Nanoquartz in Late Permian C1 coal and the high incidence of female lung cancer in the Pearl River Origin area: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The Pearl River Origin area, Qujing District of Yunnan Province, has one of the highest female lung cancer mortality rates in China. Smoking was excluded as a cause of the lung cancer excess because almost all women were non-smokers. Crystalline silica embedded in the soot emissions from coal combustion was found to be associated with the lung cancer risk in a geographical correlation study. Lung cancer rates tend to be higher in places where the Late Permian C1 coal is produced. Therefore, we have hypothesized the two processes: C1 coal combustion --> nanoquartz in ambient air --> lung cancer excess in non-smoking women.</p> <p>Methods/Design</p> <p>We propose to conduct a retrospective cohort study to test the hypothesis above. We will search historical records and compile an inventory of the coal mines in operation during 1930–2009. To estimate the study subjects' retrospective exposure, we will reconstruct the historical exposure scenario by burning the coal samples, collected from operating or deserted coal mines by coal geologists, in a traditional firepit of an old house. Indoor air particulate samples will be collected for nanoquartz and polycyclic aromatic hydrocarbons (PAHs) analyses. Bulk quartz content will be quantified by X-ray diffraction analysis. Size distribution of quartz will be examined by electron microscopes and by centrifugation techniques. Lifetime cumulative exposure to nanoquartz will be estimated for each subject. Using the epidemiology data, we will examine whether the use of C1 coal and the cumulative exposure to nanoquartz are associated with an elevated risk of lung cancer.</p> <p>Discussion</p> <p>The high incidence rate of lung cancer in Xuan Wei, one of the counties in the current study area, was once attributed to high indoor air concentrations of PAHs. The research results have been cited for qualitative and quantitative cancer risk assessment of PAHs by the World Health Organization and other agencies. If nanoquartz is found to be the main underlying cause of the lung cancer epidemic in the study area, cancer potency estimates for PAHs by the international agencies based on the lung cancer data in this study setting should then be updated.</p

Ergothioneine: an underrecognised dietary micronutrient required for healthy ageing?

Ergothioneine is a naturally occurring amino acid and thiol antioxidant found in high amounts in mushrooms and fermented foods. Humans and animals acquire ergothioneine from the diet through the pH-dependent activity of a membrane transporter, the large solute carrier 22A member 4 (SLC22A4), expressed on the apical membrane of the small intestine. The SLC22A4 transporter also functions in the renal reabsorption of ergothioneine in the kidney, with avid absorption and retention of ergothioneine from the diet observed in both animals and humans. Ergothioneine is capable of scavenging a diverse range of reactive oxygen and nitrogen species, has metal chelation properties, and is predicted to directly regulate nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Although not lethal, the genetic knockout of the SLC22A4 gene in multiple organisms increases susceptibility to oxidative stress, damage and inflammation; in agreement with a large body of preclinical data suggesting the physiological function of ergothioneine is as a cellular antioxidant and cytoprotectant agent. In humans, blood levels of ergothioneine decline after the age of 60 years, and lower levels of ergothioneine are associated with more rapid cognitive decline. Conversely, high plasma ergothioneine levels have been associated with significantly reduced cardiovascular mortality and overall mortality risks. In this horizon’s manuscript, we review evidence suggesting critical roles for dietary ergothioneine in healthy ageing and the prevention of cardiometabolic disease. We comment on some of the outstanding research questions in the field and consider the question of whether or not ergothioneine should be considered a conditionally essential micronutrient

Partially linear censored quantile regression

Censored regression quantile (CRQ) methods provide a powerful and flexible approach to the analysis of censored survival data when standard linear models are felt to be appropriate. In many cases however, greater flexibility is desired to go beyond the usual multiple regression paradigm. One area of common interest is that of partially linear models: one (or more) of the explanatory covariates are assumed to act on the response through a non-linear function. Here the CRQ approach of Portnoy (J Am Stat Assoc 98:1001–1012, 2003) is extended to this partially linear setting. Basic consistency results are presented. A simulation experiment and unemployment example justify the value of the partially linear approach over methods based on the Cox proportional hazards model and on methods not permitting nonlinearity

Self-assembled carbon nanoribbons with the heteroatom doping used as ultrafast charging cathodes in zinc-ion hybrid supercapacitors

Zinc-ion hybrid supercapacitors (ZHSs) are highly desirable for large-scale energy storage applications owing to the merits of high safety, low cost and ultra-long cycle life. The poor rate performance of cathodes, however, severely hinders their application. Herein, aqueous ZHSs with superior performance were fabricated by employing a series of ultrathin carbon nanobelts modified with B, N, O (CPTHB-Bx). The heteroatom doping can significantly modify the chemical behaviors of carbon frameworks, which could generate numerous active sites and accelerate the charge transport. The systematic investigation reveals that the B–N groups are active species for fast Zn-ion adsorption and desorption. As a result, the best-performed CPTHB-B2 exhibits an excellent electrochemical performance as cathodes in ZHSs, delivering a high specific capacitance of 415.3 F g−1 at 0.5 A g−1, a record high capacitance retention of 81% when increasing the current densities from 0.5 to 100 A g−1, an outstanding energy density of 131.9 W h kg−1 and an exceptionally high power density of 42.1 kW kg−1. Our work provides a new cathode design for ultrafast charging Zn-ion storage devices

Nonlinear characteristics identification of an impact oscillator with a one-sided elastic constraint

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Data availability: Data will be made available on request.Impacting systems are widely used in many engineering applications, such as self-propelled robots, energy harvesting and percussive drilling, which exhibit rich and complex nonlinear phenomena. Among these applications, predicting nonlinearities and estimating system parameters are of great interest of nonlinear dynamics research community. Backbone curve is an analytical tool that captures the frequencyamplitude dependence of nonlinear systems. In this paper, we estimate the impacting stiffness of a single-degree-of-freedom non-smooth dynamical system qualitatively by using the backbone curve. It was found that an increase of the impacting stiffness may lead to lowering the backbone curve. An adaptive differential evolution algorithm with the Metropolis criterion is proposed to identify the parameters of the impacting system quantitatively using experimental data, which are consistent with our theoretical predictions. Finally, the identified parameters are verified, and the limitations of the backbone curve are drawn. The nonlinear characteristics identification method studied in this paper could be extended to other vibro-impact systems and is potentially applicable to structural health monitoring and robotic sensing.European Union’s Horizon 202

Metal-based imaging agents: progress towards interrogating neurodegenerative disease.

Central nervous system (CNS) neurodegeneration is defined by a complex series of pathological processes that ultimately lead to death. The precise etiology of these disorders remains unknown. Recent efforts show that a mechanistic understanding of the malfunctions underpinning disease progression will prove requisite in developing new treatments and cures. Transition metals and lanthanide ions display unique characteristics (i.e., magnetism, radioactivity, and luminescence), often with biological relevance, allowing for direct application in CNS focused imaging modalities. These techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and luminescent-based imaging (LumI). In this Tutorial Review, we have aimed to highlight the various metal-based imaging techniques developed in the effort to understand the pathophysiological processes associated with neurodegeneration. Each section has been divided so as to include an introduction to the particular imaging technique in question. This is then followed by a summary of key demonstrations that have enabled visualization of a specific neuropathological biomarker. These strategies have either exploited the high binding affinity of a receptor for its corresponding biomarker or a specific molecular transformation caused by a target species, all of which produce a concomitant change in diagnostic signal. Advantages and disadvantages of each method with perspectives on the utility of molecular imaging agents for understanding the complexities of neurodegenerative disease are discussed

Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells

Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to by-pass chemoresistance in cancer cells. Therefore, we explored the potential of this approach in breast cancer cells. Cisplatin and paclitaxel induced apoptosis in a dose-dependent manner in MCF-7 (drug-sensitive) and MDA-MB-231 (drug-insensitive) cells. Furthermore, when we transiently silenced Bcl-2, both cisplatin and paclitaxel induced apoptosis more than parental cells. Dose dependent induction of apoptosis by drugs was enhanced by the pre-treatment of these cells with HA14-1, a Bcl-2 inhibitor. Although the effect of cisplatin was significant on both cell lines, the effect of paclitaxel was much less potent only in MDA-MB-231 cells. To further understand the distinct role of drugs in MDA-MB-231 cells pretreated with HA14-1, caspases and Bcl-2 family proteins were studied. The apoptotic effect of cisplatin with or without HA14-1 pre-treatment is shown to be caspase-dependent. Among pro-apoptotic Bcl-2 proteins, Bax and Puma were found to be up-regulated whereas Bcl-2 and Bcl-x(L) were down-regulated when cells were pretreated with HA14-1 followed by paclitaxel or cisplatin. Enforced Bcl-2 expression in MDA-MB-231 cells abrogated the sensitizing effect of HA14-1 in cisplatin induced apoptosis. These results suggest that the potentiating effect of HA14-1 is drug and cell type specific and may not only depend on the inhibition of Bcl-2. Importantly, alteration of other pro-apoptotic or anti-apoptotic Bcl-2 family members may dictate the apoptotic response when HA14-1 is combined with chemotherapeutic drugs

The relationship of parental longevity with the aging brain - results from UK Biobank

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordCode and data availability: upon requestA few studies report that parental longevity is associated with preserved cognition and physical function and lower risk of Alzheimer’s disease. However, data on structural neuroimaging correlates of parental longevity and its spatial distribution are limited. This study aims to examine relationships of parental longevity with regional brain structure and to explore sex differences. We identified 12,970 UK Biobank participants (mean age = 64.4, 51.5%women) with data on parental longevity, regional gray matter volumes, and white matter microstructure. Participants were categorized based on whether at least one parent lived to age 85 or older or neither parent survived to age 85. Associations of parental longevity, maternal, and paternal longevity with each neuroimaging marker of interest were examined using linear regression, adjusted for demographics, APOE e4 status, lifestyle, and cardiometabolic conditions. Compared to participants whose both parents died before 85 (43%), those with at least one parent surviving to 85 (57%) had greater volumes in hippocampus, parahippocampal gyrus, middle temporal lobe, and primary sensorimotor cortex and had lower mean diffusivity in posterior thalamic radiation and uncinate fasciculus. Associations were prominent with maternal longevity. Adjustment for cardiometabolic conditions did not affect observed associations except mean diffusivity in posterior thalamic radiation. There were no structural differences in other areas. Parental longevity is associated with preserved brain structure localized in primary sensorimotor cortex and temporal areas including hippocampus. These relationships are prominent with maternal longevity. Longitudinal studies are needed to determine whether changes in these brain structures account for the association between parental longevity and dementia.National Institute on Agin

Alleviating the non-ultralocality of coset sigma models through a generalized Faddeev-Reshetikhin procedure

The Faddeev-Reshetikhin procedure corresponds to a removal of the non-ultralocality of the classical SU(2) principal chiral model. It is realized by defining another field theory, which has the same Lax pair and equations of motion but a different Poisson structure and Hamiltonian. Following earlier work of M. Semenov-Tian-Shansky and A. Sevostyanov, we show how it is possible to alleviate in a similar way the non-ultralocality of symmetric space sigma models. The equivalence of the equations of motion holds only at the level of the Pohlmeyer reduction of these models, which corresponds to symmetric space sine-Gordon models. This work therefore shows indirectly that symmetric space sine-Gordon models, defined by a gauged Wess-Zumino-Witten action with an integrable potential, have a mild non-ultralocality. The first step needed to construct an integrable discretization of these models is performed by determining the discrete analogue of the Poisson algebra of their Lax matrices.Comment: 31 pages; v2: minor change

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure