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Self-hybridizing structures based on transition metal dichalcogenides (TMDCs) are becoming promising candidates for the study of an intrinsic strong light-matter coupling because of the efficient mode overlap with much simplified geometries. However, realizing flexible tuning of intrinsic strong coupling in such TMDC-based structures is still challenging. Here, we propose a strategy for flexible tuning of the intrinsic strong light-matter coupling based on a bulk TMDC material. We report the first demonstration of the strong coupling of intrinsic excitons to whispering gallery modes (WGMs) supported by an all-TMDC nanocavity. Importantly, by simply controlling angles of incidence, a selective excitation of WGMs and an anapole can be realized, which enables a direct modulation of self-hybridized interactions from a bright WGM-exciton coupling to a dark anapole-exciton coupling. Our work is expected to provide unique opportunities for engineering a strong light-matter coupling and to open exciting avenues for highly integrated novel nanophotonic devices.
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BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.
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Complemento C1q , Complemento C3 , Depresión , Modelos Animales de Enfermedad , Microglía , Fagocitosis , Transducción de Señal , Sinapsis , Animales , Complemento C1q/metabolismo , Microglía/metabolismo , Sinapsis/metabolismo , Ratones , Transducción de Señal/fisiología , Depresión/metabolismo , Fagocitosis/fisiología , Complemento C3/metabolismo , Masculino , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BLRESUMEN
Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.
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Derrota Social , Sinaptosomas , Animales , Ratones , Hipocampo , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Estrés PsicológicoRESUMEN
Carrier mobility in titanium dioxide (TiO2) systems is a key factor for their application as energy materials, especially in solar cells and lithium-ion batteries. Studies on the diffusion of Li-ions and polarons in rutile TiO2 systems have attracted extensive attention. However, how their interaction affects the diffusion of Li-ions and electron polarons is largely unclear and related studies are relatively lacking. By using first-principles calculations, we systematically investigate the interaction between the intercalated Li-ions and electron polarons in rutile TiO2 materials. Our analysis shows that the diffusion barrier of the electron polarons decreases around the Li-ion. The interaction between the Li-ions and polarons would benefit their synergistic diffusion both in the pristine and defective rutile TiO2 systems. Our study reveals the synergistic effects between the ions and polarons, which is important for understanding the carrier properties in TiO2 systems and in further improving the performance of energy materials.
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Depression is one of the most prevalent mental illnesses in the world today, and the onset of depression is usually accompanied by neuroinflammation and impaired adult neurogenesis. As a new potential member of the endocannabinoid (eCB) system, G protein coupled receptor 55 (GPR55) has been associated with mood regulation. However, the role of GPR55 in the pathophysiology of depression remains poorly understood. Thus, a 10-day chronic social defeat stress (CSDS) paradigm was utilized as an animal model of depression to explore the potential role of GPR55 in depression. After CSDS, the protein level of GPR55 decreased significantly, but the mRNA expression did not change significantly, highlighting that although the GPR55 protein was involved in the progression of the depression- and anxiety-like phenotypes, its mRNA was not. Additionally, depression- and anxiety-like behaviors were also accompanied by neuroinflammation and impaired adult neurogenesis in the hippocampus. Interestingly, O-1602, a GPR55 agonist, remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits induced by CSDS. However, after electroacupuncture (EA) alleviated depression- and anxiety-like behaviors induced by CSDS, treatment with a GPR55 antagonist (CID16020046) reversed this effect. Our research demonstrated that downregulation of GPR55 expression in the hippocampus might mediate CSDS-induced depression- and anxiety-like phenotypes, and activation and upregulation of GPR55, which might be correlated with its anti-inflammatory and subsequent neuroprotective effects, could be a potential treatment for depression.
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Fármacos Neuroprotectores , Derrota Social , Animales , Depresión/metabolismo , Hipocampo/metabolismo , Ratones , Ratones Endogámicos C57BL , Neurogénesis/fisiología , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores/farmacología , Receptores de Cannabinoides/metabolismo , Estrés Psicológico/complicacionesRESUMEN
OBJECTIVES: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. METHODS: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. RESULTS: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. CONCLUSION: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. KEY POINTS: ⢠We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. ⢠Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes ( ≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. ⢠Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately.
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Neoplasias de la Mama , Nomogramas , Humanos , Femenino , Metástasis Linfática/patología , Neoplasias de la Mama/patología , Estudios Prospectivos , Axila/patología , Ganglios Linfáticos/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
To search for multi-target directed ligands for the treatment of Alzheimer's disease (AD), eight hybrid compounds from the combination of non-steroidal anti-inflammatory drugs with donepezil were designed and synthesized. The enzyme test revealed that the synthesized compounds had remarkable inhibitory activity towards both AChE and BChE. The IC50 values of the most active compound 3a reached 0.015 and 0.80 µM for AChE and BChE, respectively, much lower than that of donepezil. Besides, the anti-inflammatory assays showed that the target compounds could effectively inhibit COX-1 and COX-2, and prevent the secretion of proinflammatory cytokines (TNF-α and IL-1ß) induced by LPS. Moreover, the target compound could also protect the neuron cells from the damage caused by Aß42 in vitro. All the results suggest that the hybrid compounds, in particular compound 3a, can be considered as potential candidates for the treatment of AD.
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Enfermedad de Alzheimer , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Ciclooxigenasa 2 , Donepezilo/farmacología , Humanos , Ligandos , Lipopolisacáridos/farmacología , Simulación del Acoplamiento Molecular , Piperidinas/farmacología , Piperidinas/uso terapéutico , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Recent studies suggest that desmoid tumors can be managed more conservatively rather than undergoing wide surgical resection (SR). Ultrasound-guided vacuum-assisted biopsy (UGVAB) is a minimally invasive technique. This retrospective study aimed to compare the outcome in patients with breast desmoid tumor (BDT) who received UGVAB alone versus SR. MATERIALS AND METHODS: The pathology database was searched for patients diagnosed with BDT ≤ 3 cm from 2007 to 2019. All patients underwent breast ultrasound examination and were then performed UGVAB alone or local SR. The Kaplan-Meier method with a log-rank test was used as a univariate analysis to compare the relapse-free survival (RFS) rates between UGVAB and SR groups. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 39 patients were included. The median follow-up was 41 mo (range, 5-110 mo). The incidence of tumor recurrence was 23.1% (9/39). The 3-y cumulative RFS was 83.1% and 95.8% in the UGVAB and SR group, respectively, which was not significantly different between the two groups (P = 0.131, log-rank test). Multivariate analysis also revealed that treatment strategy (UGVAB versus SR) was not associated with an increased risk of relapse events (P = 0.274). CONCLUSIONS: Small desmoid tumors (≤3 cm) after UGVAB alone did not have a significantly compromised RFS compared with those who underwent SR. UGVAB may be an alternative and relatively conservative method for the diagnosis and local control of BDT with a smaller size. A prospective, randomized study with large sample size is needed to confirm this observation.
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Neoplasias de la Mama/cirugía , Fibroma/cirugía , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Tratamiento Conservador , Femenino , Fibroma/diagnóstico por imagen , Fibroma/patología , Humanos , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Retrospectivos , Ultrasonografía Intervencional/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVES: To calculate the positive predictive value of biopsies performed (PPV3) of the Ultrasound section of the American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS US) atlas categories 4 and 5 in different age groups and to determine whether patient age influences the PPV3 of each category in the diagnosis of breast lesions. METHODS: We identified 2,433 ACR BI-RADS US categories 4 and 5 lesions with a known pathological diagnosis in 2,433 women. The patients were classified into three age groups (<35, 35-50, and >50 years). The age-related PPV3 of each category in the three age groups were calculated based on the pathological diagnoses and compared using the chi-squared test. RESULTS: The overall PPV3 of each category was within the reference range provided by the ACR in 2013. PPV3 gradually increased with increasing age in patients with category 4 lesions. PPV3 in the oldest group with subcategories 4A and 4B lesions were close to or exceeded the reference values. CONCLUSIONS: PPV3 and age were significantly associated in patients with category 4 lesions according to the newest edition of ACR BI-RADS US in the diagnostic setting. Closer attention should be given to older patients when assigning a final assessment category. KEY POINTS: ⢠In patients with category 4 lesions , the likelihood of malignancy is associated with age. ⢠In patients with category 5 lesions, the association is not definite. ⢠Closer attention should be given to older patients in applying the ACR BI-RADS US.
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Neoplasias de la Mama/diagnóstico por imagen , Ultrasonografía Mamaria/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/métodos , Neoplasias de la Mama/patología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Ultrasonografía Intervencional/métodos , Adulto JovenRESUMEN
BACKGROUND: Situs inversus totalis (SIT), a rare recessive autosomal disease, involves the complete transposition of the thoracic and abdominal viscera in the left-right axis. Patients with SIT combined with lung cancer are extremely uncommon. CASE PRESENTATION: We present a case of a 57-year-old woman with SIT who underwent uniportal video-assisted thoracoscopic left middle lobectomy for adenocarcinoma of the lung. The procedure was performed safely with adequate anatomical identification and careful intraoperative manipulation based on the preoperative three-dimensional-computed tomography bronchography and angiography (3D-CTBA). The patient's perioperative period was uneventful, and no recurrence was observed 2 year postoperatively. CONCLUSION: With the preoperative planning of the 3D-CTBA, uniportal video-assisted thoracoscopic lobectomy in lung cancer patients with sit can be performed safely and effectively.
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Neoplasias Pulmonares , Neumonectomía , Situs Inversus , Cirugía Torácica Asistida por Video , Humanos , Femenino , Persona de Mediana Edad , Situs Inversus/complicaciones , Situs Inversus/cirugía , Situs Inversus/diagnóstico por imagen , Cirugía Torácica Asistida por Video/métodos , Neumonectomía/métodos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Imagenología TridimensionalRESUMEN
Melon seeds have received considerable attention in recent years because of their high protein content, but they have not yet been fully used. The modification of melon seed protein (MSP) using ultrasound-assisted pH-shifting treatment was investigated in this study by analyzing structural characteristics and functional properties. The particle size, free sulfhydryl content, surface hydrophobicity, solubility, secondary structure, water-holding capacity, oil-holding capacity, emulsification activity index, and emulsification stability index of MSP were determined. MSP treated with ultrasound-assisted, pH-shifting had a smaller particle size, lower free sulfhydryl content, higher surface hydrophobicity, and solubility increased from 43.67 % to 89.12 %. The secondary structure of MSP was affected by ultrasonic treatment, manifesting as an α-helix increase and ß-helix, ß-turn, and random coil content decrease, which may be the reason why the protein structure became more compact after treatment. The water and oil holding capacities of MSP increased from 2.74 g/g and 3.14 g/g in untreated samples to 3.19 g/g and 3.97 g/g for ultrasound-treated samples, and further increased to 3.97 g/g and 5.02 g/g for ultrasound-assisted, pH-shifting treatment at pH 9.0, respectively. The emulsification activity index of MSP was 21.11 m2/g before treatment and reached a maximum of 32.34 m2/g after ultrasound-assisted, pH-shifting treatment at pH 9.0. The emulsification stability of MSP was maximized by ultrasonic treatment at pH 7.0. Ultrasound-assisted, pH-shifting treatment can effectively improve the functional properties of MSP by modifying the protein structure, which improves the potential application of melon seed protein in the food industry.
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Cucurbitaceae , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas de Plantas , Semillas , Solubilidad , Ondas Ultrasónicas , Concentración de Iones de Hidrógeno , Semillas/química , Cucurbitaceae/química , Proteínas de Plantas/química , Fenómenos Químicos , Agua/química , Tamaño de la Partícula , Emulsiones , Estructura Secundaria de ProteínaRESUMEN
Background: With the widespread use of computed tomography (CT), the detection rate of pulmonary nodules in children has gradually increased. Due to the lack of epidemiological evidence and clinical guideline on pulmonary nodule treatment in children, we aimed to provide a reference for the clinical diagnosis and management of pediatirc pulmonary nodules. Methods: This retrospective study collected consecutive cases from April 2012 to July 2021 in the Shanghai Children's Medical Center. The sample included children with pulmonary nodules on chest CT scans and met the inclusion criteria. All patients were categorized into tumor and non-tumor groups by pre-CT clinical diagnosis. Nodule characteristics between groups were analyzed. To establish a clinical assessment model for the benign versus malignant pulmonary nodules, patients who have been followed-up for three months were detected and a decision tree model for nodule malignancy prediction was constructed and validated. Results: The sample comprised 1341 patients with an average age of 7.2 ± 4.6 years. More than half of them (51.7%) were diagnosed with malignancies before CT scan. 48.3% were diagnosed with non-tumor diseases or healthy. Compared to non-tumor group, children with tumor were more likely to have multiple nodules in both lungs, with larger size and often be accompanied by osteolytic or mass lesions. Based on the decision tree model, patients' history of malignancies, nodules diameter size≥5mm, and specific nodule distribution (multiple in both lungs, multiple in the right lung or solitary in the upper or middle right lobe) were important potential predictors for malignity. In the validation set, sensitivity, specificity and AUC were 0.855, 0.833 and 0.828 (95%CI: 0.712-0.909), respectively. Conclusion: This study conducted a clinical assessment model to differentiate benignity and malignancy of pediatric pulmonary nodules. We suggested that a nodule's diameter, distribution and patient's history of malignancies are predictable factors in benign or malignant determination.
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Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.
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Depresión , Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Ratones Endogámicos C57BL , Microglía , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Derrota Social , Estrés Psicológico , Canal Aniónico 1 Dependiente del Voltaje , Animales , Mitocondrias/metabolismo , Depresión/metabolismo , Microglía/metabolismo , Microglía/patología , Ratones , Masculino , Retículo Endoplásmico/metabolismo , Estrés Psicológico/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/genética , Hipocampo/metabolismo , Hipocampo/patología , Adenosina Trifosfato/metabolismo , Inflamasomas/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Calcio/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Conducta Animal , Membranas Asociadas a Mitocondrias , Proteínas HSP70 de Choque TérmicoRESUMEN
BACKGROUND: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. LIMITATION: The cellular specificity of MAMs related protein changes in CSDS mice was not explored. CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses.
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Depresión , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Hipocampo , Ratones Endogámicos C57BL , Estrés Psicológico , Animales , Hipocampo/patología , Hipocampo/fisiopatología , Ratones , Estrés del Retículo Endoplásmico/fisiología , Masculino , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Mitocondrias , Electroacupuntura , Membranas Mitocondriales/metabolismo , Derrota Social , Conducta Animal/fisiología , Membranas Asociadas a MitocondriasRESUMEN
Background: Only a fraction of lung adenocarcinoma (LUAD) patients are eligible for immunotherapy. The identification of biomarkers for immunotherapy is crucial to improve patient outcomes. This study aims to systemically analyze LRP1B mutation and its association with the tumor immune microenvironment (TIME) and immunotherapy. Methods: A cohort of immune checkpoint inhibitors (ICIs)-treated LUAD patients was analyzed to assess the association of LRP1B mutation with immunotherapy prognosis. Another cohort of LUAD patients with genetic and transcriptomic data was also obtained from The Cancer Genome Atlas (TCGA). By investigating the ICIs and the TCGA-LUAD cohorts, we compared the differences in mutation profiles, immunogenicity, TIME, and DNA damage repair (DDR) mutations between the LRP1B-mutated and LRP1B wild-type groups. Additionally, we performed multiplex immunohistochemistry (mIHC) to validate the differences in the tumor microenvironment. Results: Our results revealed that LRP1B mutation is associated with multiple immune-related pathways. Analysis of TIME indicated that LUAD patients with LRP1B mutation expressed significant levels of genes involved in antigen presentation, cytotoxicity, chemokines, and pro-inflammatory mediators, whereas a few immune checkpoint genes were highly expressed in the LRP1B-mutated group as well. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis indicated that LRP1B-mutated LUAD patients had higher infiltration of active immune cells. Multiplex IHC analysis showed that LRP1B-mutated LUAD patients had elevated programmed death ligand-1 (PD-L1) expression and immune cell infiltration. Patients with LRP1B mutation had higher tumor mutation burden, neoantigens, as well as more mutated genes in the DDR-related pathways. Finally, LRP1B-mutated LUAD patients showed a significant prolongation of progression-free survival (PFS) in the ICIs cohort and could be effectively predicted by our constructed nomogram. Conclusions: Our study suggests that LRP1B mutation is associated with higher immune cell infiltration and elevated immune gene expression in TIME and potentially serves as a prognostic biomarker for LUAD patients treated with ICIs.
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Objective: This study aimed to develop and validate a questionnaire to evaluate nursing college students' mentally-passive and mentally-active sedentary time (M-PAST) in China. Methods: An initial M-PAST questionnaire with mentally-passive and mentally-active sedentary behaviors was developed with content validity undertaken through a consensus panel and pilot test where a convenience sample of six nursing students was recruited to assess the relevance, comprehensiveness, and comprehensibility of the refined questionnaire after expert panelists' responses. A cross-sectional online survey using a self-reported questionnaire was distributed to nursing students by email and then conducted using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to assess the construct validity of the M-PAST questionnaire and factor structures. Finally, the criterion validity was examined by exploring the associations between the M-PAST and the IPAQ sitting time, psychological distress, and insomnia. Results: Eight items regarding learning and leisure were included in the final version of the M-PAST questionnaire. A group of 650 nursing college students in China completed the study. Principal component analysis revealed two factors (i.e., mentally-passive and mentally-active sedentary behaviors), which explained 41.98% of the variance contributing to the questionnaire. The CFA reached the adaptive standard. Cronbach's α ranged from 0.730 to 0.742. The correlations between M-PAST and IPAQ total sitting time were significant (p < 0.01, r = 0.125-0.396). Mentally-passive sedentary time was associated with psychological distress and insomnia (p < 0.01, r = 0.078-0.163), while no significant associations were found in mentally-active sedentary behaviors. Conclusion and implications for practice: The M-PAST questionnaire appears to be a reliable and valid tool that reported both mentally-passive and mentally-active sedentary behaviors in nursing college students in China. However, future studies may need to further examine its validity among international nursing college students. This study further confirmed that mentally-passive sedentary behavior was positively associated with psychological distress and insomnia. Effective strategies are needed to reduce nursing college students' mentally-passive sedentary time to improve their health and wellbeing in China.
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Trastornos del Inicio y del Mantenimiento del Sueño , Estudiantes de Enfermería , Humanos , Conducta Sedentaria , Estudios Transversales , Reproducibilidad de los Resultados , Psicometría , Encuestas y CuestionariosRESUMEN
Background: Since late February 2022, a wave of coronavirus disease 2019 (COVID-19) mainly caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China. Traditional Chinese medicine treatment is recommended for pediatric patients; however, the safety and efficacy remain to be confirmed. We conducted a single-center, open-label, parallel-group randomized controlled trial to assess the efficacy and safety of a Chinese herb compound, Huashi Baidu granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19. Methods: 108 recruited children (aged 3-18 years) with laboratory-confirmed mild COVID-19 were randomly allocated 2:1 to receive oral HSBDG for five consecutive days (intervention group) and to receive compound pholcodine oral solution for five consecutive days (control group). The negative conversion time of SARS-CoV-2 nucleic acid and symptom scores were recorded. Results: The median negative conversion time of SARS-CoV-2 nucleic acid was significantly shorter in the intervention group than in the control group (median days [interquartile range (IQR)]: 3 [3-5] vs. 5 [3-6]; p = 0.047). The median total symptom score on day 3 was significantly lower in the intervention group than in the control group (median total symptom score [IQR]: 1 [0-2] vs. 2 [0-3]; p = 0.036). There was no significant differences in the frequency of antibiotic use and side effects between the two groups. Conclusion: HSBDG is a safe, effective oral Chinese herbal compound granule, which shows a good performance within the Omicron wave among pediatric patients.
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The bubble size distribution, location distribution, and gas holdup in a gas-liquid-solid flow three-phase stirred tank were numerically simulated by the Eulerian-Eulerian method and the population balance model (PBM). The Euler-Euler method combined with the PBM model included the influence of bubble aggregation and fragmentation on the interfacial force, which can better predict the bubble size distribution and phase holdups. The simulation results show that there are some differences in the fluid morphology and gas dispersion characteristics in the stirred tank under different rotating speeds. With the increase of rotating speed, the content of small-diameter bubbles increases obviously, and they are mainly concentrated in areas with higher speeds. The higher the rotational speed, the more the bubbles with small diameters, but the content of bubbles with large diameters is less affected by the rotational speed. Small-size bubbles mainly exist in the region of high fluid velocity, while large-size bubbles mainly exist in the region of low hydrostatic pressure. Compared with the change of the bubble content at different speeds, the content of bubbles with diameters of 0.50-1.90 mm is largest at 2000 rpm, while the content of bubbles with diameters of 2.65-10.09 mm is largest at 1500 rpm. The simulation work has certain guiding significance for the research and development of the forced mineralization device and the understanding of the dispersion characteristics of bubbles in the stirred tank.
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The present study sought to better understand the complex nature of emotion regulation in nursing students by exploring patterns of emotion regulation strategies (ERSs), and to examine the relationships between these unique profiles with alexithymia, nonsuicidal self-injury (NSSI) and resilience. A total of 1960 nursing students (Mage = 19.56, SD = 1.13 years) were recruited. Using latent profile analysis, nursing students were classified into four profiles based on their ERS use: high reaction profile (HRP; 11.53%), medium reaction profile (MRP; 55.46%), adaptive reaction profile (ARP; 22.86%) and low reaction profile (LRP; 10.15%). This study found that relative to HRP and MRP, ARP and LRP showed a lower incidence of NSSI and alexithymia; HRP and ARP showed a higher level of resilience than MRP and LRP. Furthermore, LRP had the lowest level of resilience. This study highlights the importance of identifying the different ERS profiles among nursing students. Targeted programs are needed to enhance adaptive strategies and reduce maladaptive strategies to improve nursing students' psychological and behavioural performance.
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Regulación Emocional , Conducta Autodestructiva , Estudiantes de Enfermería , Adulto , Síntomas Afectivos/epidemiología , Emociones , Humanos , Conducta Autodestructiva/epidemiología , Adulto JovenRESUMEN
An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, Sirt3 depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression.