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1.
IEEE Trans Vis Comput Graph ; 26(1): 811-821, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31443003

RESUMO

OD bundling is a promising method to identify key origin-destination (OD) patterns, but the bundling can mislead the interpretation of actual trajectories traveled. We present OD Morphing, an interactive OD bundling technique that improves geographical faithfulness to actual trajectories while preserving visual simplicity for OD patterns. OD Morphing iteratively identifies critical waypoints from the actual trajectory network with a min-cut algorithm and transitions OD bundles to pass through the identified waypoints with a smooth morphing method. Furthermore, we extend OD Morphing to support bundling at interaction speeds to enable users to interactively transition between degrees of faithfulness to aid sensemaking. We introduce metrics for faithfulness and simplicity to evaluate their trade-off achieved by OD morphed bundling. We demonstrate OD Morphing on real-world city-scale taxi trajectory and USA domestic planned flight datasets.

2.
J Cell Physiol ; 235(2): 1090-1102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31256427

RESUMO

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.

3.
Cell Res ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666677

RESUMO

Macroautophagy/autophagy defines an evolutionarily conserved catabolic process that targets cytoplasmic components for lysosomal degradation. The process of autophagy from initiation to closure is tightly executed and controlled by the concerted action of autophagy-related (Atg) proteins. Although substantial progress has been made in characterizing transcriptional and post-translational regulation of ATG/Atg genes/proteins, little is known about the translational control of autophagy. Here we report that Psp2, an RGG motif protein, positively regulates autophagy through promoting the translation of Atg1 and Atg13, two proteins that are crucial in the initiation of autophagy. During nitrogen starvation conditions, Psp2 interacts with the 5' UTR of ATG1 and ATG13 transcripts in an RGG motif-dependent manner and with eIF4E and eIF4G2, components of the translation initiation machinery, to regulate the translation of these transcripts. Deletion of the PSP2 gene leads to a decrease in the synthesis of Atg1 and Atg13, which correlates with reduced autophagy activity and cell survival. Furthermore, deactivation of the methyltransferase Hmt1 constitutes a molecular switch that regulates Psp2 arginine methylation status as well as its mRNA binding activity in response to starvation. These results reveal a novel mechanism by which Atg proteins become upregulated to fulfill the increased demands of autophagy activity as part of translational reprogramming during stress conditions, and help explain how ATG genes bypass the general block in protein translation that occurs during starvation.

4.
Sci Rep ; 9(1): 16095, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695103

RESUMO

Forecasts indicate that China's non-carbon dioxide (CO2) greenhouse gas (GHG) emissions will increase rapidly from the 2014 baseline of 2 billion metric tons of CO2 equivalent (CO2e). Previous studies of the potential for mitigating non-CO2 GHG emissions in China have focused on timeframes through only 2030, or only on certain sectors or gases. This study uses a novel bottom-up end-use model to estimate mitigation of China's non-CO2 GHGs under a Mitigation Scenario whereby today's cost-effective and technologically feasible CO2 and non-CO2 mitigation measures are deployed through 2050. The study determines that future non-CO2 GHG emissions are driven largely by industrial and agricultural sources and that China could reduce those emissions by 47% by 2050 while enabling total GHG emissions to peak by 2023. Except for F-gas mitigation, few national or sectoral policies have focused on reducing non-CO2 GHGs. Policy, market, and other institutional support are needed to realize the cost-effective mitigation potentials identified in this study.

5.
Adv Immunol ; 144: 173-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31699217

RESUMO

Autoimmune diseases, such as rheumatoid arthritis, systematic lupus erythematosus and Sjögren's syndrome, are a group of diseases characterized by the activation of immune cells and excessive production of autoantibodies. Although the pathogenesis of these diseases is still not completely understood, studies have shown that multiple factors including genetics, environment and immune responses play important roles in the development and progression of the diseases. In China, there are great achievements in the mechanisms of autoimmune diseases during the last decades. These studies provide new insight to understand the diseases and also shed light on the development of novel therapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31754859

RESUMO

As the composition of animal cell culture medium becomes more complex, the identification of key variables is important for simplifying and guiding the subsequent medium optimization. However, the traditional experimental design methods are impractical and limited in their ability to explore such large feature spaces. Therefore, in this work, we developed a NRGK (nonparametric regression with Gaussian kernel) method, which aimed to identify the critical components that affect product titres during the development of cell culture media. With this nonparametric model, we successfully identified the important components that were neglected by the conventional PLS (partial least squares regression) method. The superiority of the NRGK method was further verified by ANOVA (analysis of variance). Additionally, it was proven that the selection accuracy was increased with the NRGK method because of its ability to model both the nonlinear and linear relationships between the medium components and titres. The application of this NRGK method provides new perspectives for the more precise identification of the critical components that further enable the optimization of media in a shorter timeframe.

7.
Autophagy ; : 1-2, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31690182

RESUMO

Lipidation of Atg8-family ubiquitin-like proteins (UBLs) plays important roles in macroautophagy/autophagy. This process is catalyzed by an E1-E2-E3 trienzyme cascade, in which an E1 enzyme, Atg7, directs Atg8 to its E2 enzyme, Atg3, forming a thioester bond-linked Atg3~ Atg8 intermediate; then the composite E3, Atg12-Atg5-Atg16, interacts with the Atg3~ Atg8 intermediate and promotes Atg8 transfer from the catalytic cysteine of Atg3 to the head group of phosphatidylethanolamine (PE) lipids. Despite progress that has been made toward understanding the Atg8 lipidation pathway, the molecular mechanism of Atg3 as it orchestrates between the E1 and E3 remains unclear. Here we summarize our recent work reporting an element in Atg3, termed the E1, E2, and E3-interacting region (E123IR), is an allosteric switch: in the absence of other binding partners, the E123IR restrains Atg3's catalytic loop, while the E1 or E3 enzyme directly binds this region to remove this brace and thereby conformationally activate Atg3 to elicit Atg8 lipidation in vitro and in vivo.

8.
Gene ; : 144242, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743770

RESUMO

OBJECTIVE: To investigate fibroblast growth factor 21 (Fgf21) alterations that may affect hair growth and the underlying molecular mechanisms by constructing Fgf21 global knockout (KO) mice using microinjection-mediated CRISPR/Cas9. RESULTS: Following genomic DNA sequencing, we identified 18 mice carrying Ffg21 mutations among the total 63 offspring mice obtained by injecting 340 embryos, which yielded a mutation rate of 28.6 percent. Of these 18 mice, three had both alleles knocked out and 15 were monoallelic KO mice. Compared with the wild-type (WT) mice, the phenotypic analysis showed that the litter size of Fgf21 KO mice significantly reduced (p<0.05), but physiological indexes of the birth weight, gender rate, body weight(0-8 week) and body weight of adult male and female were no significant difference (p>0.05). Compared to WT mice, physiological anatomy indicated that the morphological characters of vital organs in Fgf21 KO mice were normal.Depilation experiments demonstrated that compared to the WT mice, the hair regrowth speed was reduced in the Fgf21 KO mice. The number of hair shafts in these mice considerably decreased, as indicated by the tissue sample analyses. Real-time quantitative PCR showed that Erk and Akt expression in the KO mice was significantly decreased (P < 0.05), whereas western blotting demonstrated that the expression of Erk and Akt proteins and their phosphorylation levels in KO mice decreased at different rates (P < 0.05). CONCLUSIONS: Fgf21 was shown to affect hair follicle development and growth cycle, which may be associated with Pi3k/Akt and Mapk/Erk signaling pathways.

9.
Crit Rev Eukaryot Gene Expr ; 29(4): 363-375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679297

RESUMO

A genome-wide association study first reported the association between ischemic stroke risk and two polymorphisms on chromosome 12p13: rs12425791 and rs11833579. Since then, a series of studies have investigated the association of these two polymorphisms with stroke risk, but the results were inconsistent even in Asian populations. Thus, we carried out a case-control study to uncover the potential relationship, and then conducted a meta-analysis to further address the issue. 540 ischemic stroke patients and 540 unrelated controls were enrolled in the case-control study. Genotyping was accomplished by polymerase chain reaction-ligation detection reaction. The meta-analysis was conducted by combining our study with previous published data. In our case-control study, the significant association was observed between ischemic stroke and rs12425791 (AG vs. GG: OR = 1.32, P < 0.05) but not rs11833579. When pooled with previous studies, the significant relationship of rs12425791 with ischemic stroke was found (A vs. G: OR = 1.07, P < 0.05; AA + AG vs. GG: OR = 1.10, P < 0.05) in Asian populations, as well as in subgroup analysis. A correlation approaching significance was identified between ischemic stroke risk and rs11833579 (AA + AG vs. GG: OR = 1.06, P = 0.05). New evidence from this case-control study and meta-analysis indicates that 12p13 rs12425791/rs11833579 polymorphisms are associated with ischemic stroke susceptibility in Asian populations.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31701626

RESUMO

OBJECTIVE: To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression. METHODS: A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping. RESULTS: The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001). CONCLUSION: The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.

11.
J Adv Nurs ; 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31736133

RESUMO

AIMS: To investigate workplace violence and nurse outcomes by comparing gender differences. DESIGN: A secondary analysis of cross-sectional survey data. METHODS: Workplace violence was measured by four items from the International Hospital Outcome Study. Nurse outcomes were measured by tools including burnout, job satisfaction and intention to stay. We used propensity score matching to generate a sociodemographic balanced dataset of 108 male and 288 female nurses. A hypothetical relationship model was derived from the affective events theory. Comparative statistics and multi-group structural equation modelling were conducted to analyze gender differences. Data were collected in China from December 2013 - August 2014. RESULTS: Male nurses reported more workplace violence from staff and less intention to stay than females. Besides finding the mediation of burnout sharing with female nurses consistent with the affective events theory, workplace violence was directly linked to less intention to stay in male nurses. CONCLUSION: Male nurses experience more workplace violence by staff than female nurses. Besides responding emotionally to workplace violence like female nurses, male nurses also respond behaviourally. IMPACT: What problem did the study address? Gender differences in workplace violence and its relationship to nurse outcomes. What were the main findings? Male nurses experienced more workplace violence than female nurses, linked directly to less intention to stay. Workplace violence linked to less job satisfaction and intention to stay in nurses was mediated by burnout. Where and on whom will the research have impact? Gender-based prevention of and coping with workplace violence should be included in nursing training.

13.
World J Gastroenterol ; 25(39): 6006-6015, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660036

RESUMO

BACKGROUND: In pancreatic cancer, acute pancreatitis (AP) is a serious morbidity, but its negative effect on long-term outcomes remains to be elucidated. AIM: To investigate the effects of AP on the tumor recurrence pattern of pancreatic ductal adenocarcinoma (PDAC) and tumor-specific survival. METHODS: The medical records of 219 patients with curative pancreatectomy for pancreatic cancer at the Pancreatic Surgery Center of West China Hospital from July 2012 to December 2016 were analyzed retrospectively. The severity of acute pancreatitis was classified according to the Atlanta classification of AP. The patient demographics and tumor characteristics were assessed. Early recurrence was defined as a relapse within 12 mo after surgery. Overall and disease-free survival and recurrence patterns were analyzed. Mild acute pancreatitis was excluded because its negative effects can be negligible. RESULTS: Early recurrence in AP group was significantly higher than in non-AP group (71.4% vs 41.2%; P = 0.009). Multivariate analysis of postoperative early recurrence showed that moderate or severe AP was an independent risk factor for an early recurrence [odds ratio (OR): 4.13; 95% confidence interval (CI): 1.41-12.10; P = 0.01]. The median time to recurrence was shorter in patients with AP than in those without (8.4 vs 12.8 mo; P = 0.003). Multivariate analysis identified AP as an independent prognostic factor for overall survival [relative risk (RR): 2.35; 95%CI: 1.45-3.83] and disease-free survival (RR: 2.24; 95%CI: 1.31-3.85) in patients with PDAC. CONCLUSION: Patients with moderate or severe acute pancreatitis developed recurrences earlier than those without. Moderate or severe AP is associated with shorter overall and disease-free survival of patients with PDAC.

14.
J Am Chem Soc ; 141(42): 16584-16589, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31588745

RESUMO

A nickel-catalyzed asymmetric allylation of secondary phosphine oxides (SPO) for the synthesis of tertiary phosphine oxides (TPO) was realized with high enantioselectivity. The dynamic kinetic asymmetric transformation of SPO was accomplished in the presence of nickel complex. By elucidating the absolute configurations of the reacted SPO starting material and the TPO product, we confirmed that the allylation reaction proceeded through a P-stereo retention process. The protocol represents the first example of synthesizing P-stereogenic phosphine oxides by allylation reaction.

15.
Front Immunol ; 10: 2274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611875

RESUMO

Influenza vaccines for H7N9 subtype have shown low immunogenicity in human clinical trials. Using novel adjuvants might represent the optimal available option in vaccine development. In this study, we demonstrated that the using of the STING agonist cGAMP as a mucosal adjuvant is effective in enhancing humoral, cellular and mucosal immune responses of whole virus, inactivated H7N9 vaccine in mice. A single dose of immunization was able to completely protect mice against a high lethal doses of homologous virus challenge with an significant dose-sparing effect. We also found that intranasal co-administration of H7N9 vaccine with cGAMP could provide effective cross protection against H1N1, H3N2, and H9N2 influenza virus. Furthermore, cGAMP induced significantly higher nucleoprotein specific CD4+ and CD8+ T cells responses in immunized mice, as well as upregulated the IFN-γ and Granzyme B expression in the lung tissue of mice in the early stages post a heterosubtypic virus challenge. These results indicated that STING agonist cGAMP was expected to be an effective mucosal immune adjuvant for pre-pandemic vaccines such as H7N9 vaccines, and the cGAMP combined nasal inactivated influenza vaccine will also be a promising strategy for development of broad-spectrum influenza vaccines.

16.
Org Lett ; 21(21): 8713-8717, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613104

RESUMO

The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group permits, via robust neighboring group participation (NGP) or long distance participation (LDP) effects, the stereocontrolled 1,2-trans, 1,2-cis, as well as ß-2,6-dideoxy glycosidic bond generation, while suppressing the undesired orthoester byproduct formation. The robust stereocontrol capability of the DMNPA is due to the dual-participation effect from both the ester functionality and the nitro group, verified by control reactions and DFT calculations and further corroborated by X-ray spectroscopy.

17.
MBio ; 10(5)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641092

RESUMO

Streptococcus equi subspecies zooepidemicus (SEZ) are group C streptococci that are important pathogens of economically valuable animals such as horses and pigs. Here, we found that many SEZ isolates bind to a monoclonal antibody that recognizes poly-N-acetylglucosamine (PNAG), a polymer that is found as a surface capsule-like structure on diverse microbes. A fluorescence-activated cell sorting-based transposon insertion sequencing (Tn-seq) screen, coupled with whole-genome sequencing, was used to search for genes for PNAG biosynthesis. Surprisingly, mutations in a gene encoding an M-like protein, szM, and the adjacent transcription factor, designated sezV, rendered strains PNAG negative. SezV was required for szM expression and transcriptome analysis showed that SezV has a small regulon. SEZ strains with inactivating mutations in either sezV or szM were highly attenuated in a mouse model of infection. Comparative genomic analyses revealed that linked sezV and szM homologues are present in all SEZ, S. equi subspecies equi (SEE), and M18 group A streptococcal (GAS) genomes in the database, but not in other streptococci. The antibody to PNAG bound to a wide range of SEZ, SEE, and M18 GAS strains. Immunochemical studies suggest that the SzM protein may be decorated with a PNAG-like oligosaccharide although an intact oligosaccharide substituent could not be isolated. Collectively, our findings suggest that the szM and sezV loci define a subtype of virulent streptococci and that an antibody to PNAG may have therapeutic applications in animal and human diseases caused by streptococci bearing SzM-like proteins.IMPORTANCE M proteins are surface-anchored virulence factors in group A streptococci, human pathogens. Here, we identified an M-like protein, SzM, and its positive regulator, SezV, in Streptococcus equi subspecies zooepidemicus (SEZ), an important group of pathogens for domesticated animals, including horses and pigs. SzM and SezV homologues were found in the genomes of all SEZ and S. equi subspecies equi and M18 group A streptococcal strains analyzed but not in other streptococci. Mutant SEZ strains lacking either sezV or szM were highly attenuated in a mouse model of infection. Collectively, our findings suggest that SezV-related regulators and the linked SzM family of M-like proteins define a new subset of virulent streptococci.

18.
ACS Appl Mater Interfaces ; 11(46): 43146-43155, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31647215

RESUMO

The original poly(ethylene oxide)-based polymer electrolytes normally show low ionic conductivity and inferior mechanical property, which greatly restrict their practical application in all-solid-state lithium-ion batteries (LIBs). In this work, a hyperbranched star polymer with poly(ethylene glycol) methyl ether methacrylate flexible chain segments is embedded into a three-dimensional (3D) interpenetrating cross-linking network created by the rapid one-step UV-derived photopolymerization of the cross-linker (ethoxylated trimethylolpropane triacrylate) in the presence of lithium salt. The rigid 3D network framework provides the polymer electrolyte with not only enhanced mechanical behavior, including film-forming and dendrite-inhibiting capabilities, but also nanoconfinement effects, which can speed up polymer chain segmental dynamics and reduce the crystallinity of the polymer. Depending on this unique rigid-flexible coupling network, the prepared solid polymer electrolyte shows enhanced ionic conductivity (6.8 × 10-5 S cm-1 at 50 °C), widened electrochemical stability window (5.1 V vs Li/Li+), and enough mechanical stability to suppress the growth of uneven Li dendrite (the Li symmetrical cells can operate steadily at both current densities of 0.05 and 0.1 mA cm-2 for 1000 h). Moreover, the assembled LiFePO4//Li cell also exhibited good cycle performance at 50 °C, making the hyperbranched star polymer electrolyte with a nanoconfined cross-linking structure to have potential application in high-safety and high-performance LIBs.

19.
ACS Appl Mater Interfaces ; 11(46): 42975-42987, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31657894

RESUMO

Three nonviral gene vectors, TPA-BI-A/B/C, have been designed and synthesized by the combination of one or two hydrophilic [12]aneN3 moieties and two-photon fluorescent triphenylamine-benzylideneimidazolone (TPA-BI) units through different ester linkage. Spectroscopic characterization demonstrated that TPA-BI-A/B/C had strong aggregation-induced emissions (AIE), large Stokes shifts (230, 284, and 263 nm), and large two-photon absorption cross sections (δ2PA) (67, 592, and 80 GM). Gel electrophoresis indicated that the three compounds completely condensed DNA at 15 µM in the presence of DOPE, and showed the lipase- and pH-triggered reversible release of DNA and the fluorescent recognition of the different lengths of ssDNA and dsDNA. The optimal TPA-BI-C/DOPE-mediated luciferase and GFP activity was 146% and 290% higher than those of Lipo2000. The transfection process of DNA could be traced clearly through one- and two-photon fluorescence spectra, and displayed in a 3D-video. TPA-BI-C/DOPE successfully transfected the GFP gene into zebrafish, which was superior to Lipo2000 (192%). In conclusion, TPA-BI-C/DOPE is the first nonviral gene vector with the abilities of pH/lipase enzyme responsiveness, one/two-photon fluorescent tracking of intracellular delivery of DNA, and successful transfection in vivo and in vitro, even better than Lipo2000.

20.
Eur J Pharmacol ; 864: 172694, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563648

RESUMO

Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA.

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