Abstract Lung cancer remains the leading cause of cancer mortality worldwide. Small cell lung cancer (SCLC) accounts for 10–15% of cases and has an overall 5-years survival rate of only 15%. ...Neuron-specific enolase (NSE) has been identified as a useful biomarker for early SCLC diagnosis and therapeutic monitoring. This work reports an electrochemical immunosensing platform based on a graphene-graphitic carbon nitride (g-C 3 N 4 ) nanocomposite for ultrasensitive NSE detection. The g-C 3 N 4 nanosheets and graphene nanosheets were synthesized via liquid exfoliation and integrated through self-assembly to form the nanocomposite. This nanocomposite was used to modify screen-printed carbon electrodes followed by covalent immobilization of anti-NSE antibodies. The unique properties of the graphene-g-C 3 N 4 composite facilitated efficient antibody loading while also enhancing electron transfer efficiency and electrochemical response. Systematic optimization of experimental parameters was performed. The immunosensor exhibited a wide linear detection range of 10 pg/mL to 100 ng/mL and low limit of detection of 3 pg/mL for NSE along with excellent selectivity against interferences. Real serum matrix analysis validated the applicability of the developed platform for sensitive and accurate NSE quantifica-tion at clinically relevant levels. This novel graphene-g-C 3 N 4 nanocomposite based electro-chemical immunoassay demonstrates great promise for early diagnosis of SCLC.
Abstract Elemental metal nanoparticles like cadmium and silver are known to cause oxidative stress and are also highly toxic. Yet for gold nanoparticles (AuNPs), it is not well established whether ...these particles are biologically toxic. Here we show that AuNPs, which were taken up by MRC-5 human lung fibroblasts in vitro , induce autophagy concomitant with oxidative stress. We also observed formation of autophagosomes together with the uptake of AuNPs in the lung fibroblasts as well as upregulation of autophagy proteins, microtubule-associated protein 1 light chain 3 (MAP-LC3) and autophagy gene 7 (ATG 7) in treated samples. AuNP treated cells also generated significantly more lipid hydroperoxides ( p -value < 0.05), a positive indication of lipid peroxidation. Verification with western blot analysis for malondialdehyde (MDA) protein adducts confirmed the presence of oxidative damage. In addition, AuNP treatment also induced upregulation of antioxidants, stress response genes and protein expression. Exposure to AuNPs is a potential source of oxidative stress in human lung fibroblasts and autophagy may be a cellular defence mechanism against oxidative stress toxicity.
Cardiac fibroblasts account for about 75% of all cardiac cells, but because of their small size contribute only ∼10-15% of total cardiac cell volume. They play a crucial role in cardiac ...pathophysiology. For a long time, it has been recognized that fibroblasts and related cell types are the principal sources of extracellular matrix (ECM) proteins, which organize cardiac cellular architecture. In disease states, fibroblast production of increased quantities of ECM proteins leads to tissue fibrosis, which can impair both mechanical and electrical function of the heart, contributing to heart failure and arrhythmogenesis. Atrial fibrosis is known to play a particularly important role in atrial fibrillation (AF). This review article focuses on recent advances in understanding the molecular electrophysiology of cardiac fibroblasts. Cardiac fibroblasts express a variety of ion channels, in particular voltage-gated K(+) channels and non-selective cation channels of the transient receptor potential (TRP) family. Both K(+) and TRP channels are important determinants of fibroblast function, with TRP channels acting as Ca(2+)-entry pathways that stimulate fibroblast differentiation into secretory myofibroblast phenotypes producing ECM proteins. Fibroblasts can couple to cardiomyocytes and substantially affect their cellular electrical properties, including conduction, resting potential, repolarization, and excitability. Co-cultured preparations of cardiomyocytes and fibroblasts generate arrhythmias by a variety of mechanisms, including spontaneous impulse formation and rotor-driven reentry. In addition, the excess ECM proteins produced by fibroblasts can interrupt cardiomyocyte-bundle continuity, leading to local conduction disturbances and reentrant arrhythmias. A better understanding of the electrical properties of fibroblasts should lead to an improved comprehension of AF pathophysiology and a variety of novel targets for antiarrhythmic intervention.
The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium
, which is assumed to dominate the total extragalactic dispersion. ...Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs
, in at least one case there is evidence for an extreme magneto-ionic local environment
and a compact persistent radio source
. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately Formula: see text parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies
, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.
Itraconazole is an FDA‐approved antifungal agent, which has been reported to possess promising anticancer activities in recent years. This study investigates the antiproliferative effects of ...itraconazole on pancreatic cancer cells and the molecular mechanism of its apoptosis‐inducing effects. In this study, our results showed that itraconazole inhibited the growth of pancreatic cancer cells in vitro, and it also significantly inhibited the tumor growth of CFPAC‐1 xenografts in vivo. Itraconazole induced apoptosis through ROS generation and mitochondrial membrane depolarization. A Bak‐1 activation dependent apoptosis was identified in CFPAC‐1 cells. These data suggested that itraconazole exhibited antiproliferative effects in pancreatic cancer cells by inducing apoptosis through Bak‐1 activation.
Itraconazole inhibited the growth of pancreatic cancer cells in vitro, and it also significantly inhibited the tumor growth of CFPAC‐1 xenografts in vivo. Itraconazole induced apoptosis through ROS generation and mitochondrial membrane depolarization.
Abstract Impurities in the synthesized gold nanoparticle (AuNP) solution are systematically identified followed by determining an optimal purification process and evaluating the stability as well as ...oxidation state of the purified 20-nm AuNPs. Quantified non-AuNP components and a newly speciated byproduct (acetate) complete the stoichiometric equation of AuNP synthesis through the citrate reduction method. Among the five tested centrifugation forces (3000–11,000 g ) and durations (10–60 min), optimal purification of AuNPs was achieved by centrifugation operating at 7000 g for 20 min which satisfactorily recovers ∼80% of AuNPs without detectable impurities. Storage in the dark at 4 °C prolongs the stability of the purified AuNP suspensions up to 20 days. AuNPs employed in this study persist in their atomic status without being oxidized, even after they were aerosolized in air or heated at 500 °C. This work demonstrates how impurities are identified and removed, and the purified AuNPs can be a reference material to evaluate toxicity or reactivity of other engineered nanomaterials.
The properties of quantum materials are commonly tuned using experimental variables such as pressure, magnetic field and doping. Here we explore a different approach using irreversible, plastic ...deformation of single crystals. We show that compressive plastic deformation induces low-dimensional superconductivity well above the superconducting transition temperature (T
) of undeformed SrTiO
, with evidence of possible superconducting correlations at temperatures two orders of magnitude above the bulk T
. The enhanced superconductivity is correlated with the appearance of self-organized dislocation structures, as revealed by diffuse neutron and X-ray scattering. We also observe deformation-induced signatures of quantum-critical ferroelectric fluctuations and inhomogeneous ferroelectric order using Raman scattering. Our results suggest that strain surrounding the self-organized dislocation structures induces local ferroelectricity and quantum-critical dynamics that strongly influence T
, consistent with a theory of superconductivity enhanced by soft polar fluctuations. Our results demonstrate the potential of plastic deformation and dislocation engineering for the manipulation of electronic properties of quantum materials.
Aim
3‐Phenyllactic acid (3‐PLA) has been widely used in food and material industries. Three Lactobacillus crustorum strains have shown greater 3‐PLA production ability in our previous study. The ...objectives of this study were to further improve 3‐PLA yields in batch and continuous fermentation systems using of free‐whole‐cells of the three L. crustorum strains.
Materials and Results
The fermentation conditions of free‐whole‐cells of the three L. crustorum strains for 3‐PLA production were optimized. Among these strains, L. crustorum NWAFU 1078 showed excellent reusability and significantly (P < 0·05) greater 3‐PLA production ability than the other strains after 10th recycle. The strain possesses three l‐lactate dehydrogenase and three d‐lactate dehydrogenase catalysing 3‐PLA production from phenylpyruvic acid (PPA). Under the optimal conditions, the strain produced 15·2 mmol l−1 3‐PLA (76% PPA conversion rate) in a batch fermentation system and 6·5 mmol l−1 h−1 3‐PLA (55% PPA conversion rate) in a continuous fermentation system using a 0·6 dilution rate.
Conclusions
Free‐whole‐cells of L. crustorum NWAFU 1078 showed excellent reusability and higher 3‐PLA yields under optimal biotransformation conditions in both batch and continuous fermentation systems.
Significance and Impact of the Study
This study provides the possibility to use the free‐whole‐cells of L. crustorum NWAFU 1078 as a biocatalyst for effective production of 3‐PLA.
The relationship between atomic-scale and micromagnetic Dzyaloshinski-Moriya (DM) interactions has been investigated. By analyzing the Lifshitz invariants for different point groups, we have found ...that there is no unique link between the absence of inversion symmetry and DM interactions. The absence of inversion symmetry is a necessary condition for a net DM interaction in crystals, but several noncentrosymmetric point groups have zero DM interactions. In many cases, the key consideration is whether the crystals are polar and/or chiral. For example, MnSi-type spin spirals, which violate helical spin symmetry, are caused by the insertion of chiral atomic-scale building blocks into an achiral cubic lattice, and the scalar interaction parameter D used to describe the spirals is only loosely related to the DM vector D. It contains, in fact, magnetostatic and magnetocrystalline contributions of unknown magnitude. Finally, we discuss some aspects of the micromagnetism of the skyrmionics of nanoparticles and granular nanostructures.
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