Publications by authors named "Xuemin Cheng"

62 Publications

Description method with automatically configurable Gaussian radial basis function for complex freeform surface.

Opt Express 2021 May;29(11):16804-16819

The description of deformable mirror (DM) surface, which is usually a complex freeform surface, affects the measurement speed and accuracy in a real-time interferometric measurement system with a DM as the dynamic compensator. We propose an accurate and fast description method with automatically configurable Gaussian radial basis function. The distribution and shape factors of GRBFs are related to the complexity of the surface with sufficient flexibility to improve the accuracy, and the fitting results are automatically obtained using a traversal optimization algorithm, which can improve the fitting speed by reducing the number of time-consuming calculations. The feasibility is verified by numerical and practical experiment.
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http://dx.doi.org/10.1364/OE.426130DOI Listing
May 2021

Resveratrol improved hippocampal neurogenesis following lead exposure in rats through activation of SIRT1 signaling.

Environ Toxicol 2021 May 12. Epub 2021 May 12.

Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, China.

Lead (Pb) poses a potential environmental risk factor for cognitive dysfunction during early life and childhood. Resveratrol is considered a promising antioxidant with respect to the prevention of cognitive deficits and act as a potent SIRT1 agonist. Here in, this study aims to investigate the profile of neurogenesis markers following Pb exposure and to determine the regulatory role of resveratrol in this process. We confirmed firstly the protective effects of resveratrol against Pb-induced impairments of hippocampal neurogenesis in Male SD rats. Pb exposure early in life caused the altered expression of Ki-67, NeuN, caspase-3 and SIRT1signaling, thereby resulting in spatial cognitive impairment of adolescent rats. As expected, resveratrol reduced cognitive damage and promoted neurogenesis in Pb-induced injury by regulation of SIRT1 pathway. Collectively, our study establishes the efficacy of resveratrol as a neuroprotective agent and providesa strong rationale for further studies on SIRT1-mediated mechanisms of neuroprotective functions.
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http://dx.doi.org/10.1002/tox.23162DOI Listing
May 2021

Synthetic system design method for off-axis stabilized zoom systems with a high zoom ratio.

Opt Express 2021 Mar;29(7):10592-10612

Stabilized zoom systems possess the advantages such as the simplified system layout, improved system stability, enhanced imaging performance, and a high zoom speed. The complex system design to achieve high performances requires calculations or investigations of the initial system for optimization and improvements, and thus, specific design techniques are pursued. In this study, we propose an automatic optical design scheme of synthetic characteristics for the off-axis stabilized zoom systems, which using focal length variable (FLV) opto-electronic elements and with a high zoom ratio. The study aims at evaluating and synthetically achieving the zooming properties and the image quality balance of entire focus imaging. The multi-element stabilized zoom systems are characterized using the Gaussian brackets expressions and their optimal solution ranges for high zoom ratios are deduced to achieve non-defocusing imaging in specific stroke ranges of FLV elements. Then considering the analytical characterization of the off-axis-induced primary aberrations at multi-conjugate positions, we use a conic surface to deduce the basic expression of the nodal aberration. Thereby the nonlinear global merit function is established with a semi-empirical mathematical model based on nodal aberration theory and nonlinear zoom equation for maintaining the stability of focal length and image plane drift. And the theory of Pareto Optimality is employed in the process of verifying the superiority of the solutions. Finally, a series of solutions for a high zoom ratio and aberration compensation are implemented and the optimal configurations with conical surfaces for an off-axis stabilized zoom system are obtained.
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http://dx.doi.org/10.1364/OE.420182DOI Listing
March 2021

Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility.

BMC Public Health 2020 Nov 4;20(1):1657. Epub 2020 Nov 4.

Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.

Background: The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children's intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ).

Methods: We recruited 633 local children aged 7-13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven's Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ.

Results: The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (β = - 4.965, 95% CI: - 9.198, - 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children's IQ scores (95% CI: - 19.2, - 3.5, P = 0.005).

Conclusions: Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.
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http://dx.doi.org/10.1186/s12889-020-09765-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640398PMC
November 2020

Exploring Aldol Reactions on DNA and Applications to Produce Diverse Structures: An Example of Expanding Chemical Space of DNA-Encoded Compounds by Diversity-Oriented Synthesis.

Chem Asian J 2020 Dec 6;15(23):4033-4037. Epub 2020 Nov 6.

HitGen Inc. Building 6, No 8 Huigu 1st East Road, Tianfu International Bio-Town, Shuangliu District, Chengdu, 610200, Sichuan, P. R. China.

A DNA-encoded chemical library (DECL) is built with combinatorial chemistry, which works by bringing chemical fragments together to generate diverse structures. However, chemical diversity of DNA-encoded chemical libraries is often limited by DNA compatible synthetic reactions. This report shows a conceptual strategy to expand chemical space of DNA-encoded chemical libraries by incorporation of diversity-oriented synthesis in DECL synthesis. We developed Aldol reactions on DNA in a combinatorial way. After obtaining DNA-tagged α, β-unsaturated ketones which represent important chemical intermediates, many distinct structures with skeletal diversities are achieved by diversity-oriented synthesis.
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http://dx.doi.org/10.1002/asia.202001105DOI Listing
December 2020

Characterization of Specific -α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.

ACS Med Chem Lett 2020 Jun 10;11(6):1175-1184. Epub 2020 Apr 10.

Worldwide Research and Development, Pfizer Inc., 10770 Science Center Drive, San Diego, California 92121, United States.

Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds ( and ) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor were also evaluated to study the binding mode observed in the cocrystal structures.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294708PMC
June 2020

Method for Training Convolutional Neural Networks for In Situ Plankton Image Recognition and Classification Based on the Mechanisms of the Human Eye.

Sensors (Basel) 2020 May 2;20(9). Epub 2020 May 2.

School of Optics and Photonics, Beijing Institute of Technology, Beijing 100081, China.

In this study, we propose a method for training convolutional neural networks to make them identify and classify images with higher classification accuracy. By combining the Cartesian and polar coordinate systems when describing the images, the method of recognition and classification for plankton images is discussed. The optimized classification and recognition networks are constructed. They are available for in situ plankton images, exploiting the advantages of both coordinate systems in the network training process. Fusing the two types of vectors and using them as the input for conventional machine learning models for classification, support vector machines (SVMs) are selected as the classifiers to combine these two features of vectors, coming from different image coordinate descriptions. The accuracy of the proposed model was markedly higher than those of the initial classical convolutional neural networks when using the in situ plankton image data, with the increases in classification accuracy and recall rate being 5.3% and 5.1% respectively. In addition, the proposed training method can improve the classification performance considerably when used on the public CIFAR-10 dataset.
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http://dx.doi.org/10.3390/s20092592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248961PMC
May 2020

Fluoride exposure and CALCA methylation is associated with the bone mineral density of Chinese women.

Chemosphere 2020 Aug 29;253:126616. Epub 2020 Mar 29.

Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, China; Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, China. Electronic address:

Excessive exposure to fluoride has been reported to affect bone mineral density (BMD). CALCA expression plays a critical part in bone formation. However, the role of CALCA in the association between fluoride and BMD is not known. We conducted a cross-sectional study and recruited 722 women in rural areas of Henan Province, China, to assess the relationship between fluoride exposure, CALCA methylation, and BMD. Urinary levels of fluoride, CALCA methylation, and BMD were measured by a fluoride ion-selective electrode, standalone ultrasound bone densitometer, and quantitative methylation-specific polymerases chain reaction, respectively. The association among fluoride exposure, CALCA methylation, and BMD was age-specific. Specifically, BMD was negatively correlated with methylation (β: -0.008; 95% CI: -0.016, 0.000) and fluoride exposure (β: -0.063; 95% CI: -0.129, -0.002) in women over 45 years and 50-54 years of age, respectively, whereas methylation was positively correlated with fluoride exposure (β: 4.953; 95% CI: 1.162, 8.743) in women aged 40-44 years. Besides, increased BMD in women aged 45-49 years induced by the interactive effect of the highest methylation of CALCA exon 1 (tertile 3) and fluoride exposure was observed (P for interaction < 0.05). Our findings suggest an age-specific association between exposure to excessive fluoride, CALCA methylation, and BMD in a rural population of women in China. Notably, the susceptibility of BMD to fluoride exposure may be modified by CALCA methylation.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126616DOI Listing
August 2020

Association between fluoride exposure and behavioural outcomes of school-age children: a pilot study in China.

Int J Environ Health Res 2020 Apr 13:1-10. Epub 2020 Apr 13.

Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China.

To assess the association between fluoride exposure and children's behavioural outcomes, we recruited 325 resident school-age children (7-13 years old) lived in Tongxu County of Henan Province in China. We measured urinary fluoride (UF) concentrations using the ion-selective electrode method. Children's behavioural outcomes were assessed by Conners' Parent Rating Scale-Revised, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and ADHD index. It turned out that each 1.0 mg/L increment in UF concentration corresponded with an elevation in the psychosomatic problem score of 4.01 (95% : 2.74, 5.28) and a 97% (= 1.97, 95% : 1.19, 3.27) increase in the prevalence of psychosomatic problems after adjusting for potential influencing factors. The sensitivity analysis results were consistent with those observed in our preliminary analysis. Our study suggests that fluoride exposure is positively related to the behavioural problem in school-age children, psychosomatic problem in particular.
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http://dx.doi.org/10.1080/09603123.2020.1747601DOI Listing
April 2020

Dynamic Deformation Measurement of Specular Surface with Deflectometry and Speckle Digital Image Correlation.

Sensors (Basel) 2020 Feb 26;20(5). Epub 2020 Feb 26.

Beijing Key Lab. for Precision Optoelectronic Measurement Instrument and Technology, School of Optics and Photonics, Beijing Institute of Technology, Beijing 100081, China.

The deformation measurement of a specular surface is of great importance during the quality inspection and installation of optical elements or wafers, especially those with large apertures. We propose a deflectometry method with speckle digital image correlation (DeSDIC) to realize the dynamic and high-accuracy measurement of the deformation on specular surfaces, with a simple system structure and robustness to noises and environmental vibrations. Random speckle pattern displayed on liquid crystal display is reflected by the original surface under test (SUT), and the distorted pattern is recorded by a camera. This originally distorted pattern is taken as the reference image, and the patterns captured afterwards are digitally correlated with the reference image to calculate the gradient change and deformation of the SUT. The theoretical relationships and an experimental one-step calibration scheme are proposed. Both static and dynamic deformations of a deformable mirror were experimentally measured to demonstrate the feasibility and accuracy of DeSDIC, which is comparable to phase-measuring deflectometry and interferometry.
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http://dx.doi.org/10.3390/s20051278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085654PMC
February 2020

The independent risks and specific biomarker of breast cancer-related ischemic stroke.

Int J Neurosci 2021 Feb 2;131(2):135-143. Epub 2020 Mar 2.

Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, Guangxi, China.

Aim: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS).

Methods: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index.

Results: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all < 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003;  = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008;  = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015;  = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479;  = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 10/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity.

Conclusions: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.
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http://dx.doi.org/10.1080/00207454.2020.1733562DOI Listing
February 2021

Disruption of synaptic expression pattern and age-related DNA oxidation in a neuronal model of lead-induced toxicity.

Environ Toxicol Pharmacol 2020 May 3;76:103350. Epub 2020 Feb 3.

College of Public Health, Zhengzhou University, Zhengzhou, PR China. Electronic address:

Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (proBDNF) increased, while that of mature BDNF (mBDNF), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of BACE1 protein and tau phosphorylation level in PFC and hippocampus increased, APP mRNAs in PFC and prolonged induction of BACE1 in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.
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http://dx.doi.org/10.1016/j.etap.2020.103350DOI Listing
May 2020

Exploring the Lower Limit of Individual DNA-Encoded Library Molecules in Selection.

SLAS Discov 2020 Jun 20;25(5):523-529. Epub 2019 Dec 20.

Lead Generation Unit, HitGen Inc., Shuangliu District, Chengdu, China.

DNA-encoded library (DEL) technology has been used as an ultra-high-throughput screening approach for hit identification of drug targets. This process is an affinity-based selection and requires incubation of DEL molecules with the target. Currently, in most reported cases, the input (i.e., the copy number) of individual DEL molecules varies from 10 to 10. With the ever-increasing DEL size and screening cost, lowering the input of DEL molecules while maintaining an appropriate signal-to-noise ratio in a selection is of paramount importance. In this article, we varied the input of DEL ranging from 10 to 10 in selections with two different protein targets to explore the lower limit of DEL molecule input. The results could facilitate the optimization of the DEL selection process and reduce costs related to library consumption.
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http://dx.doi.org/10.1177/2472555219893949DOI Listing
June 2020

Epigenetic modification of H3K4 and oxidative stress are involved in MC-LR-induced apoptosis in testicular cells of SD rats.

Environ Toxicol 2020 Feb 5;35(2):277-291. Epub 2019 Nov 5.

College of Public Health, Zhengzhou University, Zhengzhou, China.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide, produced by aquatic cyanobacteria such as microcystis, with strong reproductive toxicity which poses greater threat to the reproductive abilities of humans and animals. By exploring the role of trimethylation of histone H3 at lysine 4 (H3K4me3) and the role of oxidative stress in MC-LR-induced apoptosis in testicular Sertoli cells in Sprague-Dawley (SD) rats, this study indicated that MC-LR increased the expression levels of apoptosis-related genes by raising the levels of H3K4me3. 5'-Deoxy-5'-methylthioadenosine (MTA), the inhibitor of H3K4me3, reduced apoptosis, indicating for the first time that epigenetic modification is closely related to the testicular reproductive toxicity induced by MC-LR. MC-LR also induced oxidative stress by stimulating the generation of reactive oxygen species (ROS), and subsequently triggering mitochondria-mediated apoptotic pathway by decreasing mitochondrial membrane potential and increasing the levels of Bax, Bcl-2, Caspase-3, and so on. MC-LR-induced apoptosis of testicular cells could be decreased after pretreatment with oxidative stress inhibitor N-acetyl-cysteine (NAC). Furthermore, the pathological damage to mitochondria and testes were observed in SD rats. These results show that MC-LR can induce apoptosis by raising the levels of H3K4me3, and pretreatment with MTA can ameliorate the MC-LR-induced apoptosis of cocultured cells by lowering the levels of H3K4me3. Furthermore, NAC has a protective effect on MC-LR-induced apoptosis of testicular cells in SD rats by inhibiting the oxidative stress.
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http://dx.doi.org/10.1002/tox.22865DOI Listing
February 2020

Histone acetylation plays an important role in MC-LR-induced apoptosis and cycle disorder in SD rat testicular cells.

Chemosphere 2020 Feb 12;241:125073. Epub 2019 Oct 12.

College of Public Health, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:

Microcystin-leucine arginine (MC-LR) is a variant of microcystins (MCs), which poses a serious threat to the reproductive system. Histone acetylation modification can regulate the expressions of apoptosis-related genes. However the mechanisms of histone acetylation involving MC-LR-induced apoptosis were not understood. This study investigated the change of histone acetylation and its role in apoptosis and cell cycle arrest induced by MC-LR. MC-LR enhanced the activity of histone deacetylase (HDAC), decreased the activity of histone acetylase (HAT), up-regulated the expression of HDAC1, and down-regulated the expressions of Ac-H3 and Ac-H4 in vitro and vivo. Meanwhile, MC-LR induced testicular tissue injury and increased the expressions of apoptosis-related genes, such as Bax, Caspase3 and Caspase8, ultimately causing cells apoptosis in testicular tissues. Furthermore, MC-LR also induced cell cycle arrest in S phase, increased the expression of P21, and inhibited the expressions of cyclinD1, cyclinE1, CDK2 and E2F1. Importantly, HDAC inhibitor Trichostatin A (TSA) could ameliorate MC-LR-induced apoptosis and cell cycle arrest by reverse-regulating the expressions of these proteins. These results indicated that MC-LR could activate the mitochondrial apoptotic pathway and disorder the cell cycle pathway to induce the cell apoptosis by enhancing HDAC activity and reducing histone acetylation of normal testicular cells in SD rats. Hence, histone acetylation has a vital function in MC-LR-induced apoptosis in SD rat testicular cells, which provides a new insight on the reproductive toxicity of male induced by MC-LR.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125073DOI Listing
February 2020

Enhanced convolutional neural network for plankton identification and enumeration.

PLoS One 2019 10;14(7):e0219570. Epub 2019 Jul 10.

Department of Oceanography and Coastal Sciences, Louisiana State University, Baton Rouge, Louisiana, United States of America.

Despite the rapid increase in the number and applications of plankton imaging systems in marine science, processing large numbers of images remains a major challenge due to large variations in image content and quality in different marine environments. We constructed an automatic plankton image recognition and enumeration system using an enhanced Convolutional Neural Network (CNN) and examined the performance of different network structures on automatic plankton image classification. The procedure started with an adaptive thresholding approach to extract Region of Interest (ROIs) from in situ plankton images, followed by a procedure to suppress the background noise and enhance target features for each extracted ROI. The enhanced ROIs were classified into seven categories by a pre-trained classifier which was a combination of a CNN and a Support Vector Machine (SVM). The CNN was selected to improve feature description and the SVM was utilized to improve classification accuracy. A series of comparison experiments were then conducted to test the effectiveness of the pre-trained classifier including the combination of CNN and SVM versus CNN alone, and the performance of different CNN models. Compared to CNN model alone, the combination of CNN and SVM increased classification accuracy and recall rate by 7.13% and 6.41%, respectively. Among the selected CNN models, the ResNet50 performed the best with accuracy and recall at 94.52% and 94.13% respectively. The present study demonstrates that deep learning technique can improve plankton image recognition and that the results can provide useful information on the selection of different CNN models for plankton recognition. The proposed algorithm could be generally applied to images acquired from different imaging systems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219570PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619811PMC
February 2020

p53-Dependent pathway and the opening of mPTP mediate the apoptosis of co-cultured Sertoli-germ cells induced by microcystin-LR.

Environ Toxicol 2019 Oct 3;34(10):1074-1084. Epub 2019 Jun 3.

College of Public Health, Zhengzhou University, Zhengzhou, China.

Microcystin-LR (MC-LR), a potent endotoxin, can induce reproductive toxicity. In order to investigate the role and mechanisms of apoptosis (p53-dependent and mitochondrial pathways) of germ cells induced by MC-LR, the co-cultured primary Sertoli-germ cells from Sprague-Dawley rats were used for the experiments. Expression levels of proteins, genes, and mitochondrial membrane potential (MMP) were obtained after exposing co-cultured Sertoli-germ cells to MC-LR with or without the addition of the p53 inhibitor, pifithrin-α (PFT-α), and MMP inhibitor, cyclosporin A (CsA). Results indicated that MC-LR could activate p53-dependent pathway-associated proteins in Sertoli-germ cells, leading to a decrease in MMP (indicating the opening of mitochondrial permeability transition pore [mPTP] and the release of Cytochrome-c [Cyt-c]) from the mitochondria into the cytoplasm and eventually the induction of apoptosis. PFT-α inhibited the expression ofp53, ameliorated the MMP of the co-cultured Sertoli-germ cells, and prevented the release of Cyt-c from the mitochondria into the cytoplasm, which reduces the occurrence of apoptosis. Similarly, the decreased release of Cyt-c from the mitochondria into the cytoplasm and the declined level of apoptosis in Sertoli-germ cells induced by MC-LR were observed after the addition of CsA. These results indicated that the apoptosis of the co-cultured Sertoli-germ cells induced by MC-LR was mediated by the p53-dependent pathway, with the involvement of the opening of mPTP.
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http://dx.doi.org/10.1002/tox.22808DOI Listing
October 2019

Trends of SHBG and ABP levels in male farmers: Influences of environmental fluoride exposure and ESR alpha gene polymorphisms.

Ecotoxicol Environ Saf 2019 May 21;172:40-44. Epub 2019 Jan 21.

Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address:

A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESRα) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen binding protein (ABP) of male farmers has not been detailed. Here, we conducted a cross-sectional study including 348 male farmers with different fluoride exposure levels from drinking water in Henan province of China to explore effects of fluoride exposure and ESRα genetic variation on serum SHBG and ABP levels. We found serum SHBG levels in male farmers from the high exposure group to be lower than those of the low exposure group. We also found that concentrations of SHBG affected ABP levels. Furthermore, fluoride exposure and single nucleotide polymorphisms at the XbaI and rs3798577 loci of the ESRα gene affected serum ABP levels. Our findings suggest that chronic fluoride exposure from drinking water is associated with alterations of serum SHBG and ABP concentrations in local male farmers and that the effect of fluoride exposure on ABP levels vary depending on ESRα gene polymorphisms.
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http://dx.doi.org/10.1016/j.ecoenv.2019.01.062DOI Listing
May 2019

N-acetylcysteine alleviates fluoride-induced testicular apoptosis by modulating IRE1α/JNK signaling and nuclear Nrf2 activation.

Reprod Toxicol 2019 03 8;84:98-107. Epub 2019 Jan 8.

College of Public Health, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, 450001, Henan, PR China. Electronic address:

We previously investigated excessive fluoride exposure elicited intracellular endoplasmic reticulum (ER) stress and led to Sertoli cells dysfunction in vitro. However, the mechanisms underlying fluoride-mediated male reproductive damage in vivo remain largely unknown. Considerable evidence has now revealed ER stress is closely linked with testicular oxidative damage. Hence, we aimed to explore whether ER stress signaling was involved in the testicular protective effects of antioxidant N-acetylcysteine (NAC) against testicular apoptosis induced by fluoride. Male SD rats were oral gavaged with sodium fluoride (NaF) for 7 weeks to induce fluorosis. The animals were pretreatment with or without NAC (150 mg/Bw•d). Our results demonstrated that sub-chronic NaF exposure triggered testicular apoptosis and sex hormonal disturbance in pituitary-testicular (PT) axis, promoted oxidative stress and the expression of ER stress mediators. Antioxidant NAC, however, prevented NaF-induced testicular apoptosis accompanied by activating Nrf2-mediated antioxidant potential. Simultaneously, NAC pretreatment downregulated XBP1 splicing, reduced JNK phosphorylation and further blocked cleavage of caspase-3, all these might contribute to the inhibition of testicular cell apoptosis. Collectively, the present results suggested that prolonged administration of NAC preserved testicular function and normalized sex hormonal disruption induced by NaF via the inhibition of Nrf2-associated oxidative damage and Ire1α-JNK-mediated apoptosis in rat testis.
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http://dx.doi.org/10.1016/j.reprotox.2019.01.001DOI Listing
March 2019

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications.

Environ Toxicol Pharmacol 2019 Feb 19;66:14-23. Epub 2018 Dec 19.

College of Public Health, Zhengzhou University, Zhengzhou, PR China. Electronic address:

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.
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http://dx.doi.org/10.1016/j.etap.2018.12.015DOI Listing
February 2019

MC-LR induces dysregulation of iron homeostasis by inhibiting hepcidin expression: A preliminary study.

Chemosphere 2018 Dec 27;212:572-584. Epub 2018 Aug 27.

Department of Chemistry and Biochemistry, St Mary's University, San Antonio, TX, USA.

The liver is an important iron storage site and a primary MC-LR target. C57BL/6 and Hfe mice were used to investigate effects and mechanisms of MC-LR on systematic iron homeostasis. Body weight, tissue iron content, hematological and serological indexes, and histopathological were evaluated. Ultrastructure and iron metabolism-related genes and proteins were analyzed. MC-LR induced dose-dependent increases in red blood cells, hemoglobin, and hematocrit. In contrast MC-LR-induced dose-dependent decreases in mean corpuscular volume, hemoglobin, and hemoglobin concentration were observed both C57BL/6 and Hfe mice. In both mouse species, serological indexes increased. Aggravated liver and spleen iron were observed in C57BL/6 mice, consistent with Perls' Prussian blue staining. However, an opposite trend was observed in Hfe mice. C57BL/6 mice had lower Hamp1 (Hepcidn), Bmp6, Il-6, and Tmprss6. Significant increased Hjv, Hif-1α and Hif-2α were observed in both C57BL/6 and Hfe mice. MC-LR-induced pathological lesions were dose-dependent increase in C57BL/6 mice. More severe pathological injuries in MC-LR groups (25 μg/kg) were observed in Hfe mice than in C57BL/6 mice. In Hfe mice, upon exposure to 25 μg/kg MC-LR, mitochondrial membranes were damaged and mitochondrial counts increased with significant swelling. These results indicated that MC-LR can induce the accumulation of iron in C57BL/6 mice with the occurrence of anemia, similar to thalassemia. Moreover, dysregulation of iron homeostasis may be due to MC-LR-induced Hamp1 downregulation, possibly mediated by hypoxia or the IL6-STAT3 and BMP-SMAD signaling pathways.
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http://dx.doi.org/10.1016/j.chemosphere.2018.08.077DOI Listing
December 2018

Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries.

Front Physiol 2018 6;9:1058. Epub 2018 Aug 6.

Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, China.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. However, little is known about its biotoxicity to the female reproductive system. The present study investigates unexplored molecular pathways by which oxidative stress acts on MC-LR-induced endoplasmic reticulum stress (ERs) and autophagy. In the present study, immortalized murine ovarian granular cells (KK-1 cells) were exposed to 8.5, 17, and 34 μg/mL (IC) of MC-LR with or without -acetyl-l-cysteine (NAC, 10 mM) for 24 h, and C57BL/6 mice were treated with 12.5, 25.0, and 40.0 μg/kg⋅bw of MC-LR with or without NAC (200 mg/kg⋅bw) for 14 days. The results revealed that MC-LR could induce cells apoptosis and morphologic changes in ovarian tissues, induce oxidative stress by stimulating the generation of reactive oxygen species (ROS), destroying antioxidant capacity, and subsequently trigger ERs and autophagy by inducing the hyper-expression of ATG12, ATG5, ATG16, EIF2α (phosphorylated at S51), CHOP, XBP1, GRP78, Beclin1, and PERK (Thr980). Furthermore, NAC pretreatment partly inhibited MC-LR-induced ERs and autophagy the PERK/ATG12 and XBP1/Beclin1 pathways. These results suggest that oxidative stress mediated MC-LR-induced ERs and autophagy in KK-1 cells and C57BL/6 mice ovaries. Therefore, oxidative stress plays an important role in female toxicity induced by MC-LR.
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http://dx.doi.org/10.3389/fphys.2018.01058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090159PMC
August 2018

Resveratrol Ameliorates Microcystin-LR-Induced Testis Germ Cell Apoptosis in Rats via SIRT1 Signaling Pathway Activation.

Toxins (Basel) 2018 06 9;10(6). Epub 2018 Jun 9.

College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. Studies performed in rat Sertoli cells and Chinese hamster ovary cells have demonstrated typical apoptosis after MC-LR exposure. However, little is known on how to protect against the reproductive toxicity induced by MC-LR. The present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (RES) on the co-culture of Sertoli⁻germ cells and rat testes. The results demonstrated that MC-LR treatment inhibited the proliferation of Sertoli⁻germ cells and induced apoptosis. Furthermore, sirtuin 1 (SIRT1) and Bcl-2 were inhibited, while p53 and Ku70 acetylation, Bax expression, and cleaved caspase-3 were upregulated by MC-LR. However, RES pretreatment ameliorated MC-LR-induced apoptosis and SIRT1 inhibition, and downregulated the MC-LR-induced increase in p53 and Ku70 acetylation, Bax expression, and caspase-3 activation. In addition, RES reversed the MC-LR-mediated reduction in Ku70 binding to Bax. The present study indicated that the administration of RES could ameliorate MC-LR-induced Sertoli⁻germ cell apoptosis and protect against reproductive toxicity in rats by stimulating the SIRT1/p53 pathway, suppressing p53 and Ku70 acetylation and enhancing the binding of Ku70 to Bax.
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http://dx.doi.org/10.3390/toxins10060235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024601PMC
June 2018

Bacterial community structure and abundances of antibiotic resistance genes in heavy metals contaminated agricultural soil.

Environ Sci Pollut Res Int 2018 Apr 22;25(10):9547-9555. Epub 2018 Jan 22.

College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.

Soil contamination with heavy metals is a worldwide problem especially in China. The interrelation of soil bacterial community structure, antibiotic resistance genes, and heavy metal contamination in soil is still unclear. Here, seven agricultural areas (G1-G7) with heavy metal contamination were sampled with different distances (741 to 2556 m) to the factory. Denaturing gradient gel electrophoresis (DGGE) and Shannon index were used to analyze bacterial community diversity. Real-time fluorescence quantitative PCR was used to detect the relative abundance of ARGs sul1, sul2, tetA, tetM, tetW, one mobile genetic elements (MGE) inti1. Results showed that all samples were polluted by Cadmium (Cd), and some of them were polluted by lead (Pb), mercury (Hg), arsenic (As), copper (Cu), and zinc (Zn). DGGE showed that the most abundant bacterial species were found in G7 with the lightest heavy metal contamination. The results of the principal component analysis and clustering analysis both showed that G7 could not be classified with other samples. The relative abundance of sul1 was correlated with Cu, Zn concentration. Gene sul2 are positively related with total phosphorus, and tetM was associated with organic matter. Total gene abundances and relative abundance of inti1 both correlated with organic matter. Redundancy analysis showed that Zn and sul2 were significantly related with bacterial community structure. Together, our results indicate a complex linkage between soil heavy metal concentration, bacterial community composition, and some global disseminated ARG abundance.
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http://dx.doi.org/10.1007/s11356-018-1251-8DOI Listing
April 2018

Error analysis of the calibration of a dual-rotating-retarder Mueller matrix polarimeter.

Appl Opt 2017 Sep;56(25):7067-7074

We previously developed a Mueller matrix microscope by combining a dual-rotating-retarder device with a commercial microscope, which holds promise for pathologic diagnosis applications. In practical applications, the signals to be measured are sensitive to systematic errors, and the measurement accuracy and the instrument calibration affect the capacity to characterize the data. In conventional calibration, the initial positions of the rotating devices are constrained, causing calibration instability. To improve the calibration, we examine the mathematical model of the calibration process using previous studies, and derive a calibration algorithm with reduced error magnification. Our experimental results show the proposed algorithm improves calibration accuracy, and provides more robust results.
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http://dx.doi.org/10.1364/AO.56.007067DOI Listing
September 2017

Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?

Chemosphere 2017 Dec 8;188:525-531. Epub 2017 Sep 8.

Department of Environmental Health, Zhengzhou University, Zhengzhou, Henan, 450001, China. Electronic address:

The occurrence of endemic fluorosis is derived from high fluoride levels in drinking water and industrial fumes or dust. Reproductive disruption is also a major harm caused by fluoride exposure besides dental and skeletal lesions. However, few studies focus on the mechanism of fluoride exposure on male reproductive function, especially the possible interaction of fluoride exposure and gene polymorphism on male reproductive hormones. Therefore, we conducted a cross-sectional study in rural areas of Henan province in China to explore the interaction between the estrogen receptor alpha (ERα) gene and fluoride exposure on reproductive hormone levels in male farmers living in the endemic fluorosis villages. The results showed that fluoride exposure significantly increased the serum level of estradiol in the hypothalamic-pituitary-testicular (HPT) axis in male farmers. Moreover, the observations indicated that fluoride exposure and genetic markers had an interaction on serum concentration of follicle-stimulating hormone and estradiol, and the interaction among different loci of the ERα gene could impact the serum testosterone level. Findings in the present work suggest that chronic fluoride exposure in drinking water could modulate the levels of reproductive hormones in males living in endemic fluorosis areas, and the interaction between fluoride exposure and ERα polymorphisms might affect the serum levels of hormones in the HPT axis in male farmers.
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http://dx.doi.org/10.1016/j.chemosphere.2017.08.166DOI Listing
December 2017

Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations.

Front Physiol 2017 29;8:446. Epub 2017 Jun 29.

College of Public Health, Zhengzhou UniversityZhengzhou, China.

Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given Pb(Ac) treatment or deionized HO for 12 weeks, and subjected to resveratrol gavage at the dose of 50 mg/kgBw•d or vehicle after Pb exposure. Results from biochemical analysis and immunohistofluorescence showed that Pb induced oxidative DNA damage and decreased cortical antioxidant biomarker. As expected, these abnormalities were improved by resveratrol treatment. Morris water maze test, Western blotting, immunohistofluorescence staining and RT-qPCR indicated that resveratrol ameliorated spatial learning and memory deficits with alterations in hippocampal BDNF-TrkB signaling, promoted nuclear localization and phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and PGC-1α involving in modulation of antioxidant response in Pb-exposed mice. Our results support the hypothesis that resveratrol could attenuate Pb-induced cognitive impairment which was associated with activating SIRT1 via modulation of oxidative stress. Additionally, resveratrol also repressed the Pb-induce amyloidogenic processing with resultant decline in cortical Aβ. Noteworthy, such effects were not mediated by resveratrol treatment alone. These findings emphasize the potential of SIRT1 activator as an efficacious dietary intervention to downgrade the Pb-induced neurotoxic lesion.
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http://dx.doi.org/10.3389/fphys.2017.00446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489681PMC
June 2017

Do Environmental Fluoride Exposure and ESRα Genetic Variation Modulate Methylation Modification on Bone Changes in Chinese Farmers?

Chem Res Toxicol 2017 06 23;30(6):1302-1308. Epub 2017 May 23.

Department of Occupational and Environmental Health, School of Public Health, Zhengzhou University , Zhengzhou, Henan 450001, People's Republic of China.

Although increasing evidence suggests that estrogen receptor α (ESRα) genetic variation could modify bone damage caused by environmental fluoride exposure, little is known about epigenetic mechanisms in relation to bone changes. A case-control study was conducted among farmers aged 18-55 years in Henan Province, China. X-ray was used to detect bone changes. Methylation status was determined by methylation-specific PCR. Genotypes were identified by Taqman probe and real-time PCR. In this study, we found that methylation status in the promoter region of the ESRα gene was lower in bone change cases than that in controls, which was only observed in male farmers after stratification by gender. Furthermore, methylation level was negatively associated with the urinary fluoride concentration in male farmers. No significant association was found between the distribution of ESRα rs2941740 genotypes and the risk of bone changes. Multivariate logistic regression analysis showed that after adjusting for age and gender, increased serum calcium and methylation status were protective factors for bone changes. No interaction effect was observed between fluoride exposure and ESRα rs2941740 polymorphism on bone changes. In conclusion, the current work suggests that bone changes are associated with methylation status, which might be modulated by fluoride exposure in male farmers. Methylation status and bone changes were not modified by ESRα gene rs2941740 polymorphism in the promoter region.
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http://dx.doi.org/10.1021/acs.chemrestox.7b00047DOI Listing
June 2017

Does Fluoride Affect Serum Testosterone and Androgen Binding Protein with Age-Specificity? A Population-Based Cross-Sectional Study in Chinese Male Farmers.

Biol Trace Elem Res 2016 Dec 6;174(2):294-299. Epub 2016 May 6.

Department of Occupational and Environmental Health, Institute of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.

Many studies have demonstrated that exposure to excess fluoride was associated with a variety of diseases. Little is known about the variation of testosterone (T) levels caused by fluoride exposure. The aim of this study is to explore the association of fluoride exposure and age with serum T and androgen-binding protein (ABP) levels in male farmers. A cross-sectional study was conducted in a county of Henan Province, China, including high fluoride exposure from drinking water villages and control villages. Male farmers aged 18-55 years old who lived in these villages were recruited by cluster sampling and divided into a higher fluoride exposure group (HFG) and a lower fluoride exposure group (LFG) according to the level of urinary fluoride. Levels of T and ABP in serum were measured using chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) respectively. Markedly lower T levels were observed in male farmers from the HFG than in those from the LFG (t = 2.496, P < 0.05). Furthermore, younger farmers, 18-29 and 30-39 years old, may be the most likely to have lower T levels when exposed to fluoride (P < 0.05). No significant differences were observed in serum ABP levels in all male farmers between the two groups with different fluoride exposure. These results supported that excess fluoride exposure decreased serum T levels of male farmers with age-specificity.
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http://dx.doi.org/10.1007/s12011-016-0726-zDOI Listing
December 2016

Analysis of the Effects of Thermal Environment on Optical Systems for Navigation Guidance and Control in Supersonic Aircraft Based on Empirical Equations.

Sensors (Basel) 2016 Oct 17;16(10). Epub 2016 Oct 17.

Beijing Key Lab for Precision Optoelectronic Measurement Instrument and Technology, School of Optoelectronics, Beijing Institute of Technology, Beijing 100081, China.

The thermal environment is an important factor in the design of optical systems. This study investigated the thermal analysis technology of optical systems for navigation guidance and control in supersonic aircraft by developing empirical equations for the front temperature gradient and rear thermal diffusion distance, and for basic factors such as flying parameters and the structure of the optical system. Finite element analysis (FEA) was used to study the relationship between flying and front dome parameters and the system temperature field. Systematic deduction was then conducted based on the effects of the temperature field on the physical geometry and ray tracing performance of the front dome and rear optical lenses, by deriving the relational expressions between the system temperature field and the spot size and positioning precision of the rear optical lens. The optical systems used for navigation guidance and control in supersonic aircraft when the flight speed is in the range of 1-5 Ma were analysed using the derived equations. Using this new method it was possible to control the precision within 10% when considering the light spot received by the four-quadrant detector, and computation time was reduced compared with the traditional method of separately analysing the temperature field of the front dome and rear optical lens using FEA. Thus, the method can effectively increase the efficiency of parameter analysis and computation in an airborne optical system, facilitating the systematic, effective and integrated thermal analysis of airborne optical systems for navigation guidance and control.
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http://dx.doi.org/10.3390/s16101717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087504PMC
October 2016