Search

The land surface layer is an important interface between the ground and atmosphere, and cross-surface ground heat flux (G 0) has a significant impact on land surface energy processes and associated cycles. Therefore, understanding dynamics in G 0 is critical for predicting climate changes and developing adaptation strategies. However, the harsh environment and geographic barriers of the Tibetan Plateau have led to a significant lack of observations and soil samples, ultimately limiting the accuracy and application of G 0 calculations. Here we investigated the changes in G 0 at the BJ station, a typical seasonally frozen ground region of the Tibetan Plateau, through soil sampling and long-term in-situ observations. We used the calorimetric method to minimize reliance on model assumptions, aiming to achieve consistent and broadly applicable results. During the freezing-to-thawing and thawing-to-freezing stages, daytime G 0 decreased while nighttime G 0 increased. Conversely, daytime G 0 increased while nighttime G 0 decreased in the completely thawed and completely frozen stages. In moist conditions, more energy was directed toward soil moisture evaporation and vegetation transpiration, whereas in dry conditions, net radiation primarily increased soil temperature, enhancing G 0. Our results revealed the dynamic changes in G 0 across different environmental conditions and their impact on land-atmosphere interactions, and that climate warming and humidifying will diminish the regulatory capacity of G 0. This study highlights the essential requirement for accurate G 0 to predict future climate changes accurately, emphasizing its importance for researchers focusing on land-atmosphere feedback mechanisms and climate modeling. • The minimum and mean G 0 have been increasing while the maximum G 0 decreasing. • More energy is directed toward latent heat flux under moist and warm conditions. • Net radiation primarily increases soil temperature under dry and warm conditions. • The reduction in daytime G 0 leads to insufficient heat release at night. [ABSTRACT FROM AUTHOR]

Currently, deep-learning-based methods have been widely used in fault diagnosis to improve the diagnosis efficiency and intelligence. However, most schemes require a great deal of labeled data and many iterations for training parameters. They suffer from low accuracy and over fitting under the few-shot scenario. In addition, a large number of parameters in the model consumes high computing resources, which is far from practical. In this paper, a multi-scale and lightweight Siamese network architecture is proposed for the fault diagnosis with few samples. The architecture proposed contains two main modules. The first part implements the feature vector extraction of sample pairs. It is composed of two lightweight convolutional networks with shared weights symmetrically. Multi-scale convolutional kernels and dimensionality reduction are used in these two symmetric networks to improve feature extraction and reduce the total number of model parameters. The second part takes charge of calculating the similarity of two feature vectors to achieve fault classification. The proposed network is validated by multiple datasets with different loads and speeds. The results show that the model has better accuracy, fewer model parameters and a scale compared to the baseline approach through our experiments. Furthermore, the model is also proven to have good generalization capability. [ABSTRACT FROM AUTHOR]

In this paper, crack growth in orthotropic materials subjected to dynamic loading is numerically studied using an adaptive phase-field method. The study starts with a coarse structured mesh and the adaptive refinement strategy based on a user-defined threshold on the phase-field variable is proposed for computational efficiency, and variable-node elements are employed to treat the hanging nodes as a result of local adaptive refinement. The Hughes-Hilbert-Taylor (HHT) time integration scheme is adopted for temporal discretization. The directionality of orthotropic materials is represented by a penalized second-order structural matrix, which is incorporated in the crack face energy density. Through numerical examples, the influence of the material orientation on the dynamic crack growth in orthotropic materials is studied and the reliability of the proposed framework is validated. • An adaptive PFM is proposed to simulate dynamic crack growth in orthotropic materials. • Time integration method HHT is combined with a staggered solving scheme. • A robust local adaptive refinement strategy is used based on a phase-field threshold. • Variable-node elements are used to overcome incompatibility in the refined mesh. • Performance of the proposed framework is demonstrated by numerical examples. [ABSTRACT FROM AUTHOR]

As a lower vertebrate, the immune defense mechanism of fish mainly depends on the innate immune system. Nucleotide-binding oligomerization domain-like receptors (NLRs) are an important class of pattern recognition receptors in the innate immune system. In this study, NOD1 gene was cloned and characterized in Nile tilapia (Oreochromis niloticus). The ORF of Nile tilapia NOD1 gene was 2826 bp long and encoded 941 amino acid residues with a structure of CARD-NACHT-LRRs that was similar to the other counterparts in mammals and fishes. Phylogenetic and synteny analysis showed that NOD1 was conserved among different fishes and existed at least in the early stage of fish evolution. Expression pattern revealed that NOD1 mRNA was constitutively expressed in the tested tissues, while had high expression level in main immune organs and mucosal immune tissues (liver, head kidney, spleen, blood, gill, and intestine). Following Streptococcus agalactiae challenge, Nile tilapia NOD1 mRNA expression levels were altered in immune organs (liver, head kidney, spleen, blood), and the expression pattern was similar in liver, spleen and blood. Furthermore, the ligand recognition and signaling pathway of Nile tilapia NOD1 were also analyzed, it showed that NOD1 could recognize Tri-DAP intracellularly and activated NF-κB signaling pathway. In summary, our results indicated that the Nile tilapia NOD1 may play an important role in innate immune system and provided a basis for the functional study of NOD1 in teleost. • The recognition mechanism between Nile tilapia NOD1 and its specific ligand was determined. • Nile tilapia NOD1 could significantly activate the NF-κB, type I interferon and MAPK signaling pathway. • Nile tilapia NOD1 could recognize Tri-DAP intracellularly, but not extracellularly. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association between expressions of five periodontal pathogens (Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf), Treponema denticola (Td) and Prevotella intermedia (Pi) and the periodontal pocket depth (PD) in people suffering from periodontitis. A study of 1164 plaque samples from individuals with periodontitis were conducted by multiplex real-time quantitative fluorescence-polymerase chain reaction to evaluate the PD and loads of five periodontal pathogens. The total bacterial number did not differ significantly between people with different subtypes of periodontitis. However, expression of specific pathogens (Pg, Td, Tf, Pi) showed a significant increase with the development of periodontitis. Expression of Pg, Td and Tf showed close correlation between them as well as with PD. Analyses of receiver operating characteristic curves showed that expression of Pg, Td, Tf and Pi had good potential for grading periodontitis severity. We found a close correlation between the relative expression of Pg, Td and Tf and PD. Measuring expression of target bacteria in the oral cavity could facilitate the understanding of the role of bacteria in periodontitis. Taking the appropriate steps to eliminate these pathogens might aid the prevention of periodontitis development. [ABSTRACT FROM AUTHOR]

• Mo 2 C/CFP-Act is prepared via continuous cathode polarization technique. • Mo 2 C/CFP-Act is an excellent electrocatalyst for the hydrogen evolution reaction. • Mechanism study unveils the Pt single atom intrinsic role in Mo 2 C/CFP catalysts. Dispersing catalytically active metals as single atoms on supports offer an efficient pathway to minimize amount of precious metals. Although platinum (Pt) is highly active for HER, it is highly desirable to find ways to improve the HER performance and also keeping them stable during catalytic reactions while minimizing the Pt loading. Herein, we report a cathode polarization technique to disperse isolated single Pt atoms on β-Mo 2 C as a catalyst for HER. The isolated Pt atoms partially occupy Mo sites in Mo 2 C lattice by forming Pt-Mo shells, which maximize the utilization ratio of platinum noble metals. The single atoms catalyst Mo 2 C/CFP-Act even exhibited 1.9 and 1.1 times higher current density (@ potential of 0.4 V vs. RHE) than that of Pt NPs catalysts (Mo 2 C/CFP-Pt) after mass normalization in both acidic and alkali solution. Furthermore, DFT calculations demonstrate that Mo 2 C/CFP-Act exhibits favorable ΔG H* for the adsorption and desorption of hydrogen. The high HER activity of the Mo 2 C/CFP-Act catalyst is related to the Mo-Pt center located in Mo 2 C matrix, where the electronic structure of the Mo-Pt centers more efficient in donating electron to the σ* antiorbital of the H 3 O+ molecule. This study sheds new light on the HER catalysis mechanism of isolated metal atoms based on fundamental understanding in molecular governing factors. [ABSTRACT FROM AUTHOR]

Seamless image mosaicking is a crucial technique in the production of orthophotos in photogrammetry and remote sensing. There are many studies focused on generating high-quality ortho-mosaics and many algorithms have been put forward for this purpose. Some of the existing methods concentrate on guiding the seamline to bypass ground objects, while others focus on generating a seamline network with better global quality, based on a regular and consistent initial network. However, the former may result in an irregular seamline network structure and the latter cannot guarantee the seamline bypasses ground objects in some cases, due to limited optimization. In this study, an improved image mosaicking approach, taking both the local optimization of a single seamline and the global regularity and consistency of the whole seamline network into consideration, is proposed in order to generate a globally consistent seamline network for aerial images. Firstly, the seamline is selected using a coarse-to-fine strategy between adjacent overlapping orthoimages, in which the initial seamline is generated based on our previous work and further refined based on texture difference. Then, an effective mosaic polygon of each orthoimage is obtained through a novel method, before being used to compose a globally consistent seamline network. Furthermore, an evaluation index called the Area Weighted Distance is introduced to quantitatively evaluate the global consistency and regularity of the generated seamline network. Experiment results demonstrate that the proposed approach is feasible and promising in terms of its performance. Compared to the comparison methods, the proposed approach is 1.35 and 2.15 times smaller in the average and standard deviation of the area weighted distance, respectively, and 3.6-6.5 times faster in terms of efficiency. [ABSTRACT FROM AUTHOR]

In this paper, we report the development of a label-free biosensor, based on surface plasmon resonance, for real-time monitoring of captured human CD4+T-cells, and their dynamic cytokine production upon specific antigen stimulation. Microarrays of CD4+T-cells, and interferon gamma (IFN-γ) specific antibody (Ab) spots were printed side by side onto the poly(OEGMA-co-HEMA) matrix. The placement of CD4+ T-cells near the anti IFN-γ Ab-coated spots ensured a high local concentration of secreted IFN-γ for detection. We have demonstrated that this approach enables the detection of tuberculosis (TB) infection in clinical samples, with an overall sensitivity of 85.5% and an overall specificity of 97.7%. [ABSTRACT FROM AUTHOR]

The disabled homolog 2 interactive protein (DAB2IP) gene is a member of the family of Ras GTPases and functions as a tumor suppressor in many types of carcinoma; however, its function in osteosarcoma remains unclear. The aim of the present study was to determine the function of DAB2IP in osteosarcoma and normal bone cells in vitro. The expression of DAB2IP protein was assessed in osteoblast and osteosarcoma cell lines by western blot analysis. The effects of DAB2IP expression on cell proliferation, colony formation, apoptosis, cell cycle, and cell migration and invasion were evaluated by in vitro studies. DAB2IP expression was lower in osteosarcoma cell lines than in normal osteoblast cell lines. DAB2IP expression affected cell proliferation, apoptosis and cell cycle distribution. In addition, DAB2IP inhibited the migration and invasion of osteosarcoma and normal osteoblast cells. Therefore, DAB2IP may function as a tumor suppressor in osteosarcoma cell lines by inhibiting cell proliferation and invasion. [ABSTRACT FROM AUTHOR]

Synthesis and characterization of a cost-effective electrocatalyst for oxygen reduction reaction (ORR) are attempted for sustainable development in energy storage protocol. Ordered mesoporous carbon (OMC) has emerged as a promising candidate for such purposes, particularly in alkaline conditions. However, the scarceness of active sites is responsible for considerably lower catalytic performance of OMC. Herein, we report a new facile route to synthesize α-FeO nanoparticles supported on ordered mesoporous carbons forming a new hybrid ORR catalyst. This catalyst displayed excellent catalytic properties, long-term stability and impressive methanol tolerance. [ABSTRACT FROM AUTHOR]

This study on the aged population in China first used a large-scale longitudinal survey database to explore how different life factors affect their ability to engage in daily activities. We select and integrate multiple machine models to obtain an excellent model for analyzing relationships. Based on the identified factors, our goal is to help them maintain a good daily life and quality of life. We analyzed data from 13,220 older individuals participating in the China Longitudinal Health Longevity Survey (CLHLS) from 2002 to 2018. ADL was measured based on participants' self-reported results. Nine machine learning algorithms, including neural networks and an ensemble model, were employed with a 2/3 training and 1/3 testing split. Model performance was evaluated using the area under the curve (AUC), sensitivity, and specificity, while logistic regression assessed the relationship between lifestyle changes and ADL disorders. The K-nearest neighbors (KNN) and decision tree algorithms showed the best performance, with AUCs of 0.8598 and 0.8322, respectively. Combining results from all models improved the AUC to 0.8619. Activities, such as playing mahjong, engaging in outdoor work, and reducing TV time, were linked to lower ADL decline, with greater participation in social activities and pet care also being beneficial. Machine learning algorithms, especially ensemble models, can effectively identify older adults at risk for ADL disorders. Increased outdoor activity, social engagement, and dietary adjustments are associated with a decreased risk of ADL deterioration. 1) The primary question addressed by this study is: What modifiable risk factors can impact Activities of Daily Living (ADL) in older adults? 2) The main finding of this study is that specific daily activities, such as playing mahjong and engaging in outdoor activities, significantly reduce the risk of future ADL disorders in older adults. Additionally, a robust predictive model was developed using longitudinal data from 13,220 individuals, improving the accuracy of ADL disorder risk predictions. 3) The meaning of the finding is that incorporating behavioral interventions into community care strategies can effectively enhance the well-being of older adults by minimizing their risk of ADL dysfunction. • This study asks: What modifiable factors affect older adults' ADL? • Certain daily activities like mahjong and outdoor ones reduce ADL disorder risk. • A model from 13,220 - person data enhances ADL disorder prediction accuracy. • Behavioral interventions in care can lower ADL dysfunction risk. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the efficacy of betahistine mesylate in treating vertigo and angioneurotic headache, enhancing microcirculation, and facilitating histamine release. However, limited research has been conducted on the drug's potential in mitigating blue light-induced damage. Thus, this study utilized Drosophila as the model organism and employed the Siler model to investigate the impact of various concentrations of betahistine mesylate on the lifespan, under 3000 lx blue light irradiation. At the same time we measure food intake, spontaneous activity, and sleep duration of Drosophila. The findings of this study indicate that a high concentration of betahistine mesylate can decrease the initial mortality (b0) in male flies, mitigating the damage of blue light to Drosophila. Consequently, this delays the aging process in male Drosophila and extends their average lifespan. After betahistine mesylate ingestion, locomotor activity upon blue light exposure decreased significantly in male Drosophila. In conclusion, this study offers initial evidence supporting the investigation of the regulatory mechanisms of betahistine mesylate on lifespan and its potential anti-blue light effects. • Feeding fruit flies with the highest concentration of the betahistine mesylate reduced the risk of death during adulthood. • Male flies given the highest concentration of betahistine mesylate had prolonged lifespan and lower initial aging rate (b0). • These findings offer valuable insights for exploring strategies to delay aging when exposed to blue light-induced damage. [ABSTRACT FROM AUTHOR]

The NOD-like receptors (NLRs) are an important part of the innate immune system, capable of recognizing or sensing pathogens or cell homeostasis imbalance, and play an important role in pathogen removal and body protection. NOD2 is one of the important members in NLR family. In present study, NOD2 was cloned and identified from Nile tilapia (Oreochromis niloticus). The Nile tilapia NOD2 ORF was 2961 bp in length encoding a peptide of 986 amino acid residues with a typical structure of CARD-CARD-NACHT-LRRs. Phylogenetic and synteny analysis illustrated that NOD2 was highly conserved between different species. Tissue distribution of NOD2 mRNA showed that it was widely expressed and highly expressed in immune-related tissues (blood, head kidney, liver and spleen). Post Streptococcus agalactiae challenge, NOD2 mRNA expression levels were altered in immune organs or tissues (liver, head kidney, spleen and blood). Subcellular localization of Nile tilapia NOD2 illuminated that it was an intracellular PRR like mammalian counterparts, most of which was co-localized with mitochondria, and a few of which was co-localized with endosome and endoplasmic reticulum. In addition, Nile tilapia NOD2-mediated signaling pathway and ligand recognition were also studied, it illuminated that Nile tilapia NOD2 could recognize MDP intracellularly and activate NF-κB signaling pathway. In conclusion, this study indicated that the Nile tilapia NOD2 was conservative and had a significant role in innate immune defense against bacterial infection. • The recognition mechanism between fish NOD2 and its specific ligand was determined. • Nile tilapia NOD2 could significantly activate the NF-κB, type I interferon and MAPK signaling pathway. • Nile tilapia NOD2 was mainly co-localized with mitochondria. • NOD2 was highly conserved between different species. [ABSTRACT FROM AUTHOR]

Scavenger receptors play a central role in defending against infectious diseases in mammals. However, the function of SRECII remains unknown in teleost fish. In this study, type F scavenger receptor expressed by endothelial cells-II (SRECII) cDNA sequence was first identified from Epinephelus coioides , named Ec SRECII, which contained an N-terminal signal peptide, eight EGF/EGF-like cysteine-rich motifs and a C-terminal low-complexity region. The gene location maps revealed that Ec SRECII has the conservation of synteny among selected species. Subcellular localization showed that Ec SRECII was mainly located in the cytoplasm in HEK293T cells and GS cells. In healthy E. coioides , Ec SRECII mRNA was highly expressed in spleen, skin, gill, thymus and head kidney. The relative Ec SRECII mRNA expression after Vibrio parahaemolyticus infection was significantly up-regulated at 12 h in spleen, head kidney and thymus, but downregulated at 1 d in skin and reduced at 3 d and 1 w in spleen. Furthermore, overexpression of Ec SRECII activated NF-κB and IFN-β signaling pathway in vitro. Taken together, these results indicated that Ec SRECII could be as the potential pathogen recognition receptor for involving in bacterial infection by regulating innate immunity responses in E. coioides. • Ec SRECII from E. coioides was first identified and characterized. • Ec SRECII might be involved in respective to V. parahaemolyticus infection. • The overexpression of Ec SRECII activated NF-κB or IFN-β signaling pathway in vitro. [ABSTRACT FROM AUTHOR]

• ERα, ERβ1, ERβ2 and GPER are all involved in the regulation of vitellogenesis. • ERα is the central factor, acting interactively with ERβ1, ERβ2 and GPER in zebrafish. • GPER gets involved in vitellogenesis directly and interactively with ERα, ERβ1 and ERβ2 in zebrafish. Estrogens exert their biological functions through the estrogen receptors (ERs). In zebrafish, three nuclear estrogen receptors (nERs) named ERα, ERβ1 and ERβ2 and one membrane-bound G protein-coupled estrogen receptor (GPER) are identified. Vitellogenin (Vtg) is predominantly expressed in liver and strongly response to the stimulation of estrogen. It has been proposed that all three nERs are functionally involved in vitellogenesis and ERα may act as the major mediator in teleost. However, the role of GPER and its interaction with nERs in this process are not yet defined in teleost species. In the present study, we provide genetic evidence for the functional significance of ERα that the expression of Vtg genes (vtg1 , vtg2 , vtg3) and their response to estradiol stimulation were significantly decreased in esr1 mutant zebrafish. Activation of ERβ1 and ERβ2 induced Vtg expression through ERα. Moreover, the involvement of GPER in vitellogenesis and its interaction with nERs in zebrafish were firstly proposed in this work. Activation of GPER induced Vtg genes expression while inhibition of GPER significantly attenuated the estrogenic effect on Vtg. Both treatments altered the expression levels of nERs, suggesting GPER acts interactively with nERs. Collectively, the involvement of both nERs and GPER in regulation of vitellogenesis is demonstrated. ERα is the central factor, acting interactively with ERβ1, ERβ2 and GPER, and GPER regulates vitellogenesis directly and interactively with nERs. [ABSTRACT FROM AUTHOR]

"Earth summit mission 2022" is one of the landmark scientific research activities of the Second Tibetan Plateau Scientific Expedition and Research (STEP). This scientific expedition firstly used advanced technology and methods to detect vertical meteorological elements and produce forecasts for mountain climbing. The "Earth summit mission 2022" Qomolangma scientific expedition exceeded an altitude of over 8000 meters for the first time and carried out a comprehensive scientific investigation mission on the summit of Mt. Qomolangma. Among the participants, the westerly-monsoon synergy and influence team stationed in the Mt. Qomolangma region had two tasks: 1) detecting the vertical structure of the atmosphere for parameters such as wind, temperature, humidity, and pressure with advanced instruments for high-altitude detection at the Mt. Qomolangma base camp; and 2) observing extreme weather processes to ensure that members of the mountaineering team could successfully reach the top. Through this scientific expedition, a better understanding of the vertical structure and weather characteristics of the complex area of Mt. Qomolangma is gained. [ABSTRACT FROM AUTHOR]

Accelerated tree growth in the alpine treeline ecotone (ATE) has been linked to the recent rapid climate warming. However, the role of tree age and elevation in the growth response of trees to climate change remains unclear. Here, we developed basal area increment chronologies of Betula ermanii from the closed forest belt (CFB) at lower elevation to the ATE of Changbai Mountain with three tree age classes (young: 0–60 years, middle-aged: 60–120 years, and old: > 120 years). In ATE, all age classes of B. ermanii have been experiencing dramatic growth acceleration since 1981. Young trees, with higher temperature sensitivity, exhibited the most prominent warming-induced growth enhancement relative to middle and old-aged trees. In CFB, young and middle-aged trees exhibited similar sensitivity to the temperature increase during the warm period relative to the cold period, with strikingly accelerated growth enhancement trends. In contrast, old trees did not show any significant growth trend. Moreover, young trees in ATE showed significantly (p < 0.01) higher growth rates than those in CFB, whereas middle-aged trees in ATE showed significantly (p < 0.05) lower growth rates than those in CFB. Our results reveal that the response of tree growth to climate change varies with tree age and elevation. Therefore, these factors should be considered to avoid overestimation or underestimation of tree growth trends and bias in estimating potential forest production. [ABSTRACT FROM AUTHOR]

Using temporal and spatial correlations to predict wind speed is still one of the most challenging and least-researched fields in wind speed prediction. How to make full use of the spatial correlation of wind speed between adjacent wind turbines to improve the accuracy of wind speed prediction is significant. Therefore, to address the challenges of making multi-location, short-term wind speed predictions, we propose a multi-location wind speed prediction model based on spatiotemporal joint learning, which called Mixed-SqueezeNet-BiGRU. By designing the SqueezeNet model with a deformable convolutional network, the spatial correlation of a multi-location time series is learned by using the spatial wind speed matrix; by introducing the Channel Shuffle operation of ShuffleNet, the characteristics of multi-location and multi-channel are output to ensure the orderly flow of information among the channels. To describe the dynamic information of the time series, a time series dynamic network model based on the bi-directional gating cycle unit, BiGRU, is introduced to model the long-term and nonlinear dependence of the time series. Experiments were carried out on three wind farm's wind speed dataset to verify that the Mixed-SqueezeNet-BiGRU short-term wind speed prediction model has a better prediction performance than some advanced methods. •Using spatial correlation of wind speed to improve the performance of prediction. •Using spatial wind speed matrix as the input of the multi-location prediction model. •Obtaining Relative position of each wind turbine by DCN learning position offset. •Multi-location wind speed prediction model based on the space-time joint learning. [ABSTRACT FROM AUTHOR]

At present, the inspection mode of China's import ports is generally manual based on experience, or random inspection by the document review system according to a preset random inspection ratio. In order to improve the detection rate of unqualified goods and realize the best allocation of limited human and material resources of inspection and quarantine institutions, a method composed of fuzzy reasoning, deep neural network, and factorization machine (DeepFM) was proposed for the intelligent evaluation of risk sources of imported goods. Fuzzy reasoning is used to realize the fuzzy normalization of the dataset samples, the DeepFM deep neural network is finally used for training and learning to classify and evaluate the risks of goods. Results of experimental tests on a specific customs import and export dataset verify the effectiveness of the proposed research method. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of amino acid identification, a model based on the convolutional neural network (CNN) and bidirectional gated recurrent network (BiGRU) is proposed for terahertz spectrum identification of amino acids. First, we use the CNN to extract the feature information of the terahertz spectrum; then, we use the BiGRU to process the feature vector of the amino acid time-domain spectrum, describe the time series dynamic change information, and finally achieve amino acid identification through the fully connected network. Experiments are carried out on the terahertz spectra of various amino acids. The experimental results show that the CNN-BiGRU model proposed in this study can effectively realize the terahertz spectrum identification of amino acids and will provide a new and effective analysis method for the identification of amino acids by terahertz spectroscopy technology. [ABSTRACT FROM AUTHOR]

• Novel sulfonamide derivatives containing dithiocarbamate moiety were synthesized as potent PKM2 activators. • Compound 8k has good PKM2 activation potency (AC 50 = 56 nM). • Compound 8k has great anti-proliferation activities on 6 tumor cell lines (IC 50 = 0.28 ~ 1.86 µM). • Compound 8k could effectively inhibit the colony formation of MCF7 cells. • Compound 8k could reduce the PKM2 nuclear localization and block the downstream signaling pathways of PKM2. Pyruvate kinase M2 isoform (PKM2) plays a key role in cancer progression through both metabolic and non-metabolic functions, thus it is recognized as a potential target for cancer diagnosis and treatment. In this study, we discovered a sulfonamide-dithiocarbamate compound 8a as a novel PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8a analogs were designed and synthesized for screening as potent PKM2 activators. Among them, compound 8b (AC 50 = 0.136 µM) and 8k (AC 50 = 0.056 µM) showed higher PKM2 activation activities than positive control NZT (AC 50 = 0.228 µM), and they (IC 50 < 1 µM) exhibited more significant anti-proliferative activities against human tumor cell lines than NZT (IC 50 > 10 µM). Especially, compound 8k inhibited the proliferation of multiple cancer cells, but showed little toxicity on normal cells. In addition, we found that compound 8k inhibit the colony formation of MCF7 cells. Western blot analysis demonstrated that 8k could reduce PKM2 nuclear localization and block the downstream signaling pathway of PKM2, resulting in suppression of tumor cell proliferation. Overall, compound 8k may be a promising candidate for further mechanistic investigation of PKM2 and cancer therapy. [ABSTRACT FROM AUTHOR]

Electronic component recognition plays an important role in industrial production, electronic manufacturing, and testing. In order to address the problem of the low recognition recall and accuracy of traditional image recognition technologies (such as principal component analysis (PCA) and support vector machine (SVM)), this paper selects multiple deep learning networks for testing and optimizes the SqueezeNet network. The paper then presents an electronic component recognition algorithm based on the Faster SqueezeNet network. This structure can reduce the size of network parameters and computational complexity without deteriorating the performance of the network. The results show that the proposed algorithm performs well, where the Receiver Operating Characteristic Curve (ROC) and Area Under the Curve (AUC), capacitor and inductor, reach 1.0. When the FPR is less than or equal 10 − 6 level, the TPR is greater than or equal to 0.99; its reasoning time is about 2.67 ms, achieving the industrial application level in terms of time consumption and performance. [ABSTRACT FROM AUTHOR]

Electronic component recognition plays an important role in industrial production, electronic manufacturing, and testing. In order to address the problem of the low recognition recall and accuracy of traditional image recognition technologies (such as principal component analysis (PCA) and support vector machine (SVM)), this paper selects multiple deep learning networks for testing and optimizes the SqueezeNet network. The paper then presents an electronic component recognition algorithm based on the Faster SqueezeNet network. This structure can reduce the size of network parameters and computational complexity without deteriorating the performance of the network. The results show that the proposed algorithm performs well, where the Receiver Operating Characteristic Curve (ROC) and Area Under the Curve (AUC), capacitor and inductor, reach 1.0. When the FPR is less than or equal 10 − 6 level, the TPR is greater than or equal to 0.99; its reasoning time is about 2.67 ms, achieving the industrial application level in terms of time consumption and performance. [ABSTRACT FROM AUTHOR]

Face detection and alignment in unconstrained environment is always deployed on edge devices which have limited memory storage and low computing power. This paper proposes a one-stage method named CenterFace to simultaneously predict facial box and landmark location with real-time speed and high accuracy. The proposed method also belongs to the anchor-free category. This is achieved by (a) learning face existing possibility by the semantic maps, (b) learning bounding box, offsets, and five landmarks for each position that potentially contains a face. Specifically, the method can run in real time on a single CPU core and 200 FPS using NVIDIA 2080TI for VGA-resolution images and can simultaneously achieve superior accuracy (WIDER FACE Val/Test-Easy: 0.935/0.932, Medium: 0.924/0.921, Hard: 0.875/0.873, and FDDB discontinuous: 0.980 and continuous: 0.732). [ABSTRACT FROM AUTHOR]

• Endothelium-targeted Ddx24 conditional knockout exhibited aggravation of ConA-induced hepatitis in mice. • Vascular hyper-permeability is involved in the exacerbation of ConA-induced hepatitis in endothelium-targeted Ddx24 conditional knockout mice. • Endothelium-targeted Ddx24 conditional knockout aggravates ConA-induced hepatitis, possibly due to inflammation-related permeable barrier signaling. • The findings provide evidence DDX24 plays a crucial role in regulating immune-mediated hepatitis, may potentially be used for the therapeutic target of the disorder. Acute hepatitis is a progressive inflammatory disorder that can lead to liver failure. Endothelial permeability is the vital pathophysiological change involved in infiltrating inflammatory factors. DDX24 has been implicated in immune signaling. However, the precise role of DDX24 in immune-mediated hepatitis remains unclear. Here, we investigate the phenotype of endothelium-targeted Ddx24 conditional knockout mice with Concanavalin A (ConA)-induced hepatitis. Mice with homozygous endothelium-targeted Ddx24 conditional knockout (Ddx24flox/flox; Cdh5-Cre+) were established using the CRISPR/Cas9 mediated Cre-loxP system. We investigated the biological functions of endothelial cells derived from transgenic mice and explored the effects of Ddx24 in mice with ConA-induced hepatitis in vivo. The mass spectrometry was performed to identify the differentially expressed proteins in liver tissues of transgenic mice. We successfully established mice with endothelium-targeted Ddx24 conditional knockout. The results showed migration and tube formation potentials of murine aortic endothelial cells with DDX24 silencing were significantly promoted. No differences were observed between Ddx24flox/flox; Cdh5-Cre+ and control regarding body weight and length, pathological tissue change and embryogenesis. We demonstrated Ddx24flox/flox; Cdh5-Cre+ exhibited exacerbation of ConA-induced hepatitis by up-regulating TNF-α and IFN-γ. Furthermore, endothelium-targeted Ddx24 conditional knockout caused vascular hyper-permeability in ConA-injected mice by down-regulating vascular integrity-associated proteins. Mechanistically, we identified Ddx24 might regulate immune-mediated hepatitis by inflammation-related permeable barrier pathways. These findings prove that endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice because of vascular hyper-permeability. The findings indicate a crucial role of DDX24 in regulating immune-mediated hepatitis, suggesting DDX24 as a potential therapeutic target in the disorder. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 2,4-diarylaminopyrimidine derivatives containing sulfonamide moiety were synthesized as FAK inhibitors. • Compound 7b exhibits potent FAK inhibitory activity with an IC 50 value of 0.27 nM. • Compound 7b arrests cell cycle at G2/M phase and induces cell apoptosis by production of ROS. • Compound 7b can inhibit the clone formation and migration of HCT-116 cells. • Compound 7b has better safety than TAE226. Two series of 2,4-diarylaminopyrimidine derivatives containing sulfonamide moiety were designed and synthesized for screening as inhibitors of focal adhesion kinase (FAK). Most compounds significantly inhibited the enzymatic activities of FAK, and the best compound was 7b (IC 50 = 0.27 nM). A majority of aminoethyl sulfonamide derivatives could effectively inhibit the proliferation of human cancer cell lines (HCT116, A549, MDA-MB-231 and Hela) expressing high levels of FAK. Particularly, compounds 7b , 7c , and 7o exhibited more significant efficacy against all of four cancer cell lines within concentrations of 1.5 μM. Furthermore, these three compounds displayed higher selectivity of cancer cells over normal cells (SI value > 14), compared to the positive control TAE226 (SI value = 1.63). Interestingly, introduction of dithiocarbamate moiety to the aminoethyl sulfonamide derivatives can indeed improve the antiproliferative activities against A549 cells. Especially, compound 8d demonstrated most significant cytotoxicity activity against A549 cells with an IC 50 value of 0.08 μM, which is 20-fold superior to parent compound 7k. Additionally, compound 7b , which display the best anti-FAK potency, can inhibit the clone formation and migration of HCT-116 cells, and cause cell cycle arrest at G2/M phase, inducing apoptosis by promoting ROS production. Overall, these results suggest that 7b is a valuable FAK inhibitor that deserves further optimization to improve its druggability. [ABSTRACT FROM AUTHOR]

Abstract Stem-loop binding protein (SLBP) binds a stem-loop structure of the mRNA, which is important for the stability of histone mRNAs and translation process. In the present study, two slbp cDNAs (Ecslbp1 and Ecslbp2) were cloned from a protogynous hermaphroditic orange-spotted grouper, Epinephelus coioides. Ecslbp1 cDNA contained a 678 base pair (bp) open reading frame (ORF), encoding a predicted polypeptide of 225 amino acids. Ecslbp2 cDNA contained a 1041 bp, encoding a predicted protein of 346 amino acids. The result of real-time PCR revealed that Ecslbp2 mRNA was exclusively detected in the ovary. Moreover, it was found to be restricted to oocytes according to in situ hybridization (ISH) analysis. Ecslbp2 was found to be hardly detected in gonia and significantly increase in the cytoplasm of primary-growth stage oocytes, but decreased during the process of vitellogenesis. Interestingly, Ecslbp2 expression centralized as a perinuclear speckle in early-primary-growth stage oocytes, which appeared to form into the Balbiani body (Bb) in late-primary-growth stage oocytes. These data indicated that Ecslbp2 might play an important role in the process of oocyte development, and could serve as an oocyte-specific molecular marker for the study of ovary development and sex reversal in groupers. Highlights • The stem-loop binding protein genes (Ecslbp1 , Ecslbp2) were isolated and characterized from orange-spotted grouper. • Ecslbp2 could be an oocyte-specific molecular marker in orange-spotted grouper. • Ecslbp2 might involve with the regulation of Bb formation, condensation and degradation. [ABSTRACT FROM AUTHOR]

Abstract Vibrio parahaemolyticus is the major pathogen of vibriosis in aquatic animals and causes inflammation that may be related to tissue damage. Here, we have established a V. parahaemolyticus flagellin stimulation model using grouper spleen (GS) cell line. Purified V. parahaemolyticus flagellin was used to stimulate GS cells. Our results showed that the mRNA levels of orange-spotted grouper (Epinephelus coioides) toll-like receptor 5M (Ec TLR5M), Ec TLR5S and downstream cytokines, such as interferon-γ2 (IFN-γ2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were all significantly increased after stimulation with V. parahaemolyticus flagellin in GS cells. Gene silencing of the Ec TLR5M and Ec TLR5S in GS cells by using small interfering RNA resulted in suppression of the V. parahaemolyticus flagellin-induced cytokines expression. We further demonstrated that activation of both mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) were required for cytokines expression. We observed that the phosphorylation of NF-κB inhibitor-α (IκBα), extracellular signal-regulated kinase (ERK) and p38 were induced following treatment with flagellin. Additionally, most of p65, a NF-κB subunit, was found to translocate to the nucleus after 60 min stimulation. Overall, our results suggest that V. parahaemolyticus flagellin influences cytokines expression, such as IFN-γ2, IL-6 and TNF-α, via Ec TLR5s recognition and MAPKs/NF-κB signaling pathway activation in GS cells. Highlights • V. parahaemolyticus flagellin induced IFN-γ2, IL-6 and TNF-α mRNA expressions. • V. parahaemolyticus flagellin induced MAPKs and NF-κB pathways activation in GS cell. • Gene silencing of the Ec TLR5s suppressed flagellin-induced cytokines expression. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of theEpinephelus fuscoguttatuswas presented in this study. The mitochondrial genome is 16,648 bp long and consists of 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and a control region. The gene order and the composition ofE. fuscoguttatusmitochondrial genome were similar to that of most other vertebrates. The nucleotide compositions of the light strand are 26.91% of A, 15.58% of C, 29.19% of T, and 28.32% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. [ABSTRACT FROM AUTHOR]

The effects of the preovulatory luteinizing hormone (LH) surge on the ovulatory process are mediated by prostaglandins (PGs), the synthesis of which involves prostaglandin synthetase and cytosolic phospholipase A2 (cPLA2). In our previous study, we systematically investigated the function of prostaglandin endoperoxide synthase ( ptgs ) genes on ovulation in zebrafish. However, the role of cPLA2 in ovulation was not determined in zebrafish. In this study, we investigated the function of cpla2α in PGs production and ovulation in periovulatory follicles. Our data showed that the expression of pla2g4aa increased during zebrafish folliculogenesis and the follicular layer was the primary region with expression of pla2g4aa. In addition, the expression of pla2g4aa was regulated by LH in vitro and in vivo . Furthermore, injection of AACOCF3, a specific inhibitor of cPLA2, significantly reduced ovarian PGs level and blocked hCG-induced ovulation. Collectively, these findings suggest that pla2g4aa is related to the ovulation process in zebrafish. [ABSTRACT FROM AUTHOR]

A novel non-noble metal catalyst towards the hydrolysis of ammonia borane, Mo-doped Cu 0.5 Ni 0.5 Co 2 O 4 nanowires, are designed and prepared. For the sample with the optimized doping amount of Mo, the turnover frequency value can reach 195.25 mol hydrogen min −1 mol cat −1 . This value is much higher than those of all the other non-noble metal catalysts ever reported in the literature. In addition, there is nearly no activity loss for that catalyst after 6 catalytic cycles. Considering its high performance and low cost, our catalyst can be a strong substitute for noble-metal-based catalysts in AB hydrolysis for hydrogen production. [ABSTRACT FROM AUTHOR]

Based on our discovered novel lead compound 1 through phenotypic drug discovery (PDD) approaches, systematic structural optimization was performed. A series of 2-allylthio-5-amino substituted benzoquinones were synthesized and evaluated for their in-vitro anticancer activities against human prostate cancer cell line PC3. The compound 7a was found inhibit the growth of PC3 with an IC 50 of 0.22 μM, which is over 20-fold improvement compared to lead compound 1 . It is noteworthy that compound 7a also showed potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cell, as well as good water solubility. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are important innate immune receptors that recognize multiple pathogen-associated molecular patterns (PAMPs) and activate the immune responses to resist the invasion of pathogens. Many TLRs need assistance from trafficking chaperones to transport to the specific cell compartments and then are processed before they are activated. In this study, we identified an important trafficking chaperone, Unc-93 homolog B1 ( unc93b1 ), from the Epinephelus coioides (orange-spotted grouper). The deduced protein sequence of Eco.unc93b1 was 632 amino acids, containing 12 transmembrane domains, consistent with other UNC93B1 proteins from other species. Phylogenetic analysis showed that Eco. Unc93b1 was clustered with teleost Unc93b1 and had the closest relationship with Larimichthys crocea (large yellow croaker) Unc93b1. Eco.unc93b1 was expressed the highest in the spleen, and its protein was co-localized with the endoplasmic reticulum and early endosomes in both human embryonic kidney 293T cells and grouper spleen cells (GS cells). Moreover, the stimulation of lipopolysaccharide (LPS), high-molecular-weight poly (I:C) (HMW), imidazoquinoline (R848), polyadenylic-polyuridylic acid (poly AU), and 19-mer Staphylococcus aureus 23S rRNA-derived oligoribonucleotide (ORN Sa 19) promoted the mRNA expression of unc93b1 in GS cells with different patterns. Furthermore, the cytokine expression induced by these PAMPs was suppressed, while Eco.unc93b1 was knocked down, by small interfering RNA. In conclusion, these results suggest that Eco.unc93b1 plays an essential role in several PAMP-induced immune responses. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are one of the most important innate immune receptors, which recognize various pathogen-associated molecular patterns and activate the downstream immune response. Mouse TLR13 has been found to recognize a highly conserved sequence from bacterial or viral RNA and activate the myeloid differentiation primary response gene 88-dependent signaling response. The function of teleost tlr13 is still not fully understood, especially its relationship with bacterial RNA. In our study, we identified and characterized a tlr13 from Epinephelus coioides (orange-spotted grouper). The full-length cDNA of Eco. tlr13 contained a 2844 bp open reading frame, encoding 947 amino acids. The polypeptide was constitutive of a signal peptide, 13 leucine-rich repeats domains, a C-terminal leucine-rich repeats, a transmembrane domain and a conserved Toll/interleukin (IL)-1 receptor domain, indicating that Eco. Tlr13 exhibited a typical TLR structure. Multiple alignments showed that the Toll/IL-1 receptor domain of Eco. Tlr13 was identical with other homologues, and the phylogenetic tree suggested that Eco. Tlr13 was clustered with other TLR13s and had the closest relationship with predicted Lates calcarifer (sea bass) Tlr13. Subcellular localization analysis revealed that Eco. Tlr13 colocalized with the endoplasmic reticulum and early endosome. Moreover, Eco. tlr13 was broadly observed in all tested tissues with the relatively high expressions in the brain and immune-related tissues. After challenged with 19-mer Staphylococcus aureus 23S ribosomal RNA-derived oligoribonucleotide (ORN Sa19), the expression of Eco. tlr13 was significantly up-regulated in grouper spleen cells. Also, the luciferase assay further revealed that with the overexpression of Eco. Tlr13 in human embryonic kidney 293T cells, ORN Sa19 activated the promoter activity of interferon-β in a dose-dependent pattern. These results indicate that Eco. tlr13 may involve in the recognition of bacterial RNA. [ABSTRACT FROM AUTHOR]

Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β) and inhibits the secretion of vascular endothelial growth factor (VEGF). The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs), and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000) by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α) (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001) and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008) were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of the hybrid grouper (Epinephelus coioides♀ × Epinephelus lanceolatus♂) was presented in this study. The mitochondrial genome is 16,743 bp long and consists of 13 protein-coding genes, two rRNA genes, 22tRNAgenes, and a control region. The gene order and the composition of the hybrid grouper mitochondrial genome were similar to that of most other vertebrates. The nucleotide compositions of the light strand are 26.56% of A, 15.79% of C, 28.74% of T, and 28.91% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of theEpinephelus lanceolatuswas presented in this study. The mitochondrial genome is 16,743 bp long and consists of 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a control region. The gene order and composition ofE. lanceolatusmitochondrial genome was similar to that of most other vertebrates. The nucleotide compositions of the light strand are 26.55% of A, 15.02% of C, 29.67% of T and 28.76% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. [ABSTRACT FROM PUBLISHER]