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Along with the booming research on zinc metal batteries (ZMBs) in recent years, operational issues originated from inferior interfacial reversibility have become inevitable. Presently, single-component electrolytes represented by aqueous solution, "water-in-salt," solid, eutectic, ionic liquids, hydrogel, or organic solvent system are hard to undertake independently the task of guiding the practical application of ZMBs due to their specific limitations. The hybrid electrolytes modulate microscopic interaction mode between Zn2+ and other ions/molecules, integrating vantage of respective electrolyte systems. They even demonstrate original Zn2+ mobility pattern or interfacial chemistries mechanism distinct from single-component electrolytes, providing considerable opportunities for solving electromigration and interfacial problems in ZMBs. Therefore, it is urgent to comprehensively summarize the zinc chemistries principles, characteristics, and applications of various hybrid electrolytes employed in ZMBs. This review begins with elucidating the chemical bonding mode of Zn2+ and interfacial physicochemical theory, and then systematically elaborates the microscopic solvent structure, Zn2+ migration forms, physicochemical properties, and the zinc chemistries mechanisms at the anode/cathode interfaces in each type of hybrid electrolytes. Among of which, the scotoma and amelioration strategies for the current hybrid electrolytes are actively exposited, expecting to provide referenceable insights for further progress of future high-quality ZMBs.
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O3-type layered oxide cathode exhibits great application potential for practical sodium-ion batteries, due to its cost-effectiveness, abundant sodium and manganese resources, and high theoretical capacity. However, the irreversible phase transition, coupled with rapid capacity decay, which is primarily attributed to the Jahn-Teller effect of Mn3+, remains a significant bottleneck for commercial application. Additionally, the sluggish kinetics during the (de)sodiation process require urgent improvement. Herein, an electronic structure regulation strategy is proposed by low-valence Li/Cu co-substitution to address these issues. The roles of Li/Cu on the electronic structure, structural evolution, and electrochemical properties in the Na0.96Ni0.22Fe0.2Mn0.5Li0.04Cu0.04O2 (NFMLC) cathode are comprehensively explored through systematic in situ/ex situ characterization techniques and theoretical calculations. The results reveal that this strategy effectively activates more Ni2+/3+ and Fe3+/4+ redox reactions above 2.5 V, while suppressing Mn3+/4+ redox activity below 2.5 V, thereby achieving highly structural reversibility. Therefore, the NFMLC electrode displays excellent long-term cycling stability (81.5% capacity retention after 2000 cycles at 5 C), and significantly enhanced rate performance (from 45.5% to 80.4% under a ratio of 5 C to 0.5 C). This work provides a valuable perspective on the design of low-cost, long-life, and high-performance layered oxide cathodes for practical sodium-ion batteries.
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Liver fibrosis is the pathological deposition of extracellular matrix rich in fibrillar collagen within the hepatocytes in response to chronic liver injury due to various causes. As the condition advances, it can progress to cirrhosis, the late stages of which are irreversible. Multiple pathophysiological mechanisms and cell types are responsible for the progression of liver fibrosis and cirrhosis. Hepatic stellate cells and myofibroblast activation represent a key event in fibrosis. Capillarization of liver sinusoidal endothelial cells further contributes to extracellular matrix deposition and an increase in portal pressure. Macrophages and neutrophils produce inflammatory cytokines and participate in activating hepatic stellate cells. Although initially believed to be irreversible, early stages of fibrosis are now found to be reversible. Furthermore, advances in noninvasive imaging and serum studies have changed and improved how cirrhosis can be evaluated and monitored. Although there are currently no specific approved therapies to reverse liver fibrosis, management of underlying diseases has been found to halt the progression, and to an extent, even reverse liver fibrosis, preventing further liver injury and cirrhosis-related complications.
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The 134-residue phage L decoration protein (Dec) forms a capsid-stabilizing homotrimer that has an asymmetric tripod-like structure when bound to phage L capsids. The N-termini of the trimer subunits consist of spatially separated globular OB-fold domains that interact with the virions of phage L or the related phage P22. The C-termini of the trimer form a three-stranded intertwined spike structure that accounts for nearly all the interactions that stabilize the trimer. A Dec mutant with the spike residues 99-134 deleted (Dec 1-98 ) was used to demonstrate that the stable globular OB-fold domain folds independently of the C-terminal residues. However, Dec 1-98 was unable to bind phage P22 virions, indicating the C-terminal spike is essential for stable capsid interaction. The full-length Dec trimer is disassembled into monomers by acidification to pH <2. These monomers retain the folded globular OB-fold domain structure, but the spike is unfolded. Increasing the pH of the Dec monomer solution to pH 6 allowed for slow trimer formation in vitro over the course of days. The infectious cycle of phage L is only around an hour, however, implying Dec trimer assembly in vivo is templated by the phage capsid. The Thermodynamic Hypothesis holds that protein folding is determined by the amino acid sequence. Dec serves as an unusual example of an oligomeric folding step that is kinetically accelerated by a viral capsid template. The capsid templating mechanism could satisfy the flexibility needed for Dec to adapt to the unusual quasi-symmetric binding site on the mature phage L capsid.
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OBJECTIVE: Aim: To develop the criteria of small airways response to bronchodilators (by spirometry indices maximal expiratory flow (MEF50 and MEF25) as the markers of uncontrolled asthma course. PATIENTS AND METHODS: Materials and Methods: The study involved 92 participants (64 boys and 28 girls) aged 6 to 17 years (60 were less than 12 years old) with diagnosed asthma. Asthma control was assessed with the use of Asthma Control Test and Asthma Control Questionnaire. Spirometry and bronchodilator responsiveness testing were performed for all participants. RESULTS: Results: Mostly, the studied children had a normal level of forced expiratory volume in the first second (FEV1), even at unsatisfactory symptoms control. The indicators of the medium and small airways patency were significantly worse in uncontrolled asthma children even in normal FEV1. Among children, the lack of asthma control can be caused by small airways obstruction in up to 80% cases. Among children who need the high dose inhaled corticosteroids treatment 93.3% have uncontrolled asthma with small airways obstruction. We found out that MEF50 and MEF25 could be the signs of the reversibility of bronchial obstruction and uncontrolled asthma with high sensitivity and specificity. CONCLUSION: Conclusions: Indices MEF50 and MEF25 allow detecting the small airways obstruction and their reversibility as a mark of uncontrolled asthma (MEF25 has a higher diagnostic value). In case of MEF50 and/or MEF25 increasing for 22% or 25% accordingly in bronchodilator test in children, the asthma should be considered uncontrolled.
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Asma , Broncodilatadores , Espirometria , Humanos , Asma/tratamento farmacológico , Asma/diagnóstico , Asma/fisiopatologia , Criança , Feminino , Masculino , Adolescente , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Volume Expiratório Forçado/efeitos dos fármacos , BiomarcadoresRESUMO
BACKGROUND: Moderate mechanical stress generated by normal joint loading and movements helps maintain the health of articular cartilage. Despite growing interest in the pathogenesis of cartilage degeneration caused by reduced mechanical stress, its reversibility by mechanical reloading is less understood. This study aimed to investigate the response of articular cartilage exposed to mechanical reloading after unloading in vivo and in vitro. METHODS AND RESULTS: Disuse atrophy was induced in the knee joint cartilage of adult mice through hindlimb unloading by tail suspension. For in vivo experiments, mice were subjected to reloading with or without daily exercise intervention or surgical destabilization of the knee joint. Microcomputed tomography and histomorphometric analyses were performed on the harvested knee joints. Matrix loss and thinning of articular cartilage due to unloading were fully or partially restored by reloading, and exercise intervention enhanced the restoration. Subchondral bone density decreased by unloading and increased to above-normal levels by reloading. The severity of cartilage damage caused by joint instability was not different even with prior non-weight bearing. For in vitro experiments, articular chondrocytes isolated from the healthy or unloaded joints of the mice were embedded in agarose gel. After dynamic compression loading, the expression levels of anabolic (Sox9, Col2a1, and Acan) and catabolic (Mmp13 and Adamts5) factors of cartilage were analyzed. In chondrocytes isolated from the unloaded joints, similar to those from healthy joints, dynamic compression increased the expression of anabolic factors but suppressed the expression of catabolic factors. CONCLUSION: The results of this study indicate that the morphological changes in articular cartilage exposed to mechanical unloading may be restored in response to mechanical reloading by shifting extracellular matrix metabolism in chondrocytes to anabolism.
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Proteína ADAMTS5 , Cartilagem Articular , Condrócitos , Elevação dos Membros Posteriores , Estresse Mecânico , Animais , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , Camundongos , Condrócitos/metabolismo , Condrócitos/patologia , Proteína ADAMTS5/metabolismo , Proteína ADAMTS5/genética , Elevação dos Membros Posteriores/efeitos adversos , Metaloproteinase 13 da Matriz/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOX9/genética , Agrecanas/metabolismo , Colágeno Tipo II/metabolismo , Masculino , Microtomografia por Raio-X , Suporte de Carga/fisiologia , Atrofia , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Articulação do Joelho/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Condicionamento Físico AnimalRESUMO
Background: The American Thoracic Society has published general guidelines for sterility when testing for bronchodilator responsiveness. However, the extent to which practicing allergists implement sterility measures is currently unknown. Objective: This study aims to understand the adherence to the American Thoracic Society guidelines for sterility among practicing allergists. Methods: In 2015, a questionnaire was approved and distributed by the American Academy of Allergy, Asthma & Immunology to all its members. The anonymous responses were recorded and tabulated after a 3-week period. Results: Of the 6800 allergists who received surveys from the American Academy of Allergy, Asthma & Immunology members, 496 participated in the survey (response rate 7.3%). Using metered dose inhalers with a spacer and nebulizers were the most common bronchodilator administration techniques, as indicated by 59.35% and 58.52% of responses, respectively. Whereas 69.25% of the allergists considered their bronchodilator administration techniques to be sterile, 14.05% did not consider their administration technique to be sterile and 16.70% were unsure. For maintaining sterility, 38.75% of the respondents indicated using a new disposable attachment for reused inhalers, 18.71% indicated using a new inhaler for each patient, and 9.13% reported wiping inhalers with a cleaning agent. Conclusions: When asked about the sterility of the techniques used by them, nearly one-third of the allergists either stated that the measures used by them were unsterile or stated that they were were unsure. To increase adherence to sterility measures among North American allergists, promoting guideline awareness and proposing updated guidelines focused on the most common bronchodilator administration techniques is essential.
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OBJECTIVES: Knowledge of frailty prevalence and incidence trends over time is essential for planning the necessary health and social resources. The objective of this study was to assess frailty prevalence, incidence, reversibility and mortality rates, and trends for the population aged ≥65 years in Catalonia over the period 2017-2021. STUDY DESIGN: Longitudinal epidemiological study. METHODS: An observational longitudinal 5-year study (1 January 2017 to 31 December 2021) of the population aged ≥65 years in Catalonia (approximately 1.5 million individuals) was performed using retrospectively collected data from different health databases. Frailty status was evaluated using the electronic Screening Index of Frailty (e-SIF) and categorised as robust, pre-frail, moderately frail or severely frail. RESULTS: Standardised frailty prevalence rates were 10.5 % (2017), 11.8 % (2018), 13.1 % (2019), 12.9 % (2020) and 14.3 % (2021) [p-value for trend = 0.010]. Standardised frailty incidence rates per 1000 non-frail persons/year were 35 (2018), 36 (2019), 28 (2020) and 33 (2021) [p-value for trend = 0.492]. Both prevalence and incidence were higher in women and increased with age. Standardised frailty reversibility rates per 1000 frail persons/year were 123 (2018), 108 (2019) and 121 (2020) [p-value for trend = 0.406], and decreased with age. Standardised mortality rates for frail individuals per 1000 frail persons/year were 93 (2018), 84 (2019) and 110 (2020) [p-value for trend = 0.555], and increased with frailty severity. CONCLUSIONS: Frailty prevalence in Catalonia increased by 36 % between 2017 and 2021; however, no clear trend was evident for frailty incidence and reversibility, while results for mortality were likely to have been influenced by the COVID-19 pandemic.
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While lithium borohydride is one of the most promising hydrogen storage materials due to its ultrahigh hydrogen storage density, high thermodynamic stability, kinetic barriers, and poor reversibility, it is far from being used in practical applications. Herein, we prepare a cubic hollow carbon dodecahedron uniformly modified with a bimetallic CoNi alloy (CoNi/NC) for preserving the stable catalytic effect of CoNi alloys toward reversible hydrogen storage. It is theoretically confirmed that bimetallic CoNi alloys effectively weaken the B-H bonds of LiBH4 by extending their average length to 1.33, 0.09 and 0.04 Å longer than that of LiBH4 and LiBH4 under metallic Co, respectively. More importantly, the alloying of Co with Ni avoids the reattachment of H from LiBH4 to the Co surface, which prevents LiBH4 from dehydrogenation for the formation of H2 on the Co surface, thus resulting in an ultralow hydrogen desorption energy of 0.1, 1.85 and 0.52 eV lower than that of LiBH4 and LiBH4 under metallic Co. Therefore, the onset and peak hydrogen desorption temperatures decrease to 130 and 355 °C, respectively, 170 and 97 °C lower than that of bulk LiBH4. More importantly, a reversible H2 capacity of 9.4 wt % is achieved even after 10 cycles.
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The endothelialization of cardiovascular implants is supposed to improve the long-term patency of these implants. In addition, in previous studies, it has been shown, that the conditioning of endothelial cells by dynamic cultivation leads to the expression of an anti-thrombogenic phenotype. For the creation of a tissue-engineered vascular graft (TEVG), these two strategies were combined to achieve optimal hemocompatibility. In a clinical setup, this would require the transfer of the already endothelialized construct from the conditioning bioreactor to the patient. Therefore, the reversibility of the dynamic conditioning of the endothelial cells with arterial-like high shear stress (20 dyn/cm2) was investigated to define the timeframe (tested in a range of up to 24 h) for the perseverance of dynamically induced phenotypical changes. Two types of endothelial cells were compared: endothelial colony-forming cells (ECFCs) and human aortic endothelial cells (HAECs). The results showed that ECFCs respond far more sensitively and rapidly to flow than HAECs. The resulting cell alignment and increased protein expression of KLF-2, Notch-4, Thrombomodulin, Tie2 and eNOS monomer was paralleled by increased eNOS and unaltered KLF-2 mRNA levels even under stopped-flow conditions. VCAM-1 mRNA and protein expression was downregulated under flow and did not recover under stopped flow. From these time kinetic results, we concluded, that the maximum time gap between the TEVG cultivated with autologous ECFCs in future reactor cultivations and the transfer to the potential TEVG recipient should be limited to â¼6 h.
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Binomials have been relatively understudied compared to other types of multiword expressions (MWEs) in second language research, such as collocations and idioms. This study investigated English as a Foreign Language (EFL) learners' processing of English binomials and how it is influenced by interlexical factors (L1-L2 congruency and L1-lexicalization) and intralexical factors (word and binomial frequency, binomial reversibility, and binomial predictability). Forty Chinese EFL learners participated in a phrase acceptability judgment task of 64 target binomials (16 congruent L1-lexicalized, 16 congruent L1-nonlexicalized, and 32 incongruent) and 64 non-binomial controls. Results revealed that learners experienced difficulty judging the formulaicity of binomials. They processed binomial stimuli significantly faster than non-binomial baselines, demonstrating a binomial phrase effect. They also processed L1-L2 congruent items faster and more accurately than incongruent items, showing a robust congruency effect. The congruent items which are lexicalized in the L1 showed further processing advantage than the non-lexicalized items, indicating a graded congruency effect. Moreover, binomial reversibility and binomial predictability (measured with cloze probability) also showed significant effects. These findings highlight the need to distinguish and investigate different types of congruency, explore appropriate measures for MWE predictability, and to examine binomials focusing on their unique features.
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Enzymes serve as pivotal components in various biotechnological applications across several industries. Understanding enzyme inhibition sheds light on how certain compounds disrupt biochemical pathways, facilitating the design of targeted drugs for combating diseases. On the other hand, reversible inhibition or enhancement of activity can unlock new ways of controlling industrial reactions and boosting the catalytic activity of native enzymes that are taken out of their natural environments. Over the last two decades, immobilizing enzymes on nanomaterial-based solid supports has emerged as an especially promising approach for tuning enzyme activity. Nanomaterials not only inhibit enzymes but also enhance their performance, showcasing their versatility. This Concept highlights significant advancements in utilizing nanomaterials for enzyme modulation and discusses future prospects for leveraging this phenomenon in developing sophisticated molecular systems and downstream applications.
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Neuroprotection aims to safeguard neurons from damage caused by various factors like stress, potentially leading to the rescue, recovery, or regeneration of the nervous system and its functions [J Clin Neurosci. 2002;9(1):4-8]. Conversely, neuroplasticity refers to the brain's ability to adapt and change throughout life, involving structural and functional alterations in cells and synaptic transmission [Neural Plast. 2014;2014:541870]. Neuroprotection is a broad and multidisciplinary field encompassing various approaches and strategies aimed at preserving and promoting neuronal health. It is a critical area of research in neuroscience and neurology, with the potential to lead to new therapies for a wide range of neurological disorders and conditions. Neuroprotection can take various forms and may involve pharmacological agents, lifestyle modifications, or behavioral interventions. Accordingly, also the perspective and the meaning of neuroprotection differs due to different angles of interpretation. The primary interpretation is from the pharmacological point of view since the most consistent data come from this field. In addition, we will discuss also alternative, yet less considered, perspectives on neuroprotection, focusing on specific neuroprotective targets, interactions with surrounding microglia, different levels of neuroprotective effects, the reversive/adaptative dimension, and its use as anticipatory/prophylactic intervention.
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Neuroproteção , Fármacos Neuroprotetores , Humanos , Neuroproteção/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Plasticidade Neuronal/fisiologiaRESUMO
Eighteen compounds derived from two sub-series, (HC1-HC9) and (HF1-HF9), were synthesized and evaluated for their inhibitory activities against monoamine oxidase (MAO). HC (chalcone) series showed higher inhibitory activity against MAO-B than against MAO-A, whereas the HF (chromone) series showed reversed inhibitory activity. Compound HC4 most potently inhibited MAO-B with an IC50 value of 0.040 µM, followed by HC3 (IC50 = 0.049 µM), while compound HF4 most potently inhibited MAO-A (IC50 = 0.046 µM), followed by HF2 (IC50 = 0.075 µM). The selectivity index (SI) values of HC4 and HF4 were 50.40 and 0.59, respectively. Structurally, HC4 (4-OC2H5 in B-ring) showed higher MAO-B inhibition than other derivatives, suggesting that the -OC2H5 substitution of the 4-position in the B-ring contributes to the increase of MAO-B inhibition, especially -OC2H5 (HC4) > -OCH3 (HC3) > -F (HC7) > -CH3 (HC2) > -Br (HC8) > -H (HC1) in order. In MAO-A inhibition, the substituent 4-OC2H5 in the B-ring of HF4 contributed to an increase in inhibitory activity, followed by -CH3 (HF2), -F (HF7), -Br (HF8), -OCH3 (HF3), and-H (HF1). In the enzyme kinetics and reversibility study, the Ki value of HC4 for MAO-B was 0.035 ± 0.005 µM, and that of HF4 for MAO-A was 0.035 ± 0.005 µM, and both were reversible competitive inhibitors. We confirmed that HC4 and HF4 significantly ameliorated rotenone-induced neurotoxicity, as evidenced by the reactive oxygen species and superoxide dismutase assays. This study also supports the significant effect of HC4 and HF4 on mitochondrial membrane potential in rotenone-induced toxicity. A lead molecule was used for molecular docking and dynamic simulation studies. These results show that HC4 is a potent selective MAO-B inhibitor and HF4 is a potent MAO-A inhibitor, suggesting that both compounds can be used as treatment agents for neurological disorders.
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Chemical nerve agents are hazardous compounds that terrorists can exploit to pose a significant threat to public safety and national security. The nucleophilic behaviour of these agents enables their interaction with acetyl cholinesterase in the body, leading to paralysis and potentially fatal consequences. Therefore, developing robust and efficient detection methods for these agents is crucial for preventing their misuse. In this manuscript, (E)-12-(1-hydrazineylideneethyl)benzo[f]pyrido[1,2-a]indole-6,11-dione (HBID) is developed as a novel colorimetric and fluorometric probe for the detection of specific chemical nerve agent simulants in both liquid and vapor phase. HBID reacts rapidly with diethyl chlorophosphate (DCP), a common nerve agent simulant, leading to a significant increase in the fluorescence intensity. Under optimized conditions, HBID exhibits high sensitivity, good recyclability, fast response and low limit of detection (0.092 µM). NMR and mass spectral studies suggest that the reaction involves the nucleophilic addition of HBID to DCP, forming a phosphate ester. Additionally, the developed sensor demonstrates viscosity-sensitive AIE phenomena thus greatly expanding its potential applications in biological systems. This sensitivity enables precise detection and visualization of viscosity changes within cellular environments, making the sensor an invaluable tool for studying complex biological processes. The developed probe also detects pH within biologically relevant range (4-6). In practical applications, the probe-treated strips efficiently detected DCP vapor in real time, showing a noticeable fluorescence response. Further, the probe has a strong potential to detect the presence of DCP in the soil samples.
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Agentes Neurotóxicos , Agentes Neurotóxicos/análise , Agentes Neurotóxicos/química , Corantes Fluorescentes/química , Colorimetria/métodos , Organofosfatos/química , Organofosfatos/análise , Espectrometria de Fluorescência , Limite de Detecção , Reprodutibilidade dos Testes , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/química , Indóis/química , Fluorometria/métodos , Compostos OrganofosforadosRESUMO
In recent years, the Na-ion SuperIonic CONductor (NASICON) based polyanionics are considered pertinent cathode materials in sodium-ion batteries due to their 3D open framework, which can accommodate a wide range of Na content and can offer high ionic conductivity with great structural stability. However, owing to the inferior electronic conductivity, these materials suffer from unappealing rate capability and cyclic stability for practical applications. Therefore, in this work we investigate the effect of Co substitution at the V site on the electrochemical performance and diffusion kinetics of Na3V2-xCox(PO4)3/C (x = 0-0.15) cathodes. All the samples are characterized through Rietveld refinement of the X-ray diffraction patterns, Raman spectroscopy, transmission electron microscopy, etc. We demonstrate improved electrochemical performance for the x = 0.05 electrode with a reversible capacity of 105 mAh g-1 at 0.1 C. Interestingly, the specific capacity of 80 mAh g-1 is achieved at 10 C with retention of about 92% after 500 cycles and 79.5% after 1500 cycles and having nearly 100% Coulombic efficiency. The extracted diffusion coefficient values through the galvanostatic intermittent titration technique and cyclic voltammetry are found to be in the range of 10-9 to 10-11 cm2 s-1. The post-mortem studies show excellent structural and morphological stability after testing for 500 cycles at 10 C. Our study reveals the role of optimal dopant of Co3+ ions at the V site in improving the cyclic stability at a high current rate.
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BACKGROUND: Due to a special hemodynamic feature, pulmonary vascular disease in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has two stages: reversible and irreversible. So far, the mechanism involved in the transition from reversible to irreversible stage is elusive. Moreover, no recognized and reliable assessments to distinguish these two stages are available. Furthermore, we found that compared with control and reversible PAH, thrombospondin-4 (THBS4) was significantly upregulated in irreversible group by bioinformatic analysis. Hence, we further verify and investigate the expression and role of THBS4 in PAH-CHD. METHODS: We established the monocrotaline plus aorto-cava shunt-induced (MCT-AV) rat model. We measured the expression of THBS4 in lung tissues from MCT-AV rats. Double immunofluorescence staining of lung tissue for THBS4 and α-SMA (biomarker of smooth muscle cells) or vWF (biomarker of endothelial cells) to identify the location of THBS4 in the pulmonary artery. Primary pulmonary artery smooth muscle cells (PASMCs) were cultivated, identified, and used in this study. THBS4 was inhibited and overexpressed by siRNA and plasmid, respectively, to explore the effect of THBS4 on phenotype transformation, proliferation, apoptosis, and migration of PASMCs. The effect of THBS4 on pulmonary vascular remodeling was evaluated in vivo by adeno-associated virus which suppressed THBS4 expression. Circulating level of THBS4 in patients with PAH-CHD was measured by ELISA. RESULTS: THBS4 was upregulated in the lung tissues of MCT-AV rats, and was further upregulated in severe pulmonary vascular lesions. And THBS4 was expressed mainly in PASMCs. When THBS4 was inhibited, contractile markers α-SMA and MYH11 were upregulated, while the proliferative marker PCNA was decreased, the endothelial-mensenchymal transition marker N-cad was downregulated, proapototic marker BAX was increased. Additionally, proliferation and migration of PASMCs was inhibited and apoptosis was increased. Conversely, THBS4 overexpression resulted in opposite effects. And the impact of THBS4 on PASMCs was probably achieved through the regulation of the PI3K/AKT pathway. THBS4 suppression attenuated pulmonary vascular remodeling. Furthermore, compared with patients with simple congenital heart disease and mild PAH-CHD, the circulating level of THBS4 was higher in patients with severe PAH-CHD. CONCLUSIONS: THBS4 is a promising biomarker to distinguish reversible from irreversible PAH-CHD before repairing the shunt. THBS4 is a potential treatment target in PAH-CHD, especially in irreversible stage.
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Cardiopatias Congênitas , Hipertensão Arterial Pulmonar , Ratos Sprague-Dawley , Trombospondinas , Animais , Humanos , Masculino , Ratos , Células Cultivadas , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/complicações , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Trombospondinas/metabolismo , Trombospondinas/biossíntese , Trombospondinas/genéticaRESUMO
Supramolecular adhesion material systems based on small molecules have shown great potential to unite the great contradiction between strong adhesion and reversibility. However, these material systems suffer from low adhesion strength/narrow adhesion span, limited designability, and single interaction due to fewer covalent bond content and action sites in small molecules. Herein, an ultrahigh-strength and large-span reversible adhesive enabled by a branched oligomer controllable self-aggregation strategy is developed. The dense covalent bonds present in the branched oligomers greatly enhance adhesion strength without compromising reversibility. The resulting adhesive exhibits a large-span reversible adhesion of ≈140 times, switching between ultra-strong and tough adhesion strength (5.58 MPa and 5093.92 N m-1) and ultralow adhesion (0.04 MPa and 87.656 N m-1) with alternating temperature. Moreover, reversible dynamic double cross-linking endows the adhesive with stable reversible adhesion transitions even after 100 cycles. This reversible adhesion property can also be remotely controlled via a voltage of 8 V, with a loading voltage duration of 45 s. This work paves the way for the design of reversible adhesives with long-span outstanding properties using covalent polymers and offers a pathway for the rational design of high-performance adhesives featuring both robust toughness and exceptional reversibility.
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The development of highly reversible zinc (Zn) metal anodes is pivotal for determining the feasibility of rechargeable aqueous Zn batteries. Our research quantitively evalulates how the hydrogen evolution reaction (HER) adversely affects Zn reversibility in batteries and emphasizes the importance of substrate design in modulating HER and its associated side reactions. When the cathodic reaction is dominated by HER, the Zn electrode exhibits low plating/stripping efficiency, characterized by extensive coverage of a passivation layer that encompasses the electrochemical inactive Zn. Therefore, we propose a strike-plating strategy that modifies the pristine substrate by initiating Zn plating at a high current density for a short time. This straightforward and effective approach has been proven to suppress hydrogen evolution and transform the electrodeposition mode into one dominated by Zn reduction. Notably, Zn metal exhibits exceptionally high average reversibility of 98.80% over 200 h on a stainless steel substrate, which was typically precluded in aqueous electrolytes because of their favorable HER capability. Additionally, our strike-plating strategy demonstrates an appliable pathway to achieve high Zn reversibility on Cu substrate, showing an average efficiency of 99.83% over 540 h at a high areal capacity of 10 mAh cm-2 and high-performance Zn full cells with low N/P ratios. This research provides a foundation for future investigations into the underlying mechanisms of HER and strategies to optimize Zn-based battery performance.
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Dynamic bonds can facilitate reversible formation and dissociation of connections in response to external stimuli, endowing materials with shape memory and self-healing capabilities. Temperature is an external stimulus that can be easily controlled through heat. Dynamic covalent bonds in response to temperature can reversibly connect, exchange, and convert chains in the polymer. In this review, we introduce dynamic covalent bonds that operate without catalysts in various temperature ranges. The basic bonding mechanism and the kinetics are examined to understand dynamic covalent chemistry reversibly performed by equilibrium control. Furthermore, a recent synthesis method that implements dynamic covalent coupling based on various polymers is introduced. Dynamic covalent bonds that operate depending on temperature can be applied and expand the use of polymers, providing predictions for the development of future smart materials.