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Glucose is catabolized in yeast via two fundamental routes, glycolysis and the oxidative pentose phosphate pathway, which produces NADPH and the essential nucleotide component ribose-5-phosphate. Here, we describe riboneogenesis, a thermodynamically driven pathway that converts glycolytic intermediates into ribose-5-phosphate without production of NADPH. Riboneogenesis begins with synthesis, by the combined action of transketolase and aldolase, of the seven-carbon bisphosphorylated sugar sedoheptulose-1,7-bisphosphate. In the pathway's committed step, sedoheptulose bisphosphate is hydrolyzed to sedoheptulose-7-phosphate by the enzyme sedoheptulose-1,7-bisphosphatase (SHB17), whose activity we identified based on metabolomic analysis of the corresponding knockout strain. The crystal structure of Shb17 in complex with sedoheptulose-1,7-bisphosphate reveals that the substrate binds in the closed furan form in the active site. Sedoheptulose-7-phosphate is ultimately converted by known enzymes of the nonoxidative pentose phosphate pathway to ribose-5-phosphate. Flux through SHB17 increases when ribose demand is high relative to demand for NADPH, including during ribosome biogenesis in metabolically synchronized yeast cells.
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Ribosemonofosfatos/biossíntese , Saccharomyces cerevisiae/metabolismo , Vias Biossintéticas , Cristalografia por Raios X , Deleção de Genes , Modelos Moleculares , Via de Pentose Fosfato , Monoéster Fosfórico Hidrolases/química , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genéticaRESUMO
Metal-organic frameworks (MOFs)1-3 are known for their specific interactions with gas molecules4,5; this, combined with their rich and ordered porosity, makes them promising candidates for the photocatalytic conversion of gas molecules to useful products6. However, attempts to use MOFs or MOF-based composites for CO2 photoreduction6-13 usually result in far lower CO2 conversion efficiency than that obtained from state-of-the-art solid-state or molecular catalysts14-18, even when facilitated by sacrificial reagents. Here we create 'molecular compartments' inside MOF crystals by growing TiO2 inside different pores of a chromium terephthalate-based MOF (MIL-101) and its derivatives. This allows for synergy between the light-absorbing/electron-generating TiO2 units and the catalytic metal clusters in the backbones of MOFs, and therefore facilitates photocatalytic CO2 reduction, concurrent with production of O2. An apparent quantum efficiency for CO2 photoreduction of 11.3 per cent at a wavelength of 350 nanometres is observed in a composite that consists of 42 per cent TiO2 in a MIL-101 derivative, namely, 42%-TiO2-in-MIL-101-Cr-NO2. TiO2 units in one type of compartment in this composite are estimated to be 44 times more active than those in the other type, underlining the role of precise positioning of TiO2 in this system.
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The discovery of quantum interference (QI) is widely considered as an important advance in molecular electronics since it provides unique opportunities for achieving single-molecule devices with unprecedented performance. Although some pioneering studies suggested the presence of spin qubit coherence and QI in collective systems such as thin films, it remains unclear whether the QI can be transferred step-by-step from single molecules to different length scales, which hinders the application of QI in fabricating active molecular devices. Here, we found that QI can be transferred from a single molecule to their assemblies. We synthesized and investigated the charge transport through the molecular cages using 1,3-dipyridylbenzene (DPB) as a ligand block with a destructive quantum interference (DQI) effect and 2,5-dipyridylfuran (DPF) as a control building block with a constructive quantum interference (CQI) effect using both single-molecule break junction and large area junction techniques. Combined experiments and calculations revealed that both DQI and CQI had been transferred from the ligand blocks to the molecular cages and the monolayer thin film of the cages. Our work introduced QI effects from a ligand to the molecular cage comprising 732 atoms and even their monolayers, suggesting that the quantum interference could be scaled up within the phase-coherent distance.
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Identification of translocator protein-related genes involved in bensulfuron-methyl (BSM) uptake and transport in rice could facilitate the development of herbicide-tolerant cultivars by inactivating them. This study found that the OsCNGC12 mutants not only reduced BSM uptake but also compromised the Ca2 ⺠efflux caused by BSM in the roots, regulating dynamic equilibrium of Ca2 ⺠inside the cell and conferring non-target-site tolerance to BSM.
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Herbicidas , Oryza , Herbicidas/farmacologia , Plântula/genética , CálcioRESUMO
One of the biggest challenges in biotechnology and medical diagnostics is finding extremely sensitive and adaptable biosensors. Since metal-based enzyme-mimetic biocatalysts may lead to biosafety concerns on accumulative toxicity, it is essential to synthesize metal-free enzyme-mimics with optimal biocatalytic activity and superior selectivity. Here, the pyridine-bridged covalent organic frameworks (COFs) with specific oxidase-like (OXD-like) activities as intelligent artificial enzymes for light-augmented biocatalytic sensing of biomarkers are disclosed. Because of the adjustable bandgaps of pyridine structures on the photocatalytic properties of the pristine COF structures, the pyridine-bridged COF exhibit efficient, selective, and light-responsive OXD-like biocatalytic activity. Moreover, the pyridine-bridged COF structures show tunable and light-augmented biocatalytic detection capabilities, which outperform the recently reported state-of-the-art OXD-mimics regarding biosensing efficiency. Notably, the pyridine-bridged COF exhibits efficient and multifaceted diagnostic activity, including the extremely low limit of detection (LOD), which enables visual assays for abundant reducibility biomarkers. It is believed that this design will offer unique metal-free biocatalysts for high-sensitive and low-cost colorimetric detection and also provide new insights to create highly efficient enzyme-like COF materials via linkage-modulation strategies for future biocatalytic applications.
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Decompensated cardiac hypertrophy is accompanied by impaired mitochondrial homeostasis, whether histone acetylation is involved in this process is yet to be determined. The role of HDAC1-mediated NRF1 histone deacetylation was investigated in transverse aortic constriction (TAC)-induced hypertrophy in rats and phenylephrine (PE)-induced hypertrophic cardiomyocytes. Administration of epigallocatechin-3-gallate (EGCG), an inhibitor of HDAC1, restored cardiac function, decreased heart/body weight and fibrosis, increased the ratio of mtDNA/nDNA and the percentage of LysoTracker+ CMs in TAC, compared with TAC without receiving EGCG. In PE-treated hypertrophic H9C2 cells, EGCG attenuated cell hypertrophy and increased LC3B II+MitoTracker+ puncta, as well as the ratio of mtDNA/nDNA. Interestingly, NRF1 but not PGC-1α expression was decreased in TAC- or PE-induced hypertrophic hearts or cells, respectively, while EGCG upregulated both NRF1 and PGC-1α in vitro. EGCG treatment also increased the interaction between PGC-1α and NRF1. In addition to inhibiting HDAC1 expression, EGCG decreased the binding of HDAC1 and increased the binding of acH3K9 or acH3K14 in the promotor regions of PGC-1α and NRF1. In neonatal rat cardiomyocytes, restored NRF1, TFAM and FUNDC1 were abolished by the overexpression of HDAC1. Collectively, data suggest that NRF1 reduction was averted by EGCG via inhibiting HDAC1-mediated histone deacetylation. Acetylation of NRF1 histone may play a key role in maintaining mitochondrial homeostasis associated with cardiac hypertrophy.
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Cardiomegalia , Catequina/análogos & derivados , Histonas , Ratos , Animais , Histonas/metabolismo , Cardiomegalia/metabolismo , DNA Mitocondrial , Homeostase , Miócitos Cardíacos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
OBJECTIVES: Gout patients are at high risk of carotid atherosclerosis, which could be convincingly reflected by common carotid artery intima-media thickness (CCAIMT) and carotid plaque. The current study aimed to investigate the prevalence and risk factors of thick CCAIMT and carotid plaque in gout patients. METHODS: Comprehensive demographic characteristics, chronic comorbidities, disease features, and biochemical indexes (42 parameters) were obtained from 237 gout patients. CCAIMT and carotid plaque were evaluated by bilateral carotid artery ultrasound in gout patients and 80 healthy controls. RESULTS: The CCAIMT and carotid plaque percentage were increased in gout patients compared to healthy controls (both p<0.001). In detail, the prevalence of thick CCAIMT (>0.9 mm) and carotid plaque was 22.4% and 34.6% in gout patients, respectively. Forward-stepwise multivariate logistic regression model revealed that age (p<0.001, odds ratio (OR)=1.143], disease duration (p=0.001, OR=1.176), alkaline phosphatase (ALP) (p=0.002, OR=1.037), and low-density lipoprotein cholesterol (LDLC) (p=0.039, OR=2.144) were independently associated with elevated thick CCAIMT risk, while serum uric acid (SUA) (p=0.002, OR=0.992) exhibited an opposite trend; their combination well-identified thick CCAIMT risk [area under the curve (AUC)=0.910] by receiver operator characteristic (ROC) curve. Meanwhile, age (p<0001, OR=1.116), tophus (p=0.009, OR=3.523), and triglycerides (TG) (p=0.014, OR=1.323) were independently associated with a higher risk of carotid plaque, while SUA (p=0.008, OR=0.995) showed an opposite trend; their combination also well-identified carotid plaque risk (AUC=0.886) by ROC curve. CONCLUSIONS: Thick CCAIMT and carotid plaque are prevalent in gout patients, whose occurrence relates to age, disease duration, ALP, LDLC, SUA, TG, and tophus.
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Doenças das Artérias Carótidas , Gota , Placa Aterosclerótica , Humanos , Espessura Intima-Media Carotídea , Prevalência , Ácido Úrico , Artérias Carótidas/diagnóstico por imagem , Fatores de Risco , Artéria Carótida Primitiva/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Gota/diagnóstico por imagem , Gota/epidemiologiaRESUMO
The hepatopancreas is the biggest digestive organ in Amphioctopus fangsiao (A. fangsiao), but also undertakes critical functions like detoxification and immune defense. Generally, pathogenic bacteria or endotoxin from the gut microbiota would be arrested and detoxified in the hepatopancreas, which could be accompanied by the inevitable immune responses. In recent years, studies related to cephalopods immune have been increasing, but the molecular mechanisms associated with the hepatopancreatic immunity are still unclear. In this study, lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, was used for imitating bacteria infection to stimulate the hepatopancreas of A. fangsiao. To investigate the immune process happened in A. fangsiao hepatopancreas, we performed transcriptome analysis of hepatopancreas tissue after LPS injection, and identified 2615 and 1943 differentially expressed genes (DEGs) at 6 and 24 h post-injection, respectively. GO and KEGG enrichment analysis showed that these DEGs were mainly involved in immune-related biological processes and signaling pathways, including ECM-receptor interaction signaling pathway, Phagosome signaling pathway, Lysosome signaling pathway, and JAK-STAT signaling pathways. The function relationships between these DEGs were further analyzed through protein-protein interaction (PPI) networks. It was found that Mtor, Mapk14 and Atm were the three top interacting DEGs under LPS stimulation. Finally, 15 hub genes involving multiple KEGG signaling pathways and PPI relationships were selected for qRT-PCR validation. In this study, for the first time we explored the molecular mechanisms associated with hepatopancreatic immunity in A. fangsiao using a PPI networks approach, and provided new insights for understanding hepatopancreatic immunity in A. fangsiao.
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Perfilação da Expressão Gênica , Hepatopâncreas , Lipopolissacarídeos , Transcriptoma , Animais , Lipopolissacarídeos/farmacologia , Hepatopâncreas/imunologia , Perfilação da Expressão Gênica/veterinária , Imunidade Inata/genética , Transdução de SinaisRESUMO
Lipotoxicity refers to the accumulation of lipids in tissues other than adipose tissue (body fat). It is one of the major pathophysiological mechanisms responsible for the progression of diabetes complications such as non-alcoholic fatty liver disease and diabetic nephropathy. Accumulating evidence indicates that lipotoxicity also contributes significantly to the toxic effects of diabetes on periodontitis. Therefore, we reviewed the current in vivo, in vitro, and clinical evidence of the detrimental effects of lipotoxicity on periodontitis, focusing on its molecular mechanisms, especially oxidative and endoplasmic reticulum stress, inflammation, ceramides, adipokines, and programmed cell death pathways. By elucidating potential therapeutic strategies targeting lipotoxicity and describing their associated mechanisms and clinical outcomes, including metformin, statins, liraglutide, adiponectin, and omega-3 PUFA, this review seeks to provide a more comprehensive and effective treatment framework against diabetes-associated periodontitis. Furthermore, the challenges and future research directions are proposed, aiming to contribute to a more profound understanding of the impact of lipotoxicity on periodontitis.
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Estresse Oxidativo , Periodontite , Humanos , Periodontite/metabolismo , Periodontite/complicações , Estresse do Retículo Endoplasmático/fisiologia , Inflamação/metabolismo , Adipocinas/metabolismo , Animais , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Ceramidas/metabolismo , Metabolismo dos LipídeosRESUMO
BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved ß-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of ß-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND RESULTS: RYGB or sham surgery was conducted in GK rats. mRNA and protein expression of SNAP25 was assessed by qPCR and Western blot, respectively. Occupancy of CREB and acetyltransferase CBP and acetylation of histone H3 (ACH3) at the Snap25 promoter were determined using ChIP assay. RYGB led to increased SNAP25 expression and CREB phosphorylation in islets from GK rats. Increased SNAP25 improved GSIS in ß-cells cultured in high glucose conditions. Consistent with increased plasma GLP-1 after RYGB, GLP-1R agonist exendin4 increased SNAP25 expression and CREB phosphorylation in ß-cells. Mechanistically, exendin4 promoted the recruitment of CREB and CBP, thereby increasing ACH3 at the Snap25 promoter. Consistently, inhibition of CBP attenuated the effect of exendin4 on SNAP25 expression. Furthermore, the knockdown of SNAP25 diminished the increase of GSIS potentiated by chronic GLP-1 culture in INS-1 832/13 cells. CONCLUSIONS: Our findings unravel the novel mechanisms of RYGB-enhanced SNAP25 expression in ß-cells, and SNAP25 may contribute to the improved ß-cell secretory function induced by RYGB.
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Diabetes Mellitus Tipo 2 , Derivação Gástrica , Secreção de Insulina , Proteína 25 Associada a Sinaptossoma , Animais , Ratos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirurgia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucose , Histonas , Proteína 25 Associada a Sinaptossoma/genéticaRESUMO
Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.
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Canabidiol , Carcinoma Epitelial do Ovário , Microbioma Gastrointestinal , Neoplasias Ovarianas , Canabidiol/farmacologia , Canabidiol/química , Microbioma Gastrointestinal/efeitos dos fármacos , Feminino , Humanos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Animais , Camundongos , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura MolecularRESUMO
The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.
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Diferenciação Celular/genética , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/embriologia , RNA/análise , Análise de Sequência de RNA , Análise de Célula Única , Humanos , Interneurônios/citologia , Interneurônios/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Neurônios/classificação , Neurônios/citologia , Neurônios/metabolismo , RNA/genética , Transdução de SinaisRESUMO
BACKGROUND: Increasing evidence links higher air pollution exposures to increased risk of cognitive impairment. While midlife risk factors are often most strongly linked to dementia risk, few studies have considered associations between midlife roadway proximity or ambient air pollution exposure and incident dementia decades later, in late life. OBJECTIVES: Our objective was to determine if midlife exposures to ambient air pollution or roadway proximity are associated with increased risk of dementia in the Atherosclerosis Risk in Communities (ARIC) study over up to 29 years of follow-up. METHODS: Our eligible sample included Black and White ARIC participants without dementia at Visit 2 (1990-1992). Participants were followed through Visit 7 (2018-2019), with dementia status and onset date defined based on formal dementia ascertainment at study visits, informant interviews, and surveillance efforts. We used adjusted Weibull survival models to assess the associations of midlife ambient air pollution and road proximity with incident dementia. RESULTS: The median age at baseline (1990-1992, Visit 2) of the 12,700 eligible ARIC participants was 57.0 years; 56.0% were female, 24.2% were Black, and 78.9% had at least a high school education. Over up to 29 years of follow-up, 2511 (19.8%) persons developed dementia. No associations were found between ambient air pollutants and proximity to major roadways with risk of incident dementia. In exploratory analyses, living closer to roadways in midlife increased dementia risk in individuals younger at baseline and those without midlife hypertension, and there was evidence of increased risk of dementia with increased midlife exposure to NOx, several PM2.5 components, and trace metals among those with diabetes in midlife. CONCLUSIONS: Midlife exposure to ambient air pollution and midlife roadway proximity was not associated with dementia risk over decades of follow-up. Further investigation to explore potential for greater susceptibility among specific subgroups identified here is needed.
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Poluentes Atmosféricos , Poluição do Ar , Demência , Exposição Ambiental , Humanos , Pessoa de Meia-Idade , Demência/epidemiologia , Demência/induzido quimicamente , Demência/etiologia , Feminino , Masculino , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Incidência , Fatores de Risco , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Material Particulado/análise , Material Particulado/efeitos adversos , Emissões de Veículos/análiseRESUMO
BACKGROUND: Reported associations between particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity. OBJECTIVES: To assess agreement between PM2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM2.5 and cognitive or MRI outcomes. METHODS: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM2.5 exposure estimates with cognitive scores (n = 4678) and MRI outcomes (n = 1518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors. RESULTS: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM2.5-cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors. DISCUSSION: PM2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health.
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Poluentes Atmosféricos , Encéfalo , Cognição , Exposição Ambiental , Imageamento por Ressonância Magnética , Material Particulado , Material Particulado/análise , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Cognição/efeitos dos fármacos , Poluentes Atmosféricos/análise , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Idoso , Poluição do Ar/efeitos adversos , Poluição do Ar/análiseRESUMO
PURPOSE: This study aimed to investigate the efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of synovial hyperplasia in the knee joints of antigen-induced arthritis (AIA) model rabbits. METHODS: Forty Japanese large-eared white rabbits were divided into AIA and control groups. After successful induction of the AIA model, the knee joints were randomly assigned to RFA and non-RFA groups. The RFA group underwent ultrasound-guided RFA to treat synovial hyperplasia in the knee joint. Dynamic observation of various detection indices was conducted to evaluate the safety and effectiveness of the RFA procedure. RESULTS: Successful synovial ablation was achieved in the RFA group, with no intraoperative or perioperative mortality. Postoperative the circumference of the knee joint reached a peak before decreasing in the third week after surgery. The incidence and diameter of postoperative skin ulcers were not significantly different compared to the non-RFA group (p > .05). Anatomical examination revealed an intact intermuscular fascia around the ablated area in the RFA group. The ablated synovial tissue initially presented as a white mass, which subsequently liquefied into a milky white viscous fluid. Gross articular cartilage was observed, along with liquefied necrosis of the synovium on pathological histology and infiltration of inflammatory cells in the surrounding soft tissue. CONCLUSION: The experimental results demonstrated that ultrasound-guided RFA of the knee in the treatment of synovial hyperplasia in AIA model animals was both effective and safe.
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Hiperplasia , Ablação por Radiofrequência , Animais , Coelhos , Ablação por Radiofrequência/métodos , Hiperplasia/cirurgia , Hiperplasia/patologia , Membrana Sinovial/patologia , Membrana Sinovial/diagnóstico por imagem , Ultrassonografia/métodos , Masculino , Ultrassonografia de Intervenção/métodosRESUMO
Tubers of Gymnadenia conopsea (L.) R. Br. (Orchidaceae), a traditional medicine and food homologous plant, has a broad application and development prospect in the food and drug industries. Benzylester glucosides, the main effective active components in this plant, are difficult to separate due to their similar structures and high polarity. In this study, linear gradient counter-current chromatography was used to separate benzylester glucosides and derivatives, combined with elution-extrusion mode. The main separation parameters were optimized, including the ratio of mobile phase and sample loading. Finally, seven compounds were successfully separated, including 4-hydroxybenzyl alcohol (1), 4-hydroxybenzaldehyde (2), dactylorhin B (3), loroglossin (4), dactylorhin A (5), 4-(ethoxymethyl) phenol (6), and militarine (7). The structures were analyzed by mass spectrometry and nuclear magnetic resonance spectrometry. According to our findings, the established method was an efficient approach to separate benzylester glucosides and derivatives from tubers of G. conopsea. The established strategy could be applied to purify other similar high-polarity compounds from complex natural products.
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Distribuição Contracorrente , Glucosídeos , Orchidaceae , Tubérculos , Tubérculos/química , Orchidaceae/química , Glucosídeos/isolamento & purificação , Glucosídeos/química , Estrutura Molecular , Ésteres/química , Ésteres/isolamento & purificaçãoRESUMO
PURPOSE: The air health index (AHI) captures the combined effects of air pollution and non-optimal temperatures and helps assess the atmospheric environment's overall health risk. Shandong Province is a crucial industrial base in China, and the health effects of air pollution and non-optimal temperature cannot be ignored. To construct an AHI for Shandong Province and assess the district-level mortality burden due to AHI in the study area. METHODS: Daily district-specific mortality, meteorological, and air pollution data over 2013-2018 were collected in Shandong Province, China. The AHI construction eventually incorporated PM2.5 and NO2, O3, and non-optimal temperatures. Attributable fraction (AF) and attributable number (AN) were used to estimate the district-specific mortality burden attributable to AHI. RESULTS: The average AHI value observed in Shandong Province was 6. Our research revealed a positive association between the total AHI and total mortality, with an overall trend of a slow increase followed by a rapid increase. The exposure-response curves, when stratified by gender, age, and cause of death, were approximately consistent with the overall trend. The provincial attributable fraction (AF) was 5.31% (95% CI 4.58%, 5.91%), and the attributable number (AN) was 188,246 (95% CI 162,396, 209,533). Overall, higher ANs mainly appeared in the southwestern area, while higher values of AF were observed in the central-eastern and central-northern areas. CONCLUSIONS: The air health index performs well in predicting death burden and can convey health risks related to exposure to the ambient environment to the public.
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Poluentes Atmosféricos , Poluição do Ar , Humanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Temperatura , Material Particulado/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análiseRESUMO
The negatively charged boron vacancy (VB-) defect in hexagonal boron nitride (hBN) with optically addressable spin states has emerged due to its potential use in quantum sensing. Remarkably, VB- preserves its spin coherence when it is implanted at nanometer-scale distances from the hBN surface, potentially enabling ultrathin quantum sensors. However, its low quantum efficiency hinders its practical applications. Studies have reported improving the overall quantum efficiency of VB- defects with plasmonics; however, the overall enhancements of up to 17 times reported to date are relatively modest. Here, we demonstrate much higher emission enhancements of VB- with low-loss nanopatch antennas (NPAs). An overall intensity enhancement of up to 250 times is observed, corresponding to an actual emission enhancement of â¼1685 times by the NPA, along with preserved optically detected magnetic resonance contrast. Our results establish NPA-coupled VB- defects as high-resolution magnetic field sensors and provide a promising approach to obtaining single VB- defects.
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DNA is susceptible to various factors in vitro and in vivo and experience different forms of damage,among which double-strand break(DSB)is a deleterious form.To maintain the stability of genetic information,organisms have developed multiple mechanisms to repair DNA damage.Among these mechanisms,homologous recombination(HR)is praised for the high accuracy.The MRE11-RAD50-NBS1(MRN)complex plays an important role in HR and is conserved across different species.The knowledge on the MRN complex mainly came from the previous studies in Saccharomyces cerevisiae and Caenorhabditis elegans,while studies in the last decades have revealed the role of mammalian MRN complex in DNA repair of higher animals.In this review,we first introduces the MRN complex regarding the composition,structure,and roles in HR.In addition,we discuss the human diseases such as ataxia-telangiectasia-like disorder,Nijmegen breakage syndrome,and Nijmegen breakage syndrome-like disorder that are caused by dysfunctions in the MRN complex.Furthermore,we summarize the mouse models established to study the clinical phenotypes of the above diseases.
Assuntos
Hidrolases Anidrido Ácido , Proteínas de Ciclo Celular , Enzimas Reparadoras do DNA , Proteínas de Ligação a DNA , Proteína Homóloga a MRE11 , Proteínas Nucleares , Humanos , Hidrolases Anidrido Ácido/metabolismo , Hidrolases Anidrido Ácido/genética , Proteína Homóloga a MRE11/metabolismo , Proteína Homóloga a MRE11/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Animais , Reparo do DNA , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/metabolismo , Síndrome de Quebra de Nijmegen/metabolismo , Síndrome de Quebra de Nijmegen/genéticaRESUMO
Developing artificial enzymes based on organic molecules or polymers for reactive oxygen species (ROS)-related catalysis has broad applicability. Herein, inspired by porphyrin-based heme mimics, we report the synthesis of polyphthalocyanine-based conjugated polymers (Fe-PPc-AE) as a new porphyrin-evolving structure to serve as efficient and versatile artificial enzymes for augmented reactive oxygen catalysis. Owing to the structural advantages, such as enhanced π-conjugation networks and π-electron delocalization, promoted electron transfer, and unique Fe-N coordination centers, Fe-PPc-AE showed more efficient ROS-production activity in terms of Vmax and turnover numbers as compared with porphyrin-based conjugated polymers (Fe-PPor-AE), which also surpassed reported state-of-the-art artificial enzymes in their activity. More interestingly, by changing the reaction medium and substrates, Fe-PPc-AE also revealed significantly improved activity and environmental adaptivity in many other ROS-related biocatalytic processes, validating the potential of Fe-PPc-AE to replace conventional (poly)porphyrin-based heme mimics for ROS-related catalysis, biosensors, or biotherapeutics. It is suggested that this study will offer essential guidance for designing artificial enzymes based on organic molecules or polymers.