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In vitro or in vivo fluorescence imaging based on quantum dots (QDs) has shown promise for the noninvasive diagnosis of atherosclerosis. However, simultaneous in vitro and in vivo imaging remains challenging due to the limitation of the current synthesis method of dual-emission QDs (dual-emitting hybrid QDs, and broad-spectrum emitting QDs). Herein, we fabricate a dual-emission (visible region and near-infrared region emission) QDs (ZAISe/ZnS) via the "bottom to up" method of a quaternary inorganic compound for the foam cells and atherosclerosis plaque imaging simultaneously without the intricate size modulation and the strict optical filter requirements. The oil-soluble ZAISe/ZnS is further encapsulated with bovine serum albumin (BSA) to realize phase transfer and ultimately possess the inflammation-targeting properties via biomimetic treatment with MMV (macrophage-derived micro-vesicle). The results first indicate that the as-constructed ZAISe/ZnS@BSA@MMV could accurately locate the foam cells and conduct long-term imaging of the atherosclerotic plaque, which provides a new strategy for the early and noninvasive diagnosis of atherosclerosis.

The development of efficient, durable and economical catalysts based on non-precious metals for the controllable and fast hydrogen evolution from chemical hydrogen storage materials is highly desirable for the hydrogen economy.

Peatlands play a crucial role in mediating the emissions of methane through active biogeochemical cycling of accumulated carbon driven by methane-metabolizing microorganisms; meanwhile, they serve as vital archives of atmospheric heavy metal deposition. Despite many edaphic factors confirmed as determinants to modulate the structure of methanotrophic and methanogenic communities, recognition of interactions among them is limited. In this study, peat soils were collected from Dajiuhu peatland to assess the presence of heavy metals, and methanotrophs and methanogens were investigated via high-throughput sequencing for functional genes mcrA and pmoA. Further analyses of the correlations between methane-related functional groups were conducted. The results demonstrated that both methane-metabolizing microorganisms and heavy metals have prominent vertical heterogeneity upward and downward along the depth of 20 cm. Pb, Cd, and Hg strongly correlated with methanotrophs and methanogens across all seasons and depths, serving as forceful factors in structural variations of methanogenic and methanotrophic communities. Particularly, Pb, Cd, and Hg were identified as excessive elements in Dajiuhu peatland. Furthermore, seasonal variations of networks among methane-related functional groups and environmental factors significantly affected the changes of methane fluxes across different seasons. Concretely, the complicated interactions were detrimental to methane emissions in the Dajiuhu peatland, leading to the minimum methane emissions in winter. Our study identified the key heavy metals affecting the composition of methane-metabolizing microorganisms and linkages between seasonal variations of methane emissions and interaction among heavy metals and methane-metabolizing microorganisms, which provided much new reference and theoretical basis for integrated management of natural peatlands.

Black phase CsPbI

Suppression of gluconeogenesis elevates glycolysis and is commonly observed in tumors derived from gluconeogenic tissues including liver and kidney, yet the definitive regulatory mechanism remains elusive. Here, we screened an array of transcription regulators and identified the enhancer of zeste homolog 2 (EZH2) as a key factor that inhibits gluconeogenesis in cancer cells. Specifically, EZH2 repressed the expression of a rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1) and promoted tumor growth primarily through FBP1 suppression. Furthermore, EZH2 was upregulated by genotoxins that commonly induce hepatic and renal tumorigenesis. Genotoxin treatments augmented EZH2 acetylation, leading to reduced association between EZH2 and its E3 ubiquitin ligase SMURF2. Consequently, EZH2 became less ubiquitinated and more stabilized, promoting FBP1 attenuation and tumor formation. Intriguingly, FBP1 physically interacted with EZH2, competed for EZH2 binding, and dissembled the polycomb complex. Therefore, FBP1 suppresses polycomb-initiated transcriptional responses and constitutes a double-negative feedback loop indispensable for EZH2-promoted tumorigenesis. Finally, EZH2 and FBP1 levels were inversely correlated in tumor tissues and accurately predicted patient survival. This work reveals an unexpected cross-talk between epigenetic and metabolic events, and identifies a new feedback circuitry that highlights EZH2 inhibitors as liver and kidney cancer therapeutics.Significance:A novel feedback loop involving EZH2 and suppression of the gluconeogenesis enzyme FBP1 promotes hepatocellular cancer growth.See related commentary by Leithner, p. 657

Supplementary tables S1-S4 show analytic details of the ENCODE ChIP-Seq data and TCGA RNA-Seq data, together with primer sequences used in this study.

Supplementary Figures S1-S6 describe additional data to support the EZH2-FBP1 feedback circuitry in hepatic and renal cells upon genotoxin-induced tumorigenesis. Supplementary Materials and Methods provide experimental details on standard assays using commercial reagents and kits.

Supplementary Table 1, Figures 1-5. Supplemental Table 1 (Table S1) - Affinity of a bivalent antibody (IgG KD) is largely different from it monovalent form (scFv KD). Supplemental Figure 1 (Fig. S1) - Surface expression level of ErbB2 detected by flow cytometry is correlated with mRNA level detected by quantitative PCR. Supplemental Figure 2 (Fig. S2) - CD107a up-regulation was different between higher affinity ErbB2 CART cells and lower affinity CART cells when stimulated with tumor cell lines expressing ErbB2 at different levels. Supplemental Figure 3 (Fig. S3) - More tumor cell lines tested in a CD107a assay confirmed that lower affinity ErbB2 CART cells only recognized ErbB2 over expression tumors. Supplemental Figure 4 (Fig. S4) - ErbB2 target dependent upregulation of CD107a of lower affinity ErbB2 CAR lentiviral transduced, as well as lower affinity ErbB2 CAR mRNA electroporated T cells. Supplemental Figure 5 (Fig. S5) - ErbB2 CART cells with decreased affinity controlled tumor growth as efficiently as ErbB2 CART cells with higher affinity.

Whether depression can be adaptive has long been discussed, but systematically investigation of the adaptive evolution of its genetic basis at the genomic level is sparse. Here, we conducted genome-wide analyses on 320 depression genes at two levels, i.e., across the primate phylogeny (large timescale selection), and in modern human populations (recent selection). We identified seven genes under positive selection in the human lineage, and 46 genes under positive selection in modern human populations. Most positively selected variants in modern human populations were at UTR regions and non-coding exons, indicating the importance of gene expression regulation in the adaptive evolution of depression gene networks. Positively selected genes are not only related to immune response, but also function in reproduction and dietary adaptation, extending the pathogen host defense hypothesis. Notably, the proportion of positively selected depression genes was significantly larger than the proportion of positively selected genes at the genomic level in certain modern human populations. We also identified two positively selected variants that happened to be depression-associated variants. We thus propose that recent selection plays important roles on the adaptive evolution of depression genes. Depression can be adaptive, or is a by-product of evolution, which is still an open question.

2D N-doped V2O3 (N-V2O3) is synthesized as an anode material for Li-ion batteries by a facile strategy. Benefiting from the 3D V–V tunnel structure, sufficient active sites and N modifications, N-V2O3 exhibits stable and ultrafast Li-ion storage.

A multimodal anti-tumor nano-agent enhanced the efficiency of photodynamic therapy via photothermal therapy, alleviating hypoxia and Cu2+-mediated reactions.

ZIF-derived acid-activated ZCD with lysosome-Golgi transport property can achieve self-monitoring deep-tumour penetration via hierarchical size/charge dual-transformable strategy and Golgi-mediated transcytosis.

Photoemission spectroscopy reveals halogen cleavage from bulky cation organics and the formation process of 2D-like perovskites on the parent perovskite as well as their impact on band alignment and device performance.

Rare earth is an important strategic resource related to the environment and has been included in the national development strategies of major developed countries. This paper uses the import and export data of rare earth industry in the United Nations Commodity Trade Database to build a global rare earth trade network as a whole with the help of network analysis methods. Among them, China has the highest export centrality, while the United States has the highest import centrality. China, Japan, the United States and some Southeast Asian countries are the core countries of the rare earth trade network. Economic level, macroeconomic management level and logistics level are three major factors that affect the evolution of rare earth permanent magnet product trade network. Therefore, the research on innovation management in this direction is extremely important.

Model predictive control (MPC) for building energy management has exhibited a huge potential for largely cutting down energy use and improving human comfort. However, the high demand for computational power for solving the optimization is challenging the widespread deployment of MPC in real buildings. Typical MPC employs a time-triggered mechanism (TTM) that runs optimization recurrently at each time step without considering the necessity, which could cause excessive computation resource usage. This paper proposes an event-triggered mechanism (ETM) that only runs optimization when triggering events occur. Contrary to conventional ETMs that only considers the current information (e.g., room conditions), the ETM proposed is based on a cost function that covers the past, current, and future information. Based on the proposed ETM, a machine-learning-based event-triggered model predictive control (ETMPC) system that optimizes both building energy efficiency and thermal comfort is developed. The developed ETMPC system is then employed for air-conditioning control for performance evaluation through simulations. The control performance of the proposed ETMPC is compared to an MPC employing TTM and a common thermostat. Compared to the MPC employing TTM, the proposed ETMPC reduced the computational load in terms of the number of optimization runs by 77.6%–88.2%, meanwhile, achieving similar energy savings (more than 9.3% energy saving over the thermostat) as the MPC employing TTM does (9% energy saving over the thermostat). With the significant reduction of computational load, the ETMPC achieves similar thermal comfort performance as the MPC employing TTM does, and it is significantly better over the thermostat. National Research Foundation (NRF) This research is supported by the National Research Foundation (NRF) of Singapore through grant no. NRF2016IDM-TRANS001-031.

Background: The metalloprotease ADAMTS-7 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 7) is a novel locus associated with human coronary atherosclerosis. ADAMTS-7 deletion protects against atherosclerosis and vascular restenosis in rodents. Methods: We designed 3 potential vaccines consisting of distinct B cell epitopic peptides derived from ADAMTS-7 and conjugated with the carrier protein KLH (keyhole limpet hemocyanin) as well as aluminum hydroxide as an adjuvant. Arterial ligation or wire injury was used to induce neointima in mice, whereas ApoE -/- and LDLR -/- (LDLR [low-density lipoprotein receptor]) mice fed a high-fat diet were applied to assess atherosclerosis. In addition, coronary stent implantation was performed on vaccine-immunized Bama miniature pigs, followed by optical coherence tomography to evaluate coronary intimal hyperplasia. Results: A vaccine, ATS7vac, was screened out from 3 candidates to effectively inhibit intimal thickening in murine carotid artery ligation models after vaccination. As well, immunization with ATS7vac alleviated neointima formation in murine wire injury models and mitigated atherosclerotic lesions in both hyperlipidemic ApoE -/- and LDLR -/- mice without lowering lipid levels. Preclinically, ATS7vac markedly impeded intimal hyperplasia in swine stented coronary arteries, but without significant immune-related organ injuries. Mechanistically, ATS7vac vaccination produced specific antibodies against ADAMTS-7, which markedly repressed ADAMTS-7–mediated COMP (cartilage oligomeric matrix protein) and TSP-1 (thrombospondin-1) degradation and subsequently inhibited vascular smooth muscle cell migration but promoted re-endothelialization. Conclusions: ATS7vac is a novel atherosclerosis vaccine that also alleviates in-stent restenosis. The application of ATS7vac would be a complementary therapeutic avenue to the current lipid-lowering strategy for atherosclerotic disease.

Due to the growing popularity of indoor location-based services, indoor data management has received significant research attention in the past few years. However, we observe that the existing indexing and query processing techniques for the indoor space do not fully exploit the properties of the indoor space. Consequently, they provide below par performance which makes them unsuitable for large indoor venues with high query workloads. In this paper, we first propose two novel indexes called Indoor Partitioning Tree (IP-Tree) and Vivid IP-Tree (VIP-Tree) that are carefully designed by utilizing the properties of indoor venues. The proposed indexes are lightweight, have small pre-processing cost and provide near-optimal performance for shortest distance and shortest path queries. We are also the first to study spatial keyword queries in indoor venues. We propose a novel data structure called Keyword Partitioning Tree (KP-Tree) that indexes objects in an indoor partition. We propose an efficient algorithm based on VIP-Tree and KP-Trees to efficiently answer spatial keyword queries. Our extensive experimental study on real and synthetic data sets demonstrates that our proposed indexes outperform the existing solutions by several orders of magnitude.

Porous carbon nanostructures are promising supports for stabilizing the highly dispersed metal nanoparticles and facilitating the mass transfer during the reaction, which are critical to achieve the high efficiency of hydrogen generation from sodium borohydride dehydrogenation. Herein, the catalytically active porous architectures are simply prepared by using 2-methylimidazole and melamine as reactive sources. The structural and compositional characterizations reveal the coexistence of metallic cobalt and N-doped carbon in porous architectures. Electron microscopy observations indicate that the synthesized products are smartly constructed from the carbon nanosheets with densely dispersed Co nanoparticles. Due to the notable structural features, the prepared Co@NC-600 sample presents the highly efficient activity for catalytic hydrolysis of NaBH4 with a hydrogen generation rate of 2574 mL min−1 gcat−1 and an activation energy of 47.6 kJ mol−1. The catalytically active metallic Co and suitable support-effect of N-doped carbon are responsible for catalytic dehydrogenation.