Pharmacokinetics of Zilurgisertib With and Without Food from Single and Multiple Ascending Dose Phase 1 Studies in Healthy Adults.

Background And Objectives: The oral, potent, and highly selective activin receptor-like kinase 2 (ALK2) inhibitor zilurgisertib (INCB000928) is in development as a treatment for fibrodysplasia ossificans progressiva (FOP), and for anemia due to myelofibrosis, myelodysplastic syndromes, and multiple myeloma. Saliva is an attractive alternative to blood for drug monitoring and pharmacokinetic analysis, as it is non-invasive to retrieve. This is beneficial for patients, such as those with FOP, for whom blood draws can be challenging due to soft tissue damage susceptibility that can cause progressive heterotopic ossification, and for whom tourniquet time and blood draws must be minimized.

De Novo Genome Assembly of the Whitespot Parrotfish (): A Valuable Scaridae Genomic Resource.

, a whitespot parrotfish from the Scaridae family, is a herbivorous fish inhabiting coral reef ecosystems. The deterioration of coral reefs has highly affected the habitats of the parrotfish. The decline in genetic diversity of parrotfish emphasizes the critical importance of conserving their genetic variability to ensure the resilience and sustainability of marine ecosystems for future generations.

Discovery of 5,7-Dihydro-6-pyrrolo[2,3-]pyrimidin-6-ones as Highly Selective CDK2 Inhibitors.

A series of exceptionally selective CDK2 inhibitors are described. Starting from an HTS hit, we successfully scaffold hopped to a 5,7-dihydro-6-pyrrolo[2,3-]pyrimidin-6-one core structure, which imparted a promising initial selectivity within the CDK family. Extensive further SAR identified additional factors that drove selectivity to above 200× for CDKs 1/4/6/7/9.

Discovery of Novel Pyrazolopyrimidines as Potent, Selective, and Orally Bioavailable Inhibitors of ALK2.

Activin receptor-like kinase 2 (ALK2) is a transmembrane kinase receptor that mediates the signaling of the members of the TGF-β superfamily. The aberrant activation of ALK2 has been linked to the rare genetic disorder fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) that are associated with severely reduced life expectancy in pediatric patients. ALK2 has also been shown to play an essential role in iron metabolism by regulating hepcidin levels and affecting anemia of chronic disease.

Itacitinib (INCB039110), a JAK1 Inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-cell Therapy.

Purpose: T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown long-term relapse-free survival in patients with B-cell leukemia and lymphoma. However, cytokine release syndrome (CRS) represents a serious, potentially life-threatening side effect often associated with CAR T-cell therapy.

Obstructive sleep apnea, COPD, the overlap syndrome, and mortality: results from the 2005-2008 National Health and Nutrition Examination Survey.

Objective: The aim of this study was to investigate the role of obstructive sleep apnea (OSA) on all-cause mortality in patients with COPD.

Methods: Data for this cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES) data (year 2005-2008). Eligible subjects were ≥20 years who had no COPD or OSA (n=9,237), had only OSA (n=366), had only COPD (n=695), and had OSA/COPD overlap syndrome (n=90).

Relation Between Cellular Senescence and Liver Diseases.

Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline. Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases.

Development and characterization of polymorphic microsatellite markers (SSRs) for an endemic plant, Pseudolarix amabilis (Nelson) Rehd. (Pinaceae).

Pseudolarix (Pinaceae) is a vulnerable (sensu IUCN) monotypic genus restricted to southeastern China. To better understand levels of genetic diversity, population structure and gene flow among populations of P. amabilis, we developed five compound SSR markers and ten novel polymorphic expressed sequence tags (EST) derived microsatellites.

Conjugated linoleic acid alters growth performance, tissue lipid deposition, and fatty acid composition of darkbarbel catfish (Pelteobagrus vachelli).

Fatty liver syndrome is a prevalent problem of farmed fish. Conjugated linoleic acid (CLA) has received increased attention recently as a fat-reducing fatty acid to control fat deposition in mammals. Therefore, the aim of the present study was to determine whether dietary CLA can reduce tissue lipid content of darkbarbel catfish (Pelteobagrus vachelli) and whether decreased lipid content is partially due to alterations in lipid metabolism enzyme activities and fatty acid profiles.

Roles of the lipid metabolism in hepatic stellate cells activation △.

The lipids present in hepatic stellate cells (HSCs) lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix.

Bis{μ-2-[(2-oxidobenzyl-idene)amino-meth-yl]phenolato-κO,N,O'}bis-[(pyridine-κN)zinc(II)].

In the title centrosymmetric zinc(II) complex, [Zn(2)(C(4)H(13)NO(2))(2)(C(6)H(5)N)(2)], each Zn(II) atom is coordinated by two 2-[(2-oxidobenzyl-idene)amino-meth-yl]phenolate (L) ligands and one pyridine (py) mol-ecule in a distorted trigonal-bipyramidal geometry. Each L ligand behaves as a tridentate ligand and provides a phenolate oxygen bridge which links the two Zn(II) atoms. The ZnL(py) units are linked by π-π inter-actions between adjacent pyridine mol-ecules, with a centroid-centroid distance of 3.

2D warp-and-woof interwoven networks constructed by helical chains with different chirality.

Two unprecedented 2D entangled layers of warp-and-woof threads interwoven by left- and right-handed helical chains, {[Mn(salen)Au(CN)2]4(H2O)}n (salen = N,N'-ethylenebis(salicylideneaminato)) and {Mn(acacen)Ag(CN)2}n (acacen = N,N'-ethylenebis(acetylacetonylideneiminate)) 2, have been synthesized and characterized.

P450 phenotyping of the metabolism of selegiline to desmethylselegiline and methamphetamine.

Although there is evidence in the literature of the participation of CYP2B6 in the metabolism of selegiline, it is not clear which other CYP isoforms contribute to its metabolism. The aim of this study was to investigate the P450 isozymes (CYPs) involved in the metabolism of selegiline to desmethylselegiline (DMS) and methamphetamine (MA) using four assays: incubation of selegiline with cDNA expressed CYPs, inhibition of DMS and MA formations in human liver microsomes by CYP-selective chemical inhibitors or CYP-specific antibodies, and correlation analysis. Correlation analysis, performed in a bank of 15 individual human liver microsomes, yielded correlation coefficients for DMS and MA formation of 0.

Structure of an I- x (H2O)6 anion cluster in a 3D anion crystal host [I x (H2O)6Fe(CN)6 x H2O]4-.

A planar structure of an anion cluster I- x (H2O)6 in a 3D supramolecular complex [Ru(bpy)3]2[I x (H2O)6Fe(CN)6 x H2O] has been determined by single-crystal X-ray analysis. In the supramolecule, the anion cluster I- x (H2O)6, together with the anion [Fe(CN)6 x H2O]2-, acts as a 3D crystal host, and the [Ru(bpy)3]2+ cations, as the guest molecules, occupy the vacancies of the 3D host framework. This is the first crystal example of the anion cluster I- x (H2O)6.