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2.
Nat Commun ; 11(1): 706, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024836

RESUMO

The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal cell subpopulation. The Zeb1+ prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single-cell transcriptomic analysis of over 9000 mouse prostate basal cells, we confirm the existence of the Zeb1+ basal cell subset. Moreover, Zeb1+ epithelial cells can be detected in mouse and human prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.

3.
J Membr Biol ; 253(1): 43-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820013

RESUMO

Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial reactive oxygen species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the lactate dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1ß and cytotoxicity through cellular and mitochondrial Ca2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

4.
Front Hum Neurosci ; 13: 343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708758

RESUMO

Bilateral cerebral palsy (BCP) is a common movement disorder in children, which often results in lifelong motor disability. One main symptom of BCP is the limitation of hand function in everyday activities. However, the neuroanatomical basis of this prominent hand impairment is yet to discover. Recent advances mainly focus on the lesions of BCP, but the views on the atypical development of cortical parcellations are extremely lacking. Here, in our study, neuroimaging with network analysis was employed to evaluate the changes of structural covariance networks (SCNs) in BCP children. We aimed to elucidate the alteration of SCNs based on cortical thickness (CT), and to reveal the relationship of CT and hand function in the participants with BCP. SCNs were constructed using covariance between regional CT, which was acquired from T1-weighted images of 19 children with BCP and 19 demographically matched healthy controls (HCs). Compared with HCs, BCP children showed increased CT in several regions involving the bilateral areas (lateral occipital, lingual, and fusiform) and right areas (cuneus, pericalcarine, inferior temporal, middle temporal, superior temporal, and insula). Decreased CT was found in the left superior temporal and right superior parietal cortices. Global network analyses revealed significantly decreased normalized clustering and small-worldness in the BCP network. The area under the curve (AUC) of global network measures varied slightly between the BCP and HC networks. The resistance of the both SCNs to the target and random attack showed no significant difference. Also, the BCP foci (right superior temporal and subtemporal cortex) showed a significantly negative correlation between the CT and manual ability. In this work, we identified the CT-based SCNs changes in children with BCP. The abnormal topological organization of SCNs was revealed, indicating abnormal CT, incongruous development of structural wiring, destructive nodal profiles of betweenness, and moved hub distribution in BCP children. This may provide a neuroanatomical hallmark of BCP in the developing brain. Therefore, our results may not only reflect neurodevelopmental aberrations but also compensatory mechanisms.

5.
Stem Cell Res ; 40: 101571, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31520889

RESUMO

Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C > T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

6.
Data Brief ; 25: 104413, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31516933

RESUMO

The data presented in this article are related to the research article entitled "Structure-antioxidant activity relationship of active oxygen catalytic lignin and lignin-carbohydrate complex" (Jiang et al.). It supplements the article with thermostability of milled wood lignin (MWL) and alkali-oxygen lignin (AOL), main substructures of lignin in rice straw, main products and yield of nitrobenzene oxidation of lignin-carbohydrate complexes (LCCs), Fourier transform infrared spectroscopy of LCCs, radical (ABTS·) scavenging ability of lignins and signal assignment of lignins and LCCs in nuclear magnetic resonance spectra (1H, 13C, 2D HSQC NMR). The dataset is made publicly available and can be useful for extending the structural and bioactive research and critical analyses of lignin and LCC.

7.
Quant Imaging Med Surg ; 9(8): 1402-1412, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31559169

RESUMO

Background: Cerebral palsy (CP) is a major cause of chronic childhood disability worldwide, causing activity limitation as well as impairments in sensation, cognition, and communication. Leveraging biomarkers to establish individualized predictions of future treatment responses will be of great value. We aim to develop and validate a model that can be used to predict the individualized treatment response in Children with CP. Methods: A multicenter prospective cohort study will be conducted in 4 hospitals in west China. One hundred and thirty children with CP will be recruited and undergo clinical assessment using the Peabody Developmental Motor Scales, Manual Ability Classification System (MACS), Hand Assessment for Infants (HAI), Assisting Hand Assessment (AHA), and Gross Motor Function Classification System (GMFCS). The data collected will include MRI image, clinical status, and socioeconomic status. The clinical information and MRI features extracted using radiomics strategy will be combined for exploratory analysis. The accuracy, sensitivity, and specificity of the model will be assessed using multiple modeling methodologies. Internal and external validation will be used to evaluate the performance of the radiomics model. Discussion: We hypothesized that the findings from this study could provide a critical step towards the prediction of treatment response in children with CP, which could also complement other biomarkers in the development of precision medicine approaches for this severe disorder. Trial registration: The study was registered with clinicaltrials.gov (NCT02979743).

8.
Stem Cell Res ; 40: 101555, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31491691

RESUMO

The induced pluripotent stem cell (iPSC) line XHCSUi001-A generated from urine cells of a female spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patient by using the integration-free methods. The induced XHCSUi001-A retained the disease-causing ATXN3 mutation, expressed pluripotency markers, exhibited a normal karyotype and retained the ability to differentiate into the three germ layers in-vitro and in-vivo. This newly induced iPSC line could be a potential tool for researching the disease-specific mechanisms and drug screening of SCA3/MJD.

9.
Int J Biol Macromol ; 139: 21-29, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31374268

RESUMO

Lignin, as a natural antioxidant, has a great potential to replace the chemosynthetic ones due to this material benefits of being biodegradable, eco-friendly, abundant and low-cost. However, the commonly-used lignins, such as acid, kraft and alkali lignins, have the poor antioxidant ability, and their antioxidative mechanism and kinetics remain poorly understood. Moreover, the understanding of the effect of polysaccharides in lignin-carbohydrate complex (LCC) on lignin antioxidant activity is also extremely insufficient. Herein, we isolated lignin and LCC from rice straw and its alkali-oxygen spent liquor to investigate their structure-antioxidant activity relationship and antioxidative mechanism. Experimental results illustrated that the alkali-oxygen treatment can significantly enhance the antioxidant activity of lignin. Demethoxylation, ring-opening and the cleavage of aryl ether bonds occur to lignin structure leading to the decrease of molecular weight, while the more stable condensed ß-1', 5-5' and ß-5' linkages maintain the thermostability of this antioxidant. The synergistic effect of adjacent methoxyl with phenolic hydroxyl is the key factor that endows lignin with the outstanding antioxidant activity. In contrast, oligosaccharides formed by alkali-oxygen treatment have a negative influence on the antioxidant activity of lignin. This work demonstrates that alkali-oxygen lignin is a promising antioxidant to replace chemosynthetic ones for polymeric materials.

10.
Inorg Chem ; 58(15): 10304-10312, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31328509

RESUMO

In recent years, although low-dimensional hybrid lead halides have received great attention due to the fascinating photoluminescent (PL) properties, the research is still on the early stage and only limited phases have been explored and characterized. Here, by introducing heterometals as mixed structural compositions and optical activity centers, we prepared a series of low-dimensional hybrid heterometallic halides, namely as, [(Me)-DABCO]2Cu2PbI6, [(Me)2-DABCO]2M5Pb2I13 (M = Cu and Ag) and [(Me)2-DABCO]Ag2PbBr6 (Me = methyl group, DABCO = 1,4-diazabicyclo[2.2.2]octane). These hybrid halides feature a low-dimensional 0D [Cu2PbI6]2- cluster, a 1D [M5Pb2I13]4- chain, and a 2D [Ag2PbBr6]2- layer, respectively, on the basis of corner-, edge- and face-sharing connecting of [MX4] tetrahedrons, [PbX5] quadrangular pyramids, and [PbX6] octahedrons. Under the photoexcitation, these hybrid heterometallic halides exhibit deep-red luminescent emissions from 711 to 801 nm with the largest Stocks shift of 395 nm. The temperature-dependent PL emissions, PL lifetime, and theoretical calculations are also investigated to probe into the intrinsic nature of photoluminescent emissions. This work affords new types of hybrid halides by introducing different metal centers to probe into the structural evolution and photoluminescent properties.

11.
Nat Commun ; 10(1): 3353, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350389

RESUMO

The diverse repertoire of T cell receptors (TCR) and immunoglobulins is generated through the somatic rearrangement of respective V, D and J gene segments, termed V(D)J recombination, during early T or B cell development. However, epigenetic regulation of V(D)J recombination is still not fully understood. Here we show that the deficiency of Setd2, a histone methyltransferase that catalyzes lysine 36 trimethylation on histone 3 (H3K36me3) in mice, causes a severe developmental block of thymocytes at the CD4-CD8- DN3 stage. While H3K36me3 is normally enriched at the TCRß locus, Setd2 deficiency reduces TCRß H3K36me3 and suppresses TCRß V(D)J rearrangement by impairing RAG1 binding to TCRß loci and the DNA double-strand break repair. Similarly, Setd2 ablation also impairs immunoglobulin V(D)J rearrangement to induce B cell development block at the pro-B stage. Lastly, SETD2 is frequently mutated in patients with primary immunodeficiency. Our study thus demonstrates that Setd2 is required for optimal V(D)J recombination and normal lymphocyte development.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , Recombinação V(D)J , Motivos de Aminoácidos , Animais , Linfócitos B/citologia , Linfócitos B/enzimologia , Diferenciação Celular , Pré-Escolar , Epigênese Genética , Histona-Lisina N-Metiltransferase/genética , Histonas/química , Histonas/metabolismo , Humanos , Lactente , Lisina/genética , Lisina/metabolismo , Masculino , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , /genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T/citologia
12.
Environ Int ; 131: 104971, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31284107

RESUMO

In mercury (Hg) contaminated areas of Asia, human exposure to toxic methyl-Hg (MeHg) through a rice-based diet of locally produced crop may pose a health threat. Alternative cropping system to rice in such areas would be most desirable. In this study, corn, the leading cereal source in the world with large biomass, was demonstrated to accumulate an insignificant amount of MeHg from the soil in its edible portion compared to that in rice, suggesting corn being a very competitive alternative crop. By examining Hg stable isotope composition, Hg in the aerial parts of corn was found to be mostly from the atmosphere. Maize cropping worldwide is estimated to be a discemible sink of atmospheric Hg with approximately 44 Mg Hg accumulated in each growing season on a yearly basis, most of which is from foliar uptake of atmospheric Hg and this amount is comparable to litterfall Hg observed in North America and Europe. It is thus recommended to use corn as a replacement of rice in highly Hg-contaminated areas for remediation of Hg pollution in the food supply.

13.
Eur J Radiol ; 116: 152-159, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153558

RESUMO

BACKGROUND AND PURPOSE: Periventricular pseudocysts (PVPCs) are cystic cavities originating from the germinal matrix. The effects of PVPCs on the development of white matter (WM) in neonates remain unclear. This study aimed to characterise WM microstructural variations in neonates with PVPCs with and without additional abnormities on MRI. MATERIALS AND METHODS: Neonates with PVPCs and controls with no MRI abnormalities were retrospectively enrolled. Test subjects were divided into groups 1 (isolated PVPCs) and 2 (PVPCs with additional MRI abnormalities). The PVPC MRI features collected included lateralisation, locularity, anatomic location, and the maximum anteroposterior diameter. Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were compared between the PVPC and control groups using tract-based spatial statistics. RESULTS: Thirty-eight neonates with PVPCs and 60 controls were enrolled. Groups 1 and 2 contained 15 and 23 subjects, respectively. The additional MRI findings in group 2 included intracranial haemorrhage, punctate WM lesions, hypoxic-ischaemic encephalopathy, and acute cerebral infarction. No significant differences were found in PVPC MRI features between the 2 test groups. Compared to controls, no significant changes in DTI metrics were observed in group 1 neonates; whereas extensive WM regions with decreased FA, increased RD, and unchanged/increased AD were found in group 2. CONCLUSIONS: Isolated PVPCs are not independently correlated with WM microstructural variations in neonates. This result provides further evidence for supporting the benign outcome of fetuses with isolated PVPCs.


Assuntos
Encefalopatias/patologia , Cistos/patologia , Substância Branca/patologia , Anisotropia , Encefalopatias/congênito , Estudos de Casos e Controles , Cistos/congênito , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos
14.
J Phys Chem Lett ; 10(11): 3064-3070, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31120761

RESUMO

Electron transfer (ET) and Auger recombination (AR) processes in quantum dots (QDs) are key mechanisms for the advance of QD-based devices. However, it still remains a challenge to promote ET and suppress AR simultaneously. Here, we use in situ high-pressure ultrafast transient absorption spectroscopy to explore the impact of pressure on the ET between CdSe/ZnS and anthraquinone (AQ) and AR dissolved in cyclohexane. Remarkably, under compression, ET lifetimes are shorten, while suppression of AR lifetimes is present. The promotion of ET is attributed to the shortened distance between CdSe/ZnS and AQ induced by pressure. We rationalize that for the AR suppression, pressure may enhance the formation of an alloy layer at the core/shell interface. These findings indicate that compression is an effective approach to promote ET and suppress AR simultaneously. This study highlights a brand-new approach for modulating ET and AR and provides new routes toward QD-based applications.

15.
Sci Rep ; 9(1): 7756, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123306

RESUMO

We use femtosecond transient absorption spectroscopy to study ultrafast electron transfer (ET) dynamics in a model donor and acceptor system using CdSe/ZnS core/shell structure quantum dots (QDs) as donors and anthraquinone (AQ) molecules as acceptors. The ET rate can be enhanced by decreasing the number of chlorine substituents in the AQ molecules because that increases the driving force, which is the energy level offset between the conduction band energy of CdSe/ZnS and the lowest upper molecular orbital potential of AQ derivatives, as confirmed by cyclic voltammetry measurements. However, the electronic coupling between the QDs and AQ derivatives, and the sum of reorganization energy of AQ molecules and solvent calculated by density functional theory are not the main reasons for the change in ET rate in three systems. Our findings provide new insights into selecting an acceptor molecule and will be useful in tuning ET processes for advanced QD-based applications.

16.
Cell Prolif ; 52(4): e12611, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054182

RESUMO

OBJECTIVES: Epigenetic modifiers were important players in the development of haematological malignancies and sensitivity to therapy. Mutations of SET domain-containing 2 (SETD2), a methyltransferase that catalyses the trimethylation of histone 3 on lysine 36 (H3K36me3), were found in various myeloid malignancies. However, the detailed mechanisms through which SETD2 confers chronic myeloid leukaemia progression and resistance to therapy targeting on BCR-ABL remain unclear. MATERIALS AND METHODS: The level of SETD2 in imatinib-sensitive and imatinib-resistant chronic myeloid leukaemia (CML) cells was examined by immunoblotting and quantitative real-time PCR. We analysed CD34+ CD38- leukaemic stem cells by flow cytometry and colony formation assays upon SETD2 knockdown or overexpression. The impact of SETD2 expression alterations or small-molecule inhibitor JIB-04 targeting H3K36me3 loss on imatinib sensitivity was assessed by IC50, cell apoptosis and proliferation assays. Finally, RNA sequencing and ChIP-quantitative PCR were performed to verify putative downstream targets. RESULTS: SETD2 was found to act as a tumour suppressor in CML. The novel oncogenic targets MYCN and ERG were shown to be the direct downstream targets of SETD2, where their overexpression induced by SETD2 knockdown caused imatinib insensitivity and leukaemic stem cell enrichment in CML cell lines. Treatment with JIB-04, an inhibitor that restores H3K36me3 levels through blockade of its demethylation, successfully improved the cell imatinib sensitivity and enhanced the chemotherapeutic effect. CONCLUSIONS: Our study not only emphasizes the regulatory mechanism of SETD2 in CML, but also provides promising therapeutic strategies for overcoming the imatinib resistance in patients with CML.


Assuntos
Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Histona Metiltransferases/genética , Histona-Lisina N-Metiltransferase/genética , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Fusão bcr-abl/genética , Humanos , Hidrazonas/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 218: 237-242, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31003048

RESUMO

The electron transfer (ET) rate in quantum dot (QD)-molecular acceptor systems is dependent upon system reorganization energy (RE, λ), which comprises contributions from solvent (λ0) and reactants (λi). However, to date, the effect of λi on ET rate has been largely ignored. Herein, the ET from CdSe/ZnS QDs to 1-chloroanthraquinone (1-CAQ) in different solvents was investigated using ultrafast transient absorption spectroscopy as a means to evaluate the effect of λi on ET rate. The results revealed that ET rate is strongly solvent dependent. Amazingly, the ET rate in carbon disulfide is 300-times higher than that in n-dodecane. Theoretical calculations indicated that the λi contribution from 1-CAQ alone accounts for a large proportion of system RE and varies greatly in different solvents. Furthermore, the ET rate increases first and, then, decreases with the λ value in different solvents. This trend was interpreted consistently in terms of Marcus theory by adding λi to λ for different solvents. Thus, our present work demonstrates that the RE of the acceptor molecule has a non-negligible effect on ET rate, providing new insight into the mechanisms of ET process and for the development of QD-based devices.

18.
J Nanosci Nanotechnol ; 19(9): 5435-5440, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961693

RESUMO

Vitamin D plays a major role in the regulation of calcium homeostasis and affects bone metabolism. There is currently limited detailed knowledge about the vitamin D endocrine system in human bone cells. Here, we investigated the direct effects of 1α, 25-dihydroxyvitamin D3 (1α, 25-(OH)2D3 or 'VD3') on osteogenesis of human umbilical cord mesenchymal stem cells (HUCMSCs). We also studied the impact of VD3 on intracellular Ca2+ concentrations in osteogenic cells. The results of alizarin red staining and alkaline phosphatase activity tests showed that VD3 could not induce osteogenic differentiation in HUCMSCs. However, addition of VD3 to the osteogenic differentiationinducing medium could promote HUCMSC to differentiate into osteoblasts. Calcium imaging showed that the addition of VD3 increased intracellular Ca2+ concentrations in osteogenic HUCMSCs. Thus, we concluded that adding VD3 increased intracellular Ca2+ concentrations in osteogenic HUCMSCs and promoted their osteogenesis.

20.
Environ Int ; 126: 406-412, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826619

RESUMO

Rice samples were collected at 560 sites in 15 provinces across China in areas without known point mercury (Hg) sources. Total mercury (THg) and methylmercury (MeHg) concentrations were analyzed in these rice samples for risk assessment. Relatively low THg and MeHg concentrations were found in the majority of the white rice samples with an overall mean of 4.74 (1.06-22.7) µg kg-1 and 0.682 (0.03-8.71) µg kg-1, respectively. The means (range of) THg concentration of rice in each geographical region were 5.23 (1.07-19.5) µg kg-1, 5.14 (1.06-17.2) µg kg-1, 4.45 (1.41-17.2) µg kg-1, 4.20 (1.48-19.4) µg kg-1, 3.49 (1.49-10.7) µg kg-1, and 4.53 (1.30-19.4) µg kg-1 in east, centre, south, southwest, northwest and northeast, China, respectively, and the corresponding values for MeHg concentrations were 0.898 (0.127-8.35) µg kg-1, 0.603 (0.207-2.48) µg kg-1, 0.516 (0.032-1.50) µg kg-1, 0.615 (0.050-5.03) µg kg-1, 0.704 (0.148-2.41) µg kg-1 and 0.565 (0.035-8.71) µg kg-1, respectively. Hg contents in rice across China were found to be at background levels. Both the probable daily intakes (PDIs) of inorganic Hg (IHg) and MeHg from rice consumption showed low risks for general population in the investigated regions.


Assuntos
Contaminação de Alimentos/análise , Mercúrio/análise , Compostos de Metilmercúrio/análise , Oryza/química , Poluentes do Solo/análise , Adulto , China , Monitoramento Ambiental , Humanos , Medição de Risco
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