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BACKGROUND: The prevalence of left ventricular (LV) diastolic dysfunction has been increasing over the past decade, and to date, effective pharmacotherapies that enhance LV diastolic function have not yet been identified. Though some data has demonstrated the beneficial effects of exercise training on LV diastolic function, little is known about the adaptations of diastolic function to daily physical activity (PA). Accordingly, our study aimed to investigate the impact of daily PA on tissue Doppler indices of LV diastolic function. METHODS: A total of 432 participants were enrolled for clinically indicated echocardiography from July 2019 to July 2020 at Peking University People's Hospital. Participants aged ≥ 18 years were included if they had stable PA in the past six months and normal LV systolic function. A questionnaire was used to collect demographic characteristics, medical history, and daily PA. According to PA Guidelines for Americans, we identified these participants into low-intensity PA (LPA) group and moderate-high-intensity PA (MHPA) group. Propensity score matching (PSM) was performed to match potential confounding factors between the two groups. The clinical characteristics and echocardiographic parameters between LPA group and MHPA group were compared using student's t-test, Mann-Whitney U test, and chi-square test as appropriate. RESULTS: After matching potential confounding factors using PSM with a 1:3 matching ratio, our final analysis included 86 cases in the MHPA group and 214 cases in the LPA group. All demographic characteristics and comorbidities were statistically similar between the two groups. Compared to the LPA group, the MHPA group showed higher septal e' (7.9 ± 2.9 cm/s versus 7.2 ± 2.6 cm/s, P = 0.047). Other echocardiographic parameters associated with LV diastolic function concerning lateral e' and average E/e', also trended towards improved LV diastolic function in the MHPA group, but failed to reach statistical significance. CONCLUSIONS: Our study demonstrated that moderate-high-intensity daily PA was associated with improved septal e', suggesting that moderate-high-intensity PA could potentially ameliorate LV diastolic dysfunction.
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Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Humanos , Estudos Transversais , Ecocardiografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/terapia , Disfunção Ventricular Esquerda/epidemiologia , Comorbidade , DiástoleRESUMO
The activity of heterogeneous photocatalytic H2 O2 activation in Fenton-like processes is closely related to the local electron density of reaction centre atoms. However, the recombination of electron-hole pairs arising from random charge transfer greatly restricts the oriented electron delivery to active center. Here we show a defect engineered iron single atom photocatalyst (Fe1 -Nv /CN, single Fe atoms dispersed on carbon nitride with abundant nitrogen vacancies) for the activation of H2 O2 under visible light irradiation. Based on DFT calculations and transient absorption spectroscopy results, the engineered nitrogen vacancies serve as the electron trap sites, which can directionally drive the electrons to concentrate on Fe atoms. The formation of highly concentrated electrons density at Fe sites significantly improves the H2 O2 conversion efficiency. Therefore, the optimized single atom catalyst exhibiting a higher ciprofloxacin degradation activity, which was up to 18 times that of pristine CN.
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Single-atom CoN4 active sites have demonstrated excellent efficiency in peroxymonosulfate activation. However, the identification of CoN4 active sites and the detailed singlet oxygen generation mechanism in peroxymonosulfate activation remains ambiguous. We demonstrate a strategy to regulate the generation of reactive oxygen species by atomically dispersed cobalt anchored on nitrogen-doped carbon. As indicated by experiment and DFT calculations, CoN2+2 was the active site and singlet oxygen was the predominant reactive oxygen species with a proportion of 98.89 %. Spontaneous dissociation of adsorbed peroxymonosulfate on the CoN2+2 active sites was energetically unfavorable because of the weakly positive Co atoms and CoN2+2 coordination, which directed PMS oxidation by a non-radical pathway and with simultaneous singlet oxygen generation. The generated singlet oxygen degraded several organic pollutants with high efficiency across a broad pH range.
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Growing evidence shows that activation of inflammation in the heart provokes left ventricular (LV) remodeling and dysfunction in humans and experimental animals with heart failure (HF). Moreover, recent studies found that cyclic GMP-AMP synthase (cGAS), serving as a cytosolic DNA sensor, was essential for activating innate immunity against infection and cellular damage by initiating the STING-IRFs-type I IFN signaling cascade, which played important roles in regulating the inflammatory response. However, the pathophysiological role of cGAS in pressure overload-induced HF is unclear. Wild-type C57BL/6J mice and cGAS inhibition mice were subjected to transverse aortic constriction (TAC) to induce HF or sham operation. Inhibition of cGAS in the murine heart was performed using adeno-associated virus 9 (AAV9). Alterations of the cGAS/STING pathway were examined by qPCR and Western blotting. Cardiac remodeling was assessed by echocardiography as well as histological and molecular phenotyping. Compared with sham-operated mice, the cGAS/STING pathway was activated in LV tissues in TAC mice. Whereas TAC mice exhibited significant pathological cardiac remodeling and LV dysfunction, inhibition of cGAS improved early survival rates after TAC, preserved LV contractile function, and blunted pathological remodeling, including cardiac hypertrophy, fibrosis, and apoptosis. Furthermore, downregulation of cGAS diminished early inflammatory cell infiltration and inflammatory cytokine expression in response to TAC. These results demonstrated that cGAS played an essential pathogenetic role in pressure overload-induced HF to promote pathological cardiac remodeling and dysfunction. Our results suggest that inhibition of cGAS may be a novel therapeutic approach for HF.NEW & NOTEWORTHY In this study, we first revealed a novel role of cGAS in the regulation of pathological cardiac remodeling and dysfunction upon pressure overload. We found that the cGAS/STING pathway was activated during pressure overload. Moreover, we also demonstrated that inhibition of the cGAS/STING pathway alleviated pathological cardiac remodeling and downregulated the early inflammatory response during pressure overload-induced HF. Together, these findings will provide a new therapeutic target for HF.
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Pressão Sanguínea/fisiologia , Insuficiência Cardíaca/metabolismo , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Remodelação Ventricular/fisiologia , Animais , Coração/fisiopatologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Nucleotidiltransferases/genética , Transdução de SinaisRESUMO
PURPOSE: To perform a comprehensive meta-analysis of all available evidence on the efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction. METHODS: We searched English and Chinese databases and calculated the weighted mean difference or standardized mean difference and 95% confidence intervals to estimate the efficacy and safety of renal denervation for heart failure. All relevant studies were screened and a meta-analysis was conducted using Review Manager 5.4. RESULTS: A total of 11 studies were identified for the meta-analysis. For the primary outcomes, the results showed that renal denervation significantly improved ejection fraction (weighted mean difference 6.42), left ventricular end-systolic diameter (weighted mean difference -3.95), left ventricular end-diastolic diameter (weighted mean difference -4.17) and left atrial diameter (weighted mean difference -4.09). For the secondary outcomes, renal denervation reduced the B-type natriuretic peptide level, heart rate, systolic blood pressure and diastolic blood pressure. However, further analysis revealed that renal denervation improved heart function but did not further reduce the heart rate and blood pressure compared with the control group. CONCLUSION: Treatment with renal denervation can significantly improve heart function and structure in patients with heart failure. In addition, the level of B-type natriuretic peptide can be reduced after renal denervation treatment. Renal denervation did not further reduce heart rate and blood pressure compared with the control group. Therefore, the treatment of heart failure with renal denervation is effective and safe.
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Insuficiência Cardíaca , Simpatectomia , Pressão Sanguínea , Catéteres , Insuficiência Cardíaca/cirurgia , Humanos , Rim/cirurgiaRESUMO
We examined the effects of long-term exercise on age-related decline in static balance control through centre-of-pressure (CoP) measurements of four groups of participants: older controls, younger controls, older Tai Chi exercisers and older joggers. The participants stood quietly in a tandem stance on a force platform for 30 s with eyes open (EO) and eyes closed (EC). The older controls showed remarkably larger CoP and EC/EO ratios than younger controls and older Tai Chi exercisers. The EC/EO ratios of velocity in the mediolateral direction of older joggers were significantly smaller than those of older controls. Results suggest that the static balance of older controls showed a significant decline caused by age-related changes. Long-term Tai Chi and jogging, particularly the former, contributed to static balance control in older people. Older adults relied more on visual information in static postural control than young people. Tai Chi would be an ideal exercise for improving static balance in older people.
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Exercício Físico/fisiologia , Corrida Moderada/fisiologia , Equilíbrio Postural/fisiologia , Tai Chi Chuan , Adulto , Idoso , Envelhecimento/fisiologia , Estudos Transversais , Humanos , Masculino , Fatores de Tempo , Percepção Visual/fisiologia , Adulto JovemRESUMO
Advances in zeolites research emerging from interdisciplinary efforts have opened new opportunities beyond conventional applications. Colloids drive much current research owing to their distinct collective behaviors, but so far, using zeolites as a colloidal building block to construct ordered superstructures remains unexplored. Herein we show that self-assembly of colloidal zeolite LTA superball (ZAS) by tilted-angle sedimentation forms macroscopic films with micro-mesoporosity and 3D long-range periodicity featuring a photonic band gap (PBG) that is tunable through the superball geometry and responds reversibly to chemical vapors. Remarkably, self-assembly of ZAS at elevated temperature forms 3D chiral photonic crystals that enable negative circular dichroism, selective reflection of right-handed circularly polarized (CP) light and left-handed CP luminescence based on PBG. We present a novel class of functional colloids and zeolite-based photonic crystals with the ability to manipulate light in several ways.
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BACKGROUND: Angoroside C, cinnamic acid, and harpagoside are bioactive constituents in Scrophularia ningpoensis. Currently, an infrared-assisted extraction (IRAE) method coupled with high-performance liquid chromatography with ultraviolet detection (HPLC-UV) for the analysis of bioactive constituents in this plant is lacking. METHODS: A method based on HPLC following IRAE has been developed for quantifying angoroside C, cinnamic acid, and harpagoside in Scrophularia ningpoensis. Four main factors, namely, extraction solvent, solid/liquid ratio, illumination time, and distance between the infrared lamp and the round-bottom flask, were optimized for extraction. Furthermore, conventional ultrasonic extraction (USE) and microwave-assisted extraction (MAE) were also investigated to validate the developed method. RESULTS: The optimal extraction conditions were as follows: ethanol concentration, 37.5%; solid/liquid ratio, 1:25; illumination time, 10 min; and distance between infrared lamp and round-bottom flask, 3 cm. The results of method validation demonstrated that the developed method meets the requirement of analysis. CONCLUSION: The results show that the IRAE-HPLC is a simple, accurate, and green analytical preparatory method for the potential extraction and quantification of angoroside C, cinnamic acid, and harpagoside in Scrophularia ningpoensis.
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Cromatografia Líquida de Alta Pressão/métodos , Cinamatos/análise , Ácidos Cumáricos/análise , Glicosídeos/análise , Piranos/análise , Scrophularia/química , Trissacarídeos/análiseRESUMO
A highly efficient Z-scheme photocatalytic system constructed with 1D CdS and 2D CoS2 exhibited high photocatalytic hydrogen-evolution activity of 5.54â mmol h-1 g-1 with an apparent quantum efficiency of 10.2 % at 420â nm. More importantly, its interfacial charge migration pathway was unraveled: The electrons are efficiently transferred from CdS to CoS2 through a transition atomic layer connected by Co-S5.8 coordination, thus resulting in more photogenerated carriers participating in surface reactions. Furthermore, the charge-trapping and charge-transfer processes were investigated by transient absorption spectroscopy, which gave an estimated charge-separation yield of approximately 91.5 % and a charge-separated-state lifetime of approximately (5.2±0.5)â ns in CdS/CoS2 . This study elucidates the key role of interfacial atomic layers in heterojunctions and will facilitate the development of more efficient Z-scheme photocatalytic systems.
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NLRC (the nucleotide-oligomerization domain (NOD)-like receptor subfamily C) consists of teleost-specific NLRs (NOD-like receptors) and plays pivotal roles in microbial recognition and regulation of innate immune response. In this study, we cloned and characterized a NLRC3-like gene (MamNLRC3-like) from blunt snout bream (Megalobrama amblycephala) by using the quantitative real-time PCR method, and analyzed the correlation between its polymorphisms and resistance to Aeromonas hydrophila infection. The full length cDNA of MamNLRC3-like was 2863 bp, with a 5'-UTR of 169 bp, ORF of 2301 bp and 3'-UTR of 393 bp, encoding 766 amino acid residues. MamNLRC3-like consisted of a conserved NACHT domain, a fish-specific NACHT associated domain (FISNA) and a PYRIN effective domain. During early developmental stages, MamNLRC3-like was most highly expressed at 39.4 hpf (hours post fertilization, hatching stage) and constitutively detected in various healthy tissues. The expression of MamNLRC3-like was strongly induced by A. hydrophila infection and peaked in the head kidney, liver, intestine, and trunk kidney at 12 h post infection. Six SNPs (single nucleotide polymorphisms) from MamNLRC3-like, with 2 in introns and 4 in exons, were identified by direct sequencing, in which 6515C/T was a novel non-synonymous mutation. HRM (high resolution melting) genotyping of the 6 loci showed that locus 6515C/T SNP was associated with the resistance/susceptibility of blunt snout bream to A. hydrophila infection (P < 0.01). The CC genotype fish were more resistant than CT carriers (P < 0.01). This study suggests that the MamNLRC3-like gene might play an important role in the innate immunity of blunt snout bream and could be used as a candidate marker for genetic selection of A. hydrophila-resistant blunt snout bream.
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Cyprinidae , Resistência à Doença , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Infecções por Bactérias Gram-Negativas/veterinária , Peptídeos e Proteínas de Sinalização Intercelular/genética , Polimorfismo de Nucleotídeo Único , Aeromonas hydrophila/fisiologia , Animais , Clonagem Molecular , Cyprinidae/embriologia , Cyprinidae/genética , DNA Complementar/genética , DNA Complementar/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Proteínas de Peixes/química , Proteínas de Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de DNA/veterináriaRESUMO
UVA1 phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of palmoplantar pustulosis (PPP). The purpose of this study was to compare the efficacy of UVA1 and narrowband UVB (NB-UVB) therapy in the treatment of PPP. Patients with PPP were randomly assigned to either UVA1 or NB-UVB therapy according to a left-right randomization table. Both treatments were performed three times weekly for up to 30 sessions. Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally 64 patients completed the study. Both UVA1 and NB-UVB therapy showed a statistically significant reduction of PPPASI score compared with the baseline value at the end of the treatment period (P < 0.05). There was a significantly greater mean reduction of PPPASI score in the UVA1 treated group when compared to the NB-UVB treated patients at 30 sessions (6.0 ± 2.4 vs. 4.4 ± 1.4, P < 0.05). No phototoxic reaction or bullous changes were observed in either group. Both NB-UVB and UVA1 phototherapy of PPP resulted in significant improvement. UVA1 phototherapy was more effective than NB-UVB irradiation in the treatment of PPP.
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Psoríase/radioterapia , Terapia Ultravioleta/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Raios UltravioletaRESUMO
GNB2L1 is an intercellular scaffold protein of the Trp-Asp (WD) repeat protein family, and has been reported to play suppressive roles in the progression of gastric cancer. However, the regulatory mechanisms of GNB2L1 in gastric cancer still remain largely elusive. In the present study, we found that OGT was capable to interact with GNB2L1 directly and modify GNB2L1 with O-GlcNAcylation in gastric cancer, and this O-GlcNAcylation hindered the inhibition of GNB2L1 on migration of gastric cancer cells. Moreover, O-GlcNAcylation regulated the degradation instead of the synthesis of GNB2L1 in gastric cancer, and our data suggested the O-GlcNAcylation on GNB2L1 influenced its stability directly. In addition, the clinical data revealed the negative correlation of the protein level instead of the mRNA level of GNB2L1 with OGT expression, and showed that OGT reversed the inhibition of GNB2L1 on metastasis, and worsened the prognosis of GNB2L1(High) patients. In summary, this study indicated the O-GlcNAcylation on GNB2L1 reversed its inhibition on gastric tumour metastasis via promoting its degradation.
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Acetilglucosamina/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Superfície Celular/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proteínas de Ligação ao GTP/genética , Regulação Neoplásica da Expressão Gênica , Glicosilação , Humanos , N-Acetilglucosaminiltransferases/metabolismo , Metástase Neoplásica , Proteínas de Neoplasias/genética , Ligação Proteica , Proteólise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Quinase C Ativada , Receptores de Superfície Celular/genética , Neoplasias Gástricas/genéticaRESUMO
What is the central question of this study? Does Danzhi Qing'e (DZQE) regulate lipid metabolism and improve ovarian function in a rat model of perimenopausal hyperlipidaemia, and could this effect be mediated through the AMPK pathway? What is the main finding and its importance? We revealed that DZQE is a pharmacotherapy that could activate the AMPK pathway to improve ovarian function and lipid metabolism during perimenopause complicated with hyperlipidaemia syndrome in an animal model. Thus, this study provides a novel therapeutic option for treating perimenopausal syndrome and highlights the therapeutic potential of DZQE in perimenopausal rats. Menopause is an important event in a woman's life. During perimenopause, accompanied by development of osteoporosis and dyslipidaemia, ovarian function gradually declines. Dyslipidaemia is a risk factor for cardiovascular disorders, cerebrovascular disease and breast cancer in postmenopausal women. All of these contribute to impairment of liver function, particularly fatty liver disease, because liver dysfunction is associated with ovarian dysfunction and hyperlipidaemia. The aim of this study was to define a therapeutic approach to improve ovarian function and attenuate lipid accumulation in order to prevent perimenopause-induced ovarian dysfunction and hyperlipidaemia. Four-week-old female Wistar rats were injected i.p. with 4-vinylcyclohexene diepoxide (4-VCD) and fed with a high-fat diet (HFD) to serve as a model of perimenopause complicated with hyperlipidaemia. The 4-VCD induces perimenopause, while the HFD causes hyperlipidaemia. Five days after administration of 4-VCD, the 4-VCD + HFD-treated rats were assessed daily for oestrous cycle stage by vaginal cytology. Rats were then assigned into groups, in which 2.5, 5.0 or 10.0 g kg-1 Danzhi Qing'e (DZQE) or estradiol valerate was administered intragastrically for 8 weeks. Expression levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen and testosterone measured by enzyme-linked immunosorbent assay served as biomarkers for perimenopause and ovarian dysfunction. The expression levels of AMPK and acetyl-CoA carboxylase in the liver were determined with Western blotting, and aspartate aminotransferase and alanine aminotransferase were analysed using an automated biochemical analyser to examine liver function. The DZQE improved ovarian function by upregulating oestrogen and testosterone concentrations in serum and downregulating FSH and LH serum concentrations. Moreover, DZQE reduced serum concentrations of triglyceride, total cholesterol and low-density lipoprotein in a dose-dependent manner to regulate lipid levels during perimenopause. Furthermore, DZQE increased AMPK at both the transcriptional and translational levels and decreased the expression of SREBP-1c gene as well as its downstream target gene, fatty acid synthase. Danzhi Qing'e improved dyslipidaemia during menopause and also had an effect on liver function. Danzhi Qing'e is an effective Chinese herbal compound, which improves ovarian function and lipid metabolism in perimenopause complicated with hyperlipidaemia at least in part through the AMPK pathway.
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Adenilato Quinase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Perimenopausa/efeitos dos fármacos , Acetil-CoA Carboxilase/metabolismo , Animais , Cicloexenos/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ratos , Ratos Wistar , Compostos de Vinila/farmacologiaRESUMO
Palmoplantar pustulosis (PPP) is recalcitrant to traditional topical and systemic therapies. Ultraviolet A1 (UVA1) phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of PPP. The purpose of this study was to evaluate the efficacy and safety of UVA1 therapy for the treatment of PPP. Patients with PPP were treated with UVA1 irradiation three times a week for up to 30 sessions and had a 3-month follow-up visit. UVA1 therapy was conducted with a fixed dose (80 J/cm2). Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally, 62 patients completed the study. The mean PPPASI score decreased from a baseline value of 9.4 ± 2.8 to a value of 4.9 ± 2.4 at 15 sessions, 1.7 ± 1.9 at 30 sessions, and 2.0 ± 2.1 at follow-up visit. A reduction of 75 % in the PPPASI score was observed in 4 (6.5 %) patients at 15 sessions and 45 (72.6 %) patients at 30 sessions. The adverse effects were limited including burning sensation, pruritus, and hyperpigmentation. UVA1 is an effective therapy for PPP with mild side effects.
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Psoríase/radioterapia , Raios Ultravioleta , Terapia Ultravioleta , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Dermatopatias Vesiculobolhosas , Adulto JovemRESUMO
Developing an intermediate-temperature solid oxide fuel cell (IT-SOFC) is one of the most promising ways of achieving carbon neutrality, but its air-electrode is restricted by the conflict between the sluggish catalytic activity and durability. Herein, an A-site high-entropy perovskite composite La0.2Ba0.2Sr0.2Ca0.2Ce0.2-xCoO3-δ-xCeO2 (LBSCCC-CeO2) air-electrode material is fabricated via a one-step self-constructing strategy, which shows excellent oxygen reduction activity and stability due to the high-entropy structure and the synergy effect between LBSCCC and interfacial CeO2. This work provides a new way of fabricating high-performance air-electrodes in IT-SOFCs.
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Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate (ATP) for fuel, including damage repair, apoptosis resistance, and immune evasion. Inspired by the naturally enzymatic reaction of glucose oxidase (GOx) with glucose, here a novel "two birds with one stone" technique for amplifying enzyme-mediated tumor apoptosis and enzyme-promoted metabolic clearance is proposed and achieved using GOx-functionalized rhenium nanoclusters-doped polypyrrole (Re@ReP-G). Re@ReP-G reduces ATP production while increasing H2O2 concentrations in the tumor microenvironment through GOx-induced enzymatic oxidation, which in turn results in the downregulation of defense (HSP70 and HSP90) and anti-apoptotic Bcl-2 proteins, the upregulation of pro-apoptotic Bax, and the release of cytochrome c. These processes are further facilitated by laser-induced hyperthermia effect, ultimately leading to severe tumor apoptosis. As an enzymatic byproduct, H2O2 catalyzes the conversion of rhenium nanoclusters in Re@ReP-G nanostructures into rhenate from the outside in, which accelerates their metabolic clearance in vivo. This Re@ReP-G-based "two birds with one stone" therapeutic strategy provides an effective tool for amplifying tumor apoptosis and safe metabolic mechanisms.
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Apoptose , Animais , Camundongos , Glucose Oxidase/metabolismo , Neoplasias/metabolismo , Humanos , Modelos Animais de Doenças , Linhagem Celular Tumoral , Nanomedicina/métodos , Microambiente Tumoral , Peróxido de Hidrogênio/metabolismo , Polímeros/química , Polímeros/metabolismoRESUMO
Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.
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Corantes Fluorescentes , Insuficiência Cardíaca , Corantes Fluorescentes/química , Insuficiência Cardíaca/diagnóstico por imagem , Animais , Camundongos , Viscosidade , Miócitos Cardíacos , Diagnóstico Precoce , Ratos , Linhagem Celular , Isoproterenol , Humanos , Imagem Óptica , Raios Infravermelhos , MasculinoRESUMO
Galanin-like peptide (GALP) gene, encoding a member of the galanin family of neuropeptides involved in reproduction, was differentially expressed in PMSG-hCG stimulated pre-ovulatory ovarian follicles of Chinese Taihu and Large White sows in our previous study. In the present study, promoter region and genetic mutations of the porcine GALP gene were determined. A 1,322 bp contig in 5'-flanking region was predicted to contain 5 potential transcription promoters by Neural Network Promoter Prediction version 2.2. 5'-deletion expression in both CHO and hela cells showed that there were a negative regulatory element at -852 to -803 bp and a positive regulatory element at -1,318 to -1,269 bp. Comparative sequence analyses of Chinese Taihu and Large White GALP gene sequence revealed the c.*27C>G mutation in the 3'-UTR and the c.88-1225C>G mutation in intron 1, which can be detected by HhaI and AluI PCR-RFLP, respectively. The association analysis with litter size traits showed that at both loci CC and GG genotypes were different for NBA for all parities in DIV pigs (P < 0.05). However, two SNPs were not in significant linkage disequilibrium analyzed using SHEsis online software, and could be used in pig breeding individually.
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Peptídeo Semelhante a Galanina/genética , Tamanho da Ninhada de Vivíparos/genética , Regiões Promotoras Genéticas , Suínos/genética , Animais , Estudos de Associação Genética , Mutação , Locos de Características QuantitativasRESUMO
All-trans retinoic acid (ATRA) is an important therapeutic agent for prevention of the renal diseases. Transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling pathway is a key signaling pathway which takes part in the progression of renal interstitial fibrosis (RIF). This investigation was performed to study the effect of ATRA in RIF rats and its effect on the TGF-ß1/Smad3 signaling pathway. Sixty Wistar male rats were divided into three groups at random: sham operation group (SHO), model group subjected to unilateral ureteral obstruction (GU), model group treated with ATRA (GA), n = 20, respectively. RIF index, protein expression of TGF-ß1, collagen-IV (Col-IV) and fibronectin (FN) in renal interstitium, and mRNA and protein expressions of Smad3 in renal tissue were detected at 14-day and 28-day after surgery. The RIF index was markedly elevated in group GU than in SHO group (p < 0.01), and the RIF index of GA group was alleviated when compared with that in GU group (p < 0.01). Compared with in group SHO, the mRNA/protein expression of Smad3 in renal tissue was significantly increased in group GU (p < 0.01). However, the mRNA and protein expressions of Smad3 in renal tissue in GA group were not markedly alleviated by ATRA treatment when compared with those in GU (each p > 0.05). Protein expressions of TGF-ß1, Col-IV, and FN in GU group were markedly increased than those in SHO group (each p < 0.01), and their expressions in GA group were markedly down-regulated by ATRA treatment than those of GU group (all p < 0.01). The protein expression of Smad3 was positively correlated with RIF index, protein expression of TGF-ß1, Col-IV or FN (each p < 0.01). In conclusion, ATRA treatment can alleviate the RIF progression in UUO rats. However, ATRA cannot affect the signaling pathway of TGF-ß1/Smad3 in the progression of RIF.
Assuntos
Nefrite Intersticial/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética , Tretinoína/farmacologia , Análise de Variância , Animais , Biópsia por Agulha , Western Blotting , Modelos Animais de Doenças , Progressão da Doença , Regulação para Baixo , Fibrose/patologia , Regulação da Expressão Gênica , Imuno-Histoquímica , Masculino , Nefrite Intersticial/genética , Nefrite Intersticial/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real/métodos , Valores de Referência , Fatores de Risco , Transdução de Sinais/genética , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVE: To study the constituents of essential oil from Shunaoxin dropping pills by GC-MS. METHODS: The essential oil from Shunaoxin dropping pills were extracted by absolute alcohol and analyzed by GC-MS. RESULTS: 15 components from the essential oil of Shunaoxin dropping pills were identified. CONCLUSION: The main components in the essential oil of Shunaoxin dropping pills are lactones such as Z-ligustilide, senkyunolide A,3-butylphthalide and 3-butylidenephthalide, other components are organic acids such as ethyl linoleate, 9,12-octadecadienoic acid and ethyl palmitate.