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UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.
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Neoplasias de la Mama , Resistencia a Antineoplásicos , Receptor alfa de Estrógeno , Retroalimentación Fisiológica , Enzimas Ubiquitina-Conjugadoras , Humanos , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Animales , Progresión de la Enfermedad , Ratones Desnudos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Fulvestrant/farmacología , Ubiquitinación , Células MCF-7RESUMEN
Spin-wave excitations of magnetic moments (or magnons) can transport spin angular momentum in insulating magnetic materials. This property distinguishes magnonic devices from traditional electronics, where power consumption results from electrons' movement. Recently, magnon torques have been used to switch perpendicular magnetization in the presence of an external magnetic field. Here we present a material system composed of WTe2/antiferromagnetic insulator NiO/ferromagnet CoFeB heterostructures that allows magnetic field-free switching of the perpendicular magnetization. The magnon currents, with a spin polarization canting of -8.5° relative to the sample plane, traverse the 25-nm-thick polycrystalline NiO layer while preserving their original polarization direction, subsequently exerting an out-of-plane anti-damping magnon torque on the ferromagnetic layer. Using this mechanism, we achieve a 190-fold reduction in power consumption in PtTe2/WTe2/NiO/CoFeB heterostructures compared to Bi2Te3/NiO/CoFeB control samples, which only exhibit in-plane magnon torques. Our field-free demonstration contributes to the realization of all-electric, low-power, perpendicular magnetization switching devices.
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Gastric cancer (GC) is one of the most common digestive tract malignant tumors in the world. At the time of initial diagnosis, it frequently presents with local or distant metastasis, contributing to poor prognosis in patients. Neutrophil extracellular traps (NETs) constitute a mechanism employed by neutrophils that is intricately associated with tumor progression, prognosis, and response to immunotherapy and chemotherapy. Despite this, the specific involvement of NETs-related long non-coding RNAs (lncRNAs) in gastric cancer remains unclear. A prognostic model for NETs-related lncRNAs was constructed through correlation analysis, COX regression analysis, and least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the model was assessed using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, facilitating the exploration of the relationship between disease onset and prognosis in gastric cancer. Additionally, differences in the tumor microenvironment and response to immunotherapy among gastric cancer patients across high- and low-risk groups were analyzed. Furthermore, a prognostic nomogram integrating the risk score with relevant clinicopathological parameters was developed. The prognostic prediction model for gastric cancer, derived from NETs-related lncRNAs in this study, demonstrates robust prognostic capabilities, serving as a valuable adjunct to traditional tumor staging. This model holds promise in offering novel guidelines for the precise treatment of gastric cancer, thereby potentially improving patient outcomes.
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Background: Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. Methods: In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. Findings: We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02-21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97-4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%-8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. Interpretation: This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. Funding: None.
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Objectives: To investigate the association between the blood concentration of lipocalin-2 (LCN2) in local multiethnic residents and the increased risk for the development of metabolic syndrome (MS) in the Yanbian Korean Autonomous Prefecture population. Methods: A total of 2078 subjects with (study group) or without (control group) MS (1217 Korean-Chinese and 861 Han-Chinese subjects) were included in this study. MS subjects were divided into five groups according to ethnicity and MS components. They were assessed for smoking history, drinking history, past medical history, general demographic characteristics, and LCN2 concentrations. Results: LCN2 concentrations were higher in all ethnic MS groups than in the control group, and the highest concentrations were detected in Han-Chinese subjects with dyslipidemia. Moreover, LCN2 concentrations were significantly higher in Korean-Chinese individuals with all MS components than in the control group. Logistic regression analyses were conducted. In the unadjusted models, Korean-Chinese and Han-Chinese individuals with high LCN2 concentrations both faced a risk of MS with odds ratios (ORs) of 2.339 (95% confidence interval [CI]: 1.632-3.352) and 1.523 (95% CI: 1.101-2. 108), respectively. After the adjustment, the risk only remained in Korean-Chinese individuals, with an OR of 1.818 (95% CI: 1.031-3.207). Conclusion: Elevated circulating LCN2 was associated with the increased incidence of MS, and the effect in Korean-Chinese individuals was stronger than that in Han-Chinese individuals.
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OBJECTIVES: To detect the expression changes of interleukin-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) during the development of deep vein thrombosis in mice, and to explore the application value of them in thrombus age estimation. METHODS: The mice in the experimental group were subjected to ligation of inferior vena cava. The mice were sacrificed by excessive anesthesia at 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 21 d after ligation, respectively. The inferior vena cava segment with thrombosis was extracted below the ligation point. The mice in the control group were not ligated, and the inferior vena cava segment at the same position as the experimental group was extracted. The expression changes of IL-10 and TGF-ß1 were detected by immunohistochemistry (IHC), Western blotting and real-time qPCR. RESULTS: IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-ß1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis. Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-ß1 in each experimental group were higher than those in the control group. The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation, respectively. The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group, and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group. The mRNA and protein levels of TGF-ß1 reached the peak at 10 d and 14 d after ligation, respectively. The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group, and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group. CONCLUSIONS: The expressions of IL-10 and TGF-ß1 during the evolution of deep vein thrombosis present time-dependent sequential changes, and the expression levels of IL-10 and TGF-ß1 can provide a reference basis for thrombus age estimation.
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Modelos Animales de Enfermedad , Inmunohistoquímica , Interleucina-10 , Factor de Crecimiento Transformador beta1 , Vena Cava Inferior , Trombosis de la Vena , Animales , Interleucina-10/metabolismo , Interleucina-10/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Trombosis de la Vena/metabolismo , Trombosis de la Vena/etiología , Ratones , Vena Cava Inferior/metabolismo , Vena Cava Inferior/patología , Masculino , Factores de Tiempo , Monocitos/metabolismo , Western Blotting , ARN Mensajero/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Ligadura , Fibroblastos/metabolismoRESUMEN
BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive form of malignant melanoma with poor prognosis and high mortality rates. Disulfidptosis is a newly discovered cell death regulatory mechanism caused by the abnormal accumulation of disulfides. This unique pathway is guiding significant new research to understand cancer progression for targeted treatment. However, the correlation between disulfidptosis with long non-coding RNAs (lncRNAs) in SKCM remains unknown at present. METHODS: The Cancer Genome Atlas database furnished lncRNA expression data and clinical information for SKCM patients. Pearson correlation and Cox regression analyses identified disulfidptosis-related lncRNAs associated with SKCM prognosis. ROC curves and a nomogram validated the model. TME, immune infiltration, GSEA analysis, immune checkpoint gene expression profiling, and drug sensitivity were assessed in high and low-risk groups. Consistent clustering categorized SKCM patients for personalized clinical treatment guidance. RESULTS: A total of twelve disulfidptosis-related lncRNAs were identified for the development of prognosis prediction models. The area under the curve (AUC) values of the ROC curve and the nomogram provided reliable discrimination to evaluate the prognostic potential for SKCM patients. The TME played a crucial role in tumorigenesis, progression and prognosis, and the risk scores were closely related to immune cell infiltration. Meanwhile, the combination of chemotherapy, targeted therapy, and immunotherapy was recommended for low-risk patients based on drug sensitivity and immune efficacy analyses. CONCLUSION: We identified a risk model of twelve disulfidptosis-related lncRNAs that could be used to predict the prognosis of SKCM patients and help guide immunotherapy and chemotherapy for personalized treatment plans.
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Melanoma , ARN Largo no Codificante , Neoplasias Cutáneas , Microambiente Tumoral , Humanos , ARN Largo no Codificante/genética , Melanoma/genética , Melanoma/inmunología , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/tratamiento farmacológico , Pronóstico , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Masculino , Femenino , Persona de Mediana Edad , Nomogramas , Melanoma Cutáneo Maligno , Biomarcadores de Tumor/genética , Curva ROCRESUMEN
BACKGROUND: Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple studies has indicated that EPF/EPFLs might play significant roles in coordinating plant development and growth, especially as the morphogenesis processes of stoma, awn, stamen, and fruit skin. However, few research on EPF/EPFL gene family was reported in Gossypium. RESULTS: We separately identified 20 G. raimondii, 24 G. arboreum, 44 G. hirsutum, and 44 G. barbadense EPF/EPFL genes in the 4 representative cotton species, which were divided into four clades together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 17 Selaginella moellendorffii ones based on their evolutionary relationships. The similar gene structure and common motifs indicated the high conservation among the EPF/EPFL members, while the uneven distribution in chromosomes implied the variability during the long-term evolutionary process. Hundreds of collinearity relationships were identified from the pairwise comparisons of intraspecifc and interspecific genomes, which illustrated gene duplication might contribute to the expansion of cotton EPF/EPFL gene family. A total of 15 kinds of cis-regulatory elements were predicted in the promoter regions, and divided into three major categories relevant to the biological processes of development and growth, plant hormone response, and abiotic stress response. Having performing the expression pattern analyses with the basic of the published RNA-seq data, we found most of GhEPF/EPFL and GbEPF/EPFL genes presented the relatively low expression levels among the 9 tissues or organs, while showed more dramatically different responses to high/low temperature and salt or drought stresses. Combined with transcriptome data of developing ovules and fibers and quantitative Real-time PCR results (qRT-PCR) of 15 highly expressed GhEPF/EPFL genes, it could be deduced that the cotton EPF/EPFL genes were closely related with fiber development. Additionally, the networks of protein-protein interacting among EPF/EPFLs concentrated on the cores of GhEPF1 and GhEPF7, and thosefunctional enrichment analyses indicated that most of EPF/EPFLs participate in the GO (Gene Ontology) terms of stomatal development and plant epidermis development, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of DNA or base excision repair. CONCLUSION: Totally, 132 EPF/EPFL genes were identified for the first time in cotton, whose bioinformatic analyses of cis-regulatory elements and expression patterns combined with qRT-PCR experiments to prove the potential functions in the biological processes of plant growth and responding to abiotic stresses, specifically in the fiber development. These results not only provide comprehensive and valuable information for cotton EPF/EPFL gene family, but also lay solid foundation for screening candidate EPF/EPFL genes in further cotton breeding.
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Gossypium , Familia de Multigenes , Proteínas de Plantas , Gossypium/genética , Gossypium/metabolismo , Gossypium/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Genes de Plantas , Estudio de Asociación del Genoma Completo , Perfilación de la Expresión Génica , Mapas de Interacción de ProteínasRESUMEN
This longitudinal study in Mainland China (2021-2022) explored the impact of adverse childhood experiences (ACEs) on complex posttraumatic stress disorder (CPTSD) symptoms, with a focus on the role of self-compassion. Among 18,933 surveyed university students, 21.2% reported experiencing at least one ACE. Results revealed a clear relationship between ACEs and CPTSD symptoms. Furthermore, self-compassion, particularly the dimensions of self-judgment and isolation, moderated the association between retrospective ACEs and posttraumatic stress disorder (PTSD) and disturbance in self-organization (DSO) symptoms. These findings highlight the enduring impact of ACEs on CPTSD symptoms and emphasize the importance of early identification and targeted interventions, especially addressing self-judgment and isolation, to mitigate CPTSD risk among young Chinese adults.
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Experiencias Adversas de la Infancia , Empatía , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/psicología , Masculino , Femenino , China , Estudios Longitudinales , Adulto Joven , Experiencias Adversas de la Infancia/psicología , Adulto , Autoimagen , Adolescente , Estudios Retrospectivos , Estudiantes/psicología , Pueblos del Este de AsiaRESUMEN
The triple-network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple-network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange-I datasets. Spatial reference-based independent component analysis was used to identify the anterior and posterior part of default-mode network (aDMN and pDMN), salience network (SN), and bilateral executive-control network (ECN) from resting-state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple-network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self-inhibition in aDMN and pDMN, stronger inhibition in pDMNâaDMN, weaker inhibition in aDMNâLECN, pDMNâSN, LECNâSN, and LECNâRECN. Furthermore, negative relationships between ADOS scores and pDMN self-inhibition strength, as well as with the EC of pDMNâaDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple-networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments.
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Trastorno del Espectro Autista , Red en Modo Predeterminado , Imagen por Resonancia Magnética , Humanos , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/fisiopatología , Masculino , Niño , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatología , Conectoma , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Función Ejecutiva/fisiología , Adolescente , Teorema de BayesRESUMEN
Klebsiella pneumoniae (K. pneumoniae) is recognized as a zoonotic pathogen with an increasing threat to livestock and poultry. However, research on K. pneumoniae of animal origin remains limited. To address the gap, a comprehensive investigation was carried out by collecting a total of 311 samples from the farms of four animal species (dairy cow, chicken, sheep, and pig) in selected areas of Xinjiang, China. Isolates were identified by khe gene amplification and 16S rRNA gene sequencing. Genotyping of K. pneumonia isolates was performed using wzi typing and multilocus sequence typing (MLST). PCR was employed to identify virulence and resistance genes. An antibiotic susceptibility test was conducted using the Kirby-Bauer method. The findings revealed an isolation of 62 K. pneumoniae strains, with an average isolation rate of 19.94%, with the highest proportion originating from cattle sources (33.33%). Over 85.00% of these isolates harbored six virulence genes (wabG, uge, fimH, markD, entB, and ureA); while more than 75.00% of isolates possessed four resistance genes (blaTEM, blaSHV, oqxA, and gyrA). All isolates exhibited complete resistance to ampicillin and demonstrated substantial resistance to sulfisoxazole, amoxicillin/clavulanic acid, and enrofloxacin, with an antibiotic resistance rate of more than 50%. Furthermore, 48.39% (30/62) of isolates were classified as multidrug-resistant (MDR) strains, with a significantly higher isolation rate observed in the swine farms (66.67%) compared to other farms. Genetic characterization revealed the classification of the 62 isolates into 30 distinct wzi allele types or 35 different sequence types (STs). Notably, we identified K. pneumoniae strains of dairy and swine origin belonging to the same ST42 and wzi33-KL64 types, as well as strains of dairy and chicken origin belonging to the same wzi31-KL31-K31 type. These findings emphasize the widespread occurrence of drug-resistant K. pneumoniae across diverse animal sources in Xinjiang, underscoring the high prevalence of multidrug resistance. Additionally, our results suggest the potential for animal-to-animal transmission of K. pneumoniae and there was a correlation between virulence genes and antibiotic resistance genes. Moreover, the current study provides valuable data on the prevalence, antibiotic resistance, and genetic diversity of K. pneumoniae originating from diverse animal sources in Xinjiang, China.
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Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. ß-amyloid (Aß) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aß activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aß injury. Therefore, Aß-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aß injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aß-induced oxidative damage, and reduced apoptosis via the PI3â K/Akt signaling pathway. HG inhibited Aß deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aß; therefore, more natural active products are expected to be applied in AD therapy.
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With the exacerbation of global climate change and the growing environmental awareness among the general public, the concept of green consumption has gained significant attention across various sectors of society. As a representative example of green consumer products, energy-saving products play a crucial role in the timely realization of dual carbon goals. However, an analysis of online comments regarding energy-saving products reveals that the majority of these products still exhibit shortcomings in terms of efficacy, noise level, cost-effectiveness, and particularly, energy-saving appliances. This study focuses on the user-generated online comments data from the Taobao e-commerce platform for Grade 1 energy-saving refrigerators. By employing text mining techniques, the study aims to extract the essential information and sentiments expressed in the comments, in order to explore the consumption characteristics of Grade 1 energy-saving refrigerators. Moreover, the LBBA (LDA-Bert-BiLSTM-Attention) model is utilized to investigate the consumer topics of interest and emotional features. Initially, the LDA model is adopted to identify the attributes and weights of consumer concerns. Subsequently, the Bert model is pre-trained with the online comment data, and combined with the BiLSTM algorithm and Attention mechanism to predict sentiment categories. Finally, a transfer learning approach is utilized to determine the sentiment inclination of user-generated online comments and to identify the primary driving factors behind each sentiment category. This research employs sentiment analysis on online comments data regarding energy-saving products to uncover consumer sentiment attributes and emotional characteristics. It provides decision-makers with a comprehensive and systematic understanding of public consumption intentions, offering decision support for the efficient operation and management of the energy-saving product market.
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Algoritmos , Cambio Climático , HumanosRESUMEN
Introduction: Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. Materials and Methods: Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. Results: The IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. Conclusion: This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.
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Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Estenosis Espinal , Humanos , Microbioma Gastrointestinal/genética , Estenosis Espinal/genética , Estenosis Espinal/microbiología , Predisposición Genética a la EnfermedadRESUMEN
Sulfate transporter (SULTR) proteins are in charge of the transport and absorption on sulfate substances, and have been reported to play vital roles in the biological processes of plant growth and stress response. However, there were few reports of genome-wide identification and expression-pattern analysis of SULTRs in Hibiscus mutabilis. Gossypium genus is a ideal model for studying the allopolyploidy, therefore two diploid species (G. raimondii and G. arboreum) and two tetraploid species (G. hirsutum and G. barbadense) were chosen in this study to perform bioinformatic analyses, identifying 18, 18, 35, and 35 SULTR members, respectively. All the 106 cotton SULTR genes were utilized to construct the phylogenetic tree together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 8 Zea mays ones, which was divided into Group1-Group4. The clustering analyses of gene structures and 10 conserved motifs among the cotton SULTR genes showed the consistent evolutionary relationship with the phylogenetic tree, and the results of gene-duplication identification among the four representative Gossypium species indicated that genome-wide or segment duplication might make main contributions to the expansion of SULTR gene family in cotton. Having conducted the cis-regulatory element analysis in promoter region, we noticed that the existing salicylic acid (SA), jasmonic acid (JA), and abscisic acid (ABA) elements could have influences with expression levels of cotton SULTR genes. The expression patterns of GhSULTR genes were also investigated on the 7 different tissues or organs and the developing ovules and fibers, most of which were highly expressed in root, stem, sepal, receptacel, ovule at 10 DPA, and fiber at 20 and 25 DPA. In addition, more active regulatory were observed in GhSULTR genes responding to multiple abiotic stresses, and 12 highly expressed genes showed the similar expression patterns in the quantitative Real-time PCR experiments under cold, heat, salt, and drought treatments. These findings broaden our insight into the evolutionary relationships and expression patterns of the SULTR gene family in cotton, and provide the valuable information for further screening the vital candidate genes on trait improvement.
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Regulación de la Expresión Génica de las Plantas , Gossypium , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Gossypium/genética , Gossypium/crecimiento & desarrollo , Gossypium/metabolismo , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Familia de Multigenes , Genoma de Planta , Proteínas de Transporte de Anión/genética , Proteínas de Transporte de Anión/metabolismoRESUMEN
Polysaccharides from natural sources can regulate the composition of intestinal flora through the "gut-liver axis" pathway, potentially ameliorating alcoholic liver injury. Aspalathus linearis, also known as rooibos, is one such natural product that has shown promise in this regard. This study looked at the structural properties of A. linearis polysaccharide (ALP) and how well it would work to treat acute alcoholic liver impairment. This study looks at the composition of monosaccharides, functional groups, and molecular weight (Mw) of a newly discovered water-soluble polysaccharide, named ALP. The polysaccharide is composed of pyranose rings, amide groups, and sulfate groups linked by ß-glycosidic linkage. It has a relative Mw of 4.30 × 103 kDa and is composed of glucose, rhamnose, and some other monosaccharides. The study found that treating mice with the model of acute alcoholic liver disease with ALP could alleviate pathological symptoms, inhibit the release of inflammatory cytokines, and suppress indicators of oxidative stress. Experiments have shown that different doses of ALP can activate the P4502E1/Keap1-Nrf2-HO-1 signaling pathway. The regulation of inflammatory factors and downstream antioxidant enzymes occurs as a result. Based on these data, it is likely that ALP protects the liver via the "gut-liver axis" pathway by reducing oxidative stress-related damage, inflammation, and alcohol-related alterations to the gut microbiome. The results indicate that ALP mitigates injury caused by oxidative stress, inflammatory responses, and changes in the gut microbiota induced by alcohol through the "gut-liver axis" pathway, which provides protection to the liver. This provides preliminary evidence for the development of related drugs. PRACTICAL APPLICATION: Researchers extracted a polysaccharide from fresh leaves of Auricularia auricula. The polysaccharide was purified and determined to have a predominantly homogeneous molecular weight. An acute alcoholic liver damage mouse model was established, and it was concluded that the polysaccharide could ameliorate liver injury in mice through the "gut-liver axis" pathway. This novel polysaccharide can be used as an additive to develop functional foods with beneficial effects, which can positively impact the daily maintenance of consumers.
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Hepatopatías Alcohólicas , Estrés Oxidativo , Polisacáridos , Animales , Polisacáridos/farmacología , Polisacáridos/química , Ratones , Hepatopatías Alcohólicas/tratamiento farmacológico , Masculino , Estrés Oxidativo/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Antioxidantes/farmacología , Peso Molecular , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Citocinas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Citocromo P-450 CYP2E1/metabolismoRESUMEN
Interleukin 6 (IL-6), a pleiotropic cytokine, is crucial in a variety of inflammatory and immunological disorders. In recent years, mendelian randomization, which is a widely used and successful method of analyzing causality, has recently been investigated for the relationship between the IL-6 pathway and related diseases. However, no studies have been conducted to review the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization. In this study, the Web of Science Core Collection (WoSCC) served as our literature source database to gather articles about the IL-6 signaling pathway in Mendelian randomization from 2013 to 2023. VOSviewer (version 1.6.18), Microsoft Excel 2021, and Scimago Graphica were employed for bibliometric and visualization analysis. A total of 164 documents that were written by 981 authors coming from 407 institutions across 41 countries and published in 107 journals were located from January 2013 to August 2023. With 64 and 25, respectively, England and the University of Bristol had the highest number of publications. Frontiers in Immunology is the most prolific journal, and Golam M Khandaker has published the highest number of significant articles. The most co-cited article was an article entitled the interleukin-6 receptor as a target for prevention of coronary-heart-disease: a Mendelian randomization analysis, written by Daniel I Swerdlow. The most popular keywords were "mendelian randomization," "interleukin-6," "il-6," "c-reactive protein," "association," "coronary-heart-disease," "inflammation," "instruments," "risk," "rheumatoid arthritis," "depression." The full extent of the existing literature over the last 10 years is systematically revealed in this study, which can provide readers with a valuable reference for fully comprehending the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization.
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Artritis Reumatoide , Interleucina-6 , Humanos , Bibliometría , Citocinas , Transducción de SeñalRESUMEN
OBJECTIVE: To enhance understanding of the longitudinal progression of complex posttraumatic stress disorder (CPTSD) symptoms, this longitudinal study examined how CPTSD symptoms interact over time in Chinese college students with childhood trauma. METHODS: From 18,933 college students who took part in two surveys 12 months apart, 4,006 participants who reported adverse childhood experiences were screened. Cross-sectional network comparisons and cross-lagged panel network (CLPN) analysis characterized interactions among CPTSD symptoms. RESULTS: In the cross-sectional networks, feeling like a failure and avoid activities reminiscent of the trauma were the central symptoms. Takes long time to calm down and exaggerated startle are important bridge symptoms in the two networks respectively. The comparison of cross-sectional networks indicates that the global network strength was stable. The findings of the CLPN model reveal that feel worthless and feel like a failure had the highest "out" expected influence; exaggerated startle and avoid thoughts and feelings about the trauma had the highest "in" expected influence. CONCLUSIONS: By conducting cross-sectional network analyses, the study illuminated the attributes of CPTSD networks across various time points. Additionally, the CLPN analysis uncovered the longitudinal patterns of CPTSD symptoms.
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Experiencias Adversas de la Infancia , Trastornos por Estrés Postraumático , Estudiantes , Humanos , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/fisiopatología , Masculino , Estudios Longitudinales , Femenino , Estudiantes/psicología , Estudios Transversales , Adulto Joven , China , Universidades , Adulto , AdolescenteRESUMEN
OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation. This study aimed to investigate the anti-OA effect of scutellarein (SCU), a single-unit flavonoid compound obtained from Scutellaria barbata D. Don, in rats. METHODS: The extracted rat chondrocytes were treated with SCU and IL-1ß. The chondrocytes were divided into control group, IL-1ß group, IL-1ß+SCU 50 µmol/L group, and IL-1ß+SCU 100 µmol/L group. Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining. CCK-8 method was used to detect the cytotoxicity of SCU. ELISA, qRT-PCR, Western blotting, immunofluorescence, SAß-gal staining, flow cytometry, and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1ß intervention. Additionally, anterior cruciate ligament transection (ACL-T) was used to establish a rat OA model. Histological changes were detected by safranin O/fast green, hematoxylin-eosin (HE) staining, and immunohistochemistry. RESULTS: SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms. Specifically, it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation. In addition, SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase (NF-κB/MAPK) pathway, thereby reducing inflammatory cytokine production in the joint cartilage. Furthermore, SCU significantly reduced IL-1ß-induced apoptosis and senescence in rat chondrocytes, further highlighting its potential role in OA treatment. In vivo experiments revealed that SCU (at a dose of 50 mg/kg) administered for 2 months could significantly delay the progression of cartilage damage, which was reflected in a lower Osteoarthritis Research Society International (OARSI) score, and reduced expression of matrix metalloproteinase 13 (MMP13) in cartilage. CONCLUSION: SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.
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Apigenina , Condrocitos , Osteoartritis , Ratas , Animales , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Inflamación/patología , CartílagoRESUMEN
Osteoporosis is a metabolic disease characterized by bone density and trabecular bone loss. Bone loss may affect dental implant osseointegration in patients with osteoporosis. To promote implant osseointegration in osteoporotic patients, we further used a nonthermal atmospheric plasma (NTAP) treatment device previously developed by our research group. After the titanium implant (Ti) is placed into the device, the working gas flow and the electrode switches are turned on, and the treatment is completed in 30 s. Previous studies showed that this NTAP device can remove carbon contamination from the implant surface, increase the hydroxyl groups, and improve its wettability to promote osseointegration in normal conditions. In this study, we demonstrated the tremendous osteogenic enhancement effect of NTAP-Ti in osteoporotic conditions in rats for the first time. Compared to Ti, the proliferative potential of osteoporotic bone marrow mesenchymal stem cells on NTAP-Ti increased by 180% at 1 day (P = 0.004), while their osteogenic differentiation increased by 149% at 14 days (P < 0.001). In addition, the results indicated that NTAP-Ti significantly improved osseointegration in osteoporotic rats in vivo. Compared to the Ti, the bone volume fraction (BV/TV) and trabecular number (Tb.N) values of NTAP-Ti in osteoporotic rats, respectively, increased by 18% (P < 0.001) and 25% (P = 0.007) at 6 weeks and the trabecular separation (Tb.Sp) value decreased by 26% (P = 0.02) at 6 weeks. In conclusion, this study proved a novel NTAP irradiation titanium implant that can significantly promote osseointegration in osteoporotic conditions.