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Septic cardiomyopathy is a secondary myocardial injury caused by sepsis. N6-methyl-adenosine (m6A) modification is involved in the pathological progression of septic cardiomyopathy; however, the pathological mechanism remains unclear. In this study, we identified the overall m6A modification pattern in septic myocardial injury and determined its potential interactions with differentially expressed genes (DEGs). A sepsis mouse model exhibiting septic symptoms and myocardial tissue damage was induced by lipopolysaccharide (LPS). LPS-induced septic myocardial tissues and control myocardial tissues were subjected to methylated RNA immunoprecipitation sequencing and RNA sequencing to screen for differentially expressed m6A peaks and DEGs. We identified 859 significantly m6A-modified genes in septic myocardial tissues, including 432 upregulated and 427 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the biological importance of differentially expressed m6A methylated genes and DEGs. Differentially expressed m6A methylated genes were enriched in immune- and inflammation-related pathways. Conjoint analysis revealed co-expression of differentially expressed m6A genes and DEGs, including genes that were upregulated or downregulated and those showing opposite trends. High expression of m6A-related genes (WTAP and IGF2BP2), interleukin-17, and interleukin-17 pathway-related genes (MAPK11 and TRAF3IP2) was verified using reverse transcription-quantitative PCR. We confirmed the presence of m6A modification of the transcriptome and m6A-mediated gene expression in septic myocardial tissues. [ABSTRACT FROM AUTHOR]

The terminal mining is an essential part of fully mechanized mining, and the reasonable length of the flap roof during the terminal mining is an important basis for the smooth operation of the terminal mining. With the research background of the 213 working face of the Longde Coal Mine, the contribution of this study is the influence law of hydraulic fracturing on the terminal mining mechanical behavior of the working face. Four different numerical calculation models of terminal mining hydraulic fracturing are established, and the optimal hydraulic fracturing site plan is determined according to the length of the terminal mining flap top and the working resistance of hydraulic support. The effect of hydraulic fracturing construction and the law of mechanical behavior in the terminal mining stage in the field test are analyzed. The results show that through hydraulic fracturing technology, the control of the length of the flap roof of the working face during the terminal mining period has been realized. [ABSTRACT FROM AUTHOR]

This study aims to understand the connectivity characteristics of construction land during the spatial evolution of historic urban areas. The complex network analysis method is employed to examine the evolution of the spatial structure of construction land in the four periods of the Changsha historic urban area. The results indicate that the spatial network morphology of construction land follows a repeated development pattern resembling a cluster–mother–child relationship. Additionally, the vulnerability in the evolution of land use spatial relationships is very low, while the overall stability of the land use network structure decreases. The spatial equilibrium of land use shows a downwards trend, the accessibility of land where existing cultural relics and historic sites are located is generally moderate to low, and some plots require improvement. In the evolution of connectivity in the construction land of historic urban areas, the main development challenges are the uneven growth caused by imbalanced land value influenced by capital and the need to balance the preservation of land use patterns with improved accessibility to cultural relics and historic sites. Therefore, it is highly important to dynamically detect and optimize the network structure of construction land to protect and develop historic urban areas. [ABSTRACT FROM AUTHOR]

The SUS304/45 multilayer steels with laminated/network coupling interfaces were fabricated by cold rolling, and the interface evolution behavior and strengthening–toughening mechanism were clarified by microstructure characteristics, tensile testing, and detailed finite element analysis. The results show that when the cold rolling reduction increases from 75 to 87.6 pct, the interface transitions from straight to wavy, and finally forms a laminated/network coupling interface (i.e., the reconstruction of the "Damascus pattern"). The coupling interface is attributed to the uncoordinated deformation of two constituent layers with different crystal structures and stacking fault energy during the cold rolling deformation process. The commercial finite element software ABAQUS was used to simulate the rolling process with different reduction ratios, and the formation mechanism of the laminated/network coupling interface structure is attributed to incoordination deformation of heterogeneous layers. The laminated/network coupling interface and deformation microstructure of constituent layers were further optimized by annealing treatment. The multilayer steel annealed at 700 °C for 30 minutes had the best strength–toughness combination, which is due to the synergistic effect of solid solution, grain refining, dislocation and heterogeneous deformation-induced strengthening. This work provides a novel design idea for strengthening–toughening multilayer steels. [ABSTRACT FROM AUTHOR]

Methane (CH4) emissions from ruminants are of a significant environmental concern, necessitating accurate prediction for emission inventories. Existing models rely solely on dietary and host animal-related data, ignoring the predicting power of rumen microbiota, the source of CH4. To address this limitation, we developed novel CH4 prediction models incorporating rumen microbes as predictors, alongside animal- and feed-related predictors using four statistical/machine learning (ML) methods. These include random forest combined with boosting (RF-B), least absolute shrinkage and selection operator (LASSO), generalized linear mixed model with LASSO (glmmLasso), and smoothly clipped absolute deviation (SCAD) implemented on linear mixed models. With a sheep dataset (218 observations) of both animal data and rumen microbiota data (relative sequence abundance of 330 genera of rumen bacteria, archaea, protozoa, and fungi), we developed linear mixed models to predict CH4 production (g CH4/animal·d, ANIM-B models) and CH4 yield (g CH4/kg of dry matter intake, DMI-B models). We also developed models solely based on animal-related data. Prediction performance was evaluated 200 times with random data splits, while fitting performance was assessed without data splitting. The inclusion of microbial predictors improved the models, as indicated by decreased root mean square prediction error (RMSPE) and mean absolute error (MAE), and increased Lin's concordance correlation coefficient (CCC). Both glmmLasso and SCAD reduced the Akaike information criterion (AIC) and Bayesian information criterion (BIC) for both the ANIM-B and the DMI-B models, while the other two ML methods had mixed outcomes. By balancing prediction performance and fitting performance, we obtained one ANIM-B model (containing 10 genera of bacteria and 3 animal data) fitted using glmmLasso and one DMI-B model (5 genera of bacteria and 1 animal datum) fitted using SCAD. This study highlights the importance of incorporating rumen microbiota data in CH4 prediction models to enhance accuracy and robustness. Additionally, ML methods facilitate the selection of microbial predictors from high-dimensional metataxonomic data of the rumen microbiota without overfitting. Moreover, the identified microbial predictors can serve as biomarkers of CH4 emissions from sheep, providing valuable insights for future research and mitigation strategies. [ABSTRACT FROM AUTHOR]

Conduction between the unique geological formation karst collapse pillar (KCP) and the fractures caused by mining in the coal seam floor can lead to catastrophic water inrush disasters in many coalmines in Northern China. It is widely recognized that seepage mutation induced by the migration/loss of KCP fillings (highly broken rocks filling the fractured rocks) happens during occurrence of the KCP-related water inrush. However, roles of fluid path (mining-induced fracture) scale and KCP filling porosity in seepage mutation evolution remain unclear. Here, we conducted seepage tests on natural KCP fillings containing rock particles of different sizes. The filling specimens were deformed to different porosities from 14 to 26% through axial compression, and small to large fluid paths were simulated by seepage plates with distinct pore sizes from 2.5 to 12.5 mm. We found that seepage mutation occurs with significant permeability enhancement by 2 orders of magnitude under a pore diameter of 12.5 mm and a specimen porosity of 26%. There is a strong linear relationship between specimen permeability and Reynolds number (Re) over seepage mutation. The mutation is caused by the sudden collapse of the specimen skeleton and subsequent quick outflow of the particles. Therefore, it is inferred that the KCP-related water inrush is more likely to happen when highly porous KCP fillings are present and mining-induced fractures are well developed. [ABSTRACT FROM AUTHOR]

Post-combustion carbon capture is a direct and effective way for onboard carbon capture. Therefore, it is important to develop onboard carbon capture absorbent that can both ensure a high absorption rate and reduce the energy consumption of the desorption process. In this paper, a K2CO3 solution was first established using Aspen Plus to simulate CO2 capture from the exhaust gases of a marine dual-fuel engine in diesel mode. The lean and rich CO2 loading results from the simulation were used to guide the selection and optimization of the activators used in the experiment. During the experiment, five amino acid salt activators including SarK, GlyK, ProK, LysK, and AlaK and four organic amine activators including MEA, PZ, AEEA, and TEPA were used. Experiments only considered the activation effect of CO2 loading between lean and rich conditions. The results showed that after adding a small amount of activator, the absorption rate of CO2 by the absorbent was greatly improved, and the activation effect of organic amine activators was stronger than that of amino acid salts. Among the amino acid salts, the SarK-K2CO3 composite solution showed the best performance in both absorption and desorption. Among the amino acid salts and the organic amino activators, SarK-K2CO3 showed the best performance in strengthening the CO2 desorption while PZ-K2CO3 enhanced the CO2 absorption process the most. In the study of the concentration ratio, it was found that when the mass concentration ratio was 1:1 for SarK:K2CO3 and PZ:K2CO3, the CO2 absorption and desorption processes improved well. [ABSTRACT FROM AUTHOR]

The Jacobi iterative algorithm has the characteristic of low computational load, and multiple components of the solution can be solved independently. This paper applies these characteristics to the ternary optical computer, which can be used for parallel optimization because it has a large number of data bits and reconfigurable processor bits. Therefore, a new parallel design scheme is constructed to solve the problem of slow efficiency in solving large linear equations. And the elaborate experiment is used to verify. The experimental method is to simulate the calculation on the ternary optical computer experimental platform. Then, the resource consumption is numerically calculated and summarized to measure the feasibility of the parallel design. Eventually, the results show that the parallel design has obvious advantages in computing speed. The Jacobi iterative algorithm is optimized in parallel on ternary optical processor for the first time. There are two parallel highlights of the scheme. First, the n components are calculated in full parallel. Second, the modified signed-digit (MSD) multiplier based on the minimum module and one-step MSD adder are used to calculate each component to eliminate the impact of large amount of data on calculation time. The research provides a new method for fast solution of large linear equations. [ABSTRACT FROM AUTHOR]

PD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a ‘barcode’ to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein–Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThigh TRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.Single-cell RNA sequencing and T cell receptor sequencing are combined to identify transcriptional programs specific to mutation-associated neoantigen-specific T cells in non-small cell lung cancers treated with anti-PD-1, providing insights into resistance to PD-1 blockade. [ABSTRACT FROM AUTHOR]

The Karst collapse pillar (KCP) is a special geological structure, which is easy to form the fissure channels between the coal seam working face and the aquifer to cause the water inrush disasters. The KCP was sampled on site in this paper. The confined uniaxial compression test was carried out on the KCP to simulate its field consolidation, and seepage test on the KCP under different axial loads was conducted by using self-developed seepage test system. The KCP connecting to the underground Ordovician limestone aquifer in the sampling area was considered; the difference in the seepage properties between the KCP and the broken limestone was analyzed. The results show that the water-resisting capacity of the KCPs in 3# coal seam floor is 6.24–13.74 MPa, which is far greater than the water pressure of aquifer on 3# coal seam. The water-resisting capacity of the KCPs in 15# coal seam floor is in the range of 1.89–4.71 MPa, which is less than the water pressure of aquifer on 15# coal seam. The specific measures were conducted to prevent the water inrush during the mining process. Before exposing the X3 KCP, the roof drainage borehole drained the roof water to avoid the excessive water inflow in a short time. The grouting holes were arranged to reinforce the floor of sandstone aquifer. According to these treatment methods, the mining work safely passed through the X3 KCP, ensuring engineering safety and economic production. It is not recommended to directly expose the X3 KCP in the roadway or working face of 15# coal seam, and the floor of 15# coal seam should be grouted and reinforced in the future. [ABSTRACT FROM AUTHOR]

Understanding the hydraulic fracture (HF) re-orientation mechanism from artificial weaknesses is critical to screen-out prevention in the petroleum industry and caveability management in the mining industry. An improved discrete element method is proposed and incorporated in the Universal Distinct Element Code (UDEC) to simulate hydraulic fracturing in heterogeneous rocks, and its reliability is validated against previous laboratory experiments. The effects of rock heterogeneity and rock strength on HF re-orientation are unveiled to fill the research gaps in the existing knowledge. The results show that the proposed UDEC T-W (Trigon-Weibull distribution) model can well simulate HF propagation in rock samples of different homogeneity degrees and yields more realistic simulation results compared with the classic extended finite element method (XFEM). The HF re-orientation process depends on the combined effect of all the influencing factors. HFs tend to be directed by perforations if hydraulic fracturing is performed in relatively heterogeneous rocks, while the differential stress is more likely to dictate the HF propagation paths if rocks become relatively homogeneous. We also find that higher rock strength weakens the impact of the differential stress and favours the control of perforations over HF propagation. Finally, recommendations are provided for effective utilization of hydraulic fracturing at the mine site. [ABSTRACT FROM AUTHOR]

Outside the explosive successful applications of deep learning (DL) in natural language processing, computer vision, and information retrieval, there have been numerous Deep Neural Networks (DNNs) based alternatives for common security-related scenarios with malware detection among more popular. Recently, adversarial learning has gained much focus. However, unlike computer vision applications, malware adversarial attack is expected to guarantee malwares' original maliciousness semantics. This paper proposes a novel adversarial instruction learning technique, DeepMal, based on an adversarial instruction learning approach for static malware detection. So far as we know, DeepMal is the first practical and systematical adversarial learning method, which could directly produce adversarial samples and effectively bypass static malware detectors powered by DL and machine learning (ML) models while preserving attack functionality in the real world. Moreover, our method conducts small-scale attacks, which could evade typical malware variants analysis (e.g., duplication check). We evaluate DeepMal on two real-world datasets, six typical DL models, and three typical ML models. Experimental results demonstrate that, on both datasets, DeepMal can attack typical malware detectors with the mean F1-score and F1-score decreasing maximal 93.94% and 82.86% respectively. Besides, three typical types of malware samples (Trojan horses, Backdoors, Ransomware) prove to preserve original attack functionality, and the mean duplication check ratio of malware adversarial samples is below 2.0%. Besides, DeepMal can evade dynamic detectors and be easily enhanced by learning more dynamic features with specific constraints. [ABSTRACT FROM AUTHOR]

Single-cell transcriptomics uncovers potential marker genes of ochratoxin A-sensitive renal cells in an acute toxicity rat model Keywords: Precision toxicology; Single-cell sequencing; Cell type classification; Ochratoxin A; Renal toxicity EN Precision toxicology Single-cell sequencing Cell type classification Ochratoxin A Renal toxicity 7 13 7 02/03/21 20210201 NES 210201 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10565-020-09531-7) contains supplementary material, which is available to authorized users. Since single-cell sequencing has made it possible to define cell types and states, it offers promising potential for the investigation of target renal cell types of OTA and the underlying mechanisms of OTA-induced nephrotoxicity at single-cell resolution. The tubule epithelial cells are the main target cell types of OTA, and the genes such as I Slc5a2 i , I Cyp4a8 i , and I Havcr1 i are potential markers of OTA-sensitive cells. [Extracted from the article]

The design of bifunctional non-precious metal catalyst with good ORR and OER activity is of great significance for the development and commercialization of fuel cells. However, the sluggish and strong irreversible nature of the oxygen electrochemical kinetics makes it difficult to manufacture single bifunctional material. Therefore, we prepared a bifunctional catalyst (Co3O4/N-rGO) with different particle diameters through a one-pot synthesis method, and studied the dependence of the electrocatalytic performance of the catalyst on the particle size of Co3O4. The results showed that Co3O4/N-rGO with 27–31 nm particle size prepared by using N-rGO as the carrier, cobalt acetate concentration of 0.075 M, hydrothermal temperature of 190 °C, and hydrothermal time of 3 h takes a 4e-reaction pathway, which exhibited better ORR and OER activity, excellent current stability and methanol tolerance than JM 20% Pt/C and JM 5% RuO2/C. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is widely distributed in nature and is confirmed to be the most toxic of all the aflatoxins, whose predominant metabolism site is the liver. As a well-studied and vital mode of epigenetic modifications, aberrant methylation of the promoters in eukaryotic cells may cause the silence of essential genes, affecting their related transcriptional pathways and ultimately leading to the development of disease and cancers. This study investigated the mechanisms of AFB1-induced hepatotoxicity in S phase-arrested L02 cells using single-cell RNA-seq and single-cell reduced representation bisulfite sequencing (RRBS). AFB1 induced apoptosis and cell cycle S phase arrest, reduced mitochondrial membrane potential (ΔΨm), and increased reactive oxygen species (ROS) generation, as well as the DNA methylation level. Hepatotoxicity mechanism patterns induced by AFB1 in S phase-arrested L02 cells were revealed by combining single-cell RNA-seq with single-cell RRBS analysis, in which DNA methylation played a role via regulating the gonadotropin-releasing hormone receptor pathway, the Wnt signaling pathway, and the TGF-beta signaling pathway. Moreover, a novel strategy for precision toxicology exploration was obtained, including the selection of target cells, multi-group non-directional sequencing, and pathway analysis. [ABSTRACT FROM AUTHOR]

The complicated and constrained reconfiguration optimisation for unmanned aerial vehicles (UAVs) is a challenge, particularly when multi-mission requirements are taken into account. In this study, we evaluate the use of the adaptive differential evolution-based centralised receding horizon control approach to achieve the formation reconfiguration along a given formation group trajectory for multiple unmanned aerial vehicles in a three-dimensional (3D) environment. A rolling optimisation approach which combines the receding horizon control method with the adaptive differential evolution algorithm is proposed, where the receding horizon control method divides the global control problem into a series of local optimisations and each local optimisation problem is solved by an adaptive differential evolution algorithm. Furthermore, a novel quadratic reconfiguration cost function with the topology information of UAVs is presented, and the asymptotic convergence of the rolling optimisation is analysed. Finally, simulation examples are provided to illustrate the validity of the proposed control structure. [ABSTRACT FROM AUTHOR]

Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia. [ABSTRACT FROM AUTHOR]

Extreme learning machine (ELM) is a well-known cognitive model, that has been extended to cross-domain tasks. Nonetheless, most existing paradigms that are based on ELM either concern about a case in which a specific number of instances are labelled in the target domain or a learner is trained without sufficient capacity to eliminate the gap between domains. To cope with the scenario in which there are no target labels and to acquire a better adaptive learner, we propose a joint unsupervised cross-domain model via scalable discriminative ELM, which is abbreviated as JUC-SDELM. Within the framework, the scalable factor is integrated into discriminative ELM (DELM) to adjust the output margin, which strengthens the discriminative capacity of the ELM classifier. In addition, we follow the basic strategy of joint distribution adaptation (JDA) to align the subspaces generated by JUC-SDELM in terms of their statistics. The discrepancy across domains is alleviated after a few iterations. Moreover, a metric on the outputs of ELM is utilized to filter unreliable pseudo labels in the target domain, with the aim of eliminating the negative transfer effect. Results are obtained by comparing JUC-SDELM with state-of-the-art baseline methods on 16 cross-domain benchmarks that were constructed based on three combined datasets. Likewise, the outcomes in terms of key parameters are also examined. According to the experiments, our proposed model achieves competitive overall performance. [ABSTRACT FROM AUTHOR]

As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation to promote cell survival, cell proliferation, epithelial-mesenchymal transition, and cell migration, which was attributed to the up-regulation of NADH:ubiquinone oxidoreductase core subunit S8 via interaction with chaperone Lon under hypoxic or oxidative stress in tumorigenesis. In addition, Lon also participated in protein kinase RNA (PKR)-like endoplasmic reticulum kinase signaling pathway under endoplasmic reticulum (ER) stress. In short, Lon, as a pivotal stress-responsive protein that involved in the crosstalks among mitochondria, ER and nucleus, participated in multifarious important cellular processes crucial for cell survival, such as the mitochondrial protein quality control system, the mitochondrial unfolded protein response, the mtDNA maintenance, and the ER unfolded protein response. [ABSTRACT FROM AUTHOR]

In this work, a multilayer-modified paper-based colorimetric sensing platform with improved color uniformity and intensity was developed for the sensitive and selective determination of uric acid and glucose with smartphone as signal readout. In detail, chitosan, different kinds of chromogenic reagents, and horseradish peroxidase (HRP) combined with a specific oxidase, e.g., uricase or glucose oxidase (GOD), were immoblized onto the paper substrate to form a multilayer-modified test paper. Hydrogen peroxide produced by the oxidases (uricase or GOD) reacts with the substrates (uric acid or glucose), and could oxidize the co-immoblized chromogenic reagents to form colored products with HRP as catalyst. A simple strategy by placing the test paper on top of a light-emitting diode lamp was adopted to efficiently prevent influence from the external light. The color images were recorded by the smartphone camera, and then the gray values of the color images were calculated for quantitative analysis. The developed method provided a wide linear response from 0.01 to 1.0 mM for uric acid detection and from 0.02 to 4.0 mM for glucose detection, with a limit of detection (LOD) as low as 0.003 and 0.014 mM, respectively, which was much lower than for previously reported paper-based colorimetric assays. The proposed assays were successfully applied to uric acid and glucose detection in real serum samples. Furthermore, the enhanced analytical performance of the proposed method allowed the non-invasive detection of glucose levels in tear samples, which holds great potential for point-of-care analysis.ᅟ [ABSTRACT FROM AUTHOR]

Bat algorithm (BA) is a new approach designed by imitating bat's behavior of searching and capturing preys. The existing results have demonstrated the effectiveness and efficiency in comparison with other heuristic algorithms such as genetic algorithms and particle swarm optimization. In this paper, we design a novel framework for bat algorithm named two-stage bat algorithm (TSBA) using a trade-off strategy which balances the relationship between exploration and exploitation at the most extent. Inspired by the multi-population methods (e.g., artificial bee colony), we not only concern some technologies to avoid premature inevitably encountered when using BA, but also use a trade-off strategy to improve the comprehensive search performance for optimization. Some typical test sets which consist of 27 benchmark functions are utilized in comparative experiment, and the simulation results in terms of convergence rate and accuracy illustrate that the TSBA has a competitive performance than other swarm intelligent optimization algorithms. In addition, the proposed algorithm will not lend to the tremendous increase in computing time and thus will be a powerful tool in practical applications. [ABSTRACT FROM AUTHOR]

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology. [ABSTRACT FROM AUTHOR]

A wideband low-noise transconductance amplifier (LNTA) with high linearity is proposed. The differential LNTA adopts complementary common-gate (CG), current mirror (CM) and common-source (CS) schemes to obtain noise and distortion cancellation, and $$g_{m}$$ -enhancement. A high third-order input intercept point (IIP3) is obtained due to the distortion cancellation and the complementary characteristics of NMOS and PMOS transistors. The gain expansion of the class-AB CS stage compensates the gain compression of the CG-CM stage, which leads to a high large-signal linearity. A wide input matching bandwidth is achieved by utilizing a $$\uppi $$ -type input matching network without the use of on-chip bulky inductors, and the passive voltage gain of the $$\uppi $$ -network further enhances the effective transconductance. Designed in a 0.18- $$\upmu \hbox {m}$$ CMOS process, the simulation results show that it provides a minimum noise figure (NF) of 2.95 dB and a maximum transconductance of 79 mS from 0.1 to 3.6 GHz. An input 1-dB compression/desensitization point and an IIP3 of 8.1/5.59 and 18.14 dBm are obtained, respectively. The NF is degraded by 0.3 dB with a 0-dBm blocker. The circuit draws 10.7 mA from a 2.5-V supply, and the core area is only $$0.5 \times 0.12\,\hbox {mm}^{2}$$ . [ABSTRACT FROM AUTHOR]

The mounting number of patients with pulmonary adenocarcinoma (ADCA) is subjected to poor prognosis and heavy mortality, which prompts us to explore new potential therapeutics for lung ADCA. Herein, we reported a novel approach for lung ADCA therapy by abolishing autophagy and asparagine. We demonstrated that deprivation of asparagine by asparaginase could induce significant cytotoxicity and apoptosis in A549 and H1975 cells. During this process, autophagy was triggered by the asparaginase treatment, characterized by the autophagic flux with three main stages including formation of autophagosomes, lysosomes fused with autophagosomes, and degradation of autophagosomes by lysosomes. Importantly, suppression of autophagy could notably enhance the cytotoxicity and accelerate the caspase 3-dependent apoptosis induced by asparaginase. Furthermore, suppression of reactive oxygen species (ROS) could attenuated both the cytotoxicity and autophagy induced by asparaginase, while inhibition of autophagy promoted the generation of ROS in A549 and H1975 cells, indicating the essential role of ROS in asparagine deprivation therapy in lung ADCA cells. Our results demonstrated that targeting cytoprotective autophagy and asparagine could potently kill the ADCA cells, which highlighted a novel approach for lung ADCA therapy in the clinics. [ABSTRACT FROM AUTHOR]

This paper presents a spatiotemporal super-resolution method to enhance both the spatial resolution and the frame rate in a hybrid stereo video system. In this system, a scene is captured by two cameras to form two videos, including a low spatial resolution with high-frame-rate video and a high spatial resolution with low-frame-rate video. For the low-spatial-resolution video, the low-resolution frames are spatially super-resolved by the high-resolution video via the stereo matching, the bilateral overlapped block motion estimation, and the adaptive overlapped block motion compensation algorithms, while for the low-frame-rate video, those missed frames are interpolated using the high-resolution frames obtained by fusing the disparity compensation and the motion compensation frame rate up-conversion. Experimental results demonstrate that the proposed mixed spatiotemporal super-resolution method has a more significant contribution to both the subjective and objective qualities than the pure spatial super-resolution or the frame rate up-conversion. [ABSTRACT FROM AUTHOR]

The accelerated life test was carried out to investigate the change of spectral transmittance of di-methyl silicon oil and the effects on the electrical performance of silicon solar cell. The di-methyl silicon oil samples before and after accelerated life test were analyzed by FT-IR, GC-MS and LC-MS. The ring compounds and linear compounds with larger molecular weight were detected. The spectral transmittance of di-methyl silicon oil decreased because the chromophore and auxochrome of the products made a sunlight receive decrease on the surface of the solar cell, and resulted in the reduction of cell performance. According to the decrease of spectral transmittance of di-methyl silicon oil, two recovery methods were proposed. The results showed that extraction was superior to vacuum distillation in recovering the aged di-methyl silicon oil. [ABSTRACT FROM AUTHOR]

Directed differentiation protocols enable derivation of cardiomyocytes from human pluripotent stem cells (hPSCs) and permit engineering of human myocardium in vitro. However, hPSC-derived cardiomyocytes are reflective of very early human development, limiting their utility in the generation of in vitro models of mature myocardium. Here we describe a platform that combines three-dimensional cell cultivation with electrical stimulation to mature hPSC-derived cardiac tissues. We used quantitative structural, molecular and electrophysiological analyses to explain the responses of immature human myocardium to electrical stimulation and pacing. We demonstrated that the engineered platform allows for the generation of three-dimensional, aligned cardiac tissues (biowires) with frequent striations. Biowires submitted to electrical stimulation had markedly increased myofibril ultrastructural organization, elevated conduction velocity and improved both electrophysiological and Ca2+ handling properties compared to nonstimulated controls. These changes were in agreement with cardiomyocyte maturation and were dependent on the stimulation rate. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR). In parallel, it suppressed urinary norepinephrine excretion, and induced c-Fos expressions in the area postrema (AP) and nucleus tractus solitarius (NTS) of brainstem including the NTS neurons immunoreactive to dopamine beta-hydroxylase (DBH). Acute administration of liraglutide into fourth ventricle, the area with easy access to the AP and NTS, transiently decreased BP in SHR and this effect was attenuated after lesion of NTS DBH neurons with anti-DBH conjugated to saporin (anti-DBH-SAP). In anti-DBH-SAP injected SHR, the antihypertensive effect of repeated LV injection of liraglutide for 14 days was also attenuated. These findings demonstrate that the central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

Aflatoxin-B1 (AFB1), a hepatocarcinogenic mycotoxin, was demonstrated to induce the high rate of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the regulation of several biological processes in HCC. However, the function of miRNAs in AFB1-induced HCC has received a little attention. Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1. Analysis of the differential expression profile of miRNAs in two libraries, we identified 9 known miRNAs and 1 novel miRNA which exhibited abnormal expression. KEGG analysis indicated that predicted target genes of differentially expressed miRNAs are involved in cancer-related pathways. Down-regulated of Drosha, DGCR8 and Dicer 1 indicated an impairment of miRNA biogenesis in response to AFB1. miR-34a was up-regulated significantly, down-regulating the expression of Wnt/β-catenin signaling pathway by target gene β-catenin. Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved. These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis. [ABSTRACT FROM AUTHOR]

Oxidative stress and apoptosis are involved in Ochratoxin A (OTA)-induced renal cytotoxicity. Apoptosis signal-regulating kinase 1 (ASK1) is a Mitogen-Activated Protein Kinase Kinase Kinase (MAPKKK, MAP3K) family member that plays an important role in oxidative stress-induced cell apoptosis. In this study, we performed RNA interference of ASK1 in HEK293 cells and employed an iTRAQ-based quantitative proteomics approach to globally investigate the regulatory mechanism of ASK1 in OTA-induced renal cytotoxicity. Our results showed that ASK1 knockdown alleviated OTA-induced ROS generation and Δψm loss and thus desensitized the cells to OTA-induced apoptosis. We identified 33 and 24 differentially expressed proteins upon OTA treatment in scrambled and ASK1 knockdown cells, respectively. Pathway classification and analysis revealed that ASK1 participated in OTA-induced inhibition of mRNA splicing, nucleotide metabolism, the cell cycle, DNA repair, and the activation of lipid metabolism. We concluded that ASK1 plays an essential role in promoting OTA-induced renal cytotoxicity. [ABSTRACT FROM AUTHOR]

Diabetic cataract (DC) is a major cause of blindness in diabetic patients and it is characterized by early onset and rapid progression. MiR-204-5p was previously identified as one of the top five down-regulated miRNAs in human DC lens tissues. We aimed to determine the expression of miR-204-5p in human lens epithelial cells (HLECs) and explore its effects and mechanisms in regulating the progression of DC. The expression of miR-204-5p in the anterior capsules of DC patients and HLECs was examined by RT-qPCR. Bioinformatics tools were then used to identify the potential target of miR-204-5p. The relationship between miR-204-5p and the target gene was confirmed through a dual luciferase reporter assay. Additionally, the regulatory mechanism of oxidative stress, apoptosis, and inflammation in DC was investigated by overexpressing miR-204-5p using miR-204-5p agomir. The expression of miR-204-5p was downregulated in the anterior capsules of DC patients and HLECs. Overexpression of miR-204-5p reduced ROS levels, pro-apoptosis genes (Bid, Bax, caspase-3), and IL-1β production in HG-treated HLECs. TXNIP was the direct target of miR-204-5p by dual luciferase reporter assay. Therefore, this study demonstrated that miR-204-5p effectively reduced oxidative damage, apoptosis, and inflammation in HLECs under HG conditions by targeting TXNIP. Targeting miR-204-5p could be a promising therapeutic strategy for the potential treatment of DC. [ABSTRACT FROM AUTHOR]