Downregulating Notch counteracts KrasG12D-induced ERK activation and oxidative phosphorylation in myeloproliferative neoplasm.

The Notch signaling pathway contributes to the pathogenesis of a wide spectrum of human cancers, including hematopoietic malignancies. Its functions are highly dependent on the specific cellular context. Gain-of-function NOTCH1 mutations are prevalent in human T-cell leukemia, while loss of Notch signaling is reported in myeloid leukemias. Here, we report a novel oncogenic function of Notch signaling in oncogenic Kras-induced myeloproliferative neoplasm (MPN). We find that downregulation of Notch signaling in hematopoietic cells via DNMAML expression or Pofut1 deletion significantly blocks MPN development in KrasG12D mice in a cell-autonomous manner. Further mechanistic studies indicate that inhibition of Notch signaling upregulates Dusp1, a dual phosphatase that inactivates p-ERK, and downregulates cytokine-evoked ERK activation in KrasG12D cells. Moreover, mitochondrial metabolism is greatly enhanced in KrasG12D cells but significantly reprogrammed by DNMAML close to that in control cells. Consequently, cell proliferation and expanded myeloid compartment in KrasG12D mice are significantly reduced. Consistent with these findings, combined inhibition of the MEK/ERK pathway and mitochondrial oxidative phosphorylation effectively inhibited the growth of human and mouse leukemia cells in vitro. Our study provides a strong rational to target both ERK signaling and aberrant metabolism in oncogenic Ras-driven myeloid leukemia

Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in Breast Cancer Stem Cells

Breast cancer stem cells (CSCs) are believed to be responsible for tumor initiation, invasion, metastasis, and recurrence, which lead to treatment failure. Thus, developing effective CSC-targeted therapeutic strategies is crucial for enhancing therapeutic efficacy. In this work, GNSs-dPG-3BP, TPP, and HA nanocomposite particles are developed by simultaneously conjugating hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP), mitochondrial targeting molecule triphenyl phosphonium (TPP), and CSCs targeting agent hyaluronic acid (HA) onto gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatforms for efficient eradication of CSCs. The nanocomposite particles possess good biocompatibility and exhibit superior mitochondrial-bound HK2 binding ability via 3BP to inhibit metabolism, and further induce cellular apoptosis by releasing the cytochrome c. Therefore, it enhanced the therapeutic efficacy of CSCs-specific targeted photothermal therapy (PTT), and achieved a synergistic effect for the eradication of breast CSCs. After administration of the synergistic treatment, the self-renewal of breast CSCs and the stemness gene expression are suppressed, CSC-driven mammosphere formation is diminished, the in vivo tumor growth is effectively inhibited, and CSCs are eradicated. Altogether, GNSs-dPG-3BP, TPP, and HA nanocomposite particles have been developed, which will provide a novel strategy for precise and highly efficient targeted eradication of CSCs

Efficient Silicon Metasurfaces for Visible Light

Dielectric metasurfaces require high refractive index contrast materials for optimum performance. This requirement imposes a severe restraint; either devices have been demonstrated at wavelengths of 700 nm and above using high-index semiconductors such as silicon, or they use lower index dielectric materials such as TiO2 or Si3N4 and operate in the visible wavelength regime. Here, we show that the high refractive index of silicon can be exploited at wavelengths as short as 532 nm by demonstrating a crystalline silicon metasurface with a transmission efficiency of 71% at this wavelength and a diffraction efficiency of 95% into the desired diffraction order. The metasurfaces consist of a graded array of silicon posts arranged in a square lattice on a quartz substrate. We show full 2π phase control, and we experimentally demonstrate polarization-independent beam deflection at 532 nm wavelength. Our results open a new way for realizing efficient metasurfaces based on silicon for the technologically all-important display applications

The next widespread bamboo flowering poses a massive risk to the giant panda

The IUCN Red List has downgraded several species from “endangered” to “vulnerable” that still have largely unknown extinction risks. We consider one of those downgraded species, the giant panda, a bamboo specialist. Massive bamboo flowering could be a natural disaster for giant pandas. Using scenario analysis, we explored possible impacts of the next bamboo flowering in the Qinling and Minshan Mountains that are home to most giant pandas. Our results showed that the Qinling Mountains could experience large-scale bamboo flowering leading to a high risk of widespread food shortages for the giant pandas by 2020. The Minshan Mountains could similarly experience a large-scale bamboo flowering with a high risk for giant pandas between 2020 and 2030 without suitable alternative habitat in the surrounding areas. These scenarios highlight thus-far unforeseen dangers of conserving giant pandas in a fragmented habitat. We recommend advance measures to protect giant panda from severe population crashes when flowering happens. This study also suggests the need to anticipate and manage long-term risks to other downgraded species

Flexible nanowire cluster as wearable colorimetric humidity sensor

This work was supported by Ministry of Science and Technology of China (2016YFA0301300), National Natural Science Foundation of China (61675237, 11511130056, 21405183), the Guangdong Natural Science Foundation (2014A030313140, 2016A030312012), Guangzhou Science and Technology Projects (201607020023), and the fundamental research funds for the central universities (16lgjc85 and 16lgjc62).Wearable plasmonic devices combine the advantages of high flexibility, ultrathinness, light weight, and excellent integration with the optical benefits mediated by plasmon-enhanced electric fields. However, two obstacles severely hinder further developments and applications of a wearable plasmonic device. One is the lack of efficient approach to obtaining devices with robust antimotion-interference property, i.e., the devices can work independently on the morphology changes of their working structures caused by arbitrary wearing conditions. The other issue is to seek a facile and high-throughput fabrication method to satisfy the financial requirement of industrialization. In order to overcome these two challenges, a functional flexible film of nanowire cluster is developed, which can be easily fabricated by taking the advantages of both conventional electrochemical and sputtering methods. Such flexible plasmonic films can be made into wearable devices that work independently on shape changes induced by various wearing conditions (such as bending, twisting and stretching). Furthermore, due to plasmonic advantages of color controlling and high sensitivity to environment changes, the flexible film of nanowire cluster can be used to fabricate wearable items (such as bracelet, clothes, bag, or even commercial markers), with the ability of wireless visualization for humidity sensing.PostprintPeer reviewe

Atmospheric nitrous acid (HONO) at a rural coastal site in North China: Seasonal variations and effects of biomass burning

Nitrous acid (HONO) plays a significant role in atmospheric chemistry due to its contribution to hydroxyl radical (OH). However, no scientific consensus has been achieved about the daytime HONO formation mechanisms. To identify the seasonal variations of HONO chemistry and the impacts of biomass burning (BB), we performed a two-phased field study in winter-spring and summer (covering a harvest season) in 2017 at a rural coastal site in North China. Though the mean HONO concentration in winter-spring (0.26 +/- 0.28 ppbv) was higher than in summer (0.17 + 0.19 ppbv), the maximum HONO concentrations were comparable (similar to 2 ppbv) in the two campaigns. Both the HONO/NOx ratio and nocturnal heterogeneous conversion efficiency of HONO (C-HONO) in summer were over twice of that in winter-spring. The daytime budget analysis also revealed that the strength of P(othe)r (i.e., the HONO sources apart from the reaction of OH + NO) in summer was double of that in winter-spring. BB affected the HONO concentration by enhancing the contribution of heterogeneous HONO production on the aerosol surface but weakening the role of photo-related HONO formation. HONO photolysis was a significant source of OH in both winter-spring and summer, and its contribution could be further enhanced during the BB episode in summer. Our study demonstrates the significant seasonal variations of HONO and the effects of BB, and suggests needs for more multi-season observations and considerations of BB, especially during the harvest time, in HONO research

The Histone Variant H2A.W Defines Heterochromatin and Promotes Chromatin Condensation in Arabidopsis

SummaryHistone variants play crucial roles in gene expression, genome integrity, and chromosome segregation. We report that the four H2A variants in Arabidopsis define different genomic features, contributing to overall genomic organization. The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. Similarities in conserved motifs between H2A.W and another H2A variant in metazoans suggest that plants and animals share common mechanisms for heterochromatin condensation