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The cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4‐based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS‐DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4‐PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4‐PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy. Tailor‐designed ZnFe2O4‐based nanosystem can respond to the tumour microenvironment and stimulate anti‐tumour immune responses by enhancing the cGAS/STING pathway. Moreover, it remodels immunosuppressive microenvironment, and effectively inhibits tumour growth as well as postoperative recurrence.

Ring rot, caused by Botryosphaeria dothidea , is an important fungal disease of pear fruit during postharvest storage. Melatonin, as a plant growth regulator, plays an important role in enhancing the stress resistance of pear fruits. It enhances the resistance of pear fruits to ring rot by enhancing their antioxidant capacity. However, the underlying mechanism remains unclear. In this study, we examined the effect of melatonin on the growth of B. dothidea . Results showed that melatonin did not limit the growth of B. dothidea during in vitro culture. However, metabolomics and transcriptomics analyses of ‘Whangkeumbae’ pear ( Pyrus pyrifolia ) revealed that melatonin increased the activity of antioxidant enzymes, including peroxidase (POD), superoxide dismutase (SOD), and polyphenol oxidase (PPO), in the fruit and activated the phenylpropanoid metabolic pathway to improve fruit resistance. Furthermore, melatonin treatment significantly increased the contents of jasmonic acid and phlorizin in pear fruit, both of which could improve disease resistance. Jasmonic acid regulates melatonin synthesis and can also promote phlorizin synthesis, ultimately improving the resistance of pear fruit to ring rot. In summary, the interaction between melatonin and jasmonic acid and phlorizin enhances the antioxidant defense response and phenylpropanoid metabolism pathway of pear fruit, thereby enhancing the resistance of pear fruit to ring rot disease. Our results provide new insights into the application of melatonin in the resistance to pear fruit ring rot.

Background Crown gall disease, caused by the pathogenic bacterium Agrobacterium tumefaciens , is responsible for extensive economic losses in orchards. Cherry rootstock ‘CDR-1’ ( Prunus mahaleb ) shows high resistance but the mechanism remains unclear. Here, we examined the morphology of pathogen-infected root neck surface, determined the activity of 10 defense-related enzymes and the content of salicylic acid (SA) and jasmonic acid (JA), and also applied transcriptome analysis, transient expression and transgenic verification to explore the crown gall resistance genes in ‘CDR-1’ plants. Results In our study, peroxidase increased in the first 10 days, while phenylalanine ammonialyase and lipoxygenase increased in the first 15 days post-infection. Four key enzymes in the AsA-GSH cycle also responded, to a certain extent; although JA content increased significantly after the treatment, the SA content did not. In a follow-up transcriptome analysis, the differentially expressed genes Pm4CL2 , PmCYP450 , PmHCT1 , PmHCT2 , and PmCAD were up-regulated. Based on the above results, we focused on the lignin biosynthetic pathway, and further measured lignin content, and found it increased significantly. The Pm4CL2 gene was used to conduct transient expression and transgenic experiments to verify its function in crown gall disease resistance. It showed the relative expression of the treatment group was almost 14-fold that of the control group at 12 h post-treatment. After the infection treatment, clear signs of resistance were found in the transgenic lines; this indicated that under the higher expression level and earlier activation of Pm4CL2 , plant resistance was enhanced. Conclusions The crown gall resistance of ‘CDR-1’ is likely related to the lignin biosynthetic pathway, in which Pm4CL2 functions crucially during the plant defense response to the pathogen A. tumefaciens . The results thus offer novel insights into the defense responses and resistance mechanism of cherry rootstock ‘CDR-1’ against crown gall disease.

Background Iron is essential for the growth and development of trace elements in plants, and iron deficiency can lead to leaf chlorosis. Ammonium and nitrate are the major forms of nitrogen present in soils. Ammonium nitrate alleviates the chlorosis of leaves caused by iron deficiency, but the mechanism is not clear in pear. Results Ammonium nitrate induced the increase of nitric oxide (NO) under iron deficiency. We further analyzed the effect of NO by exogenous NO treatment. The results showed that ammonium nitrate and NO increased the activity of ferric chelate reductase. NO induced the expression of multiple IRT genes and promoted the transmembrane transport of irons. Ammonium nitrate and NO promoted the activity of nitrogen assimilation-related enzymes and the nitrogen absorption capacity, and they also increased glutamine synthetase activity. Finally, ammonium nitrate and NO increased chlorophyll synthesis, with subsequent increase in the photosynthetic capacity of plants and accumulation of biomass. Conclusion Ammonium nitrate indirectly alleviates the symptoms of plant yellowing by promoting the increase of NO, which increases the response of iron transporters. Both substances increase the nitrogen accumulation in plants. This study demonstrates a new option for minimizing Fe deficiency by regulating the balance between nutrients.

Although cytotoxic T lymphocytes (CTLs) activation combined with programmed cell death‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) axis blockade have emerged as an effective strategy to improve immunotherapeutic potency, it remains challenging to realize the spatiotemporal synergy of these two components. Herein, the study reports an engineered bacterial‐based delivery system that can simultaneously promote CTLs infiltration and control PD‐L1 binding protein (PD‐L1 trap) release on demand at tumor site. The drug release button of this tumor targeting system is the specific temperature, which is accomplished by dual‐modified melanin nanoparticles with photothermal conversion capacity on the engineered bacterial. These dual‐modified nanoparticles can form in situ reservoir of heat supplier and antitumor immunity activator once arriving at tumor microenvironment (TME). Importantly, the study establishes the personalized administration regimen according to TME changes, and perform local laser irradiation to trigger PD‐L1 trap production only in TME when infiltrated CTLs reach the highest level. This work provides a flexible platform for optimizing cancer immunotherapy. EB@MPCM with spatiotemporal synergistic delivery system can effectively activate cGAS‐STING signaling pathway and realize in situ blockade of PD‐1/PD‐L1 axis at the time of maximal CTLs infiltration in tumor microenvironment (TME).

Drought is one of the main factors affecting sweet cherry yields, and cherry rootstocks can provide a range of tree vigor levels to better match sweet cherries with the characteristics of the soil. To investigate the molecular events of the cherry to water deficiency, we performed transcriptomic and metabolomic analyses of Prunus mahaleb CDR-1 (drought-tolerant cherry rootstock (DT)) and P. cerasus × P. canescens Gisela 5 (drought-susceptible cherry rootstock (DS)), respectively. The results revealed 253 common drought-responsive genes in leaves and roots in DT and 17 in DS; 59 upregulated metabolites were explored in leaves in DT and 19 were explored in DS. Differentially expressed metabolites related to the cyanoamino acid metabolism pathway and phenylpropanoid biosynthesis pathway may be key factors in the difference in drought resistance in the two rootstocks. Moreover, six central metabolites—3-cyanoalanine, phenylalanine, quinic acid, asparagine, p-benzoquinone, and phytosphingosine—were identified as potential biological markers of drought response in cherries and may be key factors in the difference in drought resistance, along with caffeic acid and chlorogenic acid. We also selected 17 differentially expressed genes as core candidate genes and the mechanism of DT in response to drought is summarized.

The quality of seedlings is an important factor for development of the pear industry. A strong seedling with few branches and suitable internodes is ideal material as a rootstock for grafting and breeding. Several branching mutants of pear rootstocks were identified previously. In the present study, ‘QAU-D03’ ( Pyrus communis L.) and it’s mutants were used to explore the mechanism that affects branch formation by conducting phenotypic trait assessment, hormone content analysis, and transcriptome analysis. The mutant plant (MP) showed fewer branches, shorter 1-year-old shoots, and longer petiole length, compared to original plants (OP), i.e., wild type. Endogenous hormone analysis revealed that auxin, cytokinin, and jasmonic acid contents in the stem tips of MP were significantly higher than those of the original plants. In particular, the jasmonic acid content of the MP was 1.8 times higher than that of the original plants. Transcriptome analysis revealed that PcCOI1 , which is a transcriptional regulatory gene downstream of the jasmonic acid signaling pathway, was expressed more highly in the MP than in the original plants, whereas the expression levels of PcJAZ and PcMYC were reduced in the MP compared with that of the original plants. In response to treatment with exogenous methyl jasmonate, the original plants phenotype was consistent with that of the MP in developing less branches. These results indicate that jasmonic acid negatively regulates branch growth of pear trees and that jasmonic acid downstream regulatory genes play a crucial role in regulating branching.

Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self‐propelled tumor penetration fueled by hydrogen peroxide (H 2 O 2 ) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H 2 O 2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag + release, which could downregulate intracellular Cl − through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt–DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe 2+ -dependent DNA repair enzyme) by chelating intracellular Fe 2+ to increase the proportion of irreparable Pt–DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt–DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy. Graphical Abstract

KNOTTED1-like homeobox (KNOX) transcription factors (TFs) belonging to the homeobox TF family play important roles in plant growth, development, and responses to abiotic and biotic stress. However, little information is available on KNOX TF in pear ( Pyrus ). In this study, 19 PbKNOXs TFs were re-identified in pear ( Pyrus bretschneideri Rehd.). Phylogenetic analysis revealed that the TFs were clustered into three groups with 10 conserved motifs, some of which were group- or subgroup-specific, implying that they are important for the functions of the KNOX in these clades. PbKNM1 and PbKNM2 are KNM (encodes a MEINOX domain but not a homeodomain) genes identified in pear for the first time. KNOX genes in Pyrus and Malus were closely related, and a collinear relationship among PbKNOX genes in Pyrus and Malus was observed. Analysis of the expression patterns of PbKNOX genes in different tissues, at various growth stages, and in response to abiotic and biotic stress revealed that PbKNOXs are involved in plant growth and development. Our comparative transcriptional analysis of dwarf mutant varieties revealed that genes belonging to class I are highly expressed compared with genes in other classes. Analysis of the expression of PbKNOX genes in the hybrid offspring of vigorous and dwarf varieties revealed that PbKNOX genes were highly expressed in the vigorous offspring and weakly expressed in the dwarf offspring. These findings provide new insight into the function of KNOX TFs in pear and will aid future studies of dwarf fruit trees.

Pear (Pyrus L.) is an important temperate fruit worldwide, and grafting is widely used in pear vegetative propagation. However, the mechanisms of graft healing or incompatibility remain poorly understood in Pyrus. To study the differences in graft healing in Pyrus, the homograft “Qingzhen D1/Qingzhen D1” and the heterograft “QAUP-1/Qingzhen D1” as compatibility and incompatibility combinations were compared. Anatomical differences indicated the healing process was faster in homografts than in heterografts. During the healing process, four critical stages in graft union formation were identified in the two types of grafts. The expression of the genes associated with hormone signaling (auxin and cytokinins), and lignin biosynthesis was delayed in the healing process of heterografts. In addition, the PbBglu13 gene, encoded β-glucosidase, was more highly up-regulated in heterografts than in homografts to promote healing. Meanwhile, the most of DEGs related starch and sucrose metabolism were found to be up-regulated in heterografts; those results indicated that cellulose and sugar signals were also involved in graft healing. The results of this study improved the understanding of the differences in the mechanisms of graft healing between homografts and heterografts.