Use of machine learning-based integration to develop an immune-related signature for improving prognosis in patients with gastric cancer.

Gastric cancer is one of the most common malignancies. Although some patients benefit from immunotherapy, the majority of patients have unsatisfactory immunotherapy outcomes, and the clinical significance of immune-related genes in gastric cancer remains unknown. We used the single-sample gene set enrichment analysis (ssGSEA) method to evaluate the immune cell content of gastric cancer patients from TCGA and clustered patients based on immune cell scores. The Weighted Correlation Network Analysis (WGCNA) algorithm was used to identify immune subtype-related genes. The patients in TCGA were randomly divided into test 1 and test 2 in a 1:1 ratio, and a machine learning integration process was used to determine the best prognostic signatures in the total cohort. The signatures were then validated in the test 1 and the test 2 cohort. Based on a literature search, we selected 93 previously published prognostic signatures for gastric cancer and compared them with our prognostic signatures. At the single-cell level, the algorithms "Seurat," "SCEVAN", "scissor", and "Cellchat" were used to demonstrate the cell communication disturbance of high-risk cells. WGCNA and univariate Cox regression analysis identified 52 prognosis-related genes, which were subjected to 98 machine-learning integration processes. A prognostic signature consisting of 24 genes was identified using the StepCox[backward] and Enet[alpha = 0.7] machine learning algorithms. This signature demonstrated the best prognostic performance in the overall, test1 and test2 cohort, and outperformed 93 previously published prognostic signatures. Interaction perturbations in cellular communication of high-risk T cells were identified at the single-cell level, which may promote disease progression in patients with gastric cancer. We developed an immune-related prognostic signature with reliable validity and high accuracy for clinical use for predicting the prognosis of patients with gastric cancer.

Screening potential ligands of endothelin receptor A from Choerospondias axillaris and evaluation of their drug-like properties by affinity chromatographic methods.

Tibetan medicine is traditionally prescribed as crude extracts or mixtures owing to the theoretical basis with cross fertilization from other medical systems like Ayurveda and traditional Chinese medicine. This is challenged to elucidate the action mechanism and material foundation of Tibetan medicine due to lacking a method to confirm the bioactive compounds determining the therapy. This work created a new strategy for screening and evaluating the bioactive compounds against cardiovascular ailments from Choerospondias axillaris. It involved the immobilization of endothelin receptor A (ETAR) by a one-step covalent assay, the screening and identification of the bioactive compounds by ETAR column combined with tandem mass spectrometry, and the evaluation of their drug-like properties by calculating the efficiency indexes using the data collected by frontal analysis and adsorption energy distribution. The immobilized ETAR remained good stability in three weeks in terms of specificity and repeatability. Catechin, pinocembrin, and hyperoside were identified as potential ETAR ligands from Choerospondias axillaris with two types of binding sites on the immobilized receptor. Their association constants on the high and low affinity binding sites were (2.53 ± 0.11) × 105 and (9.94 ± 0.02) × 103 M-1 for catechin, (1.01 ± 0.12) × 106 and (7.40 ± 0.03) × 104 for hyperoside, and (2.05 ± 0.04) × 105 and (2.47 ± 0.09)× 104 M-1 for pinocembrin, respectively. Owing to the highest association constant, hyperoside presented a surface efficiency index of 7.95, and binding efficiency index of 20.7, and the ligand-lipophilicity efficiency of 1.38. These indicated that the three compounds were the main ingredients for the therapy of Choerospondias axillaris, and had potential to become lead compounds for anti-cardiovascular drugs based on drug-ETAR interaction. The immobilized receptor-based strategy is possible to become an alternative for screening and assessing bioactive compounds from Tibetan medicine.

Sex Difference in Emotion Recognition under Sleep Deprivation: Evidence from EEG and Eye-tracking.

Many psychiatric disorders are accompanied with sleep abnormalities, having significant influence on emotions which might worsen the disorder conditions. Previous studies discovered that the emotion recognition task with objective physiological signals, such as electroencephalography (EEG) and eye movements, provides a reliable way to figure out the complicated relationship between emotion and sleep. However, both of the emotion and EEG signals are affected by sex. This study aims to investigate how sex differences influence emotion recognition under three different sleep conditions. We firstly developed a four-class emotion recognition task based on various sleep conditions to augment the existing dataset. Then we improved the current state-of-the-art deep-learning model with the attention mechanism. It outperforms the best model with higher accuracy about 91.3% and more stabilization. After that, we compared the results of the male and the female group given by this model. The classification accuracy of happy emotion obviously decreases under sleep deprivation for both males and females, which indicates that sleep deprivation impairs the stimulation of happy emotion. Sleep deprivation also notably weakens the discrimination ability of sad emotion for males while females maintain the same as under common sleep. Our study is instructively beneficial to the real application of emotion recognition in disorder diagnosis.

A facile approach to synthesize CdS-attapulgite as a photocatalyst for reduction reactions in water.

At room temperature, a facile approach has been utilized for preparing novel CdS-attapulgite (CdS-ATP) composites and the composites were applied in photocatalytic reduction of p-nitrophenol and Cr(vi). The effect of ATP on the photocatalytic activity of the CdS-ATP composites were studied by controlling the mass ratio of attapulgite. The results showed that the CdS-20%ATP composite has an excellent photocatalytic activity. In order to figure out the key to improve the photocatalytic efficiency, the prepared composites were characterized by Brunauer-Emmett-Teller (BET) specific surface area, UV-vis diffuse reflectance spectroscopy (DRS) and electrochemical impedance spectroscopy (EIS). The superior photocatalytic performance of the CdS-20%ATP composite can be ascribed to the existence of the ATP which can fix the CdS and prevent agglomeration. The interaction between ATP and CdS in the composites facilitates the electron transfer and also promoted their photocatalytic performance. This work provides us with some significant guidance in the development of CdS-ATP composite photocatalysts.

Genomic variations of the mevalonate pathway in porokeratosis.

Porokeratosis (PK) is a heterogeneous group of keratinization disorders. No causal genes except MVK have been identified, even though the disease was linked to several genomic loci. Here, we performed massively parallel sequencing and exonic CNV screening of 12 isoprenoid genes in 134 index PK patients (61 familial and 73 sporadic) and identified causal mutations in three novel genes (PMVK, MVD, and FDPS) in addition to MVK in the mevalonate pathway. Allelic expression imbalance (AEI) assays were performed in 13 lesional tissues. At least one mutation in one of the four genes in the mevalonate pathway was found in 60 (98%) familial and 53 (73%) sporadic patients, which suggests that isoprenoid biosynthesis via the mevalonate pathway may play a role in the pathogenesis of PK. Significantly reduced expression of the wild allele was common in lesional tissues due to gene conversion or some other unknown mechanism. A G-to-A RNA editing was observed in one lesional tissue without AEI. In addition, we observed correlations between the mutations in the four mevalonate pathway genes and clinical manifestations in the PK patients, which might support a new and simplified classification of PK under the guidance of genetic testing.

Efficient typing of copy number variations in a segmental duplication-mediated rearrangement hotspot using multiplex competitive amplification.

Local genomic architecture, such as segmental duplications (SDs), can induce copy number variations (CNVs) hotspots in the human genome, many of which manifest as genomic disorders. Significant technological advances have been achieved for genome-wide CNV investigations, but these costly methods are not suitable for genotyping certain disease-associated CNVs or other loci of interest in populations. Recently, two independent studies showed that the murine meiosis expressed gene 1 (Meig1) was critical to spermatogenesis. We found that the human orthologue MEIG1 is flanked by an SD pair, between which non-allelic homologous recombination (NAHR) can cause recurrent CNVs. To study this potential CNV hotspot and its role in spermatogenesis, we developed a new CNV genotyping method, AccuCopy, based on multiplex competitive amplification to investigate 320 patients with spermatogenic impairment and 93 healthy controls. Three MEIG1 duplications (two in patients and one in controls) were identified, whereas no deletion was found. As NAHR results in more recurrent deletions than duplications at a locus, the over representation of recurrent MEIG1 duplications suggests a potential purifying selection operating on this hotspot, possibly via fecundity. We also showed that AccuCopy is an efficient and reliable method for multiplex CNV genotyping.