Synthesis and Pharmacological Characterization of Fluorescent Ligands Targeting the Angiotensin II Receptors Derived from Agonists, β-Arrestin-Biased Agonists, and Antagonists.

Angiotensin II (AngII) regulates cerebral circulation and binds with a similar affinity to AT and AT receptors. Biased AT agonists, such as TRV027, which are able to selectively activate β-arrestin while blocking the G pathway, appear promising as new therapeutics. New pharmacological tools are needed to further explore the impact of biased AT agonists on cells or tissues, such as the cerebral vessels.

Phytate metabolism is mediated by microbial cross-feeding in the gut microbiota.

Dietary intake of phytate has various reported health benefits. Previous work showed that the gut microbiota can convert phytate to short-chain fatty acids (SCFAs), but the microbial species and metabolic pathway are unclear. Here we identified Mitsuokella jalaludinii as an efficient phytate degrader, which works synergistically with Anaerostipes rhamnosivorans to produce the SCFA propionate.

Ibrutinib-associated cutaneous mucormycosis due to an species: report of a case and review of the literature.

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors.

Exceptionally well-preserved crocodilian coprolites from the Late Eocene of Northern Vietnam: Ichnology and paleoecological significance.

This study examines 55 coprolites from the Na Duong Basin to reconstruct the paleoenvironment. Coproecology sheds light on understanding the complex prey-predator relationships, trophic dynamics, and ecosystem evolution. Through quantitative and multidisciplinary analysis, the putative coprolites were attributed to crocodilian producers, leading to the establishment of a new ichnogenus and species, igen.

Stable Isotopomers of Inositol Uncover a Complex MINPP1-Dependent Inositol Phosphate Network.

The water-soluble inositol phosphates (InsPs) represent a functionally diverse group of small-molecule messengers involved in a myriad of cellular processes. Despite their centrality, our understanding of human InsP metabolism is incomplete because the available analytical toolset to characterize and quantify InsPs in complex samples is limited. Here, we have synthesized and applied symmetrically and unsymmetrically C-labeled -inositol and inositol phosphates.

Versatile signaling mechanisms of inositol pyrophosphates.

Inositol pyrophosphates (PP-InsPs) constitute a group of highly charged messengers, which regulate central biological processes in health and disease, such as cellular phosphate and general energy homeostasis. Deciphering the molecular mechanisms underlying PP-InsP-mediated signaling remains a challenge due to the unique properties of these molecules, the different modes of action they can access, and a somewhat limited chemical and analytical toolset. Herein, we summarize the most recent mechanistic insights into PP-InsP signaling, which illustrate our progress in connecting mechanism and function of PP-InsPs.

Harnessing C-labeled -inositol to interrogate inositol phosphate messengers by NMR.

Inositol poly- and pyrophosphates (InsPs and PP-InsPs) are an important group of metabolites and mediate a wide range of processes in eukaryotic cells. To elucidate the functions of these molecules, robust techniques for the characterization of inositol phosphate metabolism are required, both at the biochemical and the cellular level. Here, a new tool-set is reported, which employs uniformly C-labeled compounds ([C]-inositol, [C]InsP, [C]InsP, and [C]5PP-InsP), in combination with commonly accessible NMR technology.

Multicomponent Cascade Reactions of Unprotected Ketoses and Amino Acids--Access to a Defined Configured Quaternary Stereogenic Center.

A highly stereoselective multicomponent cascade reaction of ketones with unprotected amino acids was developed. This operationally simple methodology was expanded to reactions of unprotected ketohexoses and unprotected amino acids. By the careful choice of amino acid and isonitrile, an optional access to all possible enantiomers is given.