Maize rough dwarf disease (MRDD) is a viral disease that causes substantial yield loss, especially in China's summer planted maize area. Discovery of resistance genes would help in developing high-yielding resista...
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Maize rough dwarf disease (MRDD) is a viral disease that causes substantial yield loss, especially in China's summer planted maize area. Discovery of resistance genes would help in developing high-yielding resistant maize hybrids. Genome-wide association studies (GWASs) have advanced quickly and are now a powerful tool for dissecting complex genetic architectures. In this study, the disease severity index (DSI) of 292 maize inbred lines and an F6 linkage population were investigated across multiple environments for two years. Using the genotypes obtained from the Maize SNP 50K chip, a GWAS was performed with four analytical models. The results showed that 22 SNPs distributed on chromosomes 1, 3, 4, 6, 7 and 8 were significantly associated with resistance to MRDD (P<0.0001). The SNPs on chromosomes 3, 6 and 8 were consistent with the quantitative trait locus (QTL) regions from linkage mapping in an RIL population. Candidate genes identified by GWAS included an LRR receptor-like serine/threonine-protein kinase (GRMZM2G141288), and a DRE-binding protein (GRMZM2G006745). In addition, we performed an allele variation analysis of the SNP loci selected by GWAS and linkage mapping and found that the main alleles of the two SNP loci PZE_101170408 and PZE_106082685 on chromosome 1 differed in terms of disease-resistant materials and disease-susceptible materials. The identified SNPs and genes provide useful information for MRDD-related gene cloning and insights on the underlying disease resistance mechanisms, and they can be used in marker-assisted breeding to develop MRDD-resistant maize.
Apart from the blood-brain barrier (BBB), the efficacy of immunotherapy for glioblastoma (GBM) is limited by the presence of intrinsic and adaptive immune resistance, implying that co-delivery of various immunotherape...
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Apart from the blood-brain barrier (BBB), the efficacy of immunotherapy for glioblastoma (GBM) is limited by the presence of intrinsic and adaptive immune resistance, implying that co-delivery of various immunotherapeutic agents or simultaneous regulation of different cells is urgently needed. Bacterial outer membrane vesicles (OMVs) offer a unique advantage in the treatment of GBM, owing to their multifunctional properties as carriers and immune adjuvants and their ability to cross the BBB. However, traditional OMVs can lead to toxic side effects and disruption of tight junctions in the BBB. Therefore, to enhance the in vivo safety and targeting capability of OMVs, we introduced engineered OMVs to reduce toxicity and further constructed a modularly assembled nanoplatform by performing simple peptide modifications. This nanoplatform demonstrates satisfactory biosafety and is able to continuously cross the BBB and target GBM with the assistance of Angiopep-2. Subsequently, immunogenic substances on OMVs, along with carried small-interfering RNA (siRNA) and doxorubicin, can promote and enhance the reprogramming and phagocytic abilities of macrophages and microglia, respectively, and increase the immunogenicity of GBM, ultimately overcoming GBM immune resistance to enhance the efficacy of immunotherapy. This OMVs-based nanoplatform provides a new paradigm and insights into the development of immunotherapy for GBM.
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