Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative comparison of C-X-C chemokines produced by endotoxin-stimulated human alveolar macrophages.

The C-X-C chemokines are a structurally related and functionally redundant family of proteins with neutrophil chemotactic activity. Many of the C-X-C chemokines are produced by endotoxin-stimulated alveolar macrophages (AMs), but knowledge of their relative quantities and their relative contributions to the total chemotactic activity released from these cells is incomplete. Human AMs were stimulated with or without Escherichia coli endotoxin for 2, 4, 8, and 24 h. The mRNA sequences of interleukin (IL)-8, the 78-amino acid epithelial cell-derived neutrophil activator (ENA-78), growth-related protein (GRO) α, GROβ, and GROγ were cloned by PCR and identified by sequence analysis. The relative mRNA quantities were compared by Northern analysis, and IL-8 was found to predominate. Similarly, IL-8 protein concentrations in the cell supernatants were consistently higher than either the ENA-78 or GRO concentration, and by 24 h, IL-8 concentrations were 10-fold higher than those of the other C-X-C chemokines. Blocking polyclonal antibodies to IL-8 substantially reduced the chemotactic activity in the AM supernatants, whereas antibodies to ENA-78 and GRO had little or no effect. We conclude that IL-8 is the predominant C-X-C chemokine and the dominant neutrophil chemoattractant accumulating in 24-h supernatants of lipopolysaccharide-stimulated human AMs. These studies provide insight into potentially effective strategies of interrupting AM-derived inflammatory signals in the lungs.
Dispersion relations for composite structures. Part II. Methods of determining dispersion curves

In the first part of the current review, the fundamental assumptions of the theoretical model of elastic waves propagation in multilayered composite material are presented. Next, the equations which describe elastic wave motion in the case of single orthotropic lamina are derived. In the second part of this work, the most commonly used method of determining dispersion curves for multilayered composite material are discussed, namely: the transfer matrix method (TMM), global matrix method (GMM), stiffness matrix method (SMM) and finally the semi-analytical finite element method (SAFE). The first three methods are based on the relationships which are derived in the first part of this review. Moreover, TMM and GMM should be considered numerically unstable in the case of a relatively large product value of wave frequency and the total thickness of the composite plate. However, SMM seems to be unconditionally stable. The last method is based on the finite element approach and it can be used in order to confirm the results obtained using the analytical method. Finally, exemplary dispersion curves are presented. The dispersion curves are determined for the 8-th layer of the composite material, which is made of carbon fiber and epoxy resin. It is assumed that the wave front travels in an arbitrary direction.
Curcuminoid-loaded poly(methyl methacrylate) nanoparticles for cancer therapy

Curcuminoids (Curs), oleoresins from Curcuma longa L. , have known anticarcinogenic and anti-inflammatory properties, but high toxicity, poor aqueous solubility and susceptibility to degradation in body fluids are deterrents to their clinical administration. Poly(methyl methacrylate) nanoparticles (PMMA-NPs) are biocompatible and resilient and can entrap hydrophobic drugs. The present investigation is related to solubilizing Curs by incorporating them in these nanoparticles (NPs) and is related to a study comparing the anticarcinogenic effect of drug-loaded NPs with free Cur using lung cancer (A549) cell line. Freshly extracted oleoresins were post loaded in PMMA-NPs prepared using emulsion polymerization. The presence of the three components of oleoresins was confirmed by thin-layer chromatography. The size and morphology of void and loaded NPs were determined by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. The NPs were spherical with diameters of 192.66±5 nm (void) and 199.16±5 nm (loaded). Drug loading and encapsulation efficiency were 6% and 93%, respectively. From the Fourier transform infrared spectroscopy spectra, the characteristic absorption vibration of poly(methyl methacrylate) and the bands at 1,383, 1,233 and 962 cm−1 for Cur moiety were observed. Drug release up to 10 days was estimated in buffer, saline and serum. The highest release of ~55% in ~3 days was noted in buffer that exhibited the highest bioavailability. The in vitro anticancer activity of loaded drug was evaluated up to 72 hours by MTT assay using A549 cell line. Cellular uptake of dye-loaded NPs was visualized within 30 minutes of incubation. The results revealed that the dose- and time-dependent cell death in case of loaded PMMA-NPs was comparable to that of free Cur. According to the study, the drug-loaded PMMA-NPs appear to be highly suitable for effective, localized and safe chemotherapy.
Contributions of acetylcholine and nitric oxide to forearm blood flow at exercise onset and recovery.

The contributions of acetylcholine and/or nitric oxide (NO) to the rapid changes in human forearm blood flow (FBF) at the onset and recovery from mild exercise were studied in eight subjects. Rhythmic handgrip contractions were performed during brachial artery infusions of saline (2 ml/min; control), atropine (0.2 mg over 3 min), to block acetylcholine binding to muscarinic receptors, or atropine + N G-monomethyl-l-arginine (l-NMMA; 4 mg/min for 4 min), to additionally inhibit NO synthase. Brachial artery mean blood velocity (MBV; pulsed Doppler ultrasound) and diameter (echo Doppler) were measured continuously, and FBF was calculated. Atropine reduced acetylcholine-induced increases in FBF by ∼71% ( P < 0.05). FBF at rest was reduced by atropine and further reduced with atropine +l-NMMA. Both drug conditions reduced FBF during exercise by ∼10% compared with control, with no difference between drug treatments. Brachial artery diameter was unchanged from rest by exercise, recovery, and drug treatments. Neither drug treatment altered the rate or magnitude of the increase in FBF above rest. Peak FBF after exercise was reduced by atropine and atropine + l-NMMA. Total FBF during 5 min of recovery was reduced with atropine +l-NMMA compared with control and atropine. The results suggest that 1) acetylcholine and NO mechanisms additively contribute to FBF levels at rest, 2) a cholinergic mechanism adjusts the absolute FBF levels during exercise, 3) neither acetylcholine nor NO is essential to observe the normal time course or magnitude of the exercise response, and 4) NO contributes to the FBF response during recovery from exercise.
Electrochemical Biosensors: A Solution to Pollution Detection with Reference to Environmental Contaminants

The increasing environmental pollution with particular reference to emerging contaminants, toxic heavy elements, and other hazardous agents is a serious concern worldwide. Considering this global issue, there is an urgent need to design and develop strategic measuring techniques with higher efficacy and precision to detect a broader spectrum of numerous contaminants. The development of precise instruments can further help in real-time and in-process monitoring of the generation and release of environmental pollutants from different industrial sectors. Moreover, real-time monitoring can also reduce the excessive consumption of several harsh chemicals and reagents with an added advantage of on-site determination of contaminant composition prior to discharge into the environment. With key scientific advances, electrochemical biosensors have gained considerable attention to solve this problem. Electrochemical biosensors can be an excellent fit as an analytical tool for monitoring programs to implement legislation. Herein, we reviewed the current trends in the use of electrochemical biosensors as novel tools to detect various contaminant types including toxic heavy elements. A particular emphasis was given to screen-printed electrodes, nanowire sensors, and paper-based biosensors and their role in the pollution detection processes. Towards the end, the work is wrapped up with concluding remarks and future perspectives. In summary, electrochemical biosensors and related areas such as bioelectronics, and (bio)-nanotechnology seem to be growing areas that will have a marked influence on the development of new bio-sensing strategies in future studies.
Curing Effects on Interfacial Adhesion between Recycled Carbon Fiber and Epoxy Resin Heated by Microwave Irradiation

The interfacial adhesion of recycled carbon fiber (CF) reinforced epoxy composite heated by microwave (MW) irradiation were investigated by changing the curing state of the epoxy resin. The recycled CF was recovered from the composite, which was prepared by vacuum-assisted resin transfer molding, by thermal degradation at 500 or 600 °C. Thermogravimetric analysis showed that the heating at 600 °C caused rough damage to the CF surface, whereas recycled CF recovered at 500 °C have few defects. The interfacial shear strength (IFSS) between recycled CF and epoxy resin was measured by a single-fiber fragmentation test. The test specimen was heated by MW after mixing the epoxy resin with a curing agent or pre-curing, in order to investigate the curing effects on the matrix resin. The IFSSs of the MW-irradiated samples were significantly varied by the curing state of the epoxy resin and the surface condition of recycled CF, resulting that they were 99.5 to 131.7% of oven heated samples Furthermore, rheological measurements showed that the viscosity and shrinking behaviors of epoxy resin were affected based on the curing state of epoxy resin before MW irradiation.
Assembly mechanism of the α-pore–forming toxin cytolysin A from Escherichia coli

The cytolytic toxin cytolysin A (ClyA) from Escherichia coli is probably one of the best-characterized examples of bacterial, α-pore–forming toxins (α-PFTs). Like other PFTs, ClyA exists in a soluble, monomeric form that assembles to an annular, homo-oligomeric pore complex upon contact with detergent or target membranes. Comparison of the three-dimensional structures of the 34 kDa monomer and the protomer in the context of the dodecameric pore complex revealed that ClyA undergoes one of the largest conformational transitions described for proteins so far, in which 55% of the residues change their position and 16% of the residues adopt a different secondary structure in the protomer. Studies on the assembly of ClyA revealed a unique mechanism that differs from the assembly mechanism of other PFTs. The rate-liming step of pore formation proved to be the unimolecular conversion of the monomer to an assembly-competent protomer, during which a molten globule-like off-pathway intermediate accumulates. The oligomerization of protomers to pore complexes is fast and follows a kinetic scheme in which mixtures of linear oligomers of different size are formed first, followed by very rapid and specific association of pairs of oligomers that can directly perform ring closure to the dodecameric pore complex. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.
Erythropoietin as an adjunctive treatment for methanol-induced toxic optic neuropathy

ABSTRACT Background: Methanol-induced optic neuropathy (MTON) is frequently seen in countries where alcohol consumption is banned or poorly regulated. MTON frequently results in blindness and there is no empirically validated treatment. Objective: To evaluate the effect of erythropoietin (EPO) as an adjunctive treatment for MTON. Methods: In this nonrandomized interventional comparative study, all participants were diagnosed with MTON and received the steroid methylprednisolone. Eleven participants received intravenous EPO (10000 IU twice a day) for three days as an adjuvant to methylprednisolone (EPO group); 11 participants in a historical control group received methylprednisolone only (control group). Main outcomes were best-corrected visual acuity (BCVA), peripapillary retinal nerve fiber layer thickness (PRNFLT), and visual field mean deviation (MD). Results: Mean BCVA improved significantly in both groups: from 2.93 ± 0.55 to 1.75 ± 1.16 LogMAR at month 3 (p < 0.001) in the EPO group, and from 2.65 ± 0.68 to 2.19 ± 0.75 at final visit in the control group (p = 0.001). The final BCVA was significantly better in the EPO group (p = 0.012). The mean PRNFLT decreased in both groups. However, at the final follow-up, PRNFLT was significantly thinner in the control group (53 ± 6 vs. 77 ± 26 microns, respectively; p < 0.001). Conclusion: Intravenous EPO plus high-dose intravenous steroid may be an effective combination therapy for the patients with MTON.
Profiling and identification of chlorogenic acid metabolites in rats by ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer

Abstract 1. Chlorogenic acids (CGAs), one kind of major bioactive constituents isolated from Flos Lonicera Japonica, possess many biological activities, such as antibacterial, antioxidant and antiviral activities. In this study, we established an efficient strategy using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of CGAs in rat urine and plasma. 2. The extract from Flos Lonicera Japonica was orally administrated to Sprague-Dawley (SD) rats at a dose of 1000 mg/kg body weight. Then, a combination of various post-acquisition data mining methods, including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDFs) and diagnostic product ions (DPIs), were adopted to characterize the known and unknown CGA metabolites in SD rats. 3. As a result, a total of 68 CGA metabolites were unambiguously or tentatively screened and characterized. These metabolites, including 18 prototype compounds and 50 metabolites, were deduced to be yielded via methylation, hydrogenation, demethylation, dehydration, sulfate conjugation, glucuronide conjugation, glycosylation conjugation and their composite reactions, which mainly occurred to caffeoylquinic acids, dicaffeoylquinic acids, p-coumaroylquinic acids and feruloylquinic acids. 4. In conclusion, this study profiled CGA metabolites, which are useful in understanding the in vivo metabolic fate, effective forms, and pharmacological and toxic actions of CGAs.
Non-Crop Host Sampling Yields Insights into Small-Scale Population Dynamics of Drosophila suzukii (Matsumura)

Invasive, polyphagous crop pests subsist on a number of crop and non-crop resources. While knowing the full range of host species is important, a seasonal investigation into the use of non-crop plants adjacent to cropping systems provide key insights into some of the factors determining local population dynamics. This study investigated the infestation of non-crop plants by the invasive Drosophila suzukii (Matsumura), a pest of numerous economically important stone and small fruit crops, by sampling fruit-producing non-crop hosts adjacent to commercial plantings weekly from June through November in central New York over a two-year period. We found D. suzukii infestation rates (number of flies emerged/kg fruit) peaked mid-August through early September, with Rubus allegheniensis Porter and Lonicera morrowii Asa Gray showing the highest average infestation in both years. Interannual infestation patterns were similar despite a lower number of adults caught in monitoring traps the second year, suggesting D. suzukii host use may be density independent.
Ouabain reduces net acid secretion and increases pHi by inhibiting[Formula: see text] uptake on rat tIMCD Na+-K+-ATPase.

In the rat terminal inner medullary collecting duct (tIMCD), Na+ pump inhibition reduces transepithelial net acid secretion ( J tAMM) [ J H = total CO2 absorption ( J tCO2) + total ammonia secretion] and increases resting intracellular pH (pHi). The increase in pHi and reduction in J H that follow ouabain addition do not occur in the absence of[Formula: see text] nor when [Formula: see text]is substituted with another weak base. The purpose of this study was to explore the mechanism of the [Formula: see text]-dependent reduction in J tCO2 and increase in pHi that follow ouabain addition. We hypothesized that [Formula: see text]enters the tIMCD cell through the Na+-K+-ATPase with proton release in the cytosol. To test this hypothesis, tIMCDs were dissected from deoxycorticosterone-treated rats and perfused in vitro with symmetrical physiological saline solutions containing 6 mM NH4Cl. Since K+ and[Formula: see text] compete for a common binding site on the Na+ pump, increasing extracellular K+ should limit[Formula: see text] (and hence net H+) uptake by the Na+ pump. Upon increasing extracellular K+ concentration from 3 to 12 mM, the [Formula: see text]-dependent, ouabain-induced increase in pHiand reduction in J tCO2 were attenuated. In the presence but not in the absence of[Formula: see text], reducing Na+ pump activity by limiting Na+ entry reduced J tCO2 and attenuated ouabain-induced alkalinization. Ouabain-induced alkalinization was not dependent on the presence of[Formula: see text]/CO2and was not reproduced with BaCl2or bumetanide addition. Therefore, ouabain-induced alkalinization is not mediated by the Na+-K+-2Cl-cotransporter or a [Formula: see text] transporter and is not mediated by changes in membrane potential. In conclusion, on the basolateral membrane of the tIMCD cell,[Formula: see text] uptake is mediated by the Na+-K+-ATPase. These data provide an explanation for the reduction in net acid secretion in the tIMCD observed following administration of amiloride or with dietary K+ loading.
Association of sense of coherence and supernatural beliefs with death anxiety and death depression among Romanian cancer patients

ABSTRACT The aim of this cross-sectional study was to examine the association of supernatural beliefs and sense of coherence with death anxiety and death depression in a Romanian sample of cancer patients. We found support for the terror management theory worldview defence hypothesis postulating the presence of a curvilinear relation between death anxiety and supernatural beliefs among cancer patients. Results conformed to an inverted U-shape quadratic regression, indicating that cancer patients who scored moderately on supernatural beliefs were afraid of death the most, while death anxiety was lowest for the extreme atheists and extreme believers in supernatural entities.
A synaptotagmin suppressor screen indicates SNARE binding controls the timing and Ca2+ cooperativity of vesicle fusion

The synaptic vesicle Ca2+ sensor Synaptotagmin binds Ca2+ through its two C2 domains to trigger membrane interactions. Beyond membrane insertion by the C2 domains, other requirements for Synaptotagmin activity are still being elucidated. To identify key residues within Synaptotagmin required for vesicle cycling, we took advantage of observations that mutations in the C2B domain Ca2+-binding pocket dominantly disrupt release from invertebrates to humans. We performed an intragenic screen for suppressors of lethality induced by expression of Synaptotagmin C2B Ca2+-binding mutants in Drosophila. This screen uncovered essential residues within Synaptotagmin that suggest a structural basis for several activities required for fusion, including a C2B surface implicated in SNARE complex interaction that is required for rapid synchronization and Ca2+ cooperativity of vesicle release. Using electrophysiological, morphological and computational characterization of these mutants, we propose a sequence of molecular interactions mediated by Synaptotagmin that promote Ca2+ activation of the synaptic vesicle fusion machinery.
Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor

The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.
Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of Cultured Phagocytic Cells

ABSTRACT Gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, is currently in clinical development for the treatment of bacterial infections. This study examined in vitro its activity against intracellular Staphylococcus aureus (involved in the persistent character of skin and skin structure infections) by use of a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (the apparent bacteriostatic concentration [Cs] was reached at an extracellular concentration about 0.7× its MIC and was not affected by mechanisms of resistance to the comparators) and (ii) caused a maximal reduction of the intracellular burden (maximum effect) of about −1.6 log10 CFU (which was better than that caused by linezolid, macrolides, and daptomycin and similar to that caused by moxifloxacin). After 24 h of incubation of infected cells with antibiotics at 100× their MIC, the intracellular persisting fraction was <0.1% with moxifloxacin, 0.5% with gepotidacin, and >1% with the other drugs. The accumulation and efflux of gepotidacin in phagocytes were very fast (kin and kout, ∼0.3 min−1; the plateau was reached within 15 min) but modest (intracellular concentration-to-extracellular concentration ratio, ∼1.6). In cell fractionation studies, about 40 to 60% of the drug was recovered in the soluble fraction and ∼40% was associated with lysosomes in uninfected cells. In infected cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable fraction that also contained bacteria. This study highlights the potential for further study of gepotidacin to fight infections where intracellular niches may play a determining role in bacterial persistence and relapses.