Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η⁶-arene)Ru(N,N′)L][PF₆]₂ containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ_max = 418 nm) compared with C1 and C2 (λ_max = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC₅₀ = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).     

Cloning and Characterization of a Thermostable Endolysin of Bacteriophage TP-84 as a Potential Disinfectant and Biofilm-Removing Biological Agent

The obligatory step in the life cycle of a lytic bacteriophage is the release of its progeny particles from infected bacterial cells. The main barrier to overcome is the cell wall, composed of crosslinked peptidoglycan, which counteracts the pressure prevailing in the cytoplasm and protects the cell against osmotic lysis and mechanical damage. Bacteriophages have developed two strategies leading to the release of progeny particles: the inhibition of peptidoglycan synthesis and enzymatic cleavage by a bacteriophage-coded endolysin. In this study, we cloned and investigated the TP84_28 endolysin of the bacteriophage TP-84, which infects thermophilic Geobacillus stearothermophilus, determined the enzymatic characteristics, and initially evaluated the endolysin application as a non-invasive agent for disinfecting surfaces, including those exposed to high temperatures. Both the native and recombinant TP84_28 endolysins, obtained through the Escherichia coli T7-lac expression system, are highly thermostable and retain trace activity after incubation at 100 °C for 30 min. The proteins exhibit strong bacterial wall digestion activity up to 77.6 °C, decreasing to marginal activity at ambient temperatures. We assayed the lysis of various types of bacteria using TP84_28 endolysins: Gram-positive, Gram-negative, encapsulated, and pathogenic. Significant lytic activity was observed on the thermophilic and mesophilic Gram-positive bacteria and, to a lesser extent, on the thermophilic and mesophilic Gram-negative bacteria. The thermostable TP84_28 endolysin seems to be a promising mild agent for disinfecting surfaces exposed to high temperatures.     

Possible Implications of Bacteriospermia on the Sperm Quality,Oxidative Characteristics,and Seminal Cytokine Network in Normozoospermic Men

This study focused on the identification of bacterial profiles of semen in normozoospermic men and their possible involvement in changes to the sperm structural integrity and functional activity. Furthermore, we studied possible fluctuations of selected cytokines, oxidative markers, and antibacterial proteins as a result of bacterial presence in the ejaculate. Sperm motility was assessed with computer-assisted sperm analysis, while sperm apoptosis, necrosis and acrosome integrity were examined with fluorescent methods. Reactive oxygen species (ROS) generation was quantified via luminometry, sperm DNA fragmentation was evaluated using the TUNEL protocol and chromatin-dispersion test, while the JC-1 assay was applied to evaluate the mitochondrial membrane potential. Cytokine levels were quantified with the biochip assay, whilst selected antibacterial proteins were quantified using the ELISA method. The predominant species identified by the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were Staphylococcus hominis, Staphylococcus capitis and Micrococcus luteus. The results revealed that the sperm quality decreased proportionally to the increasing bacterial load and occurrence of conditionally pathogenic bacteria, including Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Antimicrobial susceptibility tests revealed a substantial resistance of randomly selected bacterial strains to ampicillin, vancomycin, tobramycin, and tetracycline. Furthermore, an increased bacterial quantity in semen was accompanied by elevated levels of pro-inflammatory cytokines, including interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor alpha as well as ROS overproduction and lipid peroxidation of the sperm membranes. Our results suggest that semen quality may be notably affected by the bacterial quantity as well as quality. It seems that bacteriospermia may be associated with inflammatory processes, oxidative stress, sperm structural deterioration, and a subsequent risk for the development of subfertility, even in normozoospermic males.     

Strong Dependence between Tryptophan-Related Fluorescence of Urine and Malignant Melanoma

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is also a significant negative correlation between autofluorescence and Clark classification. Based on our results, it is assumed that the way malignant melanoma grows also affects urinary autofluorescence.     

Biodegradable PLA based nanocomposites for packaging applications: The effects of organo-modified bentonite concentration

The effects of concentration and surface modification of two Brazilian bentonite clays on nanocomposites' properties based on polylactic acid – (PLA) were investigated. The samples were prepared by the extrusion/injection method to obtain biodegradable packaging plastics. The raw materials and their bionanocomposites were characterized by various techniques. Natural clay samples presented a size of around 2 μm while the modified ones' size was 5–6 μm, probably due to the presence of cetyltrimethylammonium bromide in the interlayer space. The particle size and the contact angle increased with the treatment and the clay's density decreased. The organoclays were homogeneously dispersed in PLA, which can be associated with the interactions between PLA chains' carbonyl groups and the organoclays. The bionanocomposites present modified clay particles axis aligned to the flow direction of the extruder/injector. Chocolate organoclay acts as a nucleating agent to PLA crystal growth, increasing the sample's crystallinity, while Bofe organoclay interferes with the amorphous chain's mobility and diminishes the sample's crystallization. The addition of both organoclays to PLA diminished the sample's elongation at break and strength, although the organoclays increased the sample's Young modulus, even though Bofe organoclay is more active in PLA amorphous phase and Chocolate organoclay on the crystalline one.     

Nucleophilic Water Capture or Proton Loss: Single Amino Acid Switch Converts δ‐Cadinene Synthase into Germacradien‐4‐ol Synthase

δ‐Cadinene synthase is a sesquiterpene cyclase that utilises the universal achiral precursor farnesyl diphosphate (FDP) to generate predominantly the bicyclic sesquiterpene δ‐cadinene and about 2 % germacradien‐4‐ol, which is also generated from FDP by the cyclase germacradien‐4‐ol synthase. Herein, the mechanism by which sesquiterpene synthases discriminate between deprotonation and reaction with a nucleophilic water molecule was investigated by site‐directed mutagenesis of δ‐cadinene synthase. If W279 in δ‐cadinene synthase was replaced with various smaller amino acids, the ratio of alcohol versus hydrocarbon product was directly proportional to the van der Waals volume of the amino acid side chain. DCS‐W279A is a catalytically highly efficient germacradien‐4‐ol synthase (k_cat/K_M=1.4×10^?3 μm s^?1) that produces predominantly germacradien‐4‐ol in addition to 11 % δ‐cadinene. Water capture is not achieved through strategic positioning of a water molecule in the active site, but through a coordinated series of loop movements that allow bulk water access to the final carbocation in the active site prior to product release.     

Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP–PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non‐myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111‐Indium in relevant physiological buffers over 4 h, in vivo single‐photon emission computed tomography (SPECT/CT) imaging and autoradiography demonstrate increased accumulation of ANP–PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP–PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium.     

Surface modification of ultra‐high‐molecular‐weight polyethylene. I. Characterization and sintering studies

We performed surface modification of ultra‐high‐molecular‐weight polyethylene (UHMWPE) through chromic acid etching with the aim of improving the performance of UHMWPE's composites with poly(ethylene terephthalate) fibers. In part I of this study, we evaluated the effects of chemical modification on the surface properties of UHMWPE with X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle measurements. The thermal properties, rheology, and sintering behavior of the modified UHMWPE were compared to those of the base material. XPS and FTIR analysis confirmed the presence of carboxyl and hydroxyl groups on the surface of the modified powders. The substitution of polar groups into the backbone of the polymer decreased its contact angles with water and hexadecane and increased its surface energy, as evidenced by contact angle measurements. The modified UHMWPE was more crystalline than the base resin and less prone to thermal degradation. Although the rheological properties were virtually identical, the modified powders sintered more readily, presumably due to their higher surface energy, which suggested enhanced processability by compression molding. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Towards children's creative museum engagement and collaborative sense-making

Abstract

In this article, we elucidate a socio-culturally framed approach to supporting children's creative museum engagement. Specifically, we focus on social activities and socio-cultural resources that can act as boundary-permeating objects in mediating children's creative engagement and collaborative sense-making regarding cultural content within, across and beyond the spatio-material context of the museum. We contend that designing and organising children's creative engagement and collaborative sense-making in ways that cultivate boundary-crossing broadens opportunities for engagement and leverages children's creative potential and expansive learning. We build our argument by starting with a theoretical introduction to the design principles that constitute the Kids, Museums, and Technology Programme. We will illuminate the design principles of the programme with empirical examples and consider how the design principles and their situated construction can help us re-imagine museum exhibitions as hybrid, boundary-permeating spaces that afford novel transformative interactions, as well as new roles and identities for both children and museums.