A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.     

Mass Spectrometric Identification of Licania rigida Benth Leaf Extracts and Evaluation of Their Therapeutic Effects on Lipopolysaccharide-Induced Inflammatory Response

Licania rigida Benth has been evaluated as an alternative drug to treat diseases associated with inflammatory processes. This study evaluated the anti-inflammatory effects of aqueous and hydroalcoholic leaf extracts of L. rigida with inflammation induced by lipopolysaccharides in in vitro and in vivo inflammation models. The phytochemical profile of the extracts, analyzed by ultra-fast liquid chromatography coupled with tandem mass spectrometry, revealed the presence of gallic and ellagic acids in both extracts, whereas isovitexin, ferulate, bulky amino acids (e.g., phenylalanine), pheophorbide, lactic acid, and pyridoxine were detected in the hydroalcoholic extract. The extracts displayed the ability to modulate in vitro and in vivo inflammatory responses, reducing approximately 50% of pro-inflammatory cytokine secretion (TNF-α, IL-1β, and IL-6), and inhibiting both NO production and leukocyte migration by approximately 30 and 40% at 100 and 500 µg/mL, respectively. Overall, the results highlight and identify, for the first time, the ability of L. rigida leaf extract to modulate inflammatory processes. These data suggest that the leaf extracts of this plant have potential in the development of herbal formulations for the treatment of inflammation.     

Head-to-Tail and Head-to-Head Molecular Chains of Poly(p-Anisidine): Combined Experimental and Theoretical Evaluation

Poly(p-anisidine) (PPA) is a polyaniline derivative presenting a methoxy (–OCH₃) group at the para position of the phenyl ring. Considering the important role of conjugated polymers in novel technological applications, a systematic, combined experimental and theoretical investigation was performed to obtain more insight into the crystallization process of PPA. Conventional oxidative polymerization of p-anisidine monomer was based on a central composite rotational design (CCRD). The effects of the concentration of the monomer, ammonium persulfate (APS), and HCl on the percentage of crystallinity were considered. Several experimental techniques such as X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), multifractal analysis, Nuclear Magnetic Resonance (¹³C NMR), Fourier-transform Infrared spectroscopy (FTIR), and complex impedance spectroscopy analysis, in addition to Density Functional Theory (DFT), were employed to perform a systematic investigation of PPA. The experimental treatments resulted in different crystal structures with a percentage of crystallinity ranging from (29.2 ± 0.6)% (PPA1_HT) to (55.1 ± 0.2)% (PPA16_HT-HH). A broad halo in the PPA16_HT-HH pattern from 2θ = 10.0–30.0° suggested a reduced crystallinity. Needle and globular-particle morphologies were observed in both samples; the needle morphology might have been related to the crystalline contribution. A multifractal analysis showed that the PPA surface became more complex when the crystallinity was reduced. The proposed molecular structures of PPA were supported by the high-resolution ¹³C NMR results, allowing us to access the percentage of head-to-tail (HT) and head-to-head (HH) molecular structures. When comparing the calculated and experimental FTIR spectra, the most pronounced changes were observed in ν(C–H), ν(N–H), ν(C–O), and ν(C–N–C) due to the influence of counterions on the polymer backbone as well as the different mechanisms of polymerization. Finally, a significant difference in the electrical conductivity was observed in the range of 1.00 × 10⁻⁹ S.cm⁻¹ and 3.90 × 10⁻¹⁴ S.cm⁻¹, respectively, for PPA1_HT and PPA16_HT-HH.     

Luminescent Carbon Dots from Wet Olive Pomace: Structural Insights,Photophysical Properties and Cytotoxicity

Carbon nanomaterials endowed with significant luminescence have been synthesized for the first time from an abundant, highly localized waste, the wet pomace (WP), a semi-solid by-product of industrial olive oil production. Synthetic efforts were undertaken to outshine the photoluminescence (PL) of carbon nanoparticles through a systematic search of the best reaction conditions to convert the waste biomass, mainly consisting in holocellulose, lignin and proteins, into carbon dots (CDs) by hydrothermal carbonization processes. Blue-emitting CDs with high fluorescence quantum yields were obtained. Using a comprehensive set of spectroscopic tools (FTIR, Raman, XPS, and ¹H/¹³C NMR) in combination with steady-state and time-resolved fluorescence spectroscopy, a rational depiction of WP-CDs structures and their PL properties was reached. WP-CDs show the up-conversion of PL capabilities and negligible cytotoxicity against two mammalian cell lines (L929 and HeLa). Both properties are excellent indicators for their prospective application in biological imaging, biosensing, and dynamic therapies driven by light.     

Hybrid Surface Mesh Adaptation for Climate Modeling

Solution-driven mesh adaptation is becoming quite popular for spatial error control in the numerical simulation of complex computational physics applications, such as climate modeling. Typically, spatial adaptation is achieved by element subdivision （h adaptation） with a primary goal of resolving the local length scales of interest. A sec- ond, less-popular method of spatial adaptivity is called ＂mesh motion＂ （r adaptation）; the smooth repositioning of mesh node points aimed at resizing existing elements to capture the local length scales. This paper proposes an adaptation method based on a combination of both element subdivision and node point repositioning （rh adaptation）. By combining these two methods using the notion of a mobility function, the proposed approach seeks to increase the flexibility and extensibility of mesh motion algorithms while providing a somewhat smoother transition between refined regions than is pro- duced by element subdivision alone. Further, in an attempt to support the requirements of a very general class of climate simulation applications, the proposed method is designed to accommodate unstructured, polygonal mesh topologies in addition to the most popular mesh types.     

X-ray photoemission study of fluorozirconate glass and related crystals

Silicate glasses with the composition (in per cent by weight) of 74 SiO₂, 20 Na₂O, 6 CaO and different Fe₂O₃ concentrations were subjected to X-ray irradiation and the behaviour of the iron as well as that of the radiation-induced defects was investigated systematically using ESR. The defects which are abundant in iron-free glasses (they produce a strong signal at g = 2.01) and which lead to colouring of the glass, decrease with rising Fe₂O₃ concentration and cease to exist at 2% Fe₂O₃. These glasses are radiation-resistant.Because of the X-rays a valence change of the iron takes place. This process is initiated by a radiation-induced redox interaction between Fe³⁺ and Fe²⁺ according to:

$\text{Fe}{}^{\mathrm{2+}}\text{+}\text{Fe}{}^{\mathrm{3+}}\text{→}\text{hv}\text{Fe}{}^{\mathrm{3+1}}\text{+}\text{Fe}{}^{\mathrm{2+1}}$

Because of the different structures (coordinations) of Fe²⁺ and Fe³⁺ the process leads to a decrease in Fe³⁺ at g = 4.2 in glasses with low Fe₂O₃ concentration. This decrease is reduced with increasing concentration of Fe₂O₃.     

Electrospray ionization mass spectrometry fingerprinting of beer

After just simple degassing, dilution, pH adjustment and direct flow injection, characteristic fingerprint spectra of beer samples have been obtained by fast (few seconds) electrospray ionization mass spectrometry (ESI-MS) analysis in both the negative and positive ion modes. A total of 29 samples belonging to the two main beer types (lagers and ales) and several beer subtypes from USA, Europe and Brazil could be clearly divided into three groups both by simple visual inspection of their ESI(+)-MS and ESI(-)-MS fingerprints as well as by chemometric treatment of the MS data. Diagnostic ions with contrasting relative abundances in both the positive and negative ion modes allow classification of beers into three major types: P = pale (light) colored (pilsener, pale ale), D = dark colored (bock, stout, porter, mild ale) and M = malt beer. For M beers, samples of a dark and artificially sweetened caramel beer produced in Brazil and known as Malzbiers were used. ESI-MS/MS on these diagnostic beer cations and anions, most of which are characterized as arising from ionization of simple sugars, oligosaccharides, and iso-alpha-acids, yield characteristic tandem mass spectra adding a second and optional MS dimension for improved selectivity for beer characterization by fingerprinting. Direct ESI-MS or ESI-MS/MS analysis can therefore provide fast and reliable fingerprinting characterization of beers, distinguishing between types with different chemical compositions. Other unusual polar components, impurities or additives, as well as fermentation defects or degradation products, could eventually be detected, making the technique promising for beer quality control.     

Nitric oxide modulates tumor cell death induced by photodynamic therapy through a cGMP-dependent mechanism

Photodynamic therapy (PDT) of cancer is a very promising technique based on the formation of singlet oxygen induced by a sensitizer after irradiation with visible light. The stimulation of tumor growth by nitric oxide (NO) was reported recently, and NO was shown to have a protective effect against PDT-induced tumor death. We investigated a putative direct effect of NO on tumor cell death induced by PDT, using the human lymphoblastoid CCRF-CEM cells and bisulfonated aluminum phthalocyanine (AlPcS2) as a sensitizer. Cells were incubated with AlPcS2 in the presence or absence of NO donors ((Z)-1-[(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, hydroxylamine and S-nitroso-N-acetylpenicillamine) or L-arginine. Under these conditions, in the absence of NO donors or L-arginine the cells died rapidly by apoptosis upon photosensitization. In the presence of NO donors or L-arginine, apoptotic cell death after photosensitization was significantly decreased. Modulation of cell death by NO was not due to S-nitrosylation of caspases and occurred at the level or upstream of caspase-9 processing. The protective effect of NO was reversed by incubating the cells with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of guanylyl cyclase, or with KT5823, an inhibitor of protein kinase G (PKG). Incubation with 8-bromo-cyclic guanosine monophosphate, a membrane permeable cyclic guanosine monophosphate analog, also decreased cell death induced by PDT. Although the protective effect of NO against apoptotic cell death in several models has been attributed to an increase in the expression of heme oxygenase-1, heat shock protein 70 or Bcl-2, this was not the case under our experimental conditions. These results show that NO decreases the extent of apoptotic cell death after PDT treatment through a PKG-dependent mechanism, upstream or at the level of caspase activation.     

Improvement in solar-pumped Nd:YAG laser beam brightness

Solar-pumped solid-state lasers are promising for renewable extreme-temperature material processing. Here we report a large improvement in solar laser beam brightness by pumping a thin Nd:YAG single crystal rod. A fused silica light guide of 14 mm×22 mm rectangular cross-section is used to both transmit and homogenize the concentrated solar radiation from the focal zone of a 2.88 m² parabolic mirror to the entrance aperture of a modified 2D-CPC flooded pump cavity, within which a 4 mm diameter rod is efficiently pumped. 2.2% slope efficiency is reached. Laser beam brightness figure of merit B is three times higher than that of the most recent solar-pumped Nd:YAG laser by a Fresnel lens. The introduction of the rectangular cross-section light guide has also ensured a much more stable laser emission than previous pumping schemes.