Biology subjects

Gu, H.

Publications and source records attributed to Gu, H..

At least 73 records · Page 4Linked to original sources

bioRxiv2023

Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood

Polybrominated diphenyl ethers (PBDEs) are a class of legacy flame retardants that bioaccumulate in the environment, raising global health concerns. The gut microbiome is an important regulator of liver including xenobiotic biotransformation, nutrient homeostasis, and immune regulation. Using bulk RNA-Seq, we recently showed that neonatal exposure to BDE-99, a human breast milk-enriched PBDE congener, up-regulated pro-inflammation- and down-regulated drug metabolism-related genes predominantly in males in young adulthood. However, it remains unknown whether such dysregulation persists into late adulthood, how various cell types in the liver contribute to the hepatotoxicity, and to what extent gut microbiome is involved in BDE-99 mediated developmental reprogramming of the liver. To address these knowledge gaps, male C57BL/6 mouse pups were orally exposed to corn oil (10 ml/kg) or BDE-99 (57 mg/kg) once daily from postnatal days 2-4. At 15 months of age, single cell transcriptomics (scRNA-seq) in liver showed that neonatal BDE-99 exposure down-regulated key xenobiotic- and fatty acid metabolizing enzymes and up-regulated genes involved in microbial influx in hepatocytes. Neonatal BDE-99 exposure also led to a persistent increase in the hepatic proportion of neutrophils, a predicted increase of macrophage migration inhibitory factor (MIF) signaling, which activates macrophage populations, as well as histopathological abnormalities of the liver in 15 months of age. The BDE-99 mediated hepatic reprogramming is associated with decreased intestinal tight junction protein (Tjp) transcripts, persistent dysbiosis of the gut microbiome, and dysregulation of inflammation-related fatty acid metabolites. ScRNA-seq in germ-free (GF) mice demonstrated the necessity of a normal gut microbiome in maintaining hepatic immunotolerance. Fecal microbiome transplant to GF mice using large intestinal microbiome from adults that were neonatally exposed to BDE-99 down-regulated Tjp transcripts and up-regulated several cytokines in the large intestine. In conclusion, neonatal BDE-99 exposure reprogrammed the cell type-specific gene expression and cell-cell communication networks in liver towards a pro-inflammation with compromised metabolic functions at late adulthood. Importantly, gut microbiome is necessary in promoting immunotolerance in the liver, and BDE-99-mediated pro-inflammatory signaling may be partly due to the dysregulated gut environment.

pharmacology and toxicology↗

bioRxiv2023

In Vivo Tissue Distribution of Microplastics and Systemic Metabolomic Alterations After Gastrointestinal Exposure

Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored. To investigate the impact of ingested MPs on target metabolomic pathways, mice were subjected to either polystyrene microspheres or a mixed plastics (5 {micro}m) exposure consisting of polystyrene, polyethylene and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid). Exposures were performed twice a week for four weeks at a dose of either 0, 2, or 4 mg/week via oral gastric gavage. Our findings demonstrate that, in mice, ingested MPs can pass through the gut barrier, be translocated through the systemic circulation, and accumulate in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolomic changes that occur in the colon, liver and brain which show differential responses that are dependent on dose and type of MPs exposure. Lastly, our study provides proof of concept for identifying metabolomic alterations associated with MPs exposure and adds insight into the potential health risks that mixed MPs contamination may pose to humans.

pharmacology and toxicology↗

bioRxiv2023

A data-fusion approach to identifying developmental dyslexia from multi-omics datasets

This exploratory study tested and validated the use of data fusion and machine learning techniques to probe high-throughput omics and clinical data with a goal of exploring the etiology of developmental dyslexia. Developmental dyslexia is the leading learning disability in school aged children affecting roughly 5-10% of the US population. The complex biological and neurological phenotype of this life altering disability complicates its diagnosis. Phenome, exome, and metabolome data was collected allowing us to fully explore this system from a behavioral, cellular, and molecular point of view. This study provides a proof of concept showing that data fusion and ensemble learning techniques can outperform traditional machine learning techniques when provided small and complex multi-omics and clinical datasets. Heterogenous stacking classifiers consisting of single-omic experts/models achieved an accuracy of 86%, F1 score of 0.89, and AUC value of 0.83. Ensemble methods also provided a ranked list of important features that suggests exome single nucleotide polymorphisms found in the thalamus and cerebellum could be potential biomarkers for developmental dyslexia and heavily influenced the classification of DD within our machine learning models.

bioinformatics↗

bioRxiv2023

Proliferating cell nuclear antigen involves in temperature stress tolerance of Ulva prolifera

Ulva prolifera is the dominant species of "green tide", and has higher tolerance to environmental stresses such as temperature. However, the molecular mechanisms are still unclear. Here, transcriptome analysis, Western blot and RT-qPCR analysis of U. prolifera suggested that, under temperature stresses (4{degrees}C, 36{degrees}C), the expression of PCNA and CyclinA was promoted, and the MAPK signaling was activated. Besides, the results showed that PCNA interacted with CyclinA. Interestingly, the expression of miR-2916, which was predicted to bind PCNA at -552[~]-772, was negatively correlated with the expression of PCNA under temperature stresses (4{degrees}C, 36{degrees}C). In addition, the results showed that low temperature (4{degrees}C) had no obvious effect on the survival, the formation of cell walls, and the division of protoplasts. However, high temperature (36{degrees}C) had obvious effect on them. PCNA inhibitors increased the sensitivity of the protoplasts under temperature stresses. Together, our results suggested PCNA regulating the proliferation in response to the temperature stress of U. prolifera was associated with miR-2916/PCNA/CyclinA/MAPK pathway. In conclusion, the study preliminarily illuminates the molecular mechanism in response to temperature stress of U. prolifera, and may provide a new insight for prevention of green tide.

cell biology↗

bioRxiv2023

Redefinition of archetypal phytoplankton-associated bacteria taxa based on globally distributed dinoflagellates and diatoms

Bacteria colonizing in the phycosphere formed by phytoplankton exudates play important roles in marine ecosystems, yet their taxonomy is poorly defined. Here, we customized the analytical approaches for the microalga-attached microbiotas from 110 diatom and 86 dinoflagellate samples to reveal key bacterial players and their ecological significance in the phycosphere. The results demonstrated a co-occurrence of host-specificity and conservation of phytoplankton-associated bacterial communities, defined 8 diatom- and 23 dinoflagellate-affiliated characteristic genera, as well as identifying 14 core genera prevalent with phytoplankton populations. Further classification of these 14 core genera into three tiers showed their distinct ecological features regarding occupancy, connectivity and community-stabilizing, whilst also matching their inherent metabolic properties. Our study redefines the archetypal phytoplankton-associated bacteria taxa more specifically up to the genus level, highlighting the significance of rarely noticed bacteria in the phycosphere, which is invaluable when selecting target bacteria for studying phytoplankton-bacteria interactions.

microbiology↗

bioRxiv2023

High frequency soil polarization can phenotype crop roots noninvasively

Noninvasive and nondestructive root phenotyping techniques under field conditions are sorely needed to advance plant root science. Soil polarization measured by electrical capacitance (ECsoil) has the potential to meet this requirement, but whether it specifically detects root properties remains unexplored. We carried out manipulative experiments where wheat (Triticum aestivum L.) and maize (Zea mays L.) roots were buried in soil or immersed in hydroponic solution combined with pot trials to reveal the mechanism of root trait detection by ECsoil, while a field experiment was conducted to test its feasibility to determine root depth distribution. We found that ECsoil measured at low current frequency (< 1 kHz) was not significantly affected by the addition of roots to the system either by burying roots in soil or immersing them in solution. At frequency greater than10 kHz a shift occurred, and root polarization contributed more to ECsoil which was positively correlated with root volume. When ECsoil was measured at high frequency (30 kHz -100 kHz) it was well correlated with root volume vertical distribution in the field. The measurement error after soil moisture calibration at depths of 10 cm, 20 cm, 30 cm and 40 cm was 0.4%, 12.0%, 1% and 34%, respectively. Our results demonstrate that ECsoil is a robust method to measure in situ root distribution and we believe the newly available high frequency measurement equipment combined with novel root prediction models will enable ECsoil to be widely used for root phenotyping in the future.

plant biology↗

bioRxiv2022

Enhanced mTORC1 signaling and Protein Synthesis in Parkinson Disease Pathogenesis

Pathologic -syn destabilizes the TSC 1 and 2 complex leading to mTORC1 activation, enhanced protein translation and neurodegeneration in PD. AbstractPathological -synuclein (-syn) plays an important role in the pathogenesis of -synucleinopathies such as Parkinsons disease (PD). Disruption of protein homeostasis is thought be central to PD pathogenesis, however the molecular mechanism of this deregulation is poorly understood. Here we report that pathologic -syn binds to tuberous sclerosis protein (TSC) 2 and destabilizes the TSC1-TSC2 complex leading to activation of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and enhanced mRNA translation. Dopamine neuron loss, behavioral deficits and aberrant biochemical signaling in the -syn preformed fibril (PFF) and Drosophila -syn transgenic models of pathologic -syn induced degeneration were attenuated by genetic and pharmacologic inhibition of mTOR and protein translation. Our findings establish a potential molecular mechanism by which pathologic -syn activates mTORC1 leading to enhanced protein translation and concomitant neurodegeneration in PD.

neuroscience↗

bioRxiv2022

Boreal Forest Height Mapping using Sentinel-1 Time Series and improved LSTM model

Here, a novel semi-supervised Long Short-Term Memory (LSTM) model is developed and demonstrated for predicting forest tree height using time series of Sentinel-1 images. The model uses a Helix-Elapse (HE) projection approach to capture relationship between forest temporal patterns and Sentinel-1 time series, when the acquisition time intervals are irregular. A skip-link based LSTM block is introduced and a novel backbone network, Helix-LSTM, is proposed to retrieve temporal features at different receptive scales. Additionally, a novel semi-supervised strategy, Cross-Pseudo Regression, is employed to achieve better model performance. The developed model is compared versus basic LSTM model, attention-based bidirectional LSTM and several other established regression approaches used in forest variable mapping, demonstrating consistent improvement of forest height prediction accuracy. The study site is located in Central Finland and represents boreal forestland. At best, the achieved accuracy of forest height mapping was 28.3% rRMSE for pixel-level predictions, and 18.0% rRMSE on stand level. We expect that the developed model can also be used for modeling relationships between other forest variables and satellite image time series.

ecology↗

bioRxiv2022

Reduced stroke outcome in old-aged female mice maintained on a dietary vitamin B12 deficiency

The global population is aging and the prevalence of age-related diseases, such as stroke, is predicted to increase. A vitamin B12 deficiency (vit. B12 def.) is common in the elderly, because of changes in metabolism. Clinical studies have reported that a vit. B12 def results in worse outcome after stroke, the mechanisms through which a vit. B12 def. changes the brain requires further investigation. This study investigated the role of vit. B12 def. on stroke outcome and mechanisms using aged female mice. Eighteen month old females were put on a control or vit. B12 def. diet for four weeks, after which an ischemic stroke was induced in the sensorimotor cortex. After damage, motor function was measured and animals were euthanized and tissues were collected for analysis. Vit. B12 def. animals had increased levels of total homocysteine in plasma and liver, choline levels were also increased in the liver. Vit. B12 def. animals had larger damage volume in brain tissue and more apoptosis. In the cecum, changes in creatinine and methylmalonic acid were observed in vit. B12 def. animals, pathway analysis showed dysfunction in B12 transport. Analysis of mitochondrial metabolomics in brain tissue showed reduced levels of metabolites involved in the TCA cycle in vit. B12 def animals. Meanwhile, pathway analysis showed significant, widespread dysfunction in phenylalanine, tyrosine, and tryptophan biosynthesis. Motor function after stroke was impaired in vit. B12 def. animals. A dietary vitamin B12 deficiency impairs motor function through increased apoptosis and changes in mitochondrial metabolism in brain tissue.

physiology↗

bioRxiv2022

Genomic analyses identify biological processes and functions between M1 and M2 macrophages

Macrophages can be induced by a variety of factors to change their phenotype and functions. M1 and M2 macrophages play converse roles during inflammation or other diseases. However, the mechanism and function of M1 and M2 macrophages are still not clear. This study aims to identify the different molecules and functions by analyzing the RNA-seq data. The GSE189354 was created by the Illumina HiSeq 4000 (Mus musculus). The KEGG and GO analyses indicated the Phagosome and Hematopoietic cell lineage are the major biological processes between M1 and M2 macrophages. Moreover, we further identified ten molecules including Il6, Il1b, Tlr2, Myc, Fn1, Itgax, Cxcl10, Ccl5, Cxcr4, and Pparg. Therefore, our study may provide novel knowledge of innate immunity.

bioinformatics↗

bioRxiv2022

Identification of biological processes and signaling pathways in lactate-treated cancer cells

Cancer is a complex disease that involves the alterations of metabolic pathways and tumor microenvironment. Lactate in the tumor microenvironment leads to cancer proliferation, metastasis, and angiogenesis. However, the effect of lactate on prostate cancer cells is still unclear. Here, our objective is to identify the significant molecules and biological processes by analyzing the RNA-seq data. The GSE195639 was produced by the Illumina NextSeq 500 (Homo sapiens). The KEGG and GO analyses show that Herpes simplex virus 1 infection and Rap1 signaling pathway are considered major pathways during the lactate-treated cancer cells. Furthermore, we identified the top ten essential molecules including IL6, CASP3, JUN, MAPK3, BRCA1, PIK3R1, CCNA2, TPI1, APOE, and EXO1. Therefore, our study may provide novel insights into the mechanism of prostate cancers.

bioinformatics↗

bioRxiv2022

Identification of significant molecules and signaling pathways between 2D and 3D culture methods of renal cancer cells

The majority of cancer studies are conducted with the two-dimensional (2D) culture method, which does not reflect tumor in vivo structure. The 3D culture method can form free bundles of cancer cells and spheroid, which mimics the tumor microenvironment in vivo. However, the molecules and signaling pathways between the 2D and 3D culture methods are still unknown. In this study, we aim to identify the key molecules and signaling pathways by analyzing the RNA-seq data. The GSE190296 was created by the BGISEQ-500 (Homo sapiens). The KEGG and GO analyses indicated sulfur compound metabolic process and regulation of leukocyte mediated immunity are the major differences between 2D and 3D renal cancer cell cultures. Moreover, we figured out several interactive genes including MYC, EGF, VEGFA, STAT3, NOTCH1, CAT, CCND1, HSPA8, DLG4, and HSPA5. Our study may provide new knowledge on the differences between 2D and 3D cancer cell cultures.

bioinformatics↗

bioRxiv2022

Genomic analyses identify key molecules and significant signaling pathways in AZIN1 regulated prostate cancer cells

Antizyme inhibitor 1 (AZIN1) is a critical target in prostate cancer, which regulates the adenosine-to-inosine (A to I) RNA editing during the cancer progression. However, the potential signaling pathways and functions remain unknown. Here, our objective is to figure out the functional molecules and signaling pathways by analyzing the RNA-seq data. The GSE189379 was produced by the Illumina HiSeq 2000 (Homo sapiens). The KEGG and GO analyses showed that focal adhesion and proteoglycans are the mainly affected processes in prostate cancer with the loss of AZIN1. Moreover, we identified ten key molecules including FN1, HRAS, CCND1, RAD51, PCNA, TYMS, CASP3, RRM2, BIRC5, and CCNE2. Therefore, this study provides novel knowledge of AZIN1 mediated prostate cancer.

bioinformatics↗

bioRxiv2022

Genomic analyses identify significant molecules and biological processes in colorectal cancer cells with DNA damage

Colorectal cancer is a major cause of cancer deaths in the US. DNA damage is considered to be a novel target for the treatment of colorectal cancer. However, the molecular mechanisms and functions are still unclear. In this study, we aim to identify the significant molecules and signaling by analyzing the RNA-seq data. The GSE189366 was created by the BGISEQ-500 (Homo sapiens). The KEGG and GO analyses indicated the p53 signaling pathway and Hippo signaling pathway are major affected processes in colorectal cancer by DNA damage. Furthermore, we identified ten key interactive molecules including CDK1, STAT3, MDM2, CCNB1, CCNA2, CDKN1A, PCNA, AURKA, PLK1, and CDC6. Our study may provide potential drug targets for colorectal cancer.

bioinformatics↗

bioRxiv2022

Genomic analyses identify biological processes in ZKSCAN3-deficient colorectal cancer cells

Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) is associated with cell differentiation, cell proliferation and apoptosis, which has been reported as a critical driver of colorectal cancer. However, the mechanism and function of ZKSCAN3 in colorectal cancer is still unclear. Here, our objective is to identify the functional molecules and signaling by analyzing the RNA-seq data. The GSE172201 was created by the Illumina NovaSeq 6000 (Homo sapiens). The KEGG and GO analyses indicated the immune defense response to virus and transcription activity are major processes in the ZKSCAN3 KO colorectal cancer cells. Moreover, we determined ten key molecules including STAT1, MX1, DDX58, PPARG, EGFR, APP, BST2, DLG4, OASL, and IFIT2. Therefore, our study may provide the novel knowledge of ZKSCAN3 mediated colorectal cancer.

bioinformatics↗

bioRxiv2021

Identification of critical genes and biological signaling for metformin treated liver cancer

Liver cancer is a leading source of cancer-related mortality in the world. A number of studies have shown the correlation of metformin treatment with a decrease in cancer risk. However, the relevant molecules and mechanisms are not clear during the treatment. In this study, our aim is to identify the significant molecules and signaling pathways in the treatment of metformin in liver cancer cells by analyzing the RNA sequence. The GSE190076 dataset was created by performing the Illumina NovaSeq 6000 (Homo sapiens). The KEGG and GO analyses indicated that DNA synthesis and cell cycle are the main processes during the treatment of metformin. Moreover, we determined numerous genes including RRM2, CDC6, CDC45, UHRF1, ASF1B, ZWINT, PCNA, ASPM, MYC, and TK1 by using the PPI network. Therefore, our study may guide the clinical work on the treatment of liver cancer by using metformin.

bioinformatics↗

bioRxiv2021

Identification of biological processes and signaling pathways in the stretched nucleus pulposus cells

Low back pain is mostly caused by disc degeneration, which is due to the alterations in the osmotic pressure of nucleus pulposus cells. However, the knowledge about the mechanism and therapies for disc degeneration is not fully understood. Here, our objective is to identify significantly changed genes and biological processes in the stretched nucleus pulposus cells. The GSE175710 dataset was originally produced by using the Illumina HiSeq 4000 (Rattus norvegicus). The KEGG and GO analyses indicated that "MAPK signaling", "TNF signaling", "IL17 signaling", and the "NF-{kappa}B signaling pathway" are mostly affected in the stretched nucleus pulposus cells. Moreover, we identified several genes according to the PPI network such as Mmp9, Cxcl12, Col1a1, and Col3a1 in the stretched nucleus pulposus cells. Thus, our study provides further insights into the study of disc deterioration.

bioinformatics↗

bioRxiv2021

Identification of biological processes and signaling pathways for the knockout of REV-ERB in mouse brain

REV-ERB is an orphan nuclear receptor that is widely expressed in the brain and inhibits transcriptional activities. A variety of genes affect the activity and expression of REV-ERB. In this study, our objective is to identify significant signaling pathways and biological processes in the knockout of the REV-ERB mouse brain. The GSE152919 dataset was originally created by using the Illumina HiSeq 4000 (Mus musculus). The KEGG and GO analyses suggested that biological processes "PPAR signaling", "Hippo signaling", and "Hypertrophic cardiomyopathy (HCM)" are mostly affected in the knockout of REV-ERB. Furthermore, we identified a number of genes according to the PPI network including NPAS2, CRY2, BMAL1, and CRY1 which were involved in the lack of REV-ERB in the brain. Therefore, our study provides further insights into the study of circadian clocks.

bioinformatics↗