Porous Tellurium-Doped Ruthenium Dioxide Nanotubes for Enhanced Acidic Water Oxidation.

Electrocatalysts with high activity and durability for acidic oxygen evolution reaction (OER) play a crucial role in achieving cost-effective hydrogen production via proton exchange membrane water electrolysis. A novel electrocatalyst, Te-doped RuO2 (Te-RuO2) nanotubes, synthesized using a template-directed process, which significantly enhances the OER performance in acidic media is reported. The Te-RuO2 nanotubes exhibit remarkable OER activity in acidic media, requiring an overpotential of only 171 mV to achieve an anodic current density of 10 mA cm-2. Furthermore, they maintain stable chronopotentiometric performance under 10 mA cm-2 in acidic media for up to 50 h. Based on the experimental results and density functional calculations, this significant improvement in OER performance to the synergistic effect of large specific surface area and modulated electronic structure resulting from the doping of Te cations is attributed.

Phthalates Promote Dissemination of Antibiotic Resistance Genes: An Overlooked Environmental Risk.

Plastics-microorganism interactions have aroused growing environmental and ecological concerns. However, previous studies concentrated mainly on the direct interactions and paid little attention to the ecotoxicology effects of phthalates (PAEs), a common plastic additive that is continuously released and accumulates in the environment. Here, we provide insights into the impacts of PAEs on the dissemination of antibiotic resistance genes (ARGs) among environmental microorganisms. Dimethyl phthalate (DMP, a model PAE) at environmentally relevant concentrations (2-50 µg/L) significantly boosted the plasmid-mediated conjugation transfer of ARGs among intrageneric, intergeneric, and wastewater microbiota by up to 3.82, 4.96, and 4.77 times, respectively. The experimental and molecular dynamics simulation results unveil a strong interaction between the DMP molecules and phosphatidylcholine bilayer of the cell membrane, which lowers the membrane lipid fluidity and increases the membrane permeability to favor transfer of ARGs. In addition, the increased reactive oxygen species generation and conjugation-associated gene overexpression under DMP stress also contribute to the increased gene transfer. This study provides fundamental knowledge of the PAE-bacteria interactions to broaden our understanding of the environmental and ecological risks of plastics, especially in niches with colonized microbes, and to guide the control of ARG environmental spreading.

Biomolecular Insights into Extracellular Pollutant Reduction Pathways of Geobacter sulfurreducens Using a Base Editor System.

Geobacter species are critically involved in elemental biogeochemical cycling and environmental bioremediation processes via extracellular electron transfer (EET), but the underlying biomolecular mechanisms remain elusive due to lack of effective analytical tools to explore into complicated EET networks. Here, a simple and highly efficient cytosine base editor was developed for engineering of the slow-growing Geobacter sulfurreducens (a doubling time of 5 h with acetate as the electron donor and fumarate as the electron acceptor). A single-plasmid cytosine base editor (pYYDT-BE) was constructed in G. sulfurreducens by fusing cytosine deaminase, Cas9 nickase, and a uracil glycosylase inhibitor. This system enabled single-locus editing at 100% efficiency and showed obvious preference at the cytosines in a TC, AC, or CC context than in a GC context. Gene inactivation tests confirmed that it could effectively edit 87.7-93.4% genes of the entire genome in nine model Geobacter species. With the aid of this base editor to construct a series of G. sulfurreducens mutants, we unveiled important roles of both pili and outer membrane c-type cytochromes in long-range EET, thereby providing important evidence to clarify the long-term controversy surrounding their specific roles. Furthermore, we find that pili were also involved in the extracellular reduction of uranium and clarified the key roles of the ExtHIJKL conduit complex and outer membrane c-type cytochromes in the selenite reduction process. This work developed an effective base editor tool for the genetic modification of Geobacter species and provided new insights into the EET network, which lay a basis for a better understanding and engineering of these microbes to favor environmental applications.

Reusing Sulfur-Poisoned Palladium Waste as a Highly Active, Nonradical Fenton-like Catalyst for Selective Degradation of Phenolic Pollutants.

Recycling of deactivated palladium (Pd)-based catalysts can not only lower the economic cost of their industrial use but also save the cost for waste disposal. Considering that the sulfur-poisoned Pd (PdxSy) with a strong Pd-S bond is difficult to regenerate, here, we propose a direct reuse of such waste materials as an efficient catalyst for decontamination via Fenton-like processes. Among the PdxSy materials with different poisoning degrees, Pd4S stood out as the most active catalyst for peroxymonosulfate activation, exhibiting pollutant-degradation performance rivaling the Pd and Co2+ benchmarks. Moreover, the incorporated S atom was found to tune the surface electrostatic potentials and charge densities of the Pd active site, triggering a shift in catalytic pathway from surface-bound radicals to predominantly direct electron transfer pathway that favors a highly selective oxidation of phenols. The catalyst stability was also improved due to the formation of strong Pd-S bond that reduces corrosion. Our work paves a new way for upcycling of Pd-based industrial wastes and for guiding the development of advanced oxidation technologies toward higher sustainability.

[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

LncRNA SNHG5 upregulation induced by YY1 contributes to angiogenesis via miR-26b/CTGF/VEGFA axis in acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is the most common acute leukemia in adults. Despite great progress has been made in this field, the pathogenesis of AML is still not fully understood. We report here the biological role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in the pathogenesis of AML and the underlying mechanisms. The results showed that lncRNA SNHG5 was highly expressed in AML cancer cell lines. In vitro studies displayed that inhibition of SNHG5 with shRNA resulted in suppression of survival, cell cycle progression, migration/invasion of AML and capacity of adhesion and angiogenesis in human umbilical vein endothelial cells. Mechanistic studies revealed a SNHG5/miR-26b/connective tissue growth factor (CTGF)/vascular endothelial growth factor A (VEGFA) axis in the regulation of AML angiogenesis. Finally, Yin Yang 1 (YY1) was found to transactivate and interact with SNHG5 promoter, leading to the upregulation of SNHG5 in AML. Collectively, upregulation of lncRNA SNHG5 mediated by YY1, activates CTGF/VEGFA via targeting miR-26b to regulate angiogenesis of AML. Our work provides new insights into the molecular mechanisms of AML.

Controlling pathogenic risks of water treatment biotechnologies at the source by genetic editing means.

Antimicrobial-resistant pathogens in the environment and wastewater treatment systems, many of which are also important pollutant degraders and are difficult to control by traditional disinfection approaches, have become an unprecedented treat to ecological security and human health. Here, we propose the adoption of genetic editing techniques as a highly targeted, efficient and simple tool to control the risks of environmental pathogens at the source. An 'all-in-one' plasmid system was constructed in Aeromonas hydrophila to accurately identify and selectively inactivate multiple key virulence factor genes and antibiotic resistance genes via base editing, enabling significantly suppressed bacterial virulence and resistance without impairing their normal phenotype and pollutant-degradation functions. Its safe application for bioaugmented treatment of synthetic textile wastewater was also demonstrated. This genetic-editing technique may offer a promising solution to control the health risks of environmental microorganisms via targeted gene inactivation, thereby facilitating safer application of water treatment biotechnologies.

Abnormal regional homogeneity and its relationship with symptom severity in cervical dystonia: a rest state fMRI study.

BACKGROUND: Although several brain networks play important roles in cervical dystonia (CD) patients, regional homogeneity (ReHo) changes in CD patients have not been clarified. We investigated to explore ReHo in CD patients at rest and analyzed its correlations with symptom severity as measured by Tsui scale. METHODS: A total of 19 CD patients and 21 gender-, age-, and education-matched healthy controls underwent fMRI scans at rest state. Data were analyzed by ReHo method. RESULTS: Patients showed increased ReHo in the right cerebellum crus I and decreased ReHo in the right superior medial prefrontal cortex (MPFC). Moreover, the right precentral gyrus, right insula, and bilateral middle cingulate gyrus also showed increased ReHo values. A significantly positive correlation was observed between ReHo value in the right cerebellum crus I and symptom severity (p < 0.05). CONCLUSIONS: Our investigation suggested abnormal ReHo existed in brain regions of the "pain matrix" and salience network (the right insula and bilateral middle cingulate gyrus), the motor network (the right precentral gyrus), the cerebellum and MPFC and further highlighted the significance of these networks in the pathology of CD.

Identification of loci controlling adaptation in Chinese soya bean landraces via a combination of conventional and bioclimatic GWAS.

Landraces often contain genetic diversity that has been lost in modern cultivars, including alleles that confer enhanced local adaptation. To comprehensively identify loci associated with adaptive traits in soya bean landraces, for example flowering time, a population of 1938 diverse landraces and 97 accessions of the wild progenitor of cultivated soya bean, Glycine soja was genotyped using tGBS® . Based on 99 085 high-quality SNPs, landraces were classified into three sub-populations which exhibit geographical genetic differentiation. Clustering was inferred from STRUCTURE, principal component analyses and neighbour-joining tree analyses. Using phenotypic data collected at two locations separated by 10 degrees of latitude, 17 trait-associated SNPs (TASs) for flowering time were identified, including a stable locus Chr12:5914898 and previously undetected candidate QTL/genes for flowering time in the vicinity of the previously cloned flowering genes, E1 and E2. Using passport data associated with the collection sites of the landraces, 27 SNPs associated with adaptation to three bioclimatic variables (temperature, daylength, and precipitation) were identified. A series of candidate flowering genes were detected within linkage disequilibrium (LD) blocks surrounding 12 bioclimatic TASs. Nine of these TASs exhibit significant differences in flowering time between alleles within one or more of the three individual sub-populations. Signals of selection during domestication and/or subsequent landrace diversification and adaptation were detected at 38 of the 44 flowering and bioclimatic TASs. Hence, this study lays the groundwork to begin breeding for novel environments predicted to arise following global climate change.

Exposure of pregnant rats to staphylococcal enterotoxin B attenuates the response of increased Tregs to re-exposure to SEB in the thymus of adult offspring.

Regulatory T cells (Tregs) play an essential role during homeostasis and tolerance of the immune system. Based on our previous study that exposure of pregnant rats to staphylococcal enterotoxin B (SEB) can alter the percentage of CD4/CD8 subsets in the thymus of the offspring, in this study, we focus on the influence of exposure of pregnant rats to SEB on number, function and response of Tregs in the thymus of the offspring. Pregnant rats at gestational day of 16 were intravenously injected with 15 µg SEB and the thymuses of the neonatal and adult offspring were harvested for this study. We found that exposure of pregnant rats to SEB could significantly increase the absolute number of Tregs and the FoxP3 expression level in the thymus of not only neonatal but also adult offspring. Re-exposure of adult offspring to SEB remarkably reduced the suppressive capacity of Tregs to CD4+ T cells and the expression levels of TGF-ß and IL-10 in the thymus, but had no effect on production of IL-4 and IFN-γ. Furthermore, it also notedly decreased the absolute number of Tregs and the FoxP3 expression level. These data suggest that prenatal exposure of pregnant rats to SEB attenuates the response of increased Tregs to re-exposure to SEB in the thymus of adult offspring.

Composition Modulation of Pt-Based Nanowire Electrocatalysts Enhances Methanol Oxidation Performance.

Composition modulation is an efficient strategy for improving the performance of Pt-based electrocatalysts for direct methanol fuel cells. Unfortunately, a robust route for the composition modulation of one-dimensional multicomponent nanowire electrocatalysts remains a tremendous challenge. Herein, we report a versatile method for high-quality Pt-based nanowires and nanotubes, which exhibit composition-dependent performance for the methanol oxidation reaction, through a simple solvothermal process. Among these catalysts, quaternary PtRuAgTe nanotubes possess the lowest onset potential of 0.387 V and display the highest activity of 1145 mA mg-1 Pt, which is ∼3.0 times that of commercial Pt/C, exhibiting the best long-term durability over 30000 s owing to the synergistic effect between compositions as well as the favorable tubelike structure. Moreover, synchrotron radiation photoelectron spectroscopy is introduced to investigate the structural behavior of the catalysts before and after the catalytic process. This work contributes a simple method toward scalable production of high-performance Pt-based nanowires and nanotubes for applications in electrocatalysts and affords an inspiring route to enhance both the catalytic activity and the durability.

23,24-Dihydrocucurbitacin B promotes lipid clearance by dual transcriptional regulation of LDLR and PCSK9.

23,24-Dihydrocucurbitacin B (designated as C95 in this article) is a cucurbitane triterpenoid that has been shown to possess a variety of pharmacological activities, such as anti-inflammatory and anti-HIV-1 activities etc. In this study, we investigated the effects of 23,24-dihydrocucurbitacin B on lipid regulation. We showed that 23,24-dihydrocucurbitacin B (1-5 µM) dose-dependently promoted DiI-LDL uptake in HepG2 cells by upregulating low-density lipoprotein receptor (LDLR) protein. In HepG2 cells, 23,24-dihydrocucurbitacin B (1-10 µM) dose-dependently enhanced LDLR promoter activity by elevating the mature form of SREBP2 (sterol regulatory element binding protein 2) protein levels on one hand, and inhibited PCSK9 (proprotein convertase subtilisin/kexin type 9) promoter activity by attenuating HNF1α (hepatocyte nuclear factor-1α) protein levels in nuclei on the other hand. Consequently, the expression of LDLR protein markedly increased, whereas the PCSK9-mediated LDLR protein degradation decreased. In a high-cholesterol LVG golden Syrian Hamster model, administration of 23,24-dihydrocucurbitacin B (30 mg · kg-1⋅ d-1, intragastric, for 3 weeks) significantly decreased the serum LDL-cholesterol (LDL-C) levels. PCSK9 protein levels in the serum and liver tissues were significantly decreased, whereas LDLR protein levels in liver tissues were significantly increased in the treated animals as compared with the control animals. In conclusion, our study demonstrates for the first time that 23,24-dihydrocucurbitacin B exhibits dual transcriptional regulation of LDLR and PCSK9 in HepG2 cells by increasing SREBP2 protein levels and decreasing HNF1α protein levels in the nuclei. These results propose a new strategy to simultaneously manage LDLR and PCSK9 protein expression and provide a promising lead compound for drug development.

In Situ Seed-Mediated High-Yield Synthesis of Copper Nanowires on Large Scale.

Copper nanowires (Cu NWs) are among ideal candidates for fabricating various advanced nanodevices, especially flexible electronics and transparent conductive electrodes. However, although many efforts have been made, the commercialization of Cu NWs is still difficult. Herein, we report an in situ seed-mediated two-step strategy to synthesize well-defined Cu NWs in high yield. In the first step, that is, seed formation process, most Cu ions (85%) in situ transform to nondecahedral Cu nanodots (NDs). These Cu NDs can promote the formation of decahedral multiply twinned particles (DMTPs) and the subsequent growth of Cu NWs by selectively inhibiting the spontaneous ripening of nanoparticle (NP) byproducts in the second step. The amount and quality of Cu NDs play an important role in high-yield production of Cu NWs, and the yield was successfully increased to 2.4 times higher than that of the conventional methods. Furthermore, an effective shaking-rotating purification technique was developed to fully separate Cu NWs from the final product solution. After scaling up the reaction, 50 g of high-quality Cu NWs can be produced with a uniform size and high aspect ratio at a very low material cost of $ 0.99/g. These promising results not only provide a high-yield and low-cost synthetic route but also can promote the widespread commercialization of Cu NWs in advanced nanodevices.

Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway.

Magnesium lithospermate B (MLB) is an active component of Salvia miltiorrhiza Radix, a traditional Chinese herb used in treating cardiovascular diseases. In this study, we investigated the protective effects of MLB against inflammation-induced endothelial dysfunction in vitro and in vivo, and the underlying mechanisms. Endothelial dysfunction was induced in human dermal microvascular endothelial cells (HMEC-1) in vitro by lipopolysaccharide (LPS, 1 µg/mL). We showed that pretreatment with MLB (10-100 µM) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNFα, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10 mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25-100 mg/kg, ip) dose-dependently restored LPS-impaired endothelial-dependent vasodilation in superior mesenteric artery (SMA), attenuated leukocyte adhesion in mesenteric venules and decreased vascular leakage in the lungs. We further elucidated the mechanisms underlying the protective effects of MLB, and revealed that MLB pretreatment inhibited NF-κB activation through inhibition of IκBα degradation and subsequent phosphorylation of NF-κB p65 in vitro and in vivo. In HMEC-1 cells, MLB pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. Knockdown of Nrf2 with siRNA abolished the inhibitory effects of MLB on IκBα degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Gö6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-κB activation through PKC- and PI3K/Akt-mediated Nrf2 activation in HMEC-1 cells and protects against LPS-induced endothelial dysfunction in murine model of acute inflammation.

Bacteria assisted protein imprinting in sol-gel derived films.

A hierarchical imprinting strategy was used to create protein imprints in a silicate film with a high binding capacity as well as selectivity toward the imprint protein and little specificity towards other proteins. In the first part of this work, rod-shaped bacteria were used as templates to create imprints in silica films of various thicknesses to open up the silica framework and increase the surface area exposed to solution. In the second part, the protein (e.g., cytochrome c (CYC) or green fluorescent protein (GFP)) was covalently attached to the surface of Bacillus subtilis and this protein-bacteria complex served as the imprint moiety. Atomic force microscopy and scanning electron microscopy were used to image the micron-size rod-shaped bacteria imprints formed on the silica surface. Fluorescence microscopy, which was used to follow the fabrication process with GFP as the representative protein, clearly demonstrated protein imprinting, protein removal and protein rebinding as well as protein specificity. Visible absorption spectroscopy using CYC as the imprint protein demonstrated relatively fast uptake kinetics and also good specificity against other proteins including bovine serum albumin (BSA), horseradish peroxidase (HRP), glucose oxidase (GOD), and lysozyme (LYZ). Collectively this work demonstrates a new surface bio-imprinting approach that generates recognition sites for proteins and provides a viable means to increase the binding capacity of such imprinted thin films.

[Practice of Palliative Care:Experience of a Patient with Advanced Retroperitoneal Sarcoma at the End of Life].

According to the World Health Organization,palliative care is an approach that prevents and alleviates the pain of patients with life-threatening illness and improves the quality of life of patients and their families through early identification,assessment and treatment of pain and other physical,psychosocial and spiritual problems. It is the active holistic care accomplished by multidisciplinary team. This article describes the practice of the palliative care in a patient with advanced retroperitoneal sarcoma.

Large Area Co-Assembly of Nanowires for Flexible Transparent Smart Windows.

Electrochromic devices with controllable color switching, low cost, and energy-saving advantages have been widely used as smart windows, rear-view car mirrors, displays, and so on. However, the devices are seriously limited for flexible electronics as they are traditionally fabricated on indium tin oxide (ITO) substrates which will lose their conductivity after bending cycles (the resistance significantly changed from 200 Ω to 6.56 MΩ when the bending radius was 1.2 cm). Herein, we report a new route for large area coassembly of nanowires (NWs), resulting in the formation of multilayer ordered nanowire (NW) networks with tunable conductivity (7-40 Ω/sq) and transmittance (58-86% at 550 nm) for fabrication of flexible transparent electrochromic devices, showing good stability of electrochromic switching behaviors. The electrochromic performance of the devices can be tuned and is strongly dependent on the structures of the Ag and W18O49 NW assemblies. Unlike the ITO-based electronics, the electrochromic films can be bent to a radius of 1.2 cm for more than 1000 bending cycles without obvious failure of both conductivity (ΔR/R ≈ 8.3%) and electrochromic performance (90% retention), indicating the excellent mechanical flexibility. The present method for large area coassembly of NWs can be extended to fabricate various NW-based flexible devices in the future.

Synthesis of Low Pt-Based Quaternary PtPdRuTe Nanotubes with Optimized Incorporation of Pd for Enhanced Electrocatalytic Activity.

Improving heteroatomic interactions via alloying or forming heterogeneous catalysts is of importance to the enhancement in terms of electrocatalytic activity and stability. In this work, a simple galvanic replacement reaction was utilized to synthesize low Pt-based quaternary nanotubes (NTs). It is easy to obtain PtPdRuTe NTs with different composition and controlled shape using ultrathin Te nanowires (NWs) as sacrificial templates for its high activity. The NT wall thickness and formed NPs on the surface are closely related with the composition, especially Pd content. The optimized incorporation of Pd atoms into ternary PtRuTe NTs formed a uniform protecting PtPd surface and modified the Pt electronic structure to improve the methanol oxidation reaction (MOR) performance. X-ray photoelectron spectroscopy (XPS) reveals a larger extent of electron transfer from neighboring atoms to Pt on PtPdRuTe, consequently leading to a weaker bonding of the intermediate on Pt. As a result, the quaternary PtPdRuTe NTs exhibit enhanced activity and stability toward efficient MOR.

Association of TNF-α genetic polymorphisms with recurrent pregnancy loss risk: a systematic review and meta-analysis.

BACKGROUND: Several studies on the association of tumor necrosis factor alpha (TNF-α) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-α polymorphisms and RPL. METHODS: An extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software. RESULTS: 10 case-control studies including 1430 RPL patients and 1727 healthy controls were identified. Meta-analysis indicated that TNF-α-308G/A (rs1800629) polymorphism in the TNF-α gene correlated with elevated RPL risk whereas no significant association was observed between TNF-α-238G/A (rs361625) and RPL. CONCLUSIONS: The current meta-analysis demonstrates that TNF-α-308G/A polymorphism in the TNF-α gene is associated with susceptibility to RPL.

Betulin attenuates atherosclerosis in apoE-/- mice by up-regulating ABCA1 and ABCG1.

AIM: Betulin is a pentacyclic triterpenoid isolated from the bark of yellow and white birch trees with anti-cancer and anti-malaria activities. In this study we examined the effects of betulin on atherosclerosis in apoE-/- mice and the underlying mechanisms. METHODS: Murine macrophage RAW264.7 cells and human monocyte-derived THP-1 cells were tested. Foam cell formation was detected with Oil Red O staining. Cholesterol efflux was assessed using [3H]-cholesterol efflux assay. The expression of ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1) was examined using RT-PCR and Western-blotting. The ABCA1 promoter activity was evaluated using luciferase activity assay. Male apoE-/- mice fed on a high-fat-diet (HFD), and received betulin (20 and 40 mg·kg-1·d-1, ig) for 12 weeks. The macrophage content and ABCA1 expression in the aortic sinuses were evaluated with immunofluorescence staining. The hepatic, intestinal and fecal cholesterol were also analyzed in the mice. RESULTS: In RAW264.7 cells, betulin (0.1-2.5 µg/mL) dose-dependently ameliorated oxLDL-induced cholesterol accumulation and enhanced cholesterol efflux. In both RAW264.7 and THP-1 cells, betulin increased the expression of ABCA1 and ABCG1 via suppressing the transcriptional repressors sterol-responsive element-binding proteins (SREBPs) that bound to E-box motifs in ABCA1 promoter, whereas E-box binding site mutation markedly attenuated betulin-induced ABCA1 promoter activity. In HFD-fed apoE-/- mice, betulin administration significantly reduced lesions in en face aortas and aortic sinuses. Furthermore, betulin administration significantly increased ABCA1 expression and suppressed macrophage positive areas in the aortic sinuses. Moreover, betulin administration improved plasma lipid profiles and enhanced fecal cholesterol excretion in the mice. CONCLUSION: Betulin attenuates atherosclerosis in apoE-/- mice by promoting cholesterol efflux in macrophages.