Enhancing insights into diseases through horizontal gene transfer event detection from gut microbiome.

Horizontal gene transfer (HGT) phenomena pervade the gut microbiome and significantly impact human health. Yet, no current method can accurately identify complete HGT events, including the transferred sequence and the associated deletion and insertion breakpoints from shotgun metagenomic data. Here, we develop LocalHGT, which facilitates the reliable and swift detection of complete HGT events from shotgun metagenomic data, delivering an accuracy of 99.4%-verified by Nanopore data-across 200 gut microbiome samples, and achieving an average F1 score of 0.99 on 100 simulated data. LocalHGT enables a systematic characterization of HGT events within the human gut microbiome across 2098 samples, revealing that multiple recipient genome sites can become targets of a transferred sequence, microhomology is enriched in HGT breakpoint junctions (P-value = 3.3e-58), and HGTs can function as host-specific fingerprints indicated by the significantly higher HGT similarity of intra-personal temporal samples than inter-personal samples (P-value = 4.3e-303). Crucially, HGTs showed potential contributions to colorectal cancer (CRC) and acute diarrhoea, as evidenced by the enrichment of the butyrate metabolism pathway (P-value = 3.8e-17) and the shigellosis pathway (P-value = 5.9e-13) in the respective associated HGTs. Furthermore, differential HGTs demonstrated promise as biomarkers for predicting various diseases. Integrating HGTs into a CRC prediction model achieved an AUC of 0.87.

Coding genomes with gapped pattern graph convolutional network.

MOTIVATION: Genome sequencing technologies reveal a huge amount of genomic sequences. Neural network-based methods can be prime candidates for retrieving insights from these sequences because of their applicability to large and diverse datasets. However, the highly variable lengths of genome sequences severely impair the presentation of sequences as input to the neural network. Genetic variations further complicate tasks that involve sequence comparison or alignment. RESULTS: Inspired by the theory and applications of "spaced seeds," we propose a graph representation of genome sequences called "gapped pattern graph." These graphs can be transformed through a Graph Convolutional Network to form lower-dimensional embeddings for downstream tasks. On the basis of the gapped pattern graphs, we implemented a neural network model and demonstrated its performance on diverse tasks involving microbe and mammalian genome data. Our method consistently outperformed all the other state-of-the-art methods across various metrics on all tasks, especially for the sequences with limited homology to the training data. In addition, our model was able to identify distinct gapped pattern signatures from the sequences. AVAILABILITY AND IMPLEMENTATION: The framework is available at https://github.com/deepomicslab/GCNFrame.

Plasma Amino Acid Profile in Children with Autism Spectrum Disorder in Southern China: Analysis of 110 Cases.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, γ-Amino-n-butyric acid, glutamine, sarcosine, δ-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

PhageScope: a well-annotated bacteriophage database with automatic analyses and visualizations.

Bacteriophages are viruses that infect bacteria or archaea. Understanding the diverse and intricate genomic architectures of phages is essential to study microbial ecosystems and develop phage therapy strategies. However, the existing phage databases are short of meticulous annotations. To this end, we propose PhageScope (https://phagescope.deepomics.org), an online phage database with comprehensive annotations. PhageScope harbors a collection of 873 718 phage sequences from various sources. Applying fifteen state-of-the-art tools to perform systematic annotations and analyses, PhageScope provides annotations on genome completeness, host range, lifestyle information, taxonomy classification, nine types of structural and functional genetic elements, and three types of comparative genomic studies for curated phages. Additionally, PhageScope incorporates automatic analyses and visualizations for curated and customized phages, serving as an efficient platform for phage study.

Recent updates on pyroptosis in tumors of the digestive tract.

Pyroptosis is an inflammasome-dependent form of programmed cell death that is mediated by caspases-1, -4, -5, and -11, and the gasdermin protein family. It is characterized by the rupture of cell membrane and the subsequent release of cell contents and interleukins, leading to inflammatory reaction and activation of the immune system. Recent studies have suggested that pyroptosis plays a role in the development of gastrointestinal tumors, impeding tumor generation and progression as well as providing a favorable microenvironment for tumor growth. In this review we outlined the current knowledge regarding the implications of pyroptosis in gastrointestinal cancers.

Probabilistic tensor decomposition extracts better latent embeddings from single-cell multiomic data.

Single-cell sequencing technology enables the simultaneous capture of multiomic data from multiple cells. The captured data can be represented by tensors, i.e. the higher-rank matrices. However, the existing analysis tools often take the data as a collection of two-order matrices, renouncing the correspondences among the features. Consequently, we propose a probabilistic tensor decomposition framework, SCOIT, to extract embeddings from single-cell multiomic data. SCOIT incorporates various distributions, including Gaussian, Poisson, and negative binomial distributions, to deal with sparse, noisy, and heterogeneous single-cell data. Our framework can decompose a multiomic tensor into a cell embedding matrix, a gene embedding matrix, and an omic embedding matrix, allowing for various downstream analyses. We applied SCOIT to eight single-cell multiomic datasets from different sequencing protocols. With cell embeddings, SCOIT achieves superior performance for cell clustering compared to nine state-of-the-art tools under various metrics, demonstrating its ability to dissect cellular heterogeneity. With the gene embeddings, SCOIT enables cross-omics gene expression analysis and integrative gene regulatory network study. Furthermore, the embeddings allow cross-omics imputation simultaneously, outperforming current imputation methods with the Pearson correlation coefficient increased by 3.38-39.26%; moreover, SCOIT accommodates the scenario that subsets of the cells are with merely one omic profile available.

Sex and age differences in chronic postoperative pain among patients undergoing thoracic surgery: a retrospective cohort study.

Background: The effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences. Methods: This was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up. Results: Among the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP. Conclusion: Females have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.

The Roles of Stress-Induced Immune Response in Female Reproduction.

Stress response plays pivotal roles in physiological process, including reproduction and embryonic development. It's long been acknowledged that stress stimulates the activation of both hormone and immune system resulting in disorders of maternal immune function and infertility. However, the stress types, biological alterations, clinical outcomes, and the potential underlying mechanisms remain largely unclear. Recent studies suggest that more stress factors and relative mechanisms are identified to be involved in female reproductive immune response stimulation, and they may lead to immune dysregulations that negatively influence maternal health. In this part, we focus on the outcomes or mechanisms of common stress factors which affect female immune response before and during pregnancy.

Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis.

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.

Dual Channel Activatable Cyanine Dye for Mitochondrial Imaging and Mitochondria-Targeted Cancer Theranostics.

Because mitochondria are the key regulators for many cellular behaviors and are susceptible to hyperthermia and reactive oxygen species, mitochondria-specific reagents for simultaneous targeting, imaging, and treatment are highly desirable in cancer theranostics. Herein, we developed a mitochondria-targeted cyanine dye IR825-Cl, which possesses two separated excitation wavelength channels for both red fluorescence imaging and near-infrared (NIR) photothermal therapy (PTT). For imaging, IR825-Cl rapidly entered cells and selectively targeted mitochondria. Although IR825-Cl was completely quenched in water, interestingly, this dye had a turn-on response of red fluorescence (610 nm) in mitochondria under 552 nm excitation due to its polarity-responsive fluorescence emission. More interestingly, IR825-Cl realized the selective mitochondrial staining of cancer cells over normal cells and thus served as an ideal fluorescent probe for identifying cancer cells in normal tissues, which is extremely beneficial for cancer theranostics. For PTT, we demonstrated that under 808 nm NIR laser irradiation, this dye efficiently converted optical energy into heat, realizing mitochondria-targeted photothermal cancer therapy. Collectively, this molecule realized both high fluorescence emission (quantum yield > 43%) and effective light-to-heat conversion (17.4%), enabling its applications for wash-free fluorescence imaging for mitochondria and highly efficient fluorescence imaging-guided PTT.

[Quercetin permeability across blood-brain barrier and its effect on the viability of U251 cells].

OBJECTIVE: To investigate the permeability of quercetin across blood-brain barrier (BBB) and its impact on the proliferation and apoptosis of U251 cells. METHODS: The BBB model was established through culture of primary brain microvessel endothelial cells (BMVEC) and primary astroglia cells (AC), which was confirmed by transmission electron microscopy (TEM) and trans epithelial electric resistance (TEER). High pressure liquid chromatography (HPLC) was performed to determine quercetin permeability across BBB. U251 cells were exposed to quercetin. MTT assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), single-cell gel electrophoresis (SCGE) and flow cytometry (FCM) were performed to analyze cell proliferation, apoptosis, DNA damage and cell cycle distribution. RESULTS: The BBB was constructed successfully. Up to 65.54% of quercetin permeated across the BBB. Quercetin attenuated the proliferation of U251 and induced apoptosis. The FCM revealed that the U251 cells were inhibited at the G2/M point. CONCLUSION: Quercetin can permeate across the BBB effectively, restraining the proliferation of U251 cells and inducing apoptosis.

[The effects of human 21.5 kDa MBP gene on HepG-2 proliferation and apoptosis].

OBJECTIVE: To test the effects of the 21.5 kDa human brain myelin basic protein (MBP) on the proliferation and apoptosis of HepG-2. METHODS: pSVCEP-MBP-CAT plasmid containing the full-length 21.5 kDa MBP cDNA was transfected into human hepatoma carcinoma cells (HepG-2). The pSVCEP-CAT vector transfected HepG-2 cells served as negative control. RT-PCR and Western blot were performed to confirm the effectiveness of the transfection. MTT measures were used to determine the proliferative curve of cells. H2O2 was then added to induce cell apoptosis. DNA ladder, immunohistochemistry assay, comet electrophoresis and TUNEL (Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling) were used to detect the apoptosis and relevant protein expressions. RESULTS: The 21.5 KDa MBP cDNA was transfected into HepG-2 cells successfully. MTT measures of pSVCEP-MBP-CAT transfected group showed increased proliferation and anti-apoptosis. The control group displayed with more typical DNA ladders and much higher level of Caspase-3 than the MBP group. Comet and TUNEL assays revealed that the control group cells had significant DNA damages and serious apoptosis, whereas the MBP group showed slight changes. CONCLUSION: The 21.5 kDa MBP promotes the proliferation of HepG-2 and blocks apoptosis.

Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.

AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight. CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.

[Inhibitory effect of human brain myelin basic protein on H2O2-induced apoptosis of human lung cancer cell line YTLMC-90].

BACKGROUND & OBJECTIVE: Human brain myelin basic protein (MBP) distributes in nervous system and other tissues extensively, and can be detected in many kinds of tumor cells, such as lung cancer, breast cancer, and neuroglioma. However, it has not been reported whether MBP is relevant to the activity of neural invasion of tumors and whether MBP plays a role in biological behaviors of human lung cancer cells. This study was to investigate the inhibitory effect of MBP on hydrogen peroxide (H2O2)-induced apoptosis of human lung cancer cell line YTLMC-90. METHODS: YTLMC-90 cells were transfected with plasmid pSVCEPMBPCAT containing MBP cDNA minigene (test group), or empty vector pSVCEPCAT, or received no transfection (control group), and exposed to H2O2. The expression of MBP in YTLMC-90 cells was detected by Western blot. Cell proliferation was measured by MTT assay. The morphologic and ultra-structural changes of apoptotic cells were observed by microscopy with fluorescent staining of acridine orange (AO) and electron microscopy. The DNA fragmentation was examined by agarose gel electrophoresis. RESULTS: After exposed to 200 micromol/L H2O2 for 24 h, the inhibitory rate of cell growth was significantly lower in test group than in empty vector group and control group (36.67% vs. 78.67% and 84.00%, P<0.001). The morphologic and biochemical changes of apoptotic cells, such as shrinkage of cytoplasm and nucleus, fragmentation of chromatin, and ladder pattern of DNA, were commonly observed in cells in control group, but these apoptotic features were not discovered in test group. CONCLUSION: MBP markedly inhibits H2O2 cytotoxicity to YTLMC-90 cells through promoting cell proliferation and antagonizing H2O2-induced apoptosis.

[Suppressive effect of brain derived neurotrophic factor on H2O2-induced apoptosis in human lung cancer cell YTMLC-90].

BACKGROUND & OBJECTIVE: It has been shown that neurotrophic factors such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin (NT-3/4) are synthesized in a variety of cells inside and outside the nervous system. These factors are not only able to promote neural survival, proliferation and apoptosis of neural cells but also relevant to the activity of neural invasion of tumors. It has not been reported to date whether BDNF may play roles in the biological behavior of human lung cancer cells. The aim of this experiment was to investigate the effect of BDNF on hydrogen peroxide (H2O2)-induced apoptosis in the human lung cancer cell line YTMLC-90. METHODS: The minigene pSVCEPBFCAT containing the promoter and enhancer elements of the human a1(I) collagen gene(COLIA1) at its 3' terminus followed by hBDNF gene cDNA was transfected and derived BDNF ectopic expression in the human lung cancer cells. The cell proliferation was measured by MTT assay. The morphological and ultra-structural changes of apoptotic cells were observed by microscopy with fluorescent stain of acridine orange and electron microscopy. The DNA fragmentation was examined by agarose gel electrophoresis. RESULTS: After exposure of growing cells to 200 micromol/L H2O2 for 24 hours, the inhibition rate of cell growth was 30% in the pSVCEPBFCAT-transfected YTMLC-90, 84.60% in controls of non-transfected YTMLC-90, and 80.00% in pSVCEPCAT-transfected YTMLC-90, respectively (P< 0.001). The morphological and biochemical changes of apoptotic cells such as shrinkage of cytoplasm and nucleus,fragmentation of the chromatin, and ladder pattern of DNA were commonly observed in the cell population of controls, but these apoptotic features were not discovered in the pSVCEPBFCAT-transfected YTMLC-90. CONCLUSION: BDNF markedly inhibits H2O2 cytotoxicity on human lung cancer cell YTMLC-90 by promoting YTMLC-90 proliferation and antagonizing H2O2-induced apoptosis.