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Potent, Orally Bioavailable and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups.

Factor XIa inhibitors are promising novel anticoagulants which show excellent efficacy in preclinical thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress towards meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.

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DiscoveryPak™ HDAC Inhi DiscoveryPak™ Receptor DiscoveryPak™ PI 3 Kina 3-Amino-4-(2-furanyl)-6,7 DiscoveryPak™ EGFR Tyro 3-Amino-N-[(4-chloropheny Ofloxacin CAS Number [824 DiscoveryPak™ Stem Cell DiscoveryPak™ Hedgehog Sheep Polyclonal Antibody Rabbit Anti-Factor VII Po Bacillus anthracis (Anthr

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A new highly transparent injectable PHA-based thermogelling vitreous substitute.

Transparency is an important criterion for the application of biomaterials to the eye and essential for use as a vitreous substitute. However, there is a lack of understanding on the features of transparent hydrogels and the boundaries of transparency of various hydrogel systems. In this paper, we tune the poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx) content of biodegradable PHBHx-based polyurethane thermogels and show that the amount of hydrophobic PHBHx correlates with hydrogel cloudiness. We found that PHxEP-0.5 hydrogel shows high light transmittance and suitable gel properties as a vitreous substitute. The PHxEP-0.5 hydrogel is able to maintain transparency when implanted in rabbit eyes as opposed to a cloudy gel and shows negligible inflammation and preservation of the retinal structure over 6 months. In conclusion, we show that PHBHx-based thermogels can be tuned for transparency and are biocompatible in the rabbit eye. These results could be instructive for the design of a new generation of injectable transparent vitreous substitutes.

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Efficacy of NEMO-binding domain peptide used to treat experimental osteomyelitis caused by methicillin-resistant : an in-vivo study.

Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge. Our previous study had demonstrated that NEMO-binding domain (NBD) peptide effectively ameliorates the inhibition of osteoblast differentiation by TNF-α in vitro. In this work, NBD peptide was evaluated in vivo for treating chronic osteomyelitis induced by methicillin-resistant (MRSA) in a rabbit model.

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SH3 domain-binding protei Monoclonal Anti-Cellulose Mouse Anti-Human C-peptid Anti-ACE-2 (Angiotension- Goat Anti-Diphtheria Toxi Analysis Tool for AAH-CYT Anti-APRIL, Extracellular ATP-Binding Cassette, Sub Rabbit Anti-Human NPY C-F Goat Anti-Diphtheria Toxi Anti-ATM S1981CONTROL PEP Analysis Tool for AAH-CYT

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Dynamic prediction of fluid responsiveness during positive pressure ventilation: a review of the physiology underlying heart-lung interactions and a critical interpretation.

Cardiovascular responses to hypovolemia and hypotension are depressed during general anesthesia. A considerable number of anesthetized and critically ill animals may not benefit hemodynamically from a fluid bolus; therefore, it is important to have measures for accurate prediction of fluid responsiveness. Static measures of preload, such as central venous pressure, do not provide accurate prediction of fluid responsiveness, whereas dynamic measures of cardiovascular function, obtained during positive pressure ventilation, are highly predictive. This review describes key physiological concepts behind heart-lung interactions during positive pressure ventilation, factors that can modify this relationship and provides the basis for a rational interpretation of the information obtained from dynamic measurements, with a focus on pulse pressure variation (PPV).

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Mouse tissue array of liv Liver, kidney, lung, musc Lung cancer tissue array Non small cell lung carci Rat Anti-CCT theta Antibo Lung cancer and matched a FDA Standard Frozen Tissu Lung squamous carcinoma ( Lung cancer and normal ti Multiple organ tumor tiss Androgen Receptor (Phosph Androgen Receptor Antibod

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Correction: Safety and efficacy of tacrolimus-coated silicone plates as an alternative to mitomycin C in a rabbit model of conjunctival fibrosis.

[This corrects the article DOI: 10.1371/journal.pone.0219194.].

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Rabbit Anti-CD11b Integri CD41 Integrin alpha 2b an Rabbit Anti-Integrin alph Rabbit Anti-Insulin Recep Rabbit Anti-Integrin β2 Rabbit Anti-APIP Apaf1 In Rabbit Anti-Integrin alph Rabbit Anti-Insulin Recep Rabbit Anti-Integrin beta Rabbit Anti-APIP Apaf1 In Rabbit Anti-Insulin Recep Rabbit Anti-ASB12 Polyclo

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Multiparametric MRI Evaluation of Liposomal Prostaglandins E1 Intervention on Hepatic Warm Ischemia-Reperfusion Injury in Rabbits.

Liposomal prostaglandin E1 (Lipo-PGE1) treatment should protect against hepatic warm ischemia-reperfusion injury (WIRI). Improved methods are needed for the noninvasive evaluation of hepatic responses to prophylactic Lipo-PGE1 pretreatment approaches.

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Rabbit Anti-FGF3 Oncogene Human Kidney injury molec BMS-911543 Mechanisms: JA HSP90AB1 & TRAF2 Protein Angiogenesis (Human) Anti Adeno Associated Virus (A ELISA Human , Interleukin Pancreas cancer tissue ar Goat Anti- Dopamine recep Jurkat Cell Extract (Indu Goat Anti-Mouse mKIAA0319 Hepatocellular carcinoma

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Effect of strontium-containing on the properties of Mg-doped wollastonite bioceramic scaffolds.

Bone scaffold is one of the most effective methods to treat bone defect. The ideal scaffold of bone tissue should not only provide space for bone tissue growth, but also have sufficient mechanical strength to support the bone defect area. Moreover, the scaffold should provide a customized size or shape for the patient's bone defect.

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The combination of microfracture with induction of Wnt / β- Catenin pathway, leads to enhanced cartilage regeneration.

Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/β-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-β (Gsk3-β) and therefore induces Wnt/β-catenin signaling.

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Interspecies metabolic diversity of artocarpin in vitro mammalian liver microsomes.

Artocarpin has shown anti-inflammation and anticancer activities. However, the metabolism differences among different species have not been reported. In this work, we used liver microsomes to explore the metabolic characteristics and possible metabolites of artocarpin among different species. The structures of six metabolites were characterized by LC-MS/MS, and hydroxylated artocarpin was the main metabolite. Enzyme kinetics and depletion studies of artocarpin among different species proved that artocarpin metabolism exhibited significant species differences; rats and monkeys showed a great metabolic ability to artocarpin, and minipigs showed the highest similarity to humans. The hepatic clearances of artocarpin in rats and humans were predicted that artocarpin was classified as a high-clearance drug in humans and rats. The glucuronidation assay of artocarpin in different liver microsomes also proved that artocarpin metabolism showed significant species difference. These findings will support further pharmacological or toxicological research on artocarpin.: UGT: UDP-glucuronosyltransferase; CYP: cytochrome P450; LC-MS/MS: liquid chromatography-tandem mass spectrometry; HPLC: high-performance liquid chromatography; HLMs: human liver microsomes; MLMs: monkey liver microsomes; RAMs: rabbit liver microsomes; RLMs: rat liver microsomes; DLMs: dog liver microsomes; PLMs: minipig liver microsomes; : aximum velocity; : Michaelis constant; CL: intrinsic clearance; CL hepatic clearance; Q: hepatic blood flow.

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