The microRNA319 (miR319) family is conserved among diverse plant species. In rice (Oryza sativa L.), the miR319 gene family is comprised of two members, Osa-miR319a and Osa-miR319b. We found that overexpressing Osa-miR319b in rice resulted in wider leaf blades and delayed development. Here, we focused on the biological function and potential molecular mechanism of the Osa-miR319b gene in response to cold stress in rice. The expression of Osa-miR319b was down-regulated by cold stress, and the overexpression of Osa-miR319b led to an enhanced tolerance to cold stress, as evidenced by higher survival rates and proline content. Also, the expression of a handful of cold stress responsive genes, such as DREB1A/B/C, DREB2A, TPP1/2, was increased in Osa-miR319b transgenic lines. Furthermore, we demonstrated the nuclear localization of the transcription factors, OsPCF6 and OsTCP21, which may be Osa-miR319b-targeted genes. We also showed that OsPCF6 and OsTCP21 expression was largely induced by cold stress, and the degree of induction was obviously repressed in plants overexpressing Osa-miR319b. As expected, the down-regulation of OsPCF6 and OsTCP21 resulted in enhanced tolerance to cold stress, partially by modifying active oxygen scavenging. Taken together, our findings suggest that Osa-miR319b plays an important role in plant response to cold stress, maybe by targeting OsPCF6 and OsTCP21.

Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.

DNA methylation functions in gene silencing and the maintenance of genome integrity. In plants, non-CG DNA methylation is linked through a self-reinforcing loop with histone 3 lysine 9 dimethylation (H3K9me2). The plant-specific SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG (SUVH) family H3K9 methyltransferases (MTases) bind to DNA methylation marks and catalyze H3K9 methylation. Here, we analyzed the structure and function of SUVH6 to understand how this class of enzyme maintains methylation patterns in the genome. We reveal that SUVH6 has a distinct 5-methyl-dC (5mC) base-flipping mechanism involving a thumb loop element. Autoinhibition of H3 substrate entry is regulated by a SET domain loop, and a conformational transition in the post-SET domain upon cofactor binding may control catalysis. In vitro DNA binding and in vivo ChIP-seq data reveal that the different SUVH family H3K9 MTases have distinct DNA binding preferences, targeting H3K9 methylation to sites with different methylated DNA sequences, explaining the context biased non-CG DNA methylation in plants.

Nanotheranostics with integrated diagnostic and therapeutic functions show exciting potentials towards precision nanomedicine. However, targeted delivery of nanotheranostics is hindered by several biological barriers. Here, we report the development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD NP) for delivery of ultra-small, full active pharmaceutical ingredients (API) nanotheranostics with integrated dual-modal imaging and trimodal therapeutic functions. pPhD NPs exhibit ideal size and charge for drug transportation. In tumour microenvironment, pPhD NPs responsively transform to full API nanotheranostics with ultra-small size and higher surface charge, which dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs enable visualisation of biodistribution by near-infrared fluorescence imaging, tumour accumulation and therapeutic effect by magnetic resonance imaging. Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer models. This nanoplatform with powerful delivery efficiency and versatile theranostic functions shows enormous potentials to improve cancer treatment.

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Objectives To compare the performance of traditional G-banding karyotyping with that of copy number variation sequencing (CNV-Seq