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Biology subjects

Cao, H.

Publications and source records attributed to Cao, H..

At least 109 records · Page 6Linked to original sources

Protein turnover in the developing Triticum aestivum grain

Protein abundance in cereal grains is determined by the relative rates of protein synthesis and protein degradation during grain development. Through combining in vivo stable isotope labelling and in-depth quantitative proteomics, we have measured the turnover of 1400 different types of proteins during wheat grain development. We demonstrate that there is a spatiotemporal pattern to protein turnover rates which explain part of the variation in protein abundances that is not attributable to differences in wheat gene expression. We show that approximately 20% of total grain ATP production is used for grain proteome biogenesis and maintenance, and nearly half of this budget is invested exclusively in storage protein synthesis. We calculate that 25% of newly synthesized storage proteins are turned over during grain development rather than stored. This approach to measure protein turnover rates at proteome scale reveals how different functional categories of grain proteins accumulate, calculates the costs of protein turnover during wheat grain development and identifies the most and the least stable proteins in the developing wheat grain.

plant biology↗

Network pharmacology and chemoproteomics unveil the mechanism of Total Flavonoid Aglycones Extract inhibiting EMT in A549 cell line

Non-small cell lung cancer (NSCLC) is a worldwide disease with high morbidity and mortality, which is most derived from its metastasis. Some researches show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cells migration and invasion, leading to NSCLC metastasis. Total Flavonoid Aglycones Extract (TFAE) isolated from Scutellaria baicalensis was reported to inhibit tumor growth and induce apoptosis. In this study, we found that baicalein, wogonin, and oroxylin-A were the active compounds of TFAE. After reconstructing with these three compounds (baicalein (65.8%), wogonin (21.2%), and oroxylin-A (13.0%)), the reconstructed TFAE (reTFAE) present inhibitory effect on the EMT process of A549 cells. Then, bioinformatic technology was employed to elucidate the potential pharmacodynamic mechanism network of reTFAE. We identified the relationship between reTFAE and PI3K/Akt signaling pathways, with TWIST1 as the key protein. LY294002, the inhibitor of PI3K/Akt signaling pathway, and knock-down TWIST1 could significantly enhance the efficacy of reTFAE, with increasing expression of epithelial markers and decreasing expression of mesenchymal markers in A549 cells at the same time. Furthermore, stable isotope dimethyl-labeled proteomics technology was conducted to complement the follow-up mechanism that the EMT-inhibition process may be realized through glycolysis pathway. In conclusion, we claim that TWIST1-targeted flavonoids could provide a new strategy to inhibit EMT progress for the treatment of NSCLC.

pharmacology and toxicology↗

Intranasal HD-Ad Vaccine Protects the Upper and Lower Respiratory Tracts of hACE2 Mice against SARS-CoV-2

The COVID-19 pandemic has affected more than 120 million people and resulted in over 2.8 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all of the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Here, we describe intranasal immunization of a COVID-19 vaccine delivered by a novel platform, the helper-dependent adenoviral (HD-Ad) vector. Since HD-Ad vectors are devoid of adenoviral coding sequences, they have a superior safety profile and a large cloning capacity for transgenes. The vaccine (HD-Ad_RBD) codes for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and intranasal immunization induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. As such, intranasal immunization based on the HD-Ad vector promises to provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

microbiology↗

FEATURE DETECTION TO SEGMENT CARDIOMYOCYTE NUCLEI FOR INVESTIGATING CARDIAC CONTRACTILITY

In vivo quantitative assessment of structural and functional biomarkers is essential for understanding pathophysiology and identifying novel therapies for congenital heart disorders. Cardiac defect analysis through fixed tissue and histology has offered revolutionary insights into the tissue architecture, but section thickness limits the tissue penetration. This study demonstrated the potential of Light Sheet Fluorescence Microscopy (LSFM) for analyzing in vivo 4D (3d + time) cardiac contractility. Furthermore, we have described the utility of an improved feature detection framework for localizing cardiomyocyte nuclei in the zebrafish atrium and ventricle. Using the Hessian Difference of Gaussian (HDoG) scale space in conjunction with the watershed algorithm, we were able to quantify a statistically significant increase in cardiomyocyte nuclei count across different developmental stages. Furthermore, we assessed individual volumes and surface areas for the cardiomyocyte nuclei in the ventricles innermost and outermost curvature during cardiac systole and diastole. Using the segmented nuclei volumes from the feature detection, we successfully performed local area ratio analysis to quantify the degree of deformation suffered by the outermost ventricular region compared to the innermost ventricular region. This paper focuses on the merits of our segmentation and demonstrates its efficacy for cell counting and morphology analysis in the presence of anisotropic illumination across the field-of-view (FOV).

bioengineering↗

Recovery of high-qualitied Genomes from a deep-inland Salt Lake Using BASALT

Metagenomic binning enables the in-depth characterization of microorganisms. To improve the resolution and efficiency of metagenomic binning, BASALT (Binning Across a Series of AssembLies Toolkit), a novel binning toolkit was present in this study, which recovers, compares and optimizes metagenomic assembled genomes (MAGs) across a series of assemblies from short-read, long-read or hybrid strategies. BASALT incorporates self-designed algorithms which automates the separation of redundant bins, elongate and refine best bins and improve contiguity. Evaluation using mock communities revealed that BASALT auto-binning obtained up to 51% more number of MAGs with up to 10 times better MAG quality from microbial community at low (132 genomes) and medium (596 genomes) complexity, compared to other binners such as DASTool, VAMB and metaWRAP. Using BASALT, a case-study analysis of a Salt Lake sediment microbial community from northwest arid region of China was performed, resulting in 426 non-redundant MAGs, including 352 and 69 bacterial and archaeal MAGs which could not be assigned to any known species from GTDB (ANI < 95%), respectively. In addition, two Lokiarchaeotal MAGs that belong to superphylum Asgardarchaeota were observed from Salt Lake sediment samples. This is the first time that candidate species from phylum Lokiarchaeota was found in the arid and deep-inland environment, filling the current knowledge gap of earth microbiome. Overall, BASALT is proven to be a robust toolkit for metagenomic binning, and more importantly, expand the Tree of Life.

bioinformatics↗

Automatic segmentation and cardiac mechanics analysis of evolving zebrafish using deep-learning

ObjectiveIn the study of early cardiac development, it is important to acquire accurate volume changes of the heart chambers. Although advanced imaging techniques, such as light-sheet fluorescent microscopy (LSFM), provide an accurate procedure for analyzing the structure of the heart, rapid and robust segmentation is required to reduce laborious time and accurately quantify developmental cardiac mechanics. MethodsThe traditional biomedical analysis involving segmentation of the intracardiac volume is usually carried out manually, presenting bottlenecks due to enormous data volume at high axial resolution. Our advanced deep-learning techniques provide a robust method to segment the volume within a few minutes. Our U-net based segmentation adopted manually segmented intracardiac volume changes as training data and produced the other LSFM zebrafish cardiac motion images automatically. ResultsThree cardiac cycles from 2 days post fertilization (dpf) to 5 dpf were successfully segmented by our U-net based network providing volume changes over time. In addition to understanding the cardiac function for each of the two chambers, the ventricle and atrium were separated by 3D erode morphology methods. Therefore, cardiac mechanical properties were measured rapidly and demonstrated incremental volume changes of both chambers separately. Interestingly, stroke volume (SV) remains similar in the atrium while that of the ventricle increases SV gradually. ConclusionOur U-net based segmentation provides a delicate method to segment the intricate inner volume of zebrafish heart during development; thus providing an accurate, robust and efficient algorithm to accelerate cardiac research by bypassing the labor-intensive task as well as improving the consistency in the results.

bioengineering↗

The Population Structure and Selection Signal Analysis of Shenxian Pigs based on Genome Resequencing Technology

Shenxian pigs are the only local black pig of Hebei Province, and were listed in the Genetics of Livestock and Poultry Resources of China in 2016. This breed of pig is considered to be a valuable local pig germplasm genetic resource in China. In the present study, in order to understand the genetic variations of Shenxian pigs, identify selected regions related to superior traits, and accelerate the breeding processes of Shenxian pigs, the whole genome of the Shenxian pigs was resequenced and compared with that of large white pigs. The goal was to explore the germplasm characteristics of Shenxian pigs.The results obtained in this research investigation revealed that the genetic relationships of the Shenxian pig breed were complex, and that sub-populations could be identified within the general population. A total of 23M SNP sites were obtained by whole genome resequencing, and 1,509 selected sites were obtained via bioinformatics analyses. It was determined after annotation that a total of 19 genes were enriched in three items of bioengineering, molecular function, and cell composition.During this research investigation, the aforementioned 19 genes were subjected to GO and KEGG analyses. Subsequently, the candidate genes related to cell proliferation were obtained (DMTF1 and WDR5), which were considered to possibly be related to the slow growth and development of Shenxian pigs. In addition, the candidate genes related to lactation were obtained (CSN2 and CSN3).

genomics↗

A transferrable and integrative type I-F Cascade for heterologous genome editing and transcription modulation

The Class 1 type I CRISPR-Cas systems represent the most abundant and diverse CRISPR systems in nature. However, their applications for generic genome editing have been hindered by difficulties of introducing the class-specific, multi-component effectors in heterologous hosts for functioning. Here we established a transferrable Cascade system that enables stable integration and expression of a complete and highly active I-F Cascade in the notoriously recalcitrant and diverse P. aeruginosa genomes by conjugation. The transferred Cascade displayed substantially higher DNA interference activity and greater editing capacity than the Cas9 system in diverse genetic backgrounds, including removal of the large (21-kb) integrated cassette with efficiency and simplicity. An advanced {lambda}red-I-F system enabled editing in genotypes with poor homologous recombination capacity, clinical isolates lacking sequence information, and cells containing anti-CRISPR elements Acrs. Lastly, an all-in-one I-F Cascade-mediated CRISPRi platform was developed for transcription modulation by simultaneous introduction of the Cascade and the mini-CRISPR array expressing desired crRNA in one-step. This study provides a framework for expanding the diverse type I Cascades for widespread, heterologous genome editing and establishment of editing techniques in non-model isolates of pathogens.

microbiology↗

Exploring the dynamic mechanisms of steady-state visual evoked potentials at the whole-brain level: evidence from a computational study

Periodic visual stimulation can induce stable steady-state visual evoked potentials (SSVEPs) distributed in multiple brain regions and has potential applications in both neural engineering and cognitive neuroscience. However, the underlying dynamic mechanisms of SSVEPs at the whole-brain level are still not completely understood. Here, we addressed this issue by simulating the rich dynamics of SSVEPs with a large-scale brain model designed with constraints of neuroimaging data acquired from the human brain. By eliciting activity of the occipital areas using an external periodic stimulus, our model was capable of replicating both the spatial distributions and response features of SSVEPs that were observed in experiments. In particular, we confirmed that alpha-band (8-12 Hz) stimulation could evoke stronger SSVEP responses; this frequency sensitivity was due to nonlinear entrainment and resonance, and could be modulated by endogenous factors in the brain. Interestingly, the stimulus-evoked brain networks also exhibited significant superiority in topological properties near this frequency-sensitivity range, and stronger SSVEP responses were demonstrated to be supported by more efficient functional connectivity at the neural activity level. These findings not only provide insights into the mechanistic understanding of SSVEPs at the whole-brain level but also indicate a bright future for large-scale brain modeling in characterizing the complicated dynamics and functions of the brain.

neuroscience↗

Predicting the current and future distribution of four original plants of Gentianae Macrophyllae Radix in China under climate change scenarios

The wild resources of the four original plants (Gentiana crasicaulis Duthie ex Burk, Gentiana daurica Fisch, Gentiana straminea Maxim, and Gentiana macrophylla Pall) of Gentianae Macrophyllae Radix are becoming exhausted. Predicting the distribution under current and future climate scenarios is of significance for the sustainable utilization of resources and ecological protection. In this study, we constructed four species distribution models (SDMs) combining species distribution informations, 19 bioclimatic variables, and the maximum entropy (MaxEnt) model. The results showed that these 4 plants prefer a cool and humid climate. Under the future climate scenarios, the areas of the highly suitable habitats for Gentiana crasicaulis Duthie ex Burk and Gentiana daurica Fisch were likely to decrease, while Gentiana straminea Maxim was likely to expand, and Gentiana macrophylla Pall was less affected. In addition, the centroids of the highly suitable habitats for the four species shifted north or west. Most notably, most of the highly suitable habitats for the four species remained unchanged, which would be the preferred area for semi-artificial cultivation. The above information in this study would contribute to the development of reasonable strategies to reduce the impact of climate change on the four original plants.

ecology↗

Response of Soil Microbiome Structure to Biological Control Agents (BCAs) in Strawberry Greenhouse

Continuous cropping always leads to severe abiotic and biotic problems, especially the high-intensity land utilization in greenhouses, which causes widespread concern. Effective Microorganisms (EM) and Bacillus subtilis (BS) have been widely used to promote plant growth and increase yields as biological control agents (BCAs). However, their effects on soil microbes are obscure. To regulate the microbial community in continuous cropping strawberry soils, we developed four soil amendments by combining EM and BS with compost. The amplicon sequencing of bacterial and fungal ribosomal markers was applied to study the response of the soil microbiome structure. We noticed a sharp increase in bacterial diversity after the addition of EM-treated high compost and BS-treated low compost, while there was no significant change in fungal diversity among treatments. Interestingly, both the relative abundance and FUNGuild predictions was consistent in revealing that BCAs may inhibit fungal pathogens in soils. Correlation analysis indicated that soil microbial community was indirectly driven by soil properties. Co-occurrence networks demonstrated that BCAs could be microecologically homogeneous through enhancing bacterial network complexity and modularity. Collectively, EM-treated high compost and BS-treated low compost can well regulate the microbial community structure and thus maintain soil health.

microbiology↗

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. In consequence, PLANE promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor patient outcomes. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

cancer biology↗

High mannose N-glycans on red blood cells as phagocytic ligands, mediating both sickle cell anaemia and resistance to malaria

In both sickle cell disease (SCD) and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. Extravascular haemolysis in SCD correlates with high mannose glycan levels on RBCs. Infection of RBCs with Plasmodium falciparum expose surface mannose N-glycans on healthy RBCs, which occurred at significantly higher levels on RBCs from subjects with sickle cell trait compared to those lacking haemoglobin S. The glycans were associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans, a novel response to cellular stress, is the first molecular mechanism common to both the pathogenesis of SCD and resistance to severe malaria in sickle cell trait.

immunology↗

Increased wheat protein content via introgression of a HMW glutenin selectively reshapes the grain proteome

Introgression of a high molecular weight glutenin subunit (HMW-GS) gene, 1Ay21*, into commercial wheat cultivars increased overall grain protein content and bread-making quality by unknown mechanisms. As well as increased abundance of 1Ay HMW-GS, 115 differentially expressed proteins (DEPs) were discovered between three cultivars and corresponding introgressed near-isogenic lines (NILs). Functional category analysis showed that the DEPs were predominantly other storage proteins, and proteins involved in protein synthesis, protein folding, protein degradation, stress response and grain development. Nearly half the genes encoding the DEPs showed strong co-expression patterns during grain development. Promoters of these genes are enriched in elements associated with transcription initiation and light response, indicating a potential connection between these cis-elements and grain protein accumulation. A model of how this HMW-GS enhances the abundance of machinery for protein synthesis and maturation during grain filling is proposed. This analysis not only provides insights into how introgression of the 1Ay21* improves grain protein content, but also directs selection of protein candidates for future wheat quality breeding programmes. One sentence summaryIntrogression of the 1Ay21* HMW-GS increases wheat grain protein content and improves bread-making quality in association with a broad reshaping of the grain proteome network.

plant biology↗

MiRNA expression profiling and zeatin dynamic changes in a new model system of in vivo indirect regeneration of tomato

Callus formation and adventitious shoot differentiation could be observed on the cut surface of completely decapitated tomato plants. We propose that this process can be used as a model system to investigate the mechanisms that regulate indirect regeneration of higher plants without the addition of exogenous hormones. This study analyzed the patterns of trans-zeatin and miRNA expression during in vivo regeneration of tomato. Analysis of trans-zeatin revealed that the hormone cytokinin played an important role in in vivo regeneration of tomato. Among 183 miRNAs and 1168 predicted target genes sequences identified, 93 miRNAs and 505 potential targets were selected based on differential expression levels for further characterization. Expression patterns of six miRNAs, including sly-miR166, sly-miR167, sly-miR396, sly-miR397, novel 156, and novel 128, were further validated by qRT-PCR. We speculate that sly-miR156, sly-miR160, sly-miR166, and sly-miR397 play major roles in callus formation of tomato during in vivo regeneration by regulating cytokinin, IAA, and laccase levels. Overall, our microRNA sequence and target analyses of callus formation during in vivo regeneration of tomato provide novel insights into the regulation of regeneration in higher plants.

molecular biology↗

Circumventing the optical diffraction limit with customized speckles

Speckle patterns have been widely used in imaging techniques such as ghost imaging, dynamic speckle illumination microscopy, structured illumination microscopy, and photoacoustic fluctuation imaging. Recent advances in the ability to control the statistical properties of speckles has enabled the customization of speckle patterns for specific imaging applications. In this work, we design and create special speckle patterns for parallelized nonlinear pattern-illumination microscopy based on fluorescence photoswitching. We present a proof-of-principle experimental demonstration where we obtain a spatial resolution three times higher than the diffraction limit of the illumination optics in our setup. Furthermore, we show that tailored speckles vastly outperform standard speckles. Our work establishes that customized speckles are a potent tool in parallelized super-resolution microscopy.

biophysics↗

A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic β-cells

Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNA (IncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a {beta}-cell- and neural cell-enriched lncRNA TUNAR (also known as TUNA, HI-LNC78 or LINC00617). We named this highly conserved 48-amino-acid micropeptide Beta cell- and Neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localized at the endoplasmic reticulum in pancreatic {beta}-cells. Overexpression of BNLN lowered ER calcium levels, increased cytosolic calcium levels, and maintained ER homeostasis in response to high glucose challenge. To determine the physiological and pathological roles of BNLN, we assessed the BNLN expression in islets from mice fed with a high-fat diet and a regular diet, and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN elevated glucose-stimulated insulin secretion in INS-1 cells. Lastly, BNLN overexpression enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic {beta}-cell function and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes.

molecular biology↗

Identifying Neural Signatures Mediating Behavioral Symptoms and Psychosis Onset: High-Dimensional Whole Brain Functional Mediation Analysis

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an brain atlas and a {beta} brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify the P mediators and the N mediators that respectively facilitate or protect against developing brain disorders among subjects with more severe behavioral symptoms and quantify the effect of each neural mediator on disease development. Taken together, the -{beta} atlases and the P-N mediators paint a brain-wide picture of neural markers that are potentially regulating behavioral symptoms and the development of psychotic disorders and highlight a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological organization.

bioinformatics↗