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This paper proposes a simulated design for a versatile terahertz absorber that can be actively tuned. The absorber utilizes the unique tuning capabilities of graphene and vanadium dioxide, enabling it to alternate between ultra-broadband absorption, broadband absorption, and almost complete reflection. In the metallic phase of vanadium dioxide, coupled with a graphene Fermi level at 0 eV, the absorber achieves ultra-broadband absorption. This spans an extensive frequency range from 3.85 THz to 9.73 THz, exhibiting an absorption rate surpassing 90%. As we shift to the insulating phase of vanadium dioxide and adjust the graphene Fermi level to 1 eV, the absorber operates in a broadband absorption mode. This mode spans 2.98 THz to 4.63 THz, demonstrating an absorption rate exceeding 90%. In the insulating state of vanadium dioxide with a graphene Fermi level at 0 eV, the absorber metamorphoses into a nearly total reflector. Its maximum absorption rate is a mere 0.52%. The unique adjustability of vanadium dioxide and graphene independently enables the fine-tuning of absorption rates for both ultra-broadband and broadband absorption without encountering interference. Additionally, thanks to the central symmetry inherent in the proposed structure, the absorber exhibits insensitivity to alterations in polarization angles and remains stable under a broad range of incident angles. With these benefits, the absorber shows promising potential for applications in electromagnetic stealth, wireless communication, and so on.
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In this paper, we innovatively stack multiple resonant units of photoconductive silicon to design an ultra-broadband metamaterial absorber. By manipulating the conductivity of the silicon with a pump beam, adjustments are made to the amplitude of the wide absorption spectrum spanning 6.6 THz, enabling functional switching from total reflection to near-perfect ultra-broadband absorption. By integrating vanadium dioxide as an intermediary layer, a dual-mode switchable absorber is realized, offering dual control functionalities. Temperature changes enable the absorber to switch between dual-band absorption and ultra-broadband absorption, while variations in pump beam intensity allow for further amplitude adjustments within the absorption spectrum. Impedance matching theory and near-field analysis provide the necessary physical foundation for understanding broadband absorption. Structural parameters, incident angle, and polarization angle of the incident electromagnetic waves are also studied to demonstrate the device's robustness. Our proposed absorbers not only greatly broaden the absorption bandwidth of silicon-based absorbers, but also offer versatility, polarization insensitivity, and robustness over a wide range of incidence angles. Moreover, our design ideas are useful for broadening the bandwidth and enhancing absorption, which enables wider applications in ultra-broadband terahertz absorption and promises extensive prospects.
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BACKGROUND AND AIMS: Recently, metabolic dysfunction-associated steatotic liver disease (MASLD) has been introduced. However, research on this new nomenclature and definition remains limited. This study aims to assess the impact of cardiometabolic risk factors and alcohol consumption on all-cause mortality in MASLD and its subgroups. METHODS AND RESULTS: We included 2408 participants with MASLD in NHANES III and their linked mortality through 2019. MASLD patients were divided into two groups based on alcohol consumption: Pure MASLD and MetALD. The Cox proportional hazard model was used to assess the association between factors and all-cause mortality. During the median 26.0-year follow-up, there were 1040 deaths. The multivariable Cox regression analysis revealed a significant increase of over two-fold in the all-cause mortality rate among patients with four or more cardiometabolic risk factors compared to those with only one. When focusing on each component of cardiometabolic risk factors individually, only diabetes and hypertension were significantly associated with all-cause mortality (p < 0.05). In a subgroup analysis, each additional cardiometabolic factor was linked to an increase in all-cause mortality in both pure MASLD (hazard ratio 1.16; 95% CI 1.06-1.28; p = 0.002) and MetALD (HR 1.77; 95% CI 1.26-2.49; p = 0.001). Notably, an elevation in alcohol consumption was significantly associated with an increase in all-cause mortality rate only in the MetALD (p < 0.001). CONCLUSIONS: This study found that the presence of diabetes or hypertension was significantly associated with all-cause mortality. We also explored the different impacts of these factors and alcohol consumption within MASLD subgroups.
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Consumo de Bebidas Alcoólicas , Fatores de Risco Cardiometabólico , Causas de Morte , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/mortalidade , Medição de Risco , Fatores de Tempo , Adulto , Estados Unidos/epidemiologia , Idoso , Prognóstico , Fígado Gorduroso/mortalidade , Fígado Gorduroso/diagnóstico , Síndrome Metabólica/mortalidade , Síndrome Metabólica/diagnósticoRESUMO
Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs.
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Técnicas de Cultura de Células em Três Dimensões , Vesículas Extracelulares , Células-Tronco , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Técnicas de Cultura de Células em Três Dimensões/métodos , Técnicas de Cultura de Células/métodosRESUMO
In this paper, a dual-band terahertz metamaterial sensor based on aluminum and silicon is proposed and simulated. The aluminum surface, which is deposited on a silicon substrate, is made of a C-shaped frame resonator, a rectangular beam, and a cross. The device is insensitive to the change of incident angle in the range of 0°-30°, which shows the great transmission stability of the sensor. By examining the resonance frequency shift, it is shown that 98.3 and 237.5 GHz/RIU refractive index sensitivity can be obtained near 1.76 and 2.404 THz transmission dips of the proposed structure, respectively. The two dips can be used to sense analytes in different refractive index ranges, respectively. For Dip 1 at 1.76 THz, the range is 1.0-1.6. For Dip 2 at 2.404 THz, the range is 1.6-2.0. Different from traditional multi-band metamaterial sensors, two dips generated by the proposed device can measure continuous and non-multiplexed refractive index ranges, respectively. Because the resonance frequencies of matters are different, such a characteristic enables the device to measure different types of analyte using the appropriate resonant peak. A central-relief design is then proposed based on perturbation theory to further improve its sensing performance. The aluminum cross is covered by polyimide, which can interfere with the scattering field on the metal surface and affect the transmission results. For both transmission dips, the optimized structure realizes higher sensitivities of 111.7 GHz/RIU and 262.5 GHz/RIU, respectively. More significantly, the optimized structure also has the characteristic of a wide and non-multiplexed refractive index range. In addition, the effects of analyte thickness and polyimide layer thickness on sensor performance are also discussed. The proposed structure opens up new prospects in the design of multiple-band terahertz metamaterial sensors. It can also meet the sensing needs of biomedical, environmental monitoring, and industrial manufacturing.
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A tunable dual broadband switchable terahertz absorber based on vanadium dioxide and graphene is proposed. The tunability of graphene and the phase transition properties of vanadium dioxide are used to switch broadband absorption between low-frequency and high-frequency, as well as the absorption rate tuning function. The simulation results indicate that when vanadium dioxide is in the insulating phase and the graphene Fermi energy is 0.7 eV, the absorber achieves low-frequency broadband absorption within the range of 2.6-4.2 THz with an absorptance greater than 90%; when vanadium dioxide is in the metallic phase and the graphene Fermi energy is 0 eV, the absorber achieves high-frequency broadband absorption within the range of 4.9-10 THz with an absorptance greater than 90%. Furthermore, the absorptance can be tuned by adjusting the conductivity of vanadium dioxide or the Fermi energy of graphene. Due to the central symmetry of the proposed structure, the absorber is completely insensitive to polarization. For TE and TM polarized waves, both low and high-frequency broadband absorption are maintained over a range of incident angles from 0° to 50°. The simple structure, tunable absorption rate, insensitivity to polarization angle and incident angle properties are advantages of our proposed absorber. It has broad application prospects in adjustable filters and electromagnetic shielding.
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BACKGROUND: The findings of the association of vaginal flora with preterm birth (PTB) or prelabor rupture of membranes (PROM) were conflicts. Moreover, vaginal flora was different by ethnicity and the evidence from China was limited. METHODS: This study was a nested case control study, based on Yiwu birth cohort. We assessed vaginal microbiota in the second or third trimester, using 16S rDNA Amplicon Sequencing and explored the association between the diversity and composition of vaginal flora and PTB or PROM. RESULTS: We finally included 144 pregnant women. In present study, the alpha diversity of TPROM (Term prelabor rupture of membranes) samples was lower than that of full term samples (Chao1 index: P < 0.05). When we further categorized PTB (Preterm birth) into SPB (PTB without PROM) and PPROM (Preterm prelabor rupture of membranes), there was no difference between SPB and full term. In addition, we found that the proportion of PCoA2 in TPROM group was different from that in full term group and preterm group. The difference between groups was significant according to anosim analysis (R = 0.059, P < 0.001). With LEfSe (Linear discriminant analysis Effect Size) analysis, we found that the abundance of Lactobacillus in the vaginal flora of pregnant women with preterm birth was the highest (P = 0.003). CONCLUSION: In Chinese pregnant women, the alpha diversity in TPROM group was significantly lower than that in both PTB and full term group. However, there was no difference between PTB and full term. Lactobacillus was the most abundant in preterm birth group. More studies should be conducted to confirm our findings.
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Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Vagina , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos de Casos e Controles , Ruptura Prematura de Membranas Fetais/epidemiologia , Terceiro Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Vagina/microbiologiaRESUMO
A functionally tunable and absorption-tunable terahertz (THz) metamaterial absorber based on vanadium dioxide (VO2) and graphene is proposed and verified numerically. Based on phase transition properties of VO2 and tunability of graphene, the switching performance between ultra-broadband and narrow-band near-perfect absorption can be achieved. We simulate and analyze the characteristics of the constructed model by finite element analysis. Theoretical calculations show that when VO2 is in the metallic state and the graphene Fermi energy is 0 eV, the designed absorber can perform ultra-broadband absorption. The absorber achieves greater than 95% absorption in the 2.85 - 10THz range. When VO2 is in the insulating state and the graphene Fermi energy is 0.7 eV, more than 99.5% absorption can be achieved at 2.3 THz. The absorption rate can be tuned by changing the conductivity of VO2 and the Fermi energy of graphene. Moreover, the proposed absorber displays good polarization insensitivity and wide incident angle stability. The design may have potential applications in terahertz imaging, sensing, electromagnetic shielding and so on.
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BACKGROUND: Spirometry quality assurance is a challenging task across levels of healthcare tiers, especially in primary care. Deep learning may serve as a support tool for enhancing spirometry quality. We aimed to develop a high accuracy and sensitive deep learning-based model aiming at assisting high-quality spirometry assurance. METHODS: Spirometry PDF files retrieved from one hospital between October 2017 and October 2020 were labeled according to ATS/ERS 2019 criteria and divided into training and internal test sets. Additional files from three hospitals were used for external testing. A deep learning-based model was constructed and assessed to determine acceptability, usability, and quality rating for FEV1 and FVC. System warning messages and patient instructions were also generated for general practitioners (GPs). RESULTS: A total of 16,502 files were labeled. Of these, 4592 curves were assigned to the internal test set, the remaining constituted the training set. In the internal test set, the model generated 95.1%, 92.4%, and 94.3% accuracy for FEV1 acceptability, usability, and rating. The accuracy for FVC acceptability, usability, and rating were 93.6%, 94.3%, and 92.2%. With the assistance of the model, the performance of GPs in terms of monthly percentages of good quality (A, B, or C grades) tests for FEV1 and FVC was higher by ~ 21% and ~ 36%, respectively. CONCLUSION: The proposed model assisted GPs in spirometry quality assurance, resulting in enhancing the performance of GPs in quality control of spirometry.
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Aprendizado Profundo , Volume Expiratório Forçado , Humanos , Controle de Qualidade , Testes de Função Respiratória , Espirometria , Capacidade VitalRESUMO
This was to study the application value of fibrinogen (FIB), D-dimer (D-D), and mean platelet volume (MPV) in the prediction of vascular re-occlusion (VRO) after intravenous thrombolysis (IVT) in patients with acute cerebral infarction (ACI). 114 patients with ACI were retrospectively included as the research objects and then were divided into the improvement group (66 cases) and the progressive group (48 cases). A multivariate Logistic regression model was applied to analyze the independent risk factors of VRO after IVT. The receiver operator characteristic (ROC) curve was also adopted to assess the predictive value of relevant factors for VRO after IVT. In addition, the expression of p53, bax and bcl-2 genes was investigated in patients with acute cerebral infarction and healthy people by real-time PCR. As a result, MPV, FIB, and D-D levels of venous blood in the improvement group were remarkably lower than those in the progressive group (P<0.05). The regression coefficients between MPV, FIB, D-D at admission and VRO after IVT were 0.411, 0.362, and 0.391, respectively, so there was a significant positive correlation (P<0.05). The combined prediction model of MPV, FIB, and D-D had greater sensitivity, specificity, and area under the curve (AUC) in predicting the risk of VRO after IVT than single MPV, FIB, or D-D, showing differences of statistical significance (P<0.05). In conclusion, MPV, FIB, and D-D in venous blood at admission were independent risk factors for the VRO after IVT. The combined model of MPV, FIB, and D-D had an excellent predictive performance on the risk of VRO after IVT. The expression level of genes p53 and bax was 4.5 and 3 times higher in patients than in controls, respectively. The expression of gene bcl-2 decreased (0.75 times) in patients (P<0.001).
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Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Volume Plaquetário Médio , Fibrinogênio/genética , Fibrinogênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Estudos Retrospectivos , Infarto Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversosRESUMO
Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.
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Injúria Renal Aguda , Exossomos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Cisplatino , Exossomos/metabolismo , Humanos , Neutrófilos , Cordão Umbilical/metabolismoRESUMO
BACKGROUND: Due to the similar symptoms of upper airway obstruction to asthma, misdiagnosis is common. Spirometry is a cost-effective screening test for upper airway obstruction and its characteristic patterns involving fixed, variable intrathoracic and extrathoracic lesions. We aimed to develop a deep learning model to detect upper airway obstruction patterns and compared its performance with that of lung function clinicians. METHODS: Spirometry records were reviewed to detect the possible condition of airway stenosis. Then they were confirmed by the gold standard (e.g., computed tomography, endoscopy, or clinic diagnosis of upper airway obstruction). Images and indices derived from flow-volume curves were used for training and testing the model. Clinicians determined cases using spirometry records from the test set. The deep learning model evaluated the same data. RESULTS: Of 45,831 patients' spirometry records, 564 subjects with curves suggesting upper airway obstruction, after verified by the gold standard, 351 patients were confirmed. These cases and another 200 cases without airway stenosis were used as the training and testing sets. 432 clinicians evaluated 20 cases of each of the three patterns and 20 no airway stenosis cases (n = 80). They assigned an accuracy of 41.2% (±15.4) (interquartile range: 27.5-52.5%), with poor agreements (κ = 0.12). For the same cases, the model generated a correct detection of 81.3% (p < 0.0001). CONCLUSIONS: Deep learning could detect upper airway obstruction patterns from other classic patterns of ventilatory defects with high accuracy, whereas clinicians presented marked errors and variabilities. The model may serve as a support tool to enhance clinicians' correct diagnosis of upper airway obstruction using spirometry.
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Obstrução das Vias Respiratórias , Asma , Aprendizado Profundo , Transtornos Respiratórios , Obstrução das Vias Respiratórias/diagnóstico , Asma/diagnóstico , Constrição Patológica , Humanos , EspirometriaRESUMO
OBJECTIVE: We evaluated the levels of sex hormones in male hepatitis B patients co-infected with Clonorchis sinensis (C. sinensis). METHODS: A total of 136 male individuals were enrolled in this study, including 27 healthy controls, 28 patients with C. sinensis mono-infection, 19 patients with only chronic hepatitis B, 18 patients with post-hepatitis B liver cirrhosis, 26 chronic hepatitis B patients co-infected with C. sinensis, and 18 post-hepatitis B liver cirrhosis patients coinfected with C. sinensis. Serum levels of progesterone (P), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), and follicle stimulating hormone (FSH) in these groups were measured. RESULTS: The results showed that compared with the LC group, the LC+ C. sinensis co-infected group had an increase in E2 but decrease in T and FSH. The levels of E2 in CHB+ C. sinensis co-infected patients were significantly higher than those in CHB mono-infected patients, but the significantly lower levels of T were observed. Compared with HCs group, the LC group showed significant increase in all terms of sex hormones, except PRL. By contrast, the CHB mono-infected group presented an apparent decrease in E2, T, and PRL than the HCs group. However, there were no significant differences in sex hormone levels between the C. sinensis mono-infected patients and HCs. CONCLUSION: This study suggests that C. sinensis co-infection aggravates the sex hormone disturbance in HBV patients at both chronic hepatitis and cirrhosis stages, providing evidences for potential strategies in disease prevention and treatment.
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Clonorchis sinensis , Coinfecção , Hepatite B Crônica , Hepatite B , Animais , Coinfecção/epidemiologia , Hormônio Foliculoestimulante , Hormônios Esteroides Gonadais , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática , Masculino , ProlactinaRESUMO
A compact temperature-refractive index (RI) flat photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) is presented in this paper. Sensing of temperature and RI takes place in the x- and y- polarization, respectively, to avoid the sensing crossover, eliminating the need for matrix calculation. Simultaneous detection of dual parameters can be implemented by monitoring the loss spectrum of core modes in two polarizations. Compared with the reported multi-function sensors, the designed PCF sensor provides higher sensitivities for both RI and temperature detection. A maximum wavelength sensitivity of -5 nm/°C is achieved in the temperature range of -30-40 °C. An excellent optimal wavelength sensitivity of 17,000 nm/RIU is accomplished in the RI range of 1.32-1.41. The best amplitude sensitivity of RI is up to 354.39 RIU-1. The resolution of RI and temperature sensing is 5.88 × 10-6 RIU and 0.02 °C, respectively. The highest value of the figure of merit (FOM) is 216.74 RIU-1. In addition, the flat polishing area of the gold layer reduces the manufacturing difficulty. The proposed sensor has the characteristics of high sensitivity, simple structure, good fabrication repeatability, and flexible operation. It has potential in medical diagnosis, chemical inspection, and many other fields.
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BACKGROUND: Small plateau (SP) on the flow-volume curve was found in parts of patients with suspected asthma or upper airway abnormalities, but it lacks clear scientific proof. Therefore, we aimed to characterize its clinical features. METHODS: We involved patients by reviewing the bronchoprovocation test (BPT) and bronchodilator test (BDT) completed between October 2017 and October 2020 to assess the characteristics of the sign. Patients who underwent laryngoscopy were assigned to perform spirometry to analyze the relationship of the sign and upper airway abnormalities. SP-Network was developed to recognition of the sign using flow-volume curves. RESULTS: Of 13,661 BPTs and 8,168 BDTs completed, we labeled 2,123 (15.5%) and 219 (2.7%) patients with the sign, respectively. Among them, there were 1,782 (83.9%) with the negative-BPT and 194 (88.6%) with the negative-BDT. Patients with SP sign had higher median FVC and FEV1% predicted (both P < .0001). Of 48 patients (16 with and 32 without the sign) who performed laryngoscopy and spirometry, the rate of laryngoscopy-diagnosis upper airway abnormalities in patients with the sign (63%) was higher than those without the sign (31%) (P = 0.038). SP-Network achieved an accuracy of 95.2% in the task of automatic recognition of the sign. CONCLUSIONS: SP sign is featured on the flow-volume curve and recognized by the SP-Network model. Patients with the sign are less likely to have airway hyperresponsiveness, automatic visualizing of this sign is helpful for primary care centers where BPT cannot available.
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Asma/diagnóstico , Testes de Provocação Brônquica/estatística & dados numéricos , Testes de Provocação Brônquica/normas , Volume Expiratório Forçado , Laringoscopia/normas , Adolescente , Adulto , Testes de Provocação Brônquica/métodos , Criança , China , Aprendizado Profundo , Feminino , Humanos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espirometria , Adulto JovemAssuntos
Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Fígado Gorduroso , Masculino , Feminino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Índice de Gravidade de Doença , AdultoRESUMO
The study was aimed to compare the satiating effect of various protein hydrolysates in rats and examine the underlying mechanism associated with the satiety hormones. Food intake and portal satiety hormone levels were measured in rats. Enteroendocrine cell-lines were employed to study the direct effect of protein hydrolysates on gut hormone secretions. The results showed that oral preload of wheat gluten hydrolysate (WGH) suppressed food intake greater and longer than other hydrolysates. The portal peptide-YY levels in WGH-treated rats at 2 h and 3 h were higher than those in control- and lactalbumin hydrolysate (LAH)-treated rats. In a distal enteroendocrine cell model, WGH more potently stimulated glucagon-like peptide-1 secretion than LAH, and the effect was largely enhanced by pepsin/pancreatin digestion of WGH. These results suggest WGH is potent in activating enteroendocrine cells to release satiety hormones leading to the prolonged suppression of food intake.
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Comportamento Alimentar/efeitos dos fármacos , Glutens/farmacologia , Peptídeo YY/metabolismo , Triticum/química , Animais , Linhagem Celular , Células Enteroendócrinas/efeitos dos fármacos , Hormônios Gastrointestinais/sangue , Hormônios Gastrointestinais/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glutens/metabolismo , Hidrólise , Masculino , Camundongos , Pancreatina/metabolismo , Pepsina A/metabolismo , Ratos Wistar , Saciação/efeitos dos fármacosRESUMO
BACKGROUND: Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer's disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. RESULTS: PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. CONCLUSION: PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.
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Doença de Alzheimer , Panax notoginseng , Saponinas , Humanos , Camundongos , Animais , Lactente , Panax notoginseng/química , Saponinas/farmacologia , Mitofagia , Estresse Oxidativo , Encéfalo/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , RNA Mensageiro/metabolismoRESUMO
Extracellular vesicles (EVs) are minute sacs released by cells into the extracellular milieu, harboring an array of biomolecules including proteins, nucleic acids, and lipids. Notably, a large number of studies have demonstrated the important involvement of EVs in both physiological and pathological aspects of renal function. EVs can facilitate communication between different renal cells, but it is important to recognize their dual role: they can either transmit beneficial information or lead to renal damage and worsening of existing conditions. The composition of EVs in the context of the kidneys offers valuable insights into the intricate mechanisms underlying specific renal functions or disease states. In addition, mesenchymal stem cell-derived EVs have the potential to alleviate acute and chronic kidney diseases. More importantly, the innate nanoparticle properties of EVs, coupled with their engineering potential, make them effective tools for drug delivery and therapeutic intervention. In this review, we focus on the intricate biological functions of EVs in the kidney. In addition, we explore the emerging role of EVs as diagnostic tools and innovative therapeutic agents in a range of renal diseases.
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Vesículas Extracelulares , Nefropatias , Rim , Humanos , Vesículas Extracelulares/metabolismo , Animais , Rim/metabolismo , Rim/fisiopatologia , Rim/patologia , Nefropatias/terapia , Nefropatias/fisiopatologia , Nefropatias/metabolismo , Sistemas de Liberação de MedicamentosRESUMO
BACKGROUND: Early identification and management of pediatric type 2 diabetes mellitus (T2DM) is crucial for improving long-term outcomes. This study aimed to assess if the severity of T2DM at presentation, inferred by the location of treatment initiation (inpatient or outpatient), influences long-term clinical outcomes. METHODS: A retrospective chart review was conducted on 116 pediatric T2DM patients. Data on treatment initiation location, initial and subsequent glycated hemoglobin (HbA1c) levels, prescribed insulin, and body mass index were collected from electronic medical records. RESULTS: Of the 116 patients, 69 were initially treated in an inpatient setting, and 47 received outpatient treatment. At treatment initiation, the inpatient group had significantly higher HbA1c levels compared to the outpatient group (p < .001), but 3 years after treatment initiation, no significant difference in HbA1c was observed between the two groups (p = .057). Prescribed insulin dosages were higher in the inpatient group at treatment initiation (p < .001) and remained higher after 3 years (p < 0.003) compared to the outpatient group. CONCLUSIONS: Pediatric patients initially treated in an inpatient setting had poorer glycemic control and higher prescribed insulin dosing at baseline. After 3 years, there was no significant difference in HbA1c levels, but patients treated as inpatients continued to have higher prescribed insulin. These findings suggest that the severity of diabetes at initial presentation may affect long-term clinical outcomes in children with T2DM.