RESUMO
The segmented negative-sense RNA genome of influenza A virus is assembled into ribonucleoprotein complexes (RNP) with viral RNA-dependent RNA polymerase and nucleoprotein (NP). It is in the context of these RNPs that the polymerase transcribes and replicates viral RNA (vRNA). Host acidic nuclear phosphoprotein 32 (ANP32) family proteins play an essential role in vRNA replication by mediating the dimerization of the viral polymerase via their N-terminal leucine-rich repeat (LRR) domain. However, whether the C-terminal low-complexity acidic region (LCAR) plays a role in RNA synthesis remains unknown. Here, we report that the LCAR is required for viral genome replication during infection. Specifically, we show that the LCAR directly interacts with NP and this interaction is mutually exclusive with RNA. Furthermore, we show that the replication of a short vRNA-like template that can be replicated in the absence of NP is less sensitive to LCAR truncations compared with the replication of full-length vRNA segments which is NP-dependent. We propose a model in which the LCAR interacts with NP to promote NP recruitment to nascent RNA during influenza virus replication, ensuring the co-replicative assembly of RNA into RNPs.
Assuntos
Proteínas Nucleares , RNA Viral , Genoma Viral , Proteínas Nucleares/metabolismo , Proteínas do Nucleocapsídeo/genética , Nucleoproteínas/genética , Nucleoproteínas/metabolismo , Fosfoproteínas/genética , RNA Viral/genética , RNA Viral/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Replicação Viral/genéticaRESUMO
The air quality in China has improved significantly in the last decade and, correspondingly, the characteristics of PM2.5 have also changed. We studied the interannual variation of PM2.5 in Chengdu, one of the most heavily polluted megacities in southwest China, during the most polluted season (winter). Our results show that the mass concentrations of PM2.5 decreased significantly year-by-year, from 195.8 ± 91.0 µg/m3 in winter 2016 to 96.1 ± 39.3 µg/m3 in winter 2020. The mass concentrations of organic matter (OM), SO42-, NH4+ and NO3- decreased by 49.6%, 57.1%, 49.7% and 28.7%, respectively. The differential reduction in the concentrations of chemical components increased the contributions from secondary organic carbon and NO3- and there was a larger contribution from mobile sources. The contribution of OM and NO3- not only increased with increasing levels of pollution, but also increased year-by-year at the same level of pollution. Four sources of PM2.5 were identified: combustion sources, vehicular emissions, dust and secondary aerosols. Secondary aerosols made the highest contribution and increased year-by-year, from 40.6% in winter 2016 to 46.3% in winter 2020. By contrast, the contribution from combustion sources decreased from 14.4% to 8.7%. Our results show the effectiveness of earlier pollution reduction policies and emphasizes that priority should be given to key pollutants (e.g., OM and NO3-) and sources (secondary aerosols and vehicular emissions) in future policies for the reduction of pollution in Chengdu during the winter months.
Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Material Particulado/análise , Estações do Ano , Monitoramento Ambiental , China , Aerossóis/análiseRESUMO
Lithium metal anode (LMA) is puzzled by the serious issues corresponding to infinite volume change and notorious lithium dendrite during long-term stripping/plating process. Herein, the transition metal nitrides array with outstanding lithiophilicity, including CoN, VN, and Ni3 N, are decorated onto carbon framework as "nests" to uniform Li nucleation and guide Li metal deposition. These transition metal nitrides with excellent conductivity can guarantee the fast electron transport, therefore maintain a stable interface for Li reduction. In addition, the designed multi-dimensional structure of metal nitride array decorated carbon framework can effectively regulate the growth of Li metal during the stripping/plating process. Of note, attributing to the lattice-matching between CoN and Li metal, the composite Li/CoN@CF anode exhibits ultra-stable cycling performance in symmetrical cells (over 4000 h@1 mA cm-2 with 1 mAh cm-2 and 1000h@20 mA cm-2 with 20 mAh cm-2 ). The assembled full cells based on Li/CoN@CF composite anode, LiFePO4 or S as cathodes, deliver excellent cycling stability and rate capability. This strategy provides an effective approach to develop a stable lithium metal anode for lithium metal batteries.
RESUMO
Structurally optimized transition metal phosphides are identified as a promising avenue for the commercialization of lithium-sulfur (Li-S) batteries. In this study, a CoP nanoparticle-doped hollow ordered mesoporous carbon sphere (CoP-OMCS) is developed as a S host with a "Confinement-Adsorption-Catalysis" triple effect for Li-S batteries. The Li-S batteries with CoP-OMCS/S cathode demonstrate excellent performance, delivering a discharge capacity of 1148 mAh g-1 at 0.5 C and good cycling stability with a low long-cycle capacity decay rate of 0.059% per cycle. Even at a high current density of 2 C after 200 cycles, a high specific discharge capacity of 524 mAh g-1 is maintained. Moreover, a reversible areal capacity of 6.56 mAh cm-2 is achieved after 100 cycles at 0.2 C, despite a high S loading of 6.8 mg cm-2 . Density functional theory (DFT) calculations show that CoP exhibits enhanced adsorption capacity for sulfur-containing substances. Additionally, the optimized electronic structure of CoP significantly reduces the energy barrier during the conversion of Li2 S4 (L) to Li2 S2 (S). In summary, this work provides a promising approach to optimize transition metal phosphide materials structurally and design cathodes for Li-S batteries.
RESUMO
Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 µg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 µM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH.
Assuntos
Adrenomedulina , Anti-Inflamatórios , Antioxidantes , Hipertensão , Obesidade , Animais , Masculino , Ratos , Adrenomedulina/farmacologia , Adrenomedulina/uso terapêutico , Proteínas Quinases Ativadas por AMP , Calcinose/complicações , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertensão/metabolismo , Inflamação/complicações , Obesidade/complicações , Ratos Sprague-Dawley , Remodelação Vascular , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
The most promising energy storage devices are lithium-sulfur batteries (LSBs), which offer a high theoretical energy density that is five times greater than that of lithium-ion batteries. However, there are still significant barriers to the commercialization of LSBs, and mesoporous carbon-based materials (MCBMs) have attracted much attention in solving LSBs' problems, due to their large specific surface area (SSA), high electrical conductivity, and other unique advantages. The synthesis of MCBMs and their applications in the anodes, cathodes, separators, and "two-in-one" hosts of LSBs are reviewed in this study. Most interestingly, we establish a systematic correlation between the structural characteristics of MCBMs and their electrochemical properties, offering recommendations for improving performance by altering the characteristics. Finally, the challenges and opportunities of LSBs under current policies are also clarified. This review provides ideas for the design of cathodes, anodes, and separators for LSBs, which could have a positive impact on the performance enhancement and commercialization of LSBs. The commercialization of high energy density secondary batteries is of great importance for the achievement of carbon neutrality and to meet the world's expanding energy demand.
Assuntos
Carbono , Lítio , Condutividade Elétrica , Fontes de Energia Elétrica , EnxofreRESUMO
BACKGROUND: Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). METHODS: DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks. RESULTS: Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 µmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-ß1 protein level, and improved aortic elastin expression. CONCLUSIONS: H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-ß1 level and increasing local elastin level.
Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Túnica Média/efeitos dos fármacos , Calcificação Vascular/prevenção & controle , Animais , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/etiologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Catepsinas/metabolismo , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Elastina/metabolismo , Masculino , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Túnica Média/metabolismo , Túnica Média/patologia , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/patologiaRESUMO
BACKGROUND: The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. METHODS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. RESULTS: Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. CONCLUSIONS: TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH.
Assuntos
Tecido Adiposo/metabolismo , Dieta Hiperlipídica , Obesidade/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tecido Adiposo Branco/patologia , Adiposidade , Animais , Peso Corporal , Inflamação/metabolismo , Masculino , NADPH Oxidases/metabolismo , Neurônios Aferentes/metabolismo , Norepinefrina/sangue , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sistema Nervoso Simpático/patologia , Sístole , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is rare, but a certain amount of mortality remains in NPC patients. Our study aimed to identify candidate genes as biomarkers for NPC screening, diagnosis, and therapy. METHODS: We investigated two microarray profile datasets GSE64634 and GSE12452 to screen the potential differentially expressed genes (DEGs) in NPC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were also performed. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized by Cytoscape software. The associated transcriptional factor regulatory network of the DEGs was also constructed. RESULTS: A total of 152 DEGs were identified from the GSE64634 and GSE12452 datasets, including 10 upregulated and 142 downregulated genes. Gene functional enrichment analysis indicated that these DEGs were enriched in the cilium movement, antimicrobial humoral response, O-glycan processing, mucosal immune response, carbohydrate transmembrane transporter activity, hormone biosynthetic process, neurotransmitter biosynthetic process, and drug metabolism-cytochrome P450 pathway. Five hub genes (DNALI1, RSPH4A, RSPH9, DNAI2, and ALDH3A1) and one significant module (score = 5.6) were obtained from the PPI network. Key transcriptional factors, such as SPI1, SIN3B, and GATA2, were identified with close interactions with these five hub DEGs from the gene-transcriptional factor network. CONCLUSIONS: With the integrated bioinformatic analysis, numerous DEGs related to NPC were screened, and the hub DEGs we identified may be potential biomarkers for NPC.
Assuntos
Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Carcinoma Nasofaríngeo/genética , Fatores de Transcrição/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Prognóstico , Mapas de Interação de Proteínas , Software , Fatores de Transcrição/metabolismoRESUMO
Increased reactive oxygen species (ROS) induced by angiotensin II (Ang II) in the paraventricular nucleus (PVN) play a critical role in sympathetic overdrive in hypertension (OH). Intermedin (IMD), a bioactive peptide, has extensive clinically prospects in preventing and treating cardiovascular diseases. The study was designed to test the hypothesis that IMD in the PVN can inhibit the generation of ROS caused by Ang II for attenuating sympathetic nerve activity (SNA) and blood pressure (BP) in rats with obesity-related hypertension (OH). Male Sprague-Dawley rats (160-180 g) were used to induce OH by feeding of a high-fat diet (42% kcal as fat) for 12 weeks. The dynamic changes of sympathetic outflow were evaluated as the alterations of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to certain chemicals. The results showed that the protein expressions of Ang II type 1 receptor (AT1R), calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2) and RAMP3 were markedly increased, but IMD was much lower in OH rats when compared to control rats. IMD itself microinjection into PVN not only lowered SNA, NADPH oxidase activity and ROS level, but also decreased Ang II-caused sympathetic overdrive, and increased NADPH oxidase activity, ROS levels and mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) activation in OH rats. However, those effects were mostly blocked by the adrenomedullin (AM) receptor antagonist AM22-52 pretreatment. The enhancement of SNA caused by Ang II can be significantly attenuated by the pretreatment of AT1R antagonist lorsatan, superoxide scavenger Tempol and NADPH oxidase inhibitor apocynin (Apo) in OH rats. ERK activation inhibitor U0126 in the PVN reversed Ang II-induced enhancement of SNA, and Apo and IMD pretreatment in the PVN decreased Ang II-induced ERK activation. Chronic IMD administration in the PVN resulted in significant reductions in basal SNA and BP in OH rats. Moreover, IMD lowered NADPH oxidase activity and ROS level in the PVN; reduced the protein expressions of AT1R and NADPH oxidase subunits NOX2 and NOX4, and ERK activation in the PVN; and decreased Ang II levels-inducing sympathetic overactivation. These results indicated that IMD via AM receptors in the PVN attenuates SNA and hypertension, and decreases Ang II-induced enhancement of SNA through the inhibition of NADPH oxidase activity and ERK activation.
Assuntos
Adrenomedulina/farmacologia , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Hipertensão/tratamento farmacológico , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Adrenomedulina/uso terapêutico , Angiotensina II/farmacologia , Animais , Anti-Hipertensivos/uso terapêutico , Antioxidantes/uso terapêutico , Pressão Sanguínea , Hipertensão/etiologia , Sistema de Sinalização das MAP Quinases , Masculino , NADPH Oxidases/metabolismo , Obesidade/complicações , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sistema Nervoso Simpático/fisiopatologiaRESUMO
There is still lack of effective treatment of esophageal cancer, and it is urgently necessary to develop a new programs to treat this disease. More and more evidence suggests that the combination of 2 or more treatment strategies can enhance the antitumor activity in cancer treatment. We have established a new therapeutic strategy that combines doxorubicin-loaded poly(ε-caprolactone) (PCL)-Pluronic micelles and miR-34a to better combat esophageal cancer. Doxorubicin was loaded into PCL-Pluronic micelle to achieve better uptake. Confocal microscopy was used to assess in vitro cellular uptake of PCL-Pluronic micelle. Finally, the in vivo effect of this new combination therapy strategy was also studied. The results showed that PCL-Plannick micelles significantly enhanced the uptake of doxorubicin in esophageal cancer cells in vitro, thereby improving the accumulation of doxorubicin in the cells. In vitro and in vivo combination of doxorubicin-loaded PCL-Pluronic micelles and miR-34a, achieving a significantly synergistic therapeutic effect over the corresponding single treatment. These results suggested that the combinational therapy based on doxorubicin-loaded PCL-Pluronic micelle and miR-34a may provide a reasonable strategy for improving the outcome of esophageal cancer treatment.
Assuntos
Doxorrubicina/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Poliésteres/química , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Feminino , Camundongos , Camundongos Nus , MicelasRESUMO
In this study, self-supported NiFeP was fabricated on Ni mesh (NiFeP/NM) via a two-step monopulse electrodeposition and phosphorization strategy. The NiFeP/NM exhibited excellent activity through electrochemical surface reconstruction to generate true active sites, requiring low overpotentials of 349 mV and 310 mV to reach a current density of 500 mA cm-2 for the HER and OER, respectively, and exhibiting satisfactory stability in 6 M NaOH.
RESUMO
Graphene aerogels (GAs) are of significant interest in the scientific community due to their unique attributes, including a three-dimensional porous structure, exceptional specific surface area, and remarkable chemical stability. Researchers have made notable breakthroughs in aerogel preparation, focusing on aspects like porous structures and chemical stability. This review explores product morphologies and properties developed between 2011 and 2023, particularly examining applications of graphene aerogels with amine or alcohol radical scavengers. It offers a roadmap for researchers, suggesting possibilities for radiation-based preparation and indicating broader applications. These findings contribute to a deeper understanding of aerogels and expand the potential applications of graphene aerogels across various fields.
RESUMO
Affordable highly efficient catalysts for electrochemical oxygen evolution reaction (OER) play pivotal roles in green hydrogen production via water electrolysis. Regarding the non-noble metal-based electrocatalysts, considerable efforts are made to decipher the cation leaching and surface reconstruction; yet, little attention is focused on correlating them with catalytical activity and stability. Herein, in situ reconstruction of Fe-modified Co2VO4 precursor catalyst to form a highly active (Fe,V)-doped CoOOH phase for OER is reported, during which partial leaching of V accelerates the surface reconstruction and the V reserved in the reconstructed CoOOH layer in the form of alkali-resistant V2O3 serves for dynamic charge compensation and prevention of excessive loss of lattice oxygen and Co dissolution. Fe substitution facilitates Co pre-oxidation and endows the catalysts with structural flexibility by elevating O 2p band level; hence, encouraging participation of lattice oxygen in OER. The optimized Co2Fe0.25V0.75O4 electrode can afford current densities of 10 and 500 mA cm-2 at low overpotentials of 205 and 320 mV, respectively, with satisfactory stability over 600 h. By coupling with Pt/C cathode, the assembled alkaline electrolyzer can deliver 500 mA cm-2 at a low cell voltage of 1.798 V, better than that of commercial RuO2 (+) || Pt/C (-).
RESUMO
Hydrophilic anti-fogging coatings have attracted considerable attention due to their ease of preparation and excellent fog resistance. In this study, a hydrophilic anti-fogging coating based on the random copolymer p(AA-co-SAS) was prepared using acrylic acid (AA) and sodium allylsulfonate (SAS) as monomers through radiation polymerization. The introduction of SAS successfully transformed the random copolymer from a gel state into a film-forming polymer solution. The presence of AA structural units in p(AA-co-SAS) improved the film-forming properties of the polymer solution. Additionally, there was a positive correlation between the proportion of SAS structural units in the random copolymer and the scratch hardness and wetting properties of the coating. After coating polycarbonate (PC) sheets, the surface hydrophilicity was significantly enhanced, with the contact angle of PC-AA10/SAS5 decreasing from 100.1° to 18.8° within 50 seconds. The outstanding wetting properties endowed the coating with exceptional anti-fogging and frost-resisting performance. It exhibited optimal transparency under both testing conditions and demonstrated good stability during cyclic testing. Tape adhesion tests indicated that the adhesion between the coating and PC reached a 5B level. When AA10/SAS5 was applied to PET film, glass, and PMMA goggles, all samples showed excellent anti-fog performance. Even after being naturally placed for one year under ambient conditions, the PMMA goggles still maintained good performance in the anti-fog and frost resistance tests. The remarkable comprehensive properties of the polymer coating based on p(AA-co-SAS) suggest enormous potential applications in industries such as packaging, healthcare, and optical equipment.
RESUMO
The poor reversibility of the zinc (Zn) anodes and the irreversible deposition/dissolution of Mn2+/MnO2 significantly impede the commercialization of Zn-Mn aqueous batteries (ZMABs). In reducing the difference between the desired interfacial reaction environments of the cathode and anode, we found that they face the same problem of interference-the generation of irreversible corrosion products. Herein, we have introduced a novel self-regulatory mechanism. This mechanism involves the addition of sodium dihydrogen phosphate, which shifts from passive protection to active regulation. It effectively captures OH- ions, prevents corrosion product formation, and facilitates the in situ generation of a solid electrolyte interface (SEI) film. This modification also homogenizes Zn ion flow and improves the reversibility of Zn plating and stripping. Furthermore, a stable and slightly acidic environment has been established to stabilize the pH at the cathodic interface, mitigate corrosion product formation, and enhance the reversible deposition and dissolution of Mn2+/MnO2. With the optimal electrolyte, ZnâZn symmetric cells demonstrate stable operation for over 3000 hours at 1 mA cm-2, 1 mA h cm-2. Additionally, the ZnâCu cells maintain high reversibility after 1000 cycles, achieving an average coulombic efficiency (CE) of 99.76%. The assembled ZnâMnO2 full cells exhibit exceptional cycling stability and rate performance. This work adopts the approach of seeking common ground and emphasizing the balance of cathode and anode interfacial requirements, which represents a new and significant insight for design of ZMABs with high reversibility and high cyclability.
RESUMO
Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.
Assuntos
Adrenomedulina , Endotélio Vascular , Células Endoteliais da Veia Umbilical Humana , Hipertensão , Óxido Nítrico Sintase Tipo III , Obesidade , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Adrenomedulina/farmacologia , Adrenomedulina/metabolismo , Masculino , Obesidade/complicações , Obesidade/metabolismo , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Dieta Hiperlipídica/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Receptores de Adrenomedulina/metabolismo , Fragmentos de PeptídeosRESUMO
In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (MÏ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 MÏ polarization. Ta-induced M2 MÏ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous MÏ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate MÏ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 MÏ, providing insights for potential bone repair applications.
Assuntos
Diferenciação Celular , Exossomos , Macrófagos , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Tantálio , Animais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Exossomos/metabolismo , Tantálio/química , Tantálio/farmacologia , Osteogênese/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Ratos , Diferenciação Celular/efeitos dos fármacos , MicroRNAs/metabolismo , Ratos Sprague-Dawley , Humanos , Masculino , Proliferação de Células/efeitos dos fármacos , Osso e Ossos/metabolismoRESUMO
BACKGROUND: Hypothalamic paraventricular nucleus (PVN) is an important central site for the control of the adipose afferent reflex (AAR) that increases sympathetic outflow and blood pressure in obesity-related hypertension (OH). METHOD: In this study, we investigated the effects of nitric oxide (NO) and cardiovascular bioactive polypeptide adrenomedullin (ADM) in the PVN on AAR and sympathetic nerve activity (SNA) in OH rats induced by a high-fat diet. RESULTS: The results showed that ADM, total neuronal NO synthase (nNOS) and phosphorylated-nNOS protein expression levels in the PVN of the OH rats were down-regulated compared to the control rats. The enhanced AAR in OH rats was attenuated by PVN acute application of NO donor sodium nitroprusside (SNP), but was strengthened by the nNOS inhibitor nNOS-I, guanylyl cyclase inhibitor (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and gamma-aminobutyric acid A type receptor (GABAA) antagonist Bicuculline. Moreover, PVN ADM microinjection not only decreased basal SNA but also attenuated the enhanced AAR in OH rats, which were effectively inhibited by ADM receptor antagonist ADM22-52, nNOS-I, ODQ or Bicuculline pretreatment. Bilateral PVN acute microinjection of ADM also caused greater increases in NO and cyclic guanosine monophosphate (cGMP) levels, and nNOS phosphorylation. Adeno-associated virus vectors encoding ADM (AAV-ADM) transfection in the PVN of OH rats not only decreased the elevated AAR, basal SNA and blood pressure (BP), but also increased the expression and activation of nNOS. Furthermore, AAV-ADM transfection improved vascular remodeling in OH rats. CONCLUSION: Taken together, our data highlight the roles of ADM in improving sympathetic overactivation, enhanced AAR and hypertension, and its related mechanisms associated with receptors mediated NO-cGMP-GABAA pathway in OH condition.
Assuntos
Hipertensão , Núcleo Hipotalâmico Paraventricular , Ratos , Animais , Núcleo Hipotalâmico Paraventricular/metabolismo , Adrenomedulina , Óxido Nítrico/metabolismo , Ratos Sprague-Dawley , Receptores de GABA/metabolismo , Bicuculina/metabolismo , Bicuculina/farmacologia , Obesidade/complicações , Reflexo/fisiologia , Pressão Sanguínea/fisiologia , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo I/farmacologia , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia , Sistema Nervoso SimpáticoRESUMO
UNLABELLED: Preventive Effectiveness of Implantable Cardioverter. INTRODUCTION: This prospective and multicenter trial of the implantable cardioverter-defibrillator (ICD) aimed to evaluate the mortality rate (including sudden cardiac death [SCD]) and the efficacy of ICD in Chinese patients with high risk of sudden death. METHODS AND RESULTS: This trial was conducted in 31 centers in China. We enrolled 497 patients who fulfilled Class I indication for ICD (2002 ACC/AHA/NASPE guideline). All patients were followed-up at 3, 6, and 12 months. Clinical characteristics and echocardiographic parameters were collected at baseline and follow-up; Kaplan-Meier survival analysis was performed. Among 497 enrolled patients with Class I indication of ICD therapy, 112 (22.5%) agreed to and received ICD implantation (ICD group). The remaining 385 patients who were not available for ICD therapy were designated as the non-ICD group. During a mean follow-up of 11 ± 3 months, there were a total of 38 deaths, 2 in the ICD group with a mortality of 1.8% and 36 in the non-ICD group, with a mortality of 9.4% and 26 due to SCD. The overall survival rate was 93% at 3 months of follow-up, 91% at 6 months, and 89% at 12 months, with an incidence of SCD of 5%, 7%, and 8% at 3, 6, and 12 months, respectively. CONCLUSIONS: In patients with Class I indication of ICD implantation, the total mortality and incidence of SCD were high. ICD therapy can effectively reduce the mortality in such patients.