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Zhang, N.

Publications and source records attributed to Zhang, N..

At least 217 records · Page 12Linked to original sources

BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

immunology↗

Sequence characterization of the complete chloroplast genome of Eupatorium fortunei

Eupatorium fortunei has been utilized as herbal medicine to cure various diseases in various regions of the world especially China, Korea, and other Asian countries. The available literature shows Eupatorium fortunei contain anti-metastatic, anti-angiogenic, anti-bacterial, and anti-oxidant, along with compounds to cure human cancer. In present study, Eupatorium fortunei was used as an experimental material, and its genome was sequenced based on high-throughput sequencing technology. We assembled the complete chloroplast genome of Eupatorium fortunei and obtained NCBI accession number (OK545755). We analyzed chloroplast genome structure of Eupatorium fortunei and systematic analysis was conducted, including the size of the entire genome sequence, genome volume, large single-copy (LSC), small single-copy (SSC), inverted repeat region (IR)-LSC/SSC boundaries, etc. The obtained results showed that chloroplast genome of Eupatorium fortunei is a typical tetrad structure with a total length of 152,401 bp and a sum of 133 annotated genes, including eight ribosomal RNA (rRNA)-encoding genes, 37 transfer RNA (tRNA)-encoding genes, 87 protein-encoding genes, and one pseudo-gene. A sum of 29 Single Sequence Repeats (SSR)s were identified for mono-nucleotide, di-nucleotide and tri-nucleotide microsatellites with mono-nucleotides in majority. The phylogenetic analysis revealed that Eupatorium fortunei is more closely related to Litothamnus nitidus and belongs to the same branch. The genome assembly and analysis of the chloroplast genome of Eupatorium fortunei provides more accurate evidence for further taxonomic identification and localization of Asteraceae/Compositae plant.

bioinformatics↗

Free fatty acid receptor 4 (FFAR4) regulates cardiac oxylipin balance to promote inflammation resolution in a model of heart failure preserved ejection fraction secondary to metabolic syndrome

Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor for long-chain fatty acids that improves metabolism and attenuates inflammation. Heart failure preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of patients has meta-bolic syndrome (MetS). Mechanistically, systemic, non-resolving inflammation associated with MetS might promote HFpEF. Interestingly, we recently demonstrated that Ffar4 is cardioprotective in pressure overload. The beneficial effects of Ffar4 on metabolism/inflammation, the high incidence of MetS in HFpEF patients, and the cardioprotective effects of Ffar4 led us to hypothesize that loss of Ffar4 would worsen remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME in their water (HFpEF-MetS diet) to induce HFpEF-MetS. In male Ffar4KO mice, the HFpEF-MetS diet induced similar metabolic deficits, but worsened diastolic function and microvascular rarefaction compared to wild-type mice. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsening of HFpEF. Loss of Ffar4 in males altered the balance of inflammatory oxylipins in the heart, decreasing the eicosapentaenoic acid derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachadonic acid derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio, reflecting a more proinflammatory state, was associated with increased macrophage numbers, which in turn correlated with worsened ventricular remodeling in male Ffar4KO hearts. In summary, our data suggest that Ffar4 controls the pro/anti-inflammatory oxylipin balance in the heart to modulate macrophage function and attenuate HFpEF remodeling.

physiology↗

Tree species and genetic diversity increase productivity via functional diversity and trophic feedbacks

Addressing global biodiversity loss requires an expanded focus on multiple dimensions of biodiversity. While most studies have focused on the consequences of plant interspecific diversity, our mechanistic understanding of how the diversity within a given plant species (genetic diversity) affects plant productivity remains limited. Here, we use a tree species x genetic diversity experiment to disentangle the effects of species diversity and genetic diversity, and how they are related to tree functional diversity and trophic feedbacks. Tree species as well as genetic diversity increased tree productivity via increased tree functional diversity, reduced soil fungal diversity and marginally reduced herbivory. The effect of tree genetic diversity on productivity was partly different between tree species monocultures and mixtures: the functional diversity effect resulting from tree genetic diversity was only found in tree species monocultures, but the trophic feedbacks via herbivory were similar in species monocultures and mixtures. Given the complexity of interactions between tree species and genetic diversity, tree functional diversity and trophic feedbacks on productivity, we suggest that both tree species and genetic diversity should be considered in reforestation.

ecology↗

Monitoring of urban ecological environment including air quality using satellite imagery

Rapid urbanisation has highlighted problems in the urban ecological environment and stimulated research on the evaluation of urban environments. In previous studies, key factors such as greenness, wetness, and temperature were extracted from satellite images to assess the urban ecological environment. Although air pollution has become increasingly serious as urbanisation proceeds, information on air pollution is not included in existing models. The Sentinel-5P satellite launched by the European Space Agency in 2017 is a reliable data source for monitoring air quality. By making full use of images from Landsat 8, Sentinel-2A, and Sentinel-5P, this work attempts to construct a new remote sensing monitoring index for urban ecology by adding air quality information to the existing remote sensing ecological index. The proposed index was tested in the Beijing metropolitan area using satellite data from 2020. The results obtained using the proposed index differ greatly in the central urban region and near large bodies of water from those obtained using the existing remote sensing monitoring model, indicating that air quality plays a significant role in evaluating the urban ecological environment. Because the model constructed in this study integrates information on vegetation, soil, humidity, heat, and air quality, it can comprehensively and objectively reflect the quality of the urban ecological environment. Consequently, the proposed remote sensing index provides a new approach to effectively monitoring the urban ecological environment.

ecology↗

Drug design and repurposing with a sequence-to-drug paradigm

Drug development based on target proteins has been a successful approach in recent decades. A conventional structure-based drug design pipeline is a complex, human-engineered pipeline with multiple independently optimized steps. Advances in end-to-end differentiable learning suggest the potential benefits of similarly reformulating drug design. Here, we proposed a new sequence-to-drug paradigm that discovers drug-like small-molecule modulators directly from protein sequences and validated this concept for the first time in three stages. First, we designed TransformerCPI2.0 as a core tool for the sequence-to-drug paradigm, which exhibited competitive performance with conventional structure-based drug design approaches. Second, we validated the binding knowledge that TransformerCPI2.0 has learned. Third, we applied a sequence-to-drug paradigm to discover new hits for E3 ubiquitin-protein ligases: speckle-type POZ protein (SPOP), ring finger protein 130 (RNF130) which does not have a 3D structure, and repurposed proton pump inhibitors (PPIs) for ADP-ribosylation factor 1 (ARF1). This first proof of concept shows that the sequence-to-drug paradigm is a promising direction for drug development.

molecular biology↗

An Orobanche cernua x Orobanche cumana segregating population provides insight into the regulation of germination specificity in a parasitic plant

Germination of seeds of Orobanche species requires specific chemicals exuded by host roots. A family of "divergent" KARRIKIN INSENSITIVE2 (KAI2d) genes encode proteins that recognize strigolactone (SL) class germination simulants. We explored specificity of germination stimulant detection by analyzing interspecific segregants of a cross between Orobanche cernua and O. cumana, closely related species that differ in stimulant response. O. cernua parasitizes tomato and germinates in response to the SL orobanchol, while O. cumana parasitizes sunflower and responds to dehydrocostus lactone (DCL). KAI2d genes were catalogued in parents and in segregants that showed stimulant specificity. KAI2d genes were also functionally assayed in the Arabidopsis kai2 mutant background. We identified five full-length KAI2d genes in O. cernua and eight in O. cumana. The O. cernua KAI2d2, as well as its ortholog in O. cumana, are associated with SL perception. A cluster of O. cumana KAI2d genes was genetically linked to DCL perception, although no specific receptor gene was identified by heterologous complementation. These findings support the KAI2d-mediated perception of SLs, but fall short of explaining how O. cumana perceives DCL. The ability of some O. cumana KAI2d genes to detect SLs points to the involvement of additional factors in regulating stimulant specificity.

plant biology↗

Alpha-1 Antitrypsin Limits Neutrophil Extracellular Trap Disruption of Airway Epithelial Barrier Function

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/484920v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@841dbforg.highwire.dtl.DTLVardef@1bd0188org.highwire.dtl.DTLVardef@1afaf97org.highwire.dtl.DTLVardef@130fd03_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Direct fluorescent labeling of NF186 and NaV1.6 in living primary neurons using bioorthogonal click chemistry

The axon initial segment (AIS) is a highly specialized neuronal compartment that regulates the generation of action potentials and maintenance of neuronal polarity. Despite its importance, live imaging of the AIS is challenging due to the limited number of suitable labeling methods. To overcome this limitation, we established a novel approach for live labeling of the AIS using unnatural amino acids (UAAs) and bioorthogonal click chemistry. The small size of the UAAs and the possibility of introducing them virtually anywhere into the target proteins make this method particularly suitable for live labeling and imaging of complex and spatially restricted proteins. With this approach, we labeled two large AIS components, the 186 kDa isoform of neurofascin (NF186) and the 260 kDa voltage-gated sodium channel (NaV1.6), and performed widefield and confocal microscopy in fixed and living neurons. Moreover, we demonstrated the applicability of this method by studying the localization of two epilepsy-causing NaV1.6 variants with a loss-of-function effect. Finally, to further improve the efficiency of the UAA incorporation, we developed adeno-associated viral (AAV) vectors for click labeling in primary neurons. The use of AAV vectors will facilitate the transfer of UAA-based click labeling technology to more complex biological systems, such as organotypic slice cultures, organoids, and animal models.

neuroscience↗

Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages (MDMs). However, whether TRMs and MDMs have functional distinction under differing pathologies is not understood. Here, we show a significant portion of macrophages that accumulated during pancreatitis and pancreatic cancer were expanded from TRMs. We further established that pancreas TRMs have a distinct extracellular matrix remodeling phenotype that was critical for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and animal death, due to impaired acinar cell survival and recovery. In pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.

immunology↗

A longitudinal CA2/3 to CA1 circuit for initiating context-dependent associative learning

Associating environmental context with emotional experience is a vital brain function that requires the activity in both dorsal and ventral hippocampus. While only ventral hippocampus connects with the amygdala, a hub for fear learning, it remains unclear how the two hippocampal areas interact during contextual fear conditioning (CFC). We found that projections from dorsal CA2/CA3 (dCA2/3) to the dorsal part of ventral CA1 (vCA1d) contributed significantly to CFC. Deep-brain Ca2+ imaging revealed a CFC-enhanced difference in neuronal activities evoked by conditioned vs. neutral environmental context in both dCA2/3 and vCA1d areas. Notably, contextual fear retrieval correlated with changes in conditioned context-evoked activity in vCA1d, but not in dCA2/3. Furthermore, slice recordings showed that CFC potentiated dCA2/3-to-vCA1d projection strength, in line with coordinated elevation of monosynaptic excitation and reduction of disynaptic inhibition mediated by somatostatin-expressing interneurons. Thus, vCA1d represents a critical site for initiating emotional association with contextual information from dCA2/3.

neuroscience↗

Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies

Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.

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↗

The vagus nerve mediates the stomach-brain coherence in rats

Interactions between the brain and the stomach shape both cognitive and digestive functions. Recent human studies report spontaneous synchronization between brain activity and gastric slow waves in the resting state. However, this finding has not been replicated in any animal models. The neural pathways underlying this apparent stomach-brain synchrony is also unclear. Here, we performed functional magnetic resonance imaging while simultaneously recording body-surface gastric slow waves from anesthetized rats in the fasting vs. postprandial conditions and performed a bilateral cervical vagotomy to assess the role of the vagus nerve. The coherence between brain fMRI signals and gastric slow waves was found in a distributed "gastric network", including subcortical and cortical regions in the sensory, motor, and limbic systems. The stomach-brain coherence was largely reduced by the bilateral vagotomy and was different between the fasting and fed states. These findings suggest that the vagus nerve mediates the spontaneous coherence between brain activity and gastric slow waves, which is likely a signature of real-time stomach-brain interactions. However, its functional significance remains to be established.

neuroscience↗

Spatially resolved single-cell deconvolution of bulk RNA-seq using Bulk2Space

Uncovering the tissue molecular architecture at single-cell resolution could help better understand organisms biological and pathological processes. However, bulk RNA-seq can only measure gene expression in cell mixtures, without revealing the transcriptional heterogeneity and spatial patterns of single cells. Herein, we introduce Bulk2Space (https://github.com/ZJUFanLab/bulk2space), a deep learning framework-based spatial deconvolution algorithm that can simultaneously disclose the spatial and cellular heterogeneity of bulk RNA-seq data using existing single-cell and spatial transcriptomics references. The use of bulk transcriptomics to validate Bulk2Space unveils, in particular, the spatial variance of immune cells in different tumor regions, the molecular and spatial heterogeneity of tissues during inflammation-induced tumorigenesis, and spatial patterns of novel genes in different cell types. Moreover, Bulk2Space is utilized to perform spatial deconvolution analysis on bulk transcriptome data from two different mouse brain regions derived from our in-house developed sequencing approach termed Spatial-seq. We have not only reconstructed the hierarchical structure of the mouse isocortex but also further annotated cell types that were not identified by original methods in the mouse hypothalamus.

bioinformatics↗

Comparative Phenotyping of Two Commonly Used Chlamydomonas reinhardtii Background Strains: CC-1690 (21gr) and CC-5325 (the CLiP Mutant Library Background)

The unicellular green alga Chlamydomonas reinhardtii is an excellent model organism to investigate many essential cellular processes in photosynthetic eukaryotes. Two commonly used background strains of Chlamydomonas are CC-1690 and CC-5325. CC-1690, also called 21gr, has been used for the Chlamydomonas genome project and several transcriptome analyses. CC-5325 is the background strain for the Chlamydomonas Library Project (CLiP). Photosynthetic performance in CC-5325 has not been evaluated in comparison with CC-1690. Additionally, CC-5325 is often considered to be cell-wall deficient, although detailed analysis is missing. The circadian rhythms in CC-5325 are also unclear. To fill these knowledge gaps and facilitate the use of the CLiP mutant library for various screens, we performed phenotypic comparisons between CC-1690 and CC-5325. Our results showed that CC-5325 grew faster heterotrophically in dark and equally well in mixotrophic liquid medium as compared to CC-1690. CC-5325 had lower photosynthetic efficiency and was more sensitive to heat than CC-1690. Furthermore, CC-5325 had an intact cell wall with comparable integrity to that in CC-1690, though appears to have reduced thickness. Finally, CC-5325 could perform phototaxis, but could not maintain a sustained circadian rhythm of phototaxis as CC160 did. Our results will be useful for researchers in the Chlamydomonas community to choose suitable background strains for mutant analysis and employ the CLiP mutant library for genome-wide mutant screens under appropriate conditions, especially in the areas of photosynthesis, thermotolerance, cell wall, and circadian rhythms.

plant biology↗

The biosynthetic-secretory pathway, supplemented by recycling routes, specifies epithelial membrane polarity

In prevailing epithelial polarity models, membrane-based polarity cues (e.g., the partitioning-defective PARs) position apicobasal cellular membrane domains. Intracellular vesicular trafficking expands these domains by sorting apicobasal cargo towards them. How the polarity cues are polarized and how sorting confers long-range vesicle directionality is still unclear. Here, a systems-based approach using two-tiered C. elegans genomics-genetics screens identifies trafficking molecules that are not implicated in apical sorting yet polarize apical membrane and PAR complex components. Live tracking of polarized membrane biogenesis suggests that the biosynthetic-secretory pathway, linked to recycling routes, is asymmetrically oriented towards the apical domain during its biosynthesis, upstream of PARs and independent of polarized target domains. This mode of membrane polarization could offer solutions to questions of current models of polarity and polarized trafficking. One-Sentence SummaryBiosynthetic trafficking polarizes epithelial membranes by asymmetrically expanding the apical domain into the growing membrane.

cell biology↗

Elevated ozone concentration and nitrogen addition increase poplar rust severity by shifting the phyllosphere microbial community

The tropospheric ozone and nitrogen deposition are two major environmental pollutants. Numerous studies have focused on the negative impacts of elevated O3 and the complementary effect of soil N addition to tree physiological characteristics. However, it was notoriously ignored of how elevated O3 with N addition affect tree immunity in face of pathogen infection, as well as of the important roles of phyllosphere microbiome community in host-pathogen-environment interplay. Here, we examined the effects of elevated O3 and soil N addition on poplar leaf rust (Melampsora larici-populina) severity of two susceptible hybrid poplars (clone 107: Populus euramericana cv. 74/76; clone 546: P. deltoides {subseteq} P. cathayana) in Free-Air-Controlled-Environment plots, besides, the link between Mlp-susceptibility and changes in microbial community was determined using Miseq amplicon sequencing. Rust severity of clone 107 significantly increased under elevated O3 or N addition only, however, the negative impact of elevated O3 could be significantly alleviated when simultaneously conducting N addition, likewise, this trade-off was also found in its phyllosphere microbial -diversity responding to elevated O3 and N addition. However, the rust severity of clone 546 did not significantly differ in the cases of elevated O3 and N addition. Mlp infection altered microbial community composition and increased its sensitivity to elevated O3 assessed by significantly different abundance of taxa. Elevated O3 and N addition reduced the complexity of microbial community, which may explain the increased severity of poplar rust. These findings demonstrated that poplars need shifting phyllosphere microbial associations to optimize plant immunity in response to environmental changes. ImportanceExploitation of the interaction mechanisms between host plants and pathogens is the essential basis in disease control. However, while much was known about the molecular determinants in pathogenesis process in the past decades, less is known about the role of nonpathogenic microbial community in plant-pathogen interaction, especially when some host plants are currently encountering severe environmental stresses, such as elevated ozone concentration and superfluous nitrogen addition. Thus, we targeted at the widespread and detriment rust disease (poplar-poplar rust) to dissect the influences of elevated ozone and nitrogen addition on rust disease severity and how phyllosphere microbial groups interacting with both poplars and rust pathogen under these biotic stresses. Our findings could be used to prescribe ecological information about poplar plantation in areas with high levels of ozone pollution and better understand the important roles of microbiome in plant heath.

microbiology↗