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The aim of this study is to recognize human emotions by electroencephalographic (EEG) signals. The innovation of our research methods involves two aspects: First, we integrate the spatial characteristics, frequency domain, and temporal characteristics of the EEG signals, and map them to a two-dimensional image. With these images, we build a series of EEG Multidimensional Feature Image (EEG MFI) sequences to represent the emotion variation with EEG signals. Second, we construct a hybrid deep neural network to deal with the EEG MFI sequences to recognize human emotional states where the hybrid deep neural network combined the Convolution Neural Networks (CNN) and Long Short-Term-Memory (LSTM) Recurrent Neural Networks (RNN). Empirical research is carried out with the open-source dataset DEAP (a Dataset for Emotion Analysis using EEG, Physiological, and video signals) using our method, and the results demonstrate the significant improvements over current state-of-the-art approaches in this field. The average emotion classification accuracy of each subject with CLRNN (the hybrid neural networks that we proposed in this study) is 75.21%.

Selenite is a predominant form of selenium (Se) available to plants, especially in anaerobic soils, but the molecular mechanism of selenite uptake by plants is not well understood. ltn1, a rice mutant previously shown to have increased phosphate (Pi) uptake, was found to exhibit higher selenite uptake than the wild-type in both concentration- and time-dependent selenite uptake assays. Respiratory inhibitors significantly inhibited selenite uptake in the wildtype and the ltn1 mutant, indicating that selenite uptake was coupled with H+ and energydependent. Selenite uptake was greatly enhanced under Pi-starvation conditions, suggesting that Pi transporters are involved in selenite uptake. OsPT2, the most abundantly expressed Pi transporter in the roots, is also significantly upregulated in ltn1 and dramatically induced by Pi starvation. OsPT2-overexpressing and knockdown plants displayed significantly increased and decreased rates of selenite uptake, respectively, suggesting that OsPT2 plays a crucial role in selenite uptake. Se content in rice grains also increased significantly in OsPT2-overexpressing plants. These data strongly demonstrate that selenite and Pi share similar uptake mechanisms and that OsPT2 is involved in selenite uptake, which provides a potential strategy for breeding Seenriched rice varieties.

Although rRNA metabolism-related genes have been reported to be associated with human cancer, a systematic assessment of rRNA metabolism-related genes across human cancers is lacking. Thus, we performed a Pan-cancer analysis of rRNA metabolism-related genes across 20 human cancers. Here, we examined mRNA expression, mutation, DNA methylation, copy number variation (CNV) and clinical landscape of rRNA metabolism-related genes in more than 8600 patients across 20 human cancers from The Cancer Genome Atlas (TCGA) dataset. Besides, ten independent Gene Expression Omnibus (GEO) datasets, Cancer Cell Line Encyclopedia (CCLE) dataset and Project Achilles dataset were used to verify our study. A landscape of rRNA metabolism-related genes was established across 20 human cancers. The results suggest that rRNA metabolism-related genes are upregulated in multiple cancers, particularly in digestive and respiratory system cancers. Most of the upregulated genes were driven by CNV gain rather than mutation or DNA hypomethylation. We systematically identified CNV-driven rRNA metabolism-related genes with clinical relevance, including EXOSC8. Finally, functional experiments confirmed the oncogenic roles of EXOSC8 in colorectal carcinoma. Our study highlights the important roles of rRNA metabolism-related genes in tumorigenesis as prognostic biomarkers.

Mitochondrial apoptosis is strictly controlled by BCL-2 family proteins through a subtle network of protein interactions. The tumor suppressor protein p53 triggers transcription-independent apoptosis through direct interactions with BCL-2 family proteins, but the molecular mechanism is not well understood. In this study, we present three crystal structures of p53-DBD in complex with the anti-apoptotic protein BCL-2 at resolutions of 2.3–2.7 Å. The structures show that two loops of p53-DBD penetrate directly into the BH3-binding pocket of BCL-2. Structure-based mutations at the interface impair the p53/BCL-2 interaction. Specifically, the binding sites for p53 and the pro-apoptotic protein Bax in the BCL-2 pocket are mostly identical. In addition, formation of the p53/BCL-2 complex is negatively correlated with the formation of BCL-2 complexes with pro-apoptotic BCL-2 family members. Defects in the p53/BCL-2 interaction attenuate p53-mediated cell apoptosis. Overall, our study provides a structural basis for the interaction between p53 and BCL-2, and suggests a molecular mechanism by which p53 regulates transcription-independent apoptosis by antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family members. The human tumor suppressor p53 interacts with the BCL-2 family proteins to regulate apoptosis. Here, the authors solve the structures of p53 in complex with the antiapoptotic protein BCL-2 and suggest a mechanism by which p53 promotes apoptosis by competitively antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family proteins.

Tumor cells reprogram their metabolism to produce specialized metabolites that both fuel their own growth and license tumor immune evasion. However, the relationships between these functions remain poorly understood. Here, we report CRISPR screens in a mouse model of colo-rectal cancer (CRC) that implicates the dual specificity phosphatase 18 (DUSP18) in the establishment of tumor-directed immune evasion. Dusp18 inhibition reduces CRC growth rates, which correlate with high levels of CD8 + T cell activation. Mechanistically, DUSP18 dephosphorylates and stabilizes the USF1 bHLH-ZIP transcription factor. In turn, USF1 induces the SREBF2 gene, which allows cells to accumulate the cholesterol biosynthesis intermediate lanosterol and release it into the tumor microenvironment (TME). There, lanosterol uptake by CD8 + T cells suppresses the mevalonate pathway and reduces KRAS protein prenylation and function, which in turn inhibits their activation and establishes a molecular basis for tumor cell immune escape. Finally, the combination of an anti-PD-1 antibody and Lumacaftor, an FDA-approved small molecule inhibitor of DUSP18, inhibits CRC growth in mice and synergistically enhances anti-tumor immunity. Collectively, our findings support the idea that a combination of immune checkpoint and metabolic blockade represents a rationally-designed, mechanistically-based and potential therapy for CRC. Dual-specificity phosphatases regulate several processes associated with carcinogenesis. Here the authors show that inhibition of the dual-specificity phosphatase DUSP18 improves the activity of tumor-infiltrating CD8 T cells, enhancing response to immune checkpoint blockade in preclinical models of colorectal cancer.

Transcranial direct current stimulation (tDCS) can improve cognitive function. However, it is not clear how high-definition tDCS (HD-tDCS) regulates the cognitive function and its neural mechanism, especially in individuals with mild cognitive impairment (MCI). This study aimed to examine whether HD-tDCS can modulate cognitive function in individuals with MCI and to determine whether the potential variety is related to spontaneous brain activity changes recorded by resting-state functional magnetic resonance imaging (rs-fMRI). Forty-three individuals with MCI were randomly assigned to receive either 10 HD-tDCS sessions or 10 sham sessions to the left dorsolateral prefrontal cortex (L-DLPFC). The fractional amplitude of low-frequency fluctuation (fALFF) and the regional homogeneity (ReHo) was computed using rs-fMRI data from all participants. The results showed that the fALFF and ReHo values changed in multiple areas following HD-tDCS. Brain regions with significant decreases in fALFF values include the Insula R, Precuneus R, Thalamus L, and Parietal Sup R, while the Temporal Inf R, Fusiform L, Occipital Sup L, Calcarine R, and Angular R showed significantly increased in their fALFF values. The brain regions with significant increases in ReHo values include the Temporal Inf R, Putamen L, Frontal Mid L, Precentral R, Frontal Sup Medial L, Frontal Sup R, and Precentral L. We found that HD-tDCS can alter the intensity and synchrony of brain activity, and our results indicate that fALFF and ReHo analysis are sensitive indicators for the detection of HD-tDCS during spontaneous brain activity. Interestingly, HD-tDCS increases the ReHo values of multiple brain regions, which may be related to the underlying mechanism of its clinical effects, these may also be related to a potential compensation mechanism involving the mobilization of more regions to complete a function following a functional decline.

The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway kinases Latsl/2 and Mst1/2, as well as the nuclear E3 ubiquitin ligase CRL4DcAF1. Numerous mutations of Merlin have been identified in Neurofibromatosis type 2 and other cancer patients. Despite more than two decades of research, the upstream regulator of Merlin in the Hippo pathway remains unknown. Here we show by high-resolution crystal structures that the Latsl/2-binding site on the Merlin FERM domain is physically blocked by Merlin＇s auto-inhibitory tail. Angiomotin binding releases the auto-inhibition and promotes Merlin＇s binding to Latsl/2. Phosphorylation of Ser518 outside the Merlin＇s auto-inhibitory tail does not obviously alter Merlin＇s conformation, but instead prevents angiomotin from binding and thus inhibits Hippo pathway kinase activation. Cancer-causing mutations clustered in the angiomotin- binding domain impair angiomotin-mediated Merlin activation. Our findings reveal that angiomotin and Merlin respectively interface cortical actin filaments and core kinases in Hippo signaling, and allow construction of a complete Hippo signaling pathway.

Background Enhancing flag leaf nitrogen use efficiency (NUE) in wheat production can substantially increase crop productivity while minimizing nitrogen application. Quantitative trait loci (QTLs) for NUE-related have been rarely reported in wheat flag leaf traits. Results In this study, a natural population of 243 varieties and an RIL population of 123 F 7 recombinants were subjected to different nitrogen treatments. A genome-wide association study (GWAS) and linkage analysis were performed for four agronomic traits in terms of flag leaf length, flag leaf width, flag leaf area, and SPAD (chlorophyll content) under low and normal nitrogen conditions. Through GWAS, 1,016 significant SNP loci were identified and clustered into 290 QTLs, including 11 stably mapped QTLs (stable detection in multiple environments). Additionally, an AC population was established to verify the GWAS results and identify reliable QTL intervals. Three stable loci, namely, QFLLR6D.3 QFLWR6A.6 , and QSPADR5B.3 , were validated in the AC population, located 1.34 Mb, 2.84 Mb, and 5 Mb away from linkage mapping significant QTL, respectively. Through further transcriptome analysis of Chilero leaves at the jointing, anthesis and grain filling stages, four DEGs were identified within QSPADR5B.3 . Among them, TraesCS5B02G394300 , TraesCS5B02G394200 , and TraesCS5B02G39390 encode beta-glucosidases, and TraesCS5B02G396400 encodes a potassium channel. Conclusions These findings offer potential candidate genes for wheat breeding, and provide a foundation for exploring the molecular targets underlying wheat NUE.

miR-148a has been shown to regulate inflammation, immunity and the growth of certain tumors, but its roles in colitis and colorectal tumorigenesis remain largely undetermined. Here we found miR-148a-deficient mice to be more susceptible to colitis and colitis-associated tumorigenesis. Both were associated with increased nuclear factor κ B (NF- κ B) and signal transducer and activator of transcription 3 (STAT3) signaling. Bone marrow- and non-bone marrow-derived miR-148a contributed to colitis and colitis-associated tumorigenesis. miR-148a loss of heterozygosity exacerbated Apc min/+ colon and small intestinal spontaneous tumor development. Restoring miR-148a expression prevented both spontaneous and carcinogen-induced colon tumor development. miR-148a was downregulated in human inflammatory bowel disease (IBD) and colorectal cancer patient tissues. This correlated with a high degree of miR-148a promoter methylation mediated by a complex comprised of P65 and DNA methyltransferase 3 alpha (DNMT3A). miR-148a directly targets several well-accepted upstream regulators of NF- κ B and STAT3 signaling, including GP130, IKK α , IKK β , IL1R1 and TNFR2, which leads to decreased NF- κ B and STAT3 activation in macrophages and colon tissues. Our findings reveal that miR-148a is an indirect tumor suppressor that modulates colitis and colitis-associated tumorigenesis by suppressing the expression of signaling by NF- κ B and STAT3 and their pro-inflammatory consequences.

Deubiquitinases (DUBs) play essential roles in normal cell proliferation and tumor growth. However, the molecular mechanisms of DUBs on hepatocellular carcinoma (HCC) remains largely unknown. In this study, based on analysis of several HCC datasets, we found that the USP21 gene, which encodes a member of the ubiquitin-specific protease family, is highly amplified and overexpressed in HCCs, with the extent of this up-regulation significantly correlating with poor clinical outcomes. Inhibition of USP21 in HCC cell lines decreased cell proliferation, anchorage-independent growth, cell cycle progression, and in vivo tumor growth. Conversely, ectopic expression of USP21 transformed the normal human hepatocyte line HL-7702 and increased the tumorigenicity of the HCC cell line MHCC97L. Mechanistically, USP21 stabilized MEK2 by decreasing its polyubiquitination at Lys48, thereby activating the ERK signaling pathway. Importantly, MEK2 partially mediated the optimal expression of USP21-mediated oncogenic phenotypes. These findings indicate that USP21-mediated deubiquitination and stabilization of MEK2 play a critical role in HCC development.