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Mechano-bioconjugation Strategy Empowering Fusion Protein Therapeutics with Aggregation Resistance, Prolonged Circulation, and Enhanced Antitumor Efficacy
No full textBioconjugation is a powerful protein modification strategy to improve protein properties. Herein, we report mechano-bioconjugation as a novel approach to empower fusion protein therapeutics and demonstrate its utility by a protein heterocatenane (cat-IFN-ABD) containing interferon-alpha 2b (IFN) mechanically interlocked with a consensus albumin-binding domain (ABD). The conjugate was selectively synthesized in cellulo following a cascade of post-translational events using a pair of heterodimerizing p53dim variants and two orthogonal split-intein reactions. The catenane topology was proven by combined techniques of LC-MS, SDS-PAGE, SEC, and controlled proteolytic digestion. Not only did caiIFN-ABD retain activities comparable to those of the wild-type IFN and ABD, the conjugate also exhibited enhanced aggregation resistance and prolonged circulation time over the simple linear and cyclic fusions. Consequently, cat-IFN-ABD potently inhibited tumor growth in the mouse xenograft model. Therefore, mechano-bioconjugation by catenation accomplishes function integration with additional benefits, providing an alternative pathway for developing advanced protein therapeutics
Critical comparison of polydisperse kinetic theories using bidisperse DEM data
No full textKinetic theories have been developed to describe the hydrodynamics of polydisperse granular flows under different theoretical assumptions. In this study, six species theories are assessed using the DEM data obtained from simple shear flow containing bidisperse particles with low and moderate solid vol-ume fraction (Galvin, 2007). It was shown that (i) only the theories of Iddir and Arastoopour (2005) and Zhao and Wang (2021) can qualitatively capture all of the effects of various parameters on the gran-ular temperature ratio and the normal and shear stresses; (ii) the granular temperature ratio can be pre-dicted accurately either by Iddir and Arastoopour (2005) or Zhao and Wang (2021), depending on the input parameters; and (iii) the predictions of normal and shear stresses by Iddir and Arastoopour (2005) are superior in matching the DEM data for most tested cases. Present study not only discusses the fundamental differences between different species kinetic theories, but also offers a critical assess-ment of their suitability in modeling simple shear flow. (c) 2022 Elsevier Ltd. All rights reserved
Funding for school-level research projects of Yancheng Institute of Technology[xjr2021054]
No full textA novel vertical dual-loop reactor for rapid start-up of simultaneous partial nitrification and anammox process in treating landfill leachate: Performances and mechanisms
No full textA novel vertical dual-loop reactor (VDLR) was developed to start and conduct a single-stage partial nitritation (PN) and anammox (PN/A) process for treating landfill leachate. Results showed that the total nitrogen (TN) removal reached 1.54 kg N/m3 center dot d in the VDLR. It exhibited excellent mixing uniformity and buffer performance, which can increase the nitrogen removal performance up to 42.1 % via the improvement of anammox granular sludge activity (a particle size of 0.5-1 mm). Mass balance and microbial analysis indicated that the VDLR achieved efficient TN removal via anammox (99.24 %) and AOB (Nitrosomonas and Ellin6067) and anAOB (Candidatus kuenenia) played a vital role in this process
Thiolated, Reduced Palladium Nanoclusters with Resolved Structures for the Electrocatalytic Reduction of Oxygen
No full textAlthough thiolated, reduced Group 11 metal nanoclusters with atomic monodispersity have been repeatedly reported in the past decade, their Pd analogues have not been reported thus far. In this work, we provide a resolution for the challenging synthesis and obtain for the first time an atomically monodisperse thiolated, reduced Pd (q=+0.75) nanocluster with a di-tetrahedron Pd-8 kernel and a +3 charged interstitial B atom, as revealed by ESI-MS, SCXRD, etc. mu-6 B is found for the first time in Group 10 and 11 metal nanoclusters. More importantly, the as-obtained Pd nanoclusters show better catalytic activity compared to 1.4 nm Pd nanoparticles, Pd-2 complexes and even a commercial Pt/C catalyst for the oxygen reduction reaction (ORR), having significant implications for the influence of the metal charge state and space structure on the catalytic activity
