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1.
JAMA Netw Open ; 4(11): e2132262, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34762112

RESUMO

Importance: In the IMspire150 trial, triplet treatment with atezolizumab and vemurafenib plus cobimetinib significantly improved progression-free survival (PFS) compared with vemurafenib plus cobimetinib alone for treatment of BRAF V600 variation metastatic melanoma. However, considering high cost of this combination, it is unclear if the incremental cost is worth the additional survival benefit. Objective: To evaluate the cost-effectiveness of atezolizumab and vemurafenib plus cobimetinib vs vemurafenib plus cobimetinib alone in patients with newly diagnosed unresectable BRAF V600 variation metastatic melanoma from the US health care perspective. Design, Setting, and Participants: This economic evaluation study used a 3-state partitioned survival model to assess the cost-effectiveness of the combination of atezolizumab with vemurafenib plus cobimetinib vs vemurafenib plus cobimetinib alone. The observed Kaplan-Meier curves for overall survival and PFS were digitized from the IMspire150 trial (January 2017-April 2018) and the long-term survivals (over a lifetime horizon) beyond the end of the trial were extrapolated using 7 different survival models. The cost and health preference data were collected from a literature review. This study was performed from March 2021 through June 2021. Main Outcomes and Measures: The outcomes of interest were expected life-years (LYs) gained and quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio (ICER), expressed as cost per LYs and per QALYs saved. Results: Adding atezolizumab to vemurafenib and cobimetinib provided an additional 3.267 QALYs compared with the doublet regimen of vemurafenib plus cobimetinib, at an ICER of $271 669 per QALY, which is not considered cost-effective at the willingness-to-pay threshold of $150 000 per QALY. However, the scenario analyses found that atezolizumab combined with vemurafenib plus cobimetinib could be cost-effective at 20-year (ICER, $121 432 per QALY) and 30-year ($98 092 per QALY) time horizons when both strategies were stopped after 2 years of treatments, and over a lifetime horizon ($122 220 per QALY) when only immunotherapy with atezolizumab was stopped after 2 years of treatment. Conclusions and Relevance: These findings suggest that the atezolizumab and vemurafenib plus cobimetinib regimen provides significant survival benefits over vemurafenib plus cobimetinib alone, and a price reduction would be encouraged to maximize the value of its survival gain.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34822728

RESUMO

Ruthenium (Ru)-based catalysts, with considerable performance and desirable cost, become highly concerned candidates to replace platinum (Pt) in alkaline hydrogen evolution reaction (HER). The hydrogen binding at Ru sites (Ru-H) is an important factor limiting the HER activity. Herein, density functional theory (DFT) simulations show that the essence of Ru-H binding energy is the strong interaction between the 4dz 2 orbital of Ru and 1s orbital of H. The charge transfer between Ru sites and substrates (Co and Ni) causes the appropriate downward shift of the 4dz 2 -band center of Ru, which results in a Gibbs free energy of 0.022 eV for H* in RuCo system, much decrease compared to 0.133 eV in pure Ru system. This theoretical prediction has been experimentally confirmed using RuCo alloy nanosheets (RuCo ANSs). They were prepared via fast co-precipitation method followed with a mild electrochemical reduction. Structure characterizations reveal that the Ru atoms are embed into Co substrate as isolated active sites with the planar symmetric and Z-direction asymmetric coordination structure, obtaining an optimal 4dz 2 modulated electronic structure. Hydrogen sensor and temperature program desorption (TPD) tests demonstrate the enhanced Ru-H interactions in RuCo ANSs than pure Ru nanoparticles. As a result, the RuCo ANSs reach an ultra-low overpotential of 10 mV at 10 mA/cm 2 and a Tafel slope of 20.6 mV/dec in 1 M KOH, outperforming that of the commercial Pt/C. This holistic work provides a new insight to promote alkaline HER by optimizing metal-H binding energy of active sites.

3.
Int Arch Allergy Immunol ; : 1-14, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736257

RESUMO

BACKGROUND: Fine particulate matter (PM) (PM with an aerodynamic diameter <2.5 µm, PM2.5) exposure contributes to respiratory disease development and exacerbation. OBJECTIVE: We sought to investigate the effect of PM2.5 exposure on mucociliary function in primary human nasal epithelial cells (HNECs) and the underlying mechanism. METHODS: HNECs derived from control subjects and patients with chronic rhinosinusitis with nasal polyps were established as air-liquid interface cultures. Confluent cultures were exposed to 100 or 200 µg/mL PM2.5 for 24 h and assessed for expression of specific mucociliary-associated factors, the percentage of ß-tubulin IV-positive and MUC5AC-positive cells, expression of epidermal growth factor receptor (EGFR) ligand and activation of phosphoinositide 3-kinase (PI3K)-AKT/ERK. In addition, cultures pretreated for 30 min with AG1478 (an EGFR inhibitor) or LY294002 (a PI3K inhibitor) following PM2.5 exposure were assessed for MUC5AC mRNA and protein expression. RESULTS: PM2.5 exposure at 100 or 200 µg/mL for 24 h did not affect geminin coiled-coil domain containing, multiciliate differentiation and DNA synthesis associated cell cycle protein, FOXJ1, or DNAI2 mRNA expression or the percentage of ß-tubulin IV-positive cells. However, 200 µg/mL PM2.5 exposure significantly increased mRNA expression of SAM-pointed domain-containing ETS transcription factor and MUC5AC and the percentage of MUC5AC-positive cells. PM2.5 also increased expression of EGFR ligands, including heparin-binding EGF-like growth factor and amphiregulin. Furthermore, PM2.5induced activation of PI3K, AKT, and ERK, and pretreatment of HNECs with AG1478 or LY294002 attenuated PM2.5-induced MUC5AC mRNA and protein expression. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrates that short-term PM2.5 exposure increases MUC5AC expression in HNECs. Furthermore, this study shows that PM2.5-induced MUC5AC expression is likely mediated through the EGFR-PI3K pathway.

5.
Phys Rev E ; 104(4-1): 044303, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781529

RESUMO

The phase transition of epidemic spreading model on networks is one of the most important concerns of physicists to theoretical epidemiology. In this paper, we present an analytical expression of epidemic threshold for interplay between epidemic spreading and human behavior on multiplex networks. The threshold formula proposed in this paper reveals the relation between the threshold on single-layer networks and that on multiplex networks, which means that the theoretical conclusions of single-layer networks can be used to improve the threshold accuracy of multiplex networks. To verify how well our formula works in different networks, we build a network model with constant total number of edges but gradually changing the heterogeneity of the network, from scale-free network to Erdos-Rényi random network. By use of theoretical analysis and computer simulations, we find that the heterogeneity of information layer behaves as a "double-edged sword" on the epidemic threshold: The strong heterogeneity can effectively improve the epidemic threshold (which means the disease outbreak requires a higher infection probability) when the awareness probability α is low, while the opposite effect takes place for high α. Meanwhile, the weak heterogeneity of the information layer is effective in suppressing the epidemic prevalence when the awareness probability is neither too high nor too low.

6.
Adv Mater ; : e2100245, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613635

RESUMO

The synthesis and the evaluation of the efficacy of a cycloruthenated complex, RuZ, is reported, to overcome multi-drug resistance (MDR) in cancer cells. RuZ can self-assemble into nanoaggregates in the cell culture medium, resulting in a high intracellular concentration of RuZ in MDR cancer cells. The self-assembly significantly decreases oxygen consumption and inhibits glycolysis, which decreases cellular adenosine triphosphate (ATP) levels. The decrease in ATP levels and its low affinity for the ABCB1 and ABCG2 transporters (which mediate MDR) significantly increase the retention of RuZ by MDR cancer cells. Furthermore, RuZ increases cellular oxidative stress, inducing DNA damage, and, in combination with the aforementioned effects of RuZ, increases the apoptosis of cancer cells. Proteomic profiling analysis suggests that the RuZ primarily decreases the expression of proteins that mediate glycolysis and aerobic mitochondrial respiration and increases the expression of proteins involved in apoptosis. RuZ inhibits the proliferation of 35 cancer cell lines, of which 7 cell lines are resistant to clinical drugs. It is also active in doxorubicin-resistant MDA-MB-231/Adr mouse tumor xenografts. To the best of our knowledge, the results are the first to show that self-assembled cycloruthenated complexes are efficacious in inhibiting the growth of MDR cancer cells.

7.
Am J Transl Res ; 13(9): 10421-10427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650711

RESUMO

OBJECTIVE: This study aimed to investigate the value of Gensini score and interleukin-1 receptor antagonist (IL-1ra) in assessing the condition and prognosis of patients with coronary heart disease (CHD). METHODS: According to their condition, 175 patients were divided into stable angina group (SA, 60 cases), unstable angina group (UA, 60 cases) and acute myocardial infarction group (AMI, 55 cases). The Gensini score, GRACE score, IL-1ra and troponin (Tn) were compared in the three groups. The correlation between Gensini score and GRACE score, IL-1ra and Tn, were explored. The patients were divided into death group (21 cases), adverse cardiovascular events group (MACE, 50 cases) and good prognosis group (104 cases) according to clinical outcomes. The ROC curve with regard to Gensini score, IL-1ra and the clinical outcome was plotted. RESULTS: With the exacerbation of the disease, the Gensini score, GRACE score, IL-1ra and Tn were significantly higher in patients with CHD (P<0.05). Correlation analysis showed a positive association between Gensini score and GRACE score (r=0.9751, P<0.05). IL-1ra showed a positive association with Tn level (r=0.9731, P<0.05); Gensini score and IL-1ra had an area under the curve (AUC) of 0.9350 and 0.9499 for adverse CHD outcome, respectively (P<0.001). CONCLUSION: Gensini score and IL-1ra reflect better the severity of CHD in patients with CHD, and also the AUC of 0.9350 and 0.9499 (P<0.001). It can be used in the prognostic evaluation of patients with CHD.

8.
ACS Appl Mater Interfaces ; 13(41): 48709-48719, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34636242

RESUMO

Hierarchically porous-structured materials show tremendous potential for catalytic applications. In this work, a facile method through the combination of three-dimensional (3D) printing and chemical dealloying was employed to synthesize a nanoporous-copper-encapsulating microporous-diamond-cellular-structure (NPC@DCS) catalyst. The developed NPC@DCS catalyst was utilized as a heterogeneous photo-Fenton-like catalyst where its catalytic applications in the remediation of organic wastewater were exemplified. The experimental results demonstrated that the NPC@DCS catalyst possessed a remarkable degradation efficiency in the removal of rhodamine B with a reaction rate of 8.24 × 10-2 min-1 and displayed attractive stability, durability, mineralization capability, and versatility. This work not only manifests the applicability of the proposed NPC@DCS catalyst for wastewater purification in practical applications but also is anticipated to inspire the incorporation of the 3D printing technology and chemical synthesis to design high-performance metal catalysts with tunable hierarchical micro- and nanopores for functional applications.

9.
J Am Chem Soc ; 143(34): 13605-13615, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465098

RESUMO

Single-atom catalysts (SACs) with 100% active sites have excellent prospects for application in the oxygen evolution reaction (OER). However, further enhancement of the catalytic activity for OER is quite challenging, particularly for the development of stable SACs with overpotentials <180 mV. Here, we report an iridium single atom on Ni2P catalyst (IrSA-Ni2P) with a record low overpotential of 149 mV at a current density of 10 mA·cm-2 in 1.0 M KOH. The IrSA-Ni2P catalyst delivers a current density up to ∼28-fold higher than that of the widely used IrO2 at 1.53 V vs RHE. Both the experimental results and computational simulations indicate that Ir single atoms preferentially occupy Ni sites on the top surface. The reconstructed Ir-O-P/Ni-O-P bonding environment plays a vital role for optimal adsorption and desorption of the OER intermediate species, which leads to marked enhancement of the OER activity. Additionally, the dynamic "top-down" evolution of the specific structure of the Ni@Ir particles is responsible for the robust single-atom structure and, thus, the stability property. This IrSA-Ni2P catalyst offers novel prospects for simplifying decoration strategies and further enhancing OER performance.

10.
Front Oncol ; 11: 726290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568056

RESUMO

[This corrects the article DOI: 10.3389/fonc.2021.611081.].

11.
Nanoscale ; 13(32): 13604-13609, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34477634

RESUMO

The alkaline electrocatalytic hydrogen evolution reaction (HER) is a potential way to realize industrial hydrogen production. However, the sluggish process of H2O dissociation, as well as the accumulation of OH- around the active sites, seriously limit the alkaline HER performance. In this work, we developed a unique CoS2 needle array grown on a carbon cloth (NAs@C) electrode as an alkaline HER catalyst. Finite-element simulations revealed that CoS2 needle arrays (NAs) induce stronger local electric field (LEF) than CoS2 disordered needles (DNs). This LEF can greatly repel the local OH- around the active sites, and then promote the forward H2O dissociation process. The local pH changes of the electrode surface confirmed the lower OH- concentration and stronger local pseudo-acidic environment of NAs@C compared to those of DNs@C. As a result, the NAs@C catalyst exhibited a low HER overpotential of 121 mV at a current density of 10 mA cm-2 in 1 M KOH, with the Tafel slope of 59.87 mV dec-1. This work provides a new insight into nanoneedle arrays for the alkaline HER by electric field-promoted H2O dissociation.

12.
Cancers (Basel) ; 13(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34572902

RESUMO

The emergence of multidrug resistance (MDR) to chemotherapeutic drugs is a major problem in the therapy of cancer. Knowledge of the mechanisms of drug resistance in cancer is necessary for developing efficacious therapies. ATP-binding cassette (ABC) transporters are transmembrane proteins that efflux chemotherapeutic drugs from cancer cells, thereby producing MDR. Our research efforts have led to the discovery of VKNG-1, a compound that selectively inhibits the ABCG2 transporter and reverses resistanctabe to standard anticancer drugs both in vitro and in vivo. VKNG-1, at 6 µM, selectively inhibited ABCG2 transporter and sensitized ABCG2-overexpressing drug-resistant cancer cells to the ABCG2 substrate anticancer drugs mitoxantrone, SN-38, and doxorubicin in ABCG2-overexpressing colon cancers. VKNG- 1 reverses ABCG2-mediated MDR by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the mRNA and protein levels. Moreover, VKNG-1 inhibits the level of phosphorylated protein kinase B (PKB/p-AKT), and B-cell lymphoma-2 (Bcl-2) protein which may overcome resistance to anticancer drugs. However, the in vitro translocation of ABCG2 protein did not occur in the presence of 6 µM of VKNG-1. In addition, VKNG-1 enhanced the anticancer efficacy of irinotecan in ABCG2- overexpressing mouse tumor xenografts. Overall, our results suggest that VKNG-1 may, in combination with certain anticancer drugs, represent a treatment to overcome ABCG2-mediated MDR colon cancers.

13.
Angew Chem Int Ed Engl ; 60(48): 25241-25245, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550636

RESUMO

Atomically dispersed transition metal sites have been extensively studied for CO2 electroreduction reaction (CO2 RR) to CO due to their robust CO2 activation ability. However, the strong hybridization between directionally localized d orbits and CO vastly limits CO desorption and thus the activities of atomically dispersed transition metal sites. In contrast, s-block metal sites possess nondirectionally delocalized 3s orbits and hence weak CO adsorption ability, providing a promising way to solve the suffered CO desorption issue. Herein, we constructed atomically dispersed magnesium atoms embedded in graphitic carbon nitride (Mg-C3 N4 ) through a facile heat treatment for CO2 RR. Theoretical calculations show that the CO desorption on Mg sites is easier than that on Fe and Co sites. This theoretical prediction is demonstrated by experimental CO temperature program desorption and in situ attenuated total reflection infrared spectroscopy. As a result, Mg-C3 N4 exhibits a high turnover frequency of ≈18 000 per hour in H-cell and a large current density of -300 mA cm-2 in flow cell, under a high CO Faradaic efficiency ≥90 % in KHCO3 electrolyte. This work sheds a new light on s-block metal sites for efficient CO2 RR to CO.

14.
Front Immunol ; 12: 735170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531875

RESUMO

The aim of this study was to elucidate the correlation between m6A modification and the tumor immune microenvironment (TIME) in prostate cancer (PCa) and to identify the m6A regulation patterns suitable for immune checkpoint inhibitors (ICIs) therapy. We evaluated the m6A regulation patterns of PCa based on 24 m6A regulators and correlated these modification patterns with TIME characteristics. Three distinct m6A regulation patterns were determined in PCa. The m6A regulators cluster with the best prognosis had significantly increased METTL14 and ZC3H13 expression and was characterized by low mutation rate, tumor heterogeneity, and neoantigens. The m6A regulators cluster with a poor prognosis had markedly high KIAA1429 and HNRNPA2B1 expression and was characterized by high intratumor heterogeneity and Th2 cell infiltration, while low Th17 cell infiltration and Macrophages M1/M2. The m6Ascore was constructed to quantify the m6A modification pattern of individual PCa patients based on m6A-associated genes. We found that the low-m6Ascore group with poor prognosis had a higher immunotherapeutic response rate than the high-m6Ascore group. The low-m6Ascore group was more likely to benefit from ICIs therapy. This study was determined that immunotherapy is more effective in low-m6Ascore PCa patients with poor prognosis.

15.
Polymers (Basel) ; 13(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209747

RESUMO

Multi Jet Fusion (MJF) is a recently developed polymeric powder bed fusion (PBF) additive manufacturing technique that has received considerable attention in the industrial and scientific community due to its ability to fabricate functional and complex polymeric parts efficiently. In this work, a systematic characterization of the physicochemical properties of MJF-certified polyamide 11 (PA11) and thermoplastic polyurethane (TPU) powder was conducted. The mechanical performance and print quality of the specimens printed using both powders were then evaluated. Both PA11 and TPU powders showed irregular morphology with sharp features and had broad particle size distribution, but such features did not impair their printability significantly. According to the DSC scans, the PA11 specimen exhibited two endothermic peaks, while the TPU specimen exhibited a broad endothermic peak (116-150 °C). The PA11 specimens possessed the highest tensile strength in the Z orientation, as opposed to the TPU specimens which possessed the lowest tensile strength along the same orientation. The flexural properties of the PA11 and TPU specimens displayed a similar anisotropy where the flexural strength was highest in the Z orientation and lowest in the X orientation. The porosity values of both the PA11 and the TPU specimens were observed to be the lowest in the Z orientation and highest in the X orientation, which was the opposite of the trend observed for the flexural strength of the specimens. The PA11 specimen possessed a low coefficient of friction (COF) of 0.13 and wear rate of 8.68 × 10-5 mm3/Nm as compared to the TPU specimen, which had a COF of 0.55 and wear rate of 0.012 mm3/Nm. The PA11 specimens generally had lower roughness values on their surfaces (Ra < 25 µm), while the TPU specimens had much rougher surfaces (Ra > 40 µm). This investigation aims to uncover and explain phenomena that are unique to the MJF process of PA11 and TPU while also serving as a benchmark against similar polymeric parts printed using other PBF processes.

16.
BMC Infect Dis ; 21(1): 626, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210269

RESUMO

OBJECTIVE: To quantitatively evaluate the effectiveness of Fangcang shelter hospitals, designated hospitals, and the time interval from illness onset to diagnosis toward the prevention and control of the COVID-19 epidemic. METHODS: We used SEIAR and SEIA-CQFH warehouse models to simulate the two-period epidemic in Wuhan and calculate the time dependent basic reproduction numbers (BRNs) of symptomatic infected individuals, asymptomatic infected individuals, exposed individuals, and community-isolated infected individuals. Scenarios that varied in terms of the maximum numbers of open beds in Fangcang shelter hospitals and designated hospitals, and the time intervals from illness onset to hospitals visit and diagnosis were considered to quantitatively assess the optimal measures. RESULTS: The BRN decreased from 4.50 on Jan 22, 2020 to 0.18 on March 18, 2020. Without Fangcang shelter hospitals, the cumulative numbers of cases and deaths would increase by 18.58 and 51.73%, respectively. If the number of beds in the designated hospitals decreased by 1/2 and 1/4, the number of cumulative cases would increase by 178.04 and 92.1%, respectively. If the time interval from illness onset to hospital visit was 4 days, the number of cumulative cases and deaths would increase by 2.79 and 6.19%, respectively. If Fangcang shelter hospitals were not established, the number of beds in designated hospitals reduced 1/4, and the time interval from visiting hospitals to diagnosis became 4 days, the cumulative number of cases would increase by 268.97%. CONCLUSION: The declining BRNs indicate the high effectiveness of the joint measures. The joint measures led by Fangcang shelter hospitals are crucial and need to be rolled out globally, especially when medical resources are limited.


Assuntos
COVID-19/prevenção & controle , COVID-19/terapia , Simulação por Computador , Unidades Móveis de Saúde , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/mortalidade , China/epidemiologia , Hospitais Especializados , Humanos , Modelos Biológicos , Saúde Pública
17.
RNA Biol ; 18(12): 2531-2545, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34110975

RESUMO

Methylation is a common post-transcriptional modification of tRNAs, particularly in the anticodon loop region. The cytosine 38 (C38) in tRNAs, such as tRNAAsp-GUC, tRNAGly-GCC, tRNAVal-AAC, and tRNAGlu-CUC, can be methylated by human DNMT2/TRDMT1 and some homologs found in bacteria, plants, and animals. However, the substrate properties and recognition mechanism of DNMT2/TRDMT1 remain to be explored. Here, taking into consideration common features of the four known substrate tRNAs, we investigated methylation activities of DNMT2/TRDMT1 on the tRNAGly-GCC truncation and point mutants, and conformational changes of mutants. The results demonstrated that human DNMT2/TRDMT1 preferred substrate tRNAGly-GCC in vitro. L-shaped conformation of classical tRNA could be favourable for DNMT2/TRDMT1 activity. The complete sequence and structure of tRNA were dispensable for DNMT2/TRDMT1 activity, whereas T-arm was indispensable to this activity. G19, U20, and A21 in D-loop were identified as the important bases for DNMT2/TRDMT1 activity, while G53, C56, A58, and C61 in T-loop were found as the critical bases. The conserved CUXXCAC sequence in the anticodon loop was confirmed to be the most critical determinant, and it could stabilize C38-flipping to promote C38 methylation. Based on these tRNA properties, new substrates, tRNAVal-CAC and tRNAGln-CUG, were discovered in vitro. Moreover, a single nucleotide substitute, U32C, could convert non-substrate tRNAAla-AGC into a substrate for DNMT2/TRDMT1. Altogether, our findings imply that DNMT2/TRDMT1 relies on a delicate network involving both the primary sequence and tertiary structure of tRNA for substrate recognition.

18.
Angew Chem Int Ed Engl ; 60(30): 16607-16614, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-33982396

RESUMO

Electrochemical production of hydrogen peroxide (H2 O2 ) through two-electron (2 e- ) oxygen reduction reaction (ORR) is an on-site and clean route. Oxygen-doped carbon materials with high ORR activity and H2 O2 selectivity have been considered as the promising catalysts, however, there is still a lack of direct experimental evidence to identify true active sites at the complex carbon surface. Herein, we propose a chemical titration strategy to decipher the oxygen-doped carbon nanosheet (OCNS900 ) catalyst for 2 e- ORR. The OCNS900 exhibits outstanding 2 e- ORR performances with onset potential of 0.825 V (vs. RHE), mass activity of 14.5 A g-1 at 0.75 V (vs. RHE) and H2 O2 production rate of 770 mmol g-1 h-1 in flow cell, surpassing most reported carbon catalysts. Through selective chemical titration of C=O, C-OH, and COOH groups, we found that C=O species contributed to the most electrocatalytic activity and were the most active sites for 2 e- ORR, which were corroborated by theoretical calculations.

19.
FASEB J ; 35(6): e21458, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948987

RESUMO

Porphyran and its derivatives possess a variety of biological activities, such as ameliorations of oxidative stress, inflammation, hyperlipemia, and immune deficiencies. In this study, we evaluated the potential efficacy of porphyran-derived oligosaccharides from Porphyra yezoensis (PYOs) in alleviating nonalcoholic fatty liver disease (NAFLD) and preliminarily clarified the underlying mechanism. NAFLD was induced by a high-fat diet for six months in C57BL/6J mice, followed by treatment with PYOs (100 or 300 mg/kg/d) for another six weeks. We found that PYOs reduced hepatic oxidative stress in mice with NAFLD, which plays a critical role in the occurrence and development of NAFLD. In addition, PYOs could markedly decrease lipid accumulation in liver by activating the IRS-1/AKT/GSK-3ß signaling pathway and the AMPK signaling pathway in mice with NAFLD. PYOs also apparently relieved the hepatic fibrosis induced by oxidative stress via downregulation of TGF-ß and its related proteins, so that liver injury was markedly alleviated. Furthermore, PYOs treatment relieved cecal microbiota dysbiosis (such as increasing the relative abundance of Akkermansia, while decreasing the Helicobacter abundance), which could alleviate oxidative stress, inflammation, and lipid metabolism, and protect the liver to a certain degree. In summary, PYOs treatment remarkably improved NAFLD via a specific molecular mechanism and reshaped the cecal microbiota.


Assuntos
Ceco/efeitos dos fármacos , Modelos Animais de Doenças , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Oligossacarídeos/farmacologia , Sefarose/análogos & derivados , Animais , Ceco/microbiologia , Disbiose/complicações , Disbiose/microbiologia , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Oligossacarídeos/química , Estresse Oxidativo , Sefarose/química , Transdução de Sinais
20.
Huan Jing Ke Xue ; 42(6): 2668-2678, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032066

RESUMO

As an important component of atmospheric aerosols, black carbon (BC) has a great influence on the regional and global radiation balance, climate, and human health due to its small particle size, large specific surface area, and radiative forcing potential. Here, the spatio-temporal characteristics of atmospheric BC were investigated based on modern-era retrospective analysis for research and applications version 2 (MERRA-2) reanalysis data and ground observation data during 1980-2019 in Shanghai, a highly urbanized city in mainland China. The influences of local emissions and regional transmission on regional-scale BC concentrations were examined using the M-K trend test, backward trajectory analysis, and the potential source contribution function (PSCF). The results showed that:① MERRA-2 BC and ground observation datasets showed good consistency (R∈[0.68, 0.72]), indicating that MERRA-2 reanalysis data can be used to reveal long-term changes in ground-level atmospheric BC concentrations; ② Atmospheric BC concentrations in Shanghai over the past 40 years can be divided into three stages:a "low value" stage of slow growth[1980-1986, (1.75±0.17) µg·m-3], a relatively stable "median value" stage[1987-1999, (2.18 ±0.07) µg·m-3], and a fluctuating "high value" stage[2000-2019, (3.07±0.31) µg·m-3]. Seasonally, Shanghai's BC concentrations generally show a "U" pattern with low concentrations in summer and high concentrations in winter. As a result of black carbon emissions from marine diesel engines and other engines used for water transportation, a small peak also occurs in July; ③ The diagnostic quality ratio of air pollutants and the bivariate correlation analysis[R(BC-NO2)>R(BC-CO)>R(BC-SO2)] indicated that traffic emissions were the main sources of atmospheric BC in Shanghai, especially by heavy diesel vehicles; ④ The backward trajectory and PSCF analyses found that the air mass of Shanghai in summer was dominated by a clean sea breeze, accounting for 77.18%. In contrast, during the other seasons, more than 50% of the air mass came from the north. The potential source regions of atmospheric BC in Shanghai are mainly distributed in eastern China, expanding outwards and centering on the Yangtze River Delta, and the expansion direction is consistent with the directions of the backward trajectories.

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