Active Site Mapping of Human Cathepsin F with Dipeptide Nitrile Inhibitors

Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex class II. Cathepsin S is the major processing enzyme of the invariant chain, but cathepsin F acts in macrophages as its functional synergist which is as potent as cathepsin S in invariant chain cleavage. Dedicated low‐molecular‐weight inhibitors for cathepsin F have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent–reversible inhibitors, was performed to draw structure–activity relationships for the non‐primed binding region of human cathepsin F. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsins F, B, L, K and S. Compounds 10 (N‐(4‐phenylbenzoyl)‐leucylglycine nitrile) and 12 (N‐(4‐phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsin F, with K_i values <10 nM . With all dipeptide nitriles from our study, a 3D activity landscape was generated to visualize structure–activity relationships for this series of cathepsin F inhibitors.     

Microwave Sol–Gel Synthesis of CaGd2(MoO4)4:Er3+/Yb3+ Phosphors and Their Upconversion Photoluminescence Properties

CaGd₂(MoO₄)₄:Er³⁺/Yb³⁺ phosphors with the doping concentrations of Er³⁺ and Yb³⁺ (x = Er³⁺ + Yb³⁺, Er³⁺ = 0.05, 0.1, 0.2, and Yb³⁺ = 0.2, 0.45) have been successfully synthesized by the microwave sol–gel method, and the crystal structure refinement and upconversion photoluminescence properties have been investigated. The synthesized particles, being formed after heat‐treatment at 900°C for 16 h, showed a well‐crystallized morphology. Under the excitation at 980 nm, CaGd₂(MoO₄)₄:Er³⁺/Yb³⁺ particles exhibited strong 525 and 550‐nm emission bands in the green region and a weak 655‐nm emission band in the red region. The Raman spectrum of undoped CaGd₂(MoO₄)₄ revealed about 15 narrow lines. The strongest band observed at 903 cm^?1 was assigned to the ν₁ symmetric stretching vibration of MoO₄ tetrahedrons. The spectra of the samples doped with Er and Yb obtained under 514.5 nm excitation were dominated by Er³⁺ luminescence preventing the recording Raman spectra of these samples. Concentration quenching of the erbium luminescence at ²H_11/2→⁴I_15/2 and ⁴S_3/2→⁴I_15/2 transitions in the CaGd₂(MoO₄)₄:Er³⁺/Yb³⁺ crystal structure was established to be approximately at the 10 at.% doping level.     

Exchange reactions control for selective separation of glyoxylic acid in technological mixtures of glyoxal oxidation

Separation of glyoxylic acid from unpurified multicomponent technological mixtures, resulting in the process of direct oxidation of glyoxal, and preparation of sodium glyoxylate are developed. The mixtures are treated with an optimal amount of CaCO_3, which has to be prespecified by acidic–basic titration of the technological mixtures. Both separation of glyoxylic acid and preparation of sodium glyoxylate take place owing to ionic exchange reactions: calcium glyoxylate is easily converted into glyoxylic acid by action of oxalic acid. Reaction with Na₂CO₃ leads to the formation of sodium glyoxylate.     

Enhanced photoluminescence of porous silicon nanoparticles coated by bioresorbable polymers

A significant enhancement of the photoluminescence (PL) efficiency is observed for aqueous suspensions of porous silicon nanoparticles (PSiNPs) coated by bioresorbable polymers, i.e., polylactic-co-glycolic acid (PLGA) and polyvinyl alcohol (PVA). PSiNPs with average size about 100 nm prepared by mechanical grinding of electrochemically etched porous silicon were dispersed in water to prepare the stable suspension. The inner hydrophobic PLGA layer prevents the PSiNPs from the dissolution in water, while the outer PVA layer makes the PSiNPs hydrophilic. The PL quantum yield of PLGA/PVA-coated PSiNPs was found to increase by three times for 2 weeks of the storage in water. The observed effect is explained by taking into account both suppression of the dissolution of PSiNPs in water and a process of the passivation of nonradiative defects in PSiNPs. The obtained results are interesting in view of the potential applications of PSiNPs in bioimaging.     

大塑性变形纳米结构Al-Mg合金中的形变缺陷和电子辐照效应

为澄清大塑性变形纳米结构Al-Mg合金中形变缺陷形成的本质,采用高分辨透射电子显微镜（HRTEM）研究电子辐照对高压扭转合金中面缺陷形成的影响。结果表明：对已有高密度面缺陷的HRTEM图像,经电子束照射一段时间后,这些面缺陷会完全消失;而在没有缺陷的HRTEM图像区域进行电子辐照,即使电子束的照射提高到足以在该区域击出孔洞,整个过程均未观察到任何晶格缺陷。因此,高压扭转合金中的面缺陷主要来源于极度的塑性变形,而与HRTEM观察过程中的电子辐照效应无关。     

Quantifying adherence of oxide scales on steels exposed to high temperature and pressure steam

Oxide scale exfoliation is a major concern in fossil fuel power generation because it can cause tube blockages and erode valves and steam turbine components downstream. There is still considerable scientific and commercial interest to improve the mechanistic understanding of oxide failures by developing models to predict exfoliation and the extent of tube blockage as a function of operating conditions and component geometries. Tensile testing inside a scanning electron microscope was conducted on ferritic–martensitic and austenitic steel specimens with the steam side (Fe,Cr)-rich oxides grown after exposures for up to 1000 h in steam with ~100 ppb O₂ at 276 bar and 550°C. Multiple oxide layer cracks and delamination events were observed and analyzed in detail during the tests. Results from the testing agreed well with earlier observations that had identified the failure location at the outer–inner oxide layer for all tested materials. Calculated adhesion energies identified the outer–inner oxide interface of alloy 347HFG as the weakest interface.     

Thermal stability of the nanolayered Fe2AlB2 in nitrogen and argon atmospheres

The thermal stability and decomposition mechanisms of Fe₂AlB₂ powders, synthesized by reactive powder metallurgy, were studied under nitrogen (N₂) or argon (Ar) atmospheres. The effects of using different FeB precursors to synthesize the Fe₂AlB₂ and hydrochloric acid (HCl) purification treatments on the thermal stability were also investigated. When as-synthesized Fe₂AlB₂ powders are treated in dilute HCl to dissolve impurity phases, decomposition in N₂ atmospheres occurs readily above 1200 K. The decomposition reaction involves β-FeB precipitation and the liberated Al atoms reacting with the ambient N₂ to form AlN. Under Ar environments, HCl-treated Fe₂AlB₂ powders decompose and precipitate β-FeB, by the out-diffusion of Al from the nanolaminated structure. Interestingly, isothermal annealing under N₂ atmospheres revealed that Fe₂AlB₂ was more thermally stable when synthesized from lab-synthesized, instead of commercially available, FeB precursors and when the HCl treatment was avoided. The effects of the various factors on the decomposition temperature and decomposition mechanisms are discussed herein.     

Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.     

hTERT-Driven Immortalization of RDEB Fibroblast and Keratinocyte Cell Lines Followed by Cre-Mediated Transgene Elimination

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a crippling disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Using ectopic expression of hTERT/hTERT + BMI-1 in primary cells, we developed expansible cultures of RDEB fibroblasts and keratinocytes. We showed that they display the properties of their founders, including morphology, contraction ability and expression of the respective specific markers including reduced secretion of type VII collagen (C7). The immortalized keratinocytes retained normal stratification in 3D skin equivalents. The comparison of secreted protein patterns from immortalized RDEB and healthy keratinocytes revealed the differences in the contents of the extracellular matrix that were earlier observed specifically for RDEB. We demonstrated the possibility to reverse the genotype of immortalized cells to the state closer to the progenitors by the Cre-dependent hTERT switch off. Increased β-galactosidase activity and reduced proliferation of fibroblasts were shown after splitting out of transgenes. We anticipate our cell lines to be tractable models for studying RDEB from the level of single-cell changes to the evaluation of 3D skin equivalents. Our approach permits the creation of standardized and expandable models of RDEB that can be compared with the models based on primary cell cultures.     

Shelf Life and Sensory Characteristics of Baby Spinach Subjected to Electron Beam Irradiation

Abstract: The use of ionizing radiation for the control of foodborne pathogens and extending the shelf life of fresh iceberg lettuce and fresh spinach has recently been approved by the U.S. Food and Drug Administration. The efficacy of electron beam irradiation for controlling foodborne pathogens has been reported. For this experiment, the effectiveness of electron beam irradiation on the microbiological and sensory characteristics of fresh spinach was studied. Total aerobic plate counts were reduced by 2.6 and 3.2 log CFU/g at 0.7 and 1.4 kGy, respectively. Lactic acid bacteria were reduced at both doses of e-beam but grew slowly over the 35 d of the experiment. Yeasts and molds were not reduced in samples exposed to 0.7 kGy whereas 1.4 kGy significantly reduced microbial counts. Gas compositions (O₂ and CO₂) were significantly different than controls. Oxygen levels inside the spinach sample bags decreased over time; however, O₂ levels did not drop below 1% that can induce anaerobic fermentation. CO₂ levels for all treatments increased through day 4; yet 7 d after irradiation, CO₂ level differences were not significant in both control and irradiated samples. Irradiation dose did not affect the basic tastes, aromatics, or mouth feels of fresh spinach, however; hardness attributes decreased as irradiated dose increased and slimy attributes of fresh spinach were higher in control samples compared to irradiated samples.