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Type 2 diabetes (T2D) is associated with insulin resistance and progressive dysfunction of ß-pancreatic cells, leading to persistent hyperglycemia. Macrophages play a crucial role in this context, influencing both the development and progression of insulin resistance. These innate immune cells respond to inflammatory stimuli and reprogram their metabolism, directly impacting the pathophysiology of T2D. Macrophages are highly plastic and can adopt either pro-inflammatory or pro-resolutive phenotypic profiles. In T2D, pro-inflammatory macrophages, which rely on glycolysis, exacerbate insulin resistance through increased production of pro-inflammatory cytokines and nitric oxide. In contrast, pro-resolutive macrophages, which prioritize fatty acid metabolism, have different effects on glucose homeostasis. Metaflammation, a chronic low-grade inflammation, is induced by pro-inflammatory macrophages and significantly contributes to the progression of T2D, creating an environment conducive to metabolic dysfunction. This review aims to clarify the contribution of macrophages to the progression of T2D by detailing how their inflammatory responses and metabolic reprogramming influence insulin resistance and the disease's pathophysiology. The review seeks to deepen the understanding of the biochemical and metabolic mechanisms involved, offering broader insights into the impact on the quality of life for millions of patients worldwide.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Macrófagos , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Inflamação/metabolismo , Animais , Reprogramação Celular , Reprogramação MetabólicaRESUMO
2D dilute magnetic semiconductors (DMS) based on transition metal dichalcogenides (TMD) offer an innovative pathway for advancing spintronic technologies, including the potential to exploit phenomena such as the valley Zeeman effect. However, the impact of magnetic ordering on the valley degeneracy breaking and on the enhancement of the optical transitions g-factors of these materials remains an open question. Here, a giant effective g-factors ranging between ≈-27 and -69 for the bound exciton at 4 K in vanadium-doped WSe2 monolayers, obtained through magneto-photoluminescence (PL) experiments is reported. This giant g-factor disappears at room temperature, suggesting that this response is associated with a magnetic ordering of the vanadium impurity states at low temperatures. Ab initio calculations for the vanadium-doped WSe2 monolayer confirm the existence of magnetic ordering of the vanadium states, which leads to degeneracy breaking of the valence bands at K and K'. A phenomenological analysis is employed to correlate this splitting with the measured enhanced effective g-factor. The findings shed light on the potential of defect engineering of 2D materials for spintronic applications.
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Each collective trauma holds its own particularities and forms of horror. When the violence is exerted by the government responsible for the care of the population it is termed state terrorism. The traumatic experience and its subsequent negation create a profound dissociation between two narratives: the explicit, which conceals the true facts, and the implicit, which remains unconscious and unbridgeable. In the gap between the two, life becomes suspended. From a Jungian perspective, this can be understood as the interruption of the process of translation and integration (terms that I will explore in some depth) from implicit sensory phenomena to an explicit representational narrative. This profoundly affects the development of the ego-self axis. In turn, it creates a special challenge for analytic technique that calls for new ways of listening to, and meeting the patient in, that non-verbal, unrepresented territory. Drawing upon clinical material, an embodied perspective of Jungian clinical work is offered to show how the inclusion of the body of patient and analyst enables access to the non-represented, though implicitly encoded, traumatic affective memories stored in the somatic unconscious.
Chaque traumatisme collectif a ses particularités et ses formes d'horreur. Lorsque la violence est exercée par le gouvernement responsable de la prise en charge de la population, on parle de terrorisme d'État. L'expérience traumatique et sa négation ultérieure créent une dissociation profonde entre deux récits : l'explicite, qui dissimule les faits réels, et l'implicite, qui reste inconscient et insurmontable. Dans l'écart entre les deux, la vie est suspendue. D'un point de vue jungien, cela peut être compris comme l'interruption du processus de «traduction et d'intégration¼ (termes que j'explorerai plus en profondeur) des phénomènes sensoriels implicites à un récit représentationnel explicite. Cela affecte profondément le développement de l'axe egosoi. En conséquence, cela crée un défi particulier pour la technique analytique et invite à de nouvelles façons d'écouter et de rencontrer le patient dans ce territoire non verbal et non représenté. En s'appuyant sur le matériel clinique, une perspective incarnée du travail clinique jungien est proposée. Il s'agit de montrer qu'inclure les corps du patient et de l'analyste permet d'accéder à ce qui n'est pas représenté, par le biais de mémoires affectives traumatiques implicitement encodées et stockées dans l'inconscient somatique.
Cada trauma colectivo tiene sus propias particularidades y formas del horror. Cuando la violencia es ejercida por el gobierno responsable del cuidado de la población se denomina Terrorismo de Estado. La experiencia traumática y su posterior negación crean una profunda disociación entre dos narrativas: la explícita, que oculta los verdaderos hechos, y la implícita, que permanece inconsciente e inabordable. En la brecha entre ambas, la vida queda suspendida. Desde una perspectiva Junguiana, dicha suspensión puede entenderse como la interrupción en el proceso de "traslación e integración" (términos que exploraré con cierta profundidad) de los fenómenos sensoriales implícitos en una narrativa representacional explícita, afectando profundamente el desarrollo del eje egoself. A su vez, crea un desafío especial para la técnica analítica que exige nuevas formas de escuchar y encontrarse con el paciente en ese territorio noverbal y norepresentado. A partir de material clínico, se ofrece una perspectiva somática del trabajo clínico Junguiano para mostrar cómo la inclusión del cuerpo de paciente y analista posibilita el acceso a estados norepresentados, a través de memorias afectivas traumáticas codificadas implícitamente y almacenadas en el inconsciente somático.
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Imaginação , Terapia Psicanalítica , Terrorismo , Humanos , Terapia Psicanalítica/métodos , Terrorismo/psicologia , Teoria Junguiana , Trauma Psicológico/terapia , Trauma Psicológico/psicologia , Adulto , Vítimas de Crime/psicologia , Inconsciente PsicológicoRESUMO
MXenes are the newest class of two-dimensional nanomaterials characterized by large surface area, high conductivity, and hydrophilicity. To further improve their performance for use in energy storage devices, heteroatoms or functional groups can be inserted into the Mxenes' structure increasing their stability. This work proposes insertion of lanthanum atoms into niobium-MXene (Nb-MX/La) that was characterized in terms of morphogy, structure, and electrochemical behavior. The addition of La to the Nb-MXene structure was essential to increase the spacing between the layers, improving the interaction with the electrolyte and enabling charge/discharge cycling in a higher potential window and at higher current densities. Nb-MX/La achieved a specific capacitance of up to 157 mF cm-2, a specific capacity of 42 mAh cm-2 at 250 mV s-1, a specific power of 37.5 mW cm-2, and a specific energy of 14.1 mWh cm-2 after 1000 charge/discharge cycles at 50 mA cm-2.
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Several studies have demonstrated that low-dimensional structures (e.g., two-dimensional (2D)) associated with three-dimensional (3D) perovskite films enhance the efficiency and stability of perovskite solar cells. Here, we aim to track the formation sites of the 2D phase on top of the 3D perovskite and to establish correlations between molecular stiffness and steric hindrance of the organic cations and their influence on the formation and crystallization of 2D/3D. Using cathodoluminescence combined with a scanning electron microscopy technique, we verified that the formation of the 2D phase occurs preferentially on the grain boundaries of the 3D perovskite. This helps explain some passivation mechanisms conferred by the 2D phase on 3D perovskite films. Furthermore, by employing in situ grazing-incidence wide-angle X-ray scattering, we monitored the formation and crystallization of the 2D/3D perovskite using three cations with varying molecular stiffness. In this series of molecules, the formation and crystallization of the 2D phase are found to be dependent on both steric hindrance around the ammonium group and molecular stiffness. Finally, we employed a 2D/3D perovskite heterointerface in a solar cell. The presence of the 2D phase, particularly those formed from flexible cations, resulted in a maximum power conversion efficiency of 21.5%. This study provides insight into critical aspects related to how bulky organic cations' stiffness and steric hindrance influence the formation, crystallization, and distribution of 2D perovskite phases.
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Cortical organoids derived from human induced pluripotent stem cells (hiPSCs) represent a powerful in vitro experimental system to investigate human brain development and disease, often inaccessible to direct experimentation. However, despite steady progress in organoid technology, several limitations remain, including high cost and variability, use of hiPSCs derived from tissues harvested invasively, unexplored three-dimensional (3D) structural features and neuronal connectivity. Here, using a cost-effective and reproducible protocol as well as conventional two-dimensional (2D) immunostaining, we show that cortical organoids generated from hiPSCs obtained by reprogramming stem cells from human exfoliated deciduous teeth (SHED) recapitulate key aspects of human corticogenesis, such as polarized organization of neural progenitor zones with the presence of outer radial glial stem cells, and differentiation of superficial- and deep-layer cortical neurons and glial cells. We also show that 3D bioprinting and magnetic resonance imaging of intact cortical organoids are alternative and complementary approaches to unravel critical features of the 3D architecture of organoids. Finally, extracellular electrical recordings in whole organoids showed functional neuronal networks. Together, our findings suggest that SHED-derived cortical organoids constitute an attractive model of human neurodevelopment, and support the notion that a combination of 2D and 3D techniques to analyze organoid structure and function may help improve this promising technology.
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Córtex Cerebral , Polpa Dentária , Células-Tronco Pluripotentes Induzidas , Organoides , Humanos , Organoides/fisiologia , Organoides/citologia , Polpa Dentária/citologia , Polpa Dentária/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Neurônios/citologia , Neurônios/fisiologiaRESUMO
We study the role of underlying substrates on interfacial heat transfer within supported graphene nanochannels. Due to graphene's translucency, the underlying substrate, apart from its known hydrodynamic impact on fluid flow, also influences heat transport. We introduce the term "thermal translucency" to describe this phenomenon in the context of interfacial heat transfer. Our findings reveal that the Kapitza resistance, RK, is dependent on the specific underlying substrate. The specific underlying substrate alters the water-graphene interface potential landscape due to graphene's translucency, leading to a breakdown in the inverse relationship between interfacial water density peaks and RK values, typically observed at water-graphene and water-graphite interfaces. Remarkably, higher interfacial water density peaks correlate with more ordered energy patterns, not necessarily tied to more hydrophilic substrates as the literature commonly suggests for lower RK values. The insights provided have implications for controlling and tuning thermal transport and heat storage in nanofluidic devices.
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BACKGROUND: Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility. METHODS: A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA. RESULTS: Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic ß cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur. CONCLUSIONS: LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic ß-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture. PLAIN LANGUAGE SUMMARY: In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.
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PURPOSE: To introduce a computational tool for peri-interventional intracranial aneurysm treatment guidance that maps preoperative planning information from simulation onto real-time X-Ray imaging. METHODS: Preoperatively, multiple flow diverter (FD) devices are simulated based on the 3D mesh of the vessel to treat, to choose the optimal size and location. In the peri-operative stage, this 3D information is aligned and mapped to the continuous 2D-X-Ray scan feed from the operating room. The current flow diverter position in the 3D model is estimated by automatically detecting the distal FD marker locations and mapping them to the treated vessel. This allows to visually assess the possible outcome of releasing the device at the current position, and compare it with the one chosen pre-operatively. RESULTS: The full pipeline was validated using retrospectively collected biplane images from four different patients (5 3D-DSA datasets in total). The distal FD marker detector obtained an average F1-score of 0.67 ( ± 0.224 ) in 412 2D-X-Ray scans. After aligning 3D-DSA + 2D-X-Ray datasets, the average difference between simulated and deployed positions was 0.832 mm ( ± 0.521 mm). Finally, we qualitatively show that the proposed approach is able to display the current location of the FD compared to their pre-operatively planned position. CONCLUSIONS: The proposed method allows to support the FD deployment procedure by merging and presenting preoperative simulation information to the interventionists, aiding them to make more accurate and less risky decisions.
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Silicon-based two-dimensional (2D) materials have garnered significant attention due to their unique properties and potential applications in electronics, optoelectronics, and other advanced technologies. Here, we present a comprehensive investigation of a novel silicon allotrope, Popsilicene (Pop-Si), derived from the structure of Popgraphene. Using density functional theory and ab initio molecular dynamics simulations, we explore the thermal stability, mechanical and electronic properties, and optical characteristics of Pop-Si. Our results demonstrate that Pop-Si exhibits good thermal stability at 1000 K. Electronic structure calculations reveal that Pop-Si is metallic, with a high density of states at the Fermi level. Furthermore, our analysis of the optical properties indicates that Pop-Si has pronounced UV-Vis optical activity, making it a promising candidate for optoelectronic devices. Mechanical property assessments show that Pop-Si has Young's modulus ranging from 10 to 92 GPa and a Poisson's ratio of 0.95. These results combined suggest its potential for practical applications.
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Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal Toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulated NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, and the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and we evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced the activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased the secretion of seven cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.
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Imiquimode , Células Matadoras Naturais , Ativação Linfocitária , Poli I-C , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Toll-Like , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Poli I-C/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Imiquimode/farmacologia , Receptores Toll-Like/metabolismo , Receptores Toll-Like/agonistas , Criança , Oligodesoxirribonucleotídeos/farmacologia , Citocinas/metabolismo , Feminino , Interferon gama/metabolismo , Masculino , Imidazóis/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Pré-Escolar , Agonistas do Receptor Semelhante a TollRESUMO
Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.
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BACKGROUND: The newly discovered CircUBE2D2 has been shown to abnormally upregulate and promote cancer progression in a variety of cancers. The present study explored circUBE2D2 (hsa_circ_0005728) in Ovarian Cancer (OC) progression. METHODS: CircUBE2D2, miR-885-5p, and HMGB1 were examined by RT-qPCR or WB. SKOV-3 cell functions (including cell viability, apoptosis, migration, and invasion) were validated using the CCK-8, flow cytometry, scratch assay, and transwell assay, respectively. The direct relationship between miR-885-5p and circUBE2D2 or HMGB1 was confirmed by a dual-luciferase reporter and RNA pull-down analysis. circUBE2D2's role in vivo tumor xenograft experiment was further probed. RESULTS: OC tissue and cell lines had higher circUBE2D2 and HMGB1 and lower miR-885-5p. Mechanically, CircUBE2D2 shared a binding relation with miR-885-5p, while miR-885-5p can directly target HMGB1. Eliminating circUBE2D2 or miR-885-5p induction inhibited OC cell activities. However, these functions were relieved by down-regulating miR-885-5p or HMGB1 induction. Furthermore, circUBE2D2 knockout reduced tumor growth. CONCLUSION: CircUBE2D2 regulates the expression of HMGB1 by acting as a sponge of ceRNA as miR-885-5p, thereby promoting the control of OC cell proliferation and migration and inhibiting cell apoptosis. Targeting CircUBE2D2 could serve as a new potential treatment strategy for OC.
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Apoptose , Proteína HMGB1 , MicroRNAs , Neoplasias Ovarianas , RNA Circular , Animais , Feminino , Humanos , Camundongos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , RNA Circular/genéticaRESUMO
Resonating valence bond (RVB) states are fundamental for understanding quantum spin liquids in two-dimensional (2D) systems. The RVB state is a collective phenomenon in which spins are uncoupled. 2D lattices such as triangular, honeycomb, and dice lattices were investigated using the Hubbard model and exact diagonalization method. We analyzed the total spin, spin-spin correlation functions, local magnetic moments, and spin and charge gaps as a function of on-site Coulomb repulsion, electron concentration, and electronic hopping parameters. Phase diagrams showed that RVB states can live in half-filled and hole-doped anisotropic triangular lattices. We found two types of RVB states: one in the honeycomb sublattice and the other in the centered hexagons in the triangular lattices. Owing to the novel discovery of exotic magnetic ordering in triangular moiré patterns in twisted bilayer graphene and transition metal dichalcogenide systems, our results provide physical insights into the onset of magnetism and possible spin liquid states in these layered materials.
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BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. RESULTS: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cellsãMacrophages M2ãCD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. CONCLUSIONS: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.
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Biomarcadores Tumorais , Neoplasias , Microambiente Tumoral , Enzimas de Conjugação de Ubiquitina , Humanos , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Imunoterapia , Feminino , Melanoma/genética , Melanoma/imunologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Antígeno CTLA-4/genética , Neoplasias Uveais , Antígeno B7-H1RESUMO
This study aimed to characterize the population pharmacokinetics of sertraline in Mexican patients with psychiatric and substance use disorders. Fifty-nine patients (13 to 76 years old) treated with doses of sertraline between 12.5 and 100 mg/day were included. Plasma sertraline concentrations were determined in blood samples and five of the main substances of abuse were determined by rapid tests in urine samples. Demographic, clinical, and pharmacogenetic factors were also evaluated. Population pharmacokinetic analysis was performed using NONMEM software with first-order conditional estimation method. A one-compartment model with proportional residual error adequately described the sertraline concentrations versus time. CYP2D6*2 polymorphism and CYP2C19 phenotypes significantly influenced sertraline clearance, which had a population mean value of 66 L/h in the final model. The absorption constant and volume of distribution were fixed at 0.855 1/h and 20.2 L/kg, respectively. The model explained 11.3% of the interindividual variability in sertraline clearance. The presence of the CYP2D6*2 polymorphism caused a 23.1% decrease in sertraline clearance, whereas patients with intermediate and poor phenotype of CYP2C19 showed 19.06% and 48.26% decreases in sertraline clearance, respectively. The model was internally validated by bootstrap and visual predictive check. Finally, stochastic simulations were performed to propose dosing regimens to achieve therapeutic levels that contribute to improving treatment response.
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Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2D6 , Sertralina , Transtornos Relacionados ao Uso de Substâncias , Humanos , Sertralina/farmacocinética , Sertralina/uso terapêutico , Sertralina/sangue , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Idoso , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Adolescente , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Transtornos Relacionados ao Uso de Substâncias/sangue , Adulto Jovem , Modelos Biológicos , Transtornos Mentais/tratamento farmacológico , Polimorfismo Genético , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/sangue , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , México , Antidepressivos/farmacocinética , Antidepressivos/uso terapêutico , Antidepressivos/sangueRESUMO
During nematode surveys of natural vegetation in forests of La Cima de Copey de Dota, San José, San José province, Costa Rica, a Xenocriconemella species closely resembling X. macrodora and related species was found. Integrative taxonomical approaches demonstrated that it is a new species described herein as X. costaricense sp. nov. The new species is parthenogenetic (only females have been detected) and characterised by a short body (276-404 µm); lip region with two annuli, not offset, not separated from body contour; first lip annulus partially covering the second lip annulus. Stylet thin, very long (113-133 µm) and flexible, occupying 30.5-47.8% of body length. Excretory pore located from one or two annuli anterior to one or two annuli posterior to level of stylet knobs, at 42 (37-45) µm from anterior end. Female genital tract monodelphic, prodelphic, outstretched, and occupying 35-45% of body length, with vagina slightly ventrally curved (14-18 µm long). Anus located 6-11 annuli from the tail terminus. Tail conoid and bluntly rounded terminus, the last 2-3 annuli oriented dorsally. Results of molecular characterisation and phylogenetic analyses of D2-D3 expansion segments of 28S rRNA, ITS, and partial 18S rRNA, as well as cytochrome oxidase c subunit 1 gene sequences further characterised the new species and clearly separated it from X. macrodora and other related species (X. iberica, X. paraiberica, and X. pradense).
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Filogenia , Animais , Costa Rica , Feminino , Masculino , Nematoides/classificação , Nematoides/anatomia & histologia , Nematoides/genética , DNA Ribossômico/genética , RNA Ribossômico 28S/genética , DNA de Helmintos/genética , Florestas , Análise de Sequência de DNARESUMO
The development of engineered nanomaterials has been considered a promising strategy to control oral infections. In this study, silver-embedded carbon nitrides (Ag@g-CN) were synthesized and tested against Candida albicans, investigating their antifungal action and biocompatibility in animal cells. Ag@g-CN was synthesized by a simple one-pot thermal polymerization technique and characterized by various analytical techniques. X-ray diffraction (XRD) analysis revealed slight alterations in the crystal structure of g-CN upon the incorporation of Ag. Fourier transform infrared (FT-IR) spectroscopy confirmed the presence of Ag-N bonds, indicating successful silver incorporation and potential interactions with g-CN's amino groups. UV-vis spectroscopy demonstrated a red shift in the absorption edge of Ag@g-CN compared with g-CN, attributed to the surface plasmon resonance effect of silver nanoparticles. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) confirmed the 2D layered sheet like morphology of both materials. The Ag 3d peaks found in X-ray photoelectron spectroscopy (XPS) confirmed the presence of metallic Ag0 nanoparticles in Ag@g-CN. The Ag@g-CN materials exhibited high antifungal activity against reference and oral clinical strains of C. albicans, with minimal inhibitory concentration (MIC) ranges between 16-256 µg/mL. The mechanism of Ag@g-CN on C. albicans was attributed to the disruption of the membrane integrity and disturbance of the biofilm. In addition, the Ag@g-CN material showed good biocompatibility in the fibroblastic cell line and in Galleria mellonella, with no apparent cytotoxicity observed at a concentration up to 1000 µg/mL. These findings demonstrate the potential of the Ag@g-CN material as an effective and safe antifungal agent for the treatment of oral fungal infections.
Assuntos
Antifúngicos , Candida albicans , Nanopartículas Metálicas , Prata , Candida albicans/efeitos dos fármacos , Prata/química , Prata/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Animais , Testes de Sensibilidade Microbiana , Compostos de Nitrogênio/química , Compostos de Nitrogênio/farmacologia , Compostos de Nitrogênio/toxicidade , Camundongos , NitrilasRESUMO
In this paper, we investigate the optical, electronic, vibrational, and excitonic properties of four two-dimensional ß -pnictogen materials-nitrogenene, phosphorene, arsenene, and antimonene-via density functional theory calculations and the Bethe-Salpeter equation. These materials possess indirect gaps with significant exciton binding energies, demonstrating isotropic behavior under circular light polarization and anisotropic behavior under linear polarization by absorbing light within the visible solar spectrum (except for nitrogenene). Furthermore, we observed that Raman frequencies red-shift in heavier pnictogen atoms aligning with experimental observations; simultaneously, quasi-particle effects notably influence the linear optical response intensively. These monolayers' excitonic effects lead to optical band gaps optimized for solar energy harvesting, positioning them as promising candidates for advanced optoelectronic device applications.
RESUMO
This work reports the development of an efficient and precise indoor positioning system utilizing two-dimensional (2D) light detection and ranging (LiDAR) technology, aiming to address the challenging sensing and positioning requirements of the beyond fifth-generation (B5G) mobile networks. The core of this work is the implementation of a 2D-LiDAR system enhanced by an artificial neural network (ANN), chosen due to its robustness against electromagnetic interference and higher accuracy over traditional radiofrequency signal-based methods. The proposed system uses 2D-LiDAR sensors for data acquisition and digital filters for signal improvement. Moreover, a camera and an image-processing algorithm are used to automate the labeling of samples that will be used to train the ANN by means of indicating the regions where the pedestrians are positioned. This accurate positioning information is essential for the optimization of B5G network operation, including the control of antenna arrays and reconfigurable intelligent surfaces (RIS). The experimental validation demonstrates the efficiency of mapping pedestrian locations with a precision of up to 98.787%, accuracy of 95.25%, recall of 98.537%, and an F1 score of 98.571%. These results show that the proposed system has the potential to solve the problem of sensing and positioning in indoor environments with high reliability and accuracy.