Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Impact of quenched random fields on the ferroelectric-to-relaxor crossover in the solid solution (1−x)BaTiO3−xDyFeO3

Lead-based perovskite relaxor ferroelectrics are widely used as materials for numerous applications due to their extraordinary dielectric, piezoelectric, and electrostrictive properties. While the mechanisms of relaxor behavior are disputable, the importance of quenched (static) random electric fields created at nanoscale by the disordered heterovalent cations has been well recognized. Meanwhile, an increasing amount of scientific and technological efforts has been concentrated on lead-free perovskites, in particular, solid solutions of classical ferroelectric BaTiO 3 (BT), which better meet ecological requirements. Among BT-based solutions the homovalent systems are elaborately studied where strong random electric fields are absent, while the solubility limit of heterovalent solutions is typically too low to fully reveal the peculiarities of relaxor behavior. In this paper, we prepare a perovskite solid solution system (1 − x )Ba 2 + Ti 4 + O 3 − x Dy 3 + Fe 3 + O 3 (0 x 0 . 3) and study it as a model heterovalent lead-free system. We determine crystal structure, ferroelectric, and dielectric properties of ceramics in a wide range of temperatures and concentrations, construct a phase diagram, and find and analyze the concentration-induced crossover from normal ferroelectric to relaxor behavior. We demonstrate that quenched random electric fields of moderate strength promote the ferroelectric-to-relaxor crossover, but do not change qualitatively the peculiarities of relaxor behavior, while strong enough fields destroy the relaxor state, so that the material becomes an ordinary linear dielectric. The experimental results are compared with the predictions of known theories of relaxor ferroelectricity

Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma

Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL

Ecological strategies of Hyphantria cunea (Lepidoptera: Arctiidae) response to different larval densities

Population density is an essential factor affecting the life history traits of insects and their trade-off relationships, as increasing density intensifies intraspecific competition. It decreases the average resources available to individuals within a population, affecting their morphology, physiology, behavior, and fitness. The fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), has been an invasive pest of forest trees, ornamental plants, and fruit trees in China for many years. The larvae have a typical aggregation habit before the fourth instar and keep spitting silk to gather the damaged leaves into silk webs. However, the fitness of H. cunea in response to population density remains unclear. In this study, the critical biological parameters, food utilization, and population parameters of H. cunea in response to different rearing densities were investigated. The results showed that under high population density, H. cunea larvae showed better performance, with faster development, higher survival rates, and shorter generation time, but pupal weight and female fecundity decreased as population density increased. In contrast, for larvae raised in low density, the developmental period was prolonged, and mortality was increased, while higher food utilization, greater body size, and female fecundity were observed. Both males and females had similar development strategies in response to the density, but females may be more resistant to crowding than males. In conclusion, H. cunea could adopt different ecological strategies against the stress of density. High population densities result in shorter generation cycles and higher survival rates. Conversely, the low-density generation period becomes longer but with greater fecundity. The results may help determine the possible outbreak mechanism and develop effective population monitoring and forecasting measures for H. cunea

In vivo reactive astrocyte imaging using 18FSMBT-1 in tauopathy and familial Alzheimer’s disease mouse models: A multi-tracer study

Background: Reactive astrocytes play an important role in the development of Alzheimer's disease and primary tauopathies. Here, we aimed to investigate the relationships between reactive astrocytes. Microgliosis and glucose metabolism with Tau and amyloid beta pathology by using multi-tracer imaging in widely used tauopathy and familial Alzheimer's disease mouse models. Results: Positron emission tomography imaging using 18FPM-PBB3 (tau), 18Fflorbetapir (amyloid-beta), 18FSMBT-1 (monoamine oxidase-B), 18FDPA-714 (translocator protein) and 18Ffluorodeoxyglucose was carried out in 3- and 7-month-old rTg4510 tau mice, 5 × FAD familial Alzheimer's disease mice and wild-type mice. Immunofluorescence staining was performed to validate the pathological distribution in the mouse brain after in vivo imaging. We found increased regional levels of 18FPM-PBB3, 18FSMBT-1, and 18FDPA-714 and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice compared to age-matched wild-type mice. Increased 18FSMBT-1 uptake was observed in the brains of 3, 7-month-old 5 × FAD mice, with elevated regional 18Fflorbetapir and 18FDPA-714 uptakes in the brains of 7-month-old 5 × FAD mice, compared to age-matched wild-type mice. Positive correlations were shown between 18FSMBT-1 and 18FPM-PBB3, 18FDPA-714 and 18FPM-PBB3 in rTg4510 mice, and between 18Fflorbetapir and 18FDPA-714 SUVRs in 5 × FAD mice. Conclusion: In summary, these findings provide in vivo evidence that reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism are associated with tau and amyloid pathology development in animal models of tauopathy and familial Alzheimer's disease

Exposure to low-level metalaxyl impacts the cardiac development and function of zebrafish embryos.

Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species. In order to study the toxic effects, zebrafish embryos were exposed to metalaxyl at nominal concentrations of 5, 50 and 500 ng/L for 72 hr, and the cardiac development and functioning of larvae were observed. The results showed that metalaxyl exposure resulted in increased rates of pericardial edema, heart hemorrhage and cardiac malformation. The distance between the sinus venosus and bulbus arteriosus, stroke volume, cardiac output and heart rate were significantly increased in larvae exposed to 50 and 500 ng/L metalaxyl compared to solvent control larvae. Significant upregulation in the transcription of tbx5, gata4 and myh6 was observed in the 50 and 500 ng/L treatments, and that of nkx2.5 and myl7 was observed in the 5, 50 and 500 ng/L groups. These disturbances may be related to cardiac developmental and functional defects in the larvae. The activity of Na+/K+-ATPase and Ca2+-ATPase was significantly increased in zebrafish embryos exposed to 500 ng/L metalaxyl, and the mRNA levels of genes related to ATPase (atp2a11, atp1b2b, and atp1a3b) (in the 50 and 500 ng/L groups) and calcium channels (cacna1ab) (in the 500 ng/L group) were significantly downregulated; these changes might be associated with heart arrhythmia and functional failure

Impact of COVID-19 on iot adoption in healthcare, smart homes, smart buildings, smart cities, transportation and industrial IoT

COVID-19 has disrupted normal life and has enforced a substantial change in the policies, priorities and activities of individuals, organisations and governments. These changes are proving to be a catalyst for technology and innovation. In this paper, we discuss the pandemic's potential impact on the adoption of the Internet of Things (IoT) in various broad sectors namely healthcare, smart homes, smart buildings, smart cities, transportation and industrial IoT. Our perspective and forecast of this impact on IoT adoption is based on a thorough research literature review, a careful examination of reports from leading consulting firms and interactions with several industry experts. For each of these sectors, we also provide the details of notable IoT initiatives taken in wake of COVID-19. We also highlight the challenges that need to be addressed and important research directions that will facilitate accelerated IoT adoption.Comment: This is the version accepted at Sensors 202