Pulmonary hypertension is a highly morbid disease with no cure. Available treatments are limited by systemic adverse effects due to non‐specific biodistribution. Self‐assembled peptide amphiphile ...(PA) nanofibers are biocompatible nanomaterials that can be modified to recognize specific biological markers to provide targeted drug delivery and reduce off‐target toxicity. Here, PA nanofibers that target the angiotensin I‐converting enzyme and the receptor for advanced glycation end‐products (RAGE) are developed, as both proteins are overexpressed in the lung with pulmonary hypertension. It is demonstrated that intravenous delivery of RAGE‐targeted nanofibers containing the targeting epitope LVFFAED (LVFF) significantly accumulated within the lung in a chronic hypoxia‐induced pulmonary hypertension mouse model. Using 3D light sheet fluorescence microscopy, it is shown that LVFF nanofiber localization is specific to the diseased pulmonary tissue with immunofluorescence analysis demonstrating colocalization of the targeted nanofiber to RAGE in the hypoxic lung. Furthermore, biodistribution studies show that significantly more LVFF nanofibers localized to the lung compared to major off‐target organs. Targeted nanofibers are retained within the pulmonary tissue for 24 h after injection. Collectively, these data demonstrate the potential of a RAGE‐targeted nanomaterial as a drug delivery platform to treat pulmonary hypertension.
Peptide amphiphile nanofibers targeted to the receptor for advanced glycation end‐products (RAGE) significantly accumulate within diseased lungs of mice with hypoxia‐induced pulmonary hypertension following intravascular delivery. The targeted nanofibers remain localized to the pulmonary tissue for up to 24 h after injection. PA nanofibers may be effective delivery vehicles to provide targeted therapies for pulmonary hypertension.
•The effects of different drying procedures on bioactive polymer acemannan were studied.•All drying methods caused considerable degradation of the acemannan structure.•Deacetylation of the acemannan ...polymer was confirmed by 1H NMR analysis.•Degradation of the acemannan structure led to a dramatic reduction of the functional properties.•Modification of acemannan structure could also affect the beneficial properties of Aloe vera.
The main effects of different drying procedures: spray-, industrial freeze-, refractance window- and radiant zone-drying, on acemannan, the main bioactive polysaccharide from Aloe vera gel, were investigated. All the drying procedures caused a considerable decrease in the acemannan yield (∼40%). Degradation affected not only the backbone, as indicated by the important losses of (1→4)-linked mannose units, but also the side-chains formed by galactose. In addition, methylation analysis suggested the deacetylation of mannose units (>60%), which was confirmed by 1H NMR analysis. Interestingly, all these changes were reflected in the functional properties which were severely affected. Thus, water retention capacity values from processed samples decreased ∼50%, and a reduction greater than 80% was determined in swelling and fat adsorption capacity values. Therefore, these important modifications should be taken into consideration, since not only the functionality but also the physiological effects attributed to many Aloe vera-based products could also be affected.
Zinc substituted nickel ferrite (Zn
x
Ni
1 − x
Fe
2
O
4
) is investigated under density functional theory (DFT) within the DFT + U approximation for
x
≤ 0.50, with particular interest in ...understanding the effect of Zn on the net magnetization. Using as a reference ZnFe
2
O
4
, the localization of the Zn
d
band is proved to have a large impact on the preference for Zn to occupy either tetrahedral (Zn
A
) or octahedral (Zn
B
) coordination sites, which in ZnFe
2
O
4
is equivalent to the relative stability of the direct and inverse spinel forms. This affects the lattice volume, with Zn
A
favoring larger lattice expansions. Additional important consequences emerge on the magnetism of the system, as Zn
A
and Zn
B
alter the balance of atoms at the magnetic sublattices in a different way: while Zn
A
enhances the global magnetization by reducing the minority spin contribution, the opposite occurs for Zn
B
. On the other hand, the dominant magnetic exchange interactions are not significantly altered by Zn independently of its distribution, while the magnetic anisotropy of soft NiFe
2
O
4
is further weakened. Our simulations support the presence of a significant ratio of Zn atoms at octahedral positions at Zn
x
Ni
1 − x
Fe
2
O
4
, mainly as the Zn concentration increases, putting limits to the ability to increase the magnetization of NiFe
2
O
4
by Zn substitution.
Liquid fuels produced via Fischer-Tropsch synthesis from biomass-derived syngas constitute an attractive and sustainable energy vector for the transportation sector. This study focuses on the role of ...potassium as a promoter in Ni-based catalysts for reducing coke deposition during catalytic dry reforming. The study provides a new structural link between catalytic performance and physicochemical properties. We identify new Ni-O-K chemical states associated with high stability in the reforming process, evidenced by different characterization techniques. The nickel particles form a core surrounded by a Ni-O-K phase layer (Ni@Ni-O-K) during the reduction of the catalyst. This phase likely presents an alkali-nickelate-type structure, in which nickel is stabilized in oxidation state + 3. The Ni-O-K formation induces essential changes in the electronic, physical, structural, and morphological properties of the catalysts, notably enhancing their long-term stability in dry reforming. This work thus provides new directions for designing more efficient catalysts for sustainable gas-to-liquids processes.
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•Deep insights into Ni-K-O catalysts for DRM.•Experimental evidence of Ni@Ni-O-K layer phase.•Ni-O-K sites inhibit CO dissociation.•Ni-O-K sites lead to ultra-resistant DRM catalysts.
Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the ...p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity.Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.
This work represents a systematic study of four conductive salts and their influence on the physicochemical properties of propylene‐carbonate‐based electrolytes for electrochemical double‐layer ...capacitors (EDLCs). State‐of‐the‐art tetraethylammonium tetrafluoroborate is compared with tetraethylammonium bis(trifluoromethanesulfonyl)imide, N‐butyl‐N‐methylpyrrolidinium tetrafluoroborate, and N‐butyl‐N‐methylpyrrolidinium bis(trifluoromethanesulfonyl)imide. By applying these salts, operating voltages of up to 3.5 V can be achieved while retaining a high performance. Furthermore, the influence of the conductive salts on the carbon–electrolyte interface is studied by comparing the electrochemical performance of five commercial porous carbons in the respective electrolytes. The choice of conductive salt has a great influence on the electrochemical performance and maximum operating voltage of an EDLC system, as well as on the specific capacitance of the chosen carbon material; this makes the choice of both materials crucial for successful EDLC design.
Optimum selection: The operating voltage of propylene carbonate based electrolytes is strongly dependent on the chosen conductive salt, and the change in ion size has a large influence on the electrolyte–carbon interface (see picture).
The impact derived from incorporating water into CH 4 /CO 2 biogas stream for the generation of syngas was investigated over the Rh/MgAl 2 O 4 catalyst using operando steady-state and transient DRIFT ...spectroscopy coupled with MS. The incorporation of steam resulted in improved CH 4 conversion rates and attained syngas streams with higher H 2 /CO ratios. It was demonstrated that in the presence of steam, the generation of CH x O species through the reaction of CO* with active *OH species is favored at the metal support surface. Besides, the enhanced resistance delivered by water molecules towards deactivating the coking phenomena was associated with easier carbonaceous decomposition and the exposition of the very active Rh (100) surfaces for methane decomposition. The Rh/MgAl 2 O 4 catalyst was demonstrated to be an effective catalyst for the production of H 2 -rich syngas streams. More importantly, the insights reported herein provide new evidences regarding the impact of steam on biogas reforming reactions.
The RWGS reaction is gathering momentum as an effective route for CO2 valorisation and given its endothermic nature the challenge lies in the design of active low-temperature catalysts. Herein we ...have designed two catalysts based on subnanometric Pt clusters providing effective CO2 conversion and, more importantly, high CO selectivity in the low-temperature range. The impact of Cs as a dopant in the catalyst's formulation is crucial leading to full selectivity at 300 °C. The reaction mechanisms for the studied systems namely Pt/TiO2 and PtCs/TiO2 are significantly different due to the presence of the alkali promoter. The presence of Cs neutralises the hydroxide groups of the TiO2 surface, changing the reaction pathway. The Pt/TiO2 catalyst follows a redox mechanism where CO2 dissociates to CO in the oxygen vacancies, and then these vacancies are recovered by the migration of H2 by spill over phenomena. On the other hand, the Cs doped catalyst has two possible mechanism pathways: the (ii) formyl/acyl pathway, where –CHO species are formed and, depending on the reaction conditions, evolve to CO gas or oxygenated compounds, and (ii) frustrated Lewis pair (FLP) assisted CO2 reduction route, in which the FLP induces the heterolytic dissociation of H2 and the subsequent hydrogenation of CO2 to CO. The latter route enabled by Cs-doping combined with the subnanometric Pt domains seems to be responsible for the excellent catalytic behaviour leading to fully selective low-temperature RWGS systems and thus unlocking new possibilities for less energy demanding CO2 valorisation units based on RWGS.
Adipose tissue has emerged as an important regulator of whole-body metabolism, and its capacity to dissipate energy in the form of heat has acquired a special relevance in recent years as potential ...treatment for obesity. In this context, the p38MAPK pathway has arisen as a key player in the thermogenic program because it is required for the activation of brown adipose tissue (BAT) thermogenesis and participates also in the transformation of white adipose tissue (WAT) into BAT-like depot called beige/brite tissue. Here, using mice that are deficient in p38α specifically in adipose tissue (p38αFab-KO), we unexpectedly found that lack of p38α protected against high-fat diet (HFD)-induced obesity. We also showed that p38αFab-KO mice presented higher energy expenditure due to increased BAT thermogenesis. Mechanistically, we found that lack of p38α resulted in the activation of the related protein kinase family member p38δ. Our results showed that p38δ is activated in BAT by cold exposure, and lack of this kinase specifically in adipose tissue (p38δ Fab-KO) resulted in overweight together with reduced energy expenditure and lower body and skin surface temperature in the BAT region. These observations indicate that p38α probably blocks BAT thermogenesis through p38δ inhibition. Consistent with the results obtained in animals, p38α was reduced in visceral and subcutaneous adipose tissue of subjects with obesity and was inversely correlated with body mass index (BMI). Altogether, we have elucidated a mechanism implicated in physiological BAT activation that has potential clinical implications for the treatment of obesity and related diseases such as diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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