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The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression. In addition, mTOR also negatively regulates autophagy via different ways. We discuss mTOR signaling and its key upstream and downstream factors, the specific genetic changes in the mTOR pathway and the inhibitors of mTOR applied as therapeutic strategies in eight solid tumors. Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need, and new biomarkers and deep sequencing technologies will facilitate these mTOR targeting drugs benefit the cancer patients in personalized therapy.

Ship segmentation with small imaging size, which challenges ship detection and visual navigation model performance due to imaging noise interference, has attracted significant attention in the field. To address the issues, this study proposed a novel combined attention mechanism and efficient channel attention high-resolution representation network (CA2HRNET). More specially, the proposed model fulfills accurate ship segmentation by introducing a channel attention mechanism, a multi-scale spatial attention mechanism, and a weight self-adjusted attention mechanism. Overall, the proposed CA2HRNET model enhances attention mechanism performance by focusing on the trivial yet important features and pixels of a ship against background-interference pixels. The proposed ship segmentation model can accurately focus on ship features by implementing both channel and spatial fusion attention mechanisms at each scale feature layer. Moreover, the channel attention mechanism helps the proposed framework allocate higher weights to ship-feature-related pixels. The experimental results show that the proposed CA2HRNET model outperforms its counterparts in terms of accuracy (Accs), precision (Pc), F1-score (F1s), intersection over union (IoU), and frequency-weighted IoU (FIoU). The average Accs, Pc, F1s, IoU, and FIoU for the proposed CA2HRNET model were 99.77%, 97.55%, 97%, 96.97%, and 99.55%, respectively. The research findings can promote intelligent ship visual navigation and maritime traffic management in the smart shipping era.

The emergence of the Internet of Things (IoT) has subverted people’s lives, causing the rapid development of sensor technologies. However, traditional sensor energy sources, like batteries, suffer from the pollution problem and the limited lifetime for powering widely implemented electronics or sensors. Therefore, it is essential to obtain self-powered sensors integrated with renewable energy harvesters. The triboelectric nanogenerator (TENG), which can convert the surrounding mechanical energy into electrical energy based on the surface triboelectrification effect, was born of this background. This paper systematically introduces the working principle of the TENG-based self-powered sensor, including the triboelectrification effect, Maxwell’s displacement current, and quantitative analysis method. Meanwhile, this paper also reviews the recent application of TENG in different fields and summarizes the future development and current problems of TENG. We believe that there will be a rise of TENG-based self-powered sensors in the future.

•The Iowa Gambling Task revealed an interaction between sex and BAS.•Males with high BAS performed worse than those with low BAS in IGT.•The rsFC of left VLPFC-left SOG is correlated with IGT performance in males.•The rsFC of left VLPFC-left SOG mediates the relationship of BAS and IGT in males. It has been observed that one's Behavioral Approach System (BAS) can have an effect on decision-making under uncertainty, although the results have been mixed. To discern the underlying neural substrates, we hypothesize that sex may explain the conflicting results. To test this idea, a large sample of participants was studied using resting state fMRI, utilizing fractional Amplitude of Low Frequency Fluctuations (fALFF) and Resting-State Functional Connectivity (rsFC) techniques. The results of the Iowa Gambling Task (IGT) revealed an interaction between sex and BAS, particularly in the last 60 trials (decision-making under risk). Males with high BAS showed poorer performance than those with low BAS. fALFF analysis showed a significant interaction between BAS group and sex in the left superior occipital gyrus, as well as the functional connectivity between this region and the left ventrolateral prefrontal cortex. Additionally, this functional connectivity was further positively correlated with male performance in the IGT, particularly in the decision-making under risk stage. Furthermore, it was found that the functional connectivity between left ventrolateral prefrontal cortex and left superior occipital gyrus could mediate the relationship between BAS and decision-making in males, particularly in the decision-making under risk stage. These results suggest possible sex-based differences in decision-making, providing an explanation for the inconsistent results found in prior research. Since the research was carried out exclusively with Chinese university students, it is essential to conduct further studies to investigate whether the findings can be generalized.

Background Four-Coumarate:CoA ligase gene ( 4CL ) plays multiple important roles in plant growth and development by catalyzing the formation of CoA ester. 4CL belongs to the plant phenylpropane derivative, which is related to the synthesis of flavonoids and lignin and is a key enzyme in the biosynthetic pathway. Results In this study, 12 4CL genes of Fraxinus mandschurica were identified and named Fm4CL1 - Fm4CL12 , respectively. The analysis of the expression pattern of Fm4CL genes indicate that Fm4CL-like 1 gene may play a role in the lignin synthesis pathway. Our study indicate that overexpression of Fm4CL-like 1 increases the lignin content of transgenic tobacco by 39.5% compared to WT, and the S/G ratio of transgenic tobacco increased by 19.7% compared with WT. The xylem cell layer of transgenic line is increased by 40% compared to WT, the xylem cell wall thickness increased by 21.6% compared to the WT. Under mannitol-simulated drought stress, the root length of transgenic tobacco is 64% longer than WT, and the seed germination rate of the transgenic lines is 47% higher than that of WT. In addition, the H 2 O 2 content in the transgenic tobacco was 22% lower than that of WT, while the POD and SOD content was higher than WT by 30 and 24% respectively, which showed Fm4CL-like 1 affect the accumulation of reactive oxygen species (ROS). The MDA content and relative conductivity was 25 and 15% lower than WT, respectively. The water loss rate is 16.7% lower than that of WT. The relative expression levels of stress-related genes NtHAK , NtAPX , NtCAT , NtABF2 , and NtZFP were higher than those of WT under stress treatment. The stomatal apertures of OE (Overexpression) were 30% smaller than those of WT, and the photosynthetic rate of OE was 48% higher than that of WT. These results showed that the overexpression line exhibited stronger adaptability to osmotic stress than WT. Conclusions Our results indicate that Fm4CL-like 1 is involved in secondary cell wall development and lignin synthesis. Fm4CL-like 1 play an important role in osmotic stress by affecting cell wall and stomatal development.

Background Histone modifications are critical for transcriptional regulation. A notable genetic innovation in land plants is the emergence of histone lysine methyltransferases ATXR5/6, which specifically catalyze the repressive histone H3 lysine 27 monomethylation (H3K27me1) . Current knowledge of ATXR5/6 function is largely based on Arabidopsis studies using a weak atxr5;atxr6 hypomorphic mutant, in which ATXR6 is still partially expressed and defects are primarily observed in heterochromatin. However, the significance for land plants to evolve these enzymes remains unclear. Results In this study, we generate strong atxr5;atxr6 mutants with further reduced ATXR6 expression in Arabidopsis to explore the broader roles of ATXR5/6. Our results show that ATXR5/6 are essential for plant reproductive development and play a critical role in supporting normal plant growth by repressing the transcription of stress responsive genes. In addition, ATXR5/6 are necessary for maintaining H3K27 trimethylation (H3K27me3), likely by providing H3K27me1 as a substrate for further methylation. We also demonstrate that the function of ATXR5/6 in regulating development and responsive genes is conserved in the monocot rice. Conclusions Our findings suggest that land plants evolved ATXR5/6 not only to maintain heterochromatin, but also to regulate development and environmental responses, providing new insights into the functional significance of ATXR5/6 in land plants.

Accurate predictions of wheat yields are essential to farmers’production plans and to the international trade in wheat. However, only poor approximations of the productivity of wheat crops in China can be obtained using traditional linear regression models based on vegetation indices and observations of the yield. In this study, Sentinel-2 (multispectral data) and ZY-1 02D (hyperspectral data) were used together with 15709 gridded yield data (with a resolution of 5 m × 5 m) to predict the winter wheat yield. These estimates were based on four mainstream data-driven approaches: Long Short-Term Memory (LSTM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and Support Vector Regression (SVR). The method that gave the best estimate of the winter wheat yield was determined, and the accuracy of the estimates based on multispectral and hyperspectral data were compared. The results showed that the LSTM model, for which the RMSE of the estimates was 0.201 t/ha, performed better than the RF (RMSE = 0.260 t/ha), GBDT (RMSE = 0.306 t/ha), and SVR (RMSE = 0.489 t/ha) methods. The estimates based on the ZY-1 02D hyperspectral data were more accurate than those based on the 30-m Sentinel-2 data: RMSE = 0.237 t/ha for the ZY-1 02D data, which is about a 5% improvement on the RSME of 0.307 t/ha for the 30-m Sentinel-2 data. However, the 10-m Sentinel-2 data performed even better, giving an RMSE of 0.219 t/ha. In addition, it was found that the greenness vegetation index SR (simple ratio index) outperformed the traditional vegetation indices. The results highlight the potential of the shortwave infrared bands to replace the visible and near-infrared bands for predicting crop yields Our study demonstrates the advantages of the deep learning method LSTM over machine learning methods in terms of its ability to make accurate estimates of the winter wheat yield.

Atherosclerosis, a serious threat to human cardiovascular health, involves inflammation throughout its various stages of development. MicroRNAs play an important regulatory role in macrophages that respond to inflammation, but the underlying mechanisms are largely unknown. In this work, we study the impact of miR-19a in macrophage-derived foam cell formation during atherogenesis. A microarray-based analysis of serums from patients with coronary heart disease in comparison with healthy controls reveals a significant enrichment of miR-19a in the serums of atherosclerosis patients. A higher level of miR-19a is also observed in atherosclerosis-prone ascending aortic wall tissues than in internal mammary artery amongst patients with coronary heart disease. We identify HMG-Box Transcription Factor 1 ( HBP-1 ) as a target gene of miR-19a. HBP1 is repressor of macrophage migration inhibiting factor (MIF) and overexpression of miR-19a increases MIF expression. By administering a miR-19a antagonist to the caudal vein, we found a decrease in atherosclerotic plaques and lipids load in apoE-null mice fed with high-fat diet. These results support inhibition of miR-19a reduces inflammatory reaction and constitutes a potent therapeutic approach against atherosclerosis.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy. Activated Notch signalling promotes cancer metastasis and stemness. Here the authors show that Notch1 activates transcription of DNA replication factor RCF4 and that RCF4 binds and stabilises Notch1 intracellular domain (NICD1) to promote cancer metastasis.

Metal halide perovskites possess intriguing optoelectronic properties, however, the lack of precise control of on-chip fabrication of the large-scale perovskite single crystal arrays restricts its application in integrated devices. Here, we report a space confinement and antisolvent-assisted crystallization method for the homogeneous perovskite single crystal arrays spanning 100 square centimeter areas. This method enables precise control over the crystal arrays, including different array shapes and resolutions with less than 10%-pixel position variation, tunable pixel dimensions from 2 to 8 μm as well as the in-plane rotation of each pixel. The crystal pixel could serve as a high-quality whispering gallery mode (WGM) microcavity with a quality factor of 2915 and a threshold of 4.14 μJ cm −2 . Through directly on-chip fabrication on the patterned electrodes, a vertical structured photodetector array is demonstrated with stable photoswitching behavior and the capability to image the input patterns, indicating the potential application in the integrated systems of this method.