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1.
Nanotechnology ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31978900

RESUMO

Heteroatom doping has recently been utilized to improve the catalytic performance of transition metal-based electrocatalysts. However, the doping process is inevitably accompanied by the introduction of oxygen, influencing the heteroatom-induced asymmetric spin density over the active sites and leading to inconspicuous promotion in the property. Herein, by wiping off the undesired heteroatom-oxygen bonding, we maximize the heteroatom-induced improvement in oxygen reaction activity of metal site, providing descendant energy barrier and favorable reaction efficiency for zinc-air batteries. The proof-of-concept material delivers a superior half-wave potential of 0.88 V versus reversible hydrogen electrode for oxygen reduction reaction, a small overpotential of 410 mV at the current density of 10 mA cm-2 for oxygen evolution reaction, and a reversible oxygen electrode index of 0.76 V in electrochemical measurements. Aqueous zinc-air battery with such catalysts delivers an excellent power density of 162.3 mW cm-2 and superior durability over 635 cycles. Moreover, in consideration of high safety and flexibility of solid-state batteries, all-solid-state zinc-air battery adopting gel as electrolyte is assembled and used to illumine an LED wristband, showing great promises for the next-generation energy system.

2.
J Hazard Mater ; 388: 122081, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31958610

RESUMO

The heavy metals, namely lead (Pb), cadmium (Cd), and mercury (Hg), have been studied extensively in various independent studies. It has been seen that these metals are usually detected simultaneously in the human blood at low levels. However, it is unknown whether exposure to these heavy metal mixtures (MM) can induce neurological damages at these low levels. Therefore, we investigated the influence of the Pb, Cd, and Hg mixture on the nervous system in rats at exposure doses equivalent to those normally found in the human blood. After pregnant rats being exposed to MM via drinking water throughout the gestation and lactation, their offspring were followed-up till adulthood. MM caused cognitive deficits and impairments in a dose-dependent manner. Furthermore, MM disrupted dendritic spines, the structural basis of learning and memory, and induced changes in spine-related pathways. Meanwhile, we explored an early and safe way to remedy these impairments through a postnatal enriched environment. The enriched environment ameliorated MM-impaired cognitive function, synaptic plasticity, and spine-related pathways. This study demonstrated that low-dose co-exposure to Pb, Cd, and Hg can cause cognitive and synaptic plasticity deficits and timely intervention through the enriched environment has a certain corrective effect.

3.
ACS Appl Mater Interfaces ; 12(3): 3603-3609, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31891482

RESUMO

Metal-air batteries have exhibited unlimited potential and economic value because of their considerably high energy density. However, under repeated cycling, air cathodes undergo a well-known problem, the deposition of metal oxide, clogging the active surface and ultimately leading to the severe degradation of the cyclic performance. Herein, we address this challenge in a zinc-air battery by introducing ketone as the Lewis base into the air catalyst. As illustrated by in situ X-ray diffraction observations, the ketone-enriched material could generate an ultrahigh negative potential to prevent the access of negatively charged zincate ions and thus enable the nondeposition of zinc oxide on the air cathode because of the strong electrostatic repulsion. Using this strategy, we demonstrate 650 highly stable cycles of a zinc-air battery under a high rate (25 mA cm-2). Such a Lewis-base-assisted method opens up new avenues to prevent air cathodes from being poisoned for highly durable metal-air batteries.

4.
Sci Total Environ ; 706: 135691, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31784180

RESUMO

The diffusion coefficient (D) is a key physicochemical parameter for the diffusive gradients in thin films technique (DGT) for environmental sampling, which has been extended to organic chemicals (so called o-DGT). D can be measured in the laboratory, although for organic chemicals this parameter might be predicted based on chemical structure. Here we developed for the first time a Quantitative Structure-Property Relationship (QSPR) model to predict the D values. Twenty quantum chemical descriptors that quantify the electronic and energy properties of 120 organic compounds were selected together with molecular mass, solubility and hydrophobicity. The best QSPR model was established by using genetic algorithm and multiple linear regression (GA-MLR). The results indicated that the model derived from the average molecular polarizability (α), the chemical potential (ξ) and the global electrophilicity index (ω) could explain the diffusion of organics in o-DGT and had good statistical performance (R2 = 0.767, RMSE = 0.101). Different validation strategies confirmed that the developed model was robust and predictive. 93% of tested compounds were within the applicability domain (AD) and predicted accurately. We concluded that the proposed QSPR model can serve as an efficient predictive tool for new chemicals in the AD, would be useful to cross validate measured D values and provide a better the understanding of the diffusive behaviour of organics in o-DGT and measurements in the environment. It might also be useful in the non-target analysis with o-DGT for chemicals without measured D values.

5.
J Neurochem ; 152(2): 221-234, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31390677

RESUMO

Histone deacetylase 6 (HDAC6) activity contributes to the malignant proliferation, invasion, and migration of glioma cells (GCs), but the molecular mechanisms underlying the processes remains elusive. Here, we reported that HDAC6 inhibition by Ricolinostat (ACY-1215) or CAY10603 led to a remarkable decrease in the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun, which preceded its suppressive effects on glioma cell growth. Further investigation showed that these effects resulted from HDAC6 inhibitor-induced suppression of MAPK kinase 7 (MKK7), which was identified to be critical for JNK activation and exerts the oncogenic roles in GCs. Selectively silencing HDAC6 by siRNAs had the same responses, whereas transient transfections expressing HDAC6 promoted MKK7 expression. Interestingly, by performing Q-PCR, HDAC6 inhibition did not cause a down-regulation of MKK7 mRNA level, whereas the suppressive effects on MKK7 protein can be efficiently blocked by the proteasomal inhibitor MG132. As a further test, elevating MKK7-JNK activity was sufficient to rescue HDAC6 inhibitor-mediated-suppressive effects on c-Jun activation and the malignant features. The suppression of both MKK7 expression and JNK/c-Jun activities was involved in the tumor-growth inhibitory effects induced by CAY10603 in U87-xenograft mice. Collectively, our findings provide new insights into the molecular mechanism of glioma malignancy regarding HDAC6 in the selective regulation of MKK7 expression and JNK/c-Jun activity. MKK7 protein stability critically depends on HDAC6 activity, and inhibition of HDAC6 probably presents a potential strategy for suppressing the oncogenic roles of MKK7/JNK/c-Jun axis in GCs.

6.
Pestic Biochem Physiol ; 162: 6-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31836055

RESUMO

The beet armyworm (Spodoptera exigua) is a highly polyphagous agricultural pest that is distributed worldwide. However, the adaptive mechanisms of S. exigua for various insecticides and defensive substances in host plants are unknown. Insect P450 monooxygenases play an important role in the detoxification of plant toxins and insecticides, leading to insecticides resistance. We investigated the induced effects of xanthotoxin exposure on detoxification enzyme activity and larval tolerance to α-cypermethrin in S. exigua. Our results showed that the lethal concentration (LC50) of α-cypermethrin for xanthotoxin-exposed larvae was 2.1-fold higher than in the control. Moreover, cytochrome P450 enzyme activity was significantly elevated by upregulation of P450 genes in treated larvae. RT-qPCR results showed that CYP9A10 expression level was significantly increased in all treatments, while maximal expression level was observed in xanthotoxin+α-cypermethrin-fed larvae. RNAi-mediated silencing of CYP9A10 further increased mortality by 18%, 26% and 35% at 48 h and by 27%, 43% and 55% at 72 h when larvae were exposed to diets containing chemicals as compared to the control. The results show that CYP9A10 might play an important role in xanthotoxin and α-cypermethrin detoxification in S. exigua. RNAi-mediated silencing could provide an effective synergistic agent for pest control or insecticide resistance management.

7.
ACS Appl Mater Interfaces ; 12(2): 2566-2571, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31854183

RESUMO

PbSe colloidal quantum dots (CQDs) are widely used in solar cells because of their tunable band gap, solution processability, and efficient multiple exciton generation effect. The most efficient PbSe CQD solar cells use high-temperature-processed ZnO as the electron transport layer (ETL), limiting their applications in flexible photovoltaics. Currently, low-temperature solution-processed SnO2 has been demonstrated as an efficient ETL for high-efficient PbS CQD and perovskite solar cells because of less parasitic light absorption and higher electron mobility. Herein, we introduce low-temperature solution-processed SnO2 as ETL for PbSe CQD solar cells, and fabricate the PbSe CQD absorber layer with a one-step spin-coating method. The champion device with the structure of FTO (SnO2:F)/SnO2/PbSe-PbI2/PbS-EDT (1,2-ethanedithiol)/Au achieves a high open-circuit voltage of 577.1 mV, a short-circuit current density of 24.87 mA cm-2, a fill factor of 67%, and an impressive power conversion efficiency of 9.67%. Our results pave the way for the development of low-temperature flexible PbSe CQD solar cells.

8.
J Magn Reson Imaging ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785074

RESUMO

BACKGROUND: Central nervous system inflammation is associated with neurodegenerative diseases and is thought to play a part in the pathophysiological cascade leading to cognitive impairment. Madecassoside (MA) has shown potential for the treatment of neuroinflammation. Lipopolysaccharide (LPS) can be used to establish an animal model of cognitive dysfunction induced by neuroinflammation. Intravoxel incoherent motion (IVIM) may potentially provide diffusion and perfusion data. PURPOSE: To investigate the effect of MA on neurocognitive impairment induced by LPS in rats, and to explore the changes of brain microstructure and microcirculatory perfusion by IVIM imaging. STUDY TYPE: Prospective. POPULATION: Thirty-six male Sprague-Dawley rats were randomly divided into six groups (control group, sham operation group, LPS group, low-dose MA group, middle-dose MA group, and high-dose MA group) in a model of neurocognitive impairment induced by LPS (150 µg / 5 µL, 5 µL). FIELD STRENGTH/SEQUENCE: IVIM-DWI sequence at 3.0T MRI; the scan time was 2 minutes and 17 seconds. ASSESSMENT: The escape latency times of a Morris water maze test was used to evaluate the cognitive impairment rat model and the changes of learning ability of rats treated with different doses of MA (30 mg/kg, 60 mg/kg, 120 mg/kg). A GE postprocessing workstation (adw 4.5) was used to analyze the changes of each parameter (f value, D value, and D* value) in the IVIM data of each group. STATISTICAL TESTS: All the data were analyzed by one-way and two-way analysis of variance (ANOVA). RESULTS: The escape latency of the LPS group was significantly longer than the sham group (P = 0.05, 0.001, 0.006, and 0.042, respectively), and the high-dose group was significantly shorter than the LPS group on the sixth day (P = 0.034). Compared with the control group, the D values and f values of cerebral cortex and hippocampus were decreased significantly in the LPS group (P = 0.043 and 0.003; P = 0.029 and 0.016, respectively). With the increasing dose of MA, the D and f values of hippocampus and cortex increased, and there was a significant difference between the high-dose MA group and LPS group (D values: P = 0.038, 0.036; f values: P = 0.048, 0.039, respectively) DATA CONCLUSION: MA can improve the cognitive impairment induced by LPS by reducing neuroinflammation, and the changes of microcirculation and microperfusion in the brain tissue of these rats can be detected by IVIM imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31840197

RESUMO

During our investigation on the endophytic fungi of Azadirachta indica, the strain YM 311593 was obtained from the fruit of the plant. The culture extract of the strain showed antifungal activities against four phytopathogenic fungi. Based on the morphological features and phylogenetic definition, the strain YM 311593 was identified as Paraconiothyrium sp. Four xanthones and one anthraquinone were obtained from the extract of the fermentation broth of the strain. They were characterized to be globosuxanthone A (1), vertixanthone (2), hydroxyvertixanthone (3), 3,8-dihydroxy-1-methy1-9H- xanthen-9-one (4), and danthron (5), respectively, by spectroscopic elucidation. Furthermore, the absolute configuration of 1 was deduced by X-ray diffraction analysis. Besides, compound 4 was firstly found from natural sources. The antifungal activities of compounds 1-5 towards four phytopathogens were assayed using broth microdilution method. Among them, globosuxanthone A (1) showed obvious antifungal activity towards Fusarium graminearum, Fusarium solani, and Botrytis cinerea with MIC values of 4, 8, and 16 µg/mL, respectively.

10.
Front Oncol ; 9: 1319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828041

RESUMO

Background: ALK and ROS1 rearrangement accounts for 3-6% and 1-3% of non-small cell lung cancers, respectively, while coexistence of them in the same patient is extremely rare. Only three cases have ever been reported with concurrent ALK/ROS1 fusions in the same tumor indicating tumor heterogeneity. Therefore, comprehensive genetic profiling via next-generation sequencing (NGS) is needed to provide fully molecular diagnosis. Case Presentation: A 50-year old Chinese female with resectable stage IB bilateral lung adenocarcinomas (ADCs) harbored EML4 exon 6-ALK exon 19 and TPM3 exon 8-ROS1 exon 35 fusions in the right lower and the left upper tumors, respectively, identified by clinical NGS test targeting 425 cancer-relevant genes. The results were further confirmed at RNA level using RNA-seq. Genomic evolution analysis reveals that these bilateral tumors are synchronous multiple primary lung cancers with no shared somatic alterations for both genes and arm-level copy number variations (CNVs). No recurrence was observed during 12 months of post-surgery follow-up. Conclusions: Our case is the first report of concurrent ALK/ROS1 fusions as distinct driver events of synchronous multiple primary lung cancers, and highlights the importance of individual genetic testing for each of the multiple primary tumors for fully molecular diagnosis and precise treatment decision-making.

11.
Front Cell Neurosci ; 13: 468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708743

RESUMO

The c-Jun N-terminal kinase (JNK)/c-Jun cascade-dependent neuronal apoptosis has been identified as a central element for early brain injury (EBI) following subarachnoid hemorrhage (SAH), but the molecular mechanisms underlying this process are still thoroughly undefined to date. In this study, we found that pan-histone deacetylase (HDAC) inhibition by TSA, SAHA, VPA, and M344 led to a remarkable decrease in the phosphorylation of JNK and c-Jun, concomitant with a significant abrogation of apoptosis caused by potassium deprivation in cultured cerebellar granule neurons (CGNs). Further investigation showed that these effects resulted from HDAC inhibition-induced transcriptional suppression of MKK7, a well-known upstream kinase of JNK. Using small interference RNAs (siRNAs) to silence the respective HDAC members, HDAC4 was screened to be required for MKK7 transcription and JNK/c-Jun activation. LMK235, a specific HDAC4 inhibitor, dose-dependently suppressed MKK7 transcription and JNK/c-Jun activity. Functionally, HDAC4 inhibition via knockdown or LMK235 significantly rescued CGN apoptosis induced by potassium deprivation. Moreover, administration of LMK235 remarkably ameliorated the EBI process in SAH rats, associated with an obvious reduction in MKK7 transcription, JNK/c-Jun activity, and neuronal apoptosis. Collectively, the findings provide new insights into the molecular mechanism of neuronal apoptosis regarding HDAC4 in the selective regulation of MKK7 transcription and JNK/c-Jun activity. HDAC4 inhibition could be a potential alternative to prevent MKK7/JNK/c-Jun axis-mediated nervous disorders, including SAH-caused EBI.

12.
Int J Mol Sci ; 20(22)2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718025

RESUMO

Lagerstroemia indica is an important ornamental tree worldwide. The development of cultivars with colorful leaves and increased ornamental value represents one of the current main research topics. We investigated the anthocyanin profiles in two contrasting cultivars for leaf color phenotypes and explored the underlying molecular basis. Both cultivars display purple-red young leaves (Stage 1), and when the leaves mature (Stage 2), they turn green in HD (Lagerstroemia Dynamite) but remain unchanged in ZD (Lagerstroemia Ebony Embers). Seven different anthocyanins were detected, and globally, the leaves of ZD contained higher levels of anthocyanins than those of HD at the two stages with the most pronounced difference observed at Stage 2. Transcriptome sequencing revealed that in contrast to HD, ZD tends to keep a higher activity level of key genes involved in the flavonoid-anthocyanin biosynthesis pathways throughout the leaf developmental stages in order to maintain the synthesis, accumulation, and modification of anthocyanins. By applying gene co-expression analysis, we detected 19 key MYB regulators were co-expressed with the flavonoid-anthocyanin biosynthetic genes and were found strongly down-regulated in HD. This study lays the foundation for the artificial manipulation of the anthocyanin biosynthesis in order to create new L. indica cultivars with colorful leaves and increased ornamental value.

13.
Nanoscale ; 11(46): 22230-22236, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31735944

RESUMO

Surface-enhanced Raman scattering (SERS) spectroscopy aims to augment the relatively weak molecular vibrations based on electromagnetic enhancement (EE) and chemical enhancement (CE) mechanisms, and offers a potential way for material identification, even up to the single-molecule level, under atmospheric conditions. We have subtly combined the advantages of EE and CE, and propose new MXene (Ti3C2TX) nano-sheet/Au nanostructure architectures to break through the limitations of the Raman detection with long-time stability. The MXene nanosheets with excellent biocompatibility can effectively prevent structural distortion from the interaction with the Au NSs, and can also guarantee a high enhancement effect owing to the spatially extended electromagnetic field distribution and electron injection into the molecules. The self-assembled Au nanostructures are aggregated based on the Volmer-Weber growth model, and the electromagnetic field distribution radically evolves depending on the morphologies of the resultant Au nanostructures, leading to a drastic compensation for the limited EE of the MXene nano-sheets. Consequently, the intensified Raman vibrational signals of R6G molecules lead to a high enhancement factor of 2.9 × 107, even at an ultra-low concentration of 10-10 M. Similarly, the Raman signals of the methylene blue (MB) and crystal violet (CV) molecules can also be detected at low concentrations below 10-8 M, manifesting universal applications of the MXene/Au architectures for ultra-sensitive molecular detection under atmospheric conditions.

14.
Acta Biomater ; 100: 52-60, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606530

RESUMO

Vascular stiffening is associated with the prognosis of cardiovascular disease (CVD). Endothelial dysfunction, as shown by reduced vasodilation and increased vasoconstriction, not only affects vascular tone, but also accelerates the progression of CVD. However, the precise effect of vascular stiffening on endothelial function and its mechanism is unclear and a possible underlying has not been determined. In this study, we found that increasing substrate stiffness promoted endothelin-1 (ET-1) expression and inhibited endothelial nitric oxide synthase expression in human umbilical vein endothelial cells. Additionally, miR-6740-5p was identified as a stiffness-sensitive microRNA, which was downregulated by a stiff substrate, resulting in increased ET-1 expression. Furthermore, we found that substrate stiffening reduced the expression and activity of the calcium channel TRPV4, which subsequently enhanced ET-1 expression by inhibiting miR-6740-5p. Finally, analysis of clinical plasma samples showed that plasma miR-6740-5p levels in patients with carotid atherosclerosis were significantly lower than those in healthy people. Taken together, our findings show a novel mechanically regulated TRPV4/miR-6740/ET-1 signaling axis by which substrate stiffness affects endothelial function. Our findings indicate that vascular stiffening induces endothelial dysfunction, thereby accelerating progression of CVD. Furthermore, this study indicates that endothelial dysfunction induced by improper biophysical cues from cardiovascular implants may be an important reason for complications arising from the use of cardiovascular implants. STATEMENT OF SIGNIFICANCE: Cardiovascular disease is the leading cause of morbidity and mortality worldwide. The incidence of cardiovascular disease is accompanied by increased vascular stiffness. Our work indicated that increased vascular stiffness accelerates the development of cardiovascular disease by inducing endothelial dysfunction, which is a key contributor to the pathogenesis of cardiovascular disease. In addition, we identified a novel underlying molecular pathophysiological mechanism by which increased stiffness induce endothelial dysfunction. Our work could help determine the pathogenesis of cardiovascular disease induced by biomechanical factors.

15.
G3 (Bethesda) ; 9(11): 3663-3672, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31506321

RESUMO

Platycladus orientalis is an ecologically important native conifer in Northern China and exotic species in many parts of the world; however, knowledge about the species' genetics and genome are very limited. The availability of well-developed battery of genetic markers, with large genome coverage, is a prerequisite for the species genetic dissection of adaptive attributes and efficient selective breeding. Here, we present a genome-wide genotyping method with double-digestion restriction site associated DNA sequencing (ddRAD-seq) that is effective in generating large number of Mendelian markers for genome mapping and other genetic applications. Using 139 megagametophytes collected from a single mother tree, we assembled 397,226 loci, of which 108,683 (27.4%) were polymorphic. After stringent filtering for 1:1 segregation ratio and missing rate of <20%, the remaining 23,926 loci (22% of the polymorphic loci) were ordered into 11 linkage groups (LGs) and distributed across 7,559 unique positions, with a total map length of 1,443 cM and an average spacing of 0.2 cM between adjacent unique positions. The 11 LGs correspond to the species' 11 haploid genome chromosome number. This genetic map is among few high-density maps available for conifers to date, and represents the first genetic map for P. orientalis The information generated serves as a solid foundation not only for marker-assisted breeding efforts, but also for comparative conifer genomic studies.

16.
Life Sci ; 235: 116802, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472150

RESUMO

Substrate stiffness is essential for cell functions, but the mechanisms by which cell sense mechanical cues are still unclear. Here we show that the frequency and the amplitude of spontaneous Ca2+ oscillations were greater in chick cardiomyocytes cultured on the stiff substrates than that on the soft substrates. The spontaneous Ca2+ oscillations were increased on stiff substrates. However, an eliminated dependence of the Ca2+ oscillations on substrate stiffness was observed after applying blocker of the large-conductance Ca2+-activated K+ (BK) channels. In addition, the activity of BK channels in cardiomyocytes cultured on the stiff substrates was decreased. These results provide compelling evidences to show that BK channels are crucial in substrate stiffness-dependent regulation of the Ca2+ oscillation in cardiomyocytes.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Ventrículos do Coração/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Embrião de Galinha , Galinhas , Miócitos Cardíacos/citologia , Especificidade por Substrato
17.
ACS Appl Mater Interfaces ; 11(36): 33054-33061, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31419105

RESUMO

Rechargeable Zn-air batteries have drawn great attention over the past decade, but their further development will require efficient bifunctional electrocatalysts to drive the sluggish cathodic reactions. Although a single-atom catalyst with maximum utilization per metal atom shows great promise, its catalytic performance is still far from satisfactory. Here we tackle this challenge by introducing a P-O bond to update the intrinsic activity of a single-atom site and thus reduce the reaction overpotential of the Zn-air battery. The critical role of the P-O bond in producing a favorable surface electronic environment of the single-atom metal site and improving its catalytic activity is identified with density functional theory simulations. The P-O-doped, atomically dispersed catalyst is shown experimentally to deliver excellent bifunctional performance, with a remarkable half-wave potential of 0.89 V versus reversible hydrogen electrode (vs RHE) for oxygen reduction reaction and a reversible oxygen electrode index of 0.74 V, exceeding those of most reported nonprecious metal catalysts. When subjected to practical application, both aqueous and all-solid-state Zn-air batteries illustrate superior power density and robust cyclic performance, confirming their potential feasibility in next-generation electronic devices.

18.
Nat Commun ; 10(1): 3898, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467283

RESUMO

Covalent organic frameworks with abundant active sites are potential metal-free catalysts for the nitrogen reduction reaction. However, the utilization ratio of active sites is restricted in an actual reaction process due to the limited nitrogen transport. Here, we demonstrate that facilitating the N2 accessibility to boron-rich covalent organic frameworks through electrochemical excitation can achieve highly efficient nitrogen reduction activity. Simulations show that the boron sites are bonded with nitrogenous species under electrochemical condition and the resultant amorphous phase of covalent organic frameworks has much stronger affinity toward N2 to enhance the molecule collision. Combined with experimental results, the excitation process is confirmed to be a virtuous cycle of more excited sites and stronger N2 affinity, which continuously proceed until the whole system reaches the optimum reaction status. As expected, the electrochemically excited catalyst delivers significantly enhanced reaction activity, with a high Faradaic efficiency of 45.43%.

19.
Neurosci Lett ; 709: 134386, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31330225

RESUMO

Neuroinflammation is a predisposing factor for several neurodegenerative diseases. The purpose of this study was to evaluate the protective effect of madecassoside (MA) in lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in rats. MA has many protective effects such as antioxidant and anti-inflammatory properties. We investigated whether MA could improve neurocognitive dysfunction caused by intracerebroventricular injection of LPS. We examined the effects and mechanisms of action of MA on LPS-induced neuroinflammation in the cortex and hippocampus. Our study revealed that MA (120 mg/kg, i.g) treatment for 14 days reduced LPS-induced neurotoxicity by reducing cognitive impairments and suppressing the production of inflammatory cytokines such as interleukin 1 beta (IL-1ß), tumor necrosis factor alpha(TNF-α), and interleukin 6(IL-6) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Furthermore, MA treatment enhanced protein levels of heme oxygenase (HO)-1 by upregulating Nrf2 in LPS-stimulated neurotoxicity. Collectively, these results suggest that MA is effective in preventing neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and activation of Keap1-Nrf2/HO-1 signaling. As such, MA may be a potential therapy for addressing memory impairment caused by neuroinflammation.

20.
EMBO J ; 38(14): e99945, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304624

RESUMO

TGF-ß controls a variety of cellular functions during development. Abnormal TGF-ß responses are commonly found in human diseases such as cancer, suggesting that TGF-ß signaling must be tightly regulated. Here, we report that protein tyrosine phosphatase non-receptor 3 (PTPN3) profoundly potentiates TGF-ß signaling independent of its phosphatase activity. PTPN3 stabilizes TGF-ß type I receptor (TßRI) through attenuating the interaction between Smurf2 and TßRI. Consequently, PTPN3 facilitates TGF-ß-induced R-Smad phosphorylation, transcriptional responses, and subsequent physiological responses. Importantly, the leucine-to-arginine substitution at amino acid residue 232 (L232R) of PTPN3, a frequent mutation found in intrahepatic cholangiocarcinoma (ICC), disables its role in enhancing TGF-ß signaling and abolishes its tumor-suppressive function. Our findings have revealed a vital role of PTPN3 in regulating TGF-ß signaling during normal physiology and pathogenesis.


Assuntos
Neoplasias Hepáticas/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 3/genética , Proteína Tirosina Fosfatase não Receptora Tipo 3/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Substituição de Aminoácidos , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Transplante de Neoplasias , Fosforilação , Estabilidade Proteica , Receptor do Fator de Crescimento Transformador beta Tipo I/química , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Proteínas Smad/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
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