effectively counteract this rapid increase, the development of innovative therapies is crucial. Small molecules possessing pyridine and urea moieties have been reported in many of the currently available anticancer agents, especially VEGFR2 inhibitors. With this in mind, a rational design approach was employed to create hybrid small molecules combining urea and pyridine. These synthesized compounds underwent in vitro testing against breast and colon cancer cell lines, revealing potent submicromolar anticancer activity. Compound
, specifically, exhibited an impressive GI
value of 0.06 μM against the MCF7 cancer cell line, while compound
displayed the highest cytotoxic activity against the HCT116 cell line, with a GI
of 0.33 ± 0.042 μM. Notably, compounds
,
, and
demonstrated excellent safety profiles when tested on normal cells. Molecular docking, dynamic studies, and free energy calculations were employed to validate the affinity of these compounds as VEGFR2 inhibitors.
Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor associated with cancer metabolism and is regarded as a potent anticancer therapeutic strategy within the hypoxic microenvironment ...of cancer. In this study, stilbenoid derivatives were designed, synthesized, and assessed for their capacity to inhibit HIF-1α-associated cancer metabolism and evaluated for inhibition of cancer cell viability and HIF activation. Through the structure-activity relationship studies, compound 28e was identified as the most potent derivative. Specifically, under the hypoxic condition, 28e reduced the accumulation of HIF-1α protein and the expression of its target genes related to glucose metabolism without affecting the expression of HIF-1α mRNA. Furthermore, 28e inhibited glucose uptake, glycolytic metabolism, and mitochondrial respiration, decreasing cellular ATP production under hypoxic conditions. In addition, 28e displayed significant anti-tumor effects and effectively suppressed the accumulation of HIF-1α protein in tumor tissue in vivo xenograft model. These findings suggest that our stilbenoid derivatives exert their anticancer effects by targeting HIF-1α-centered cancer metabolism under hypoxic conditions.
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•Stilbenoid derivatives were designed and synthesized to inhibit HIF-1α.•SAR studies identified compound 28e as the most potent derivative.•Under hypoxia, 28e reduced HIF-1α accumulation, downregulating its target genes.•In a xenograft model, 28e showed anti-tumor effects by suppressing HIF-1α activity.
Given the diminished role of biotic interactions in soils of continental Antarctica, abiotic factors are believed to play a dominant role in structuring of microbial communities. However, many ...ice-free regions remain unexplored, and it is unclear which environmental gradients are primarily responsible for the variations among bacterial communities. In this study, we investigated the soil bacterial community around Terra Nova Bay of Victoria Land by pyrosequencing and determined which environmental variables govern the bacterial community structure at the local scale. Six bacterial phyla, Actinobacteria, Proteobacteria, Acidobacteria, Chloroflexi, Cyanobacteria, and Bacteroidetes, were dominant, but their relative abundance varied greatly across locations. Bacterial community structures were affected little by spatial distance, but structured more strongly by site, which was in accordance with the soil physicochemical compositions. At both the phylum and species levels, bacterial community structure was explained primarily by pH and water content, while certain earth elements and trace metals also played important roles in shaping community variation. The higher heterogeneity of the bacterial community structure found at this site indicates how soil bacterial communities have adapted to different compositions of edaphic variables under extreme environmental conditions. Taken together, these findings greatly advance our understanding of the adaption of soil bacterial populations to this harsh environment.
Glass is widely used for various applications, including flat panel displays, solar panels, architectural windows, and exterior materials. These applications exhibit increasing complexity and ...improved functionality. In particular, glass substrates used in display panels require diverse forms of processing, prompting the exploration of laser applications to enhance processing quality, yield, and efficiency. This study aims to investigate the feasibility of using a high absorption, 257 nm femtosecond laser for processing glass substrates. The goal is to minimize damage and eliminate the need for post-processing, and ensuring superior quality and cross-sectional features. The analysis focuses on the influence of energy density and laser beam overlap ratio on processing variations. Point, line, and area processing were conducted within the achievable energy density range of 2.4–10.8 J/cm
2
. The results indicate that as the overlap ratio increases, processing depth, influenced by heat accumulation, exhibits a non-linear growth pattern. Moreover, the phenomenon of excessive processing width, surpassing design specifications, is mitigated by utilizing burst pulses that induce heat accumulation of ultra-short pulse lasers, thereby promoting increased processing depth while restraining width expansion. By comparing the outcomes of glass substrate processing using different laser wavelengths and pulse durations, it is confirmed that employing a 257 nm femtosecond laser minimizes damage, cracks, and chipping in the processed areas, obviating the need for post-processing. This paper presents the pioneering research on glass processing using deep ultraviolet femtosecond lasers. Results indicate that clear glass ablation is achieved without cracks.
Ice accumulation and proliferation adversely affect the activities of various residential, commercial, and polar research stations. Although significant efforts are devoted to preventing ice adhesion ...to various surfaces by developing various anti‐icing coatings, it is still necessary to enhance overall performance and durability. Herein, a facile approach is proposed for fabricating an icephobic coating on an aluminum 6061 (Al) substrate, by coating a poly(dimethylsiloxane) (PDMS)/ poly(tetrafluoroethylene) (PTFE) composite through a spin‐coating method, followed by sprinkling of SiO2 nanoparticles (NPs). Crosslinker/binder‐free adhesion between PDMS and PTFE is achieved by utilizing secondary‐induced electrostatic dipole‐dipole interactions, these interactions are supported by density functional theory (DFT) calculations as well as structural studies. Moreover, the controlled addition of PTFE powder to PDMS improves the water‐repellency, mechanical strength, and surface roughness of the coating. The self‐formation of the superhydrophobic state of the PDMS/PTFE composite is achieved by sprinkling SiO2 NPs. The sprinkled SiO2 NPs are protected by the PDMS/PTFE composite, which serves as a stress concentrator to achieve low ice adhesion. Furthermore, freezing at low temperatures can be delayed by controlling the heat flow rate, interfacial contact area, and surface texture. This indicates the feasibility of the proposed method for various promising anti‐icing applications.
The coating, made of PDMS, PTFE, and SiO2 NPs, exhibits excellent water repellency and easy roll‐off of water droplet capabilities. The coating exhibits high freezing delay time and low ice adhesion strength, which are associated with a reduced contact area between the solid/liquid or coating/ice interface owing to the formation of air voids.
Unmanned aerial vehicles (UAVs), also known as drones, are a cost-effective alternative to traditional surveying methods, and they can be used to collect geospatial data over inaccessible or ...hard-to-reach locations. UAV-integrated miniaturized remote sensing sensors such as hyperspectral and LiDAR sensors, which formerly operated on airborne and spaceborne platforms, have recently been developed. Their accuracies can still be guaranteed when incorporating pieces of equipment such as ground control points (GCPs) and field spectrometers. This study conducted three experiments for geometric and radiometric accuracy assessments of simultaneously acquired RGB, hyperspectral, and LiDAR data from a single mission. Our RGB and hyperspectral data generated orthorectified images based on direct georeferencing without any GCPs. Because of this, a base station is required for the post-processed Global Navigation Satellite System/Inertial Measurement Unit (GNSS/IMU) data. First, we compared the geometric accuracy of orthorectified RGB and hyperspectral images relative to the distance of the base station to determine which base station should be used. Second, point clouds could be generated from overlapped RGB images and a LiDAR sensor. We quantitatively and qualitatively compared RGB and LiDAR point clouds in this experiment. Lastly, we evaluated the radiometric quality of hyperspectral images, which is the most critical factor of the hyperspectral sensor, using reference spectra that was simultaneously measured by a field spectrometer. Consequently, the distance of the base station for post-processing the GNSS/IMU data was found to have no significant impact on the geometric accuracy, indicating that a dedicated base station is not always necessary. Our experimental results demonstrated geometric errors of less than two hyperspectral pixels without using GCPs, achieving a level of accuracy that is comparable to survey-level standards. Regarding the comparison of RGB- and LiDAR-based point clouds, RGB point clouds exhibited noise and lacked details; however, through the cleaning process, their vertical accuracy was found to be comparable with LiDAR’s accuracy. Although photogrammetry generated denser point clouds compared with LiDAR, the overall quality for extracting the elevation data greatly relies on factors such as the original image quality, including the image’s occlusions, shadows, and tie-points, for matching. Furthermore, the image spectra derived from hyperspectral data consistently demonstrated high radiometric quality without the need for in situ field spectrum information. This finding indicates that in situ field spectra are not always required to guarantee the radiometric quality of hyperspectral data, as long as well-calibrated targets are utilized.
MDH1 and MDH2 enzymes play an important role in the survival of lung cancer. In this study, a novel series of dual MDH1/2 inhibitors for lung cancer was rationally designed and synthesized, and their ...SAR was carefully investigated. Among the tested compounds, compound
containing a piperidine ring displayed an improved growth inhibition of A549 and H460 lung cancer cell lines compared with
. Compound
reduced the total ATP content in A549 cells in a dose-dependent manner; it also significantly suppressed the accumulation of hypoxia-inducible factor 1-alpha (HIF-1α) and the expression of HIF-1α target genes such as
and pyruvate dehydrogenase kinase 1 (
in a dose-dependent manner. Furthermore, compound
inhibited HIF-1α-regulated CD73 expression under hypoxia in A549 lung cancer cells. Collectively, these results indicate that compound
may pave the way for the development of next-generation dual MDH1/2 inhibitors to target lung cancer.
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