Furthermore, AMPK activation attenuates induction of endogenous SREBP-1c mRNA by T0901317. These results indicate that AMPK directly inhibits ligand-induced LXR activity in addition to blocking production of endogenous LXR ligands.”
“Aims: Lumican, a small leucine-rich proteoglycan (SLRP), has attracted attention as a molecule of the extracellular matrix possibly

involved in signalling pathways affecting cancer cell behaviour. The remodelling of the actin cytoskeleton, induced in response to external stimuli, is crucial for cell motility and intracellular signal transduction. The main goal this website of this study was to examine the effects of recombinant lumican on actin organization, the state of actin polymerization, actin isoform expression, and their sub-cellular distribution in the A375 human melanoma cell line.\n\nMain methods: Fluorescence and confocal microscopy were used to observe actin cytoskeletal Organization and the sub-cellular distribution of cytoplasmic beta- and gamma-actins. The ability of actin to inhibit DNasel activity was used to quantify actin. Western

blotting and real-time PCR were used to determine the expression levels of the actin isoforms.\n\nKey findings: A375 cells grown on lumican coatings changed in morphology and presented rearranged actin filament organization: from filaments evenly spread throughout the whole cell body to their Epigenetics inhibitor condensed submembrane localization.

In the presence of lumican, both actin isoforms were concentrated under the cellular membrane. A statistically significant increase in the total, filamentous, and monomeric Duvelisib inhibitor actin pools was observed in A375 cells grown on lumican.\n\nSignificance: Novel biological effects of lumican, an extracellular matrix SLRP, on the actin pool and organization are identified, which may extend Our understanding of the mechanism underlying the inhibitory effect of lumican on the migration of melanoma cells. (C) 2008 Elsevier Inc. All rights reserved.”
“Background: Several studies have investigated whether the polymorphism in the apolipoprotein A5 (APOA5) is associated with type 2 diabetes mellitus (T2DM) risk. However, those studies have produced inconsistent results. The purpose of this study was to investigate whether the APOA5 -1131T/C polymorphism (rs662799) confers significant susceptibility to T2DM using a meta-analysis.\n\nMethods: PubMed, Embase, Web of Science, Cochrane database, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0.

The polypropylene blends will be characterized optically at the same probing wavelength by incoherent light scattering to understand phenomena

enlightened by Raman spectroscopy. Then, a discussion on the Raman intensity evolution is conducted, with the possible contribution of Raman spectroscopy to describe stages of the volume damage micromechanism. Copyright (c) 2014 John Wiley & Sons, Ltd.”
“The killifish Fundulus heteroclitus is an estuarine species with broad physiological plasticity, enabling acclimation to diverse stressors. Previous work suggests that freshwater populations expanded their physiology to accommodate low salinity environments; however, it is unknown whether this compromises their tolerance to high salinity. We used a comparative approach to investigate the mechanisms of a derived freshwater phenotype and the fate learn more of an ancestral euryhaline phenotype after invasion of a freshwater environment. We compared physiological and transcriptomic responses to high-and low-salinity stress in fresh and brackish water populations and found an enhanced plasticity to low salinity in the freshwater population coupled with a reduced ability to acclimate to high salinity. Transcriptomic data identified genes with a conserved common response, a conserved salinity-dependent response and responses associated with population divergence. Conserved common acclimation responses revealed stress responses and alterations

in cell-cycle regulation as important mechanisms in the general osmotic response. Salinity-specific responses included the regulation of genes involved BKM120 in ion transport, intracellular calcium, energetic processes and cellular remodeling. Genes diverged between populations were primarily those showing salinity-specific

expression and included those regulating polyamine homeostasis and the cell cycle. Additionally, when populations were matched with their native salinity, expression patterns were consistent with the concept of ‘transcriptomic resilience’, suggesting local adaptation. These findings provide insight into the fate of a plastic phenotype after a hypoxia-inducible factor cancer shift in environmental salinity and help to reveal mechanisms allowing for euryhalinity.”
“Congenital left ventricular aneurysms and diverticula (LVA/Ds) are rare cardiac malformations that can be detected using echocardiography or other imaging techniques. Some of these patients present with ventricular arrhythmias. This study investigated clinical characteristics of patients with congenital LVA/D presenting with arrhythmic manifestations. Over the previous 20 years 250 patients were diagnosed to have congenital LVA/D at our institution. Diagnosis was made using echocardiography after exclusion of coronary artery disease, local cardiac inflammatory processes, traumatic causes, or cardiomyopathies. At initial presentation 32 of the 250 patients (13%, average age 45 years, range 25 to 65, 21 men and 11 women) exhibited arrhythmias.

Activities of 4 chiral congeners PCB91, 95, 132, and 149 and their respective 4- and 5-hydroxy (-OH) derivatives toward rabbit skeletal muscle GW4869 molecular weight ryanodine receptor (RyR1) are investigated using [H-3]ryanodine binding and SR Ca-2 flux analyses. Although 5-OH metabolites have comparable activity to their respective parent in both assays, 4-OH derivatives are unable to trigger Ca-2 release from SR microsomes in the presence of Ca-2-ATPase activity. PCB95 and derivatives are investigated using single channel voltage-clamp and primary murine embryonic muscle cells (myotubes). Like

PCB95, 5-OH-PCB95 quickly and persistently increases channel open probability (p(o) bigger than .9) by stabilizing the full-open channel state, whereas 4-OH-PCB95 transiently enhances p(o). Ca-2 imaging of myotubes loaded with Fluo-4 show that acute exposure to PCB95 (5M) potentiates ECC and caffeine responses and partially depletes SR Ca-2 stores. Exposure to 5-OH-PCB95 (5 M) increases cytoplasmic Ca-2, leading to 4SC-202 rapid ECC failure in 50% of myotubes with the remainder retaining negligible responses.

4-OH-PCB95 neither increases baseline Ca-2 nor causes ECC failure but depresses ECC and caffeine responses by 50%. With longer (3h) exposure to 300nM PCB95, 5-OH-PCB95, or 4-OH-PCB95 decreases the number of ECC responsive myotubes by 22%, 81%, and 51% compared with control by depleting SR Ca-2 and/or uncoupling ECC. NDL-PCBs and their 5-OH and 4-OH metabolites differentially influence RyR1 channel activity and ECC in embryonic skeletal muscle.”
“Background and Objective Vandetanib is a selective inhibitor of vascular endothelial check details growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) signalling, indicated for the treatment of medullary thyroid cancer. We investigated potential drug-drug interactions between vandetanib and metformin [organic cation transporter 2 (OCT2) substrate; NCT01551615]; digoxin [P-glycoprotein (P-gp) substrate; NCT01561781]; midazolam [cytochrome P450 (CYP) 3A4 substrate; NCT01544140];

omeprazole (proton pump inhibitor) or ranitidine (histamine H-2-receptor antagonist; both NCT01539655). Methods Four open-label, phase I studies were conducted in healthy volunteers: n = 14 (metformin), n = 14 (digoxin), n = 17 (midazolam), n = 16 (omeprazole), n = 18 (ranitidine). Three of these comprised the following regimens: metformin 1000 mg +/- vandetanib 800 mg, midazolam 7.5 mg +/- vandetanib 800 mg, or digoxin 0.25 mg +/- vandetanib 300 mg. The randomized study comprised vandetanib 300 mg alone and then either (i) omeprazole 40 mg (days 1-4), and omeprazole + vandetanib (day 5); or (ii) ranitidine 150 mg (day 1), and ranitidine + vandetanib (day 2). The primary objective assessed metformin, digoxin, midazolam and vandetanib pharmacokinetics.

Simulation results demonstrated the hydrophobic SNX-5422 Cytoskeletal Signaling inhibitor domain of BI-1001 and CX14442 engages one subunit of HIV-1 IN CCD dimer through hydrophobic interactions, and the hydrophilic group forms hydrogen bonds with HIV-1 IN CCD residues from other subunit. CX14442 has a larger tert-butyl group than the methyl of BI-1001, and forms better interactions with the highly hydrophobic binding pocket of HIV-1 IN CCD dimer interface, which can explain the stronger affinity of CX14442 than BI-1001. Analysis of the binding mode of LEDGF/p75 with HIV-1 IN CCD reveals that the LEDGF/p75 integrase binding domain residues Ile365, Asp366, Phe406 and Val408 have significant contributions to the binding of the LEDGF/p75

PLX4032 mouse to HIV1-IN. Remarkably, we found that binding of BI-1001

and CX14442 to HIV-1 IN CCD induced the structural rearrangements of the 140 s loop and oration displacements of the side chains of the three conserved catalytic residues Asp64, Asp116, and Glu152 located at the active site. These results we obtained will be valuable not only for understanding the allosteric inhibition mechanism of LEDGINs but also for the rational design of allosteric inhibitors of HIV-1 IN targeting LEDGF/p75 binding site.”
“Alpine plants like Soldanella alpina L. are subjected to high PAR and high UV radiation. Among the important photoprotective mechanisms that prevent photoinhibition under such conditions, passive optical barriers such as UV-absorbing

compounds were investigated. In this study, temporal and spatial patterns of epidermal UV-A absorbance for S. alpina find more leaves were investigated with a combination of absorbance measurements at 375nm and imaging methods. UV-A absorbance was highest in plants acclimated to full sunlight and was markedly stable during the leaves’ lifetime. UV-A absorbance was correlated with leaf structure (leaf mass per area ratio, density of epidermal cells and stomata) and biochemical features such as chlorophyll and carotenoid content and ratio, which are characteristics of light acclimation. UV-A-absorbing compounds were mainly localised in the epidermal vacuoles and trichomes. Leaves with low UV-A absorbance were significantly more photosensitive than leaves with high UV-A absorbance. However, the epidermal UV-A absorbance increased in low-absorbance leaves under full sunlight even in the absence of UV radiation. Results suggest that high epidermal UV-A absorbance protects S. alpina leaves from photoinactivation, which is especially important after snowmelt, when plants are suddenly exposed to full sunlight.”
“Background: No-reflow in ST-segment elevation acute myocardial infarction (STEMI) is associated with a poor clinical prognosis. Its pathophysiological mechanisms are not fully elucidated yet but enhanced vascular permeability plays a key role in this phenomenon.

“
“Purpose: Although at any time in the UK, there are about 20,000 women with MS who may be considering having children, healthcare system often fails to provide them with information and support they need to make informed decisions about their

health and pregnancy management. The aim of this paper is to explore the childbearing experience of women with MS to determine what support and information may be useful to this target group. Method: Interviews were conducted with women with MS (n = 9). Transcripts were analysed using thematic analysis. Results: Three major themes emerged from the interviews with women living with MS. We found women were concerned about both medical and practical issues associated with having children. Limited access to information about

relationships between MS and childbearing and receiving conflicting or wrong information was recounted. Opinions of family members and clinicians regarding GW3965 having children in the context of MS impacted on women’s Z-IETD-FMK mouse experience of making decision about having children and childbearing. Conclusions: Women with MS can benefit from having access to comprehensive, structured sources of information about MS and childbearing. Healthcare professionals and family members support could be channelled more appropriately to enhance their experience of making choices about childbearing.”
“To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients. A total of 127 breast cancer

patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d) 1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three cycles, followed by click here paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 +/- A trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2-. pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR-/HER2- (56 %) (p smaller than 0.001). The median follow-up was 81 months (r: 15-150 months). HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p = 0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2- tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007), RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR-/HER2- tumors that achieved a pCR.

Our data suggest that BMP-2 treatment may have considerable

therapeutic potential in individuals with acute and chronic myocardial ischemia by improving the contractility of cardiomyocytes and preventing cardiomyocyte cell death.”
“Poly(lactic acid) (PLA) brushes were prepared through surface initiated ring-opening polymerization of L-lactide. Their degradation (depolymerization) was characterized by tracking their ellipsometric thickness as a function of time by repeated emersion from buffered, aqueous solutions. The pH and temperature both had a large effect on the rate of degradation. PLA brushes do not degrade in a manner similar to that of bulk PLA. Several experiments were performed, the results of which suggest that intramolecular transesterification (backbiting) was the pathway see more for the degradation of the PLA brush in basic, aqueous solution, similar to what has been observed for the depolymerization of PLA oligomers in basic solution. The PLA brushes degrade very slowly in acidic solution. This behavior is similar to the degradation of PLA oligomers Transmembrane Transporters inhibitor in acidic solution.”
“Transesterification has proved to be the best option for obtaining biodiesel and, depending on the type of alcohol used in the reaction,

the type of biodiesel may be methyl ester or ethyl ester. Leaking biodiesel can reach water bodies, contaminating aquatic organisms, particularly fish. The objective of this study was to determine whether the soluble fraction of biodiesel (Bd), produced by both the ethylic (BdEt) and methylic (BdMt)

routes, can cause cytotoxic, biochemical and genotoxic alterations in the hepatocyte cell line of Danio rerio (ZFL). The metabolic activity of the cell was quantified by the KIT reduction method, while genotoxic damage was analyzed by the comet assay with the addition of specific endonucleases. Nepicastat order The production of reactive oxygen species (ROS) and antioxidant/biotransformation enzymes activity also were determined. The results indicate that both Bd increased ROS production, glutathione S-transferase activity and the occurrence of DNA damage. BdMt showed higher cytotoxicity than BdEt, and also caused oxidative damage to the DNA. In general, both Bd appear to be stressors for the cells, causing cytotoxic, biochemical and genetic alterations in ZFL cells, but the type and intensity of the changes found appear to be dependent on the biodiesel production route. (C) 2014 Elsevier Ltd. All rights reserved.”
“Diabetic vascular pathology is largely attributable to impairments in tissue recovery from hypoxia. Circulating progenitor cells have been postulated to play a role in ischemic recovery, and deficiencies in these cells have been well described in diabetic patients.

On the basis of these results we propose that during acute stress AVP interacts with, especially, the PVN and the CeA, to change their rates of biosynthesis and/or release of CRF. (C) 2011 Elsevier B.V. All rights reserved.”
“Objectives Retinal blood vessels may develop

vasculopathy and apoptosis in response to hypertension. The present study was aimed at testing the role of losartan, a specific antagonist of angiotensin II receptor type 1 receptor in regulation of vascular apoptosis in retinal vasculature with hypertension.\n\nMethods Losartan potassium was administered to spontaneously hypertensive rats (SHR). Blood pressure was measured in SHR as well as normotensive Wistar-Kyoto rats (WKY). Eye fundus was examined in living animals and then tissue specimens were collected for histochemistry by Selleckchem Fer-1 hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine NSC23766 chemical structure 5′-triphosphate nick end labeling (TUNEL), immunohistochemistry and transmission electron microscopy.\n\nResults Losartan treatment for 4-8 weeks reduced blood pressure

of SHR to the normal levels seen in WKY. The losartan-treated SHR showed marked improvement of retinal vascular morphology compared with untreated SHR. The retinal blood networks of the treated SHR developed lower degrees of vasculopathy and apoptosis. TUNEL and transmission electron microscopy also revealed that losartan exerted its protective effects not only on endothelial cells but on pericytes as well. The blood vessels of losartan-treated animals also showed decreased expression of bax with Fludarabine purchase elevation of B-cell CLL/lymphoma 2.\n\nConclusion Treatment with losartan, a medicine that lowers blood pressure by blocking angiotensin II receptor type 1 receptor, can protect the retinal vasculature against hypertensive vascular injury by inhibiting apoptosis of vascular cells and by preventing hypertensive retinopathy. J Hypertens 28:510-519 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Niosomes represent an emerging class of novel vesicular systems. They are composed

of nonionic surfactants which are biodegradable and relatively nontoxic. They were developed as stable and inexpensive alternatives to liposomes. Since their early introduction to cosmetic industry their role has diversified to other application areas. They are now being ardently explored as potential carriers for sustained and targeted drug delivery. In addition to conventional, oral, and parenteral routes, they are amenable to be delivered by ocular, transdermal, vaginal, and inhalation routes. Delivery of biotechnological products including vaccine delivery with niosomes is also an interesting and promising research area. The introduction of provesicular approach in the form of proniosomes has further increased the relevance of these systems.

The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mu mol vs. 23.5 GBq/mu mol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [(18)F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results Stattic suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional

groups, although a triazole moiety at C1 of [(18)F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1.”
“The human TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase) belongs to the PTEN (Phosphatase and TENsin homologue deleted on chromosome 10) BMS-777607 manufacturer family of dual-specific phosphatases and is expressed from the human chromosome 13 as multiple splice-variants, e.g., TPIP alpha, beta, gamma mRNAs. PTEN is a well characterized tumor suppressor, which controls survival, adhesion, motility and migration of mammalian cells, its C2-domain plays crucial role in controlling these functions. However, role of isolated C2-domain protein in regulation of cell proliferation and apoptosis is not reported. We report

sequence analysis and function of a novel human TPIP (TPIP-C2) cDNA encoding a 193 amino acid C2-domain in cell proliferation and apoptosis regulation. In silico analysis and homology modelling revealed that the C2-domain of TPIP-C2 is similar to that of PTEN but with short disorder

sequences overlapping or adjacent to the post-translational modification sites. Overexpression of TPIP-C2 cDNA in human embryonic kidney (HEK-293) cells caused cell cycle arrest, inhibition Linsitinib research buy of cell proliferation and induced apoptosis in an activated caspase 3 and PARP-dependent manner in comparison to overexpression of the full length human PTEN cDNA. TPIP-C2 overexpressed cells also showed S-phase cell cycle arrest. We suggest that C2-domain of TPIP-C2 may act as a dominant negative effector, which may bind to and arrest the cell proliferation signalling complex and isolated TPIP-C2-domain-like proteins expressed in mammalian cells/tissues may play important role in regulation of cell proliferation and apoptosis. The TPIP-C2 cDNA may be exploited for inducing cell cycle-inhibition and apoptosis in human cancer cells and tissues.”
“Trastuzumab has shown significant clinical benefits in patients with operable and metastatic HER2-positive breast cancer. However, the biological mechanism of the additional effect of trastuzumab administered in combination with conventional chemotherapy is poorly understood.

Of these, 128 (66.7%) articles were original research, predominantly trauma database case series (57 [29.7%]) and cohort studies (55 [28.6%]), whereas 37 (19.3%) were narrative reviews and 8 (4.2%) were guidelines. A total of 1572 QIs in trauma care were identified and classified into 8 categories: non-American College of Surgeons Committee on Trauma (ACS-COT) audit filters (42.0%), ACS-COT audit filters (19.1%), patient safety indicators (13.2%), trauma center/system criteria (10.2%), indicators measuring or benchmarking outcomes of care (7.4%), peer review (5.5%), general audit measures (1.8%),

and guideline availability or adherence (0.8%). Measures of prehospital and hospital processes Smoothened Agonist mouse (60.4%) and outcomes (22.8%) were the most common QIs identified. Posthospital and secondary injury prevention QIs accounted for less than 5% of QIs.\n\nConclusions: see more Many QIs for evaluating the quality of trauma care have been proposed, but the evidence to support these indicators is not strong. Practical

recommendations to select QIs to measure the quality of trauma care will require systematic reviews of identified candidate indicators and empirical studies to fill the knowledge gaps for postacute QIs.”
“The nucleation and dynamics of multiple generations of In droplets formed from Langmuir evaporation of InP (001), (111)A, and (111)B surfaces are reported. In situ mirror electron microscopy reveals that the majority of first-generation, or mother, droplets break up immediately before they run from the nucleation sites, leaving behind daughter droplets and etch trails where more droplets emerge. These subsequent droplets grow with time and run once a critical size is reached. The breakup and running characteristics are explained in terms of crystallography, viscosity, chemical potential, and temperature and will likely affect the

growth processes and designs of various droplet-catalyzed nanostructures and devices.”
“Bacterial fruit blotch (BFB) of cucurbits is caused by the Gram-negative bacterium Acidovorax avenae subsp. citrulli. The disease gained importance Selleck Bcl-2 inhibitor in the late 1980s, after devastating outbreaks in watermelon fields in several states in the US. Since then, BFB has spread worldwide, and has been reported in other cucurbits such as melon, pumpkin, squash, and cucumber. A. avenae subsp. citrulli is a seedborne pathogen of highly destructive potential. Under favorable conditions, the bacterium spreads rapidly throughout nurseries and in the field, leading to seedling blight or, at a later stage, fruit rot. Strategies for managing BFB are limited and there are no reliable sources of BFB resistance. The disease therefore represents a serious threat to the cucurbit industry. Despite its economic importance, there is little knowledge on basic aspects of the pathogen’s biology or on the molecular basis of BFB pathogenesis. Recently, the genome sequence of one A. avenae subsp.

Of the remaining 916 patients, a single abnormal Citarinostat manufacturer gland was identified on MIBI in 682 (74%), US in 731 (80%), and concordance of both in 588 (64%). Unsuspected multiglandular disease (MGD) was identified at BE in 22%, 22%, and 20% of patients, respectively. Adding intraoperative parathyroid hormone sampling

(IOPTH) further reduced the rate of unsuspected MGD to 16%, 17%, and 16%. Overall, IOPTH correctly predicted MGD in only 22%. Neither concomitant nonsurgical thyroid disease nor more stringent selection criteria (preop Ca > 11 mg/dL and PTH > 120 pg/dL) altered success rates. In patients with MGD, a subsequent gland identified was larger than the index gland in 23%. Ninety-eight percent of BE patients were cured of F HPT.\n\nConclusions: This is the largest study to evaluate the prevalence of additional

parathyroid pathology in patients who are candidates for LE. Limitations in localizing studies and IOPTH fail to identify MGD in at least 16% of patients, risking future recurrence.”
“Four check details specific forces (H-bonds, van der Waals forces, hydrophobic and charge interactions) shape the structure of proteins, and many biologists assume they will determine the shape of all structures in the cell. However, as the mass and contour length of a human chromosome are similar to 7 orders of magnitude larger than those of a typical protein, additional forces can become significant.

We review evidence that additional non-specific (entropic) forces are major determinants of chromosomal shape and position. They are sufficient to drive the segregation (de-mixing) of newly replicated DNA to the poles of bacterial cells, while an entropic centrifuge can both form human chromosomes into territories and position them appropriately in nuclei; more locally, a depletion attraction can loop bacterial and human genomes.”
“Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China(1). A total of 132 confirmed cases and 39 deaths have been reported(2). Most patients presented with severe pneumonia and acute respiratory distress syndrome(3,4). Although the first epidemic has buy CAL-101 subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (alpha 2,3-linked sialic acid) and human-type (alpha 2,6-linked sialic acid) 3 receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines.