Biology subjects

Guo, G.

Publications and source records attributed to Guo, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

The study on the impact of indoleacetic acid on enhancing the ability of the rumen's original microecology to degrade aflatoxin B1.

Aflatoxin B1 (AFB1) poses a serious threat to the health of cattle and is strictly monitored in their diets. Rumen microorganisms in cattle have the ability to degrade AFB1, but this capability is limited. Enhancing the degradation capacity of the original rumen microecology for AFB1 is a novel approach. From a molecular perspective,indoleacetic-3-acid (IAA) promotes the expression of cytochromes, which can improve the degradation of AFB1. Therefore, this study aims to investigate the impact of different concentrations of IAA on the degradation of AFB1 by the rumen microecology. Experiments used rumen fluid from three adult cows as donors, and the cows were all fed the same total mixed ration. Rumen fluid was collected from these three cannulated cows before morning feeding to prepare in vitro fermentation fluid. The experiments used a completely randomized design, with each treatment repeated four times. The results showed that as the fermentation time increased, the content of AFB1 gradually decreased, with a degradation rate of up to 75.73% after 24 h. AFB1 altered the rumen fermentation pattern, with a significant reduction in the content of acetic acid (P<0.05) and a significant decrease in the acetic acid to propionic acid ratio (P<0.05). It also affected the rumen microecology, causing a significant reduction in the abundance of Ruminococcus amylophilus, Prevotella ruminicola, and Fusobacterium succinogenes (P<0.05). In addition, this study found that with the increase in the amount of IAA added, the content of AFB1 in the rumen gradually decreased. IAA enhances the degradation capacity of the original rumen microecology for AFB1, and the addition of IAA alleviates the impact of AFB1 on Ruminococcus amylophilus, Prevotella ruminicola, and Fusobacterium succinogenes in the rumen (P<0.05). Moreover, the addition of IAA can promote the stability of the rumen microecology, with significantly higher acetic acid and acetic acid to propionic acid ratios in the fermentation fluid compared to the non-added group (P<0.05). In summary, the addition of IAA can improve the degradation capacity of the rumen microecology for AFB1, providing a new solution for alleviating the impact of AFB1 on animal health.

microbiology↗

bioRxiv2024

Horizontally acquired CSP genes contribute to wheat adaptation and improvement

Although horizontal gene transfer (HGT) often facilitates environmental adaptation of recipient organisms, whether and how they might affect crop evolution and domestication is unclear. Here we show that three genes encoding cold shock proteins (CSPs) were transferred from bacteria to the last common ancestor of Triticeae, a tribe of the grass family that includes several major staple crops such as wheat, barley, and rye. The acquired CSP genes in wheat (TaCSPs) are functionally conserved with their bacterial homologs by encoding a nucleic acid binding protein. Experimental evidence indicates that TaCSP genes positively regulate drought response and improve photosynthetic efficiency under water deficit conditions, by directly targeting a type 1 metallothionein gene to increase ROS scavenging, which in turn contributed to the geographic expansion of wheat. We identified an elite CSP haplotype in Aegilops-tauschii, introduction of which to wheat significantly increased drought tolerance, photosynthetic efficiency and grain yields. These findings not only provide major insights into the role of HGT in crop adaptation and domestication, but also demonstrate that novel microbial genes introduced through HGT offer a stable and naturally optimized resource for transgenic crop breeding and improvement.

plant biology↗

bioRxiv2024

Single-Stranded DNA with Internal Base Modifications Mediates Highly Efficient Gene Insertion in Primary Cells

Single-stranded DNA (ssDNA) templates along with Cas9 have been used for gene insertion but suffer from low efficiency. Here, we show that ssDNA with chemical modifications in 10-17% of internal bases (eDNA) is compatible with the homologous recombination machinery. Moreover, eDNA templates improve gene insertion by 2-3 fold compared to unmodified and end-modified ssDNA in airway basal stem cells (ABCs), hematopoietic stem and progenitor cells (HSPCs), T-cells and endothelial cells. Over 50% of alleles showed gene insertion in three clinically relevant loci (CFTR, HBB, and CCR5) in ABCs using eDNA and up to 70% of alleles showed gene insertion in the HBB locus in HSPCs. This level of correction is therapeutically relevant and is comparable to adeno-associated virus-based templates. Knocking out TREX1 nuclease improved gene insertion using unmodified ssDNA but not eDNA suggesting that chemical modifications inhibit TREX1. This approach can be used for therapeutic applications and biological modeling.

molecular biology↗

bioRxiv2023

Human naive stem cell models reveal the role of FGF signalling in hypoblast specification in the human embryo

The hypoblast is an essential extra-embryonic tissue set aside within the inner cell mass early in mammalian embryo development, in the blastocyst. Research with human embryos is challenging. Thus, stem cell models that reproduce hypoblast differentiation provide valuable alternatives. We show here that human naive PSC to hypoblast differentiation proceeds via reversion to a transitional ICM-like state, from which hypoblast emerges in concordance with the trajectory in human blastocysts. We identified a window when fibroblast growth factor (FGF) signalling is critical for hypoblast specification. Revisiting FGF signalling in human embryos revealed that inhibition in the early blastocyst suppresses hypoblast formation. In vitro, the induction of hypoblast is synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports and establishes a conservation in lineage specification between mouse and human. Overall, this study demonstrates the utility of human naive PSC-based models in elucidating mechanistic features of early human embryogenesis.

developmental biology↗

bioRxiv2023

Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY

Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a SPY O-fucosyltransferase inhibitor (SOFTI). Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. By contrast, SOFTI had no visible effect on the spy mutant. Similarly, SOFTI inhibited sugar-dependent growth of tomato seedlings. These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management.

plant biology↗

bioRxiv2023

SEQUENCE VS. STRUCTURE: DELVING DEEP INTO DATA DRIVEN PROTEIN FUNCTION PREDICTION

AO_SCPLOWBSTRACTC_SCPLOWPredicting protein function is a longstanding challenge that has significant scientific implications. The success of amino acid sequence-based learning methods depends on the relationship between sequence, structure, and function. However, recent advances in AlphaFold have led to highly accurate protein structure data becoming more readily available, prompting a fundamental question: given sufficient experimental and predicted structures, should we use structure-based learning methods instead of sequence-based learning methods for predicting protein function, given the intuition that a proteins structure has a closer relationship to its function than its amino acid sequence? To answer this question, we explore several key factors that affect function prediction accuracy. Firstly, we learn protein representations using state-of-the-art graph neural networks (GNNs) and compare graph construction(GC) methods at the residue and atomic levels. Secondly, we investigate whether protein structures generated by AlphaFold are as effective as experimental structures for function prediction when protein graphs are used as input. Finally, we compare the accuracy of sequence-only, structure-only, and sequence-structure fusion-based learning methods for predicting protein function. Additionally, we make several observations, provide useful tips, and share code and datasets to encourage further research and enhance reproducibility.

bioinformatics↗

bioRxiv2023

Identification and Characterization of a Novel Major Facilitator Superfamily (MFS) Efflux Pump SA09310 Mediating Tetracycline Resistance in Staphylococcus aureus

Drug efflux systems have recently been recognized as an important mechanism of multidrug resistance in bacteria. Here, we described the identification and characterization of a novel chromosomally encoded multidrug efflux pump (SA09310) in Staphylococcus aureus. SA09310 is a 43-kDa protein with 12 transmembrane helices. The conserved amino acid sequence motifs of the major facilitator superfamily (MFS) were identified in the protein SA09310, which indicated SA09310 belonged to MFS transporters. Expression of the sa09310 gene was induced by different types of antibiotics, including aminoglycoside, tetracycline, macrolides, and chloramphenicol. The sa09310 gene knockout mutant ({Delta}sa09310) was constructed, and its susceptibility to 30 different antibiotics was evaluated. Mutant{bigtriangleup} sa09310 exhibited increased sensitivity to tetracycline and doxycycline, with 64-fold and 8-fold decreased MICs, respectively. The mechanism of SA09310 mediating tetracycline resistance was demonstrated by its ability to extrude intracellular tetracycline from within the cells into the environment. The efflux activity of SA09310 was further confirmed by EtBr accumulation and efflux assays. In addition, the efflux activity of SA09310 was observed to be blocked by the known efflux pump inhibitor carbonyl cyanide-chlorophenylhydrazone (CCCP), which provided direct evidence that suggested the H+-dependent activity of SA09310 efflux pump. The conservation of SA09310 homologs in Staphylococcus indicated the universal function of these SA09310-like protein clusters. In conclusion, the function-unknown protein SA09310 has been identified and characterized as a tetracycline efflux pump, thereby mediating tetracycline resistance in S. aureus.

microbiology↗

bioRxiv2022

FunGeneTyper: An Expandable Deep Learning-based Framework for Ultra-accurate Classification and Discovery of Functional Protein-Coding Genes

High-throughput DNA sequencing technologies open the gate to tremendous (meta)genomic data from yet-to-be-explored microbial dark matter. However, accurately assigning protein functions to new gene sequences remains challenging. To this end, we developed FunGeneTyper, an expandable deep learning-based framework with models, structured databases and tools for ultra-accurate (>0.99) and fine-grained classification and discovery of antibiotic resistance genes (ARGs) and virulence factor or toxin genes. Specifically, this new framework achieves superior performance in discovering new ARGs from human gut (accuracy: 0.8512; and F1-score: 0.6948), wastewater (0.7273; 0.6072), and soil (0.8269; 0.5445) samples, beating the state-of-the-art bioinformatics tools and protein sequence-based (F1-score: 0.0556-0.5065) and domain-based (F1-score: 0.2630-0.5224) alignment approaches. We empowered the generalized application of the framework by implementing a lightweight, privacy-preserving and plug-and-play neural network module shareable among global developers and users. The FunGeneTyper* is released to promote the monitoring of key functional genes and discovery of precious enzymatic resources from diverse microbiomes.

bioinformatics↗

bioRxiv2022

Protein Language Model Predicts Mutation Pathogenicity and Clinical Prognosis

Accurately predicting the effects of mutations in cancer has the potential to improve existing treatments and identify novel therapeutic targets. In this paper, we evidence for the first time that the large-scale pre-trained protein language models (PPLMs) are zero-shot predictors for two clinically relevant tasks: identifying diseasecausing mutations and predicting patient survival rate. Then we benchmark a series of state-of-the-art (SOTA) PPLMs on 2279 protein variants across 20 cancer-related genes. Our empirical results show that the PPLMs outperform the SOTA baseline, EVE [1], trained on multiple sequence alignment (MSA) data. We also demonstrate that the evolutionary index score, generated from the PPLMs softmax layer, is good indicator for both mutation pathogenicity and patient survival rate. Our paper has taken a key step toward the clinical utility of large-scale PPLMs.

bioinformatics↗

bioRxiv2022

Suppression of YAP Safeguards Human Naïve Pluripotency

Propagation of human naive pluripotent stem cells (nPSCs) requires inhibition of MEK/ERK signalling. However, MEK/ERK inhibition also induces differentiation into trophectoderm (TE). Therefore, robust self-renewal requires active suppression of TE fate. Tankyrase inhibition using XAV939 has been shown to stabilise human nPSCs. Here we dissect the mechanism of this effect. Tankyrase inhibition blocks canonical Wnt/{beta}-catenin signalling. However, nPSCs depleted of {beta}-catenin remain dependent on XAV939. We show that XAV939 prevents TE induction by suppressing YAP activity independent of {beta}-catenin. Tankyrase inhibition stabilises angiomotin, which reduces nuclear translocation of YAP1/TAZ. Upon deletion of Angiomotin-family members AMOT and AMOTL2, nuclear YAP increases and XAV939 fails to prevent TE induction. Conversely, nPSCs lacking YAP1 fail to undergo TE differentiation and sustain efficient self-renewal without XAV939. These findings explain the distinct requirement for tankyrase inhibition in human but not mouse naive PSCs and highlight the pivotal role of YAP in human naive pluripotency.

developmental biology↗

bioRxiv2022

Investigating the Consistency of Extracellular Vesicle Production from Breast Cancer Subtypes Using CELLine Adherent Bioreactors

Extracellular vesicle (EV) research has grown rapidly in recent years, largely due to the potential use of EVs as liquid biopsy biomarkers or therapeutics. However, in-depth characterisation and validation of EVs produced using conventional in vitro cultures can be challenging due to the large area of cell monolayers and volumes of culture media required. To overcome this obstacle, multiple bioreactor designs have been tested for EV production with varying success, but the consistency of EVs produced over time in these systems has not been reported previously. In this study, we demonstrate that several breast cancer cell lines of different subtypes can be cultured simultaneously in space, resource, and time efficient manner using CELLine AD 1000 systems, allowing the consistent production of vast amounts of EVs for downstream experimentation. We report an improved workflow used for inoculating, maintaining, and monitoring the bioreactors, their EV production, and the characterisation of the EVs produced. Lastly, our proteomic analyses of the EVs produced throughout the lifetime of the bioreactors show that core EV-associated proteins are relatively consistent, with few minor variations over time, and that tracking the production of EVs may be a convenient method for indirectly monitoring the bioreactors health. These findings will aid future studies requiring the simultaneous production of large amounts of EVs from several cell lines of different subtypes of a disease and other EV biomanufacturing applications.

cancer biology↗

bioRxiv2021

Isolation, identification and molecular characterization of Aeromonas spp. from farmed loach (Misgurnus anguillicaudatus)

Gram-negative Aeromonas bacteria is known to contaminate aquaculture products and retains the ability to infect wide range of host including fishes, shrimps and humans. This study is designed to evaluate the presence of Aeromonas in healthy loaches (Misgurnus anguillicaudatus) collected from the markets in Hainan and Guangdong provinces of China. Based on the molecular sequencing and phylogenetic analysis with single 16S rRNA and concatenated genes (gyrA and ropD), 104 isolates were identified as Aeromonas species followed by further classification to A. veronii (83.65%), A. jandaei (9.62%), A. hydrophila (3.85%) and A. allosaccharophila (2.88%). More than half of the isolates displayed hemolytic activity of 87.5% and were able to form moderate biofilm (78.26%). Fourteen antibiotics from ten representative classes were screened that demonstrated complete resistance to ampicillin, 89.4% and 68.3% to lincomycin and nalidixic acid. Moreover, a notable detection and prevalence was found in screening of ten virulence-related and nine resistance genes. To our knowledge, it is the first report of its kind demonstrating potential threat of the commercial loaches carrying Aeromonas to human health. These findings will assist professionals working in clinical settings to optimize their prescription accordingly and researchers to access the impacts of Aeromonas resistance on human health. ImportanceThis study demonstrates high infection rate of loaches by Aeromonas spp. in Hainan and Guangdong provinces of China. The most prevalent species was Aeromonas veronii. Most of the isolates displayed hemolytic activity and formed moderate biofilm. Multiple virulence genes, resistance genes and multi-antibiotic resistance were detected. Aeromonads risks should be considered in loach industry.

microbiology↗

bioRxiv2021

5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes

5-methylcytosine (m5C) is an important epitranscriptomic modification involved in mRNA stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (P. yoelii) and human (P. falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knock-out of P. yoelii nsun2 (pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in rodent and human malaria parasites. Restoration of the nsun2 gene in the knock-out parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites. SignificanceModifications of RNA including methylations of cytosine (m5C) and adenosine (m6A) have important roles in RNA metabolism, cellular responses to stress, and biological processes of differentiation and development. Here, we report on the profiles of m5C mRNA modifications in malaria parasites that infect rodents (Plasmodium yoelii) and humans (Plasmodium falciparum). These parasites have genes that encode homologs of human and plant NSUN2 methyltransferases (m5C "writers"). We show that one of these homologs, termed PyNSUN2, stabilizes mRNA transcripts in P. yoelii and mediates m5C-associated development of the parasite sexual stages (gametocytes). Further research on m5C and other epitranscriptomic modifications may yield new insights into molecular pathways of gametocyte development and mosquito infectivity that can be exploited to interrupt malaria transmission.

microbiology↗

bioRxiv2021

Vaccination-induced rapid protection against bacterial pneumonia via training alveolar macrophage in mice

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here we demonstrated a single intranasal immunization of inactivated whole cell (IWC) of Acinetobacter baumannii elicits rapid protection against A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF- production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

immunology↗

bioRxiv2021

ATP-dependent Clp protease subunit C1, HvClpC1, is a strong candidate gene for barley variegation mutant luteostrians as revealed by genetic mapping and genomic re-sequencing

Implementation of next-generation sequencing in forward genetic screens greatly accelerated gene discovery in species with larger genomes, including many crop plants. In barley, extensive mutant collections are available, however, the causative mutations for many of the genes remains largely unknown. Here we demonstrate how a combination of low-resolution genetic mapping, whole-genome resequencing and comparative functional analyses provides a promising path towards candidate identification of genes involved in plastid biology and / or photosynthesis, even if genes are located in recombination poor regions of the genome. As a proof of concept, we simulated the prediction of a candidate gene for the recently cloned variegation mutant albostrians (HvAST / HvCMF7) and adopted the approach for suggesting HvClpC1 as candidate gene for the yellow-green variegation mutant luteostrians. Author SummaryForward genetics is an approach of identifying a causal gene for a mutant phenotype and has proven to be a powerful tool for dissecting the genetic control of biological processes in many species. A large number of barley mutants was generated in the 1940s to 1970s when mutation breeding programs flourished. Genetic dissection of the causative mutations responsible for the phenotype, however, lagged far behind, limited by lack of molecular markers and high-throughput genotyping platforms. Next-generation sequencing technologies have revolutionized genomics, facilitating the process of identifying mutations underlying a phenotype of interest. Multiple mapping-by-sequencing or cloning-by-sequencing strategies were established towards fast gene discovery. In this study, we used mapping-by-sequencing to identify candidate genes within coarsely delimited genetic intervals, for two variegation mutants in barley - luteostrians and albostrians. After testing the approach using the example of the previously cloned albostrians gene HvAST, the gene HvClpC1 could be delimited as candidate gene for luteostrians. The mapping-by-sequencing strategy implemented here is generally suited for surveying barley mutant collections for phenotypes affecting fundamental processes of plant morphology, physiology and development.

genetics↗

bioRxiv2020

Gut dysbiosis protects against liver injury in autophagy deficient mice by FXR-FGF15 feedback signaling

ABSTRACTObjective The gut microbiota (GM) can have complicated and often undetermined interactions with the function of many organs in the body. GM is altered in a variety of liver diseases, but the significance of such changes on the liver disease is still unclear. Hepatic autophagy deficiency causes liver injury accompanied with cholestasis. Here, we investigated the impact of such hepatic changes on GM and in turn the effect of gut dysbiosis on liver injury.Design Fecal microbiota from mice with liver-specific loss of autophagy-related gene 5 (Atg5), Atg5Δhep mice, were analyzed by 16S sequencing. Antibiotics (ABX) was used to modulate GM in mice. Cholestyramine was used to reduce the enterohepatic bile acid (BA) level. The functional role of fibroblast growth factor 15 (FGF15) and ileal farnesoid X receptor (FXR) was examined in mice over-expressing FGF15 gene, or given a fibroblast growth factor receptor 4 (FGFR4) inhibitor.Results The composition of GM was significantly changed with a notable increase of BA-metabolizing bacteria in Atg5Δhep mice, leading to a lower proportion of tauro-conjugated BAs and a higher proportion of unconjugated BAs in the intestine, which markedly activated ileal FXR with an increased expression of FGF15. ABX or cholestyramine treatment exacerbated liver injury and ductular reaction, and decreased FGF15 expression, whereas modulating FGF15 signaling altered liver phenotypes in the autophagy-deficient mice.Conclusion Gut dysbiosis can remedy liver injury in Atg5Δhep mice through the FXR-FGF15 signaling. Antibiotics use in the condition of liver injury may have unexpected adverse consequences via the gut-liver axis.What is already known about this subject?Gut microbiota (GM) can be altered during hepatic pathogenesis.GM are involved in bile acid (BA) metabolism.Autophagy deficiency in the liver disrupts BA homeostasis and causes cholestatic injury.What are the new findings?Deficiency of autophagy in the liver causes alteration of GM, which leads to a higher proportion of BA-metabolizing bacteria.GM contribute to the activation of ileal farnesoid X receptor (FXR) and a higher expression of fibroblast growth factor 15 (FGF15) in autophagy deficient condition in the liver, which is associated with decreased levels of conjugated BAs and increased levels of unconjugated BAs in the intestine.Manipulations that lead to GM alteration, intestinal BA signaling, or FGF15 signaling can all modulate the liver phenotype.BA and GM together can act as a sensor to liver injury to trigger FGF15-mediated protective mechanism.How might it impact on clinical practice in the foreseeable future?These findings indicate that gut dysbiosis in the scenario of liver disease can be beneficial, suggesting cautions should be exercised in the use of antibiotics during specific liver diseases.If antibiotics need to be used in patients with liver diseases it may be beneficial to enhance the FXR-FGF15 feedback signaling to retain the protective effect of GM.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2020

Trophectoderm Potency is Retained Exclusively in Human Naïve Cells

Classical mouse embryology has established a paradigm of early development driven by sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derived from early epiblast have lost the potency to produce extraembryonic trophectoderm. We show in contrast that human naive epiblast cells readily make trophectoderm. Inhibition of ERK signalling, instrumental in naive stem cell propagation, unexpectedly potentiates trophectoderm formation, an effect enhanced by Nodal inhibition. Transcriptome analyses authenticate conversion into trophectoderm with subsequent production of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Genetic perturbations indicate that NANOG suppresses and TFAP2C enables trophectoderm induction. Consistent with post-implantation progression, trophectoderm potential is extinguished in conventional human pluripotent stem cells, which instead make amnion. Finally, human embryo epiblasts from late blastocysts efficiently generate trophectoderm and differentiated trophoblast. Thus, pluripotent cells in the human embryo retain extraembryonic lineage plasticity and regenerative potential until implantation. Harnessing this unanticipated regulative capacity may be beneficial for assisted reproduction technology.

developmental biology↗

bioRxiv2020

Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening

2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.

pharmacology and toxicology↗