Search

STIP1 homology and U-Box containing protein 1 (STUB1) plays a key role in maintaining cell health during stress and aging. Recent evidence suggested STUB1 also helps regulate immunity with the potential of clearing malignant cells. Indeed, we and others have shown that STUB1 is a pivotal negative regulator of interferon gamma sensing – a process critical to the immunosurveillance of tumors and pathogens. Thus far, investigation of STUB1’s role relies mostly on genetic approaches as pharmacological inhibitors of this protein are lacking. Identification of a STUB1 tool compound is important as it would allow therapeutically relevant target validation in a broader sense. Accordingly, we leveraged phage display and computational modeling to identify and refine STUB1 binders. Screening of >10E9 macrocyclic peptides resulted in several conserved motifs as well as structurally diverse leads. Co-crystal structure of the peptide hit and STUB1 has enabled us to employ structure-based in silico design for further optimization. Of the modifications employed, replacing the hydrophilic solvent-exposed region of the macrocyclic peptides with a hydrophobic scaffold improved cellular permeability, while the binding conformation was maintained. Further substitution of the permeability-limiting terminal aspartic acid with a tetrazole bioisostere retained the binding to certain extent while improving permeability, suggesting a path forward. The current lead, although not optimal for cellular study, provides a valuable template for further development into selective tool compounds for STUB1 to enable target validation.

Excellent extraction ability and easy regeneration of the extractant are highly important for the recovery of acetic acid from water by solvent extraction. In this paper, the extraction capability ...

The development of new catalytic materials is conducive to solving the global energy crisis and environmental problems. In this work, multipurpose catalyst unsubstituted iron(II) phthalocyanine/car...

The efficient separation of photogenerated electron–hole pairs in photoactive materials is highly desired, allowing their transfer to specific sites for undergoing redox reaction in various applications. The construction of ternary heterojunctions is a practical strategy to enhance the migration of photogenerated electron that realizes the synergistic effect of multicomponents rather than the simple overlay of single component. Here, we demonstrate an available way to fabricate new BiOCl/BiVO4/nitrogen-doped graphene quantum dot (N-GQD) ternary heterojunctions that exhibit higher efficiency in charge separation than any binary heterojunction or pure material under visible-light irradiation. UV–vis diffuse reflectance spectroscopy demonstrated that the proposed BiOCl/BiVO4/N-GQD ternary heterojunctions possess the narrower band gap energy. More importantly, the ternary heterojunctions reveal the prolonged lifetime of photogenerated charges and enhanced the separation efficiency of photogenerated electron–h...

D-dimer is a product of the coagulation cascade and is associated with venous thromboembolism, disseminated intravascular coagulation, and additional clinical conditions. Despite its importance, D-dimer measurement has limited clinical utility due in part to the lack of reliable assays. The difficulty in developing an immunoassay that is specific for D-dimer arises from the inherent heterogeneity in its structure. In this report, we describe a highly specific method for the quantification of D-dimer level in human plasma. In our method, the reciprocally cross-linked peptide resulting from factor XIIIa-catalyzed dimerization of fibrin γ chains was selected to represent the D-dimer antigen. Using an antipeptide antibody, we enriched the cross-linked peptide from trypsin-digested plasma prior to quantitative analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The assay has a quantitative range of 500 pmol/L to 100 nmol/L in human plasma. In further characterization of the assay, we found that it exhibited good correlation with fibrinolytic activity in human donors and with thrombin generation and clot strength in an in vitro thromboelastography assay. These observations thus establish the biological relevance of the assay and suggest it may be a valuable biomarker in characterization and treatment of blood coagulation disorders.

In order to enrich the variety of copper sulfide and enhance its currently existing applications, CuS nestlike hollow spheres assembled by microflakes were successfully synthesized through an oil−w...

The activity coefficients at infinite dilution, γi∞, for 16 organic solutes, alkanes, alkenes, and alkyl benzenes in glycerol, have been measured by the gas−liquid chromatographic method at five temperatures from (303.15 to 343.15) K. The overall uncertainty was estimated to be about 5 %. The partial molar excess enthalpies at infinite dilution, HiE,∞, of the solutes in glycerol were also derived from the temperature dependence of the γi∞ values.

Densities and viscosities for the binary mixtures of H2O (1) + 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][CF3SO3]) (2) were measured over the entire mole fraction range from (303.15 to 343.15) K at atmospheric pressure. Excess molar volumes and viscosity deviations as a function of mole fraction average were derived, and the results were fitted to the Redlich−Kister equation using a multiparametric nonlinear regression method. Estimated coefficients of the Redlich−Kister equation and standard error calculated from the Redlich−Kister equation to the experimental data are also presented. The results show that the densities and viscosities are dependent on water content and temperature.

Activity coefficients at infinite dilution γi∞ have been measured for 17 polar solutes (linear and branched C1 to C5 alcohols, acetonitrile, acetone, 1,4-dioxane, tetrahydrofuran, ethyl acetate, and chloromethanes) in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][CF3SO3]) by the gas–liquid chromatographic method with the ionic liquid as the stationary phase. The measurements were carried out in the temperature range of (303.15 to 363.15) K. The partial molar excess enthalpies at infinite dilution HiE,∞ of the solutes in the ionic liquid were also derived from the temperature dependence of the γi∞ values.

Experimental data of densities and viscosities of propane-1,2,3-triol + ethane-1,2-diol binary mixtures were measured over the entire mole fraction range from (298.15 to 338.15) K at atmospheric pressure. Excess molar volumes as a function of mole fraction average have been obtained and fitted to the Redlich−Kister equation. Estimated coefficients of the Redlich−Kister equation and standard error calculated from the Redlich−Kister equation to the experimental data were also presented.

Experimental data of densities and viscosities of 1-propyl-2,3-dimethylimidazolium tetrafluoroborate ([PDMIM][BF4]) + H2O binary mixtures were measured over the entire mole fraction range from (298.15 to 343.15) K at atmospheric pressure. Excess molar volumes and viscosity deviations as a function of mole fraction average have been obtained and fitted to the Redlich−Kister equation. Estimated coefficients of the Redlich−Kister equation and standard error calculated from the Redlich−Kister equation to the experimental data were also presented.