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Yin, D.

Publications and source records attributed to Yin, D..

At least 37 records · Page 2Linked to original sources

Vulture: Cloud-enabled scalable mining of microbial reads in public scRNA-seq data

The rapidly growing collection of public single-cell sequencing data have become a valuable resource for molecular, cellular and microbial discovery. Previous studies mostly overlooked detecting pathogens in human single-cell sequencing data. Moreover, existing bioinformatics tools lack the scalability to deal with big public data. We introduce Vulture, a scalable cloud-based pipeline that performs microbial calling for single-cell RNA sequencing (scRNA-seq) data, enabling meta-analysis of host-microbial studies from the public domain. In our scalability benchmarking experiments, Vulture can outperform the state-of-the-art cloud-based pipeline Cumulus with a 40% and 80% reduction of runtime and cost, respectively. Furthermore, Vulture is 2-10 times faster than PathogenTrack and Venus, while generating comparable results. We applied Vulture to two COVID-19, three hepatocellular carcinoma (HCC), and two gastric cancer human patient cohorts with public sequencing reads data from scRNA-seq experiments and discovered cell-type specific enrichment of SARS-CoV2, hepatitis B virus (HBV), and H. pylori positive cells, respectively. In the HCC analysis, all cohorts showed hepatocyte-only enrichment of HBV, with cell subtype-associated HBV enrichment based on inferred copy number variations. In summary, Vulture presents a scalable and economical framework to mine unknown host-microbial interactions from large-scale public scRNA-seq data. Vulture is available via an open-source license at https://github.com/holab-hku/Vulture.

bioinformatics↗

A novel triptolide analog downregulates NF-κB and induces mitochondrial apoptosis pathways in human pancreatic cancer

BackgroundPancreatic cancer is the seventh leading cause of cancer-related death worldwide, and despite advancements in disease management, the 5-year survival rates stands at only 9%. Triptolides have potent anti-tumor activity against different types of cancers, including pancreatic cancer, however poor solubility and toxicity limit their translation into clinical use. MethodsWe synthesized a novel pro-drug of triptolide, (E)-19-[(1-benzoyloxy-1-phenyl)-methylidene]-Triptolide (CK21), and formulated into an emulsion for in vitro and in vivo testing in rats and mice, and using human pancreatic cancer cell lines and patient-derived pancreatic tumor organoids. A time-course transcriptomic profiling of tumor organoids treated with CK21 in vitro was conducted to define its mechanism of action, as well as transcriptomic profiling at a single time point post-CK21 administration in vivo. FindingsIntravenous administration of emulsified CK21 resulted in the stable release of triptolide, and potent anti-proliferative effects on human pancreatic cancer cell lines and patient-derived pancreatic tumor organoids in vitro, and with minimal toxicity in vivo. Time course transcriptomic profiling of tumor organoids treated with CK21 in vitro revealed <10 differentially expressed genes (DEGs) at 3 h and [~]8,000 DEGs at 12 h. Overall inhibition of general RNA transcription was observed, and Ingenuity pathway analysis together with functional cellular assays confirmed inhibition of the NF-{kappa}B pathway, increased oxidative phosphorylation and mitochondrial dysfunction, leading ultimately to increased reactive oxygen species (ROS) production, reduced B-cell-lymphoma protein 2 (BCL2) expression, and mitochondrial-mediated tumor cell apoptosis. InterpretationCK21 is a novel pro-drug of triptolide that exerts potent anti-proliferative effects on human pancreatic tumors by inhibiting the NF-{kappa}B pathway, leading ultimately to mitochondrial-mediated tumor cell apoptosis. FundingThe study of the anti-tumor efficacy of CK21 supported in part by a research grant from Cinkate Pharmaceutical Corp; the funders had no role in the study design, interpretation or decision to publish. Patient-derived pancreatic tumor organoids were a generous gift from the Organoid and Primary Culture Research Core at University of Chicago.

pharmacology and toxicology↗

Covidscope: An atlas-scale COVID-19 resource for single-cell meta analysis at sample and cell levels

With the recent advancement in single-cell technologies and the increased availability of integrative tools, challenges arise in easy and fast access to large collections of cell atlas. Existing cell atlas portals rarely are open sourced and adaptable, and do not support meta-analysis at cell level. Here, we present an open source, highly optimised and scalable architecture, named Scope+, to allow quick access, meta-analysis and cell-level selection of the atlas data. We applied this architecture to our well-curated 5 million Covid-19 blood and immune cells, as a portal, Covidscope (https://covidsc.d24h.hk/). We achieved efficient access to atlas-scale data via three strategies, such as server-side rendering, novel database optimization strategies and an innovative architectural design. Scope+ serves as an open source architecture for researchers to build on with their own atlas, and demonstrated its capability in the Covidscope portal for an effective meta-analysis to atlas data at cellular resolution for reproducible research.

bioinformatics↗

Perineuronal net loosening associates with the remodeling of GABAergic terminals on motor cortical layer 5 interneurons and precedes motor coordination recovery post stroke

Stroke remains one of the leading causes of long-term disability worldwide, and the development of effective restorative therapies is hindered by an incomplete understanding of intrinsic brain recovery mechanisms. Here we explored how perineuronal nets (PNNs), the facet-like extracellular matrix layers surrounding fast-spiking interneurons, contribute to neurological recovery after focal cerebral ischemia in mice with and without induced stroke tolerance. Due to the insufficient resolution of conventional microscopy methods, the contribution of structural changes in PNNs to post stroke brain plasticity remained unknown. Using superresolution stimulated emission depletion (STED) and structured illumination (SR-SIM) microscopy, we revealed that PNN facets become larger and less dense in the post-acute stroke phase. These morphological alterations in PNNs are transient and correlate with the increased surface of contact between activated microglia and PNN-coated neurons. The transient loosening of PNNs after stroke allows for dynamic reorganization of GABAergic axonal terminals on inhibitory interneurons in the motor cortical layer 5. The coherent remodeling of PNNs and their perforating inhibitory synapses precedes the recovery of motor coordination after stroke and depends on the severity of the ischemic injury. Our data suggest a novel mechanism of motor cortical plasticity after stroke, and we propose that prolonging PNN loosening during the post-acute period can extend the opening neuroplasticity window into the chronic stroke phase. HighlightsO_LIPNNs are degraded partially and transiently post-stroke C_LIO_LITransient attenuation of PNNs correlates with GABAergic synapse remodeling C_LIO_LITransient attenuation of PNNs precedes functional recovery post stroke C_LIO_LIActivated microglia preferentially contact PNN-coated neurons post stroke C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/510951v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@13815d3org.highwire.dtl.DTLVardef@1210182org.highwire.dtl.DTLVardef@1ea12e6org.highwire.dtl.DTLVardef@7ed5b1_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

The biology of Toxoplasma gondii, the causative pathogen of one of the most wide-spread parasitic diseases remains poorly understood. Lactate, which is derived from glucose metabolic pathways, is considered to be not only an energy source in a variety of organisms including Toxoplasma gondii, but also a regulatory molecule that participates in gene activation and protein functioning. Lysine lactylation is a type of posttranslational modifications (PTMs) that was recently associated with chromatin remodeling, but lysine lactylation of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and found 1964 lactylation sites on 955 proteins in the T. gondii RH strain. The lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and multiple signaling pathways. We also performed chromatin immunoprecipitation sequencing (ChIP-seq) analysis with a lactylation specific antibody, the results revealed that histone H4K12la and H3K14la were enriched in the promoter and exon regions of Toxoplasma gondii genes associated with microtubule-based movement and cell invasion. We further confirmed the de-lactylase activity of histone deacetylase TgHDACs 2, 3, and 4, and that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in the parasites. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissection of the functional biology of Toxoplasma gondii.

microbiology↗

Mechanistic insights into dynamic mutual regulation of USP14 and proteasome

Proteasomal degradation of ubiquitylated proteins is sophisticatedly regulated at multiple levels1-3. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme USP14 that associates reversibly with the proteasome. How USP14 is activated and regulates the proteasome function remains unknown4-7. Here we report cryo-electron microscopy (cryo-EM) structures of human USP14 in complex with the 26S proteasome in nine conformational states at 3.0-3.6 [A] resolution, captured during polyubiquitylated protein degradation. Time-resolved cryo-EM analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions induced by USP14 and captured transient conversion of substrate-engaged intermediates into substrate-inhibited intermediates. On the substrate-engaged pathway, USP14 activation allosterically reprograms conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate8-10, enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding. Dynamic USP14-ATPase interactions decouple the ATPase activity from RPN11-catalysed deubiquitylation11-13 and kinetically introduce three regulatory checkpoints on the proteasome, at the steps of ubiquitin recognition, substrate translocation initiation and ubiquitin chain recycling. These findings provide unprecedented insights into the complete functional cycles of USP14-regulated proteasome and of USP14 activation-deubiquitylation-disassembly and establish mechanistic foundations for USP14-targeted therapeutic discovery.

biochemistry↗

A multiepitope fusion protein-based p-ELISA method for diagnosing bovine and goat brucellosis

In recent years, the incidence of brucellosis has increased annually, which has caused tremendous economic losses in agriculture and husbandry in various countries. Therefore, developing rapid, sensitive and specific diagnostic techniques for brucellosis has become critical brucellosis research. Bioinformatics technology was used to predict the B cell epitopes of the main antigen proteins of Brucella, and the validity of each epitope was verified by indirect enzyme-linked immunosorbent assay (iELISA). The verified epitopes were connected in series to construct a multiepitope fusion protein, goat, bovine brucellosis sera, and rabbit sera were collected to verify the antigenicity and specificity of this protein. Then, the fusion protein was used as a diagnostic antigen to construct paper-based ELISA (p-ELISA) technology. A total of 22 effective epitopes were predicted, and a fusion protein was successfully constructed, which showed good antigenicity and specificity. The constructed p-ELISA method was used for the simultaneous detection of bovine and goat brucellosis. ROC curve analysis showed that the sensitivity and specificity of protein detection in goat serum were 98.85% and 98.51%, respectively. The positive and the negative predictive value was 99.29% and 98.15%, respectively. When assessing bovine serum, the sensitivity and specificity were 97.85% and 96.61%, respectively. The positive and the negative predictive value was 98.28% and 97.33%, respectively. This study combined bioinformatics, fusion protein development and p-ELISA technologies to establish a sensitive and specific rapid diagnosis technology for brucellosis that can be used to assess the serum of bovine, goats and other livestock. IMPORTANCEBrucellosis has caused tremendous economic losses in agriculture and husbandry in various countries. Therefore, developing rapid, sensitive and specific diagnostic techniques for brucellosis has become critical brucellosis research. In this study, we used immunoinformatic technology to predict the B cell epitopes in the major outer membrane proteins of Brucella, synthesized polypeptides and coupled them with KLH, screened these polypeptides by iELISA methods, selected effective polypeptides as diagnostic antigens, and established a p-ELISA for brucellosis diagnosis based on a multiepitope fusion protein that can be used to assess the serum of bovine, goats and other livestock.

microbiology↗

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

HIV-1 remains an incurable infection that is associated with substantial economic and epidemiologic impacts. HIV-associated neurocognitive disorders (HAND) are commonly linked with HIV-1 infection; despite the development of combination antiretroviral therapy (cART), HAND is still reported to affect at least 50% of HIV-1 infected individuals. It is believed that the over-amplification of inflammatory pathways, along with release of toxic viral proteins from infected cells, are primarily responsible for the neurological damage that is observed in HAND; however, the underlying mechanisms are not well-defined. Therefore, there is an unmet need to develop more physiologically relevant and reliable platforms for studying these pathologies. In recent years, neurospheres derived from induced pluripotent stem cells (iPSCs) have been utilized to model the effects of different neurotropic viruses. Here, we report the generation of neurospheres from iPSC-derived neural progenitor cells (NPCs) and we show that these cultures are permissive to retroviral (e.g. HIV-1, HTLV-1) replication. In addition, we also examine the potential effects of stem cell derived extracellular vesicles (EVs) on HIV-1 damaged cells as there is abundant literature supporting the reparative and regenerative properties of stem cell EVs in the context of various CNS pathologies. Consistent with the literature, our data suggests that stem cell EVs may modulate neuroprotective and anti-inflammatory properties in damaged cells. Collectively, this study demonstrates the feasibility of NPC-derived neurospheres for modeling HIV-1 infection and, subsequently, highlights the potential of stem cell EVs for rescuing cellular damage induced by HIV-1 infection.

cell biology↗

rMVP: A Memory-efficient, Visualization-enhanced, and Parallel-accelerated tool for Genome-Wide Association Study

Along with the development of high-throughout sequencing technologies, both sample size and number of SNPs are increasing rapidly in Genome-Wide Association Studies (GWAS) and the associated computation is more challenging than ever. Here we present a Memory-efficient, Visualization-enhanced, and Parallel-accelerated R package called "rMVP" to address the need for improved GWAS computation. rMVP can: (1) effectively process large GWAS data; (2) rapidly evaluate population structure; (3) efficiently estimate variance components by EMMAX, FaST-LMM, and HE regression algorithms; (4) implement parallel-accelerated association tests of markers using GLM, MLM, and FarmCPU methods; (5) compute fast with a globally efficient design in the GWAS processes; and (6) generate various visualizations of GWAS related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are approximately 5-20 times faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

genetics↗

A new method for distinguishing human and mouse cells in situ

The mouse xenograft model is one of the most widely used animal model for biomedicine research. It is vital to distinguish the cells from different species, especially for the spatial distribution information. However, the available strategies of species-specific detection are either inapplicable in situ or of low specificity. Here, we reported a method based on DAPI staining, which offers an effective, convenient way that accurately identifies human and mouse nuclei at single-cell level in situ. This method was proven to be effective in cell co-culture and tumor xenograft tissue section. Microscopic imaging results shows obvious DAPI plaques-like structures in mouse nuclei, but absent in human nuclei. Moreover, we found these structures are co-localized with mouse major satellite DNA, which is located pericentromere in mouse, but absent in human. Our study provides a high-performance method that can be widely used for distinguish human and mouse cell in situ.

cell biology↗

A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.

bioengineering↗

High glucose attenuates Ca2+ influx in cytotoxic T lymphocytes upon target recognition

The killing efficiency of cytotoxic T lymphocytes (CTLs) is tightly regulated by intracellular Ca2+ concentration. Glucose is the key energy source for CTLs, lack of which significantly impairs CTL activation, proliferation and effector functions. The impact of high glucose on Ca2+ influx in CTLs remains largely elusive. In this work, we stimulated primary human CD8+ T cells in medium containing either 25 mM (high glucose, HG) or 5.6 mM glucose (normal glucose, NG). We found that store-operated calcium entry (SOCE) induced by thapsigargin (Tg) is elevated in HG-cultured CTLs compared to their counterparts in NG. Unexpectedly, the Ca2+ influx elicited by recognition of target cells is reduced in HG-cultured CTLs. Under HG condition, STIM1 and STIM2, the calcium sensors in the endoplasmic reticulum (ER), were down-regulated; ORAI1, the main structural component of calcium-release activated channels, remained unchanged, whereas ORAI2 and ORAI3 were up-regulated. The fraction of necrosis of HG-cultured CTLs was enhanced after killing without affecting glucose uptake. Thus, our findings reveal that HG has a distinctive impact on Tg-evoked SOCE and target recognition-induced Ca2+ influx in CTLs and causes more CTL death after killing, suggesting a novel regulatory role of high glucose on modulating CTL functions.

immunology↗

Intracorneal delivery of HSV-targeting CRISPR/Cas9 mRNA prevents herpetic stromal keratitis

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus and are incapable of modulating the virus reservoir. Here, we target HSV-1 genome directly using mRNA-carrying lentiviral particle (mLP) that simultaneously delivers spCas9 mRNA and two viral genes-targeting gRNAs (designated HSV-1-erasing lentiviral particles, HELP). We showed HELP efficiently blocked HSV-1 replication in both acute and recurrent infection models, and prevented occurrence of herpetic stromal keratitis (HSK). We further showed retrograde transportation of HELP from corneas to trigeminal ganglia (TG) where HSV-1 established latency and found evidence of HELP modulating herpes reservoir. Additionally, the potent antiviral activity of HELP was also replicable in human-derived corneas. These results strongly support clinical development of HELP as a new antiviral therapy and may accelerate mRNA-based CRISPR therapeutics.

bioengineering↗

Characterization of a novel NDM-5-harboring plasmid from a carbapenem-resistant Escherichia coli isolate from China

A carbapenem-resistant Escherichia coli (sequence type 5415) strain was isolated from a male patient. S1-PFGE and Southern blotting showed that the blaNDM-5 gene was located on a novel 66-kb IncFII [F2:A-:B-] plasmid. Conjugation assays revealed that the blaNDM-5-bearing plasmid was self-transferrable. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. This study highlights the genetic complexity of an NDM-5 carbapenemase and the urgent need for continuous active monitoring. IMPORTANCECarbapenem resistance due to the NDM enzyme has become a serious clinical problem in medical care and public health. We here identified a blaNDM-5-positive E. coli strain ST5414. The blaNDM-5 gene was located on a novel self-transferrable IncFII type plasmid p2947-NDM5. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. The genetic context of NDM-5 is highly similar to that of animal origins, and we speculate that the blaNDM-harboring IncFII plasmid has a potential risk of being transmitted from animals to humans and should be paid more attention. Our findings highlight the threat of NDM-5 carbapenemase circulation and the urgency of stringent surveillance and control measures.

genomics↗

ACPT gene is inactivated in mammalian lineages that lack enamel and teeth

Loss of tooth or enamel is widespread in multiple mammal lineages. Although several studies have been reported, the evolutionary mechanisms of tooth / enamel loss are still unclear. Most previous studies have found that some tooth-related genes have been inactivated in toothless and / or enamel-less mammals, such as ENAM, ODAM, C4orf26, AMBN, AMTN, DSPP, etc. Here, we conducted evolutionary analyses on ACPT plays a key role in amelogenesis, to interrogate the mechanisms. We obtained the ACPT sequences from 116 species, including edentulous and enamel-less mammals, then evolutionary analyses were implemented. The results showed that variant ORF-disrupting mutations have been detected in ACPT coding region among nine edentulous baleen whales and three enamel-less taxa (pygmy sperm whale, aardvark, nine-banded armadillo). Furtherly, selective pressure uncovered that the selective constraints have been relaxed among all toothless and enamel-less lineages. Moreover, our results support the hypothesis that mineralized teeth were lost or degenerated in the common ancestor of crown Mysticeti through two shared single-base sites deletion in exon 4 and 5 of ACPT among all living baleen whales. DN / dS values on transitional branches were used to estimate ACPT inactivation times. In the case of aardvark, inactivation of ACPT was estimated at ~23.60-28.32 Ma, which is earlier than the oldest pangolin fossil time (Orycteropus minutus, ~19Ma), suggesting that ACPT inactivation may result in degeneration or loss of enamel. Conversely, the inactivation time of ACPT estimated in armadillo (~10.18-11.30 Ma) is later than the oldest fossil time, suggesting that inactivation of ACPT may result from degeneration or loss of enamel in these mammals. Our findings suggested that different mechanisms of degeneration of tooth / enamel might exist among toothless and enamel-less lineages during evolution. Our study further considered that ACPT is a novel gene for studying tooth evolution.

evolutionary biology↗

Antigenicity and Potential Use of A Novel Brucella Multiepitope Recombinant Protein in the Diagnosis of Brucellosis

Currently, brucellosis is a reemerged zoonotic infectious disease with an increased incidence in recent years. A simple, rapid and sensitive method for diagnosing brucellosis has important significance for early diagnosis and early treatment, which can help to reduce medical burden and economic loss. Previously, a multiple epitope recombinant protein was constructed based on linear B-cell epitope prediction tools. In this study, the recombinant protein was used as an antigen to study the immune response produced by immunized mice, and goat serum was used to verify its diagnostic accuracy.The production of antibodies was successfully induced in the vaccinated mice. Through analyzing the serum antibody subtypes, the primary antibody was identified as IgG. Flow cytometric analysis revealed that the percentage of CD4+, CD8+ and the CD4+/CD8+ ratios were increased by T cell subsets in mouse splenocytes, indicating that the recombinant protein induced a strong immune response in mice and that it had strong immunoreactivity. Using indirect ELISA, the recombinant protein correctly diagnosed positive and negative brucellosis samples. Compared with the whole bacterial antigen, the recombinant protein had a weaker sensitivity but a stronger specificity.In this study, animal experiments showed that the recombinant protein had good antigenicity, and indirect ELISA indicates that it can be used as an antigen to diagnose brucellosis. Therefore, the recombinant protein is a potential candidate antigen for brucellosis vaccine development and serological diagnosis.

zoology↗

EuRBPDB: a comprehensive resource for annotation, functional and oncological investigation of eukaryotic RNA binding proteins (RBPs)

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. In this study, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic (RBPome) data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org:8081). We identified a total of 311,571 RBPs with RBDs and 3,639 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for the RNA biology community.

bioinformatics↗

Proteome and microbiota analysis reveals alterations of liver-gut axis under different stocking density of Peking ducks

The aim of this study was to determine the impact of stocking density on the liver proteome and cecal microbiota of Peking ducks. A total of 1,200 ducks with 21-day old were randomly allotted into 5 stocking density groups of 5, 6, 7, 8 and 9 ducks/m2, with 6 replicates for each group. At 40 days of age, duck serum and pectorals were collected for biochemical tests; liver and cecal contents of ducks were gathered for proteome and microbiota analysis, respectively. Serum MDA increased while pectorals T-AOC reduced linearly with enhancing stocking density. Duck lipid metabolism was altered under different stocking density as well. Serum LDL-C increased linearly with increasing stocking density. Proteome analysis revealed fatty acid biosynthesis proteins such as acyl-CoA synthetase family member 2 and fatty acid oxidation related proteins including acyl-CoA dehydrogenase long chain and acyl-coenzyme A oxidase were enriched in high stocking density group. Additionally, high stocking density increased oxidative response related proteins such as DDRGK domain containing 1 while diminished anti-oxidant capacity related proteins including regucalcin and catalase. 16S rDNA analysis revealed that higher stocking density was accompanied with decreased microbial diversity, as well as depletion of anti-inflammatory bacterial taxa, including Bacteroidales, Butyricimonas and Alistipe. In addition, decreased bile acid metabolism-associated bacteria such as Ruminococcaceae, Clostridiales and Desulfovibrionaceae were found in the high-density group. Both proteome and 16S rDNA results showed inflammation and chronic liver disease trend in the high-density group, which suggests the involvement of the liver-gut axis in oxidative stress.

microbiology↗