A versatile route to fabricate single atom catalysts with high chemoselectivity

Preparation of single atom catalysts (SACs) is of broad interest to materials scientists and chemists but remains a formidable challenge. Herein, we develop an efficient approach to synthesize SACs via a precursor-dilution strategy, in which metalloporphyrin (MTPP) with target metals are co-polymerized with diluents (tetraphenylporphyrin, TPP), followed by pyrolysis to N-doped porous carbon supported SACs (M1/N-C). Twenty-four different SACs, including noble metals and non-noble metals, are successfully prepared. In addition, the synthesis of a series of catalysts with different surface atom densities, bi-metallic sites, and metal aggregation states are achieved. This approach shows remarkable adjustability and generality, providing sufficient freedom to design catalysts at atomic-scale and explore the unique catalytic properties of SACs. As an example, we show that the prepared Pt1/N-C exhibits superior chemoselectivity and regioselectivity in hydrogenation. It only converts terminal alkynes to alkenes while keeping other reducible functional groups such as alkenyl, nitro group, and even internal alkyne intact

Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase

Protein acetylation has emerged as a major mechanism in regulating cellular metabolism. Whereas most glycolytic steps are reversible, the reaction catalyzed by pyruvate kinase is irreversible and the reverse reaction requires phosphoenolpyruvate carboxykinase (PEPCK1) to commit for gluconeogenesis. Here we show that acetylation regulates the stability of the gluconeogenic rate limiting enzyme PEPCK1, thereby modulating cellular response to glucose. High glucose destabilizes PEPCK1 by stimulating its acetylation. PEPCK1 is acetylated by the P300 acetyltransferase and this acetylation stimulates the interaction between PEPCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore promoting PEPCK1 ubiquitinylation and degradation. Conversely, SIRT2 deacetylates and stabilizes PEPCK1. These observations represent an example that acetylation targets a metabolic enzyme to a specific E3 ligase in response to metabolic condition changes. Given that increased levels of PEPCK is linked with type II diabetes, this study also identifies potential therapeutic targets for diabetes

WT1 Recruits TET2 to Regulate Its Target Gene Expression and Suppress Leukemia Cell Proliferation

The TET2 DNA dioxygenase regulates cell identity and suppresses tumorigenesis by modulating DNA methylation and expression of a large number of genes. How TET2, like most other chromatin modifying enzymes, is recruited to specific genomic sites is unknown. Here we report that WT1, a sequence-specific transcription factor, is mutated in a mutually exclusive manner with TET2, IDH1 and IDH2 in acute myeloid leukemia (AML). WT1 physically interacts with and recruits TET2 to its target genes to activate their expression. The interaction between WT1 and TET2 is disrupted by multiple AML-derived TET2 mutations. TET2 suppresses leukemia cell proliferation and colony formation in a manner dependent on WT1. These results provide a mechanism for targeting TET2 to specific DNA sequence in the genome. Our results also provide an explanation for the mutual exclusivity of WT1 and TET2 mutations in AML and suggest an IDH1/2-TET2-WT1 pathway in suppressing AML

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Plasmon-exciton coupling of monolayer MoS2-Ag nanoparticles hybrids for surface catalytic reaction

The optical properties of monolayer molybdenum disulfide (MoS2)/Ag nanoparticle (NP) hybrids and their application to surface catalytic reactions were studied by transmission, photoluminescence (PL) and Raman spectroscopies. The local surface plasmon resonance (LSPR) of Ag nanoparticles was tuned to better match the exciton energy of monolayer MoS2. The PL of the hybrids was enhanced by more than 50 times when the local surface plasmon resonance (LSPR) peak was tuned systematically from 438 nm to 532 nm, indicating a stronger coupling and higher energy transfer rate between the plasmon of the Ag NPs and the excitons of the MoS2. Additionally, photocatalytic reactions of 4-nitrobenzenethiol (4NBT) were performed on the MoS2, the Ag nanoparticles, and the hybrid MoS2 with Ag nanoparticles. On the MoS2 substrate alone, there is no photocatalytic reaction. With a low laser intensity, the probability of a chemical reaction occurring for molecules directly adsorbed onto the Ag NPs is much lower than the probability of a reaction involving those molecules adsorbed onto the MoS2/Ag substrate. At a higher power, although the electric field was reduced by approximately 30% by the MoS2 layer, there is better efficiency for the plasmon-exciton co-driven surface catalytic reactions on the MoS2/Ag substrate compared to the Ag substrate alone. Our findings illustrate the potential to control hot carriers for better surface catalytic reactions by tuning the exciton-plasmon coupling between the 2D transition metal dichalcogenides (TMDCs) and Ag NPs

Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis

Summary: Giant cell myocarditis (GCM) is a rare, usually rapidly progressive, and potentially fatal disease. Detailed inflammatory responses remain unknown, in particular the formation of multinucleate giant cells. We performed single-cell RNA sequencing analysis on 15,714 Cd45+ cells extracted from the hearts of GCM rats and normal rats. NETosis has been found to contribute to the GCM process. An inhibitor of NETosis, GSK484, alleviated GCM inflammation in vivo. MPO (a marker of neutrophils) and H3cit (a marker of NETosis) were expressed at higher levels in patients with GCM than in patients with DCM and healthy controls. Imaging mass cytometry analysis revealed that immune cell types within multinucleate giant cells included CD4+ T cells, CD8+ T cells, neutrophils, and macrophages but not B cells. We elucidated the role of NETosis in GCM pathogenesis, which may serve as a potential therapeutic target in the clinic

Oridonin Induces Apoptosis in Esophageal Squamous Cell Carcinoma by Inhibiting Cytoskeletal Protein LASP1 and PDLIM1

Esophageal squamous cell carcinoma is a severe malignancy for its high mortality and poor prognosis. Mainstay chemotherapies cause serious side effects for their ways of inducing cell death. Oridonin is the main bioactive constituent from natural plants that has anticancer ability and weak side effects. The proteomics method is efficient to understand the anticancer mechanism. However, proteins identified by proteomics aimed at understanding oridonin’s anticancer mechanism is seldom overlapped by different groups. This study used proteomics based on two-dimensional electrophoresis sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-DE SDS-PAGE) integrated with mass spectrometry and Gene Set Enrichment Analysis (GSEA) to understand the anticancer mechanism of oridonin on esophageal squamous cell carcinoma (ESCC). The results showed that oridonin induced ESCC cell death via apoptosis by decreasing the protein expression of LASP1 and PDLIM1

Photocatalytic Boryl Radicals Triggered Sequential B─N/C─N Bond Formation to Assemble Boron‐Handled Pyrazoles

Abstract Vinyldiazo compounds are one of the most important synthons in the construction of a cyclic ring. Most photochemical transformations of vinyldiazo compounds are mainly focusing on utilization of their C═C bond site, while reactions taking place at terminal nitrogen atom are largely unexplored. Herein, a photocatalytic cascade radical cyclization of LBRs with vinyldiazo reagents through sequential B─N/C─N bond formation is described. The reaction starts with the addition of LBRs (Lewis base–boryl radicals) at diazo site, followed by intramolecular radical cyclization to access a wide range of important boron‐handled pyrazoles in good to excellent yields. Control experiments, together with detailed mechanism studies well explain the observed reactivity. Further studies demonstrate the utility of this approach for applications in pharmaceutical and agrochemical research

Association of elevated autoantibody to high expression of GNAS in hepatocellular carcinoma

Purpose: This study was based on hepatocellular carcinoma (HCC) patients of early-stage to explore the diagnostic capability and possible production causes of anti-GNAS autoantibody. Methods: We evaluated the frequency of anti-GNAS autoantibody in sera from patients with early-stage HCC by enzyme-linked immunosorbent assay (ELISA) and the expression of GNAS protein in early-stage HCC tissues by immunohistochemistry. Western blotting (WB) and real-time polymerase chain reaction (RT-PCR) were utilized to examine the expressions of GNAS protein and mRNA in cell lines. GEO and International Cancer Genome Consortium (ICGC) databases were inquired to explore mRNA expression and mutation of GNAS in HCC tissues. Results: The positive rates of anti-GNAS autoantibody in HCC patients at clinical stage I (78.1 %) and clinical stage II (57.1 %) were all significantly higher than that in healthy control (20 %). There was also a significant difference in GNAS protein expression between HCC and its adjacent normal liver tissues. The results from WB and RT-PCR showed a significant difference at the mRNA level but no statistical difference at the protein level between HCC and normal liver cell lines. The difference in mRNA level between HCC and adjacent normal liver tissues was verified to be significant. Furthermore, the ICGC database demonstrated a 10.6 % mutation frequency for GNAS in HCC patients. Conclusion: The coordination of elevated anti-GNAS autoantibody, high expression of GNAS in the mRNA and protein levels in HCC, and high frequency of GNAS mutation indicates that anti-GNAS autoantibody may be used as an early indicator of HCC