Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays.

In response to an ever-increasing demand of new small molecules therapeutics, numerous chemical and genetic tools have been developed to interrogate compound mechanism of action. Owing to its ability to approximate compound-dependent changes in thermal stability, the proteome-wide thermal shift assay has emerged as a powerful tool in this arsenal. The most recent iterations have drastically improved the overall efficiency of these assays, providing an opportunity to screen compounds at a previously unprecedented rate.

Achieving a 35-Plex Tandem Mass Tag Reagent Set through Deuterium Incorporation.

Mass spectrometry-based sample multiplexing with isobaric tags permits the development of high-throughput and precise quantitative biological assays with proteome-wide coverage and minimal missing values. Here, we nearly doubled the multiplexing capability of the TMTpro reagent set to a 35-plex through the incorporation of one deuterium isotope into the reporter group. Substituting deuterium frequently results in suboptimal peak coelution, which can compromise the accuracy of reporter ion-based quantification.

Distinctive patterns of bacterial community succession in the riverine micro-plastisphere in view of biofilm development and ecological niches.

Exploring plastic bacterial community succession is a crucial step in analyzing and predicting the ecological assembly processes of the plastisphere and its associated environmental impacts. However, microbial biofilm development and niche differentiation during plastic bacterial community succession have rarely scarcely considered. Here, we assessed the differences between three microplastics (MPs) and two natural polymers in terms of biofilm development and niche properties during bacterial community succession, and identified a genus of MPs-degrading bacteria with strong competitive potential in the plastisphere.

SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers.

Adult liver malignancies, including intrahepatic cholangiocarcinoma and hepatocellular carcinoma, are the second leading cause of cancer-related deaths worldwide. Most individuals are treated with either combination chemotherapy or immunotherapy, respectively, without specific biomarkers for selection. Here using high-throughput screens, proteomics and in vitro resistance models, we identify the small molecule YC-1 as selectively active against a defined subset of cell lines derived from both liver cancer types.

NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer.

Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator, KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers; however, the role of this pathway in cancers with wild-type KEAP1 remains poorly understood. To answer this question, we induced NRF2 via pharmacological inactivation of KEAP1 in a panel of 50+ non-small cell lung cancer cell lines.

Comparative transcriptome analysis reveals the impact of the daily rhythm on the hemolymph of the Chinese mitten crab ().

The daily rhythm affects a series of physiological functions in crustaceans. To study its effect on the physiological function in , a crustacean species of high economic value, we analyzed the hemolymph transcriptome during the daily rhythm by high-throughput sequencing. We sampled the hemolymph from crabs at four time points in a single day (06:00, 12:00, 18:00, and 24:00 h) and identified 3,01,661 and 1,03,998 transcripts and unigenes, respectively; some of the unigenes were annotated as core clock genes.

Mutant IDH Inhibits IFNγ-TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in Cholangiocarcinoma.

Unlabelled: Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate-dependent enzymes, altering epigenetics and metabolism. Here, by developing mIDH1-driven genetically engineered mouse models, we show that mIDH1 supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate-mediated mechanisms: suppression of CD8+ T-cell activity and tumor cell-autonomous inactivation of TET2 DNA demethylase.

Effects of Corrosion on Compressive Arch Action and Catenary Action of RC Frames to Resist Progressive Collapse Based on Numerical Analysis.

Many negative factors can influence the progressive collapse resistance of reinforced concrete (RC) frame structures. One of the most important factors is the corrosion of rebar within the structure. With increasing severity of corrosion, the duration, robustness, and mechanical performance can be greatly impaired.

Two novel lead-based coordination polymers for luminescence sensing of anions, cations and small organic molecules.

Two novel lead-based coordination polymers, namely [Pb(cbdcp)]·0.5HO·0.5CHOH (1) and [Pb(cbdcp)] (2), have been solvothermally constructed by using a zwitterionic ligand 4-carboxy-1-(3,4-dicarboxy-benzyl)-pyridinium chloride (abbreviated as HcbdcpCl).

The MAP Kinase CfPMK1 Is a Key Regulator of Pathogenesis, Development, and Stress Tolerance of .

The Ascomycetes fungus causes severe diseases on a wide range of crops, fruits, and vegetables. Its pathogenic mechanisms, however, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are conserved regulators of fungal development and pathogenesis.

Comparative analysis of the mitochondrial genomes of Colletotrichum gloeosporioides sensu lato: insights into the evolution of a fungal species complex interacting with diverse plants.

Background: The fungal species complex Colletotrichum gloeosporioides sensu lato contains over 20 plant-interacting species. These species exhibit different life styles (e.g.

Evaluation of disulfide scrambling during the enzymatic digestion of bevacizumab at various pH values using mass spectrometry.

Disulfide linkages play an important role in protein stability and activity. Thus, it is critical to characterize disulfide bonds to ensure the quality and function of protein pharmaceuticals. There are, however, problems associated with maintaining disulfide linkages in the conventional procedures that are used to digest a protein.