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1.
Plant Sci ; 292: 110380, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005385

RESUMO

Water deficits are a major constraint on maize growth and yield, and deep roots are one of the major mechanisms of drought tolerance. In this study, four root and shoot traits were evaluated within an association panel consisting of 209 diverse maize accessions under well-watered (WW) and water-stressed (WS) conditions. A significant positive correlation was observed between seminal root length (SRL) under WS treatment and the drought tolerance index (DI) of maize seedlings. The transcriptome profiles of maize seminal roots were compared between four drought-tolerant lines and four drought-sensitive lines under both water conditions to identify genes associated with the drought stress response. After drought stress, 343 and 177 common differentially expressed genes (DEGs) were identified in the drought-tolerant group and drought-sensitive group, respectively. In parallel, a coexpression network underlying SRL was constructed on the basis of transcriptome data, and 10 hub genes involved in two significant associated modules were identified. Additionally, a genome-wide association study (GWAS) of the SRL revealed 62 loci for the two water treatments. By integrating the results of the GWAS, the common DEGs and the coexpression network analysis, 7 promising candidate genes were prioritized for further research. Together, our results provide a foundation for the enhanced understanding of seminal root changes in response to drought stress in maize.

2.
Bioresour Technol ; 302: 122842, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32006925

RESUMO

In this work, magnetic wakame biochar nanocomposites for the first time had been synthesized to investigate their adsorption to methylene blue dye. As-prepared magnetic biochar samples were obtained by the impregnation method to load nickel on wakame biochar via one-step carbonization with activation agent KOH at 800 °C. The prepared samples were characterized by BET, XRD, FTIR, Raman, SEM, TEM and so on. The results exhibited that the maximum adsorption capacity of BW(Ni)0.5 to methylene blue could reach 479.49 mg/g at 20 °C. The adsorption behavior was more suitable for Langmuir isotherm equation and the kinetic data were most consistent with the pseudo second-order model. And also, the adsorption reaction was a spontaneous and endothermic process. After five cycles, it was found that BW(Ni)0.5 had a high adsorption capacity for methylene blue (117.58 mg/g). This study demonstrated that wakame biochar could have great potential in dye wastewater treatment.

3.
Cell Mol Immunol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066854

RESUMO

CD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed after thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticity, particularly upon TCR-mediated activation. We define a novel CD4-CD8αß+ MHC II-recognizing population generated by lineage conversion from effector CD4+ T cells. CD4-CD8αß+ effector T cells downregulated the expression of T helper cell-associated costimulatory molecules and increased the expression of cytotoxic T lymphocyte-associated cytotoxic molecules. This shift in functional potential corresponded with a CD8+-lineage skewed transcriptional profile. TCRß repertoire sequencing and in vivo genetic lineage tracing in acutely infected wild-type mice demonstrated that CD4-CD8αß+ effector T cells arise from fundamental lineage reprogramming of bona fide effector CD4+ T cells. Impairing autophagy via functional deletion of the initiating kinase Vps34 or the downstream enzyme Atg7 enhanced the generation of this cell population. These findings suggest that effector CD4+ T cells can exhibit a previously unreported degree of skewing towards the CD8+ T cell lineage, which may point towards a novel direction for HIV vaccine design.

4.
Int J Biol Macromol ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32068062

RESUMO

The aim of this study was to evaluate the spatial structure and potential antifatigue activity of polysaccharide fractions which was extracted from Inonotus obliquus. The first polysaccharide fractions of Inonotus obliquus (PIO-1) were obtained after hot-water extraction and purification by DEAE cellulose-52 chromatography. Results of the forced swimming test showed that the doses (50 mg/kg) of PIO-1 could increase the climbing duration and swimming time as well as reduced the immobility time in the PIO treated mice. The fatigue related metabolic parameters showed that PIO-1 decreased the level of blood lactic acid (BLA), urea nitrogen (BUN) and lactic dehydrogenase (LDH). Additionally, PIO-1 significantly decreased the 5-HT concentrations in the mice brain. The results of monosaccharide analysis showed that the molar ratio of mannose, glucose, galactose, xylose and arabinose with the molar ratio of 1.0:1.9:3.5:18.5:5.7. The molecular morphology of the PIO-1 observed under atomic force microscopy (AFM). There were many spherical and heterogeneous clumps existed in the images. Therefore, current study indicated polysaccharide PIO-1 not only has great potential to postpone physical fatigue but also shown potential to improve mental fatigue.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32047949

RESUMO

Biochar was prepared by mixing sewage sludge with sawdust via a co-pyrolysis with different mixture ratios and temperatures. The results showed that the sawdust addition resulted in a lower yield of biochar with higher C content. The total concentrations of Pb and Cd in biochar were reduced. Besides, pyrolysis can transform the potentially toxic Pb and Cd to stable fractions. However the sawdust addition had slight influence on the chemical forms of Pb and Cd in the biochar. The biochar with 50% sawdust at 600°C exhibited a remarkable reduction of the leachable metal concentrations. The possible transformation mechanisms of Pb and Cd were inferred as the formation of aluminum and silicon-containing minerals. These results provide insights into the influence of sawdust addition on the characteristics of biochar and the possible Pb and Cd immobilization mechanisms during co-pyrolysis process.

6.
Parasit Vectors ; 13(1): 67, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051017

RESUMO

BACKGROUND: The malaria elimination plan of the Greater Mekong Subregion (GMS) is jeopardized by the increasing number of Plasmodium vivax infections and emergence of parasite strains with reduced susceptibility to the frontline drug treatment chloroquine/primaquine. This study aimed to determine the evolution of the P. vivax multidrug resistance 1 (Pvmdr1) gene in P. vivax parasites isolated from the China-Myanmar border area during the major phase of elimination. METHODS: Clinical isolates were collected from 275 P. vivax patients in 2008, 2012-2013 and 2015 in the China-Myanmar border area and from 55 patients in central China. Comparison was made with parasites from three border regions of Thailand. RESULTS: Overall, genetic diversity of the Pvmdr1 was relatively high in all border regions, and over the seven years in the China-Myanmar border, though slight temporal fluctuation was observed. Single nucleotide polymorphisms previously implicated in reduced chloroquine sensitivity were detected. In particular, M908L approached fixation in the China-Myanmar border area. The Y976F mutation sharply decreased from 18.5% in 2008 to 1.5% in 2012-2013 and disappeared in 2015, whereas F1076L steadily increased from 33.3% in 2008 to 77.8% in 2015. While neutrality tests suggested the action of purifying selection on the pvmdr1 gene, several likelihood-based algorithms detected positive as well as purifying selections operating on specific amino acids including M908L, T958M and F1076L. Fixation and selection of the nonsynonymous mutations are differently distributed across the three border regions and central China. Comparison with the global P. vivax populations clearly indicated clustering of haplotypes according to geographic locations. It is noteworthy that the temperate-zone parasites from central China were completely separated from the parasites from other parts of the GMS. CONCLUSIONS: This study showed that P. vivax populations in the China-Myanmar border has experienced major changes in the Pvmdr1 residues proposed to be associated with chloroquine resistance, suggesting that drug selection may play an important role in the evolution of this gene in the parasite populations.

7.
Sci Total Environ ; 714: 136897, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32018999

RESUMO

Hydrochar produced from agricultural and forestry wastes and its application into the environment are very attractive. Herein, a high-efficiency dithiocarbamate-modified hydrochar (DTHC) was prepared successfully and then applied to eliminate Pb(II) from aqueous solutions. DTHC was characterized by various techniques. It was found that dithiocarbamate and amine groups were successfully grafted onto the surface of hydrochar. The surface area of DTHC was 7.94 m2·g-1, which was four folds less than pristine hydrochar (31.60 m2·g-1), but its adsorption capacity obviously increased. Adsorption experiments showed that the Pb(II) adsorption process onto DTHC well accorded with pseudo-2nd-order kinetics and Langmuir isotherms. The highest Pb(II) uptake by DTHC at 293 K determined from the Langmuir model was 151.51 mg·g-1. Fourier transform infrared spectra and X-ray photoelectron spectroscopy verified that dithiocarbamate, carboxylate, amine and sulfonate groups all facilitated the Pb(II) adsorption. The adsorption mechanism was ascribed to the inner-sphere surface complexation of Pb(II) by these groups and to the ion exchange between Pb(II) and Na(I). Thus, DTHC is an effective adsorbent for Pb(II) removal from water.

8.
Pharmacol Res ; 153: 104660, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982489

RESUMO

Multidrug resistance (MDR) represents an obstacle in anti-cancer therapy. MDR is caused by multiple mechanisms, involving ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), which reduces intracellular drug levels to sub-therapeutic concentrations. Therefore, sensitizing agents retaining effectiveness against apoptosis- or drug-resistant cancers are desired for the treatment of MDR cancers. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump is an emerging target to overcome MDR, because of its continuous expression and because the calcium transport function is crucial to the survival of tumor cells. Previous studies showed that SERCA inhibitors exhibit anti-cancer effects in Bax-Bak-deficient, apoptosis-resistant and MDR cancers, whereas specific P-gp inhibitors reverse the MDR phenotype of cancer cells by blocking efflux of chemotherapeutic agents. Here, we unraveled SERCA and P-gp as double targets of the triterpenoid, celastrol to reverse MDR. Celastrol inhibited both SERCA and P-gp to stimulate calcium-mediated autophagy and ATP depletion, thereby induced collateral sensitivity in MDR cancer cells. In vivo studies further confirmed that celastrol suppressed tumor growth and metastasis by SERCA-mediated calcium mobilization. To the best of our knowledge, our findings demonstrate collateral sensitivity in MDR cancer cells by simultaneous inhibition of SERCA and P-gp for the first time.

9.
ACS Infect Dis ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31906623

RESUMO

Streptococcus mutans is a common constituent of dental plaque and a major etiologic agent of dental caries (tooth decay). In this study, we elucidated the biosynthetic pathway encoded by muc, a hybrid polyketide synthase and nonribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC), present in a number of globally distributed S. mutans strains. The natural products synthesized by muc included three N-acyl tetramic acid compounds (reutericyclin and two novel analogues) and an unacylated tetramic acid (mutanocyclin). Furthermore, the enzyme encoded by mucF was identified as a novel class of membrane-associated aminoacylases and was responsible for the deacylation of reutericyclin to mutanocyclin. A large number of hypothetical proteins across a broad diversity of bacteria were homologous to MucF, suggesting that this may represent a large family of unexplored acylases. Finally, S. mutans utilized the reutericyclin produced by muc to impair the growth of neighboring oral commensal bacteria. Since S. mutans must be able to out-compete these health-associated organisms to persist in the oral microbiota and cause disease, the competitive advantage conferred by muc suggests that this BGC is likely to be involved in S. mutans ecology and therefore dental plaque dysbiosis and the resulting caries pathogenesis.

10.
Mol Cell Probes ; : 101504, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31904417

RESUMO

Based on the high self-renewal ability and osteoblastic differentiation capacity, dental pulp stem cells (DPSCs) are suggested to be promising cell source for osteogenesis. Therefore, illustrating the mechanism of osteoblastic differentiation of DPSCs is required. This current study aims to illustrate the role and mechanism of Sp1 in regulating osteoblastic differentiation of DPSCs. In this study, we downregulated Sp1 in DPSCs and evaluated the osteoblastic differentiation by measuring Runx2 and OCN expression with Western blot analysis and by Alizarin red staining. Furthermore, we investigated the mechanism of Sp1 regulating noggin with Firefly luciferase reporter gene assay and ChIP assay, and correspondingly evaluated the function of noggin in Sp1-regulated osteoblastic differentiation of DPSCs. We found that knockdown of Sp1 inhibits the expression of ALP, Runx2, COL1A1 and OCN, and decreases ALP staining, Alizarin red staining. Sp1 binds to noggin promoter and inhibits noggin expression, thus correspondingly regulates DPSCs osteoblastic differentiation. In conclusion, our study revealed that Sp1 regulates DPSCs osteoblastic differentiation through noggin and that Sp1/noggin can provide new perspective for enhancing DPSCs osteogenesis.

11.
J Abnorm Psychol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928031

RESUMO

Failure in translating emotional salience into effortful behavior is thought to be a core feature of anhedonia and avolition in individuals with schizophrenia (SCZ), but little is known about emotion-behavior coupling in individuals with bipolar disorder (BD) and major depressive disorder (MDD). In this study, we compared emotion-behavior correspondence in participants with SCZ, BD, and MDD. Forty-two participants with SCZ, 44 participants with MDD, 43 participants with BD, and 43 healthy controls were recruited. A computerized anticipatory and consummatory pleasure task was used to evaluate emotion-behavior correspondence. Clinical ratings of negative symptoms and self-report anhedonia questionnaires were also administered. We found that participants with SCZ, MDD, and BD exhibited different levels of negative symptoms and self-reported anhedonia, as well as emotion-behavior decoupling. In SCZ participants, both desirable and undesirable images elicited lower correspondence between self-reported liking and behavior. In MDD and BD participants, undesirable images elicited lower emotion-behavior correspondence under both direct stimulus presentation and representation conditions, whereas deficits in emotion-behavior coupling under desirable conditions were only observed when stimuli were present. Taken together, emotion-behavior decoupling showed both common and unique patterns in participants with SCZ, MDD, and BD, and showed some associations with negative symptoms and anhedonia across the combined clinical sample. This finding may be helpful for early identification and the development of novel interventions for different psychiatric diagnoses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

12.
Neuroscience ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31982470

RESUMO

OBJECTIVE: The spontaneous action potential of isolated sinoatrial node (SAN) cells is regulated by a coupled-clock system of two clocks: the calcium clock and membrane clock. However, it remains unclear whether calcium clock inhibitors have a direct effect on the membrane clock. The purpose of this study was to investigate the direct effect of cyclopiazonic acid (CPA), a selective calcium clock inhibitor, on the function of the membrane clock of SAN cells. METHODS: at SAN cells were isolated by trypsinization and identified based on morphology and electrophysiology. If and HCN currents were recorded via patch clamp technique. The expression of the HCN channel protein was determined by Western blotting analysis. RESULTS: The diastolic depolarization rate of spontaneous action potentials and the current densities of If were reduced by exposure to 10 µM CPA. The inhibitory effect of CPA was concentration-dependent with an IC50 value of 16.3 µM and a Hill coefficient of 0.98. The effect of CPA on If current was also time-dependent, and the If current amplitude was partially restored after washout. Furthermore, the steady-state activation curve of the If current was shifted to a negative potential, indicating that channel activation slowed down. Finally, the protein expression of HCN4 in HEK293 cells was markedly downregulated by CPA. CONCLUSIONS: These results indicate that the direct inhibition effect of CPA on the If current in SAN cells is both concentration- and time-dependent. The underlying mechanisms may involve slowing down steady-state activation and the downregulation of pacemaker channel protein expression.

13.
PLoS One ; 15(1): e0228390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999801

RESUMO

BACKGROUND: The safety of pirfenidone on pulmonary fibrosis patients with other kinds of interstitial lung diseases (ILDs) in addition to idiopathic pulmonary fibrosis (IPF) is unknown. Furthermore, its effectiveness-related factors on IPF patients are not quite explored. METHODS: A retrospective study, on patients prescribed pirfenidone for pulmonary fibrosis, was conducted to assess effectiveness on IPF patients and tolerability of all patients with lung fibrosis. The effectiveness of pirfenidone was tested on 110 IPF subjects receiving treatment for ≥3 months by high-resolution computed tomography (HRCT). Response-linked factors and progression-free survival (PFS) were also analyzed. The data about safety outcomes and drug dose adjustments were collected from all included subjects. RESULTS: A total of 176 subjects were included: 117 were IPF, 19 connective tissue disease-associated interstitial lung disease (CTD-ILD), and 40 unclassifiable ILD. Out of the 110 IPF subjects, 89 subjects were assessed as stable and 21 as progressive, out of which 10 died of acute exacerbation and 11 progressed. The effectiveness was significantly related to their baseline body mass index (BMI). IPF subjects with BMI>25kg/m2 or diffusion capacity of carbon monoxide (DLco)>30% had higher PFS rate. The most common adverse events were skin-related and gastrointestinal-related. Drug discontinuation owing to adverse events occurred similarly in these three groups. CONCLUSION: Pirfenidone was well tolerated in most of the lung fibrosis patients besides IPF, with a similar pattern of adverse events. Nearly 80% of IPF subjects were assessed as stable. More benefits were seen in IPF patients with higher BMI or mild-to-moderate disease.

14.
J Endourol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31813302

RESUMO

Objective: To investigate the diagnostic value of digital tomosynthesis in urolithiasis compared with multidetector computed tomography (MDCT). Subjects and Methods: This study received the approval of institutional review board and obtained the informed consents of all subjects. Fifty patients with acute renal colic and hematuria from February 2014 to February 2015 were enrolled. They underwent both MDCT and digital tomosynthesis. Images were interpreted by two experienced radiologists, and inter-reader agreement was assessed. The diagnostic performance of urinary stones with digital tomosynthesis and MDCT was compared. The entrance surface dose (ESD) in MDCT and digital tomosynthesis for patients was measured and compared. Results: No significant difference was found between digital tomosynthesis and MDCT in the diagnosis of urinary stones (X2 = 1.357, p > 0.05). The ESD in digital tomosynthesis was lower than that in both routine-dose and low-dose MDCT for patients (p < 0.05). Conclusions: Digital tomosynthesis has great diagnostic value in urolithiasis. Compared with MDCT, digital tomosynthesis can significantly decrease ESD for patients and financial loan with a similar detection rate.

15.
Environ Technol ; : 1-9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810427

RESUMO

In this study, biochars were produced by co-pyrolysis of rice husk and sewage sludge, the environmental risk of heavy metal (Pd and Cd) in the biochars was assessed. Co-pyrolysis resulted in a lower yield but a higher C content compared with sewage sludge pyrolysis alone, the relative contents of Pb and Cd in biochars were declined. Co-pyrolysis process transformed the bioavailable heavy metals into stable speciation. The environmental risk assessment codes of Pb and Cd were reduced by 1-2 grades. The co-pyrolysis technology provides a feasible method for the safe disposal of heavy metal-contaminated sewage sludge.

16.
Naunyn Schmiedebergs Arch Pharmacol ; 393(1): 77-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31420720

RESUMO

Norfloxacin, a frequently used ocular antibiotic, might have cytotoxic effect on human corneal endothelial cells (HCECs), subsequently damage the cornea and finally impair human vision. However, the possible mechanisms of cytotoxicity of norfloxacin to HCEC line are unclear. Herein, we investigated the cytotoxicity of norfloxacin and its underlying cellular and molecular mechanisms using in vitro cultured non-transfected HCECs and verified the cytotoxicity with cat corneal endothelium in vivo. In the present study, the cytotoxicity of norfloxacin in the in vitro cultured HCECs was recognized by causing abnormal morphology such as cell shrinkage and detachment from plate bottom, and decline of viability of in vitro cultured HCECs. Then, its cytotoxicity was verified by inducing reduction of cell density and morphological abnormality of in vivo cat corneal endothelial cells. Furthermore, the cytotoxicity of norfloxacin in HCECs was corroborated as apoptosis by elevation of plasma membrane permeability, S phase arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation in in vitro cultured HCECs and apoptosis-like swollen cells in the in vivo model. Moreover, norfloxacin induced extrinsic death receptor-mediated apoptosis pathway by activating caspase-2/-8/-3 and intrinsic mitochondrion-dependent apoptosis pathway by downregulating anti-apoptotic Bcl-2 and upregulating of pro-apoptotic Bad, which disrupted mitochondrial transmembrane potential, subsequently upregulated cytoplasmic cytochrome c and apoptosis-inducing factor and finally activated caspase-9/-3. Generally, norfloxacin induces HCE cell apoptosis via a death receptor-mediated and mitochondrion-dependent signaling pathway.

17.
Electrophoresis ; 41(3-4): 183-193, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31850545

RESUMO

In this paper, the development of a simple dilute-and-shoot method for quantifying urinary creatinine by CE-ESI-MS was described. The creatinine analysis time was about 7 min/sample by conventional single injection (SI) method and can be significantly reduced to less than 2 min/sample with multi-segment injection (MSI). In addition, the standard addition analysis of 5-hydroxyindole-3-acetic acid (5-HIAA) and creatinine normalization was performed within one run by the MSI technique, and the total analysis time was 14-min faster compared to the SI method for analyzing the same set of samples. The uses of isotopic and non-isotopic internal standards (ISs) were compared. Creatinine-(methyl-13 C) and 5-hydroxyindole-4,6,7-D3 -3-acetic-D2 acid (5-HIAA-D5 ) used as isotopic ISs can provide both accurate and precise results. In contrast, 1,5,5-trimethylhydantoin (1,5,5-TH) used as the non-isotopic IS for creatinine may cause a bias of over 13% in SI method and even worse when the MSI technique was used. Another compound, 2-methyl-3-indoleacetic acid (2-MIAA), was determined not suitable for MSI analysis of 5-HIAA due to endogenous interferences despite its acceptable performance in conventional methods of analysis.

18.
Colloids Surf B Biointerfaces ; 185: 110633, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31740324

RESUMO

The microcystin-LR (MC-LR) produced due to harmful cyanobacterial blooms have brought great harm to human and aquatic organisms, attracting a wide public health attention. To deal with MC-LR contamination, we synthesized a novel bio-functionalized composite for the high-efficient and sustainable biodegradation of microcystin-LR by covalent immobilizing Sphingopyxis sp. YF1 onto chitosan-grafted Fe3O4 magnetic particles (Fe3O4@CTS). The Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (SEM) and vibrating sample magnetometry (VSM) were utilized to characterize the structural properties of Fe3O4@CTS/Sphingopyxis sp. YF1. The immobilization conditions were optimized. And the MC-LR-degrading capabilities of Fe3O4@CTS/Sphingopyxis sp. YF1 were assessed under various conditions. The results showed that the optimal immobilization conditions containing 1.0 % (v/v) glutaraldehyde, immobilization for 4 h at 30 ℃. The Fe3O4@CTS/Sphingopyxis sp. YF1 showed an attractive degradation performance which possesed a wide torlerance to pH (6.0-9.0) and temperature (25-35 ℃). More interesting is that the Fe3O4@CTS/Sphingopyxis sp. YF1 exhibited significantly increased MC-LR-degrading capabilities after recycling and reusing which degradation rate reached 1.50 µg/mL/h in the sixth cycle, and it was easily recycled by using a magnet (Ms 21.5 emug-1). Two intermediates (tetrapeptide and Adda) and three degradation related genes (mlrA, mlrB and mlrC) were obtained in this study and the pathway for the degradation was proposed. These results revealed that Fe3O4@CTS/Sphingopyxis sp. YF1 can be potentially used for treatment of MC-LR contaminated environment.

19.
Nature ; 577(7790): 386-391, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875851

RESUMO

The motor cortex controls skilled arm movement by sending temporal patterns of activity to lower motor centres1. Local cortical dynamics are thought to shape these patterns throughout movement execution2-4. External inputs have been implicated in setting the initial state of the motor cortex5,6, but they may also have a pattern-generating role. Here we dissect the contribution of local dynamics and inputs to cortical pattern generation during a prehension task in mice. Perturbing cortex to an aberrant state prevented movement initiation, but after the perturbation was released, cortex either bypassed the normal initial state and immediately generated the pattern that controls reaching or failed to generate this pattern. The difference in these two outcomes was probably a result of external inputs. We directly investigated the role of inputs by inactivating the thalamus; this perturbed cortical activity and disrupted limb kinematics at any stage of the movement. Activation of thalamocortical axon terminals at different frequencies disrupted cortical activity and arm movement in a graded manner. Simultaneous recordings revealed that both thalamic activity and the current state of cortex predicted changes in cortical activity. Thus, the pattern generator for dexterous arm movement is distributed across multiple, strongly interacting brain regions.

20.
Neuroreport ; 31(3): 226-234, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31876687

RESUMO

Gliomas are the most common, malignant, and lethal tumors in adults. Furthermore, gliomas are highly resistant to current chemotherapeutic drugs. Thus, new effective anticancer drugs for glioma are urgently needed. Selenium nanoparticles have been reported to have potent anti-tumor activity, although the specific mechanism is not fully understood. This study aimed to test the anti-tumor effect of selenium nanoparticles and its mechanism. We used selenium nanoparticles to treat commercial glioma cell lines, and patient-derived glioma cells, and then used the MTT assay to determine selenium nanoparticles effect against these. Apoptotic cell death was determined by annexin V-Fluos staining kit. Glucose uptake, lactate, and adenosine triphosphate production, together with hexokinase 2 and pyruvate kinase activities were measured to determine the glucose metabolism level. Reactive oxygen species production was tested using 2',7'-dichlorodihydrofluorescein diacetate. Our results showed that selenium nanoparticles had a potent cytotoxic effect in glioma cells, regardless of whether they were drug-resistant or not, whereas it showed less toxic effect in normal healthy cells. Further tests showed that selenium nanoparticles treatment leads to apoptotic cell death enhancement and glucose metabolism reduction, and this process was in a reactive oxygen species pathway-dependent manner. These results may provide a novel direction for glioma therapy in the future.

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