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Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.
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Trastorno Depresivo Mayor , Transcriptoma , Humanos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/fisiopatología , Femenino , Masculino , Adulto , Corteza Cerebral/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Persona de Mediana Edad , Imagen por Resonancia Magnética , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Spontaneous thought is a universal, complex, and heterogeneous cognitive activity that significantly impacts mental activity and strongly correlates with mental disorders. METHODS: Utilizing the think-aloud method, we captured spontaneous thoughts during rest from 38 diagnosed with depression, alongside 36 healthy controls and 137 healthy individuals. Through a comprehensive assessment of various dimensions of thought content, we compared thought content between individuals with depression and healthy controls, and between healthy women and men. Finally, we employed natural language processing (NLP) to develop regression models for multidimensional content assessment and a classification model to differentiate between individuals with and without depression. RESULTS: Compared to healthy controls, individuals with depression had more internally oriented and less externally oriented spontaneous thoughts. They focused more on themselves and negative things, and less on positive things, experiencing higher levels of negative emotions and lower levels of positive emotions. Besides, we found that compared to healthy men, healthy women's spontaneous thoughts focus more on interoception, the self, past events, and negative events, and they experience higher levels of negative emotions. Meanwhile, we identified the potential application of the think-aloud method to collect spontaneous thoughts and integrate NLP in the field of depression. CONCLUSIONS: This study offers direct insights into the stream of thought during individuals' resting state, revealing differences between individuals with depression and healthy controls, as well as sex differences in the content of spontaneous thoughts. It enhances our understanding of spontaneous thought and offers a new perspective for preventing, diagnosing, and treating depression.
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BACKGROUND: Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection, however, articles published in recent years have concluded that the treatment outcome of laparoscopic surgery for cervical cancer is inferior to that of open surgery. Thus, we choose a surgically new approach; the laparoscopic cervical cancer surgery in the open state is compared with the traditional open cervical cancer surgery, and we hope that patients can still have a good tumor outcome and survival outcome. This trial will investigate the effectiveness of laparoscopic cervical cancer surgery in the open-state treatment of early-stage cervical cancer. METHOD AND DESIGN: This will be an open-label, 2-armed, randomized, phase-III single-center trial of comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer. A total of 740 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound, and radiology data will be collected at baseline, and then at the study assessments and procedures performed at baseline and 1 week, 6 weeks, and 3 months, and follow-up visits begin at 3 months following surgery and continue every 3 months thereafter for the first 2 years and every 6 months until year 4.5. The primary aim is the rate of disease-free survival at 4.5 years. The secondary aims include treatment-related morbidity, costs and cost-effectiveness, patterns of recurrence, quality of life, pelvic floor function, and overall survival. CONCLUSIONS: This prospective trial aims to show the equivalence of the laparoscopic cervical cancer surgery in the open state versus the transabdominal radical hysterectomy approach for patients with early-stage cervical cancer following a 2-phase protocol. TRIAL REGISTRATION: ChiCTR2300075118. Registered on August 25, 2023.
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Histerectomía , Laparoscopía , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Femenino , Histerectomía/métodos , Histerectomía/efectos adversos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Resultado del Tratamiento , Ensayos Clínicos Fase III como Asunto , Adulto , Persona de Mediana Edad , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Calidad de VidaRESUMEN
To establish a rapid real-time RT-PCR method for differentiating wild-type classical swine fever virus (CSFV) strains from vaccine strains (HCLV), we designed a universal primer targeting the NS3 gene to detect wild-type CSFV strains and vaccine strains simultaneously, and two TaqMan-MGB probes were designed to differentiate between wild-type and vaccine strains. After optimizing the RT-qPCR conditions, a rapid dual TaqMan-MGB RT-qPCR method for the detection and identification of CSFV and HCLV was developed. The results showed that method could specifically detect CSFV and HCLV with no cross-reactivity with other swine pathogens. The analytic sensitivity for the NS3 gene of CSFV and HCLV were 1.67 × 101 copies/µL, respectively. For precision testing, the repeatability and reproducibility of the test was less than 2%. This method was successfully used for the rapid detection of 193 biological samples collected from CSFV-vaccinated pigs. This fast and accurate detection technology can be used for the detection of CSFV and is suitable for differentiating between wild-type CSFV strains and vaccine strains.
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Enhancing the flame retardancy and durability of cellulose fibers, particularly environmentally friendly regenerated cellulose fibers types like Lyocell fibers, is essential for advancing their broader application. This study introduced a novel approach to address this challenge. Cationic-modified Lyocell fibers (Lyocell@CAT) were prepared by introducing quaternary ammonium structures into the molecular chain of Lyocell fibers. Simultaneously, a flame retardant, APA, containing -COO-NH4+ and -P=O(O-NH4+)2 groups was synthesized. APA was then covalently bonded to Lyocell@CAT to prepare Lyocell@CAT@APA. Even after undergoing 30 laundering cycles (LCs), Lyocell@CAT@APA maintained a LOI value of 37.2 %, exhibiting outstanding flame retardant durability. The quaternary ammonium structure within Lyocell@CAT@APA formed asymmetric ionic bonds with the phosphate and carboxylate groups in APA, effectively shielding the binding of Na+ ions with phosphate groups during laundering, thereby enhancing the durability. Additionally, the consumption of Na+ ions by carboxylate groups further prevented their binding to phosphate groups, which contributed to enhance the durability properties. Flame retardant mechanism analysis revealed that both gas and condensed phase synergistically endowed excellent flame retardancy to Lyocell fibers. Overall, this innovative strategy presented a promising prospect for developing bio-safe, durable, and flame retardant cellulose textiles.
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Celulosa , Retardadores de Llama , Celulosa/química , Metales/química , Ácidos Carboxílicos/química , Iones/química , Compuestos de Amonio Cuaternario/químicaRESUMEN
The development of highly efficient urea oxidation reaction (UOR) electrocatalysts is the key to simultaneously achieving green hydrogen production and the treatment of urea-containing wastewater. Ni-based electrocatalysts are expected to replace precious metal catalysts for UOR because of their high activity and low cost. However, the construction of Ni-based electrocatalysts that can synergistically enhance UOR still needs further in-depth study. In this study, highly active electrocatalysts of NiFe(OH)x/MnO2 p-p heterostructures are constructed on nickel foam (NF) by electrodeposition (NiFe(OH)x/MnO2/NF), illustrating the effect of electronic structure changes at heterogeneous interfaces on UOR and revealing the catalytic mechanism of UOR. The NiFe(OH)x/MnO2/NF only needs 1.364 V (vs Reversible Hydrogen Electrode, RHE) to reach 10 mA cm-2 for UOR. Structural characterizations and theoretical calculations indicate that energy gap leads to directed charge transfer and redistribution at the heterojunction interface, forming electron-rich (MnO2) and electron-poor (NiFe(OH)x) regions. This enhances the catalyst's adsorption of urea and reaction intermediates, reduces thermodynamic barriers during the UOR process, promotes the formation of Ni3+ phases at lower potentials, and thus improves UOR performance. This work provides a new idea for the development of Ni-based high-efficiency UOR electrocatalysts.
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In order to enhance energy absorption, this study draws inspiration from the diagonal bilinear robust square lattice structure found in deep-sea glass sponges, proposing a design for thin-walled structures with superior folding capabilities and high strength-to-weight ratio. Firstly, the crashworthiness of bionic glass sponge tube (BGSTO) is compared with that of equal-wall-thickness equal-mass four-X tube through both experiments and simulations, and it is obtained that the specific energy absorption of BGSTO is increased by 78.64%. And the crashworthiness of BGSTO is also most significant compared to that of multicellular tubes with the similar number of crystalline cells. Additionally, we found that the double-line spacing of the glass sponge can be freely adjusted without changing the material amount. Therefore, based on BGSTO, we designed two other double-line structures, BGSTA and BGSTB. Then with equal wall thickness and mass as a prerequisite, this study proceeds to design and compare the energy absorption properties of three bilinear thin-walled tubes in both axial and lateral cases. The deformation modes and crashworthiness of the three types of tubes with variable bilinear spacing (ßO/A/B) are comparatively analysed. The improved complex proportional assessment (COPRAS) synthesis decision is used to obtain that BGSTO exhibits superior crashworthiness over the remaining two kinds of tubes. Finally, a surrogate model is established to perform multi-objective optimization on the optimal bilinear configuration BGSTO selected by the COPRAS method.
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Biónica , Poríferos , Poríferos/química , Animales , Materiales Biomiméticos/química , Simulación por Computador , Vidrio/química , Biomimética/métodosRESUMEN
BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.
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Neoplasias de la Mama , Calgranulina B , Células Asesinas Naturales , Receptores de Estrógenos , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Femenino , Calgranulina B/genética , Calgranulina B/metabolismo , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Microambiente Tumoral/inmunología , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Pronóstico , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
Subcortical brain structure segmentation plays an important role in the diagnosis of neuroimaging and has become the basis of computer-aided diagnosis. Due to the blurred boundaries and complex shapes of subcortical brain structures, labeling these structures by hand becomes a time-consuming and subjective task, greatly limiting their potential for clinical applications. Thus, this paper proposes the sparsification transformer (STF) module for accurate brain structure segmentation. The self-attention mechanism is used to establish global dependencies to efficiently extract the global information of the feature map with low computational complexity. Also, the shallow network is used to compensate for low-level detail information through the localization of convolutional operations to promote the representation capability of the network. In addition, a hybrid residual dilated convolution (HRDC) module is introduced at the bottom layer of the network to extend the receptive field and extract multi-scale contextual information. Meanwhile, the octave convolution edge feature extraction (OCT) module is applied at the skip connections of the network to pay more attention to the edge features of brain structures. The proposed network is trained with a hybrid loss function. The experimental evaluation on two public datasets: IBSR and MALC, shows outstanding performance in terms of objective and subjective quality.
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BACKGROUND: Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients. MATERIALS AND METHODS: Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan-Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT. RESULTS: After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36-1.83) and BCSS (HR 1.70, 95% CI 1.44-2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR. CONCLUSION: Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.
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Neoplasias de la Mama , Terapia Neoadyuvante , Receptor ErbB-2 , Receptores de Progesterona , Programa de VERF , Humanos , Femenino , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante/métodos , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Estadificación de Neoplasias , Receptores de Estrógenos/metabolismo , Estimación de Kaplan-Meier , Puntaje de Propensión , Modelos de Riesgos ProporcionalesRESUMEN
The superoxide radical (â¢O2-)-mediated peroxymonosulfate (PMS)-based photo-Fenton-like reaction enables highly selective water decontamination. Nevertheless, the targeted construction of â¢O2--mediated photo-Fenton-like system has been challenging. Herein, we developed an electron-rich/-poor dual sites driven â¢O2--mediated cascade photo-Fenton-like system by modulating electron density. Experimental and theoretical results demonstrated that PMS was preferentially adsorbed on electron-poor Co site. This adsorption promoted O-O bond cleavage of PMS to generate hydrogen peroxide (H2O2), which then migrated to electron-rich O site to extract eg electrons for O-H bond cleavage, rather than competing with PMS for Co site. The developed versatile cascade reaction system could selectively eliminate contaminants with low n-octanol/water partition constants (KOW) and dissociation constants (pKa) and remarkably resist inorganics (Cl-, H2PO4- and NO3-), humic acid (HA) and even real water matrices (tap water and secondary effluent). This finding provided a novel and plausible strategy to accurately and efficiently generate â¢O2- for the selective water decontamination.
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Node-containing straws exhibit superior mechanical properties compared to node-free straw plants, particularly in terms of shear resistance and compression resistance. We explore the relationship between the structure and mechanical properties of straw materials, providing deeper insights for the field of biomechanics. In this study, we focused on two node-containing straw plants, namely sorghum and reed. The main characteristics of sorghum and reed stalks were compared using macroscopic observation, stereomicroscopy, scanning electron microscopy, infrared spectroscopy, and EDS analysis. This study revealed numerous similarities and differences in the macro- and microstructures as well as the elemental composition of sorghum and reed stalks. The functional groups in sorghum and reed stalks were largely similar, with the primary elements being C and O. Distinguishing features included a higher tapering and a slightly larger reduction in wall thickness in sorghum stalks compared to reed stalks. The cross-section of sorghum stalks was filled with pith structures, while reed stalks exhibited a hollow structure. The vascular bundles in sorghum typically showed a paired arrangement, whereas those in reeds were arranged in odd numbers. Furthermore, sorghum straws contained more Cl and no Br, while the parenchyma of reed straws contained higher Br. The C and O proportions of sorghum straws and reed straws are 50-53% (50-51%) and 45-46% (48-49%), respectively. These variations in elemental composition are believed to be correlated with the mechanical properties of the materials. By conducting a detailed study of the micro/macrostructures and material composition of sorghum and reed straw, this paper provides valuable insights for the field of biomechanics.
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There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.
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Metal immunotherapy is a novel adjuvant immunotherapy. Mn2+ can activate STING-a type I IFN response protein-that promotes innate immunity and increases anti-tumor activity by promoting macrophage phagocytosis. IL-12, a cytokine that increases the antigen-presenting ability to promote effector T-cell activation, has potent antitumor activity, albeit with severe adverse effects. In this study, we observed that the combination of Mn2+ and IL-12 has a better antitumor effect and possibly reflects a better safety profile, providing a novel approach and theoretical basis for safe and rapid cancer treatment.
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Manganeso , Neoplasias , Femenino , Humanos , Manganeso/farmacología , Microambiente Tumoral , Interleucina-12 , InmunoterapiaRESUMEN
Breast cancer (BC) is the most prevalent malignancy among women worldwide. Mounting evidence suggests that PANoptosis participates in cancer development and therapy. However, the role of PANoptosis in BC remains unclear. In this study, we identified ten PANoptosis-related genes using Cox regression analysis, random forest (RF) algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. A PANoptosis-related score (PRS) was calculated based on the coefficient of LASSO. Notably, we divided the patients into high- and low-risk groups according to the PRS and revealed a negative correlation between PRS and overall survival. Next, a nomogram model was constructed and validated to improve the clinical application of PRS. Functional enrichment analyses and the Bayesian network demonstrated that differentially expressed genes between high- and low-risk groups were mainly enriched in immune-related pathways. Besides, we found significant differences in tumor mutation burden and tumor immune microenvironment between patients in these two groups using bulk-RNA and single-cell RNA sequencing data. Furthermore, charged multivesicular body protein 2B (CHMP2B) was identified as the hub gene by combining LASSO, weighted gene co-expression network analysis, RF and eXtreme Gradient Boosting. Importantly, using immunohistochemistry analysis based on our tissue microarray, we found that CHMP2B was highly expressed in tumor tissue, and CD4 and CD8 were more likely to be positive in the CHMP2B-negative group. Survival analyses revealed that CHMP2B adversely impacted the survival of BC patients. In conclusion, we not only constructed a highly accurate predictive model based on PRS, but also revealed the importance of PANoptosis-related gene signature in the modulation of the tumor microenvironment and drug sensitivity in BC.
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Anomaly detection is a highly important task in the field of data analysis. Traditional anomaly detection approaches often strongly depend on data size, structure and features, while introducing the idea of ensemble into anomaly detection can greatly improve the generalization ability. Ensemble-based anomaly detection methods still face some challenges, however, such as data imbalance, time and space demand and the selection of base detectors. To this end, we propose a selective ensemble method for anomaly detection based on parallel learning (SEAD-PL). First, a differentiated stratified sampling method is designed to alleviate the problem of data imbalance. Then, a distributed parallel training frame is built to address the problem of excessive time and space consumption for base detector training. Finally, a clustering-based ensemble selection strategy is introduced to balance the accuracy and diversity of base detectors. Experiments are performed on six datasets, which demonstrate that the proposed method has obvious advantages over four selected methods.
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Inspired by mussel adhesion and intrinsic flame retardant alginate fibers, a biomass flame retardant (PPCA) containing adhesive catechol and sodium carboxylate structure (-COO-Na+) based on biomass amino acids and protocatechualdehyde was designed to prepare flame retardant Lyocell fibers (Lyocell@PPCA@Na). Furthermore, through the substitution and chelation of metal ions by PPCA in the cellulose molecular chain, flame retardant Lyocell fibers chelating copper and iron ions (Lyocell@PPCA@Cu, Lyocell@PPCA@Fe) were prepared. Compared with the original sample, the peak heat release rate (PHRR) and total heat release (THR) for modified Lyocell fibers were significantly reduced. In addition, the modified sample exhibited a certain flame retardant durability. TG-FTIR analysis showed that the release of flammable gaseous substances was inhibited. The introduction of Schiff bases and aromatic structures in PPCA, as well as the decomposition of carboxylic metal salts were beneficial for the formation of char residue containing metal carbonates and metal oxides to play the condensed phase flame retardant effect. This work develops a new idea for the preparation of eco-friendly flame retardant Lyocell fibers without the traditional flame retardant elements such as P, Cl, and Br.
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Retardadores de Llama , Biomasa , Celulosa , Halógenos , IonesRESUMEN
A challenge to many real-world data streams is imbalance with concept drift, which is one of the most critical tasks in anomaly detection. Learning nonstationary data streams for anomaly detection has been well studied in recent years. However, most of the researches assume that the class of data streams is relatively balanced. Only a few approaches tackle the joint issue of imbalance and concept drift. To overcome this joint issue, we propose an ensemble learning method with generative adversarial network-based sampling and consistency check (EGSCC) in this paper. First, we design a comprehensive anomaly detection framework that includes an oversampling module by generative adversarial network, an ensemble classifier, and a consistency check module. Next, we introduce double encoders into GAN to better capture the distribution characteristics of imbalanced data for oversampling. Then, we apply the stacking ensemble learning to deal with concept drift. Four base classifiers of SVM, KNN, DT and RF are used in the first layer, and LR is used as meta classifier in second layer. Last but not least, we take consistency check of the incremental instance and check set to determine whether it is anormal by statistical learning, instead of threshold-based method. And the validation set is dynamic updated according to the consistency check result. Finally, three artificial data sets obtained from Massive Online Analysis platform and two real data sets are used to verify the performance of the proposed method from four aspects: detection performance, parameter sensitivity, algorithm cost and anti-noise ability. Experimental results show that the proposed method has significant advantages in anomaly detection of imbalanced data streams with concept drift.
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Algoritmos , Aprendizaje , Aprendizaje AutomáticoRESUMEN
BACKGROUD: Downhill running has recently become a promising exercise modality for metabolic syndrome, but the effect and precise mechanism of downhill running training on insulin resistance (IR) induced skeletal muscle atrophy remains unclear. The current study aimed to explore the benefits of downhill running training accompanied by a low-fat diet on skeletal muscle atrophy in IR mice and its possible mechanisms. METHODS: For in vivo study, high fat diet (HFD) -induced IR mice were submitted to the downhill running training or/and caloric restriction for 8 weeks. In vitro study was performed using co-cultured RAW264.7 macrophages and C2C12 myoblasts model. Glucose tolerance test (GTT), insulin tolerance test (ITT), immunofluorescence staining, Western blot analysis, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), Cell counting kit-8 (CCK-8) assays and glucose uptake assays were employed to explore the benefits and possible mechanisms of downhill running training accompanied by a low-fat diet on IR mice. RESULTS: Our data revealed that HFD induces IR, which leading to skeletal muscle atrophy. Downhill running accompanied by caloric restriction mitigated HFD-induced IR and improve skeletal muscle atrophy. Further study suggested that descended TRIB3 mediated the favorable impact of downhill running on IR induced skeletal muscle atrophy by suppressing M1-like macrophages and promoting M2-like macrophages. Macrophages-specific knockdown of TRIB3 exerted similar effects on the macrophage polarization and IR related myogenesis to downhill running training accompanied by caloric restriction. In contrast, macrophages-specific overexpression of TRIB3 descended phosphorylation of AKT, further activated M1-like macrophages and aggravated IR related inhibition of myogenesis. CONCLUSIONS: This finding demonstrated the beneficial effects of downhill running training and caloric restriction on IR related skeletal muscle atrophy by promoting M2-like macrophages through TRIB3-AKT pathway.
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Resistencia a la Insulina , Carrera , Ratones , Animales , Resistencia a la Insulina/fisiología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Restricción Calórica , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Macrófagos/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
Sepsis-associated acute kidney injury (SA-AKI) has a high mortality rate and lacks effective targeted treatment. We applied lipopolysaccharides-induced injury models in human and mouse renal tubular epithelial cells, and at the same time, we selected a commonly used sedative drug, dexmedetomidine, to investigate its potential for renal protection. We found a significant increase in the expression level of HSP90, and the interaction with glutathione peroxidase 4 (GPX4) led to autophagic degradation of GPX4, triggering ferroptosis. Dexmedetomidine reduced the degradation of GPX4 by increasing the binding of KEAP1 and HSP90 in the cytoplasm. Therefore, lipid peroxidation and ferroptosis were reduced. Similarly, dexmedetomidine showed renal protective effects in C57BL/6J male mice with SA-AKI induced by cecal ligation. Our study reveals a new mechanism of renal tubular epithelial cell ferroptosis in SA-AKI treated with dexmedetomidine.