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Construction of a cancer nanovaccine that can simultaneously activate immune cells and exert efficient tumor treatment still remains a challenge. Herein, we showcase a proof-of-concept demonstration of an advanced therapeutic nanovaccine formulation based on poly(N-vinylcaprolactam) nanogels (NGs) which were loaded with manganese dioxide (MnO2), the sonosensitizer chlorin e6 (Ce6), and the immune adjuvant cyclic GMP-AMP (cGAMP). The gels were furthermore coated with apoptotic cancer cell membranes (AM). On the one hand, the AM promoted the recognition of NGs by antigen presenting cells (APCs) in lymph nodes due to their enhanced immunogenicity, then the loaded Mn and cGAMP could mature APCs via stimulator of interferon genes (STING) activation for triggering immunity to prevent tumor growth. On the other hand, the NGs could selectively release Mn2+ for hydroxyl radical production and Ce6 to generate single oxygen under ultrasound irradiation of tumors, respectively, thereby exerting local chemodynamic/sonodynamic therapy to induce immunogenic cell death (ICD). Moreover, the Mn2+ could also activate STING in tumors to synergize with ICD for potentiated immune responses. Overall, the biomimetic NG-based therapeutic nanovaccine could directly evoke immune system, and also conduct local tumor treatment to further activate ICD, thus realizing a full-cycle immunomodulation (tumor killing for ICD/antigen production, and tumor cells/APCs immune activation) to tackle bilateral tumor growth.
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Ferroptosis is a relatively recently discovered type of regulated cell death that is induced by iron-dependent lipid peroxidation. The key contributing factors to ferroptosis are the loss of glutathione peroxidase 4 which is required for reversing lipid peroxidation, the buildup of redox-active iron and the oxidation of phospholipids containing polyunsaturated fatty acids. Ferroptosis has been associated with a number of diseases, including cancers such as hepatocellular carcinoma, breast cancer, acute renal damage and neurological disorders such as Alzheimer's disease and Alzheimer's disease, and there may be an association between ferroptosis and acute myeloid leukemia (AML). The present review aims to describe the primary regulatory pathways of ferroptosis, and the relationship between ferroptosis and the occurrence and development of AML. Furthermore, the present review comprehensively summarizes the latest advances in the treatment and prognosis of ferroptosis in AML.
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BACKGROUND: The aim of this study was to elucidate the critical role of autophagy-related gene aggregation in gastric cancer tumor microenvironment cells and to investigate their major roles in cellular functions. In particular, the expression of these genes in tumor-associated fibroblast subtypes was scrutinized in an attempt to explain their cell-subpopulation-specific roles in cell-cell communication and regulation of cellular functions. METHODS: In this study, single-cell RNA sequencing data were first analyzed in multiple steps, including data preprocessing, cell clustering, and cell classification. Cell subpopulations and gene expression patterns were identified and analyzed using unsupervised non-negative matrix factorization (NMF) techniques. The dynamic expression of autophagy-related gene aggregates in various cell types was deciphered by pseudotime trajectory analysis (PTA). Intercellular communication analysis was performed using the CellChat R software package, revealing the intricate communication patterns and exchange of key signaling molecules between cell subpopulations, and SCENIC analysis was used to identify gene regulatory networks and reveal the mechanisms behind cellular heterogeneity. RESULT: Cell subpopulations associated with pan-apoptosis were identified by NMF decomposition and SCENIC analysis. Cell-cell communication analysis revealed intricate communication patterns and exchange of key signaling molecules between cell subpopulations. Dynamic expression of autophagy-related genes aggregated in the pseudotemporal trajectory of STAD was observed by PTA. In the fibroblast subtype, different ligand-receptor interactions and their key roles in immunomodulation were observed. CONCLUSION: By deeply analyzing and comparing gene expression patterns within cellular subpopulations and intercellular communication, this study provides new insights into the role of pan-apoptosis-related genes in regulating immune responses and cellular functions in gastric cancer. These findings pave the way for further exploration of the role of these genes in tumorigenesis and immune regulation, as well as laying the foundation for potential therapeutic strategies.
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Pancreatic cancer (PC) is a highly aggressive and lethal malignancy characterized by a complex tumor microenvironment (TME) and immunosuppressive features that limit the efficacy of existing treatments. This paper reviews the potential of combining ultrasound with macrophage exhaustion in the treatment of pancreatic cancer. Macrophages, particularly tumor-associated macrophages (TAMs), are crucial in pancreatic cancer progression and immune escape. Prolonged exposure to the immunosuppressive TME leads to macrophage exhaustion, reducing their anti-tumor ability and instead promoting tumor growth. The CSF1/CSF1R signaling pathway is key in macrophage recruitment and functional regulation, making it an effective target for combating macrophage exhaustion. Ultrasound technology not only plays a significant role in diagnosis and staging but also enhances therapeutic efficacy by guiding radiofrequency ablation (RFA) and percutaneous alcohol injection (PEI) in combination with immunomodulators. Additionally, ultrasound imaging can monitor the number and functional status of TAMs in real-time, providing a basis for optimizing treatment strategies. Future studies should further investigate the combined use of ultrasound and immunomodulators to refine treatment regimens, address challenges such as individual variability and long-term effects, and offer new hope for pancreatic cancer patients.
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Neoplasias Pancreáticas , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos , Transducción de Señal , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/diagnóstico por imagen , Animales , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Terapia Combinada , Ultrasonografía/métodos , Macrófagos/inmunología , Macrófagos/metabolismo , Factor Estimulante de Colonias de Macrófagos , Receptor de Factor Estimulante de Colonias de MacrófagosRESUMEN
In this study, three BODIPY-based fluorescent probes were designed and synthesized. The ultraviolet-visible spectra, fluorescence spectra, smartphone color recognition application and bioimaging were utilized to evaluate the capacity of the probes. By comparing key parameters, BDP-SIN had optimal performances including fastest response (10 min), highest signal-to-noise ratio (815 times) and lowest limit of detection (LOD = 49 nM). The recovery rate ranged from 92.04 % to 103.25 %. Meanwhile, BDP-SIN was triumphantly employed for determination of Cys in different daily food samples. Moreover, the test strips and microporous filter membrane loaded with BDP-SIN were developed for the portable real-time visualization and quantitative detection of Cys in food samples, which the contents ranged from 0.27 µM to 0.49 µM. Besides, BDP-SIN could image Cys in the living cells and mice. The novelty of this work was that developed an effective tool for researching the roles of Cys in food industry and living organisms.
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Inpatient falls are common adverse events especially for patients with hematologic malignancies. A fall-risk prediction model for patients with hematologic malignancies are still needed. Here we conducted a multicenter study that prospectively included 516 hospitalized patients with hematologic malignancies, and developed a nomogram for fall risk prediction. Patients were divided into the modeling group (n = 389) and the validation group (n = 127). A questionnaire containing sociodemographic factors, general health factors, disease-related factors, medication factors, and physical activity factors was administered to all patients. Logistic regression analysis revealed that peripheral neuropathy, pain intensity, Morse fall scale score, chemotherapy courses, and myelosuppression days were risk factors for falls in patients with hematologic malignancies. The nomogram model had a sensitivity of 0.790 and specificity of 0.800. The calibration curves demonstrated acceptable agreement between the predicted and observed outcomes. Therefore, the nomogram model has promising accuracy in predicting fall risk in patients with hematologic malignancies.
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Research purpose: This study aims to outline the fundamental status of the German academic community's research in the field of renewable energy and to foster collaboration between China and Germany in this area. Research methods: This study examines documents published by German scholars from 2008 to 2023, which are part of the "Web of Science (WOS) Core Collection" database and related to renewable energy issues, using the bibliometric visualization tool CiteSpace 6.2.R6. Research conclusions: The study examines the co-occurrence and burst of keywords, changes in publication volume, international collaboration networks, research institution collaboration networks, and researcher collaboration networks. It concluded that: (1) German academic research in the field of renewable energy can be divided into three phases: nascent (2008-2014), surge (2015-2021), and decline (2022-2023). (2) The Helmholtz Association and Reinhard Madlener, among other prominent institutions and academicians, are responsible for the close cooperation among personnel and institutions, the significant leading effect, and the emphasis on cutting-edge topics. Research in this field notably focuses on cutting-edge issues like life cycle assessment and developing countries. The study observes a transition in research concentration from macro to micro perspectives. In the context of a global collective response to climate change, the analysis of the German academic community's overall situation will enhance the collaboration between the two countries in the field of renewable energy research.
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Objective: Depression is a common mental illness with a high prevalence rate and is a significant contributor to the global burden of diseases. Various factors are associated with depression, and its etiology is complex. Instead of focusing on single-factor effects, this study aimed to explore a combination of high-risk factor sets for depression among adult community residents. Methods: We conducted a cross-sectional survey in Shenzhen, China, from January 2021 to March 2021. A simple sampling method was used to enroll participants. A total of 1,965 adult residents completed the survey and were assessed using the Patient Health Questionnaire-9 (PHQ-9), the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), and the Psychosocial Stress Survey for Groups (PSSG). The fuzzy-set qualitative comparative analysis method was used to explore the high-risk factor sets for depression among adult community residents. Results: The prevalence of depression among the surveyed adult residents in Shenzhen was 6.36%. The mean scores of PHQ-9 were higher among women and unmarried residents. The combination of low extroversion (e) and high neuroticism (N) in personality traits, along with high scores for life events (V), negative emotional responses to events (G), positive emotional responses to events (O), and positive coping styles to events (I) (denoted as e*N*V*G*O*I) constituted a high-risk factor set for depression. The overall consistency was 0.843, and the overall coverage was 0.330. Conclusion: Our study suggested that stressful life events together with personality traits including neuroticism and introversion serve as crucial factors for depression among adult community residents, regardless of the coping strategies they adopt. This study provides data for developing comprehensive interventions such as regulating neuroticism and introversion levels and reducing stressors to prevent the occurrence of depression among adult community residents.
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PURPOSE: The aim of this study was to observe the influence of differential nutritional status on bone age (BA) change according to body mass index (BMI) and analyze the risk of advanced bone age in children with overweight and obesity. METHODS: In total 23,305 children from Beijing were included in this cross-sectional study. Childhood overweight and obesity were defined according to the China and World Health Organization growth criteria. The data were analyzed by the R coding platform version 4.3.0. RESULTS: Under the Chinese criteria, 29%, 15%, and 4% of boys with overweight; 33%, 33%, and 3% of boys with obesity; 39%, 25%, and 2% of girls with overweight; and 37%, 42% and 1% of girls with obesity had advanced, significantly advanced and delayed BA, respectively. After adjustment, overweight (odds ratio, 95% confidence interval, P under the Chinese criteria: 2.52, 2.30-2.75, <0.001 and 4.54, 4.06-5.09, <0.001) and obesity (4.31, 3.85-4.82, <0.001 and 14.01, 12.39-15.85, <0.001) were risk factors for both advanced BA and significantly advanced BA. CONCLUSIONS: Different nutritional statuses lead to differences in children's BA development. Children with overweight and obesity have higher rates of advanced BA under two growth criteria, and girls have more advances in BA than boys do. Overweight and obesity are risk factors for advanced BA.
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This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.
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Edad de Inicio , Encéfalo , Epilepsias Parciales , Imagen por Resonancia Magnética , Humanos , Masculino , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/diagnóstico por imagen , Epilepsias Parciales/patología , Femenino , Persona de Mediana Edad , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Cognición/fisiología , Pruebas Neuropsicológicas , AdultoRESUMEN
OBJECTIVE: To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. METHODS: Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. RESULTS: Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (µmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/ß-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/ß-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/ß-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/ß-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). CONCLUSIONS: QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Diquat , Hígado , Ratones Endogámicos C57BL , Quercetina , Animales , Masculino , Ratones , Quercetina/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Caspasa 9/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Alanina Transaminasa/sangre , Proteínas de la Membrana , Hemo-Oxigenasa 1RESUMEN
In recent years, embedded system technologies and products for sensor networks and wearable devices used for monitoring people's activities and health have become the focus of the global IT industry. In order to enhance the speech recognition capabilities of wearable devices, this article discusses the implementation of audio positioning and enhancement in embedded systems using embedded algorithms for direction detection and mixed source separation. The two algorithms are implemented using different embedded systems: direction detection developed using TI TMS320C6713 DSK and mixed source separation developed using Raspberry Pi 2. For mixed source separation, in the first experiment, the average signal-to-interference ratio (SIR) at 1 m and 2 m distances was 16.72 and 15.76, respectively. In the second experiment, when evaluated using speech recognition, the algorithm improved speech recognition accuracy to 95%.
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Algoritmos , Dispositivos Electrónicos Vestibles , Humanos , Procesamiento de Señales Asistido por Computador , Localización de SonidosRESUMEN
In this study, to address the defects of sodium alginate (SA), such as its susceptibility to disintegration, silica was coated on the outer layer of sodium alginate hydrogel beads in order to improve its swelling and slow-release properties. Tetraethyl orthosilicate (TEOS) was used as the hydrolyzed precursor, and the solution of silica precursor was prepared by sol-gel reaction under acidic conditions. Then SA-silica hydrogel beads prepared by ionic crosslinking method were immersed into the SiO2 precursor solution to prepare SA-silica hydrogel beads. The chemical structure and morphology of the hydrogel beads were characterized by XRD, FTIR, and SEM, and the results showed that the surface of SA-silica beads was successfully encapsulated with the outer layer of SiO2, and the surface was smooth and dense. The swelling experiments showed that the swelling performance effectively decreased with the increase of TEOS molar concentration, and the maximum swelling ratio of the hydrogel beads decreased from 41.07 to 14.3, and the time to reach the maximum swelling ratio was prolonged from 4 h to 8 h. The sustained-release experiments showed that the SA-silica hydrogel beads possessed a good pH sensitivity, and the time of sustained-release was significantly prolonged in vitro. Hemolysis and cytotoxicity experiments showed that the SA-silica hydrogel beads were biocompatible when the TEOS molar concentration was lower than 0.375 M. The SA-silica-2 hydrogel beads had good biocompatibility, swelling properties, and slow-release properties at the same time.
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Alginatos , Curcumina , Portadores de Fármacos , Liberación de Fármacos , Hemólisis , Hidrogeles , Dióxido de Silicio , Alginatos/química , Dióxido de Silicio/química , Curcumina/química , Curcumina/farmacología , Curcumina/administración & dosificación , Hidrogeles/química , Hidrogeles/síntesis química , Portadores de Fármacos/química , Hemólisis/efectos de los fármacos , Concentración de Iones de Hidrógeno , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Animales , Silanos/química , Microesferas , Preparaciones de Acción Retardada/química , Supervivencia Celular/efectos de los fármacosRESUMEN
AIM: Compared to the conventional cardiopulmonary resuscitation (CCPR), potential benefits of extracorporeal cardiopulmonary resuscitation (ECPR) for patients with cardiac arrest (CA) are still controversial. We aimed to determine whether ECPR can improve the prognosis of CA patients compared with CCPR. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library from database's inception to July 2023 to identify randomized controlled trials (RCTs) or cohort studies that compared ECPR with CCPR in adults (aged ≥ 16 years) with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). This meta-analysis was performed using a random-effects model. Two researchers independently reviewed the relevance of the study, extracted data, and evaluated the quality of the included literature. The primary outcome was short-term (from hospital discharge to one month after cardiac arrest) and long-term (≥ 90 days after cardiac arrest) survival with favorable neurological status (defined as cerebral performance category scores 1 or 2). Secondary outcomes included survival at 1 months, 3-6 months, and 1 year after cardiac arrest. RESULTS: The meta-analysis included 3 RCTs and 14 cohort studies involving 167,728 patients. We found that ECPR can significantly improve good neurological prognosis (RR 1.82, 95%CI 1.42-2.34, I2 = 41%) and survival rate (RR 1.51, 95%CI 1.20-1.89, I2 = 62%). In addition, the results showed that ECPR had different effects on favorable neurological status in patients with OHCA (short-term: RR 1.50, 95%CI 0.98- 2.29, I2 = 55%; long-term: RR 1.95, 95% CI 1.06-3.59, I2 = 11%). However, ECPR had significantly better effects on neurological status than CCPR in patients with IHCA (short-term: RR 2.18, 95%CI 1.24- 3.81, I2 = 9%; long-term: RR 2.17, 95% CI 1.19-3.94, I2 = 0%). CONCLUSIONS: This meta-analysis indicated that ECPR had significantly better effects on good neurological prognosis and survival rate than CCPR, especially in patients with IHCA. However, more high-quality studies are needed to explore the role of ECPR in patients with OHCA.
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Reanimación Cardiopulmonar , Humanos , Reanimación Cardiopulmonar/métodos , Pronóstico , Paro Cardíaco/terapia , Paro Cardíaco/mortalidad , Oxigenación por Membrana Extracorpórea/métodos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidadRESUMEN
Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.
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Clorofilidas , Nanogeles , Neoplasias , Óxido Nítrico , Porfirinas , Animales , Óxido Nítrico/administración & dosificación , Óxido Nítrico/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/metabolismo , Porfirinas/administración & dosificación , Porfirinas/farmacocinética , Línea Celular Tumoral , Nanogeles/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Polietilenglicoles/química , Ratones Desnudos , Polietileneimina/química , Ratones Endogámicos BALB C , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Femenino , Ratones , Terapia por Ultrasonido/métodos , Nanoestructuras/administración & dosificaciónRESUMEN
OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.
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Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Anciano , Procedimientos Endovasculares/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Inutilidad Médica , Trombectomía/métodos , Estudios Prospectivos , PronósticoRESUMEN
Colchicine binding site inhibitors (CBSIs) have attracted much attention due to their antitumor efficacies and the advantages of inhibiting angiogenesis and overcoming multidrug resistance. However, no CBSI has been currently approved for cancer treatment due to the insufficient efficacies, serious toxicities and poor pharmacokinetic properties. Design of dual-target inhibitors is becoming a potential strategy for cancer treatment to improve anticancer efficacy, decrease adverse events and overcome drug resistance. Therefore, we reviewed dual-target inhibitors of colchicine binding site (CBS), summarized the design strategies and the biological activities of these dual-target inhibitors, expecting to provide inspiration for developing novel dual inhibitors based on CBS.
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Antineoplásicos , Colchicina , Neoplasias , Humanos , Colchicina/metabolismo , Colchicina/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Sitios de Unión/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéutico , Estructura Molecular , AnimalesRESUMEN
Synthetic micro/nanomotors have been extensively exploited over the past decade to achieve active transportation. This interest is a result of their broad range of potential applications, from environmental remediation to nanomedicine. Nevertheless, it still remains a challenge to build a fast-moving biodegradable polymeric nanomotor. Here we present a light-propelled nanomotor by introducing gold nanoparticles (Au NP) onto biodegradable bowl-shaped polymersomes (stomatocytes) via electrostatic and hydrogen bond interactions. These biodegradable nanomotors show controllable motion and remarkable velocities of up to 125 µm s-1. This unique behavior is explained via a thorough three-dimensional characterization of the nanomotor, particularly the size and the spatial distribution of Au NP, with cryogenic transmission electron microscopy (cryo-TEM) and cryo-electron tomography (cryo-ET). Our in-depth quantitative 3D analysis reveals that the motile features of these nanomotors are caused by the nonuniform distribution of Au NPs on the outer surface of the stomatocyte along the z-axial direction. Their excellent motile features are exploited for active cargo delivery into living cells. This study provides a new approach to develop robust, biodegradable soft nanomotors with application potential in biomedicine.
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Depression is a major psychological disorder with a growing impact worldwide. Traditional methods for detecting the risk of depression, predominantly reliant on psychiatric evaluations and self-assessment questionnaires, are often criticized for their inefficiency and lack of objectivity. Advancements in deep learning have paved the way for innovations in depression risk detection methods that fuse multimodal data. This paper introduces a novel framework, the Audio, Video, and Text Fusion-Three Branch Network (AVTF-TBN), designed to amalgamate auditory, visual, and textual cues for a comprehensive analysis of depression risk. Our approach encompasses three dedicated branches-Audio Branch, Video Branch, and Text Branch-each responsible for extracting salient features from the corresponding modality. These features are subsequently fused through a multimodal fusion (MMF) module, yielding a robust feature vector that feeds into a predictive modeling layer. To further our research, we devised an emotion elicitation paradigm based on two distinct tasks-reading and interviewing-implemented to gather a rich, sensor-based depression risk detection dataset. The sensory equipment, such as cameras, captures subtle facial expressions and vocal characteristics essential for our analysis. The research thoroughly investigates the data generated by varying emotional stimuli and evaluates the contribution of different tasks to emotion evocation. During the experiment, the AVTF-TBN model has the best performance when the data from the two tasks are simultaneously used for detection, where the F1 Score is 0.78, Precision is 0.76, and Recall is 0.81. Our experimental results confirm the validity of the paradigm and demonstrate the efficacy of the AVTF-TBN model in detecting depression risk, showcasing the crucial role of sensor-based data in mental health detection.