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BACKGROUND: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. PATIENTS AND METHODS: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. RESULTS: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). CONCLUSIONS: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.
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2,3-Indole-fused 1,4-diazocines represent a new family of indole alkaloid compounds and are difficult to access by the reported protocols. Herein, we report a copper-catalyzed decarboxylative cyclization of cyclic propargylic carbamates with imidazolidines via sequential C-N/C-N/C-C bond formation to deliver a series of 2,3-indole-fused 1,4-diazocines, with a broad substrate scope and mild conditions.
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OBJECTIVE: This study aimed to examine the relationship between food insecurity (FI) and eating disorder psychopathology in a large sample of rural Chinese adolescents. METHODS: Analyses included 1654 adolescents (55.4% girls; Mage = 16.54 years, SD = 1.45) from a rural high school in southwestern China. FI, eating disorder psychopathology, and psychological distress (i.e., symptoms of depression, anxiety, and stress) were assessed. Data were analyzed by sex. Pearson correlation analysis was performed to investigate the zero-order association between FI and eating disorder psychopathology. Hierarchical linear regressions were used to explore whether FI could explain meaningful variance in eating disorder psychopathology beyond psychological distress and demographic covariates (e.g., socioeconomic status). RESULTS: FI was significantly associated with higher eating disorder psychopathology for boys (r = 0.44, p < 0.001) and girls (r = 0.43, p < 0.001), with medium-to-large effect sizes. FI accounted for significant unique variance in eating disorder psychopathology beyond psychological distress and demographic covariates for boys (ΔR2 = 0.14, p < 0.001) and girls (ΔR2 = 0.10, p < 0.001). DISCUSSION: Using a large sample of rural Chinese adolescents, this study extends the connection between FI and eating disorder pathology in adolescents beyond the Western context. Future investigations on the mechanisms underlying FI and eating disorder psychopathology are warranted for developing prevention strategies for eating disorders among rural Chinese adolescents. PUBLIC SIGNIFICANCE: This is the first investigation that examined the link between FI and eating disorder psychopathology among rural Chinese adolescents. Our findings highlight the importance of incorporating FI as a potential risk factor to screen for the prevention and intervention of eating disorders among rural Chinese adolescents.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Inseguridad Alimentaria , Distrés Psicológico , Población Rural , Humanos , Masculino , Femenino , Adolescente , China/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Pueblos del Este de AsiaRESUMEN
After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The majority of patients suffer from the localized illness at primary diagnosis that could rapidly assault other organs. This disease stage is referred as metastatic castration-resistant prostate cancer (mCRPC). Surgery and radiation are still the treatment of CRPC, but have some adverse effects such as urinary symptoms and sexual dysfunction. Hormonal castration therapy interfering androgen receptor (AR) signaling pathway is indispensable for most advanced prostate cancer patients, and the first- and second-generation of novel AR inhibitors could effectively cure hormone sensitive prostate cancer (HSPC). However, the resistance to these chemical agents is inevitable, so many of patients may experience relapses. The resistance to AR inhibitor mainly involves AR mutation, splice variant formation and amplification, which indicates the important role in CRPC. Proteolysis-targeting chimera (PROTAC), a potent technique to degrade targeted protein, has recently undergone extensive development as a biological tool and therapeutic drug. This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication.
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Neoplasias de la Próstata Resistentes a la Castración , Quimera Dirigida a la Proteólisis , Receptores Androgénicos , Transducción de Señal , Animales , Humanos , Masculino , Antagonistas de Receptores Androgénicos/uso terapéutico , Antagonistas de Receptores Androgénicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Here we report the first example of iridium-catalyzed asymmetric N-allylation of pyrazoles with dienyl allylic alcohols under mild conditions with broad functional group tolerance, exhibiting excellent N1/C3-site selectivities and enantioselectivities (up to >99% ee). In addition to pyrazoles, other nucleophiles including benzotriazole, triazole, and pyrazole precursors (aryl vinyldiazos) are also suitable in this method. Notably, with the use of Sc(OTf)3 as additive and reactions performed at 30 °C for 24 h, the N1-C5 or N1-C1 selective alkylated pyrazoles are also obtained.
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A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to enhance oral delivery of paclitaxel (PTX) by targeting monocarboxylate transporters (MCT) and glucose transporters (GLUT). The synthesized NSCF was characterised by FT-IR and 1H NMR spectra. The prepared 30.78 % (degree of substitution of N-SAA) NSCF-PTX-PLip were approximately 150 nm in size, with a regular spherical shape, the zeta potential of -25.4 ± 5.13 mv, drug loading of 2.35 % ± 0.05 %, and pH-sensitive and slow-release characteristics. Compared with PTX-Lip, 30.78 % NSCF-PTX-PLip significantly enhanced Caco-2 cellular uptake via co-mediation of MCT and GLUT, showing relatively specific binding of propionic acid and MCT. Notably, the NSCF modification of PTX-Lip had no appreciable influence on their original cellular uptake pathway. The fructose modification of 30.78 % NSC-PTX-PLip significantly increased the concentration after tmax, indicating their continuous and efficient absorption. Compared with PTX-Lip, the 30.78 % NSCF-PTX-PLip resulted in a 2.09-fold extension of MRT, and a 6.06-fold increase of oral bioavailability. It significantly increased tumour drug distribution and tumour growth inhibition rate. These findings confirm that 30.78 % NSCF-PLip offer a potential oral delivery platform for PTX and targeting the dual transporters of MCT and GLUT is an effective strategy for enhancing the intestinal absorption of drugs.
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Antineoplásicos Fitogénicos , Paclitaxel , Humanos , Paclitaxel/química , Liposomas/química , Células CACO-2 , Espectroscopía Infrarroja por Transformada de Fourier , Fructosa , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos Fitogénicos/químicaRESUMEN
Wireless Sensor Networks (WSNs) have emerged as an efficient solution for numerous real-time applications, attributable to their compactness, cost-effectiveness, and ease of deployment. The rapid advancement of 5G technology and mobile edge computing (MEC) in recent years has catalyzed the transition towards large-scale deployment of WSN devices. However, the resulting data proliferation and the dynamics of communication environments introduce new challenges for WSN communication: (1) ensuring robust communication in adverse environments and (2) effectively alleviating bandwidth pressure from massive data transmission. In response to the aforementioned challenges, this paper proposes a semantic communication solution. Specifically, considering the limited computational and storage resources of WSN devices, we propose a flexible Attention-based Adaptive Coding (AAC) module. This module integrates window and channel attention mechanisms, dynamically adjusts semantic information in response to the current channel state, and facilitates adaptation of a single model across various Signal-to-Noise Ratio (SNR) environments. Furthermore, to validate the effectiveness of this approach, the paper introduces an end-to-end Joint Source Channel Coding (JSCC) scheme for image semantic communication, employing the AAC module. Experimental results demonstrate that the proposed scheme surpasses existing deep JSCC schemes across datasets of varying resolutions; furthermore, they validate the efficacy of the proposed AAC module, which is capable of dynamically adjusting critical information according to the current channel state. This enables the model to be trained over a range of SNRs and obtain better results.
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Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model. However, to enhance treatment efficiency, liver-targeted delivery needs to be improved. Therefore, human serum albumin (HSA)-encapsulated AuNCs were constructed to achieve enhanced liver targeting and more potent mitigation of Con A-induced elevations in plasma aspartate transaminase (AST), alanine transaminase (ALT), and liver injury in mice. In vivo and in vitro mechanism studies indicated that AuNCs could suppress the secretion of IFN-γ by Con A-stimulated T cells and subsequently inhibit the activation of the JAK2/STAT1 pathway and eventual hepatocyte apoptosis induced by IFN-γ. These actions ultimately protect the liver from immune cell infiltration and damage caused by Con A. These findings suggest that bio-protected AuNCs hold promise as nanodrugs for AIH therapy, with their liver targeting capabilities and therapeutic efficiency being further improved via rational surface ligand engineering.
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As an efficient and cost-effective adsorbent, biochar has been widely used in the adsorption and removal of dyes. In this study, a simple NaOH-modified biochar with the pyrolysis temperature of 300 °C (NaCBC300) was synthesized, characterized, and investigated for the adsorption performances and mechanisms of methylene blue (MB). NaCBC300 exhibited excellent MB adsorption performance with maximum removal efficiency and adsorption capacity of 99.98% and 290.71 mg g-1, which were three and four times higher than biochar without modification, respectively. This might be attributed to the increased content of -OH and the formation of irregular flakes after NaOH modification. The Freundlich isotherm suggested multilayer adsorption between NaCBC300 and MB. Spectroscopic characterizations demonstrated that multiple mechanisms including π-π interaction, H-bonding, and pore-filling were involved in the adsorption. According to density functional theory (DFT) calculations, electrostatic interaction between NaCBC300 and MB was verified. The highest possibility of the attraction between NaCBC300 and MB was between -COOH in NaCBC300 and R-N(CH3)2 in MB. This work improved our understanding of the mechanism for MB adsorption by modified biochar and provided practical and theoretical guidance for adsorbent preparation with high adsorption ability for dyes.
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As the UAV(Unmanned Aerial Vehicle) carrying target detection algorithm in transmission line insulator inspection, we propose a lightweight YOLOv7 insulator defect detection algorithm for the problems of inferior insulator defect detection speed and high model complexity. Firstly, a lightweight DSC-SE module is designed using a DSC(Depthwise Separable Convolution) fused SE channel attention mechanism to substitute the SC(Standard Convolution) of the YOLOv7 backbone extraction network to decrease the number of parameters in the network as well as to strengthen the shallow network's ability to obtain information about target features. Then, in the feature fusion part, GSConv(Grid Sensitive Convolution) is used instead of standard convolution to further lessen the number of parameters and the computational effort of the network. EIoU-loss(Efficient-IoU) is performed in the prediction head part to make the model converge faster. According to the experimental results, the recognition accuracy rate of the improved model is 95.2%, with a model size of 7.9M. Compared with YOLOv7, the GFLOPs are reduced by 54.5%, the model size is compressed by 37.8%, and the accuracy is improved by 4.9%. The single image detection time on the Jetson Nano is 105ms and the capture rate is 13FPS. With guaranteed accuracy and detection speed, it meets the demands of real-time detection.
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Algoritmos , Sistemas de Computación , Reconocimiento en Psicología , Dispositivos Aéreos No TripuladosRESUMEN
Treating chronic wounds requires transition from proinflammatory M1 to anti-inflammatory M2 dominant macrophages. Based on the role of tumor extracellular vesicles (tEVs) in regulating the phenotypic switching from M1 to M2 macrophages, we propose that tEVs may have a beneficial impact on alleviating the overactive inflammatory microenvironment associated with refractory wounds. On the other hand, as a nitric oxide donor, S-nitrosoglutathione (GSNO) can regulate inflammation, promote angiogenesis, enhance matrix deposition, and facilitate wound healing. In this study, a guar gum-based hydrogel with tEVs and GSNO was designed for the treatment of diabetic refractory wounds. This hybrid hydrogel was formed through the phenyl borate bonds, which can automatically disintegrate in response to the high reactive oxygen species (ROS) level at the site of refractory diabetic wounds, releasing tEVs and GSNO. We conducted a comprehensive evaluation of this hydrogel in vitro, which demonstrated excellent performance. Meanwhile, using a full-thickness excision model in diabetic mice, the wounds exposed to the therapeutic hydrogel healed completely within 21 days. The increased closure rate was associated with macrophage polarization and collagen deposition, accelerated fibroblast proliferation, and increased angiogenesis in the regenerating tissues. Therefore, this multifunctional hybrid hydrogel appears to be promising for clinical applications.
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Diabetes Mellitus Experimental , Hidrogeles , Ratones , Animales , Hidrogeles/farmacología , Hidrogeles/química , S-Nitrosoglutatión/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Cicatrización de Heridas , RegeneraciónRESUMEN
As one of the triterpene extracts of Taraxacum, a traditional Chinese plant, taraxerol (TRX) exhibits antitumor activity. In this study, we evaluated the effects of TRX on the migration and invasion of MDA-MB-231 cells, analyzed the molecular mechanism through network pharmacology and molecular docking, and finally verified it by in vitro experiments. The results showed that TRX could inhibit the migration and invasion of MDA-MB-231 cells in a time- and concentration-dependent manner, while MAPK3 was the most promising target and could stably combine with TRX. In addition, the relative protein expression levels were detected by Western blot, and we observed that TRX could inhibit the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis. Moreover, an ERK activator (tert-butylhydroquinone, tBHQ) partially reversed the suppressive effect of TRX on MDA-MB-231 cells. In conclusion, TRX inhibited the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis.
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Ácido Oleanólico , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Línea CelularRESUMEN
BACKGROUND: Acute pancreatitis (AP) is a disease featuring acute inflammation of the pancreas and histological destruction of acinar cells. Approximately 20% of AP patients progress to moderately severe or severe pancreatitis, with a case fatality rate of up to 30%. However, a single indicator that can serve as the gold standard for prognostic prediction has not been discovered. Therefore, gaining deeper insights into the underlying mechanism of AP progression and the evolution of the disease and exploring effective biomarkers are important for early diagnosis, progression evaluation, and precise treatment of AP. AIM: To determine the regulatory mechanisms of tRNA-derived fragments (tRFs) in AP based on small RNA sequencing and experiments. METHODS: Small RNA sequencing and functional enrichment analyses were performed to identify key tRFs and the potential mechanisms in AP. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to determine tRF expression. AP cell and mouse models were created to investigate the role of tRF36 in AP progression. Lipase, amylase, and cytokine levels were assayed to examine AP progression. Ferritin expression, reactive oxygen species, malondialdehyde, and ferric ion levels were assayed to evaluate cellular ferroptosis. RNA pull down assays and methylated RNA immunoprecipitation were performed to explore the molecular mechanisms. RESULTS: RT-qPCR results showed that tRF36 was significantly upregulated in the serum of AP patients, compared to healthy controls. Functional enrichment analysis indicated that target genes of tRF36 were involved in ferroptosis-related pathways, including the Hippo signaling pathway and ion transport. Moreover, the occurrence of pancreatic cell ferroptosis was detected in AP cells and mouse models. The results of interference experiments and AP cell models suggested that tRF-36 could promote AP progression through the regulation of ferroptosis. Furthermore, ferroptosis gene microarray, database prediction, and immunoprecipitation suggested that tRF-36 accelerated the progression of AP by recruiting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) to the p53 mRNA m6A modification site by binding to IGF2BP3, which enhanced p53 mRNA stability and promoted the ferroptosis of pancreatic follicle cells. CONCLUSION: In conclusion, regulation of nuclear pre-mRNA domain-containing protein 1B promoted AP development by regulating the ferroptosis of pancreatic cells, thereby acting as a prospective therapeutic target for AP. In addition, this study provided a basis for understanding the regulatory mechanisms of tRFs in AP.
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Pancreatitis , Animales , Ratones , Pancreatitis/genética , Enfermedad Aguda , Proteína p53 Supresora de Tumor , ARN de Transferencia/genética , ARN , ARN Mensajero/genéticaRESUMEN
Ring finger protein 213 (RNF213) is a large E3 ubiquitin ligase with a molecular weight of 591 kDa that is associated with moyamoya disease, a rare cerebrovascular disease. It is located in the cytosol and perinuclear space. Missense mutations in this gene have been found to be more prevalent in patients with moyamoya disease compared with that in healthy individuals. Understanding the molecular function of RNF213 could provide insights into moyamoya disease. RNF213 contains a C3HC4-type RING finger domain with an E3 ubiquitin ligase domain and six AAA+ adenosine triphosphatase (ATPase) domains. It is the only known protein with both AAA+ ATPase and ubiquitin ligase activities. Recent studies have highlighted the role of RNF213 in fighting against microbial infections, including viruses, parasites, bacteria, and chlamydiae. This review aims to summarize the recent research progress on the mechanisms of RNF213 in pathogenic infections, which will aid researchers in understanding the antimicrobial role of RNF213.
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Antiinfecciosos , Enfermedad de Moyamoya , Humanos , Ubiquitina-Proteína Ligasas , Genes Reguladores , Factores de Transcripción , Adenosina TrifosfatasasRESUMEN
Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of -30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm-2) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (-50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm-2) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way.
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The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of ß-catenin. Ultimately, the nuclear localization of ß-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.
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Células Madre Mesenquimatosas , ARN Largo no Codificante , Ratas , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , beta Catenina/metabolismo , Osteogénesis/genética , Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Péptidos/metabolismo , Células CultivadasRESUMEN
Objective: To identify the correlation between finger-to-floor distance(FFD) and the spinal function indices and disease activity scores of ankylosing spondylitis (AS) via a multicentre case-control study, and to calculate the optimal cutoff value of FFD using statistical methods. Methods: Patients with AS and healthy individuals were recruited, and the FFD and other spinal mobility values were measured. The correlation between the FFD and the Bath Ankylosing Spondylitis Metric Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) was analyzed using Spearman rank correlation analysis. Receiver operating characteristic (ROC) curves of FFD stratified by gender and age were drawn and their optimal cutoff values were determined. Results: A total of 246 patients with AS and 246 healthy subjects were recruited. The FFD was strongly correlated with BASMI (r = 0.72, p < 0.001), moderately correlated with BASFI (r = 0.50, p < 0.001) and weakly correlated with BASDAI (r = 0.36, p < 0.001). The lowest cutoff value of the FFD was 2.6 cm while the highest was 18.4 cm. Moreover, the FFD was significantly correlated with sex and age. Conclusion: There exists a strong correlation between the FFD and spinal mobility, a moderately correlation and function, which provides reliable data for the evaluation of patients with AS in clinical settings and the rapid screening of low back pain-related diseases in the general population. Furthermore, these findings have clinical potential in improving the missed diagnosis or delayed diagnosis of low back pain.
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Background: Glucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated. Methods: In this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown. Results: GNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells. Conclusion: GNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Mama , Inmunoterapia , Biomarcadores , Linfocitos B , Glucosamina 6-Fosfato N-AcetiltransferasaRESUMEN
Affordance is a property of object with respect to the observer, which is related to the attributes of the object. In the present study, we examined whether affordance elicitation is primarily based on the conceptual attributes or instance attributes of the object. To distinguish the role of the two types of attributes in elicitation of affordance, we manipulated the size of a pan in virtual reality (Experiment 1). The critical condition is the giant pan, which should elicit manipulability affordance if affordance is concept-based and it should not elicit manipulability affordance if affordance is instance-based. The results support the former assumption, i.e., the elicitation of affordance is concept-based. To confirm the conclusion, we created a water-handled pan in virtual reality and examined its manipulability affordance (Experiment 2). The water-handled pan looks similar to a normal pan, but its handle is composed of flowing water which, in concept, cannot be grasped. Consistent with the concept-based conclusion, the water-handled pan did not elicit manipulability affordance. The present findings provided convergent evidence that ordinary people rely primarily on conceptual attributes of the object to elicit manipulability affordance.
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Desempeño Psicomotor , Realidad Virtual , Humanos , Tiempo de ReacciónRESUMEN
Producing "green urea" using renewable energy, N2, and CO2 is a long-considered challenge. Herein, an electrocatalyst, Bi2S3/N-reduced graphene oxide (RGO), was synthesized by loading the Bi2S3 nanorods onto the N-RGO via a hydrothermal method. The Bi2S3/N-RGO composites exhibit the highest yield of urea (4.4 mmol g-1 h-1), which is 12.6 and 3.1 times higher than that of Bi2S3 (0.35 mmol g-1 h-1) and that of N-RGO (1.4 mmol g-1 h-1), respectively. N-RGO, because of its porous and open-layer structure, improves the mass transfer efficiency and stability, while the basic groups (-OH and -NH2) promote the adsorption and activation of CO2. Bi2S3 promotes the absorption and activation of inert N2. Finally, the defect sites and the synergistic effect on the Bi2S3/N-RGO composites work simultaneously to form urea from N2 and CO2. This study provides new insights into urea synthesis under ambient conditions and a strategy for the design and development of a new material for green urea synthesis.