DeepSec: a deep learning framework for secreted protein discovery in human body fluids

Motivation: Human proteins that are secreted into different body fluids from various cells and tissues can be promising disease indicators. Modern proteomics research empowered by both qualitative and quantitative profiling techniques has made great progress in protein discovery in various human fluids. However, due to the large number of proteins and diverse modifications present in the fluids, as well as the existing technical limits of major proteomics platforms (e.g. mass spectrometry), large discrepancies are often generated from different experimental studies. As a result, a comprehensive proteomics landscape across major human fluids are not well determined. Results: To bridge this gap, we have developed a deep learning framework, named DeepSec, to identify secreted proteins in 12 types of human body fluids. DeepSec adopts an end-to-end sequence-based approach, where a Convolutional Neural Network is built to learn the abstract sequence features followed by a Bidirectional Gated Recurrent Unit with fully connected layer for protein classification. DeepSec has demonstrated promising performances with average area under the ROC curves of 0.85–0.94 on testing datasets in each type of fluids, which outperforms existing state-of-the-art methods available mostly on blood proteins. As an illustration of how to apply DeepSec in biomarker discovery research, we conducted a case study on kidney cancer by using genomics data from the cancer genome atlas and have identified 104 possible marker proteins

Effect of Oral Administration of Enterococcus faecium Ef1 on Innate Immunity of Sucking Piglets

The objective of this study was to evaluate the effect of orally administered Enterococcus faecium EF1 on innate immune responses of jejunal mucosa in newborn piglets. Twenty-four commercial crossbred healthy newborn piglets were randomly divided into two groups, control (T0) and treatment (T1) group. Each group consists of 12 piglets. T1 was administered sterilized skim milk 2 ml piglet-1 day-1 with addition of E. faecium EF1 (5~6×108 cfu/ml) by oral gavage on alternative odd days (1st, 3rd and 5th) after birth. T0 fed with the same volume of sterilized skim milk without probiotics. The merciful killing of piglets at the 25th day after birth was performed to collect the samples of jejunal mucosa to measure the innate cytokine responses and the Toll-like receptors gene expression by quantitative real time PCR. The results showed that TGF-β1 and TNF-α concentrations increased and mRNA expression levels also improved significantly in T1 as compared to T0. While, the production of IFN-γ and IL-8 decreased significantly in T1 and gene expression modification was not observed. In addition, TLR (Toll-like receptor) 2 and TLR 9 transcription levels were up-regulated in treatment (T1) group. These findings revealed that oral administration of E. faecium EF1 was effective to activate innate immunity and could modulate the TLRs expression in jejunal mucosa of piglets

Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury

Kudzu (Pueraria lobata) is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE) on chronic alcoholic liver injury as well as Kupffer cells (KCs) activation to release tumor necrosis factor alpha (TNF-α) induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic gamma-glutamyl transpeptidase (GGT) activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP), CD14, Toll-like receptor (TLR) 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro

Genomic traits of multidrug resistant enterotoxigenic Escherichia coli isolates from diarrheic pigs

Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) infections poses a significant challenge in global pig farming. To address this issue, the study was conducted to identify and characterize 19 ETEC isolates from fecal samples of diarrheic pigs sourced from large-scale farms in Sichuan Province, China. Whole-genome sequencing and bioinformatic analysis were utilized for identification and characterization. The isolates exhibited substantial resistance to cefotaxime, ceftriaxone, chloramphenicol, ciprofloxacin, gentamicin, ampicillin, tetracycline, florfenicol, and sulfadiazine, but were highly susceptible to amikacin, imipenem, and cefoxitin. Genetic diversity among the isolates was observed, with serotypes O22:H10, O163orOX21:H4, and O105:H8 being dominant. Further analysis revealed 53 resistance genes and 13 categories of 195 virulence factors. Of concern was the presence of tet(X4) in some isolates, indicating potential public health risks. The ETEC isolates demonstrated the ability to produce either heat-stable enterotoxin (ST) alone or both heat-labile enterotoxin (LT) and ST simultaneously, involving various virulence genes. Notably, STa were linked to human disease. Additionally, the presence of 4 hybrid ETEC/STEC isolates harboring Shiga-like toxin-related virulence factors, namely stx2a, stx2b, and stx2e-ONT-2771, was identified. IncF plasmids carrying multiple antimicrobial resistance genes were prevalent, and a hybrid ETEC/STEC plasmid was detected, highlighting the role of plasmids in hybrid pathotype emergence. These findings emphasized the multidrug resistance and pathogenicity of porcine-origin ETEC strains and the potential risk of epidemics through horizontal transmission of drug resistance, which is crucial for effective control strategies and interventions to mitigate the impact on animal and human health

Preparation of Graphene/TiO 2

The graphene (GR) was prepared by an improved electrochemical stripping method using a high-purity graphite rod as raw material and high temperature heat reduction in hydrogen atmosphere, and the graphene/TiO2 (GR/TiO2) composite nanomaterials were manufactured by the method of sol-gel and high temperature crystallization in hydrogen atmosphere using butyl titanate and electrolysis graphene as precursors. The physical and chemical properties of the composites had been characterized by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), UV-Vis spectrophotometer (UV-Vis), scanning electron microscopy (SEM), Transmission Electron Microscope (TEM),  and specific surface area (SSA) by BET method. The photocatalytic properties of GR/TiO2 composites nanomaterials in anoxic water were studied by using 2,4-dichlorophenoxyacetic acid (2,4-D) as probe. The results showed that graphite was well intercalated and peeled by a facile electrolysis method in different electric field environment; a well dispersed and rings structure of graphene was prepared by coupling ultrasound-assisted changing voltage electrochemical stripping technology. The as-prepared GR/TiO2 composites had good performance for the photocatalytic degradation of 2,4-D in anoxic water; the chlorines were removed from benzene ring; the middle products of dichlorophenol, chlorophenol, phloroglucinol, and so forth were produced from the photocatalytic redox reaction of 2,4-D in anoxic water; parts of 2,4-D were decomposed completely, and CO2 and H2O were produced

MV-CVIB: a microbiome-based multi-view convolutional variational information bottleneck for predicting metastatic colorectal cancer

IntroductionImbalances in gut microbes have been implied in many human diseases, including colorectal cancer (CRC), inflammatory bowel disease, type 2 diabetes, obesity, autism, and Alzheimer's disease. Compared with other human diseases, CRC is a gastrointestinal malignancy with high mortality and a high probability of metastasis. However, current studies mainly focus on the prediction of colorectal cancer while neglecting the more serious malignancy of metastatic colorectal cancer (mCRC). In addition, high dimensionality and small samples lead to the complexity of gut microbial data, which increases the difficulty of traditional machine learning models.MethodsTo address these challenges, we collected and processed 16S rRNA data and calculated abundance data from patients with non-metastatic colorectal cancer (non-mCRC) and mCRC. Different from the traditional health-disease classification strategy, we adopted a novel disease-disease classification strategy and proposed a microbiome-based multi-view convolutional variational information bottleneck (MV-CVIB).ResultsThe experimental results show that MV-CVIB can effectively predict mCRC. This model can achieve AUC values above 0.9 compared to other state-of-the-art models. Not only that, MV-CVIB also achieved satisfactory predictive performance on multiple published CRC gut microbiome datasets.DiscussionFinally, multiple gut microbiota analyses were used to elucidate communities and differences between mCRC and non-mCRC, and the metastatic properties of CRC were assessed by patient age and microbiota expression

Solution Grown Se/Te Nanowires: Nucleation, Evolution, and The Role of Triganol Te seeds

We have studied the nucleation and growth of Se–Te nanowires (NWs), with different morphologies, grown by a chemical solution process. Through systematic characterization of the Se–Te NW morphology as a function of the Te nanocrystallines (NCs) precursor, the relative ratio between Se and Te, and the growth time, a number of significant insights into Se–Te NW growth by chemical solution processes have been developed. Specifically, we have found that: (i) the growth of Se–Te NWs can be initiated from either long or short triganol Te nanorods, (ii) the frequency of proximal interactions between nanorod tips and the competition between Se and Te at the end of short Te nanorods results in V-shaped structures of Se–Te NWs, the ratio between Se and Te having great effect on the morphology of Se–Te NWs, (iii) by using long Te nanorods as seeds, Se–Te NWs with straight morphology were obtained. Many of these findings on Se–Te NW growth can be further generalized and provide very useful information for the rational synthesis of group VI based semiconductor NW compounds

Construction of an artificial recombinant bicistronic plasmid DNA vaccine against porcine rotavirus

The attenuated Salmonella typhimurium χ4550 strain was used to harbour a reconstructed bicistronic DNA vaccine against porcine rotavirus, which carried the rotavirus nonstructural protein 4 (NSP4) and VP7 genes simultaneously. Using a balanced lethal system, the kanamycin resistance gene of expressing eukaryotic plasmids pVAX1 and pVAXD were replaced by the aspartate β-semialdehyde dehydrogenase (asd) gene. The NSP4 cleavage product (259–525) of rotavirus OSU strain and VP7 full-length genes were amplified by reverse transcription polymerase chain reaction and then inserted into the eukaryotic single-expression plasmid, pVAX1-asd, and the eukaryotic dual-expression plasmid, pVAXD-asd, respectively. The recombinant plasmids pVAX1-asd-NSP4, pVAX1-asd-VP7 and pVAXD-asd-NSP4-VP7 were transformed into the attenuated S. typhimurium χ4550 strain by electrotransformation. An indirect immunofluorescence assay of the expressed COS-7 cell suggested that the recombinant S. typhimurium χ4550 strain was constructed successfully. The recombinant S. typhimurium χ4550 strain was orally administered to BALB/c mice. The group immunised with dual- expression plasmids produced a significantly higher level of serum Immunoglobulin G (IgG) and intestinal Immunoglobulin A (IgA) than the group immunised with single-expression plasmids. These results indicated that eukaryotic bicistronic plasmid DNA vaccines could be successfully constructed to enhance humoural, mucosal and cellular immune response against rotavirus infection