Biology subjects

Cai, S.

Publications and source records attributed to Cai, S..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

The Hippo Pathway Regulates Corneal Endothelial Regeneration

Corneal endothelial cells (CECs) have limited regeneration capacity in primates while display a potent restorative capability in some species such as rodents after wounding. The mechanism which determines the regenerative capability of CECs remains poorly understood. Here, we identify that the Hippo signaling pathway is inhibited and the downstream effector YAP is activated during CEC wound healing in rabbit and mouse. Knockdown of Yap1 and pharmacological inhibition of YAP suppresses CECs wound healing in rodents in both in vitro and in vivo models. XMU-MP-1, a specific small molecular inhibitor for Hippo signaling pathway, can promote the corneal endothelial regeneration in rodents and corneal endothelial proliferation in cultured primate CECs, as well as in vivo non-human primate CEC wounding model. These findings suggest that Hippo pathway serves as a conserved signal to regulate corneal endothelial regeneration among various species, providing a novel target for non-invasive treatment of corneal endothelium decompensation.

cell biology↗

bioRxiv2025

Repurposed endogenous virus-like vesicles mediate dendritic cell long-range antigen presentation and T cell activation for enhanced cancer vaccination

Dendritic cells (DCs) release extracellular vesicles (DEVs) that amplify antigen presentation while incorporating patient-derived, rapidly evolving antigens. By enriching peptide-MHC and co-stimulatory ligands orders-of-magnitude above donor-cell levels, DEVs emerge as potent vesicle-vaccines, although efficacy remains limited by unclear mechanisms. We show that DCs repurpose viral components to generate endogenous virus-like vesicles (VLVs) that preferentially carry peptide-MHC and high-density co-stimulatory ligands, intensifying and extending antigen presentation. Upon antigen exposure, Arc partners with endogenous envelope proteins to assemble VLVs that directly engage T cells and trigger intrinsic adjuvanticity via viral mimicry. Arc-/- DEVs failed to prime antigen-specific T cell responses, whereas Arc overexpression with its 5'-UTR stem-loop shifted DEVs toward VLVs that trafficked to lymphoid organs, drove rapid CD4-assisted priming and durable CD8-biased memory, suppressed melanoma, and prolonged survival. These reveal a viral-mimicry mechanism enabling long-range immune activation and support Arc+ VLVs as an antigen-agnostic vaccine for cancer immunotherapy. HighlightsO_LIArc+ VLVs intensify and extend DC antigen presentation in vivo C_LIO_LIArc+ VLVs directly engage T cells and trigger viral-mimic adjuvanticity C_LIO_LIArc-/- DEVs fail to prime antigen-specific T cell responses C_LIO_LIEngineered Arc+ VLVs drive durable CD8-biased memory and tumor control C_LIO_LIArc+ VLV vaccination provides long-range and cross-tumor protection in vivo C_LI

bioengineering↗

bioRxiv2025

Extracellular matrix rigidity controls breast cancer metastasis via TYK2-mediated mechanotransduction

Mechanical cues from the extracellular matrix (ECM) regulate various cellular processes. In breast cancer, increased tumor stiffness is associated with elevated metastasis risk and poor survival. We identify a unique role of the JAK family kinase TYK2 in suppressing breast cancer metastasis under low ECM stiffness. Genetic or pharmacological inhibition of TYK2 in mammary acini and patient-derived organoids leads to invasion at low ECM stiffness by promoting Epithelial-Mesenchymal Transition, which is independent of cytokine-induced JAK/STAT signaling. TYK2 blockade promotes metastasis in breast tumor cell- and patient-derived xenografts. TYK2 localizes at the plasma membrane via IFNAR1 association under low stiffness, but it becomes cytoplasmic and inactivated at high stiffness. Normal human breast epithelium displays membrane-localized TYK2, whereas invasive breast tumors exhibit cytoplasmic TYK2. These findings uncover a TYK2-dependent mechanism by which ECM rigidity suppresses breast cancer metastasis and underscore the need for vigilant breast cancer screening in patients receiving TYK2 inhibitors.

cancer biology↗

bioRxiv2025

A neural circuit for female-specific defensive homeostasis in risk assessment

HighlightsSC CB1R+ neurons encode visual survival threats and initiate risk assessment in both sexes CB1R+ SC-LHb GABAergic circuit maintains defensive homeostasis in risk assessment in females eCBs gate this circuit by disinhibiting presynaptic GABA release exclusively in females Disruption of this mechanism female-specifically impairs risk assessment and stress coping In BriefLiu et al. identify a female-specific subcortical circuit in which eCB signaling, via CB1R on GABAergic terminals in the SC, suppresses transmission to the LHb to maintain precise defensive homeostasis in risk assessment. These findings uncover the circuit and neuronal mechanisms that contribute to the sexually dimorphic maintenance of defensive homeostasis. Risk assessment in defensive behavior is an adaptive mechanism shaped by natural selection, enabling individuals to evaluate potential threats and thereby maintain defensive homeostasis. However, it remains unknown whether specific neural circuits maintain their behavioral homeostasis in a sex-specific manner. To address this, we investigated its neural basis by hierarchical behavior analysis framework with neural circuit dissection. In mice of both sexes, visual survival threats activated cannabinoid 1 receptor (CB1R)-expressing neurons in the superior colliculus (SC) to initiate consistent risk assessment. Deletion of CB1R in SC GABAergic neurons female-specifically impairs risk assessment by disinhibiting GABA release in SC-lateral habenula (LHb) projections, resulting in shortened risk assessment. This disruption furthermore increases the occurrence of abnormal spontaneous behavior following chronic stress exclusively in females. We identified a female-specific SC-LHb GABAergic circuit gated by CB1R maintains defensive homeostasis in risk assessment. Our findings reveal how a conserved neuromodulatory system sex-specifically gates a subcortical circuit to orchestrate distinct survival strategies.

neuroscience↗

bioRxiv2025

LPS/TLR4-Activating Exosomes from M1-Polarized Avian Macrophages Enhances IBV Vaccine-Induced Protective Immunity in Chickens

Infectious bronchitis virus (IBV) presents a substantial economic burden to poultry production due to extensive serotypic diversity and limited cross-protection afforded by conventional vaccines. This study evaluated exosomes derived from M1-polarized chicken macrophages (HD11M1-exo) as a novel adjuvant for IBV vaccination. HD11M1-exo, isolated from LPS-activated HD11 macrophages via ultracentrifugation, demonstrated significant immunomodulatory properties across multiple experimental systems. In vitro analyses revealed HD11M1-exo enhanced macrophage phagocytosis and cellular immune activation via the LPS/TLR4 signaling pathway. In embryonated eggs, HD11M1-exo pre-treatment induced TNF- upregulation, enhanced viral resistance, and reduced pathological damage. In chickens, HD11M1-exo administration elevated CD80/CD86 and TGF-{beta}4 expression in respiratory tissues and increased secretory IgA in lacrimal fluid. When combined with H120 vaccine, HD11M1-exo significantly augmented both humoral immunity (elevated serum IgY and mucosal IgA) and cellular responses (increased CD80/CD86 expression), surpassing commercial adjuvants in efficacy. Following viral challenge, HD11M1-exo+H120 immunized chickens exhibited significantly reduced viral loads and attenuated histopathology compared to controls. These data collectively suggest that exosome-based formulations may serve as effective adjuvants for enhancing poultry vaccine immunogenicity and protective efficacy.

immunology↗

bioRxiv2025

Perturbing RNA localization for functional study in neurons

Spatial RNA organization plays a pivotal role in diverse cellular processes and diseases, but the functional implications of spatial RNA localization remain underexplored. We present CRISPR-mediated transcriptome organization (CRISPR-TO) that harnesses RNA-guided, nuclease-dead dCas13 for programmable control of RNA localization in live cells. CRISPR-TO enables targeted localization of RNAs to diverse subcellular compartments, including p-bodies, stress granules, telomeres, and nuclear stress bodies, across cell types. In primary cortical neurons, we demonstrate that repositioned mRNAs undergo local translation along neurites and at neurite tips and co-transport with ribosomes, with {beta}-actin mRNA localization enhancing the formation of dynamic filopodial protrusions and inhibiting axonal regeneration. Furthermore, CRISPR-TO-enabled parallel screening in primary neurons identifies Stmn2 mRNA localization as a driver of neurite outgrowth. By enabling large-scale perturbation of the spatial transcriptome, CRISPR-TO bridges a critical gap left by current sequencing and imaging technologies, offering a versatile platform for high-throughput functional interrogation of RNA localization in living cells and organisms.

bioengineering↗

bioRxiv2025

Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: implications for nociception

SUMMARYThough acetaminophen is a ubiquitous analgesic, its mechanism of action remains unknown. Thus, even though acetaminophen causes ∼500 deaths each year in the US it has not been possible to design safer alternatives. Because endocannabinoids may have a role in acetaminophen action, we examined interactions between the two. We now report that acetaminophen inhibits the activity of diacylglycerol lipase α (DAGLα), but not DAGLβ, decreasing production of the endocannabinoid 2-arachidonoyl glycerol. This gave rise to the counterintuitive hypothesis that decreasing endocannabinoid production by DAGLαinhibitionmay be antinociceptive in certain settings. Supporting this hypothesis, we find that DAGL inhibition by RHC80267 is antinociceptive in wildtype but not CB1 knockout mice in the hotplate test. We propose 1) that activation of DAGLα may exacerbate some forms of nociception and 2) a novel mechanism for the antinociceptive actions of acetaminophen whereby acetaminophen inhibits a DAGLα/CB1-based circuit that plays a permissive role in at least one form of nociception.

neuroscience↗

bioRxiv2025

Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice

Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum. This new color-neutral and reversible tissue transparency method enables optical transparency for imaging commonly used fluorophores in the green and yellow spectra. Notably, this approach facilitates tissue transparency for structural and functional imaging of the live mouse brain labeled with yellow fluorescent protein and GCaMP through the scalp and skull. We show that this method enables longitudinal imaging of the same brain regions in awake mice over multiple days during development. Histological analyses of the skin and systemic toxicology studies indicate minimal acute or chronic damage to the skin or body using this approach. This color-neutral and reversible tissue transparency technique opens new opportunities for noninvasive deep-tissue optical imaging, enabling long-term visualization of cellular structures and dynamic activity with high spatiotemporal resolution and chronic tracking capabilities. Significance StatementTissue scattering represents a major barrier to deep tissue imaging in vivo. We recently showed that tissue can be rendered transparent in the red spectrum using intensely absorbing dye molecules. Here, we introduce a new, color-neutral and reversible tissue transparency approach. We demonstrate longitudinal structural and functional imaging in the deep tissue of awake mice.

bioengineering↗

bioRxiv2024

An annotated biobank of triple negative breast cancer patient-derived xenografts featuring treatment-naive and longitudinal samples throughout neoadjuvant chemotherapy

Triple negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443) at MD Anderson Cancer Center, including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of PDX models were capable of lung metastasis. Comprehensive molecular profiling demonstrated conservation of genomes and transcriptomes between patient and corresponding PDX tumors, with representation of all major transcriptional subtypes. Transcriptional changes observed in the longitudinal PDX models highlight dysregulation in pathways associated with DNA integrity, extracellular matrix interactions, the ubiquitin-proteasome system, epigenetics, and inflammatory signaling. These alterations reveal a complex network of adaptations associated with chemoresistance. This PDX biobank provides a valuable resource for tackling the most pressing issues facing the clinical management of TNBC, namely chemoresistance and metastasis.

cancer biology↗

bioRxiv2024

Evaluation of T Cell Receptor Construction Methods from scRNA-Seq Data

T cell receptors (TCRs) serve pivotal roles in the adaptive immune system by enabling recognition and response to pathogens and irregular cells. Various methods exist for TCR construction from single-cell RNA sequencing (scRNA-seq) datasets, each with its unique characteristics regarding accuracy, sensitivity, adaptability, usability, time, and memory consumption. Yet, a comprehensive understanding of their relative strengths and weaknesses for different applications remains elusive. In our research, we implemented a benchmark analysis utilizing experimental single-cell immune profiling datasets encompassing paired scRNA-seq as input and scTCR-seq datasets as ground truth reference from human and mouse. Additionally, we introduced a novel simulator, YASIM-scTCR (Yet Another Simulator for single-cell TCR), capable of generating scTCR-seq reads containing a diverse array of TCR- derived sequences under different sequencing depths and read lengths. Our results consistently showed that TRUST4 outperformed others across multiple datasets, while MiXCR and DeRR also demonstrated considerable accuracy. We also discovered that the sequencing depth inherently imposes a critical constraint on successful TCR construction from scRNA-seq data. In summary, we present a benchmark study to aid researchers in choosing the most appropriate methods for reconstructing TCR from scRNA-seq data.

bioinformatics↗

bioRxiv2024

Phase transition of WTAP regulates m6A modification of interferon-stimulated genes

N6-methyladenosine (m6A) is the most prevalent modification of mRNA which controls diverse physiological processes. Although m6A modification has been reported to regulate type I interferon (IFN) responses by targeting the mRNA of IFN-{beta} and the interferon stimulated genes (ISGs), the detailed mechanism of how m6A methyltransferase complex (MTC) rapidly responds to conduct the modification on nascent mRNA during IFN-{beta} stimulation remains largely unclear. Here, we demonstrate that WTAP, the adaptor protein of m6A MTC, undergoes dephosphorylation-regulated phase transition from aggregates to liquid-like condensates under IFN-{beta} stimulation, thereby mediates m6A modification of a subset of ISG mRNAs to restrict their expression. The phase transition of WTAP promotes the interaction with nucleus-translocated transcription factor STAT1, which recruits MTC to the promoter regions of ISGs and directing the co-transcriptional m6A modification on ISG mRNAs. Collectively, our findings reveal a novel regulatory role of WTAP phase transition in manipulating signaling pathways and fine-tuning immune response by orchestrating dynamic m6A modification through the cooperation of transcription factors and MTC.

immunology↗

bioRxiv2024

Acarbose ameliorates Western diet-induced metabolic and cognitive impairments in the 3xTg mouse model of Alzheimer's disease

Age is the greatest risk factor for Alzheimers disease (AD) as well as for other disorders that increase the risk of AD such as diabetes and obesity. There is growing interest in determining if interventions that promote metabolic health can prevent or delay AD. Acarbose is an anti-diabetic drug that not only improves glucose homeostasis, but also extends the lifespan of wild-type mice. Here, we test the hypothesis that acarbose will not only preserve metabolic health, but also slow or prevent AD pathology and cognitive deficits in 3xTg mice, a model of AD, fed either a Control diet or a high-fat, high-sucrose Western diet (WD). We find that acarbose decreases the body weight and adiposity of WD-fed 3xTg mice, increasing energy expenditure while also stimulating food consumption, and improves glycemic control. Both male and female WD-fed 3xTg mice have worsened cognitive deficits than Control-fed mice, and these deficits are ameliorated by acarbose treatment. Molecular and histological analysis of tau and amyloid pathology identified sex-specific effects of acarbose which are uncoupled from the dramatic improvements in cognition, suggesting that the benefits of acarbose on AD are largely driven by improved metabolic health. In conclusion, our results suggest that acarbose may be a promising intervention to prevent, delay, or even treat AD, especially in individuals consuming a Western diet.

physiology↗

bioRxiv2024

Lysosome damage triggers acute formation of ER to lysosomes membrane tethers mediated by the bridge-like lipid transport protein VPS13C

Based on genetic studies, lysosome dysfunction is thought to play a pathogenetic role in Parkinsons disease (PD). Here we show that VPS13C, a bridge-like lipid transport protein and a PD gene, is a sensor of lysosome stress/damage. Upon lysosome membrane perturbation, VPS13C rapidly relocates from the cytosol to the surface of lysosomes where it tethers their membranes to the ER. This recruitment depends on Rab7 and requires a signal at the damaged lysosome surface that releases an inhibited state of VPS13C which hinders access of its VAB domain to lysosome-bound Rab7. While another PD protein, LRRK2, is also recruited to stressed/damaged lysosomes, its recruitment occurs at much later stages and by different mechanisms. Given the role of VPS13 proteins in bulk lipid transport, these findings suggest that lipid delivery to lysosomes by VPS13C is part of an early protective response to lysosome damage.

cell biology↗

bioRxiv2024

Mass mortality associated with Carpione Rhabdovirus in golden pompano (Trachinotus ovatus) in China: First report

A severe epizootic outbreak occurred in a deep-water cultured golden pompano (Trachinotus ovatus) in Guangdong Province, China (August-November 2023); the cumulative mortality was 65-82%. The diseased fish showed clinical signs of lethargy, anorexia, whirling movements, and hemorrhage at the base of the fins and in the upper and lower jaws before mass mortality. A Rhabdovirus strain, CARPV2023, was successfully isolated using FHM cells. Cytopathic effects of the tissue filtrate of the diseased golden pompano on FHM and EPC cell monolayers were characterized by rounded cells, grape-like cluster formation, detachment, and lysis. Histopathology revealed congestion, hemorrhage, and necrosis in the spleen, liver, kidney, and intestinal tissues of naturally and experimentally infected golden pompanos. Electron microscopy showed that bullet-shaped viral particles 183.5-201.6-nm long and 57.3-82.7-nm wide budded from cell membrane or aggregated around the infected FHM cells. The virus remained stable for 7 days at 4-33{degrees}C and grew optimally at 28{degrees}C. Whole-genome sequencing and phylogenetic analysis based on the full genome further indicated that the CARPV2023 strain is a member of Carpione Rhabdovirus, which is related to Novirhabdovirus with unclassification. A specific nested reverse transcriptase-polymerase chain reaction confirmed the presence of CARPV in the affected golden pompano. Much higher mortality was observed in challenged golden pompanos than in the controls through intraperitoneal injection and immersion infection. In situ hybridization showed positive reactions in the fish tissues. This is the first study to report natural CARPV infections in marine fish in the world.

microbiology↗

bioRxiv2024

Unveiling Tissue Structure and Tumor Microenvironment from Spatially Resolved Transcriptomics by Hypergraph Learning

Spatial omics technologies have revolutionized life sciences by enabling the simultaneous acquisition of biomolecular and spatial information. Identifying spatial patterns is crucial for understanding organ development and tumor microenvironments. However, the emergence of diverse spatial omics resolutions in these technologies has made it challenging to accurately characterize spatial domains at finer resolutions. To address this, we propose HyperSTAR, a hypergraph-based method designed to precisely identify spatial domains across varying resolutions by leveraging higher-order relationships among spatially adjacent tissue programs. Specifically, a gene expression-guided hyperedge decomposition module is introduced to refine the hypergraph structure to accurately delineate spatial domains boundaries. Additionally, a hypergraph attention convolutional neural network is designed to adaptively learn the importance of each hyperedge, enhancing the models ability to capture complex higher-order relationships within spatially neighboring multi-spots and/or single cells. HyperSTAR outperforms existing graph neural network models in tasks such as uncovering tissue substructures, inferring spatiotemporal patterns, and denoising spatially resolved gene expressions. It effectively handles diverse spatial omics data types and scales seamlessly to large datasets. The method successfully reveals spatial heterogeneity in breast cancer sections, with findings validated through functional and survival analyses of independent clinical data. HyperSTAR represents a significant advancement in spatial omics analysis, representing a robust tool for exploring complex spatial patterns across varying resolutions and data types. Its ability to capture intricate higher-order relationships among spatially neighboring spots/cells makes it an invaluable tool for advancing research in life sciences, particularly in cancer and developmental biology.

bioinformatics↗

bioRxiv2024

A Role for Cross-linking Proteins in Actin Filament Network Organization and Force Generation

The high turgor pressure across the plasma membrane of yeasts creates a requirement for substantial force production by actin polymerization and myosin motor activity for clathrin-mediated endocytosis (CME). Endocytic internalization is severely impeded in the absence of fimbrin, an actin filament crosslinking protein called Sac6 in budding yeast. Here, we combine live-cell imaging and mathematical modeling to gain new insights into the role of actin filament crosslinking proteins in force generation. Genetic manipulation showed that CME sites with more crosslinking proteins are more effective at internalization under high load. Simulations of an experimentally constrained, agent- based mathematical model recapitulate the result that endocytic networks with more double-bound fimbrin molecules internalize the plasma membrane against elevated turgor pressure more effectively. Networks with large numbers of crosslinks also have more growing actin filament barbed ends at the plasma membrane, where the addition of new actin monomers contributes to force generation and vesicle internalization. Our results provide a richer understanding of the crucial role played by actin filament crosslinking proteins during actin network force generation, highlighting the contribution of these proteins to the self-organization of the actin filament network and force generation under increased load.

cell biology↗

bioRxiv2024

Mechanical cues of extracellular matrix determines tumor innervation

Peripheral tumors can establish local autonomic and sensory nerve networks, termed as tumor innervation (TIN), to support tumorigenesis and metastasis. While nerve dependence in cancers is well-established, the mechanisms governing TIN remain unclear. Here, we report that extracellular matrix (ECM) stiffness, a major mechanical abnormality in the tumor microenvironment (TME), is an essential contributor of TIN. In preclinical models, reducing lysyl oxidase-mediated ECM crosslinking lowers tissue stiffness and TIN in pancreatic cancer, while inflammation-induced matrix stiffening boosts the hyperinnervation of the pancreatic precursor lesions. Mechanistically, {beta}1-containing integrins sense the mechanical cues exerted by ECM stiffness, and the translational co-activator YAP1 acts as an essential nuclear relay to induce the expression of neurotropic genes, particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). 3D imaging of the whole cleared pancreas reveals that blockade of mechanosensor integrin {beta}1 or pharmacological inhibition of the mechanotransducer YAP1 effectively reduces TIN. In clinical settings, tumor samples with a dense, crosslinked, and stiffened ECM exhibit significant TIN. In summary, these findings identify ECM stiffness as an important driver of TIN and suggest that targeting integrin {beta}1/YAP1-dependent mechanotransduction may counteract TIN.

neuroscience↗

bioRxiv2024

The molecular basis of pine wilt disease resistance in Pinus massoniana

Pine wilt disease (PWD), caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus, results in significant economic and ecological damage to Pinus forests and plantations worldwide. Pinus massoniana is the primary host of PWD in southern China, but its response to the PWN remains largely unstudied. Previously, we observed PWD in a P. massoniana nursery that contained over 71 commonly used cultivars. Through field phenotyping, we identified two groups of PWN resistant cultivars. Resistant cultivars (RC) exhibited very low PWN carrying amounts (PCA) and had relatively low mortality, and tolerant cultivars (TC) had high PCA but low mortality. In this study, we confirmed via PWN inoculation assays that the resistant and tolerant cultivars had lower mortality rates, 10% and 11%, respectively, than other cultivars (which had a mortality rate of 83.3%). The RC had a PCA that was significantly lower than that of other cultivars, while the TC exhibited a higher PCA. To explore the molecular mechanisms underlying the response of P. massoniana to PWN, the transcriptome and metabolome of the above cultivars were profiled by high throughput sequencing. As no reference genome is available for P. massoniana, we generated a new full-length transcriptome library with iso-seq. Using the transcriptome and metabolome from different P. massoniana cultivars inoculated with PWN, we found three major PWD resistance strategies. 1) The common response strategy involved three important molecular pathways. First, synthesis of indole-3-acetic acid (IAA) and abcisic acid (ABA) were suppressed during PWN invasion, thus suppressing the synthesis of polysaccharides (especially myo-inositol and trehalose) and (-)-riboflavin through ABC transporters. Second, by inhibiting aspartic acid, the synthesis of arginine and proline through APS5 (aspartate aminotransferase 5) were suppressed. Third, by reducing cysteine, GERD (germacrene D synthase) was up-regulated, and sesquiterpenoid and triterpenoid metabolites were accumulated to resist PWN invasion. 2) The most effective resistance strategy involved the accumulation of reactive oxygen species (ROS), which enhanced jasmonic acid (JA) accumulation and highly induced the expression of chitinase, thus improving resistance to PWN. 3) The tolerance strategy involved the induction of phosphatidylcholine, which promoted flavonoid and anthocyanin synthesis via LPIN (phosphatidate phosphatase), LOX2S (lipoxygenase), and LOX1_5 (linoleate 9S-lipoxygenase), thus significantly inhibiting the pathogenicity of the PWN but not the PCA. These results illustrate the molecular mechanisms by which P. massoniana cultivars resist or tolerate PWN and are of great significance in the prevention and control of PWD.

plant biology↗