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The high-concentration powder carrier bio-fluidized bed (HPB) technology is an emerging approach that enables on-site upgrading of wastewater treatment plants (WWTPs). HPB technology promotes the formation of biofilm sludge with micron-scale composite powder carriers as the core and suspended sludge mainly composed of flocs surrounding the biofilm sludge. This study proposed a novel integrated strategy for assessing and controlling the sludge ages in suspended/bio-film activated sludge supported by micron-scale composite powder carrier. Utilizing the cyclone unit and the corresponding theoretical model, the proposed strategy effectively addresses the sludge ages contradiction between denitrifying bacteria and polyphosphate-accumulating organisms (PAOs), thereby enhancing the efficiency of municipal wastewater treatment. The sludge age of the suspended (25 d) and bio-film (99 d) sludge, calculated using the model, contribute to the simultaneous removal of nitrogen and phosphorus. Meanwhile, the model further estimates distinct contributions of suspended and bio-film sludge to chemical oxygen demand (COD) and total nitrogen (TN), which are 55% and 42% for COD, 20% and 57% for TN of suspended sludge and bio-film sludge, respectively. This suggests that the contribution of suspended sludge and bio-film sludge to COD and TN removal efficiency can be determined and controlled by the operational conditions of the cyclone unit. Additionally, the simulation values for COD, ammonia nitrogen (NH4+-N), TN and total phosphorus (TP) closely align with the actual values of WWTPs over 70 days (p < 0.001) with the correlation coefficients (R2) of 0.9809, 0.9932, 0.9825, and 0.837, respectively. These results support the theoretical foundation of HPB technology for simultaneous nitrogen and phosphorus removal in sewage treatment plants. Therefore, this model serves as a valuable tool to guide the operation, design, and carrier addition in HPB technology implementation.
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Aguas del Alcantarillado , Purificación del Agua , Aguas del Alcantarillado/química , Aguas Residuales , Polvos , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos/microbiología , Fósforo , Nitrógeno , DesnitrificaciónRESUMEN
Hyperphosphorylation of the microtubule associated protein tau is associated with several neurodegenerative diseases including Alzheimer's Disease (AD), collectively referred to as tauopathies. However, the mechanisms by which tau is linked to synaptic dysfunction and memory impairment remain unclear. To address this question, we constructed a mouse model with brain-specific deficiency of SIRT1 (SIRT1 flox/Cre + ). Here, we show that increase of site-specific phosphorylation of tau is coupled with the strengthened O-GlcNAcylation of tau triggered by reduced O-GlcNAcase (OGA) and increased O-GlcNAc transferase (OGT) protein level in the brain of SIRT1 flox/Cre+ mice. SIRT1 deletion in mice brain changes the synaptosomal distribution of site-specific phospho-tau. Learning and memory deficiency induced by dendritic spine deficits and synaptic dysfunction are revealed via SIRT1 flox/Cre+ mice. Our results provide evidence for SIRT1 as a potential therapeutic target in clinical tauopathies.
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Enfermedad de Alzheimer , Tauopatías , Animales , Ratones , Sirtuina 1/genética , Sirtuina 1/metabolismo , Tauopatías/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Enfermedad de Alzheimer/metabolismo , Fosforilación , Encéfalo/metabolismoRESUMEN
Renal ischemia-reperfusion (I/R) injury leads to irreversible brain damage with serious consequences. Activation of oxidative stress and release of inflammatory mediators are considered potential pathological mechanisms. Butylphthalide (NBP) has anti-inflammatory and antioxidant effects on I/R injuries. However, it is unclear whether NBP can effectively mitigate renal I/R secondary to brain injury as well as its mechanism, which are the aims of this study. Both renal I/R injury rats and oxygen and glucose deprivation cell models were established and pre-intervened NBP. The Morris water maze assay was used to detect behavior. Hippocampal histopathology and function were examined after renal I/R. Apoptosis and tube-forming capacity of brain microvascular endothelial cells (BMVECs) were tested. Immunohistochemistry and Western blot were used to measure protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway and NOD-like receptor C2 (NOD2)/Mitogen-activated protein kinases (MAPK)/Nuclear factor kappa-B (NF-κB) pathway. NBP treatment attenuated renal I/R-induced brain tissue damage and learning and memory dysfunction. NBP treatment inhibited apoptosis and promoted blood-brain barrier restoration and microangiogenesis. Also, it decreased oxidative stress levels and pro-inflammatory factor expression in renal I/R rats. Furthermore, NBP enhanced BMVECs' viability and tube-forming capacity while inhibiting apoptosis and oxidative stress. Notably, the alleviating effects of NBP were attributed to Nrf2/HO-1 pathway activation and NOD2/MAPK/NF-κB inhibition. This study demonstrates that NBP maintains BBB function by activating the Nrf2/HO-1 pathway and inhibiting the NOD2/MAPK/NF-κB pathway to suppress inflammation and oxidative stress, thereby alleviating renal I/R-induced brain injury.
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Lesiones Encefálicas , Daño por Reperfusión , Animales , Ratas , Factor 2 Relacionado con NF-E2 , FN-kappa B , Hemo-Oxigenasa 1 , Células Endoteliales , Encéfalo , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Proteína Adaptadora de Señalización NOD2RESUMEN
PETase displays great potential in PET depolymerization. Directed evolution has been limited to engineer PETase due to the lack of high-throughput screening assay. In this study, a novel fluorescence-based high-throughput screening assay employing a newly designed substrate, bis (2-hydroxyethyl) 2-hydroxyterephthalate (termed BHET-OH), was developed for PET hydrolases. The best variant DepoPETase produced 1407-fold more products towards amorphous PET film at 50 °C and showed a 23.3 °C higher Tm value than the PETase WT. DepoPETase enabled complete depolymerization of seven untreated PET wastes and 19.1â g PET waste (0.4 % Wenzyme /WPET ) in liter-scale reactor, suggesting that it is a potential candidate for industrial PET depolymerization processes. The molecular dynamic simulations revealed that the distal substitutions stabilized the loops around the active sites and transmitted the stabilization effect to the active sites through enhancing inter-loop interactions network.
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Hidrolasas , Tereftalatos Polietilenos , Hidrolasas/metabolismo , Tereftalatos Polietilenos/química , Dominio CatalíticoRESUMEN
The wearable application of flexible organic solar cells (f-OSCs) necessitates high power conversion efficiency (PCE) and mechanical robustness. However, photoactive films based on efficient non-fullerene small molecule acceptors (NF-SMAs) are typically brittle, leading to poor mechanical stability in devices. In this study, we achieved a remarkable PCE of 18.06 % in f-OSCs while maintaining ultrahigh mechanical robustness (with a crack-onset strain (COS) of higher than 11 %) by incorporating a linker dimerized acceptor (DOY-TVT). Compared to binary blends, ternary systems exhibit reduced non-radiative recombination, suppressed crystallization and diffusion of NF-SMAs, and improved load distribution across the chain networks, enabling the dissipation of the load energy. Thus, the ternary f-OSCs developed in this study achieved, high PCE and stability, surpassing binary OSCs. Moreover, the developed f-OSCs retained 97 % of the initial PCE even after 3000 bending cycles, indicating excellent mechanical stability (9.1 % higher than binary systems). Furthermore, the rigid device with inverted structure based on the optimal active layer exhibited a substantial increase in efficiency retention, with 89.6 % after 865â h at 85 °C and 93 % after more than 1300â h of shelf storage at 25 °C. These findings highlight the potential of the linker oligomer acceptor for realizing high-performing f-OSCs with ultrahigh mechanical robustness.
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BACKGROUND: Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. METHODS AND FINDINGS: This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: -8.83; 95% CI, -14.03 to -3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. CONCLUSIONS: The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03317639.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Administración Intravenosa , Anciano , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodosRESUMEN
BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.
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BACKGROUND: The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum. METHODS: In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis. RESULTS: Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree's accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM. CONCLUSIONS: The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different "predominant regions" that generate attacks.
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Epilepsia , Migraña con Aura , Migraña sin Aura , Estudios Transversales , Epilepsia/complicaciones , Femenino , Cefalea/complicaciones , Humanos , Migraña con Aura/complicaciones , Migraña con Aura/diagnóstico , Migraña con Aura/genética , Migraña sin Aura/diagnóstico , FenómicaRESUMEN
Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila, that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons.
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Orientación del Axón/fisiología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Receptores Notch/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión/genética , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Glucosiltransferasas/metabolismo , Glicosilación , Factores de Intercambio de Guanina Nucleótido/metabolismo , Ligandos , Modelos Neurológicos , Proteínas del Tejido Nervioso/metabolismo , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteolisis , Receptores Notch/química , Receptores Notch/genética , Transducción de Señal , Tirosina/metabolismoRESUMEN
OBJECTIVE: To observe the prevalence and characteristics of premonitory symptoms in Chinese migraineurs and explore their associations with migraine-related factors. METHOD: Migraineurs who visited a tertiary headache clinic and one of nine neurology clinics between May 2014 and November 2019 were studied. RESULT: Among the 4821 patients meeting the migraine criteria (International Classification of Headache Disorders, 3rd edition), 1038 (21.5%) patients experienced at least one premonitory symptom. The most common premonitory symptoms were neck stiffness, dizziness, yawning and drowsiness. The logistic regression analysis demonstrated that aura, photophobia, aggravation by routine physical activity, triggers, family history, depression, coffee consumption and physical exercise were associated with an increased probability of experiencing premonitory symptoms (p ≤ 0.001). The premonitory symptoms of migraine with and without aura differ in prevalence and most common symptoms. The cluster analysis revealed pairwise clustering of the following premonitory symptoms: Photophobia/phonophobia, concentration change/dysesthesia, loquacity/overactivity, yawning/drowsiness, fatigue/dizziness, and mood change/irritability. The correlation analysis of triggers and premonitory symptoms revealed that temperature change, environment change, sleep disorder, activity and stress were related to multiple premonitory symptoms, and that food, light, menstruation, alcohol and odor were related to special premonitory symptoms (p ≤ 0.001). CONCLUSION: The prevalence of premonitory symptoms among migraineurs in China is 21.5%. Some factors influence the probability of experiencing premonitory symptoms. Paired premonitory symptoms in the clustering analysis may share similar origins. Certain triggers associated with multiple premonitory symptoms may induce brain dysfunction; however, other triggers that overlap with corresponding special premonitory symptoms may be premonitory symptoms or a form of premonitory symptom.
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Fatiga/epidemiología , Trastornos Migrañosos/epidemiología , Migraña con Aura/epidemiología , Migraña sin Aura/epidemiología , Fotofobia/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , China/epidemiología , Mareo , Femenino , Cefalea , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , BostezoRESUMEN
The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. Although individual components are known, the relationships among them remain unresolved. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin-regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain. Finally, we show that a key target of Abl signaling in axons is the WAVE complex that promotes the formation of branched actin networks. Thus, we show that Abl constitutes a bifurcating network, suppressing Ena activity in parallel with stimulation of WAVE. We suggest that the balancing of linear and branched actin networks by Abl is likely to be central to its regulation of axon patterning.
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Axones/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriología , Drosophila melanogaster/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas de Unión al GTP rac/metabolismo , Animales , Animales Modificados Genéticamente , Tipificación del Cuerpo , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Transferencia Resonante de Energía de Fluorescencia , Genes de Insecto , Factores de Intercambio de Guanina Nucleótido/química , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neurogénesis , Neuronas/citología , Neuronas/metabolismo , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Dominios Proteicos , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/genética , Transducción de Señal , Proteínas de Unión al GTP rac/genéticaRESUMEN
INMAP was first identified as a spindle protein that plays important roles in cell-cycle progression, and previous studies have revealed that its abnormal expression leads to mitotic disorder and the growth inhibition of human tumor xenografts, but the underlying mechanism is still unclear. In this study, we knocked out INMAP in HEK293T cells, a strain of human embryonic renal cells, through CRISPR-Cas9 gene editing technology, resulting in obvious cell growth inhibition. In this system, the deletion of INMAP caused obviously apoptosis. And we also found that knockout of INMAP caused micronuclei formation, chromosome aberration, and γH2AX expression upregulation, suggesting DNA damage induction and genomic stability impairment. As a principal component of spindle, the expression of ß-tubulin, detected through Western blot, is obviously upregulated in HEK293T-INMAP-/-. Meanwhile, the level of Cyclin B is also upregulated, whereas, that of Cyclin E, downregulated, with the postponement of mitotic exit and the assembly anomaly of spindle. These results suggest that the deletion of INMAP block the formation of spindle, leading to arrest of cell cycle and DNA damage, finally blocking cell proliferation and inducing apoptosis. Therefore, INMAP is an indispensable factor for genomic integrity and normal mitotic exit.
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Apoptosis , Proteínas de Ciclo Celular/metabolismo , Eliminación de Gen , Mitosis , Proteínas Nucleares/metabolismo , Huso Acromático/metabolismo , Puntos de Control del Ciclo Celular , Proliferación Celular , Daño del ADN , Células HEK293 , Humanos , Transducción de Señal , Tubulina (Proteína)/metabolismoRESUMEN
OBJECTIVE: We performed closure of the patent ductus arteriosus (PDA) using a hybrid approach with an Amplatzer Duct Occluder. METHODS: Six patients (two males and four females) underwent PDA closure at a mean age of 7.8 months (range 2-24 months) and a mean weight of 6.6 kg (range 4.5-13 kg). The main pulmonary artery (MPA) was exposed via a minimally invasive left parasternal second intercostal space incision. Under transesophageal echocardiography guidance, the PDA occluder was implanted via direct puncture of the MPA. RESULTS: The procedure was successful in all patients with no residual shunt. There were no hospital deaths, and the postoperative course was uneventful. All patients were discharged on the 3rd to 4th day. There was no residual shunt in any patient on midterm follow-up. CONCLUSIONS: The novel hybrid approach is a safe, minimal invasive procedure. Further experience and longer follow-up of these patients is necessary to conclude whether this technique is applicable to all the patients with a PDA.
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Procedimientos Quirúrgicos Cardíacos/métodos , Conducto Arterioso Permeable/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dispositivo Oclusor Septal , Cirugía Asistida por Computador/métodos , Preescolar , Ecocardiografía Transesofágica , Femenino , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²âº mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase ß(IKKß), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKß, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKß-AMPK-dependent restoration of myocardial autophagy. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
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Proteínas Quinasas Activadas por AMP/metabolismo , Antioxidantes/metabolismo , Autofagia , Catalasa/metabolismo , Dieta Alta en Grasa , Corazón/fisiopatología , Quinasa I-kappa B/metabolismo , Animales , Autofagia/efectos de los fármacos , Calcio/metabolismo , Cardiomegalia/enzimología , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Ecocardiografía , Conducta Alimentaria/efectos de los fármacos , Corazón/efectos de los fármacos , Espacio Intracelular/metabolismo , Masculino , Ratones Transgénicos , Modelos Biológicos , Contracción Miocárdica/efectos de los fármacos , Ácido Palmítico/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: During metamorphosis, axons and dendrites of the mushroom body (MB) in the Drosophila central brain are remodeled extensively to support the transition from larval to adult behaviors. RESULTS: We show here that the neuronal cyclin-dependent kinase, Cdk5, regulates the timing and rate of mushroom body remodeling: reduced Cdk5 activity causes a delay in pruning of MB neurites, while hyperactivation accelerates it. We further show that Cdk5 cooperates with the ubiquitin-proteasome system in this process. Finally, we show that Cdk5 modulates the first overt step in neurite disassembly, dissolution of the neuronal tubulin cytoskeleton, and provide evidence that it also acts at additional steps of MB pruning. CONCLUSIONS: These data show that Cdk5 regulates the onset and extent of remodeling of the Drosophila MB. Given the wide phylogenetic conservation of Cdk5, we suggest that it is likely to play a role in developmental remodeling in other systems, as well. Moreover, we speculate that the well-established role of Cdk5 in neurodegeneration may involve some of the same cellular mechanisms that it uses during developmental remodeling.
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Quinasa 5 Dependiente de la Ciclina/metabolismo , Proteínas de Drosophila/metabolismo , Cuerpos Pedunculados/citología , Neuronas/metabolismo , Animales , Axones/metabolismo , Dendritas/metabolismo , Drosophila melanogaster , Cuerpos Pedunculados/metabolismo , Filogenia , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitinación/fisiologíaRESUMEN
BACKGROUND: The aim of this study was to determine whether MSC are excellent materials for MSCs transplantation in the treatment of osteoporosis. MATERIAL AND METHODS: We studied normal, osteoporosis, and TERT-transfected MSC from normal and osteoporosis rats to compare the proliferation and osteogenic differentiation using RT-PCR and Western blot by constructing an ovariectomized rat model of osteoporosis (OVX). The primary MSC from model rats were extracted and cultured to evaluate the proliferation and differentiation characteristics. RESULTS: MSCs of osteoporosis rats obviously decreased in proliferation ability and osteogenic differentiation compared to that of normal rats. In contrast, in TERT-transfected MSC, the proliferation and differentiation ability, and especially the ability of osteogenic differentiation, were significantly higher than in osteoporosis MSC. CONCLUSIONS: TERT-transfected MSCs can help osteoporosis patients in whom MSC proliferation and osteogenic differentiation ability are weak, with an increase in both bone mass and bone density, becoming an effective material for autologous transplantation of MSCs in further treatment of osteoporosis. However, studies are still needed to prove the in vivo effect, biological safety, and molecular mechanism of TERT-osteoporosis treatment. Additionally, because the results are from an animal model, more research is needed in generalizing rat model findings to human osteoporosis patients.
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Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Osteoporosis/patología , Telomerasa/metabolismo , Transfección , Animales , Antígenos CD/metabolismo , Western Blotting , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Fémur/patología , Citometría de Flujo , Regulación de la Expresión Génica , Vectores Genéticos/metabolismo , Lentivirus/metabolismo , Ovariectomía , Plásmidos/metabolismo , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Telomerasa/genéticaRESUMEN
In order to analysis the oil spill situation based on the obtained data in airborne aerial work, it's needed to get the spectral reflectance characteristics of the oil film of different oils and thickness as support and to select the appropriate operating band. An experiment is set up to measure the reflectance spectroscopy from ultraviolet to near-infrared for the film of five target samples, which means petrol, diesel, lubricating oil, kerosene and fossil, using spectral measurement device. The result is compared with the reflectance spectra of water in the same experimental environment, which shows that the spectral reflection characteristics of the oil film are related to the thickness and the type of the oil film. In case of the same thickness, the spectral reflectance curve of different types of film is far different, and for the same type of film, the spectral reflectance curve changes accordingly with the change of film thickness, therefore in terms of the single film, different film thickness can be distinguished by reflectance curves. It also shows that in terms of the same film thickness, the reflectance of diesel, kerosene, lubricants reaches peak around 380 nm wavelength, obviously different from the reflectance of water, and that the reflectance of crude oil is far less than that of water in more than 340 nm wavelength, and the obtained reflection spectrum can be used to distinguish between different types of oil film to some extent. The experiment covers main types of spilled oil, with data comprehensively covering commonly used detect spectral bands, and quantitative description of the spectral reflectance properties of film. It provides comprehensive theoretical and data support for the selection of airborne oil spill detection working band and the detection and analysis of water-surface oil spill.
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Two types of fibers were prepared by using bio-based materials: a mono-filament made from poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a multi-filament made from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and polylactic acid (PLA) blend. The two fibers were evaluated for mechanical properties, biocompatibility and degradability for the potential application as medical sutures. The PHBHHx fiber showed remarkable biocompatibility by H.E. Stainning, with very little impact to the surrounding tissues. The degradation of the fiber was observed by SEM after implantation for 36 weeks, and the major degradation product was detected after 96 weeks. Consistently, the PHBHHx fiber maintained more than half of the mechanical properties after 96 weeks. The other fiber was prepared by twisting PHBV/PLA blend strands to a bunch, and showed high biocompatibility and relatively high degradability. The bunched structure loosed after 36 weeks of implantation. These low-cost and easily prepared fibers have great potential in medical applications, since they could avoid the formation of fibrous capsule, reduce the size of scar, and degrade into non-toxic and even beneficial products.
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Ácido 3-Hidroxibutírico , Caproatos , Ácido Láctico , Poliésteres , Polímeros , Suturas , Animales , Materiales Biocompatibles , Cromatografía en Gel , Masculino , Microscopía Electrónica de Rastreo , Ratas , Ratas Sprague-Dawley , Resistencia a la TracciónRESUMEN
OBJECTIVE: Study the current quality management situation of enterprises marketing corneal contact lens via systemic investigations and explore effective administration countermeasures in the future. METHODS: The quality management indicators of sixty-two corneal contact lens marketing enterprises in Xuhui district of Shanghai were systematically investigated and enterprises of different operation models was compared and analyzed. RESULTS: Wholesale enterprises and retail chain enterprises are apparently better than independent enterprises almost in all facets. CONCLUSION: Facilitate market accession of corneal contact lens marketing enterprises, encourage the business model of retail chain, enhance supervision of corneal contact lens marketing enterprises, especially independent franchisors.
Asunto(s)
Lentes de Contacto/economía , Mercadotecnía , Administración de Materiales de HospitalRESUMEN
Deep convolutional neural networks have made significant strides in the field of medical image segmentation. Although existing convolutional structures enhance performance by leveraging local image information, they often lose the interdependence information between contexts. Therefore, the article utilizes the multi-attention mechanism of the Transformer structure to more comprehensively express relationships between contexts and introduced the Transformer network architecture into the field of medical image segmentation. Most models based on this Transformer structure typically require large datasets for training. However, in the medical field, the limited size of datasets makes training models with the Transformer structure challenging. To address this, the article propose a Weighted Medical Transformer (WMT) model that imposes low requirements on dataset quantity. The weighting mechanism in the WMT model aims to improve the issue of inaccurate relative positional coding when dealing with small medical datasets. Additionally, a coarse-grained and fine-grained segmentation mechanism is introduced, focusing on both the detailed aspects within image blocks and the boundary information connecting blocks. Experimental results on a liver dataset demonstrate that the model achieves F1 and IoU scores of 88.48% and 79.41%, respectively. Results on the MoNuSeg dataset show comparable high F1 and IoU scores of 79.58% and 66.19%, respectively. The model's accuracy surpasses that of U-Net++ and U-Net models. Compared to other models, this approach is applicable to scenarios with limited datasets, exhibiting high execution efficiency and accuracy.