The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in ...recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.
Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and ...therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1α transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1α via direct binding and facilitates the recruitment of HIF-1α and p300 cofactor to the target promoters. Our results uncover an lncRNA-mediated mechanism for HIF-1 activation and establish the clinical values of LncHIFCAR in prognosis and potential therapeutic strategy for oral carcinoma.
Long noncoding RNAs (IncRNAs) have been implicated in a variety of physiological and pathological processes, including cancer. In prostate cancer, prostate cancer gene expression marker 1 (PCGEM1) is ...an androgen-induced prostate-specific IncRNA whose overexpression is highly associated with prostate tumors. PCGEM1's tumorigenie potential has been recently shown to be in part due to its ability to activate androgen receptor (AR). Here, we report a novel function of PCGEM1 that provides growth advantages for cancer cells by regulating tumor metabolism via c-Myc activation. PCGEM1 promotes glucose uptake for aerobic glycolysis, coupling with the pentose phosphate shunt to facilitate biosynthesis of nucleotide and lipid, and generates NADPH for redox homeostasis. We show that PCGEM1 regulates metabolism at a transcriptional level that affects multiple metabolic pathways, including glucose and g Iutamine metabolism, the pentose phosphate pathway, nucleotide and fatty acid biosynthesis, and the tricarboxylic acid cycle. The PCGEM1-mediated gene regulation takes place in part through AR activation, but predominantly through c-Myc activation, regardless of hormone or AR status. Significantly, PCGEM1 binds directly to target promoters, physically interacts with c-Myc, promotes chromatin recruitment of c-Myc, and enhances its transactivation activity. We also identified a c-Myc binding domain on PCGEM1 that contributes to the PCGEM1-dependent c-Myc activation and target induction. Together, our data uncover PCGEM1 as a key transcriptional regulator of central metabolic pathways in prostate cancer cells. By being a coactivator for both c-Myc and AR, PCGEM1 reprograms the androgen network and the central metabolism in a tumor-specific way, making it a promising target for therapeutic intervention.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Sediment flushing and the morphological responses to the procedure of check dam removal are still unclear. Following laboratory experiments that revealed three stages (deepening, widening, and volume ...release) of check dam adjustment, a check dam built in 2007 at Landao Creek in central Taiwan was adjusted in 2015 by removing central bars and cutting 2.5 m from the middle two piers (stage 1 + 2), with the purpose of regulating sediment transfer and keeping the thalweg at the center of the channel, while also preventing hill slope toe erosion. In 2019, four central piers were removed (stage 3) to increase the volume of sediment released. Annual surveys were conducted after the initial adjustment in 2015 through to 2020 using unmanned aerial vehicles (UAVs). The check dam adjustments revealed that the channel had narrowed and stabilized as indicated by regenerating riparian vegetation. Additionally, distinct terraces had formed on the hill slope toes of the creek channel in proximity to the check dam. The meander upstream weakened following the dam adjustments. This study combining laboratory experiments with actual field observation contributed immensely to check dam decommissioning. Additionally, this study illustrated how an adjustable check dam may aid regulation of sediment transport and thereby sediment balance. It can be adjusted accordingly based on the prevailing channel condition.
The check dam removal guide consists of three stages.
Stage 1: cutting the central portion deeper.
Stage 2: widens the opening.
Stage 3: complete removal. While the adjustable check dam can be adjusted freely in each stage according to the demand of the sediment budget.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. Combined treatment with other strategies is required to achieve the expected therapeutic effect. ...Reactive oxygen species (ROS) play an important role in regulating cancer cells and the tumor microenvironment, even in immune cells. However, rigorous regulation of the ROS level within the entire tumor tissue is difficult, limiting the application of ROS in cancer therapy. Therefore, we design an early phago-/endosome-escaping micelle that can release platinum-based drugs into the cytoplasm of macrophages and cancer cells, thereby enhancing the ROS levels of the entire tumor tissue; inducing apoptosis of cancer cells, down-regulation of CD47 expression of cancer cells, polarization of M1 macrophages, and phagocytosis of cancer cells by M1 macrophages; and achieving the dual effect of chemotherapy and macrophage-mediated immunotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In recent years, object detection became more and more important following the successful results from studies in deep learning. Two types of neural network architectures are used for object ...detection: one-stage and two-stage. In this paper, we analyze a widely used two-stage architecture called Faster R-CNN to improve the inference time and achieve real-time object detection without compromising on accuracy. To increase the computation efficiency, pruning is first adopted to reduce the weights in convolutional and fully connected (FC) layers. However, this reduces the accuracy of detection. To address this loss in accuracy, we propose a reduced region proposal network (RRPN) with dilated convolution and concatenation of multi-scale features. In the assisted multi-feature concatenation, we propose the intra-layer concatenation and proposal refinement to efficiently integrate the feature maps from different convolutional layers; this is then provided as an input to the RRPN. Using the proposed method, the network can find object bounding boxes more accurately, thus compensating for the loss arising from compression. Finally, we test the proposed architecture using ZF-Net and VGG16 as a backbone network on the image sets in PASCAL VOC 2007 or VOC 2012. The results show that we can compress the parameters of the ZF-Net-based network by 81.2% and save 66% of computation. The parameters of VGG16-based network are compressed by 73% and save 77% of computation. Consequently, the inference speed is improved from 27 to 40 frames/s for ZF-Net and 9 to 27 frames/s for VGG16. Despite significant compression rates, the accuracy of ZF-Net is increased from 2.2% to 60.2% mean average precision (mAP) and that of VGG16 is increased from 2.6% to 69.1% mAP.
The clinical characteristics of malignant melanoma are highly variable between patient populations of different ethnicities. To explore the underlining genetic variations, we reviewed the clinical ...data of 242 malignant melanoma cases from Taiwan and among them submitted formalin‐fixed paraffin‐embedded tissue samples from 37 patients for whole‐exome sequencing to identify the mutational signatures, tumor mutation burden and specific gene mutations. The genomic profiles and clinical outcomes were compared with the information derived from the publicly available TCGA and TGEN databases. Mutation signature 12 was the dominant signature in Taiwanese patients and represented approximately 45% of the mutation signatures observed. In contrast, mutation signature 7 was the most prominent among cases available in the TCGA database. Common gene mutations found in the TCGA melanoma dataset were not frequently found in melanomas from Taiwanese patients. There were a significant number of specific gene mutations that exclusively occurred in acral subtype but not in non‐acral subtype melanomas, and vice versa. While certain common mutations form a shared core of genetic features, there appear to be specific genetic pathways that are involved in the occurrence of melanomas that grow in non‐UV‐exposed areas. Our findings have shed light on the tumorigenesis pathways involved in malignant melanoma.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract While understanding the competitive adsorption behavior of gas sensor is important, it is yet to be unraveled. Especially for the influence of water molecules to the gas adsorbed on 2D ...materials. This study explores the potential of layered 2D materials as a candidate material for gas sensing, employing non‐destructive measurement, and second harmonic generation (SHG). The investigation focuses on analyzing oxygen, ammonia, and water vapor adsorbed on a WS 2 surface by studying the evolutions in electric dipole and electric field. Leveraging the simplified bond hyperpolarizability model (SBHM), a foundation is established for gas sensors utilizing high‐quality 2D materials. This approach facilitates the detection of material modifications in response to environmental influences, including the inevitable water molecules. The obtained hyperpolarizability from SBHM exhibits remarkable consistency with Langmuir's adsorption model, confirming the physical adsorption in the system. In addition, the competitive effects between gases are explored by comparing experimental results with theoretical predictions based on Boltzmann distribution and density functional theory (DFT) calculations. This highlights the effectiveness of SHG and SBHM in studying gas adsorption on layered van der Waals materials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The countervailing effects of disturbances (e.g., high mortality and enhanced recovery) on population dynamics can occur through demographic processes under rapidly increasing climatic extremes. ...Across an extreme‐event gradient, we mechanistically demonstrated how dramatic changes in streamflow have affected the population persistence of endangered salmon in monsoonal Taiwan over a three‐decade period. Our modeling indicated that the dynamics of the age‐structured population were attributed to demographic processes, in which extensive mortality was characterized as a function of climatic extremes and vulnerability in the young stage of fish. In the stochastic simulations, we found that the extensive mortality and high proportion of large fish resulted from extreme flooding, which caused high values of postimpact population recovery. Our empirical evidence suggests that the magnitudes and timing of disturbance can explain the population persistence when facing climatic extremes and thereby challenges the understanding of the mechanistic drivers of these countervailing phenomena under changing environmental conditions.
The countervailing effects of disturbances (e.g., high mortality and enhanced recovery) on population dynamics can occur through demographic processes under rapidly increasing climatic extremes. We mechanistically demonstrated how dramatic changes in streamflow have affected the population persistence of endangered salmon in monsoonal Taiwan over a three‐decade period. The extensive mortality and high proportion of large fish resulted from extreme flooding, which caused high values of postimpact population recovery. Our empirical evidence challenges the understanding of the mechanistic drivers of these countervailing phenomena under changing environmental conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Numerous studies have reported that long‐term musical training can affect brain functionality and induce structural alterations in the brain. Singing is a form of vocal musical expression with an ...unparalleled capacity for communicating emotion; however, there has been relatively little research on neuroplasticity at the network level in vocalists (i.e., noninstrumental musicians). Our objective in this study was to elucidate changes in the neural network architecture following long‐term training in the musical arts. We employed a framework based on graph theory to depict the connectivity and efficiency of structural networks in the brain, based on diffusion‐weighted images obtained from 35 vocalists, 27 pianists, and 33 nonmusicians. Our results revealed that musical training (both voice and piano) could enhance connectivity among emotion‐related regions of the brain, such as the amygdala. We also discovered that voice training reshaped the architecture of experience‐dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. It appears that vocal‐related changes in areas such as the insula, paracentral lobule, supramarginal gyrus, and putamen are associated with functional segregation, multisensory integration, and enhanced network interconnectivity. These results suggest that long‐term musical training can strengthen or prune white matter connectivity networks in an experience‐dependent manner.
Musical training (both voice and piano) could enhance connectivity among emotion‐related regions of the brain, such as the amygdala. Voice training reshaped the architecture of experience‐dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. Long‐term musical training can strengthen or prune white matter connectivity networks in an experience‐dependent manner.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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