Biology subjects

Hong, P.

Publications and source records attributed to Hong, P..

11 recordsLinked to original sources

bioRxiv2025

Lzp Ablation Ameliorates Dyslipidemia and Suppresses Atherosclerosis by Reducing Circulating Apolipoprotein B-Containing Lipoproteins

As the principal regulator of systemic lipid homeostasis, the liver uniquely orchestrates dietary lipid assimilation, de novo lipogenesis, very-low-density lipoprotein (VLDL) assembly and secretion, and clearance of atherogenic lipoprotein remnants. This central role positions liver-specific molecular targets as critical therapeutic nodes for mitigating hyperlipidemia and halting atherosclerosis progression. The liver-specific protein Lzp (also named as OIT3), previously shown to stabilize apolipoprotein B (ApoB), the core structural component of triglyceride-rich lipoproteins, has an undefined role in vascular disease pathogenesis. Here, utilizing ApoE-/-mice, a well-established model that closely mimics human atherosclerosis, we demonstrate that Lzp deletion reduces plasma cholesterol, triglycerides, and ApoB levels under both chow and Western diets, concomitant with a marked attenuation of aortic plaque burden. Additionally, Lzp deficiency reduces hepatic and circulating ApoB levels in hyperlipidemic ApoE-/- mice, without exacerbating hepatic steatosis or injury. Mechanistically, Lzp ablation is anticipated to impair hepatic VLDL-ApoB secretion based on our previous findings, resulting in reduced circulating VLDL, intermediate density lipoprotein (IDL) and low-density lipoprotein (LDL) particles, attenuated lipid deposition, and suppressed macrophage-driven plaque inflammation. These results underscore the role of Lzp as a key regulator of systemic lipid metabolism and identify it as a potential candidate for further investigation toward therapeutic intervention of atherosclerotic cardiovascular disease. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/678175v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@118ead8org.highwire.dtl.DTLVardef@e215baorg.highwire.dtl.DTLVardef@1007212org.highwire.dtl.DTLVardef@412757_HPS_FORMAT_FIGEXP M_FIG C_FIG HightlightsO_LILzp deficiency attenuates atherosclerosis and improves plasma lipid profiles in ApoE-/- mice fed chow or Western diets. C_LIO_LILzp deficiency reduces hepatic and circulating apolipoprotein B levels in hyperlipidemic ApoE-/- mice without exacerbating hepatic steatosis or injury. C_LIO_LILzp represents a candidate therapeutic target, warranting further mechanistic and translational studies for atherosclerosis. C_LI

pathology↗

bioRxiv2025

Genomic surveillance of Methicillin Resistant Staphylococcus aureus in Saudi Arabia.

Methicillin-resistant Staphylococcus aureus (MRSA) surveillance in regions with mass gatherings presents unique challenges for public health systems. Saudi Arabia, hosting millions of pilgrims annually, provides a distinctive setting for studying how human mobility shapes bacterial populations, yet comprehensive genomic surveillance data from this region remains limited. Here, we present an integrated analysis of S. aureus isolates collected across seven Saudi Arabian regions, combining whole-genome sequencing with extensive antimicrobial susceptibility testing and standardized metadata following FAIR data principles. Our analysis revealed striking differences between pilgrimage and non-pilgrimage cities. Pilgrimage cities showed significantly higher genetic diversity and antimicrobial resistance rates, harboring numerous international strains including recognized clones from diverse geographic origins. Reported lineage dynamics is changing, expanding toward community clones. While genomic prediction of antimicrobial resistance showed high accuracy for some antibiotics, particularly beta-lactams, with varying performance for others, highlighting the necessity for phenotypic testing in clinical settings. Our findings demonstrate how mass gatherings drive bacterial population structures and emphasize the importance of integrated surveillance approaches in regions with significant global connectivity and travel. ImportanceGenomic data enables the tracking of pathogens by revealing clonal expansions within populations and identifying successful lineages. However, comprehensive national-level data from Saudi Arabia remains limited on a large scale. The adoption of FAIR principles and reproducible workflows ensures robust, consistent analysis, fostering effective data sharing. The OneHealth approachs success depends on the integration and collaboration across diverse domains in todays digital landscape.

genomics↗

bioRxiv2024

A temperature-sensitive and interferon-silent Sendai virus vector for CRISPR-Cas9 delivery and gene editing in primary human cells

The transformative potential of gene editing technologies hinges on the development of safe and effective delivery methods. In this study, we developed a temperature-sensitive and interferon-silent Sendai virus (ts SeV) as a novel delivery vector for CRISPR-Cas9 and for efficient gene editing in sensitive human cell types without inducing IFN responses. ts SeV demonstrates unprecedented transduction efficiency in human CD34+ hematopoietic stem and progenitor cells (HSPCs) including transduction of the CD34+/CD38-/CD45RA-/CD90+(Thy1+)/CD49fhigh stem cell enriched subpopulation. The frequency of CCR5 editing exceeded 90% and bi-allelic CCR5 editing exceeded 70% resulting in significant inhibition of HIV-1 infection in primary human CD14+ monocytes. These results demonstrate the potential of the ts SeV platform as a safe, efficient, and flexible addition to the current gene-editing tool delivery methods, which may help to further expand the possibilities in personalized medicine and the treatment of genetic disorders.

microbiology↗

bioRxiv2021

Applications of AlphaFold beyond Protein Structure Prediction

Predicting structures accurately for natural protein sequences by DeepMinds AlphaFold is certainly one of the greatest breakthroughs in biology in the twenty-first century. For designed or engineered sequences, which can be unstable, predicting the stabilities together with their structures is essential since unstable structures will not function properly. We found that experimentally measured stability changes of point mutations correlate poorly with the confidence scores produced by AlphaFold. However, the stability changes can be accurately predicted using features extracted from the representations learned by AlphaFold, indicating greater generalizability of AlphaFold to designed or engineered sequences than previously thought. We then used AlphaFold to validate our previously developed protein design method, ProDCoNN, that designs sequences to fold to target protein structures given only the backbone structure information of the target proteins. We showed that ProDCoNN was able to design sequences that fold to structures very close to target structures. By combining a modified ProDCoNN, AlphaFold, and sequential Monte Carlo, we designed a novel framework to estimate the designability of protein structures. The designability of a protein structure is defined as the number of sequences, which encode the protein structure, and is an indicator of the functional robustness of proteins. For the first time, we estimated the designability of a real protein structure, chain A of FLT3 ligand (PDB ID: 1ETE) with 134 residues, as 3.12{+/-}2.14E85.

bioinformatics↗

bioRxiv2020

Network-based Virus-Host Interaction Prediction with Application to SARS-CoV-2

COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has quickly become a global health crisis since the first report of infection in December of 2019. However, the infection spectrum of SARS-CoV-2 and its comprehensive protein-level interactions with hosts remain unclear. There is a massive amount of under-utilized data and knowledge about RNA viruses highly relevant to SARS-CoV-2 and their hosts proteins. More in-depth and more comprehensive analyses of that knowledge and data can shed new insight into the molecular mechanisms underlying the COVID-19 pandemic and reveal potential risks. In this work, we constructed a multi-layer virus-host interaction network to incorporate these data and knowledge. A machine learning-based method, termed Infection Mechanism and Spectrum Prediction (IMSP), was developed to predict virus-host interactions at both protein and organism levels. Our approach revealed five potential infection targets of SARS-CoV-2, which deserved public health attention, and eight highly possible interactions between SARS-CoV-2 proteins and human proteins. Given a new virus, IMSP can utilize existing knowledge and data about other highly relevant viruses to predict multi-scale interactions between the new virus and potential hosts.

bioinformatics↗

bioRxiv2020

UV and bacteriophages as a chemical-free approach for cleaning membranes from anaerobic bioreactors

Anaerobic membrane bioreactor (AnMBR) for wastewater treatment has attracted much interest due to its efficacy in providing high quality effluent with minimal energy costs. However, membrane biofouling represents the main bottleneck for AnMBR because it diminishes flux and necessitates frequent replacement of membranes. In this study, we assessed the feasibility of combining bacteriophages and UV-C irradiation to provide a chemical-free approach to remove biofoulants on the membrane. The combination of bacteriophage and UV-C resulted in better log cells removal and twice higher extracellular polymeric substance (EPS) concentration reduction in mature biofoulants compared to UV-C. A reduction in the relative abundance of Acinetobacter spp. and selected gram-positive bacteria associated with the membrane biofilm was also achieved by the new cleaning approach. Microscopic analysis further revealed the formation of cavities in the biofilm due to bacteriophages and UV-C irradiation, which would be beneficial to maintain water flux through the membrane. When the combined treatment was further compared with the common chemical cleaning procedure, a similar reduction on the cell numbers was observed (1.4 log). However, combined treatment was less effective in removing EPS compared with chemical cleaning. These results suggest that the combination of UV-C and bacteriophage have an additive effect in biofouling reduction, representing a potential chemical-free method to remove reversible biofoulants on membrane fitted in an anaerobic membrane bioreactor. SIGNIFICANCEAnaerobic membrane bioreactors can achieve high quality effluent with a reduced energy consumption. However, biofouling represents the main bottleneck for membrane filtration efficiency. Biofouling is commonly reduced through chemical treatment. These agents are often detrimental for the environment and health safety due to the formation of toxic byproducts. Therefore, we present a new approach, based on the additive antifouling action of bacteriophages infection and UV-C irradiation, to reduce anaerobic membrane biofouling. This new strategy could potentially delay the occurrence of membrane fouling by removing the reversible fouling layers on membranes, in turn reducing the frequencies and amount of chemicals needed throughout the course of wastewater treatment.

microbiology↗

bioRxiv2020

Genome-wide transposon mutagenesis of paramyxoviruses reveals constraints on genomic plasticity: implications for vaccine and gene therapy

The antigenic and genomic stability of paramyxoviruses remains a mystery. Here, we evaluate the genetic plasticity of Sendai virus (SeV) and mumps virus (MuV), sialic acid-using paramyxoviruses that infect mammals from two Paramyxoviridae subfamilies (Orthoparamyxovirinae and Rubulavirinae). We performed saturating whole-genome transposon insertional mutagenesis, and identified important commonalities: disordered regions in the N and P genes near the 3 genomic end were more tolerant to insertional disruptions; but the envelope glycoproteins were not, highlighting structural constraints that contribute to the restricted antigenic drift in paramyxoviruses. Nonetheless, when we applied our strategy to a fusion-defective Newcastle disease virus (Avulavirinae subfamily), we could select for F-revertants and other insertants in the 5 end of the genome. Our genome-wide interrogation of representative paramyxovirus genomes from all three Paramyxoviridae subfamilies provides a family-wide context in which to explore specific variations within and among paramyxovirus genera and species.

microbiology↗

bioRxiv2019

DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

BackgroundIt is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (Chromosome Conformation Capture) and its derived methods are now widely applied to investigate genome organizations and gene regulation. Digestion-Ligation-Only Hi-C (DLO Hi-C) is a new technology with high efficiency and effective cost for whole-genome chromosome conformation capture.\n\nResultsHere, we introduce DLO Hi-C Tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied DLO Hi-C Tool to different DLO Hi-C datasets, and demonstrated its ability of processing large data in multi-threading.\n\nConclusionsDLO Hi-C Tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

bioinformatics↗

bioRxiv2019

Chromatin interaction analysis with updated ChIA-PET Tool (V3)

Understanding chromatin interactions is important since they create chromosome conformation and link the cis- and trans-regulatory elements to their target genes for transcriptional regulation. Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing is a genome-wide high-throughput technology that detects chromatin interactions associated with a specific protein of interest. Previously we developed ChIA-PET Tool in 2010 for ChIA-PET data analysis. Here we present the updated version of ChIA-PET Tool (V3), is a computational package to process the next-generation sequence data generated from ChIA-PET experiments. It processes the short-read data and long-read ChIA-PET data with multithreading and generates the statistics of results in a HTML file. In this paper, we provide a detailed demonstration of the design of ChIA-PET Tool V3 and how to install it and analyze a specific ChIA-PET data set with it. At present, other ChIA-PET data analysis tools have developed including ChiaSig, MICC, Mango and ChIA-PET2 and so on. We compared our tool with other tools using the same public data set in the same machine. Most of peaks detected by ChIA-PET Tool V3 overlap with those from other tools. There is higher enrichment for significant chromatin interactions of ChIA-PET Tool V3 in APA plot. ChIA-PET Tool V3 is open source and is available at GitHub (https://github.com/GuoliangLi-HZAU/ChIA-PET_Tool_V3/).

genomics↗

bioRxiv2019

CoolBox: a interactive genomic data explorer for Jupyter Notebook

SummaryCoolBox is a Python package for interactive genomic data exploration based on Jupyter notebook. It provides a ggplot2-like Application Programming Interface (API) for genomic data visualization, and a Jupyter/ipywidgets based Graphical User Interface (GUI) for interactive data exploration. CoolBox is a versatile multi-omics explorer supporting most types of data formats generated by various sequencing technologies like RNA-Seq, ChIP-Seq, ChIA-PET and Hi-C.\n\nAvailability and implementationCoolBox is purely implemented with Python, and the GUI widget in Jupyter notebook is based on the ipywidgets package. It is open-source and available under GPLv3 license at https://github.com/GangCaoLab/CoolBox.

bioinformatics↗

bioRxiv2018

Synthesis of three major auxins from glucose in Engineered Escherichia coli

Indole-3-acetic acid (IAA) is considered the most common and important naturally occurring auxin in plants and a major regulator of plant growth and development. In addition, phenylacetic acid (PAA) and 4-hydroxyphenylacetic acid (4HPA) can also play a role as auxin in some plants. In recent years, several microbes have been metabolically engineered to produce IAA from L-tryptophan. In this study, we showed that aminotransferase aro8 and decarboxylase kdc from Saccharomyces cerevisiae, and aldehyde dehydrogenase aldH from Escherichia coli have broad substrate ranges and can catalyze the conversion of three kinds of aromatic amino acids (L-tryptophan, L-tyrosine or L-phenylalanine) to the corresponding IAA, 4HPA and PAA. Subsequently, three de novo biosynthetic pathways for the production of IAA, PAA and 4HPA from glucose were constructed in E. coli through strengthening the shikimate pathway. This study described here shows the way for the development of agricultural microorganism for biosynthesis of plant auxin and promoting plant growth in the future.

bioengineering↗