Survival prediction in patients with colon adenocarcinoma via multiomics data integration using a deep learning algorithm

The present study proposed a deep learning (DL) algorithm to predict survival in patients with colon adenocarcinoma (COAD) based on multiomics integration. The survival-sensitive model was constructed using an autoencoder for DL implementation based on The Cancer Genome Atlas (TCGA) data of patients with COAD. The autoencoder framework was compared with PCA, NMF, t-SNE, and univariable Cox-PH model for identifying survival-related features. The prognostic robustness of the inferred survival risk groups was validated using three independent confirmation cohorts. Differential expression analysis, Pearson’s correlation analysis, construction of miRNA–target gene network, and function enrichment analysis were performed. Two risk groups with significant survival differences were identified in TCGA set using the autoencoder-based model (log-rank P-value = 5.51e⁻⁰⁷). The autoencoder framework showed superior performance compared with PCA, NMF, t-SNE, and the univariable Cox-PH model based on the C-index, log-rank P-value, and Brier score. The robustness of the classification model was successfully verified in three independent validation sets. There were 1271 differentially expressed genes, 10 differentially expressed miRNAs, and 12 hypermethylated genes between the survival risk groups. Among these, miR-133b and its target genes (GNB4, PTPRZ1, RUNX1T1, EPHA7, GPM6A, BICC1, and ADAMTS5) were used to construct a network. These genes were significantly enriched in ECM–receptor interaction, focal adhesion, PI3K–Akt signaling pathway, and glucose metabolism-related pathways. The risk subgroups obtained through a multiomics data integration pipeline using the DL algorithm had good robustness. miR-133b and its target genes could be potential diagnostic markers. The results would assist in elucidating the possible pathogenesis of COAD.     

Inhibition kinetics of acetosyringone on xylanase in hydrolysis of hemicellulose

ABSTRACT

Many phenolic compounds, derived from lignin during the pretreatment of lignocellulosic biomass, could obviously inhibit the activity of cellulolytic and hemicellulolytic enzymes. Acetosyringone (AS) is one of the phenolic compounds produced from lignin degradation. In this study, we investigated the inhibitory effects of AS on xylanase activity through kinetic experiments. The results showed that AS could obviously inhibit the activity of xylanase in a reversible and noncompetitive binding manner (up to 50% activity loss). Inhibitory kinetics and constants of xylanase on AS were conducted by the HCH-1 model (β = 0.0090 ± 0.0009 mM^?1). Furthermore, intrinsic and 8-anilino-1-naphthalenesulfonic (ANS)-binding fluorescence results showed that the tertiary structure of AS-mediated xylanase was altered. These findings provide new insights into the role of AS in xylanase activity. Our results also suggest that AS was an inhibitor of xylanase and targeting AS was a potential strategy to increase xylose production.     

Allicin suppresses growth and metastasis of gastric carcinoma: the key role of microRNA-383-5p-mediated inhibition of ERBB4 signaling

ABSTRACT

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.     

Neural spike train reconstruction from calcium imaging via a signal-shape composition model

Science China Life Sciences -     

Effects of Several Environmental Factors on Longevity and Health of the Human Population of Zhongxiang,Hubei, China

Increasing human health and longevity is of global interest. Environmental, genetic, and stochastic factors all affect longevity. Among these factors, the environment is extremely important. To investigate the relationship between the environment and longevity, we studied the environment in Zhongxiang (China), where the inhabitants commonly have long life spans. Air was analyzed for negative oxygen ions, SO₂, and inhalable particles, while drinking water and rice were analyzed for macro- and micro-elements. The air quality in this area was determined to be grade I with high negative oxygen ion content and low SO₂ and inhalable particle contents. Apart from Fe, Mn, and F, all tested elements and the pH were within national standards and World Health Organization guidelines. The percentage of long-lived people in the area was closely related to the macro- and micro-element contents of their staple food, rice. The elements in rice could be classified into three categories according to their effect on longevity: Sr, Ca, Al, Mo, and Se, which were positively correlated with longevity; Fe, Mn, Zn, Cr, P, Mg, and K, which had a weak effect on local longevity, and Cu and Ba, which had a negative effect on longevity.     

Modulating the synthetase activity of penicillin G acylase in organic media by addition of N-methylimidazole: using vinyl acetate as activated acyl donor

This paper reported the modulation of enzyme activity by organic small molecule. The esterification activity of Penicillin G acylase (PGA) was improved more than 70-fold by the addition of 10% N-methylimidazole. Some control experiments have been designed to demonstrate the catalytic specificity of PGA. The structure and the amount of additive were optimized to improve the product yield. The influence of N-methylimidazole on the PGA conformation was investigated by FTIR and autodock simulation. Seven substrates were used to evaluate the effect of structure on the PGA-catalyzed transesterification. A series of products were successfully synthesized with the yield ranged from 56% to 84% and PGA showed specific recognition on the substrate with phenyl group in the presence of 10% N-methylimidazole.     

Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat

-Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg(-1)·day(-1)) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes.     

Interaction between bacterial outer membrane proteins and periplasmic quality control factors: a kinetic partitioning mechanism

The OMPs (outer membrane proteins) of Gram-negative bacteria have to be translocated through the periplasmic space before reaching their final destination. The aqueous environment of the periplasmic space and high permeability of the outer membrane engender such a translocation process inevitably challenging. In Escherichia coli, although SurA, Skp and DegP have been identified to function in translocating OMPs across the periplasm, their precise roles and their relationship remain to be elucidated. In the present paper, by using fluorescence resonance energy transfer and single-molecule detection, we have studied the interaction between the OMP OmpC and these periplasmic quality control factors. The results of the present study reveal that the binding rate of OmpC to SurA or Skp is much faster than that to DegP, which may lead to sequential interaction between OMPs and different quality control factors. Such a kinetic partitioning mechanism for the chaperone-substrate interaction may be essential for the quality control of the biogenesis of OMPs.     

Variation in structural and physiological leaf traits of eight species in karst desertification area of China

Leaf traits have long been recognized as influential factors in the acquisition and processing of resources by plants. However, there is less knowledge of between-species variations in seasonal changes in leaf traits and trait interrelationships. Therefore, we examined variations in leaf area (LA), dry biomass (DM), specific leaf area (SLA), and leaf gas-exchange parameters in one non-native and seven native tree species under field environmental conditions, in a karst area in China subjected to desertification. Measurements were taken three times during the growing season. The results show that the seven native trees had higher LA, DM, and water-use efficiency (WUE) than the non-native Cinnamomum camphora. In contrast, all the native tree species except Ligustrum lucidum had lower photosynthetic rates (P _N) than the non-native species. In all species, the relationship between LA and DM was less variable than the relationship between SLA and LA. However, leaves of the non-native C. camphora and native species Sterculia lanceolata, Cleidiocarpon cavalerei and Cyclobalanopsis glauca were highly sensitive to seasonal conditions, leaves of Sapindus mukorossi and Ligustrum lucidum were less sensitive to seasonal changes, and leaves of Syzygium cumini and Cephalomappa sinensis were insensitive. An understanding of leaf traits will aid the selection of suitable species for land restoration.     

Cloning and expression of stearoyl-CoA desaturase 1 (SCD-1) in the liver of the Sichuan white goose and landes goose responding to overfeeding

The EST sequence of goose (Anser cygnoides) Stearoyl-CoA desaturase 1(SCD-1) was obtained from a subtractive cDNA library. To further investigate the role of SCD-1 in lipid metabolism in geese, 5′-RACE and 3′-RACE were carried out in this study to obtain the complete cDNA sequence of goose SCD-1, which contained a 29-bp 5′ UTR, a 1074-bp open reading frame (ORF) encoding 357 amino acids, and a 125-bp 3′ UTR. The expression of SCD-1 was measured in several tissues, and the effects of overfeeding on the expression of SCD-1 were studied. The results of real time RT-PCR demonstrated that, compared to the brain, goose SCD-1 mRNA was more abundant in the liver. Overfeeding markedly increased the mRNA expression of SCD-1 in the liver of Sichuan White and Landes geese, and gene expression was markedly higher in the Sichuan White goose than in the landes goose. The mRNA abundance of SCD-1 in the liver had significant positive correlations with triacylglycerol (TG) content in liver lipids and in the levels of plasma insulin and very low-density lipoproteins (VLDL) levels in Sichuan white geese. However, the mRNA abundance of SCD-1 in the livers of Landes geese had only significant positive correlations with the TG content in liver lipids. In conclusion, SCD-1 is not only critical for hepatic steatosis in geese but is also important for the difference in lipid deposition in the livers of the two breeds.