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A gronomy J our n al • Volume 10 0 , I s sue 3 • 2 0 0 8 517 ABSTRACT Th e improved soil N min -based N management is a promising approach to precision N management, which determines the optimum side-dress N rates based on N target values and measured soil nitrate N content in the root soil layer at diff erent growth stages. A total of 148 on-farm N-response experiments, in seven key summer maize (Zea mays L.) production regions of North China Plain (NCP) from 2003 to 2005, were conducted to evaluate the N min -based N management compared to traditional farmer's N practices. Th e recommended N rates based on the improved soil N min method were not signifi cantly diff erent ( ≤31 kg N ha -1 ) from those determined by yield response curves (n = 13). Th e average N rate determined with the soil N min method (157 kg N ha -1 ) was signifi cantly lower than farmer's practice (263 kg N ha -1 ), while maize grain yield was 0.4 Mg ha -1 higher than farmer's N practice (8.5 Mg ha -1 ) across all sites (n = 148). As a result, the improved soil N min -based N management signifi cantly increased net economic gains by $202 ha -1 , reduced residual nitrate N content and N losses by 44 kg N ha -1 and 65 kg N ha -1 , respectively, and improved recovery N effi ciency, agronomic N effi ciency and N partial factor productivity by 16%, 6 kg kg -1 and 36 kg kg -1 , respectively, compared with farmer's N practice. We conclude that the improved soil N min -based N management can be applied for summer maize production in NCP for improved N use effi ciency and reduced environmental contamination.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited therapeutic options. Temozolomide (TMZ) is a novel cytotoxic agent used as first-line chemotherapy for GBM, however, some individual cells can't be isolated for surgical resection and show treatment-resistance, thus inducing poor prognosis. By using the HiSeq sequencing and bioinformatics methods, we identified lncRNAs showing different expression levels in TMZ-resistant and non-resistant patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MALAT1 was finally identified to show considerable discriminating potential to identify responding patients from non-responding patients. Moreover, high serum MALAT1 expression was associated with poor chemoresponse and survival in GBM patients receiving TMZ treatment. Subsequently, the TMZ resistant cell lines were established, and the CCK8 assay showed that lncRNA MALAT1 knockdown significantly reversed TMZ resistance in GBM cells. The gain and loss-function experiments revealed that miR-203 was down-regulated by MALAT1 and this interaction has reciprocal effects. Besides, thymidylate synthase (TS) mRNA was identified as a direct target of miR-203. LncRNA MALAT1 inhibition re-sensitized TMZ resistant cells through up-regulating miR-203 and down-regulating TS expression. On the other hand, MALAT1 overexpression promoted resistance by suppressing miR-203 and promoting TS expression. In conclusion, our integrated approach demonstrates that enhanced expression of lncRNA MALAT1 confers a potent poor therapeutic efficacy and inhibition of MALAT1 levels could be a future direction to develop a novel therapeutic strategy to overcome TMZ resistance in GBM patients.

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Exosomes derived from mesenchymal stem cells (MSCs) have been proven to exhibit great potentials in spinal cord injury (SCI) therapy. However, conventional two-dimensional (2D) culture will inevitably lead to the loss of stemness of MSCs, which substantially limits the therapeutic potency of MSCs exosomes (2D-Exo). Exosomes derived from three-dimensional culture (3D-Exo) possess higher therapeutic efficiency which have wide applications in spinal cord therapy. Typically, conventional exosome therapy that relies on local repeated injection results in secondary injury and low efficiency. It is urgent to develop a more reliable, convenient, and effective exosome delivery method to achieve constant in situ exosomes release. Herein, we proposed a controlled 3D-exohydrogel hybrid microneedle array patch to achieve SCI repair in situ. Our studies suggested that MSCs with 3D-culturing could maintain their stemness, and consequently, 3D-Exo effectively reduced SCI-induced inflammation and glial scarring. Thus, it is a promising therapeutic strategy for the treatment of SCI.

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