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1.
Food Chem ; 337: 127654, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791428

RESUMO

This study aimed to improve the physicochemical stability of nanoliposome (NL) with enhanced functionality for the delivery of Pelargonidin-3-O-glucoside (P3G) using biopolymers, i.e. chitosan (CH) and pectin (P). In this study, we successfully developed stabilized liposomal carriers, i.e. CH-conjugated NL (CH-NL) and P-conjugated CH-NL (P-CH-NL) using an optimum concentration of CH (0.6 wt%) and P (0.5 wt%). Results revealed that P-CH-NL had better physical stability to salt and pH with maximum P3G retention (>97%) under oxidative, thermal, and UV conditions. Nanoliposomes were more stable under refrigerated-storage and ensured high P3G retention (>96%). In vitro mucoadhesion study revealed that CH-NL had better mucin adsorption efficiency (59.72%) followed by P-CH-NL and NL. Furthermore, CH-NL and P-CH-NL alternatively had better stability to serum than NL. Taken together, the stabilization of nanoliposome using chitosan and pectin can be a promising approach for the delivery of hydrophilic compounds in association with enhanced stability and functionality.

2.
Food Funct ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000849

RESUMO

Obesity is a chronic disease that has been causing serious problems all over the world. However, there is a lack of available therapeutic approaches to treat obesity. The FDA-approved drug orlistat has severe side effects, such as abdominal pain, flatulence and oily stool. As the therapeutic target of orlistat is pancreatic lipase, there is an urgent need for discovery of new pancreatic lipase inhibitors from natural sources that have reduced side effects compared with orlistat. In this study, ultrafiltration in combination with molecular simulation and spectroscopy was reported as an effective approach for identifying new pancreatic lipase inhibitors from anthocyanin-rich berry sources. Using this approach, four monomeric anthocyanins cyanidin-3-O-arabinoside (C3A), cyanidin-3-O-galactoside (C3Ga), peonidin-3-O-arabinoside (Pn3A) and peonidin-3-O-galactoside (Pn3Ga) from cranberries were discovered as potent pancreatic lipase inhibitors. These four cranberry anthocyanins were shown to form hydrophobic interactions and hydrogen bonds with pocket amino acid residues in molecular docking and molecular dynamics simulations. C3A showed greater impact on secondary structures of the enzyme and showed higher binding capacity with the enzyme compared with C3Ga, Pn3A and Pn3Ga as observed by CD and fluorescence spectroscopy. The structure-activity relationships were then investigated and summarized as both the structures of the B ring and glycosyl group were related to the inhibitory activities of anthocyanins. In short, our results suggested that cranberry anthocyanins could be developed as food supplements to facilitate the prevention and treatment of obesity.

3.
Org Lett ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021797

RESUMO

A pair of new macrocyclic spermidine alkaloids, (+)-(S)-scocycamide and (-)-(R)-scocycamide, were isolated from the roots of Scopolia tangutica. Their structures were established by extensive spectroscopic data, electronic circular dichroism analyses, and chemical synthesis. They featured a unique 6/18 fused bicyclic framework with spermidine and catechol units, representing a new subtype of natural spermidine alkaloids. A plausible biosynthetic pathway was also proposed. They inhibited butyrylcholinesterase and exhibited antioxidant capacity, suggesting beneficial constituents against Alzheimer's disease and oxidation.

4.
Diabetes Care ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023987

RESUMO

OBJECTIVE: Patients with diabetes and chronic kidney disease (CKD) have increased susceptibility to acute kidney injury (AKI), but mechanisms are unclear. We investigated the association of glycemic control with risk of AKI. RESEARCH DESIGN AND METHODS: In two observational cohorts of U.S. (Geisinger Health System, Danville, PA) and Swedish (Stockholm CREAtinine Measurements [SCREAM] project, Stockholm, Sweden) adults with type 2 diabetes and confirmed CKD stages G3-G5 undergoing routine care, we evaluated associations between baseline and time-varying hemoglobin A1c (HbA1c) with the incident AKI (defined as increase in creatinine ≥0.3 mg/dL over 48 h or 1.5 times creatinine over 7 days). RESULTS: In the U.S. cohort, there were 22,877 patients (55% women) with a median age of 72 years and estimated glomerular filtration rate (eGFR) 52 mL/min/1.73 m2. In the Swedish cohort, there were 12,157 patients (51% women) with a median age of 76 years and eGFR 51 mL/min/1.73 m2. During 3.1 and 2.3 years of follow-up, 7,060 and 2,619 AKI events were recorded in the U.S. and Swedish cohorts, respectively. The adjusted association between baseline HbA1c and AKI was similar in both cohorts. Compared with baseline HbA1c 6-6.9% (42-52 mmol/mol), the hazard ratio for AKI in patients with HbA1c >9% (75 mmol/mol) was 1.29 (95% CI 1.18-1.41) in Geisinger and 1.33 (95% CI 1.13-1.57) in the Swedish cohort. Results were consistent in stratified analysis, when using death as competing risk, and when using time-varying HbA1c. CONCLUSIONS: Higher HbA1c was associated with AKI in adults with type 2 diabetes and CKD, suggesting that improving glycemic control may reduce the risk of AKI.

5.
Int J Immunopathol Pharmacol ; 34: 2058738420962902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33045857

RESUMO

Atopic dermatitis (AD) is a skin disease characterized by chronic inflammatory condition that shows hallmark presentations in terms of sleep disturbances, pruritus, and psychological stress, and an association with increased attention deficit/hyperactivity disorder (ADHD) risk. A number of studies have suggested for the co-occurrence of the two diseased conditions. In terms of global prevalence, AD and ADHD almost exhibit a parallel increment according to epidemiological data. In addition, recent reports indicate AD to show a temporal association with later onset of ADHD. Although several studies suggest for the potential link between AD and ADHD, currently there is no definitive answer to this regard. Furthermore, epidemiological evidence of co-occurrence does not ascertain a pathophysiological link between the two conditions. The pathophysiological basis behind the association of AD and ADHD also remain poorly elucidated. The objective of this review is to present an extensive account of AD and associated comorbidities with a special attention toward ADHD as well as to elaborate on the mechanisms underlying their association. The review can provide healthcare providers with the recent updates on AD-ADHD association and help them while dealing with such patients. In general, AD and ADHD show a positive association in majority of the cross-sectional studies. However, large longitudinal studies are required to draw any conclusion on the temporal nature of such association.

6.
Foot Ankle Surg ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33046382

RESUMO

BACKGROUND: Malleolar accessory ossicles can be found in patients with chronic lateral ankle instability (CLAI). Ossicle resection combined with the modified Broström procedure is the most commonly used surgical method. However, an unrepairable gap after ossicle resection often occurs in patients with large ossicles. PURPOSE: This study analysed the clinical outcomes of ossicle resection and anatomic ligament reconstruction (ALR) for CLAI with large malleolar accessory ossicles. METHODS: This study was a retrospective case series. Since 2014, we have adopted ALR for patients with difficulties using the modified Broström procedure after ossicle resection. Sixteen patients with chronic ankle instability and malleolar accessory ossicles were treated with this method between December 2014 and February 2018. The average age of the patients at the time of surgery was 28.9 (range, 16-65) years. They were followed up for an average time of 26.9 (range, 12-47) months. The clinical outcomes were evaluated using the Visual Analogue Scale, Karlsson-Peterson ankle scoring system, subjective satisfaction of patients, and radiographic parameters. RESULTS: All unrepairable cases occurred in patients with ossicles larger than or equal to 10 mm. The VAS score improved from 3.5 ± 1.6 preoperatively to 1.4 ± 1.0 at the final follow-up (p < 0.05), and the Karlsson-Peterson score improved significantly from 52.7 ± 15.1 to 86.4 ± 8.2 (p < 0.05). There was also an obvious change in the varus talar tilt angle (15.4 ± 2.0° vs 6.2 ± 1.6°, p < 0.05) and anterior talar displacement (14.3 ± 2.1 mm vs 6.3 ± 1.4 mm, p < 0.05). Fourteen patients (87.5%) were satisfied (excellent or good) with their clinical outcomes. CONCLUSION: If modified Broström procedure is difficult to accomplish effectively after ossicle resection for chronic ankle instability with large malleolar accessory ossicles, ALR is a viable option with satisfactory clinical results.

7.
J Control Release ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031878

RESUMO

Acute myeloid leukemia (AML) is a severe blood malignancy associated with a high relapse rate. The current clinical chemotherapy is typically perplexed with serious side effects. Here, A6 peptide-tagged, small and reduction-sensitive polymersomal vincristine sulfate (A6-cPS-VCR) is reported as a novel, smart and specific treatment for CD44 positive AML. A6-cPS-VCR stably loaded with 3.3 wt% VCR displays a size of ≈ 31 nm and pronounced selectivity toward CD44-overexpressed MV4-11 leukemia cells. Intriguingly, A6-cPS-VCR effectively represses the outgrowth of orthotopic MV4-11 AML in vivo, as revealed by significant reduction of leukemia burdens in the circulation, bone marrow, liver and spleen, and significantly extends the median survival time of MV4-11 AML-bearing mice. In addition to active targetability and therapeutic benefits, A6-cPS-VCR has the advantage of easy fabrication, rendering it potentially interesting for clinical translation.

8.
Parasit Vectors ; 13(1): 514, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054862

RESUMO

BACKGROUND: Culex pipiens pallens poses a serious threat to human health because of its widespread distribution, high carrier capacity for several arboviruses, frequent human-biting, and growth in urban environments. Pyrethroid insecticides have been mainly used to control adult Cx. pipiens pallens during outbreaks of mosquito-borne diseases. Unfortunately, mosquitoes have developed resistance, rendering the insecticides ineffective. Cuticular resistance is the primary mechanism of pyrethroid resistance. Previously, we revealed that cuticular protein of low complexity CPLCG5 is a major cuticular protein associated with deltamethrin resistance in Cx. pipiens pallens, which is enriched in the cuticle of mosquitoes' legs and participates in pyrethroid resistance by forming a rigid matrix. However, the regulatory mechanisms of its transcription remain unknown. RESULTS: First, qRT-PCR analysis revealed that the expression of FTZ-F1 (encoding Fushi tarazu-Factor 1) was ~ 1.8-fold higher in the deltamethrin-resistant (DR) than deltamethrin-susceptible (DS) strains at 24 h post-eclosion (PE) and ~ 2.2-fold higher in the DR strain than in the DS strain at 48 h PE. CPLCG5 and FTZ-F1 were co-expressed in the legs, indicating that they might play an essential role in the legs. Dual luciferase reporter assays and EMSA (electrophoretic mobility shift experiments) revealed that FTZ-F1 regulates the transcription of CPLCG5 by binding to the FTZ-F1 response element (- 870/- 864). Lastly, knockdown of FTZ-F1 not only affected CPLCG5 expression but also altered the cuticle thickness and structure of the legs, increasing the susceptibility of the mosquitoes to deltamethrin in vivo. CONCLUSIONS: The results revealed that FTZ-F1 regulates the expression of CPLCG5 by binding to the CPLCG5 promoter region, altering cuticle thickness and structure, and increasing the susceptibility of mosquitoes to deltamethrin in vivo. This study revealed part of the mechanism of cuticular resistance, providing a deeper understanding of insecticide resistance.

9.
iScience ; : 101642, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33043282

RESUMO

COVID-19 has broken out since the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based on a series of analysis, we speculate that the presence of a redundant furin cut site in its Spike protein is responsible for SARS-CoV-2's stronger infectious than other coronaviruses, which leads to higher membrane fusion efficiency. Subsequently, a library of 4,000 compounds including approved drugs and natural products were screened against furin through structure-based virtual screening and then assayed for their inhibitory effects on furin activity. Among them, an anti-parasitic drug, Diminazene, showed the highest inhibition effects on furin with an IC50 of 5.42 ± 0.11 µM, which might be used for the treatment of COVID-19.

10.
Carbohydr Polym ; 250: 116979, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049867

RESUMO

In this work, 3, 3'-dithiobis (propanoic dihydrazide) modified and aldehyde-modified hyaluronic acid were respectively synthesized as precursor solutions to form redox and pH dual-responsive injectable hydrogels through dynamic acylhydrazone and disulfide linkages without exogenous stimulus conditions. The reversible sol-gel transition behavior of hydrogels could be repeated multiple times by adjusting DTT/H2O2 or HCl/TEA. Interestingly, the hydrogels shrank gradually when pH decreased, which improved significantly the storage modulus up to 8.4 times at pH 2. Furthermore, the hydrogel presented acid-switchable shape-recovery characteristics of self-healing by a dynamic recombination of acylhydrazone bonds. Moreover, the osmotic driving force derived from inner and outer concentration difference also affected the characteristic. The controlled release of bovine serum albumin (BSA) encapsulated in this hydrogel could be achieved in vitro under simulated pH/redox intracellular and intercellular microenvironment. This hydrogel could also promote chondrocytes proliferation.

11.
Medicine (Baltimore) ; 99(40): e22642, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019490

RESUMO

RATIONALE: Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. PATIENT CONCERNS: A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. DIAGNOSES: The diagnosis was MM with chronic carrier of HBV. INTERVENTIONS: He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. OUTCOMES: This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. LESSONS: This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.


Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Bortezomib/uso terapêutico , Guanina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Protocolos Clínicos , Quimioterapia Combinada , Guanina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento
12.
Sci Rep ; 10(1): 17617, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077783

RESUMO

Heterologous expression is the main approach for recombinant protein production ingenetic synthesis, for which codon optimization is necessary. The existing optimization methods are based on biological indexes. In this paper, we propose a novel codon optimization method based on deep learning. First, we introduce the concept of codon boxes, via which DNA sequences can be recoded into codon box sequences while ignoring the order of bases. Then, the problem of codon optimization can be converted to sequence annotation of corresponding amino acids with codon boxes. The codon optimization models for Escherichia Coli were trained by the Bidirectional Long-Short-Term Memory Conditional Random Field. Theoretically, deep learning is a good method to obtain the distribution characteristics of DNA. In addition to the comparison of the codon adaptation index, protein expression experiments for plasmodium falciparum candidate vaccine and polymerase acidic protein were implemented for comparison with the original sequences and the optimized sequences from Genewiz and ThermoFisher. The results show that our method for enhancing protein expression is efficient and competitive.

13.
Brain Behav ; : e01882, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33067924

RESUMO

OBJECTIVE: To study how the CD200-CD200R1 signaling pathway modulates poststroke inflammation and advances our knowledge of immune responses to ischemia insults in stroke. METHODS: Focal middle cerebral artery occlusion (MCAO) was induced in mice for 90 min, and mice were sacrificed at 1, 3, and 7 days of reperfusion. CD200, CD200R1, iNOS, and Arg-1 expression in ischemic brains was assessed by Western blotting (WB), and immunohistochemical (IHC) staining was performed to examine the expression of CD200 on neurons and CD200R1 on infiltrating lymphocytes. The severity of neurobehavioral deficits was evaluated by neurological deficit scores (NDS) and infarction volume estimated by TTC staining. To study the relationship between CD200/CD200R1 expression and the diversity of the neuroinflammatory response in stroke, CD200Fc (CD200R1 agonist) was subcutaneously injected at onset, at 1 day and 2 days after MCAO operation, and the brains were collected for detection at 3 days after MCAO/R (reperfusion). RESULTS: CD200 expression on neurons increased at 1 day and then decreased at 3 days after MCAO/R, and the expression of CD200R1 on lymphocytes showed an opposite temporal pattern as tested by IHC. The WB results showed that CD200/CD200R1 variance exhibited a similar pattern of IHC results, and the level of iNOS peaked at 1 day and then decreased gradually, but Arg-1 increased with time after MCAO/R in ischemic brains. After CD200Fc injection, CD200R1 expression significantly increased, and CD200Fc promoted Arg-1 but inhibited iNOS expression. The infarct volume and NDS of the group treated with CD200Fc were significantly smaller than those of the IgG2a-treated group. CONCLUSIONS: The CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke. Stimulation of CD200R1 by CD200Fc promotes the anti-inflammatory response and alleviates ischemic injury.

14.
Intern Emerg Med ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064253

RESUMO

BACKGROUND: The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. METHODS AND RESULTS: A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. CONCLUSION: Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality.

16.
J Dairy Sci ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33041035

RESUMO

Although odd-chain fatty acids (OCFA) and branched-chain fatty acids (BCFA) are found in bovine milk and have some positive influences on human and animal health, their concentrations in bovine colostrum and transition milk have not been reported. In this study, we reported the OCFA and BCFA concentrations in colostrum and transition milk and their stability after heating or freezing treatments (or both), which are processes commonly applied in dairy calf management. Milk samples were collected from 12 Holstein dairy cows (6 primiparous and 6 multiparous) at the first milking (colostrum), fifth milking (transition milk), and ninth milking (mature milk) after calving, respectively, and were used for fatty acid analysis using gas chromatography. The sum concentration of OCFA and BCFA (termed OBCFA) was 134 mg/100 g of milk in the colostrum, which was 24% and 35% lower than that in the transition milk and mature milk, respectively. Among these fatty acids detected, C15:0 and C17:0 were the top 2 abundant fatty acids in all milk types, accounting for 20 to 25% and 21 to 24% of the total concentration of OBCFA, respectively. Additionally, anteiso-C17:0 was the most abundant BCFA, followed by iso-C17:0, anteiso-C15:0, iso-C16:0, iso-C15:0, iso-C18:0, and iso-C14:0 in 3 types of milk. Significant interactions between milk type and cow parity were observed for all OCFA and BCFA concentrations. The milk samples were also treated with heating (at 65°C for 60 min), freezing (at -20°C for 30 d), and heating and freezing (at 65°C for 60 min and then at -20°C for 30 d), and milk OCFA and BCFA concentrations were similar between these treatments. In conclusion, the OBCFA concentration was lower in colostrum, compared with transition and mature milks, and it remained stable after heating and freezing treatments.

17.
Chemosphere ; 264(Pt 1): 128392, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33002804

RESUMO

Metallic glasses (MGs) are promising candidates for catalysts with high efficiency for dyeing wastewater remediation, due to their metastable nature, disordered structure, and large residual stresses. However, dyeing wastewater usually contains a high concentration of inorganic ions which may have adverse effects on the degradation process, while the impacts of these ions on MGs' degradation capability have often been overlooked and still remain unknown. Thus, the roles of inorganic ions (Cl-, NO3-, SO42-, and H2PO4-) on the degradation of azo dye by Fe-based MG with nominal composition of Fe81Si4B14Cu1 were systematically investigated. The results showed that the inorganic ions have significant influence on MG's surface morphology, degradation capability, mineralization and durability. All these aspects need to be considered prior to application of MGs for azo dyes degradation in real natural contaminated water or saline wastewater.

18.
Stem Cell Res ; 49: 102010, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33011360

RESUMO

Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into hepatic cells, including expandable hepato-blasts (HBs) and hepatocyte-like cells (HLCs) in vitro. Therefore, hESC-derived HBs have the potential to become a renewable cell source for cell therapy of serious liver damage. However, one of the key challenges for such cell therapy is the allogeneic immune rejection of hESC-derived HBs. To overcome this challenge, we developed a strategy to protect the hESC-derived HBs from allogeneic immune rejection by ectopically expressing immune suppressive molecules CTLA4-Ig and PD-L1, denoted CP HBs. Like HBs derived from normal hESCs, CP HBs are capable of repairing liver damage in animal models. Using humanized mice (Hu-mice) reconstituted with human immune system, we showed that CP HBs are protected from allogeneic immune system and can survive long-term in Hu-mice. These data support the feasibility to develop CP HBs into a cell therapy to treat serious liver damage.

19.
Inorg Chem ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909425

RESUMO

Developing earth-abundant and highly efficient nonprecious metal catalysts for hydrogen evolution reaction (HER) is critical for the storage and conversion of renewable energy sources. Molybdenum carbide (Mo2C) has been extensively investigated as one of the most promising nonprecious electrocatalysts for boosting HER because of its low cost, high electrical conductivity, good chemical structure, and similar electronic structure to that of Pt. However, Mo2C always exhibits the negative hydrogen-binding energy, which can largely prevent adsorbed H desorption during the HER process. Herein, we report P- and Ni-dual-doped Mo2C in porous nitrogen-doped carbon (P/Ni-Mo2C) as an electrocatalyst for the HER, exhibiting excellent activity and durability with a low overpotential of 165 mV at 10 mA cm-2 in alkaline electrolyte. Density functional theory (DFT) calculations proved that P and Ni acted as the anion and cation, respectively, to synergistically tune the electronic properties of Mo2C to decrease the negative hydrogen-binding energy, endowing the catalyst with excellent catalytic performance for the HER.

20.
J Exp Clin Cancer Res ; 39(1): 174, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867814

RESUMO

BACKGROUND: Inhibition of p38 MAPK signalling leads to glioblastoma multiform (GBM) tumourigenesis. Nevertheless, the molecular mechanism that induces p38 MAPK signalling pathway silencing during GBM genesis has yet to be determined. Identifying new factors that can regulate p38 MAPK signalling is important for tumour treatment. METHODS: Flow cytometry, TUNEL assays, immunofluorescence, JC-1 assays, and western blot analyses were used to detect the apoptosis of GBM cells. The specific methods used to detect autophagy levels in GBM cells were western blot analysis, LC3B protein immunofluorescence, LC3B puncta assays and transmission electron microscopy. The functions of these critical molecules were further confirmed in vivo by intracranial xenografts in nude mice. Tumour tissue samples and clinical information were used to identify the correlation between RND2 and p62 and LC3B expression, survival time of patients, and tumour volumes in clinical patients. RESULTS: By summarizing data from the TCGA database, we found that expression of the small GTPase RND2 was significantly increased in human glioblastomas. Our study demonstrated that RND2 functions as an endogenous repressor of the p38 MAPK phosphorylation complex. RND2 physically interacted with p38 and decreased p38 phosphorylation, thereby inhibiting p38 MAPK signalling activities. The forced expression of RND2 repressed p38 MAPK signalling, which inhibited glioblastoma cell autophagy and apoptosis in vitro and induced tumour growth in the xenografted mice in vivo. By contrast, the downregulation of RND2 enhanced p38 MAPK signalling activities and promoted glioma cell autophagy and apoptosis. The inhibition of p38 phosphorylation abolished RND2 deficiency-mediated GBM cell autophagy and apoptosis. Most importantly, our study found that RND2 expression was inversely correlated with patient survival time and was positively correlated with tumour size. CONCLUSIONS: Our findings revealed a new function for RND2 in GBM cell death and offered mechanistic insights into the inhibitory effects of RND2 with regard to the regulation of p38 MAPK activation.

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