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Biology subjects

Gao, P.

Publications and source records attributed to Gao, P..

At least 73 records · Page 4Linked to original sources

SoyDNGP: A Web-Accessible Deep Learning Framework for Genomic Prediction in Soybean Breeding

Soybean is a globally significant crop, playing a vital role in human nutrition and agriculture. Its complex genetic structure and wide trait variation, however, pose challenges for breeders and researchers aiming to optimize its yield and quality. Addressing this biological complexity requires innovative and accurate tools for trait prediction. In response to this challenge, we have developed SoyDNGP, a Convolutional Neural Networks (CNN)-based model that offers significant advancements in the field of soybean trait prediction. Compared to existing methods, such as DeepGS and DNNGP, SoyDNGP boasts a distinct advantage due to its lower parameter volume and superior predictive accuracy. Through rigorous performance comparison, including prediction accuracy and model complexity, SoyDNGP consistently outperformed its counterparts. Furthermore, it effectively predicted complex traits with remarkable precision, demonstrating robust performance across different sample sizes and trait complexities. We also tested the versatility of SoyDNGP across multiple crop species, including Cotton, Maize, Rice, and Tomato. Our results showed its consistent and comparable performance, emphasizing SoyDNGPs potential as a versatile tool for genomic prediction across a broad range of crops. To enhance its accessibility to users without extensive programming experience, we have designed a user-friendly web server, available at http://xtlab.hzau.edu.cn/SoyDNGP. The server provides two primary features: Trait Lookup, offering users the ability to access pre-existing trait predictions for over 500 soybean accessions, and Trait Prediction, allowing for the upload of VCF files for trait estimation. By providing a high-performing, accessible tool for trait prediction and genomic analysis, SoyDNGP opens up new possibilities in the quest for efficient and optimized soybean breeding.

plant biology↗

Establishment and Evaluation of Rat Models of Cervical Spondylopathy with Yin Deficiency Syndrome

ObjectiveCervical spondylosis (CS) with Yin deficiency syndrome is an important classification of traditional Chinese medicine (TCM) symptoms of CS. However, there is no animal model for studying this TCM syndrome. This study aimes to establish and evaluate rat models of cervical spondylopathy with Yin deficiency syndrome. MethodThirty-six Sprague-Dawley male rats were randomly divided into the blank control (control), CS and CS with Yin deficiency syndrome (YCS) groups (n = 12 rats/group). CS was induced using cervical static-dynamic imbalance to mimic disk degeneration (except in the control group). After 30 days of the CS rat model, rats in the YCS group were subjected to sustained sleep deprivation for 168h. After different induction times, the rats in each group were observed for behavior and weight. Pain behavior was assessed by a withdrawal response to von Frey filament application, and heart rate and blood pressure were measured using a rat noninvasive sphygmomanometer. Intervertebral disc pathology sections were observed using hematoxylin and eosin staining and an electron microscope. Western blotting was used to evaluate the protein level of collagen-II, Bcl-2, Bax and Bcl-2/Bax expression in the cervical intervertebral disc. Determination of related laboratory serum indexes, cyclic adenosine monophosphate, and cyclic guanosine phosphate were conducted using enzyme-linked immunosorbent assay. ResultsThe laboratory indexes in the YCS group were significantly different from those in the control and CS groups (P < 0.05), and indicators of 72-, 120-, and 178-h sleep deprivation showed varying degrees of difference from those of the CS group. ConclusionAfter establishing a model of CS, continuous sleep deprivation for 72 h was used to create a rat model of CS with Yin deficiency syndrome. The established rat models of CS with Yin deficiency syndrome met the clinical and Chinese medicine characteristics, and thus, they can be expected to become an ideal model for studying CS with Yin deficiency syndrome in the future.

zoology↗

A novel order-level lineage of ammonia-oxidizing Thaumarchaeota is widespread in marine and terrestrial environments

Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant groups of Archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those of marine and soil AOA. We here report a novel AOA order Candidatus Nitrosomirales that forms a deeply branching basal sister lineage to the thermophilic Ca. Nitrosocaldales. Metagenomic and 16S rRNA gene read mapping demonstrates the dominant presence of Nitrosomirales AOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Notably, terrestrial Nitrosomirales AOA show the genetic capacity of using formate as an alternative source of reductant and appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including the genes encoding urease, nitrite reductase, and V-type ATPase. Potential metabolic versatility and acquired functions may facilitate their radiation into a variety of subsurface, marine, and soil environments. Molecular thermometer-based evolutionary analysis suggests that Nitrosomirales originated from thermophilic environments and transitioned into temperate habitats in parallel with Nitrososphaerales and Nitrosopumilales. We also provide evidence that terrestrial-marine habitat transitions occurred within each one of the four AOA orders, which reveals a more complex evolutionary trajectory of major AOA lineages than previously proposed. Together, these findings establish a robust taxonomic and evolutionary framework of AOA and provide new insights into the ecology and evolution of this globally abundant functional guild.

microbiology↗

INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation

BackgroundActivation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood. MethodsBulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA called INflammatory MKL1 Interacting Long Noncoding RNA (INKILN). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation of INKILN was determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role of INKILN in VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to study INKLIN expression and function in ligation injury-induced neointimal formation. ResultsINKILN expression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-{kappa}B site within its proximal promoter. INKILN activates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically, INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-{kappa}B pathway. INKILN depletion blocks ILI{beta}-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-{kappa}B reporter. Further, INKILN knockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10. INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice. ConclusionsThese findings elucidate an important pathway of VSMC inflammation involving an INKILN/MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.

molecular biology↗

Transcription factor AhR regulates glutathione S-transferases (GSTs) conferring resistance to lambda-cyhalothrin in Cydia pomonella

Transcription factor aryl hydrocarbon receptor (AhR) can enhance insect resistance to insecticides by regulating the detoxification metabolic network. Our previous studies have confirmed that overexpression of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are both involved in lambda-cyhalothrin resistance in Cydia pomonella. In this study, we report that AhR regulates GSTs thus conferring lambda-cyhalothrin resistance in C. pomonella. Spatiotemporal expression patterns indicated that AhR gene of C. pomonella (CpAhR) was highly expressed in the Malpighian tubules of larvae. Moreover, the expression of CpAhR was induced by lambda-cyhalothrin exposure and was up-regulated in a lambda-cyhalothrin-resistant population. RNA interference (RNAi) of the expression of CpAhR could effectively decrease the relative expression level of CpGSTe3 and enzyme activity of GSTs, but not P450s, further reducing the tolerance of larvae to lambda-cyhalothrin. Furthermore, {beta}-naphthoflavone (BNF), a novel agonist of AhR, can effectively increase the expression of CpAhR and the activity of the GSTs enzyme, resulting in the enhancement of larvae tolerance to lambda-cyhalothrin. These results demonstrate that lambda-cyhalothrin exposure can effectively activate the expression of CpAhR and increase GSTs enzyme thus leading to the development of resistance to lambda-cyhalothrin, which enriches the theory of insecticide resistance regulation in C. pomonella.

molecular biology↗

The GxcM-Fbp17/RacC-WASP signaling cascade regulates polarized cortex assembly in migrating cells

The actin-rich cortex plays a fundamental role in many cellular processes. Its architecture and molecular composition vary across cell types and physiological states. The full complement of actin assembly factors driving cortex formation and how their activities are spatiotemporally regulated remain to be fully elucidated. Using Dictyostelium as a model for polarized and rapidly migrating cells, we show that GxcM, a RhoGEF localized specifically in the rear of migrating cells, functions together with F-BAR protein Fbp17, a small GTPase RacC, and the actin nucleation-promoting factor WASP to coordinately promote Arp2/3 complex-mediated cortical actin assembly. Over-activation of this signaling cascade leads to excessive actin polymerization in the rear cortex, whereas its disruption causes defects in cortical integrity and function. Therefore, different from its well-defined role in the formation of the front protrusions, the Arp2/3 complex-based actin carries out a previously unappreciated function in building the rear cortical subcompartment in rapidly migrating cells.

cell biology↗

Analysis and Exploration of the Implementation System of Mixed Ownership of Scientific and Technological Achievements in Colleges and Universities

Due to the backwardness of the management model and the rigidity of the system, the current service invention system restricts the transformation of scientific and technological achievements of colleges and universities to a certain extent. The mixed ownership system of university post achievements, which gives universities and inventors the freedom to dispose of the rights of scientific and technological achievements, and fundamentally stimulates the enthusiasm of all the achievement owners to transform their achievements, is an important exploration to promote the transformation of scientific and technological achievements. However, there are still many problems in the implementation of the mixed ownership of scientific and technological achievements in colleges and universities. Through the questionnaire survey and analysis, it is found that the four problems such as defects in the management system for the distribution of rights and interests of scientific and technological achievements, imperfect evaluation indicators of scientific and technological achievements, imbalance in the service system for the transformation of scientific and technological achievements, and lack of authoritative standards for the evaluation of the value of the transformation of scientific and technological achievements are the main problems hindering the development of mixed ownership of the current college post achievements. Based on the existing problems, it is proposed to continue to improve the management system, assessment system and service system of mixed ownership of scientific and technological achievements in colleges and universities. The research results can provide new evidence and policy enlightenment for the development of mixed ownership of scientific and technological achievements in colleges and universities in China.

scientific communication and education↗

Senescent Preosteoclast Secretome Promotes Metabolic Syndrome Associated Osteoarthritis through Cyclooxygenase 2

BackgroundMetabolic syndrome-associated osteoarthritis (MetS-OA) is a distinct osteoarthritis phenotype defined by the coexistence of MetS or its individual components. Despite the high prevalence of MetS-OA, its pathogenic mechanisms are unclear. The aim of this study was to determine the role of cellular senescence in the development of MetS-OA. MethodsAnalysis of the human osteoarthritis initiative (OAI) dataset was conducted to investigate the MRI subchondral bone features of MetS-human OA participants. Joint phenotype and senescent cells were evaluated in two MetS-OA mouse models: high-fat diet (HFD)-challenged mice and STR/Ort mice. In addition, the molecular mechanisms by which preosteoclasts become senescent as well as how the senescent preosteoclasts impair subchondral bone microenvironment were characterized using in vitro preosteoclast culture system. ResultsHumans and mice with MetS are more likely to develop osteoarthritis-related subchondral bone alterations than those without MetS. MetS-OA mice exhibited a rapid increase in joint subchondral bone plate and trabecular thickness before articular cartilage degeneration. Subchondral preosteoclasts undergo senescence at the pre- or early-osteoarthritis stage and acquire a unique secretome to stimulate osteoblast differentiation and inhibit osteoclast differentiation. Antagonizing preosteoclast senescence markedly mitigates pathological subchondral alterations and osteoarthritis progression in MetS-OA mice. At the molecular level, preosteoclast secretome activates COX2-PGE2, resulting in stimulated differentiation of osteoblast progenitors for subchondral bone formation. Administration of a selective COX2 inhibitor attenuated subchondral bone alteration and osteoarthritis progression in MetS-OA mice. Longitudinal analyses of the human Osteoarthritis Initiative (OAI) cohort dataset also revealed that COX2 inhibitor use, relative to non-selective nonsteroidal anti-inflammatory drug use, is associated with less progression of osteoarthritis and subchondral bone marrow lesion worsening in participants with MetS-OA. ConclusionsOur findings suggest a central role of a senescent preosteoclast secretome-COX2/PGE2 axis in the pathogenesis of MetS-OA, in which selective COX2 inhibitors may have disease-modifying potential. FundingThis work was supported by the National Institutes of Health grant R01AG068226 and R01AG072090 to M.W., R01AR079620 to S.D., and P01AG066603 to X.C.

cell biology↗

Chemical inhibition of prolyl hydroxylases impairs angiogenic competence of human vascular endothelium through metabolic reprogramming

Endothelial cell (EC) metabolism has emerged as a driver of angiogenesis. While hypoxia inactivates prolyl-4 hydroxylase domain containing proteins 1-3 (PHD1-3) and stabilizes hypoxia inducible factors (HIFs) stimulating angiogenesis, the effects of PHDs on EC functions remain unclear. Here, we investigated the impact of PHD inhibition by dimethyloxalylglycine (DMOG) on angiogenic competence and metabolism of human vascular ECs. PHD inhibition reduced EC proliferation, migration, and tube formation capacities. Furthermore, transcriptomic and metabolomic analyses revealed an unfavorable metabolic reprogramming for angiogenesis following treatment with DMOG. Despite the induction of glycolytic genes and high levels of lactate, multiple genes encoding sub-units of mitochondrial complex I were suppressed with concurrent decline in nicotinamide adenine dinucleotide (NAD+) levels. Importantly, defective EC migration due to DMOG could be partially restored by augmenting NAD+ levels. Combined, our data provide metabolic insights into the mechanism by which chemical PHD inhibition impairs angiogenic competence of human vascular ECs.

molecular biology↗

TidyMass: An Object-oriented Reproducible Analysis Framework for LC-MS Data

Reproducibility and transparency have been longstanding but significant problems for the metabolomics field. Here, we present the tidyMass project (https://www.tidymass.org/), a comprehensive computational framework that can achieve the shareable and reproducible workflow needs of data processing and analysis for LC-MS-based untargeted metabolomics. TidyMass was designed based on the following strategies to address the limitations of current tools: 1) Cross-platform utility. TidyMass can be installed on all platforms; 2) Uniformity, shareability, traceability, and reproducibility. A uniform data format has been developed, specifically designed to store and manage processed metabolomics data and processing parameters, making it possible to trace the prior analysis steps and parameters; 3) Flexibility and extensibility. The modular architecture makes tidyMass a highly flexible and extensible tool, so other users can improve it and integrate it with their own pipeline easily.

bioinformatics↗

The Zpr-3 antibody recognizes the 320-354 region of Rho and labels both rods and green cones in zebrafish

Retinal markers with high quality and specificity are important for the observation of pathologic changes of retinal cells during retinal development, degeneration, and regeneration. Zpr-3 is a mouse monoclonal antibody with uncharacterized antigen usually used to label rod photoreceptors. In this study, we provided evidence to demonstrate that the antigen gene of zpr-3 is rho, which encodes the rod opsin, and the exact epitope of zpr-3 is the 320-354 region of Rho protein. More importantly, our immunofluorescence assays indicated that zpr-3 labels both the outer segments of rods and green-cones on zebrafish retinal sections, probably due to the cross-reaction with the green-cone opsin. Our work is valuable for the scientific community to interpret the experimental data involving the zpr-3 antibody.

developmental biology↗

An Inducible Cre Mouse with Preferential Activity in Vascular Smooth Muscle Evades a Previously Lethal Intestinal Phenotype

All smooth muscle cell (SMC) restricted Cre mice recombine floxed alleles in vascular and visceral SMCs. We generated a new tamoxifen-inducible CreERT2 mouse, Itga8-CreERT2, and compared its activity to the widely used Myh11-CreERT2 mouse. Both CreERT2 mice showed similar activity in vascular SMCs; however, Itga8-CreERT2 displayed limited activity in visceral SMC-containing tissues (e.g., intestine). Myh11-CreERT2 (but not Itga8-CreERT2) mice displayed high levels of CreERT2 protein, tamoxifen-independent activity, and an altered transcriptome. Whereas Myh11-CreERT2-mediated knockout of Srf resulted in a lethal intestinal phenotype, loss of Srf with Itga8-CreERT2 (SrfItga8) revealed viable mice with attenuated vascular SMC contractile gene expression, but no evidence of intestinal pathology. Male and female SrfItga8 mice presented with vascular contractile incompetence; however, only male SrfItga8 mice showed systemic changes in blood pressure. These results establish the Itga8-CreERT2 mouse as an alternative to existing SMC Cre strains, including Myh11-CreERT2, where SMC gene loss results in visceral myopathies that obfuscate accurate phenotyping in vascular SMCs.

genetics↗

Stress-Mediated Attenuation of Translation Undermines T Cell Tumor Control

Protein synthesis enables cell growth and survival, but the molecular mechanisms through which T cells suppress or maintain protein translation in the stress of solid tumors are unknown. Using mouse models and human tumors we demonstrate that protein translation in T cells is repressed by the solid tumor microenvironment (TME) due to activation of the unfolded protein response (UPR) via phosphorylation of the subunit of eukaryotic translation initiation factor 2 (p-eIF2). Given that acute glucose deprivation in T cells exacerbated p-eIF2, we show that metabolic reprogramming toward glycolytic independence allays the UPR and p-eIF2, enabling sustained protein translation in T cells in TME stress. UPR mitigation was associated with enhanced degradation of proteins in antitumor T cells, as proteasome inhibition resulted in eIF2 phosphorylation, attenuation of translation, and loss of antitumor efficacy. In contrast, proteasome stimulation relieved translation inhibition, inducing robust T cell tumor control, offering a new therapeutic avenue to fuel the efficacy of tumor immunotherapy.

immunology↗

Engineering SARS-CoV-2 cocktail antibodies into a bispecific format improves neutralizing potency and breadth

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce antibody resistance. We engineered two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) increases antigen-binding and virus-neutralizing activities and spectrum against multiple SARS-CoV-2 variants including the Omicron, than the cocktail. X-ray crystallography and computational simulations reveal distinct neutralizing mechanisms for individual cocktail antibodies and suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and the Beta, Gamma, and Delta variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.

microbiology↗

A Graph Convolutional Network-based screening strategy for rapid identification of SARS-CoV-2 cell-entry inhibitors

The cell entry of SARS-CoV-2 has emerged as an attractive drug development target. We previously reported that the entry of SARS-CoV-2 depends on the cell surface heparan sulfate proteoglycan (HSPG) and the cortex actin, which can be targeted by therapeutic agents identified by conventional drug repurposing screens. However, this drug identification strategy requires laborious library screening, which is time-consuming and often limited number of compounds can be screened. As an alternative approach, we developed and trained a graph convolutional network (GCN)-based classification model using information extracted from experimentally identified HSPG and actin inhibitors. This method allowed us to virtually screen 170,000 compounds, resulting in [~]2000 potential hits. A hit confirmation assay with the uptake of a fluorescently labeled HSPG cargo further shortlisted 256 active compounds. Among them, 16 compounds had modest to strong inhibitory activities against the entry of SARS-CoV-2 pseudotyped particles into Vero E6 cells. These results establish a GCN-based virtual screen workflow for rapid identification of new small molecule inhibitors against validated drug targets. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/471787v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1632bc4org.highwire.dtl.DTLVardef@1ce912borg.highwire.dtl.DTLVardef@9cdc86org.highwire.dtl.DTLVardef@521712_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

Cellular and transcriptional diversity over the course of human lactation

Human breast milk is a dynamic fluid that contains millions of cells, but their identities and phenotypic properties are poorly understood. We used single-cell RNA-seq (scRNA-seq) to characterize the transcriptomes of cells from human breast milk (hBM) across lactational time from 3 to 632 days postpartum in 15 donors. We find that the majority of cells in human breast milk are lactocytes, a specialized epithelial subset, and cell type frequencies shift over the course of lactation yielding greater epithelial diversity at later points. Analysis of lactocytes reveals a continuum of cell states characterized by transcriptional changes in hormone, growth factor, and milk production related pathways. Generalized additive models suggest that one sub-cluster, LALBAlow epithelial cells, increase as a function of time postpartum, daycare attendance, and the use of hormonal birth control. We identify several sub-clusters of macrophages in hBM that are enriched for tolerogenic functions, possibly playing a role in protecting the mammary gland during lactation. Our description of the cellular components of breast milk, their association with maternal-infant dyad metadata and quantification of alterations at the gene and pathways levels provides the first detailed longitudinal picture of human breast milk cells across lactational time. This work paves the way for future investigations of how a potential division of cellular labor and differential hormone regulation might be leveraged therapeutically to support healthy lactation and potentially aid in milk production.

genomics↗

Rod-genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor compositions and progressive retinal degeneration

The neural retina leucine zipper (NRL) is an essential gene for the fate determination and differentiation of rod photoreceptors in mammals. Mutations in NRL have been associated with autosomal recessive enhanced S-cone syndrome and autosomal dominant retinitis pigmentosa. However, the exact role of Nrl in regulating the development and maintenance of photoreceptors in zebrafish, a popular animal model used for retinal degeneration and regeneration studies, has not been fully determined. In this study, we generated an nrl knockout zebrafish model by CRISPR-Cas9 technology and observed a surprising phenotype characterized by the reduction but not total elimination of rods and the over-grown of green-cones. By tracing the developmental process of rods, we discovered two waves of rod genesis in zebrafish, emerging at the embryonic stage with an nrl-dependent pattern and the post-embryonic stage with an nrl-independent pattern, respectively. Through bulk and single-cell RNA sequencing, we constructed the gene expression profiles for the whole retinal tissues and each of the retinal cell types in WT and nrl knockout zebrafish. We detected the rod/green-cone intermediate photoreceptors in nrl knockout zebrafish, suggesting that there may be a kind of rod/green-cone bipotent precursors and its fate choice between rod and green-cone is controlled by nrl. Besides, we identified the mafba gene as a novel regulator for nrl-independent rods, based on the cell-type-specific expression pattern and the retinal phenotype of nrl/mafba double knockout zebrafish. Furthermore, the altered photoreceptor compositions and abnormal gene expression caused progressive retinal degeneration and subsequent regeneration in nrl knockout zebrafish. Our work revealed a novel function of mafba gene in rod development and established a more suitable model for the developmental processes and regulatory mechanisms of rod and green-cone photoreceptors in zebrafish. Author SummaryVision is mediated by two types of light-sensing cells named rod and cone photoreceptors in animal eyes. Abnormal generation, dysfunction or death of photoreceptor cells can all cause irreversible vision problems. NRL is the most important gene for the occurrence and function of rod cells in mice and humans. Surprisingly, we found that in zebrafish, a popular animal model used for mimicking human diseases and testing treatments, there are two types of rod cells and breaking the function of nrl gene only affects the generation of rod cells at the embryonic stage but not the juvenile and adult stages. The rod cells produced later are proved to be driven by the mafba gene, which has not been reported to play a role in rod cells. In addition to the reduction of rod cells, deletion of nrl also results in the occurrence of rod/green-cone hybrid cells and the increasing number of green-cones. The combination of changes at cellular and molecular levels finally lead to a disease condition named retinal degeneration. These findings add new knowledge to the research field and highlight the conserved and species-specific regulatory mechanisms of photoreceptor development and maintenance.

genetics↗

Integrated Metabolomics to Reveal the Impacts of Common Antibiotics based on Drug Resistance Prediction of Gut Microbiota

Due to the close interaction between the host and the gut microbiota, the alterations in gut microbiota metabolism may therefore contribute to various diseases. How to use antibiotics more wisely in clinical practice is a promising task in the field of pathophysiology related to gut microbiota. The hope fueling this research is that the alteration of gut microbial communities are paralleled by their capacity on metabolomic from the combined perspective of microbiome and metabolomics. In order to reveal the impacts of antibiotics on microbiota-associated host metabolomic phenotypes, a feasible methodology should be well developed to assess the pervasive effects of antibiotics on the population structure of gut microbial communities. Our attempt starts from predicting specific resistance phenotypes of the individuals in isolation from the rest of the gut microbiota community, according to their resistant genotypes. Once resistance phenotypes of microbiome is determined, we integrated metabolomics with machine learning by applying various analysis algorithms to explore the relationship between the predicted resistance and metabolites, including what the microbial community is after medication, which microbes produce metabolites, and how these metabolites enrich.

bioinformatics↗