Phosphorylation of an RNA-Binding Protein Rck/Me31b by Hippo Is Essential for Adipose Tissue Aging.

The metazoan lifespan is determined in part by a complex signaling network that regulates energy metabolism and stress responses. Key signaling hubs in this network include insulin/IGF-1, AMPK, mTOR, and sirtuins. The Hippo/Mammalian Ste20-like Kinase1 (MST1) pathway has been reported to maintain lifespan in Caenorhabditis elegans, but its role has not been studied in higher metazoans.

Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs.

Activity-based protein profiling and global proteome analysis reveal MASTL as a potential therapeutic target in gastric cancer.

Background: Gastric cancer (GC) is a prevalent malignancy with limited therapeutic options for advanced stages. This study aimed to identify novel therapeutic targets for GC by profiling HSP90 client kinases.

Methods: We used mass spectrometry-based activity-based protein profiling (ABPP) with a desthiobiotin-ATP probe, combined with sensitivity analysis of HSP90 inhibitors, to profile kinases in a panel of GC cell lines.

Palladium-Catalyzed Amination of Aryl Halides with Aqueous Ammonia and Hydroxide Base Enabled by Ligand Development.

The conversion of aryl halides to primary arylamines with a convenient and inexpensive source of ammonia has been a long-standing synthetic challenge. Aqueous ammonia would be the most convenient and least expensive form of ammonia, but such a palladium-catalyzed amination reaction with a high concentration of water faces challenges concerning catalyst stability and competing hydroxylation, and palladium-catalyzed reactions with this practical reagent are rare. Further, most reactions with ammonia to form primary amines are conducted with -butoxide base, but reactions with ammonium hydroxide would contain hydroxide as base.

Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts.

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC.

Palladium-Catalyzed Aryldifluoromethylation of Aryl Halides with Aryldifluoromethyl Trimethylsilanes.

Diaryl difluoromethanes are valuable targets for medicinal chemistry because they are bioisosteres of diaryl ethers and can function as replacements for diaryl methane, ketone, and sulfone groups. However, methods to prepare diaryl difluoromethanes are scarce, especially methods starting from abundant aryl halides. We report the Pd-catalyzed aryldifluoromethylation of aryl halides with aryldifluoromethyl trimethylsilanes (TMSCF Ar).

Identification of Nucleolin as a Novel AEG-1-Interacting Protein in Breast Cancer via Interactome Profiling.

Breast cancer is one of the most common malignant diseases worldwide. Astrocyte elevated gene-1 (AEG-1) is upregulated in breast cancer and regulates breast cancer cell proliferation and invasion. However, the molecular mechanisms by which AEG-1 promotes breast cancer have yet to be fully elucidated.

Activity-Based Protein Profiling Reveals Potential Dasatinib Targets in Gastric Cancer.

Dasatinib is a multi-target kinase inhibitor, whose targets include BCR-ABL, SRC family kinases, and various cancer kinases. The elevated SRC activity in gastric cancer (GC) has prompted the need for the therapeutic application of dasatinib in GC. We observed that the efficacy of dasatinib varied with the GC cell lines.

Cross-Coupling between Hydrazine and Aryl Halides with Hydroxide Base at Low Loadings of Palladium by Rate-Determining Deprotonation of Bound Hydrazine.

Reported here is the Pd-catalyzed C-N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product.

Enhanced removal of cesium by potassium-starved microalga, Desmodesmus armatus SCK, under photoheterotrophic condition with magnetic separation.

This study investigated the feasibility of using photoheterotrophic microalga, Desmodesmus armatus SCK, for removal of cesium (Cs) followed by recovery process using magnetic nanoparticles. The comparison of three microalgae results indicated that D. armatus SCK removed the most Cs at both 25 °C and 10 °C.

Postmortem proteomics to discover biomarkers for forensic PMI estimation.

The assessment of postmortem degradation of skeletal muscle proteins has emerged as a novel approach to estimate the time since death in the early to mid-postmortem phase (approximately 24 h postmortem (hpm) to 120 hpm). Current protein-based methods are limited to a small number of skeletal muscle proteins, shown to undergo proteolysis after death. In this study, we investigated the usability of a target-based and unbiased system-wide protein analysis to gain further insights into systemic postmortem protein alterations and to identify additional markers for postmortem interval (PMI) delimitation.

Transition Metal Vinylidene- and Allenylidene-Mediated Catalysis in Organic Synthesis.

With their mechanistic novelty and various modalities of reactivity, transition metal unsaturated carbene (alkenylidene) complexes have emerged as versatile intermediates for new reaction discovery. In particular, the past decade has witnessed remarkable advances in the chemistry of metal vinylidenes and allenylidenes, leading to the evolution of a diverse array of new catalytic transformations that are mechanistically distinct from those developed in the previous two decades. This review aims to provide a survey of the recent achievements in the development of organic reactions that make use of transition metal alkenylidenes as catalytic intermediates and their applications to organic synthesis.

Prolonged MEK inhibition leads to acquired resistance and increased invasiveness in KRAS mutant gastric cancer.

Gastric cancer (GC) is one of the most common causes of cancer-associated death. However, traditional therapeutic strategies have failed to significantly improve the survival of patient with advanced GC. While KRAS mutations have been found in some patients with gastric cancer, an effective therapy to treat KRAS-driven gastric cancer has not been established yet.

Rhodium-Catalyzed Tandem Addition-Cyclization-Rearrangement of Alkynylhydrazones with Organoboronic Acids.

Transition metal-mediated catalysis routinely enables substrates of multiple π-systems to be efficiently coupled with various carbon nucleophiles along with simultaneous ring formation. This transformation, however, remains unexplored in connection with pericyclic processes. Reported here is a protocol for cycloalkene synthesis based on the merger of rhodium catalysis and a retro-ene reaction.