Structural insights into peptide self-assembly using photo-induced crosslinking experiments and discontinuous molecular dynamics

Determining the structure of the (oligomeric) intermediates that form during the self-assembly of amyloidogenic peptides is challenging because of their heterogeneous and dynamic nature. Thus, there is need for methodology to analyze the underlying molecular structure of these transient species. In this work, a combination of fluorescence quenching, photo-induced crosslinking (PIC) and molecular dynamics simulation was used to study the assembly of a synthetic amyloid-forming peptide, Aβ_16-22. A PIC amino acid containing a trifluormethyldiazirine (TFMD) group—Fmoc(TFMD)Phe—was incorporated into the sequence (Aβ*_16–22). Electrospray ionization ion-mobility spectrometry mass-spectrometry (ESI-IMS-MS) analysis of the PIC products confirmed that Aβ*_16–22 forms assemblies with the monomers arranged as anti-parallel, in-register β-strands at all time points during the aggregation assay. The assembly process was also monitored separately using fluorescence quenching to profile the fibril assembly reaction. The molecular picture resulting from discontinuous molecule dynamics simulations showed that Aβ_16-22 assembles through a single-step nucleation into a β-sheet fibril in agreement with these experimental observations. This study provides detailed structural insights into the Aβ_16-22 self-assembly processes, paving the way to explore the self-assembly mechanism of larger, more complex peptides, including those whose aggregation is responsible for human disease.     

An Injectable Hydrogel for Simultaneous Photothermal Therapy and Photodynamic Therapy with Ultrahigh Efficiency Based on Carbon Dots and Modified Cellulose Nanocrystals

The convenience of injectable hydrogels that can provide high loading of diverse phototherapy agents and further long-time retention at the tumor site has attracted tremendous interest in simultaneous photothermal and photodynamic cancer therapies. However, to incorporate the phototherapy agents into hydrogels, complex modifications are generally unavoidable. Moreover, these phototherapy agents usually suffer from low efficiency and work at different irradiation wavelengths outside the near infrared windows. Hence, a method for the fabrication of an injectable hydrogel for simultaneous photothermal therapy and photodynamic therapy, through the Schiff-base reaction between amido modified carbon dots (NCDs) and aldehyde modified cellulose nanocrystals is proposed. The NCDs act as both phototherapy agents and crosslinkers to form hydrogels. Significantly, the NCDs demonstrate an extremely high photothermal conversion efficiency of 77.6% which is among the highest levels for photothermal agents and a high singlet quantum yield of 0.37 under a single 660 nm light-emitting diode irradiation. The hydrogels are examined through in vitro and in vivo animal experiments which show nontoxic and effectively tumor inhibition. Thus, the strategy of direct reaction of phototherapy agents and the matrix not only provides new strategies for injectable hydrogel fabrication but paves a new road for advanced tumor treatment.     

Endoglin Targeting: Lessons Learned and Questions That Remain

Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab^®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.     

Electrochemical Quantification of Neurotransmitters in Single Live Cell Vesicles Shows Exocytosis is Predominantly Partial

Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types.     

Labeling and Characterization of Phenol-Containing Glycopeptides Using Chemoselective Probes with Isotope Tags

Secondary metabolites are structurally diverse natural products (NPs) and have been widely used for medical applications. Developing new tools to enrich NPs can be a promising solution to isolate novel NPs from the native and complex samples. Here, we developed native and deuterated chemoselective labeling probes to target phenol-containing glycopeptides by the ene-type labeling used in proteomic research. The clickable azido-linker was included for further biotin functionalization to facilitate the enrichment of labeled substrates. Afterward, our chemoselective method, in conjunction with LC-MS and MSn analysis, was demonstrated in bacterial cultures. A vancomycin-related phenol-containing glycopeptide was labeled and characterized by our labeling strategy, showing its potential in glycopeptide discovery in complex environments.     

Engineering Silver-Enriched Copper Core-Shell Electrocatalysts to Enhance the Production of Ethylene and C2+ Chemicals from Carbon Dioxide at Low Cell Potentials

Copper catalysts are widely studied for the electroreduction of carbon dioxide (CO₂) to value-added hydrocarbon products. Controlling the surface composition of copper nanomaterials may provide the electronic and structural properties necessary for carbon-carbon coupling, thus increasing the Faradaic efficiency (FE) towards ethylene and other multi-carbon (C₂₊) products. Synthesis and catalytic study of silver-coated copper nanoparticles (Cu@Ag NPs) for the reduction of CO₂ are presented. Bimetallic CuAg NPs are typically difficult to produce due to the bulk immiscibility between these two metals. Slow injection of the silver precursor, concentrations of organic capping agents, and gas environment proved critical to control the size and metal distribution of the Cu@Ag NPs. The optimized Cu@Ag electrocatalyst exhibited a very low onset cell potential of −2.25 V for ethylene formation, reaching a FE towards C₂₊ products (FE_C2+) of 43% at −2.50 V, which is 1.0 V lower than a reference Cu catalyst to reach a similar FE_C2+. The high ethylene formation at low potentials is attributed to enhanced C C coupling on the Ag enriched shell of the Cu@Ag electrocatalysts. This study offers a new catalyst design towards increasing the efficiency for the electroreduction of CO₂ to value-added chemicals.     

The Effect of Interface Cracks on the Electrical Performance of Solar Cells

Among a variety of solar cell types, thin-film solar cells have been rigorously investigated as cost-effective and efficient solar cells. In many cases, flexible solar cells are also fabricated as thin films and undergo frequent stress due to the rolling and bending modes of applications. These frequent motions result in crack initiation and propagation (including delamination) in the thin-film solar cells, which cause degradation in efficiency. Reliability evaluation of solar cells is essential for developing a new type of solar cell. In this paper, we investigated the effect of layer delamination and grain boundary crack on 3D thin-film solar cells. We used finite element method simulation for modeling of both electrical performance and cracked structure of 3D solar cells. Through simulations, we quantitatively calculated the effect of delamination length on 3D copper indium gallium diselenide (CIGS) solar cell performance. Moreover, it was confirmed that the grain boundary of CIGS could improve the solar cell performance and that grain boundary cracks could decrease cell performance by altering the open circuit voltage. In this paper, the investigated material is a CIGS solar cell, but our method can be applied to general polycrystalline solar cells.     

Variables Applicable to Benchmarking of Tap-Hole Life-Cycle Management Practices in Coke-Bed-Based Ferroalloy Production

Benchmarking is a tool available to furnace operators to evaluate their tap-hole life-cycle management practices against those of their peers. It allows furnace operators to challenge their own practices in order to increase furnace utilization. To facilitate the benchmarking process, it is necessary to define the variables to be considered and how they relate to one another. This article develops, from the literature and industry interviews, a holistic conceptualization of the variables that form part of tap-hole lifecycle management and performance. Specifically, the article focuses on the variables related to coke-bed-based processes (FeCr, SiMn, and HCFeMn) applying SAF technology of circular design.     

Removal of Antimony and Bismuth from Copper Electrorefining Electrolyte: Part II—An Investigation of Two Proprietary Solvent Extraction Extractants

Antimony and bismuth recovery from copper electrorefining electrolyte could reduce the impacts of these problem elements and produce a new primary source for them. Two proprietary phosphonic acid ester extractants were examined (REX-1 and REX-2) for the removal of antimony and bismuth from copper electrorefining electrolytes. Experimentation included shakeout and break tests to determine the basic parameters for the extractants in terms of maximum loading, break times, and extraction and stripping efficiency. Five permutations of extractant mixtures (100 wt.% REX-1 and 25 wt.%, 50 wt.%, 75 wt.% and 100 wt.% REX-2) were studied. It was determined that REX-2 was able to extract Sb and Bi from the electrolyte, but required some mixture with REX-1 to better facilitate stripping with 400 g/L sulfuric acid. The laboratory electrorefining electrolyte containing glue had faster disengagement times than a synthetic solution without glue.     

Measurement of Young’s Modulus and Poisson’s Ratio of Thermal Barrier Coating Based on Bending of Three-Layered Plate

Thermal barrier coatings (TBCs) are used to protect the hot sections of gas turbine engines and airplane engines. A TBC system comprises a substrate, bond coat, and TBC topcoat. The development of an accurate method for determining the Young’s modulus and Poisson’s ratio of TBC using a multilayered specimen is of importance. In this study, we applied the bending theory of a laminated plate to a three-layered material and proposed models to determine the Young’s modulus and Poisson’s ratio of the TBC layer using the bending strain of the TBC system specimen. Three methods were developed by utilizing (i) the coating biaxial strain, (ii) substrate biaxial strain, or (iii) coating and substrate biaxial strains. Subsequently, we determined appropriate dimensions of the specimen and span by using three-dimensional finite element analysis, and numerically verified the usefulness of the three proposed methods. However, the Young’s modulus and Poisson’s ratio determined using the multilayered specimen with a substrate are sensitive to experimental errors. Therefore, we evaluated the sensitivity of the three proposed methods to experimental error, and we determined the most insensitive method among them. Finally, we experimentally demonstrated the usefulness of this method.