Biology subjects

Zong, Y.

Publications and source records attributed to Zong, Y..

26 records · Page 2Linked to original sources

bioRxiv2021

An Attempt to Develop an Aptamer Lateral-Flow Assay (ALFA) for Easy, Rapid, and Sensitive Detection of Lethal Mushroom Toxin α-amanitin

Amatoxins contribute to the majority of mushroom poisoning, most prominently, -amanitin. Since mushroom is a common foodstuff worldwide, an easy, rapid, sensitive test for -amanitin is needed. Several detection methods for -amanitin have been developed, including HPLC, LC-MS, and ELISA, and LFIA. Aptamers have several advantages compared to antibodies: easy development via SELEX, longer shelf life, and higher temperature- and pH-tolerance. Aptamer Lateral Flow Assay (ALFA) is a similar technology compared to LFIA but incorporates aptamers as target-recognizing agents. This study attempted to develop an ALFA test strip for -amanitin using a previously-developed aptamer, however failure of generating a colorimetric readout at the test line is persisted throughout all experiments, even though the concept is fully-proved and the control line functions normally. The failure is attributed to the small size of the molecule, leading to immobilization difficulties on the nitrocellulose membrane to form the test line, and the hindering of effective "surround" mechanism of aptamer-target binding (instead of "adhere", when the target molecule is large, e.g. a protein). It is concluded that ALFAs for small-molecules whose aptamer-target interaction has not yet been studied and modelled in detail remains a challenge, despite ALFAs large potential.

molecular biology↗

bioRxiv2021

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

The oral microbiota contains billions of microbial cells, which could contribute to diseases in a number of body sites. Challenged by eating, drinking and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1,915 individuals, for both the tongue dorsum and saliva. We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 x 10-11). Four of the five associations were well replicated in an independent cohort of 1,439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of genetic-microbiota associations including 6 genome-wide significant associations mutually validated between the two niches. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk score dominated over oral microbiome in predicting predisposing risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

genetics↗

bioRxiv2020

The dynamic landscape of parasitaemia dependent intestinal microbiota shifting at species level and the correlated gut transcriptome during Plasmodium yoelii infection

BackgroundMalaria, caused by Plasmodium, is a global life-threatening infection disease especially during the COVID-19 pandemic. However, it is still unclear about the dynamic change and the interactions between intestinal microbiota and host immunity. Here, we investigated the change of intestinal microbiome and transcriptome during the whole Plasmodium infection process in mice to analyze the dynamic landscape of parasitaemia dependent intestinal microbiota shifting and related to host immunity. ResultsThere were significant parasitaemia dependent changes of intestinal microbiota and transcriptome, and the microbiota was significantly correlated to the intestinal immunity. We found that (i) the diversity and composition of the intestinal microbiota represented a significant correlation along with the Plasmodium infection in family, genus and species level; (ii) the up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways along with the malaria development, particularly, naive CD4+ T cells differentiation; (iii) the abundance of the parasitaemia phase-specific microbiota represented a high correlation with the phase-specific immune cells development, particularly, Th1 cell with family Bacteroidales BS11 gut group, genera Prevotella 9, Ruminococcaceae UCG 008, Moryella and specie Sutterella*, Th2 cell with specie Sutterella*, Th17 cell with family Peptococcaceae, genus Lachnospiraceae FCS020 group and spices Ruminococcus 1*, Ruminococcus UGG 014* and Eubacterium plexicaudatum ASF492, Tfh and B cell with genera Moryella and species Erysipelotrichaceae bacterium canine oral taxon 255. ConclusionThere was a remarkable dynamic landscape of the parasitaemia dependent shifting of intestinal microbiota and immunity, and a notable correlation between the abundance of intestinal microbiota.

immunology↗

bioRxiv2020

Using Engineered Escherichia coli to Synthesize Squalene with Optimized Manipulation of Squalene Synthase and Mevalonate Pathway

Squalene is the metabolic precursor of sterols and naturally synthesized in the deep-dea shark liver and human sebum. The utilization of squalene is wide such as food, cosmetical, and pharmaceutical industries. This experiment used engineered Escherichia coli to construct the gene circuit for the biosynthesis of squalene. Human squalene synthase (hSQS) efficiently catalyzes the synthesis of squalene. Also, mevalonate (MVA) pathway would increase the yield of the precursor of squalene, farnesyl diphosphate, which then increased the yield of squalene. Meanwhile, the regulation of MVA pathway via different inducer IPTG concentrations and creation of selection pressure by antibiotics were investigated.

synthetic biology↗

bioRxiv2020

A novel design of transcriptional factor-mediated dynamic control of DNA recombination.

Genetic regulation is achieved by monitoring multiple levels of gene expression, from transcription to protein interaction. Unlike common temporary transcriptional regulation methods such as the use of inducible promoters, integrases permanently edit DNA sequences. Integrases, however, require especially strict regulation when implemented in synthetic genetic systems because of the irreversible result. Here we propose to improve the regulation of site-specific integrase-based genetic system by dynamically hiding one of the attB/P sites that are essential for recombination with transcriptional factors. After effectively suppressing excessive recombination, we also validated the necessity of each of the essential components in our transcriptional factor-controlled recombination (TFCR) system. The system applied transcriptional-level regulators directly on controlling the activity of existing non-transcriptional-level trans-factor proteins by inhibiting its binding to the cis-regulatory elements. We anticipate my results to provide greater robustness for integrase components to enable safer use in systems as well as be a starting point for future cross-expression level gene regulations.

synthetic biology↗

bioRxiv2020

SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.

microbiology↗

bioRxiv2020

Inter-determination of blood metabolite levels and gut microbiome supported by Mendelian randomization

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization (MR) analyses on 3,432 Chinese individuals with whole genome, whole metagenome, anthropometric, and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate, and selenium. Two-sample MR with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.

genetics↗

bioRxiv2019

M-GWAS for the gut microbiome in Chinese adults illuminates on complex diseases

The gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no less than 20% genetic contribution to the gut microbiota. Using common variants-, rare variants- and copy number variations (CNVs)-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top 2 loci explaining 11% of the Prevotella-Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Genetically encoded responses to ectopic presence of oral bacteria in the gut appear to be a common theme in a number of diseases investigated by MWAS (Metagenome-wide association studies). Our two-stage M-GWAS (Microbiome genome-wide association studies) on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.\n\nHighlightsM-GWAS using high-depth whole genome identifies contributions from rare variants and CNVs.\n\nGut microbial modules such as butyrate, amino acids, mucin degradation show genetic associations.\n\nGender differential M-GWAS underscores differences in metabolic and psychological predispositions.\n\nSome of the MWAS markers for colorectal cancer and cardiometabolic diseases show genetic associations.

genetics↗