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Qiao, P.

Publications and source records attributed to Qiao, P..

12 recordsLinked to original sources

Dual-Binding Scaffold RRsS1 Bridges Pol IV Transcripts and DNA Templates for Robust Reproductive siRNA Biogenesis

Cytosine DNA methylation established by RNA-directed DNA methylation (RdDM) is critical for transposon silencing and genome integrity in plants. In reproductive tissues, RNA Polymerase IV (Pol IV) is recruited to specific genomic loci by DNA motifs and the transcription factor-GDE1-CLSY3/4 complex to initiate abundant siRNA biogenesis and de novo DNA methylation, but the mechanisms that stabilize the Pol IV transcription complex at these sites remain elusive. Using immunoprecipitation-mass spectrometry of the Pol IV complex, we identify Reproductive RdDM siRNA Scaffold 1 (RRsS1) as a novel Pol IV interactor. RRsS1 colocalizes genome-wide with motif-dependent RdDM factors in floral tissues. Loss of RRsS1 significantly impairs 24-nt siRNA accumulation at a subset of CLSY3/4-dependent loci, particularly those exhibiting high Pol IV enrichment. We show that chromatin association of RRsS1 is stabilized by GDE1 and CLSY3/4. Structural modeling and biochemical assays characterize RRsS1 as a chimeric protein containing HRDC, Nudix, and DRBM modules that bind single-stranded DNA (ssDNA) and double-stranded DNA (dsRNA), respectively. Together, our findings support a model in which RRsS1 acts as a dual-binding scaffold, bridging Pol IV-RDR2 transcripts to their DNA templates within transcription bubbles to ensure robust siRNA production during plant reproduction.

plant biology↗

Fibroblast-encoded inflammatory memory orchestrates recurrent skin inflammation via NNMT-dependent metabolic remodeling

Chronic skin inflammation frequently recurs at the same anatomical sites after therapy withdrawal, implying stromal cells may encode local inflammatory memory. Here, we identified nicotinamide N-methyltransferase (NNMT) as a central metabolic-epigenetic regulator of fibroblast inflammatory memory enabling psoriasis relapse. Single-cell and spatial transcriptomics revealed that dermal fibroblasts acquire a persistent senescence-associated secretory phenotype (SASP) during inflammation, maintaining pro-inflammatory niche in resolved skin that supports CD 8+CD 103+ tissue-resident memory T cell (Trm) differentiation. Multi-omics profiling demonstrated that NNMT depletes S-adenosylmethionine (SAM), reduces H 3K 27me3 deposition, and permits sustained AP-1 occupancy at SASP gene promoters. Fibroblast-specific NNMT ablation or pharmacologic inhibition suppressed SASP activity, limited Trm accumulation, and prevented both initiation and relapse of skin inflammation in mice. These findings establish NNMT as a stromal regulator linking fibroblast metabolism to durable epigenetic memory and propose its targeting to erase inflammatory memory and achieve long-term remission in psoriasis and related immune-mediated diseases. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/721223v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@34b2f4org.highwire.dtl.DTLVardef@1d0bb89org.highwire.dtl.DTLVardef@c8277borg.highwire.dtl.DTLVardef@9825ac_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphic Abstract:C_FLOATNO Proposed mechanism through which NNMT-driven fibroblast SASP facilitates the initiation and recurrence of psoriasis C_FIG

immunology↗

The Fengshu Large Model for Wugu Fengdeng: An Innovation Engine for Knowledge Integration in the Soybean Field

Against the backdrop of global population growth and the continuous escalation of food demand, the acceleration of agricultural modernization has emerged as the core pathway to safeguard food security. As the worlds fourth-largest food crop, soybean (Glycine max) possesses multiple strategic values for food security, livestock feed, and industrial raw materials, thanks to its high protein content (accounting for over 40% of the dry weight of seeds) and oil resource attributes. However, the soybean industry is confronted with multiple challenges: the long cycle of genetic breeding (8-10 years required by traditional methods), annual losses from diseases and pests reaching 40% (data from FAO 2023), and the reliance on empirical decision-making in field management, all of which urgently call for intelligent solutions.At present, agricultural knowledge is experiencing explosive growth - more than 4,000 new soybean-related literatures are added annually in PubMed, and agricultural technology Q&A platforms (Zhihu, Baidu Tieba, etc.) generate over 3,000 daily questions. However, this multi-source heterogeneous knowledge is scattered in books, literatures, Q&A communities, and gene databases, lacking systematic integration, resulting in a knowledge utilization rate of less than 30%. In response to this, this paper proposes the "Fengshu-Agri" large model, an agricultural knowledge integration and innovation engine based on the collaboration of Retrieval-Augmented Generation (RAG) and Knowledge Graph (KG). The model achieves breakthroughs through the following core technological innovations: O_LIDeep integration of multi-source heterogeneous data: For the first time, a systematic integration of 256 agricultural monographs (covering standardized knowledge such as planting techniques and pest control), 66,772 cutting-edge research literatures (genomics, agronomic trait analysis, etc.), 880,000 production practice Q&A (covering scenarios such as pest diagnosis and environmental stress response), and 120,000 gene annotation data (functional genes, expression regulation mechanisms) has been carried out to construct the largest knowledge graph in the agricultural field - containing 2 million entity nodes, realizing full-chain knowledge modeling from molecular-level gene regulation to field management. C_LIO_LIDouble-layer collaborative retrieval mechanism: Innovatively integrating RAG semantic vector retrieval with KG structured reasoning to solve problems such as low recall rate (<65%) and semantic ambiguity in traditional systems. Specifically, it achieves dual matching through local keywords (entity-level) and global keywords (relationship-level); C_LIO_LIOptimization of domain-specific generation engine: Based on the QWEN-QWQ32B large language model, a three-stage fine-tuning is carried out (pre-training, agricultural instruction fine-tuning, and reinforcement learning from human feedback) [15], which improves the professionalism of generated texts by 35% (manual evaluation index) and significantly reduces the LLM hallucination problem [12]. Experimental results show that Fengshu-Agri achieves an accuracy rate of 89.6% in soybean knowledge retrieval tasks (a 25.4% improvement over traditional RAG models), a recall rate of 87.3% (20.5% higher than pure KG reasoning models), and an F1 score of 88.4%. It can efficiently answer complex questions involving multi-entity associations (such as "the impact mechanism of CRISPR-editing the GmSWEET gene on lepidopteran pest resistance"). Analysis of typical cases indicates that the models responses not only cover technical principles (sgRNA design, Agrobacterium transformation procedures) but also integrate metabolomics data (70% improvement in insect resistance with no significant yield reduction), demonstrating cross-modal knowledge fusion capabilities. In the future, this model will be expanded to crops such as maize and potato to construct an agricultural intelligent ecosystem covering the entire process of cultivation management and breeding improvement, promoting the upgrading of precision agriculture toward a data-driven model. C_LI

plant biology↗

Integrative multi-omic analysis identifies genes associated with cuticular wax biogenesis in adult maize leaves

Studying the genetic basis of leaf wax composition and its correlation with leaf cuticular conductance (gc) is crucial for improving crop water-use efficiency. The leaf cuticle, which comprises a cutin matrix and various waxes, functions as an extracellular hydrophobic layer, protecting against water loss upon stomatal closure. To address the limited understanding of genes associated with the natural variation of leaf cuticular waxes and their connection to gc, we conducted statistical genetic analyses using leaf transcriptomic, metabolomic, and physiological data sets collected from a maize (Zea mays L.) panel of [~]300 inbred lines. Through a random forest analysis with 60 cuticular wax traits, it was shown that high molecular weight wax esters play an important role in predicting gc. Integrating results from genome-wide and transcriptome-wide studies (GWAS and TWAS) via a Fishers combined test revealed 231 candidate genes detected by all three association tests. Among these, 11 genes exhibit known or predicted roles in cuticle-related processes. Throughout the genome, multiple hotspots consisting of GWAS signals for several traits from one or more wax classes were discovered, identifying four additional plausible candidate genes and providing insights into the genetic basis of correlated wax traits. Establishing a partially shared genetic architecture, we identified 35 genes for both gc and at least one wax trait, with four considered plausible candidates. Our study uncovered the genetic control of maize leaf waxes, establishing a link between wax composition and gc, with implications for potentially breeding more water-use efficient maize. SIGNIFICANCE STATEMENTWe exploited natural variation in the abundance of maize leaf cuticular waxes to identify genetic determinants of wax composition and its relationship to cuticle function as a barrier against water loss. We identified a set of strongly supported candidate genes with plausible functions in cuticular wax biosynthesis or deposition and added to the evidence for wax esters as the most important wax for water barrier function, offering new tools for modification of cuticle-dependent traits.

genetics↗

Bayesian inference for copy number intra-tumoral heterogeneity from single-cell RNA-sequencing data

High-resolution molecular characterization of intra-tumoral clonal structure defined by genomic and epigenomic alterations is crucial in understanding the natural history of tumors and advancing cancer treatment strategies. Copy number alterations (CNA) are of notable importance as both drivers and markers of clonal structure that can now be assayed at individual cell resolution. However, specific computational methods are needed for accurate inference of clonal profiles and cell states from sparse and noisy single-cell omics data. Here, we develop a new Bayesian model to utilize single-cell RNA sequencing (scRNA-seq) data for automatic analysis of intra-tumoral clonal structure with respect to CNAs, without reliance on prior knowledge. The model clusters cells into sub-tumoral clones while simultaneously identifying CNA events in each clone, jointly modelling input from gene expression and germline single-nucleotide polymorphisms. Unlike previous methods, our approach automatically infers the number of clones present in the tumor. In detailed simulation studies our model frequently achieves very high (>90%) cell clustering accuracy and high (>80%) CN state inference accuracy, even in settings of high variance and sparsity. Overall, our method compares strongly against existing software tools. Application to human metastatic melanoma tumor data demonstrates accurate clustering of tumor and non-tumor cells, and reveals clonal CNA profiles that highlight functional gene expression differences between clones from the same tumor. Our method is implemented in a publicly-available, open-source R package, Chloris.

bioinformatics↗

De novo determination of mosquitocidal Cry11Aa and Cry11Ba structures from naturally-occurring nanocrystals

Cry11Aa and Cry11Ba are the two most potent toxins produced by mosquitocidal Bacillus thuringiensis subsp. israelensis and jegathesan, respectively. The toxins naturally crystallize within the host; however, the crystals are too small for structure determination at synchrotron sources. Therefore, we applied serial femtosecond crystallography at X-ray free electron lasers to in vivo-grown nanocrystals of these toxins. The structure of Cry11Aa was determined de novo using the single-wavelength anomalous dispersion method, which in turn enabled the determination of the Cry11Ba structure by molecular replacement. The two structures reveal a new pattern for in vivo crystallization of Cry toxins, whereby each of their three domains packs with a symmetrically identical domain, and a cleavable crystal packing motif is located within the protoxin rather than at the termini. The diversity of in vivo crystallization patterns suggests explanations for their varied levels of toxicity and rational approaches to improve these toxins for mosquito control.

molecular biology↗

Integration of GWAS and TWAS to elucidate the genetic architecture of natural variation for leaf cuticular conductance in maize

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association study (GWAS/TWAS) to identify candidate genes putatively regulating variation in leaf gc. Of the 22 plausible candidate genes identified, five were predicted to be involved in cuticle precursor biosynthesis and export, two in cell wall modification, nine in intracellular membrane trafficking, and seven in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor the ISTL1 genomic region from eight donor parents were evaluated for gc, confirming the association between gc and ISTL1 in a haplotype-based association analysis. The findings of this study provide novel insights into the role of regulatory variants in the development of the maize leaf cuticle, and will ultimately assist breeders to develop drought-tolerant maize for target environments. Sentence summaryWe performed an integrated GWAS/TWAS and identified 22 candidate genes putatively regulating variation in maize leaf gc. The association between gc and the strongest candidate causal gene, ISTL1, was validated with maize nested near-isogenic lines.

genetics↗

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

The outbreak of COVID-19 has emerged as a global pandemic. The unprecedented scale and severity call for rapid development of effective prophylactics or therapeutics. We here reported Nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin converting enzyme 2 (ACE2) with SARS-CoV-2-RBD-variants, bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among the seven candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with ND50 of 0.55 g/mL. Nb11-59 can be produced on a large-scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/242867v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@e4434org.highwire.dtl.DTLVardef@9fee79org.highwire.dtl.DTLVardef@1e15bb1org.highwire.dtl.DTLVardef@4adb0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Genome-wide association study for maize leaf cuticular conductance identifies candidate genes involved in the regulation of cuticle development

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of gc of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA in 2016 and 2017). Five genomic regions significantly associated with gc were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and {beta}-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of gc in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of gc and have the potential to help breeders more effectively develop drought-tolerant maize for target environments.\n\nArticle summaryThe cuticle serves as the major barrier to water loss when stomata are closed at night and under water-limited conditions and potentially relevant to drought tolerance in crops. We performed a genome-wide association study to elucidate the genetic architecture of natural variation for maize leaf cuticular conductance. We identified epidermally expressed candidate genes that are potentially involved in cuticle biosynthesis, trafficking and deposition, cutin polymerization, and cell wall modification. Finally, we observed moderately high predictive abilities for whole-genome prediction of leaf cuticular conductance. Collectively, these findings may help breeders more effectively develop drought-tolerant maize.

genetics↗

Network analyses implicate a role for PHYTOCHROME-mediated light signaling in the regulation of cuticle development in plant leaves

Plant cuticles are composed of wax and cutin, and evolved in the land plants as a hydrophobic boundary that reduces water loss from the plant epidermis. The expanding maize adult leaf displays a dynamic, proximodistal gradient of cuticle development, from the leaf base to the tip. Laser microdissection RNA Sequencing (LM-RNAseq) was performed along this proximodistal gradient, and complementary network analyses identified potential regulators of cuticle biosynthesis and deposition. Correlations between cuticle development and cell wall biosynthesis processes were identified, as well as evidence of roles for auxin and brassinosteroids. In addition, our network analyses suggested a previously undescribed function for PHYTOCHROME-mediated light signaling during cuticular wax deposition. Genetic analyses reveal that the phyB1 phyB2 double mutant of maize exhibits abnormal cuticle composition, supporting predictions of our coexpression analyses. Reverse genetic analyses also show that phy mutants of the moss Physcomitrella patens exhibit abnormal cuticle composition, suggesting a role for light-stimulated development of cuticular waxes during plant evolution.

plant biology↗

Double triage to identify poorly annotated genes in Maize: The missing link in community curation

The sophistication of gene prediction algorithms and the abundance of RNA-based evidence for the maize genome may suggest that manual curation of gene models is no longer necessary. However, quality metrics generated by the MAKER-P gene annotation pipeline identified 17,225 of 130,330 (13%) protein-coding transcripts in the B73 Reference Genome V4 gene set with models of low concordance to available biological evidence. Working with eight graduate students, we used the Apollo annotation editor to curate 86 transcript models flagged by quality metrics and a complimentary method using the Gramene gene tree visualizer. All of the triaged models had significant errors - including missing or extra exons, non-canonical splice sites, and incorrect UTRs. A correct transcript model existed for about 60% of genes (or transcripts) flagged by quality metrics; we attribute this to the convention of elevating the transcript with the longest coding sequence (CDS) to the canonical, or first, position. The remaining 40% of flagged genes resulted in novel annotations and represent a manual curation space of about 10% of the maize genome (~4,000 protein-coding genes). MAKER-P metrics have a specificity of 100%, and a sensitivity of 85%; the gene tree visualizer has a specificity of 100%. Together with the Apollo graphical editor, our double triage provides an infrastructure to support the community curation of eukaryotic genomes by scientists, students, and potentially even citizen scientists.

bioinformatics↗

Changes in lipid composition and ultrastructure associated with functional maturation of the cuticle during adult maize leaf development

Although extensive prior work has characterized cuticle composition, function, ultrastructure and development in many plant species, much remains to be learned about how these features are interrelated. Moreover, very little is known about the adult maize leaf cuticle in spite of its significance for agronomically important traits in this major crop. We analyzed cuticle composition, ultrastructure, and permeability along the developmental gradient of partially expanded adult maize leaves to probe the relationships between these features. The water barrier property is acquired at the cessation of cell expansion. Wax types and chain lengths accumulate asynchronously along the developmental gradient, while overall wax load does not vary. Cutin begins to accumulate prior to establishment of the water barrier and continues thereafter. Ultrastructurally, pavement cell cuticles consist of an epicuticular layer, a thin cuticle proper that acquires an inner, osmiophilic layer during development, and no cuticular layer. Cuticular waxes of the adult maize leaf are dominated by alkanes and wax esters localized mainly in the epicuticular layer. Establishment of the water barrier coincides with a switch from alkanes to esters as the major wax type, and the emergence of an osmiophilic (likely cutin-rich) layer of the cuticle proper.\n\nHiglight statementChemical, ultrastructural and functional analysis of cuticle development in partially expanded adult maize leaves revealed important roles for wax esters and an osmiophilic, likely cutin-rich, layer in protection from dehydration.

plant biology↗