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Childhood maltreatment has been demonstrated to impact brain development. However, whether childhood maltreatment can influence the effects of recent stress on brain networks remains unclear. This study aimed to investigate whether childhood maltreatment moderates the longitudinal relationship between recent life stress and within- and between-network connectivity in key brain networks, including the anterior salience (ASN), central executive (CEN), default mode (DMN), and emotional regulation network (ERN). A cohort of 172 individuals from the Neuroscience in Psychiatry Network (NSPN) underwent MRI scans at two specific time points and undertook evaluations of childhood maltreatment and recent life stress. The results showed that childhood abuse moderated the association of recent life stress with the within-network connectivity of ASN and ERN but not DMN and CEN. Furthermore, recent life stress significantly interacted with childhood abuse to be associated with the between-network connectivity of ASN-DMN, ASN-CEN, ASN-ERN, DMN-ERN and CEN-ERN. Overall, among youth exposed to higher degrees of childhood abuse, greater recent life stress was longitudinally associated with increased network connectivity. Understanding these interactions can provide valuable insights for developing prevention strategies and interventions aimed at mitigating the lasting impact of childhood maltreatment on brain development and overall well-being.
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A multifunctional sensor comprising flexible and transparent ultraviolet (UV) photodetectors (PDs) with strain gauges based on Ag nanowire (AgNW)@ZnO nanorods (ZnONRs) was fabricated using a cost-effective, simple, and efficient method. High-aspect ratio silver nanowires were synthesized using the polyol method. An AgNW@ZnONR composite was formed via the hydrothermal method to ensure the multifunctional capability of the flexible sensors. After refining the process parameters, the size of the ZnO nanorods was decreased to fabricate pliable multifunctional sensors using AgNW@ZnONRs. At a deposition of 0.207 g of AgNW@ZnONRs, the sensor achieves its maximum switching ratio and fastest response time under conditions of 2000 µW/cm2 UV optical power density. With a ton (rise time) of 2.7 s and a toff (fall time) of 2.3 s, the ratio of Ion to Ioff current is 1151. Additionally, the sensor's maximum optical current value correlates linearly with UV light's power density. The maximum response current increased from 222.5 pA to 588.1 pA, an increase of 164.3%, when the bending angle was increased from 15° to 90° for the sensor with a deposition of 0.276 g of AgNW@ZnONRs. There was no degradation in the response of the sensors after 10,000 bending cycles, as they have excellent stability and repeatability, which means they can meet the requirements of wearable sensor applications. Therefore, there is great potential for the practical application of multifunctional AgNW@ZnONRs in flexible sensors.
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In the area of flexible electronics, pressure sensors are a widely utilized variety of flexible electronics that are both indispensable and prevalent. The importance of pressure sensors in various fields is currently increasing, leading to the exploration of materials with unique structural and piezoelectric properties. Perovskite-based materials are ideal for use as flexible pressure sensors (FPSs) due to their flexibility, chemical composition, strain tolerance, high piezoelectric and piezoresistive properties, and potential integration with other technologies. This article presents a comprehensive study of perovskite-based materials used in FPSs and discusses their components, performance, and applications in detecting human movement, electronic skin, and wireless monitoring. This work also discusses challenges like material instability, durability, and toxicity, the limited widespread application due to environmental factors and toxicity concerns, and complex fabrication and future directions for perovskite-based FPSs, providing valuable insights for researchers in structural health monitoring, physical health monitoring, and industrial applications.
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Silver nanoparticles (Ag NPs) have accumulated significant interest due to their exceptional physicochemical properties and remarkable applications in biomedicine, electronics, and catalysis sensing. This comprehensive review provides an in-depth study of synthetic approaches such as biological synthesis, chemical synthesis, and physical synthesis with a detailed overview of their sub-methodologies, highlighting advantages and disadvantages. Additionally, structural properties affected by synthesis methods are discussed in detail by examining the dimensions and surface morphology. The review explores the distinctive properties of Ag NPs, including optical, electrical, catalytic, and antimicrobial properties, which render them beneficial for a range of applications. Furthermore, this review describes the diverse applications in several fields, such as medicine, environmental science, electronics, and optoelectronics. However, with numerous applications, several kinds of issues still exist. Future attempts need to address difficulties regarding synthetic techniques, environmental friendliness, and affordability. In order to ensure the secure utilization of Ag NPs, it is necessary to establish sustainability in synthetic techniques and eco-friendly production methods. This review aims to give a comprehensive overview of the synthesis, structural analysis, properties, and multifaceted applications of Ag NPs.
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BACKGROUND: Exposure to indoor air pollution from solid cooking fuel use may increase mental disorders risk through pathways such as oroxidative stress, neuroinflammation, or cerebrovascular damage. However, few studies have explored the underlying mechanism between solid cooking fuel use and psychological distress. The present study aims to investigate the mediating role of sleep quality on the relationship between solid cooking fuel use and psychological distress among older adults in rural Shandong, China. METHODS: This study used the cross-sectional data from the second follow-up survey of the Shandong Rural Elderly Health Cohort (SREHC). A total of 3,240 rural older adults were included in the analysis. Logistic regression and the Karlson, Holm, and Breen (KHB) mediation analyses were performed to investigate the relationship between solid cooking fuel use and psychological distress, as well as the mediating role of sleep quality in this association. RESULTS: This study found that solid cooking fuel use was significantly and positively associated with psychological distress among older adults in rural Shandong, China (OR = 1.38, 95% CI: 1.12,1.70). Mediation analysis revealed that sleep quality mediated the association between solid cooking fuel use and psychological distress among older adults (ß = 0.06, P = 0.011). The mediation effect accounted for 16.18% of the total effect. CONCLUSIONS: Our study showed that solid cooking fuel use was associated with psychological distress among rural older adults, and sleep quality mediated this association. Interventions should focus on addressing cooking fuel types and poor sleep quality to reduce psychological distress. In the future, more aggressive environmental protection policies would be needed to lessen the adverse effects of indoor air pollution on the health of older adults in rural China.
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Poluição do Ar em Ambientes Fechados , Culinária , População Rural , Qualidade do Sono , Humanos , China/epidemiologia , Masculino , Idoso , Feminino , Estudos Transversais , Poluição do Ar em Ambientes Fechados/efeitos adversos , Angústia Psicológica , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Robot-assisted microsurgery (RAMS) is gradually becoming the preferred method for some delicate surgical procedures. However, the lack of haptic feedback reduces the safety of the surgery. Surgeons are unable to feel the grasping force between surgical instruments and the patient's tissues, which can easily lead to grasping failure or tissue damage. METHODS: This paper proposes a tendon-driven grasping force feedback mechanism, consisting of a follower hand and a leader hand, to address the lack of grasping force feedback in flexible surgical robots. Considering the friction in the tendon transmission process, a grasping force estimation model is established for the follower hand. The admittance control model is designed for force/position control of the leader hand. RESULTS: Through experimental validation, it has been confirmed that the grasping force sensing range of the follower hand is 0.5-5 N, with a sensing accuracy of 0.3 N. The leader hand is capable of providing feedback forces in the range of 0-5 N, with a static force accuracy of 0.1 N. CONCLUSIONS: The designed mechanism and control strategy can provide the grasping force feedback function. Future work will focus on improving force feedback performance. TRIAL REGISTRATION: This research has no clinical trials.
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Desenho de Equipamento , Retroalimentação , Força da Mão , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Força da Mão/fisiologia , Microcirurgia/métodos , Microcirurgia/instrumentação , Tendões/cirurgia , Tendões/fisiologia , Reprodutibilidade dos TestesRESUMO
Pulse wave analysis, a non-invasive and cuff-less approach, holds promise for blood pressure (BP) measurement in precision medicine. In recent years, pulse wave learning for BP estimation has undergone extensive scrutiny. However, prevailing methods still encounter challenges in grasping comprehensive features from pulse waves and generalizing these insights for precise BP estimation. In this study, we propose a general pulse wave deep learning (PWDL) approach for BP estimation, introduc-ing the OVAR-BPnet model to powerfully capture intricate pulse wave features and showcasing its effectiveness on multiple types of pulse waves. The approach involves constructing population pulse waves and employing a model comprising an omni-scale convolution subnet, a Vision Transformer subnet, and a multilayer perceptron subnet. This design enables the learning of both single-period and multi-period waveform features from multiple subjects. Additionally, the approach employs a data augmentation strategy to enhance the morphological features of pulse waves and devise a label sequence regularization strategy to strengthen the intrinsic relationship of the subnets' output. Notably, this is the first study to validate the performance of the deep learning approach of BP estimation on three types of pulse waves: photoplethysmography, forehead imaging photoplethysmography, and radial artery pulse pressure waveform. Experiments show that the OVAR-BPnet model has achieved advanced levels in both evaluation indicators and international evaluation criteria, demonstrating its excellent competitiveness and generalizability. The PWDL approach has the potential for widespread application in convenient and continuous BP monitoring systems.
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Determinação da Pressão Arterial , Aprendizado Profundo , Análise de Onda de Pulso , Processamento de Sinais Assistido por Computador , Humanos , Análise de Onda de Pulso/métodos , Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Adulto , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Nickel-based catalysts are regarded as the most excellent urea oxidation reaction (UOR) catalysts in alkaline media. Whatever kind of nickel-based catalysts is utilized to catalyze UOR, it is widely believed that the in situ-formed Ni3+ moieties are the true active sites and the as-utilized nickel-based catalysts just serve as pre-catalysts. Digging the pre-catalyst effect on the activity of Ni3+ moieties helps to better design nickel-based catalysts. Herein, five different anions of OH-, CO32-, SiO32-, MoO42-, and WO42- were used to bond with Ni2+ to fabricate the pre-catalysts ß-Ni(OH)2, Ni-CO3, Ni-SiO3, Ni-MoO4, and Ni-WO4. It is found that the true active sites of the five as-fabricated catalysts are the same in situ-formed Ni3+ moieties and the five as-fabricated catalysts demonstrate different UOR activity. Although the as-synthesized five catalysts just serve as the pre-catalysts, they determine the quantity of active sites and activity per active site, thus determining the catalytic activity of the catalysts. Among the five catalysts, the amorphous nickel tungstate exhibits the most superior activity per active site and can catalyze UOR to reach 158.10 mA·cm-2 at 1.6 V, exceeding the majority of catalysts. This work makes for a deeper understanding of the pre-catalyst effect on UOR activity and helps to better design nickel-based UOR catalysts.
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INTRODUCTION: Antidepressants have adverse effects and induce drug resistance when used excessively or frequently. Therefore, adjuvants are needed to reduce the use of antidepressants during treatment. Traditional Chinese medicine (TCM) is an important adjunctive approach to depression with safety, environmental protection, and low toxicity. Glycyrrhizaglabra (licorice, GG) is a plant commonly used in various herbal remedies. METHOD: We investigated the antidepressant activity of GG, its active constituents, and potential depression-related targets. We combined animal behavioral and molecular biological assays with network pharmacology to analyze the antidepressant mechanism of GG. GG extracts reversed lipopolysaccharide (LPS)-induced depression-like behavior in behavioral tests. We selected 56 active compounds and 695 target compounds of licorice from TCMSP. The PPI network screened 80 core targets for enrichment analysis. It shows that GG significantly affected neurodegeneration pathways, neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, dopaminergic synapse, and MAPK signaling pathway. RESULT: Mechanistic studies showed that GG reduced IL-1ß, IL-6, and TNF-α levels, 5-HTRA1 expression, and GSK3ß phosphorylation in mouse hippocampus. It also increased BDNF and DRD1 expression and CREB and ERK1/2 phosphorylation. CONCLUSION: It shows that GG acted on these proteins to affect multiple pathways that mediate the pathogenesis of depression.
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Cerebral ischemia/reperfusion (CIRI) is a leading cause of death worldwide. A small GTPase known as ADP-ribosylation factor-like protein 13B (ARL13B) is essential in several illnesses. The role of ARL13B in CIRI remains unknown, though. A middle cerebral artery occlusion/reperfusion (MCAO/R) in rats as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) models in PC12 cells were constructed. The neuroprotective effects of ARL13B against MCAO/R were evaluated using neurological scores, TTC staining, rotarod testing, H&E staining, and Nissl staining. To detect the expression of proteins associated with the SHH pathway and apoptosis, western blotting and immunofluorescence were employed. Apoptosis was detected using TUNEL assays and flow cytometry. There was increased expression of ARL13B in cerebral ischemia/reperfusion models. However, ARL13B knockdown aggravated CIRI nerve injury by inhibiting the sonic hedgehog (SHH) pathway. In addition, the use of SHH pathway agonist (SAG) can increased ARL13B expression, reverse the effects of ARL13B knockdown exacerbating CIRI nerve injury. ARL13B alleviated cerebral infarction and pathological injury and played a protective role against MCAO/R. Furthermore, ARL13B significantly increased the expression of SHH pathway-related proteins and the anti-apoptotic protein BCL-2, while decreased the expression of pro-apoptotic protein BAX, thus reducing apoptosis. The results from the OGD/R model in PC12 cells were consistent with those obtained in vivo. Surprisingly, we demonstrated that ARL13B regulates the cell cycle to protect against CIRI nerve injury. Our findings indicate that ARL13B protects against CIRI by reducing apoptosis through SHH-dependent pathway activation, and suggest that ARL13B plays a crucial role in CIRI pathogenesis.
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Fatores de Ribosilação do ADP , Proteínas Hedgehog , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Apoptose/fisiologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Proteínas Hedgehog/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia , Transdução de Sinais/fisiologiaRESUMO
AIMS: Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signalling pathways involved in the development and progression of AAAs is essential for the development of medical therapy. METHODS AND RESULTS: We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE-/- mice, conducted scRNA-seq, and identified a unique population of interferon-inducible monocytes/macrophages (IFNICs), which were amply found in the AAAs. Gene set variation analysis revealed that activation of the cytosolic DNA sensing cGAS-STING and JAK-STAT pathways promoted the secretion of type I interferons in monocytes/macrophages and differentiated them into IFNICs. We generated myeloid cell-specific deletion of Sting1 (Lyz2-Cre+/-; Sting1flox/flox) mice and performed bone marrow transplantation and found that myeloid cell-specific deletion of Sting1 or Ifnar1 significantly reduced the incidence of AAA, aortic rupture rate, and diameter of the abdominal aorta. Mechanistically, the activated pyroptosis- and inflammation-related signalling pathways, regulated by IRF7 in IFNICs, play critical roles in the developing AAAs. CONCLUSION: IFNICs are a unique monocyte/macrophage subset implicated in the development of AAAs and aortic rupture.
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Angiotensina II , Aorta Abdominal , Aneurisma da Aorta Abdominal , Ruptura Aórtica , Modelos Animais de Doenças , Progressão da Doença , Macrófagos , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Monócitos , Receptor de Interferon alfa e beta , Transdução de Sinais , Análise de Célula Única , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/prevenção & controle , Animais , Macrófagos/metabolismo , Macrófagos/patologia , Macrófagos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/patologia , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Abdominal/imunologia , Ruptura Aórtica/prevenção & controle , Ruptura Aórtica/patologia , Ruptura Aórtica/metabolismo , Ruptura Aórtica/genética , Ruptura Aórtica/induzido quimicamente , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Masculino , RNA-Seq , Interferon Tipo I/metabolismo , Interferon Tipo I/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Janus Quinases/metabolismo , Células Cultivadas , Apolipoproteínas ERESUMO
AIM: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. METHODOLOGY: Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05). RESULTS: Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05). CONCLUSION: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.
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Perda do Osso Alveolar , Autofagia , Modelos Animais de Doenças , Osteoprotegerina , Periodontite Periapical , Ligante RANK , Ratos Sprague-Dawley , Receptor Ativador de Fator Nuclear kappa-B , Microtomografia por Raio-X , Animais , Feminino , Ratos , Adenina/análogos & derivados , Adenina/farmacologia , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Osteoprotegerina/metabolismo , Periodontite Periapical/metabolismo , Periodontite Periapical/patologia , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismoRESUMO
Cancer cells undergo metabolic reprogramming in response to hostile microenvironments, such as energy stress; however, the underlying mechanisms remain largely unclear. It is also unknown whether energy stress-responsive circular RNA (circRNA) is involved in the regulation of glucose metabolism. Here we report that circDDX21 is upregulated in response to glucose deprivation by the transcription factor c-Myc. Functionally, circDDX21 is shown to promote glycolysis by increasing PGAM1 expression. Mechanistically, circDDX21 interacts with the RNA binding protein PABPC1, disrupting its association with the ubiquitin E3 ligase MKRN3. This disassociation attenuates MKRN3-mediated PABPC1 ubiquitination and enhances the binding of PABPC1 to PGAM1 mRNA, thereby leading to PGAM1 mRNA stabilization. The ability of the circDDX21-PGAM1 axis to promote hepatocellular carcinogenesis is validated in a xenograft mouse model. Additionally, in clinical hepatocellular carcinoma tissues, there is a positive correlation between circDDX21 and PGAM1 expression. These findings establish circDDX21 as an important regulator of glycolysis and suggest circDDX21 as a potential therapeutic target for hepatocellular carcinoma.
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Carcinogênese , Carcinoma Hepatocelular , Glicólise , Neoplasias Hepáticas , RNA Circular , Humanos , Glicólise/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Animais , RNA Circular/genética , RNA Circular/metabolismo , Camundongos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Camundongos Nus , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Metabolismo Energético/genética , Ubiquitinação , Masculino , Camundongos Endogâmicos BALB CRESUMO
In traditional cardiac ultrasound diagnostics, the process of planning scanning paths and adjusting the ultrasound window relies solely on the experience and intuition of the physician, a method that not only affects the efficiency and quality of cardiac imaging but also increases the workload for physicians. To overcome these challenges, this study introduces a robotic system designed for autonomous cardiac ultrasound scanning, with the goal of advancing both the degree of automation and the quality of imaging in cardiac ultrasound examinations. The system achieves autonomous functionality through two key stages: initially, in the autonomous path planning stage, it utilizes a camera posture adjustment method based on the human body's central region and its planar normal vectors to achieve automatic adjustment of the camera's positioning angle; precise segmentation of the human body point cloud is accomplished through efficient point cloud processing techniques, and precise localization of the region of interest (ROI) based on keypoints of the human body. Furthermore, by applying isometric path slicing and B-spline curve fitting techniques, it independently plans the scanning path and the initial position of the probe. Subsequently, in the autonomous scanning stage, an innovative servo control strategy based on cardiac image edge correction is introduced to optimize the quality of the cardiac ultrasound window, integrating position compensation through admittance control to enhance the stability of autonomous cardiac ultrasound imaging, thereby obtaining a detailed view of the heart's structure and function. A series of experimental validations on human and cardiac models have assessed the system's effectiveness and precision in the correction of camera pose, planning of scanning paths, and control of cardiac ultrasound imaging quality, demonstrating its significant potential for clinical ultrasound scanning applications.
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BACKGROUND: The faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear. METHODS: The shRNA-specific DNMT1 knockdown was employed to target DNMT1 on oral cancer cells in vitro, as was the use of DNMT1 inhibitors. A xenografted OSCC mouse model was established to determine the effect on tumor suppression. High-throughput microarrays of DNA methylation, bulk and single-cell RNA sequencing analysis, multiplex immunohistochemistry, functional sphere formation and protein immunoblotting were utilized to explore the molecular mechanism involved. Analysis of human samples revealed associations between DNMT1 expression, global DNA methylation and collaborative molecular signaling with oral malignant transformation. RESULTS: We investigated DNMT1 expression boosted steadily during oral malignant transformation in human samples, and its inhibition considerably minimized the tumorigenicity in vitro and in a xenografted OSCC model. DNMT1 overexpression was accompanied by the accumulation of cancer-specific DNA hypomethylation during oral carcinogenesis; conversely, DNMT1 knockdown caused atypically extensive genome-wide DNA hypomethylation in cancer cells and xenografted tumors. This novel DNMT1-remodeled DNA hypomethylation pattern hampered the dual activation of PI3K-AKT and CDK2-Rb and inactivated GSK3ß collaboratively. When treating OSCC mice, targeting DNMT1 achieved greater anticancer efficacy than the PI3K inhibitor, and reduced the toxicity of blood glucose changes caused by the PI3K inhibitor or combination of PI3K and CDK inhibitors as well as adverse insulin feedback. CONCLUSIONS: Targeting DNMT1 remodels a novel global DNA hypomethylation pattern to facilitate anticancer efficacy and minimize potential toxic effects via balanced signaling synergia. Our study suggests DNMT1 is a crucial gatekeeper regarding OSCC destiny and treatment outcome.
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DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , Humanos , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , Animais , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Camundongos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Transdução de Sinais , Proliferação de CélulasRESUMO
OBJECTIVE: The fact that certain oral carcinoma patients experience radiotherapy failure implies that a more radioresistant and aggressive phenotype of surviving cancer cells potentially occurs during treatment. Our study aimed to establish radioresistant oral cancer cells through a fractionated irradiation protocol that mimics clinically relevant radiotherapy dosing strategies and to investigate all-round alterations in the malignant phenotype. METHODS: Radioresistant oral carcinoma cells were generated by exposing Cal27 and Detroit 562 cells to 60 Gy radiation in 10 dose-escalating fractions and verified by cell immunofluorescence. Specific markers related to the epithelial-mesenchymal transition (EMT) process and the cancer stem cell (CSC) phenotype were assessed by Western blotting. Cell invasion and migration were evaluated using Matrigel-coated transwell and wound healing assays, respectively. Nontargeted metabolomics was used to mechanistically delineate the potential metabolic patterns linked to EMT and CSCs; the CSC phenotype was also examined by sphere formation assays and cell immunofluorescence. RESULTS: Radioresistant oral carcinoma cell lines were successfully established and validated. These cells exhibited enhanced EMT and increase in both cell invasion and migration. These radioresistant cells further demonstrated a high metabolic profile, notably marked by lipid metabolism reprogramming and functional enrichment of ATP-binding cassette (ABC) transporters. Consistently, enhanced CSC phenotype in radioresistant cells was confirmed by elevated expression of stemness markers and increased sphere-forming capacity. CONCLUSION: Radioresistant oral carcinoma cells subjected to fractionated radiation exhibit an augmented malignant phenotype. The metabolic characteristics linked to enhanced EMT and CSC phenotypes provide potential targets for improving radiotherapy in oral carcinoma.
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Movimento Celular , Fracionamento da Dose de Radiação , Transição Epitelial-Mesenquimal , Neoplasias Bucais , Células-Tronco Neoplásicas , Fenótipo , Tolerância a Radiação , Humanos , Neoplasias Bucais/radioterapia , Neoplasias Bucais/patologia , Células-Tronco Neoplásicas/efeitos da radiação , Linhagem Celular Tumoral , Western Blotting , Invasividade Neoplásica , Transportadores de Cassetes de Ligação de ATP/metabolismoRESUMO
BACKGROUND: The objective of this study was to investigate the correlation between neutrophil-to-lymphocyte ratios (NLR) and the risk of in-hospital death in patients admitted to the intensive care unit (ICU) with both chronic kidney disease (CKD) and coronary artery disease (CAD). METHODS: Data from the MIMIC-IV database, which includes a vast collection of more than 50,000 ICU admissions occurring between 2008 and 2019, was utilized in the study and eICU-CRD was conducted for external verification. The Boruta algorithm was employed for feature selection. Univariable and multivariable logistic regression analyses and multivariate restricted cubic spline regression were employed to scrutinize the association between NLR and in-hospital mortality. The receiver operating characteristic (ROC) curves were conducted to estimate the predictive ability of NLR. RESULTS: After carefully applying criteria to include and exclude participants, a total of 2254 patients with CKD and CAD were included in the research. The findings showed a median NLR of 7.3 (4.4, 12.1). The outcomes of multivariable logistic regression demonstrated that NLR significantly elevated the risk of in-hospital mortality (OR 2.122, 95% confidence interval [CI] 1.542-2.921, P < 0.001) after accounting for all relevant factors. Further insights from subgroup analyses unveiled that age and Sequential Organ Failure Assessment (SOFA) scores displayed an interactive effect in the correlation between NLR and in-hospital deaths. The NLR combined with traditional cardiovascular risk factors showed relatively great predictive value for in-hospital mortality (AUC 0.750). CONCLUSION: The findings of this research indicate that the NLR can be used as an indicator for predicting the likelihood of death during a patient's stay in the intensive care unit, particularly for individuals with both CAD and CKD. The results indicate that NLR may serve as a valuable tool for assessing and managing risks in this group at high risk. Further investigation is required to authenticate these findings and investigate the mechanisms that underlie the correlation between NLR and mortality in individuals with CAD and CKD.
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Doença da Artéria Coronariana , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Linfócitos , Neutrófilos , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/sangue , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Linfócitos/patologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: This study aimed to explore the association between hypertension follow-up management and family doctor contract services, as well as to examine whether socioeconomic status (SES) had an interaction effect on this relationship among older adults in China. METHODS: We used data from the sixth National Health Service Survey of Shandong Province, China, including 3,112 older adults (age ≥ 60 years) with hypertension in 2018. Logistic regression models and a margins plot were used to analyze the role of SES in the relationship between hypertension follow-up management and family doctor contract services. RESULTS: The regular hypertension follow-up management rate and family doctor contracting rate were 81.8% and 70.9%, respectively, among older adults with hypertension. We found that participants with regular hypertension follow-up management were more likely to sign family doctor contract services (OR=1.28, 95%CI: 1.04, 1.58, P=0.018). The interaction effect occurred in the groups who lived in rural areas (OR=1.55, 95%CI: 1.02, 2.35), with high education level (OR=0.53, 95%CI: 0.32, 0.88) and had high incomes (OR=0.53, 95%CI: 0.35, 0.81). CONCLUSIONS: Our findings suggested that regular hypertension follow-up management was associated with family doctor contract services and SES influenced this relationship. Primary health care should improve the contracting rate of family doctors by strengthening follow-up management of chronic diseases. Family doctors should focus on improving services quality and enriching the content of service packages especially for older adults with higher income and education level.
Assuntos
Serviços Contratados , Hipertensão , Classe Social , Humanos , Hipertensão/terapia , Hipertensão/epidemiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , China , Assistência ao Convalescente , Médicos de Família , Idoso de 80 Anos ou maisRESUMO
The photoelectric characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) films significantly affect the power conversion efficiency and stability of Si/PEDOT:PSS hybrid solar cells. In this paper, we investigated PEDOT:PSS modification with alcohol ether solvents (dipropylene glycol methyl ether (DPM) and propylene glycol phenyl ether (PPH)). The reduction of PSS content and the transformation of the PEDOT chain from benzene to a quinone structure in PEDOT:PSS induced by doping with DPM or PPH are the reasons for the improved conductivity of PEDOT:PSS films. DPM and PPH doping improves the quality of silicon with the PEDOT:PSS heterojunction and silicon surface passivation, thereby reducing the surface recombination of charge carriers, which improves the photovoltaic performance of Si/PEDOT:PSS solar cells. Comparing the power conversion performance (PCE) and air stability of Si/PEDOT:PSS solar cells with DPM (13.24%), DPH (13.51%), ethylene glycol (EG, 13.07%), and dimethyl sulfoxide (DMSO, 12.62%), it is suggested that doping with DPM and DPH can replace DMSO and EG to enhance the performance of Si/PEDOT:PSS solar cells. The EG and DMSO solvents not only have a certain toxicity to the human body but also are not environmentally friendly. In comparison to DMSO and EG, DPM and DPH are more economical and environmentally friendly, helping to reduce the manufacturing cost of Si/PEDOT:PSS solar cells and making them more conducive to their commercial applications.