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Carotenoids are a diverse group of pigments known for their broad range of biological functions and applications. This study delves into multifaceted potential of carotenoids extracted from Haloferax larsenii NCIM 5678 previously isolated from Pachpadra Salt Lake in Rajasthan, India. H. larsenii NCIM 5678 was able to grow up to OD600 1.77 ± 0.03 with carotenoid concentration, 3.3 ± 0.03 µg/ml. The spectrophotometric analysis of carotenoid extract indicated the presence of three-fingered peak (460, 490 and 520 nm) which is a characteristic feature of bacterioruberin and its derivatives. The bacterioruberin was purified using silica gel column chromatography and thin layer chromatography. The carotenoid extract showed 12.3 ± 0.09 mm zone of growth inhibition with a minimum inhibitory concentration 546 ng/ml against indicator strain, H. larsenii HA4. The percentage antioxidant activity of carotenoid was found to be 84% which was higher as compared to commercially available ascorbic acid (56.74%). Thus, carotenoid extract from H. larsenii NCIM 5678 possesses unique attributes with compelling evidence of antimicrobial and antioxidant potential for the development of novel pharmaceuticals and nutraceuticals.
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Antioxidantes , Carotenoides , Haloferax , Lagos , Carotenoides/química , Carotenoides/metabolismo , Lagos/microbiologia , Antioxidantes/farmacologia , Antioxidantes/química , Haloferax/metabolismoRESUMO
The use of microorganisms as beneficial crops for human and animal health has been studied for decades, and these microorganisms have been in practical use for quite some time. Nowadays, in addition to well-known examples of beneficial properties of lactic acid bacteria, bifidobacteria, selected Bacillus spp., and yeasts, there are several other bacteria considered next-generation probiotics that have been proposed to improve host health. Aquaculture is a rapidly growing area that provides sustainable proteins for consumption by humans and other animals. Thus, there is a need to develop new technologies for the production practices associated with cleaner and environment-friendly approaches. It is a well-known fact that proper selection of the optimal probiotics for use in aquaculture is an essential step to ensure effectiveness and safety. In this critical review, we discuss the evaluation of host-specific probiotics in aquaculture, challenges in using probiotics in aquaculture, methods to improve the survival of probiotics under different environmental conditions, technological approach to improving storage, and delivery along with possible negative consequences of using probiotics in aquaculture. A critical analysis of the identified challenges for the use of beneficial microbes in aquaculture will help in sustainable aquafarming, leading to improved agricultural practices with a clear aim to increase protein production.
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Plantaricin LD1 was purified from a potential probiotic strain, Lactobacillus plantarum LD1 previously isolated from indigenous food, Dosa. In this study, we have performed a detailed mechanism of action of plantaricin LD1 against Escherichia coli ATCC 25922 considering Micrococcus luteus MTCC 106 as control. The plantaricin LD1 showed a minimum inhibitory concentration (MIC) of 34.57 µg/mL and a minimum bactericidal concentration (MBC) of 138.3 µg/mL against M. luteus MTCC 106, whereas MIC 69.15 µg/mL and MBC 276.6 µg/mL were found against E. coli ATCC 25922. The efflux of potassium ions, dissipation of membrane potential (∆ψ), and transmembrane pH gradient (∆pH) of plantaricin LD1-treated cells suggested the membrane-acting nature of plantaricin LD1. Plantaricin LD1 also caused degradation of the genomic DNA of the target strains tested. The cell killing was confirmed by staining with propidium iodide and visualized under light and electron microscopes. The bacteriocin-treated cells were found to be ruptured, swollen, and elongated. Thus, the findings indicate plantaricin LD1 kills E. coli ATCC 25922 by interacting with the cell membrane resulting in the efflux of intracellular contents and also causing degradation of nucleic acids leading to cell death.
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Spray-dried niobium oxide coated with chitosan-activated carbon (NIC) was synthesized and used to remove doxorubicin hydrochloride and crystal violet from aqueous solutions under different parameters such as solution pH (2, 4, 6, and 8), contact time (1 to 9 h), initial concentration (20 to 200 mg L-1), and competing ions (0.1 M of CaCl2 and NaCl). The addition of 5 % chitosan-activated carbon to the matrix of niobium oxide slightly increased the specific surface area from 26 to 30 m2 g-1, with the introduction of a carboxylic functional group. This led to an increase in the amount of adsorbed doxorubicin hydrochloride (DOH) from 30 to 44 mg g-1 and that of crystal violet (CV) from 15 to 32 mg g-1 from the initial respective 100 mg L-1 at pH 8. The data from the concentration study fitted into Liu isotherm having adsorption capacity of 128 and 57 mg g-1 for DOH and CV respectively, while pseudo first and second order are more suitable for adsorption kinetics. The additional functional groups on the IR spectrum of NIC after the adsorption of DOH and CV confirmed the interaction between NIC and the adsorbates' molecules. The mechanism of adsorption was supported by DFT calculations.
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Quitosana , Doxorrubicina , Violeta Genciana , Nióbio , Quitosana/química , Doxorrubicina/química , Adsorção , Nióbio/química , Violeta Genciana/química , Concentração de Íons de Hidrogênio , Carvão Vegetal/química , Cinética , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Teoria da Densidade Funcional , Óxidos/química , Água/química , Soluções , Purificação da Água/métodosRESUMO
Aim: To compare the efficacy of erenumab versus rimegepant as preventive treatment for patients with episodic and chronic migraine using an anchor-based matching-adjusted indirect comparison. Methods: Patients from two phase II/III trials for erenumab (NCT02066415 and NCT02456740) were pooled and weighted to match on the baseline effect modifiers (age, sex, race, baseline monthly migraine days [MMDs], and history of chronic migraine [CM]) reported in the phase II/III trial for rimegepant (NCT03732638). Four efficacy outcomes were compared between the two erenumab regimens (70 mg and 140 mg) and rimegepant, including changes in MMDs from baseline to month 1 and month 3, changes in Migraine-Specific Quality of Life Questionnaire role function - restrictive domain score from baseline to month 3, and change in disability from baseline to Month 3. Results: Compared with rimegepant, erenumab 70 mg was associated with a statistically significant reduction in MMDs at month 3 (-0.90 [-1.76, -0.03]; p = 0.042) and erenumab 140 mg was associated with statistically significant reductions in MMDs at month 1 (-0.94 [-1.70, -0.19]; p = 0.014) and month 3 (-1.28 [-2.17, -0.40]; p = 0.005). The erenumab regimens also had numerical advantages over rimegepant for other efficacy outcomes. Conclusion: In the present study, we found that erenumab had a more favorable efficacy profile than rimegepant in reducing MMDs at month 1 and month 3 for migraine prevention. These results may help with decision-making in clinical practice and can be further validated in future clinical trials or real-world studies.
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Anticorpos Monoclonais Humanizados , Transtornos de Enxaqueca , Piridinas , Qualidade de Vida , Humanos , Piperidinas/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controleRESUMO
Phytases are important enzymes used for eliminating the anti-nutritional properties of phytic acid in food and feed ingredients. Phytic acid is major form of organic phosphorus stored during seed setting. Monogastric animals cannot utilize this phytate-phosphorus due to lack of necessary enzymes. Therefore, phytic acid excretion is responsible for mineral deficiency and phosphorus pollution. Phytases have been reported from diverse microorganisms, however, fungal phytases are preferred due to their unique properties. Aspergillus species are the predominant producers of phytases and have been explored widely as compared to other fungi. Solid-state fermentation has been studied as an economical process for the production of phytases to utilize various agro-industrial residues. Mixed substrate fermentation has also been reported for the production of phytases. Physical and chemical parameters including pH, temperature, and concentrations of media components have significantly affected the production of phytases in solid state fermentation. Fungi produced high levels of phytases in solid state fermentation utilizing economical substrates. Optimization of culture conditions using different approaches has significantly improved the production of phytases. Fungal phytases are histidine acid phosphatases exhibiting broad substrate specificity, are relatively thermostable and protease-resistant. These phytases have been found effective in dephytinization of food and feed samples with concomitant liberation of minerals, sugars and soluble proteins. Additionally, they have improved the growth of plants by increasing the availability of phosphorus and other minerals. Furthermore, phytases from fungi have played an important roles in bread making, semi-synthesis of peroxidase, biofuel production, production of myo-inositol phosphates and management of environmental pollution. This review article describes the production of fungal phytases in solid state fermentation and their biotechnological applications.
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6-Fitase , Animais , 6-Fitase/química , 6-Fitase/metabolismo , Fermentação , Ácido Fítico/metabolismo , Fósforo , MineraisRESUMO
OBJECTIVE: To assess healthcare costs and healthcare resource utilization (HCRU) among adult patients who newly initiated erenumab in the United States. METHODS: This retrospective, non-interventional analysis included adult patients (aged ≥18 years) newly initiating erenumab and who had three consecutive monthly claims for erenumab (11/1/2017-9/1/2019) from the Komodo Health database. Outcomes included migraine-related and all-cause costs, use of other preventive/acute migraine medications, and HCRU. All outcomes were compared during the 180-day pre- versus the 180-day post-index periods. Cost outcomes were also assessed for longer periods including post-index Days 91-270 and monthly mean post-index costs for the longest time of continuous insurance enrollment. RESULTS: Overall, 1839 patients with migraine were included for analysis. Compared to the 180-day pre-index period, an increase in total migraine-related costs (+$2639; p < 0.0001), migraine-related prescription costs (+$3435, p < 0.0001), all-cause total costs (+$2977; p < 0.001), and all-cause prescription costs (+$4102; p < 0.0001) were observed during the 180-day post-index period after adjusting for covariates. Conversely, reduction in migraine-related medical costs (-$896; p < 0.0001), and significantly lower odds of migraine-related emergency room visits (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.44-0.82; p = 0.001), migraine-related office visits (OR 0.58, 95% CI 0.53-0.64; p < 0.0001), and migraine-related neurologist visits (OR 0.69, 95% CI 0.63-0.75; p < 0.0001) were observed during the 180-days post-index period. There were significant decreases in the odds of having overall preventive migraine medications (OR 0.81, 95% CI 0.75-0.87; p < 0.0001), acute-migraine medications (OR 0.92, 95% CI 0.85-1.00; p = 0.038), and triptan (OR 0.79, 95% CI 0.73-0.85; p < 0.0001) during the 180-day post-index period. Sensitivity analyses on cost outcomes found no statistically significant differences in pre-index migraine-related costs compared to post-index migraine-related costs when assessing longer post-index follow-up periods. CONCLUSION: Initiation of therapy with a novel treatment is often associated with an increase in overall healthcare costs due to the entrance costs associated with novel therapy. For a chronic condition such as migraine, cost versus health benefits should be evaluated over a long period (e.g., ≥2 years) to better understand the true benefits of therapy. Data from this study suggest that the entrance cost for erenumab, the primary driver of the high post-index prescription costs gets mitigated by reduced medical costs over long-term follow-up. The results indicate better disease management in adult patients with migraine, which should be an important consideration for both patients and payors, as these findings have shown an offset between migraine-related prescription and medical costs.
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Custos de Cuidados de Saúde , Transtornos de Enxaqueca , Adulto , Humanos , Estados Unidos , Adolescente , Estudos Retrospectivos , Transtornos de Enxaqueca/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
2D graphene the most investigated structures from nanocarbon family studied in the last three decades. It is projected as an excellent material useful for quantum computing, artificial intelligence, and next generation advanced technologies. Graphene exists in several forms and its extraordinary thermal, mechanical, and electronic properties, principally depend on the kind of perfection of the hexagonal atomic lattice. Defects are always considered as undesired components but certain defects in graphene could be an asset for electrochemistry and quantum electronics due to the engineered electronclouds and quantum tunnelling. The authors carefully discuss the Stone-Wales imperfections in graphene and its derivatives comprehensively. A specific emphasis is focused on the experimental and theoretical aspects of the Stone-Wales defects in graphene with respect to structure-property relationships. The corroboration of extrinsic defects like external atomic doping, functionalization, edge distortion in the graphene consisting of Stone-Wales imperfections, which are very significant in designing graphene-based electronic devices, are summarized.
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Aim: To assess the relative efficacy of disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) including newer therapies (ozanimod, ponesimod, ublituximab) using network meta-analysis (NMA). Materials & methods: Bayesian NMAs for annualised relapse rate (ARR) and time to 3-month and 6-month confirmed disability progression (3mCDP and 6mCDP) were conducted. Results: For each outcome, the three most efficacious treatments versus placebo were monoclonal antibody (mAb) therapies: alemtuzumab, ofatumumab, and ublituximab for ARR; alemtuzumab, ocrelizumab, and ofatumumab for 3mCDP; and alemtuzumab, natalizumab, and either ocrelizumab or ofatumumab (depending on the CDP definition used for included ofatumumab trials) for 6mCDP. Conclusion: The most efficacious DMTs for RMS were mAb therapies. Of the newer therapies, only ublituximab ranked among the three most efficacious treatments (for ARR).
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Alemtuzumab/uso terapêutico , Metanálise em Rede , Teorema de Bayes , RecidivaRESUMO
In order to prevent the growth of pathogens in food, bacteriocins produced by various probiotic lactic acid bacteria have been recognized as potential substitutes of chemical preservatives. In this study, enterocin LD3 was purified from the cell-free supernatant of a food isolate, Enterococcus hirae LD3 using multistep chromatography. In the fruit juice, lethal concentration (LC50) of enterocin LD3 was found to be 260 µg/mL against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The cells treated with enterocin LD3 were red colour indicating dead cells after propidium iodide staining, while untreated cells were found blue after staining with 4', 6-diamidino-2-phenylindole. The mechanism of cell killing was analyzed using infrared spectrum of cells treated with enterocin LD3 which was found altered in the range of 1,094.30 and 1,451.82 cm-1 corresponding to nucleic acids and phospholipids, respectively. The morphology of target cells were severely ruptured and lysed as observed under electron microscopy. Thus, the present study suggested that enterocin LD3 showed bactericidal activity against Salm. enterica subsp. enterica serovar Typhimurium ATCC 13311 and may be applied as a bio-preservative for the safety of fruit juices.
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The toxic effects of chemotherapy drugs on normal tissues are still a major limiting factor in cancer treatment. In this paper, we report a metal-organic framework (Zn-Co ZIF) with chitosan-coated outer layer as a carrier for the drug adriamycin hydrochloride (DOX), a treatment for liver cancer, as a novel anti-cancer nanodrug-enhanced carrier. Gold nanoparticles, a good photothermal conversion agent, were combined with the target SH-RGD during surface functionalisation to prepare Zn-Co ZIF@DOX-CS-Au-RGD (ZD-CAR), a nanoplatform with good photothermal conversion properties and targeting for combined liver cancer therapy. ZD-CAR was developed after RGD accurately targeted the tumour and entered the tumour microenvironment (TME), it cleaves and releases the liver cancer therapeutic agent (DOX) in a weak acidic environment to effectively kill tumour cells. The metal skeleton cleavage releases Co2+, which catalyzes the production of oxygen from H2O2 to alleviate the tumour hypoxic environment. The dissolved oxygen could reach 14 mg/L after adding 80 mg/mL of ZD-CAR. Meanwhile, gold nanoparticles could convert light energy into heat energy under 808 NIR irradiation to induce local superheating and kill tumour cells. In summary, this study developed a nanoplatform that combines chemo-photothermal-targeted therapy. It has shown good therapeutic effeciency in cellular experiments and performance tests and has promising applications in anti-cancer therapy.
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The slow kinetics of the oxygen evolution reaction (OER) is one of the significant reasons limiting the development of electrochemical hydrolysis. Doping metallic elements and building layered structures have been considered effective strategies for improving the electrocatalytic performance of the materials. Herein, we report flower-like nanosheet arrays of Mn-doped-NiMoO4/NF (where NF is nickel foam) on nickel foam by a two-step hydrothermal method and a one-step calcination method. The doping manganese metal ion not only modulated the morphologies of the nickel nanosheet but also altered the electronic structure of the nickel center, which could be the result of superior electrocatalytic performance. The Mn-doped-NiMoO4/NF electrocatalysts obtained at the optimum reaction time and the optimum Mn doping showed excellent OER activity, requiring overpotentials of 236 mV and 309 mV to drive 10 mA cm-2 (62 mV lower than the pure NiMoO4/NF) and 50 mA cm-2 current densities, respectively. Furthermore, the high catalytic activity was maintained after continuous operation at a current density of 10 mA cm-2 of 76 h in 1 M KOH. This work provides a new method to construct a high-efficiency, low-cost, stable transition metal electrocatalyst for OER electrocatalysts by using a heteroatom doping strategy.
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OBJECTIVE: The treatment landscape for the prevention of migraine has rapidly evolved in recent years with the advent of calcitonin gene-related peptide therapy, including erenumab. The objective of this study was to assess patient-reported treatment satisfaction among erenumab users. METHODS: This retrospective, cross-sectional study used data from the 2019 US National Health and Wellness Survey collected during March-July 2019. Respondents self-reporting physician-diagnosed migraine and currently using erenumab were analyzed. Treatment satisfaction was measured on a seven-point Likert scale. Data were further reported by the duration of erenumab treatment. Data on respondents' socio-demographic characteristics and treatment patterns were also collected. RESULTS: Overall, 67 respondents using erenumab with or without other migraine preventives for up to 1 year were included in the analysis. The mean (standard deviation) age was 46.7 (12.9) years. Most of the respondents were women (86.6%), White (74.6%), and commercially-insured (67.2%). Notably, 40.3% had ≥1 comorbidity per the Charlson Comorbidity Index. Approximately half of the respondents were college graduates and employed (49.3% each). Among the 67 respondents, 46 received erenumab exclusively. Across both cohorts, the percentage of respondents who were satisfied with erenumab treatment was slightly higher among those with a longer treatment duration (overall erenumab cohort: 63.6%, 69.6%, and 75.8% for 0-<3, 3-<6, and 6-12 months, respectively; erenumab monotherapy cohort: 62.5%, 71.4%, and 87.5% for 0-<3, 3-<6, and 6-12 months, respectively). Treatment patterns before switching to erenumab revealed that most respondents had used ≥1 preventive treatment for migraine (80.6%; 54/67), over two-thirds (33/54) of whom had ≥2 treatment failures owing to nonresponse. CONCLUSION: Satisfaction was high among long-term erenumab users, indicating that those using erenumab for a longer duration are more satisfied. Furthermore, this study provided insights on the basic socio-demographics, disease characteristics, and health behaviors of erenumab users as well as their treatment patterns before switching to erenumab.
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Anticorpos Monoclonais Humanizados , Transtornos de Enxaqueca , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Estudos Transversais , Anticorpos Monoclonais Humanizados/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the available clinical and economic evidence of erenumab vs onabotulinumtoxinA for chronic migraine (CM) and present de-novo indirect treatment comparisons (ITCs) based on available clinical trial data. METHODS: We conducted ITCs based on results from the pivotal 295 trial (NCT02066415) of erenumab vs placebo and published aggregate data from the PREEMPT 1 (NCT00156910) and PREEMPT 2 (NCT00168428) trials of onabotulinumtoxinA vs placebo. ITCs were conducted for CM patients with and without prior administration of onabotulinumtoxinA and among CM patients with ≥3 prior preventive treatment failures. Efficacy was assessed based on responder rates of ≥50% reductions in monthly headache days (MHDs) and monthly migraine days (MMDs) as well as change from baseline in both MHDs and MMDs. RESULTS: Among patients with CM, 140 mg erenumab was associated with a reduction of 1.2 MHD (p = .092) and a reduction of 1.0 MMD (p = .174) compared to onabotulinumtoxinA at Week 12. Among onabotulinumtoxinA-naïve patients, erenumab was associated with a reduction of 1.8 MHD (p = .026) and 1.4 MMD (p = .080) at Week 12. Among patients that had received ≥3 prior preventive treatments, the odds ratios comparing erenumab vs onabotulinumtoxinA were 1.7 for ≥50% responder rates based on reductions in MHD (p = .155) and 1.7 for ≥50% responder rates based on reductions in MMD (p = .140). CONCLUSION: These findings suggest directional benefits (although not reaching the threshold of statistical significance) associated with erenumab vs onabotulinumtoxinA for the preventive treatment of CM. Evidence from this study may inform healthcare stakeholders in treatment selection and optimization for patients with CM.
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Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Método Duplo-Cego , Cefaleia , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resultado do TratamentoRESUMO
The magnitude of variations in the level of circulating mitochondrial (cir-mtDNA) and nuclear DNA (cir-ncDNA) in different diseases has indicated the need for investigating a discriminative approach for evaluating their diagnostic significance. This study reports a typical in-house process for extracting both types of cir-DNAs from a single plasma sample and assessed their usefulness in discriminating type 2 diabetes mellitus patients from healthy individuals to eliminate the prevailing dispute about their discriminative role and improve their diagnostic value. This approach offers a more precise and valuable tool for distinguishing the impact of cir-mtDNA from cir-ncDNA in diagnostic implications.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Patologia Molecular , Mitocôndrias/genética , DNA Mitocondrial/genéticaRESUMO
Several strains of lactic acid bacteria are potent probiotics and can cure a variety of diseases using different modes of actions. These bacteria produce antimicrobial peptides, bacteriocins, which inhibit or kill generally closely related bacterial strains and other pathogenic bacteria such as Listeria, Clostridium, and Salmonella. Bacteriocins are cationic peptides that kill the target cells by pore formation and the dissipation of cytosolic contents, leading to cell death. Bacteriocins are also known to modulate native microbiota and host immunity, affecting several health-promoting functions of the host. In this review, we have discussed the ability of bacteriocin-producing probiotic lactic acid bacteria in the modulation of gut microbiota correcting dysbiosis and treatment/maintenance of a few important human disorders such as chronic infections, inflammatory bowel diseases, obesity, and cancer.
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Bacteriocinas , Microbioma Gastrointestinal , Lactobacillales , Probióticos , Bactérias/metabolismo , Bacteriocinas/metabolismo , Disbiose , Humanos , Lactobacillales/metabolismo , Probióticos/farmacologiaRESUMO
Hydrogen is regarded as a key renewable energy source to meet future energy demands. Moreover, graphene and its derivatives have many advantages, including high electronic conductivity, controllable morphology, and eco-friendliness, etc., which show great promise for electrocatalytic splitting of water to produce hydrogen. This review article highlights recent advances in the synthesis and the applications of graphene-based supported electrocatalysts in hydrogen evolution reaction (HER). Herein, powder-based and self-supporting three-dimensional (3D) electrocatalysts with doped or undoped heteroatom graphene are highlighted. Quantum dot catalysts such as carbon quantum dots, graphene quantum dots, and fullerenes are also included. Different strategies to tune and improve the structural properties and performance of HER electrocatalysts by defect engineering through synthetic approaches are discussed. The relationship between each graphene-based HER electrocatalyst is highlighted. Apart from HER electrocatalysis, the latest advances in water electrolysis by bifunctional oxygen evolution reaction (OER) and HER performed by multi-doped graphene-based electrocatalysts are also considered. This comprehensive review identifies rational strategies to direct the design and synthesis of high-performance graphene-based electrocatalysts for green and sustainable applications.
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Background: Evidence suggests that early highly efficacious therapy in relapsing multiple sclerosis is superior to escalation strategies. Objective: A cost-consequence analysis simulated different treatment scenarios with ofatumumab (OMB), dimethyl fumarate (DMF) and glatiramer acetate (GA): immediate OMB initiation as first treatment, early switch to OMB after 1 year on DMF/GA, late switch after 5 years or no switch. Methods: An EDSS-based Markov model with a 10-year time horizon was applied. Cycle transitions included EDSS progression, improvement or stabilization, treatment discontinuation, relapse or death. Input data were extracted from OMB trials, a network meta-analysis, published literature, and publicly available sources. Results: The late switch compared to the immediate OMB scenario resulted in a lower proportion of patients with EDSS 0-3 (Δ - 7.5% DMF; Δ - 10.3% GA), more relapses (Δ + 0.72 DMF; Δ + 1.23 GA) and lower employment rates (Δ - 4.0% DMF; Δ - 5.6% GA). The same applies to late versus early switches. No switch scenarios resulted in worse outcomes. Higher drug acquisition costs in the immediate OMB and early switch scenarios were almost compensated by lower costs for patient care and productivity loss. Conclusion: Immediate OMB treatment and an early switch improves clinical and productivity outcomes while remaining almost cost neutral compared to late or no switches.
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Development of a low cost, high activity, and stable nonprecious metal bifunctional catalyst for electrocatalytic water cracking is a hot topic and big challenge. In this paper, we prepared a nitrogen-doped carbon nanotube (NCNT)-enhanced three-dimensional self-supported electrocatalyst with CoP and Co2P coexistence by a two-step strategy of high-temperature carbonization and low-temperature phosphorylation. Furthermore, the induced three-dimensional carbon network skeleton facilitates rapid charge transfer. In addition, the active sites of the carbon foam (CF) are greatly increased by the construction of hollow structures. As a bifunctional electrocatalyst, CoP/Co2P/NCNT@CF exhibited excellent catalytic activity for both hydrogen evolution reaction and oxygen evolution reaction in alkaline media, requiring low overpotentials of 133 and 289 mV to obtain a current density of 10 mA cm-2, respectively. Additionally, the synthesized catalysts also exhibit good long-term stability, maintaining high catalytic activity after 20 h of continuous operation. We also confirmed the main driving force to improve the electron transfer between the heterostructures of Co and P by XPS spectra. The excellent electrocatalytic performance can be attributed to the close synergy between the highly active CoP/Co2P/NCNT and CF. This study provides a new strategy for the design of highly active bifunctional self-supporting electrocatalysts.
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Production of snake foam based on p-nitro aniline (PNA) was considered fun in old-school chemistry laboratories. Herein, we report the fabrication of a new carbon nanomaterial from PNA-based foam. The resulting material, resembling graphene and consisting of nitrogen heteroatoms, is N-doped graphenelike nanostructures, and their morphology, structure, and stability are comprehensively examined using combined techniques including C-13 NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). An optimized route was also established for their large-scale production. Further experimental validation of them as a nanofiller in polymer [SEBS (20 wt %) and paraffin wax (80 wt %)]-based nanocomposites was carried out, and we found that the thermomechanical properties of the nanocomposites were synchronously improved, which was attributed to the enshrouding effect of the nanofiller to the polymer chains. Owing to their good thermomechanical property and low-cost feature, these new nanomaterials can be further explored as a promising candidate for applications in energy storage, catalysis, and CO2 capture.