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.

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.

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.

In vivo biocompatibility evaluation of Zn-0.05Mg-(0, 0.5, 1wt%)Ag implants in New Zealand rabbits.

Bio-absorbable Zn alloys have been attractive replacements for the traditionally permanent implants due to their reasonable mechanical strength and elongation, degradation rate, and biocompatibility. The hybridization addition of Mg and Ag elements could greatly improve the mechanical properties and antibacterial ability of Zn, respectively. In the present paper, in vivo biocompatibility for the Zn-0.

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).

Thrombin-loaded alginate-calcium microspheres: A novel hemostatic embolic material for transcatheter arterial embolization.

Transcatheter arterial embolization (TAE) is the best non-laparotomy choice for solid visceral organs rupture and bleeding nowadays. In our previous study, a new biodegradable macromolecule material thrombin-loaded alginate-calcium microsphere (TACM) was prepared and its characteristics were investigated preliminarily. In this study, we further investigated the biocompatibility of TACMs, as well as physical characteristic, application method and effect of TACMs with thrombus (embolic agent).

Viral and Bacterial Etiology of Acute Diarrhea among Children under 5 Years of Age in Wuhan, China.

Background: Acute diarrhea remains the serious problem in developing countries, especially among children under 5 years of age. Currently, only two or three common diarrhea pathogens were screened at most hospitals in China. The aim of this study was to provide a wide variety of diarrhea pathogens and their antimicrobial resistance patterns in children under 5 years of age.

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.

Alginate-calcium microsphere loaded with thrombin: a new composite biomaterial for hemostatic embolization.

To date, transcatheter arterial embolization (TAE) has become a standard treatment to control intracavitary bleeding as an alternative to surgery. Due to excellent biocompatibility and no residual in vivo, biodegradable materials are preferred in TAE. However, gelfoam is the only commercially available biodegradable embolic material used to treat blunt trauma of solid abdominal viscera until now, and controversial on its stability and reliability never stopped in the past five decades.

Molecular characterization of clinical and environmental Vibrio parahaemolyticus isolates in Taiwan.

Vibrio parahaemolyticus is the most prevalent foodborne pathogen in Taiwan and it is frequently recovered from seafood. In this study, V. parahaemolyticus that was isolated in recent years from aquacultural environments and clinical specimens were comparatively analyzed by NotI-restricted pulsed-field gel electrophoresis (PFGE) and polymerase chain reaction, targeting common toxin genes (tdh, trh, ureC), MTase gene, toxR regulator, markers for pandemic strains (ORF8, group-specific toxRS) and representative genes of type three secretion systems T3SS1 (vcrD1, VP1680, vopD) and T3SS2α (vcrD2, vopD2, vopB2, vopP, vopC, vopT).

The effect of electrostatic microencapsulation process on biological properties of tumour cells.

Microencapsulation is one of the promising strategies to develop a three-dimensional in vivo tumour-mimic model in cancer research. Although previous studies have shown that tumour cells grow well during the microencapsulated culture, it is still not clear whether the electrostatic encapsulation process has an important effect on cellular characteristics. In this study, we investigated cellular response against non-physiological stress factors existing in the electrostatic microencapsulation process, such as the high-voltage electrostatic field, suspension and nutrition-free status.

Prevalence of Vibrio parahaemolyticus in oyster and clam culturing environments in Taiwan.

Vibrio parahaemolyticus is the most prevalent gastroenteritis pathogen in Taiwan and some other Asian countries, and it frequently occurs in oysters and other seafood. This study monitors changes in the density of V. parahaemolyticus and environmental parameters in oyster and hard clam aquacultural environments in Taiwan.

Spray-spinning: a novel method for making alginate/chitosan fibrous scaffold.

The subject of our investigations was the process of obtaining alginate/chitosan polyelectrolyte complex (PEC) fibers. In this study, a novel method named "spray-spinning" was developed for the making of these hybrid fibers. In spray-spinning, a chitosan solution was sprayed into a flowing sodium alginate solution and sheared into streamlines.

Hydro-spinning: a novel technology for making alginate/chitosan fibrous scaffold.

Alginate/chitosan polyelectrolyte complex (PEC) hybrid fibers are promising materials for scaffold-making in tissue engineering. In this study, a new method termed "hydro-spinning" was developed to make alginate/chitosan hybrid fibers. In hydro-spinning, a chitosan solution was pumped into a flowing sodium alginate solution and sheared into streamlines.

[Preparation and cultivation of microencapsulated recombinant CHO cells].

Transplantation of the microencapsulated recombinant cells is a novel alternative approach to gene therapy of tumors. The semi-permeable membrane of microcapsule protects cells from host's immune rejection, increases the efficiency of gene transfer and reduces the need for frequent injection. Optimization of the preparation and culture is needed to acquire biological microcapsule with high cell viability and protein production.

[Effect of the in vitro culture and cryopreservation on the growth of the microencapsulated recombinant cell and endostatin production].

Microencapsulated recombinant cells technology is a novel approach to tumors therapy. It is necessary to prepare a plenty of the microcapsules with better cell viability and higher endostatin production in order to bring this technology into the clinic. The in vitro culture and cryopreservation are very important parameters in the preparation of microencapsulated cells.

Differential role of microenvironment in microencapsulation for improved cell tolerance to stress.

The effect of the microenvironment in alginate-chitosan-alginate (ACA) microcapsules with liquid core (LCM) and solid core (SCM) on the physiology and stress tolerance of Sacchromyces cerevisiae was studied. The suspended cells were used as control. Cells cultured in liquid core microcapsules showed a nearly twofold increase in the intracellular glycerol content, trehalose content, and the superoxide dismutase (SOD) activity, which are stress tolerance substances, while SCM did not cause the significant physiological variation.

Synthesis of yttrium iron garnet using polymer-metal chelate precursor.

Two kinds of polymer-metal compounds, heterogeneous complexes (metal-chelating copolymer microspheres, MCP) and homogeneous complexes (water-soluble metal-chelating polymers, WSMCP), were synthesized to act as nucleation agents for YIG precursor preparation in this text. Both of the metal-chelating polymers have the same chelating group and high metal ion adsorption ability from the FTIR and ICP measurement. Furthermore, good YIG crystals can be obtained by treating the MCP precursor with a low calcination temperature at 600 degrees C from the XRD spectra and TEM micrograph.