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Background: The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown. Objective: In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR). Methods: We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran's Q tests. FDR correction was used to correct the p-values. Results: IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane's Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results. Conclusion: Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.
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Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier's intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.
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Aneurisma da Aorta Abdominal , Metaloproteinase 9 da Matriz , Camundongos Endogâmicos C57BL , Nanopartículas , RNA Interferente Pequeno , Aneurisma da Aorta Abdominal/tratamento farmacológico , Animais , Camundongos , Nanopartículas/química , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Polifenóis/química , Polifenóis/farmacologia , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Chá/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Humanos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Técnicas de Transferência de Genes , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Apoptose/efeitos dos fármacosRESUMO
The therapy of large defects in peripheral nerve injury (PNI) suffers from several drawbacks, especially the lack of autologous nerve donors. Nerve conduits are considered as a solution for nerve injury treatment, but biocompatibility improvements is still required for conduits prepared with synthetic materials. Cell-derived extracellular matrix (ECM) has drawn attention due to its lower risk of immunogenic response and independence from donor availability. The goal of this study is to coat bone mesenchymal stem cell-derived ECMs on poly(lactic-co-glycolic) acid (PLGA) conduits to enhance their ability to support neural growth and neurite extensions. The ECM-coated conduits have better hydrophilic properties than the pure PLGA conduits. A marked increase on PC12 and RSC96 cells' viability, proliferation and dorsal root ganglion neurite extension was observed. Quantitative PCR analysis exhibited a significant increase in markers for cell proliferation (GAP43), neurite extension (NF-H, MAP2, andßIII-tubulin) and neural function (TREK-1). These results show the potential of ECM-coated PLGA conduits in PNI therapy.
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Proliferação de Células , Sobrevivência Celular , Matriz Extracelular , Células-Tronco Mesenquimais , Regeneração Nervosa , Neuritos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Ratos , Neuritos/metabolismo , Células PC12 , Matriz Extracelular/metabolismo , Células-Tronco Mesenquimais/citologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Regeneração Nervosa/efeitos dos fármacos , Alicerces Teciduais/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Gânglios Espinais , Traumatismos dos Nervos Periféricos/terapia , Engenharia Tecidual/métodos , Polímeros/química , Teste de MateriaisRESUMO
Diurnal floret opening time (DFOT) is a pivotal trait for successful fertilization and hybrid breeding in rice. However, the molecular mechanism underlying this trait is poorly understood in rice. In this study, we combined the cytological, genetic and molecular studies to demonstrate that jasmonic acid (JA) regulates DFOT in rice through modulating the turgor and osmotic pressure of the lodicules. We show that lodicules undergo dramatic morphologic changes, accompanied by changes in water and sugar contents during the process of floret opening. Consistently, a large set of genes associated with cell osmolality and cell wall remodeling exhibits distinct expression profiles at different time points in our time-course transcriptomes of lodicules. Notably, a group of JA biosynthesis and signaling genes is continuously upregulated, accompanied by a gradual increase in JA accumulation as floret opening approaching. Furthermore, we demonstrate that the JA biosynthesis gene OsAOS1 is required for endogenous JA biosynthesis in lodicules and promoting rice DFOT. Moreover, OsMYC2, a master regulator of JA signaling, regulates rice DFOT by directly activating OsAOS1, OsSWEET4, OsPIP2;2 and OsXTH9. Collectively, our findings establish a core regulatory network mediated by JA for modulating rice DFOT and provide effective gene targets for the genetic improvement of DFOT in rice.
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Anagyrus, a genus of Encyrtidae (Hymenoptera, Chalcidoidea), represents a successful group of parasitoid insects that attack various mealybug pests of agricultural and forestry plants. Until now, only 20 complete mitochondrial genomes have been sequenced, including those in this study. To enrich the diversity of mitochondrial genomes in Encyrtidae and to gain insights into their phylogenetic relationships, the mitochondrial genomes of two species of Anagyrus were sequenced, and the mitochondrial genomes of these species were compared and analyzed. Encyrtid mitochondrial genomes exhibit similarities in nucleotide composition, gene organization, and control region patterns. Comparative analysis of protein-coding genes revealed varying molecular evolutionary rates among different genes, with six genes (ATP8, ND2, ND4L, ND6, ND4 and ND5) showing higher rates than others. A phylogenetic analysis based on mitochondrial genome sequences supports the monophyly of Encyrtidae; however, the two subfamilies, Encyrtinae and Tetracneminae, are non-monophyletic. This study provides valuable insights into the phylogenetic relationships within the Encyrtidae and underscores the utility of mitochondrial genomes in the systematics of this family.
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MYC amplification is frequently observed in approximately 50% of human cancers, rendering it a highly desired anticancer target. Given the challenge of direct pharmacological inhibiting of MYC, impairing the interaction of MYC and its key cofactor WDR5 has been proposed as a promising strategy for MYC-driven cancer treatment. Herein, we report the discovery of 5-thiocyanatothiazol-2-amines that disrupt the WDR5-MYC interaction. Hit fragments were initially identified in a fluorescence polarization (FP)-based screening of an in-house library, and structural-activity relationship exploration resulted in the lead compounds 4m and 4o with potent inhibitory activities on WDR5-MYC interaction (K i = 2.4 µM for 4m; K i = 1.0 µM for 4o). These compounds were further validated via differential scanning fluorimetry (DSF) and coimmunoprecipitation (Co-IP). Moreover, 4m and 4o exhibited good cellular activities with the IC50 values at the micromolar level (IC50 = 0.71-7.40 µM) against multiple MYC-driven cancer cell lines. Our findings afforded a potential small molecule blocking the WDR5-MYC interaction.
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Exoristobia philippinensis (Hymenoptera: Encyrtidae) is a worldwide parasitic wasp. This work presents the mitochondrial genome (mitogenome) of E. philippinensis for the first time. The complete mitochondrial genome of E. philippinensis was sequenced and annotated, which was 15,751 bp in length, and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). All 13 PCGs were initiated by the ATN (ATG, ATT, and ATA) codon, terminated with the stop codon TAA except for ND1 which ends with TAG. Phylogenetic analysis showed that E. philippinensis has a sister relationship with the genus Lamennaisia.
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The degradation of oncoproteins mediated by proteolysis-targeting chimera (PROTAC) has emerged as a potent strategy in cancer therapy. However, the clinical application of PROTACs is hampered by challenges such as poor water solubility and off-target adverse effects. Herein, we present an ultrasound (US)-activatable PROTAC prodrug termed NPCe6+PRO for actuating efficient sono-immunotherapy in a spatiotemporally controllable manner. Specifically, US irradiation, which exhibits deep-tissue penetration capability, results in Ce6-mediated generation of ROS, facilitating sonodynamic therapy (SDT) and inducing immunogenic cell death (ICD). Simultaneously, the generated ROS cleaves the thioketal (TK) linker through a ROS-responsive mechanism, realizing the on-demand activation of the PROTAC prodrug in deep tissues. This prodrug activation results in the degradation of the target protein BRD4, while simultaneously reversing the upregulation of PD-L1 expression associated with the SDT process. In the orthotopic mouse model of pancreatic tumors, NPCe6+PRO effectively suppressed tumor growth in conjunction with US stimulation.
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Imunoterapia , Neoplasias Pancreáticas , Pró-Fármacos , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Pró-Fármacos/química , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Camundongos , Humanos , Linhagem Celular Tumoral , Proteólise/efeitos dos fármacos , Terapia por Ultrassom/métodos , Antígeno B7-H1 , Fatores de Transcrição , Proteínas de Ciclo Celular , Espécies Reativas de Oxigênio/metabolismo , Proteínas que Contêm BromodomínioRESUMO
Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize. We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting. Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression.
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Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Proteínas de Plantas , Transdução de Sinais , Zea mays , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação/genética , Flores/genética , Flores/crescimento & desenvolvimento , Regiões Promotoras Genéticas/genética , Genes de Plantas , Ligação Proteica , FenótipoRESUMO
The benefits of urban green space are socially widely recognized as a direct link between plant-microbe interactions and the maintenance of biodiversity, community stability, and ecosystem functioning. Nevertheless, there is a lack of knowledge about the factors influencing microbial communities in urban green spaces, especially those related to phyllosphere epiphytes and stem epiphytes. In this study, we analyzed the microbial community assembly in leaf and stem bark samples collected from Square, Road, Campus, and Park. Illumina sequecing of 16S amplicons was performed to characterize microbial diversity and composition. The α-diversity was significantly higher in the bark epiphytic community, compared to the phyllosphere. Moreover, urban greenspaces'type altered the way communities gathered. The main soil and air properties factors of the urban greenhouse (e.g. soil temperature, atmospheric moisture, air temperature) were shaping the characteristics of bacterial communities on the leaf surface and bark epiphytic. In addition, in the co-occurrence network analysis, keystone taxa were not mostly observed in abundant species, which may be necessary to maintain ecosystem functions. Finally, our findings provide a deeper understanding of the ecological dynamics and microbial interactions within plant phyllosphere and stem epiphytes microbiomes.
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Clima , Microbiota , Folhas de Planta , Folhas de Planta/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Ecossistema , RNA Ribossômico 16S/genética , Cidades , Microbiologia do Solo , Casca de Planta/microbiologiaRESUMO
OBJECTIVE: This study investigated the expression of TGF-ß/Smad pathway-related indices in patients with isolated iliac artery aneurysms (IIAA) complicated with iliac arteriovenous fistula (IAVF) and their relationship with prognosis. METHODS: From January 2016 to June 2022, 83 patients with IIAA complicated with IAVF (Study group) and 54 patients with IIAA not complicated with IAVF (control group) were studied. The related indices of TGF-ß/Smad pathway were evaluated, and the effects of each index on the formation of IAVF were analyzed. The patients were divided into the survival group (64 cases) and death group (19 cases), and the prognostic value of indices in combination was analyzed. RESULTS: TGF-ß, p-Smad2, p-Smad3, p-JNK, and p-ERK in the study group were higher than those in the control group. Abnormal increase of pSmad3 expression was a risk factor for IAVF formation in patients with IIAA. TGF-ß level in the death group was higher than that in the survival group, and p-Smad3 and p-JNK proteins were higher than those in the survival group. The AUC value of indices in the TGF-ß/Smad pathway in combination was greater than that of each index alone. Abnormal increased expression of pSmad3 was a risk factor for prognosis of patients with IIAA complicated with IAVF. CONCLUSION: The abnormal increase of TGF-ß/Smad pathway-related indices is related to poor prognosis of patients with IIAA complicated with IAVF, and the combined detection of all indices has a predictive value for patients' prognosis.
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Fístula Arteriovenosa , Aneurisma Ilíaco , Artéria Ilíaca , Fator de Crescimento Transformador beta , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Fator de Crescimento Transformador beta/metabolismo , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/metabolismo , Idoso , Aneurisma Ilíaco/complicações , Transdução de Sinais , Proteína Smad3/metabolismo , Proteínas Smad/metabolismo , Proteína Smad2/metabolismo , Veia IlíacaRESUMO
Over the past few decades, significant improvements in maize yield have been largely attributed to increased plant density of upright hybrid varieties rather than increased yield per plant. However, dense planting triggers shade avoidance responses (SARs) that optimize light absorption but impair plant vigor and performance, limiting yield improvement through increasing plant density. In this study, we demonstrated that high-density-induced leaf angle narrowing and stem/stalk elongation are largely dependent on phytochrome B (phyB1/B2), the primary photoreceptor responsible for perceiving red (R) and far-red (FR) light in maize. We found that maize phyB physically interacts with the LIGULELESS1 (LG1), a classical key regulator of leaf angle, to coordinately regulate plant architecture and density tolerance. The abundance of LG1 is significantly increased by phyB under high R:FR light (low density) but rapidly decreases under low R:FR light (high density), correlating with variations in leaf angle and plant height under various densities. In addition, we identified the homeobox transcription factor HB53 as a target co-repressed by both phyB and LG1 but rapidly induced by canopy shade. Genetic and cellular analyses showed that HB53 regulates plant architecture by controlling the elongation and division of ligular adaxial and abaxial cells. Taken together, these findings uncover the phyB-LG1-HB53 regulatory module as a key molecular mechanism governing plant architecture and density tolerance, providing potential genetic targets for breeding maize hybrid varieties suitable for high-density planting.
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Fitocromo B , Proteínas de Plantas , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/genética , Zea mays/metabolismo , Zea mays/efeitos da radiação , Fitocromo B/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/efeitos da radiação , LuzRESUMO
In this study, we designed a novel electrochemical sensor by modifying a glass carbon electrode (GCE) with Pd confined mesoporous carbon hollow nanospheres (Pd/MCHS) for the simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The structure and morphological characteristics of the Pd/MCHS nanocomposite and the Pd/MCHS/GCE sensor are comprehensively examined using SEM, TEM, XRD and EDX. The electrochemical properties of the prepared sensor are investigated through CV and DPV, which reveal three resolved oxidation peaks for AA, DA, and UA, thereby verifying the simultaneous detection of the three analytes. Benefiting from its tailorable properties, the Pd/MCHS nanocomposite provides a large surface area, rapid electron transfer ability, good catalytic activity, and high conductivity with good electrochemical behavior for the determination of AA, DA, and UA. Under optimized conditions, the Pd/MCHS/GCE sensor exhibited a linear response in the concentration ranges of 300-9000, 2-50, and 20-500 µM for AA, DA, and UA, respectively. The corresponding limit of detection (LOD) values were determined to be 51.03, 0.14, and 4.96 µM, respectively. Moreover, the Pd/MCHS/GCE sensor demonstrated outstanding selectivity, reproducibility, and stability. The recovery percentages of AA, DA, and UA in real samples, including a vitamin C tablet, DA injection, and human urine, range from 99.8-110.9%, 99.04-100.45%, and 98.80-100.49%, respectively. Overall, the proposed sensor can serve as a useful reference for the construction of a high-performance electrochemical sensing platform.
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Ácido Ascórbico , Carbono , Dopamina , Técnicas Eletroquímicas , Limite de Detecção , Nanosferas , Paládio , Ácido Úrico , Ácido Ascórbico/análise , Ácido Ascórbico/urina , Ácido Úrico/urina , Ácido Úrico/análise , Dopamina/análise , Dopamina/urina , Nanosferas/química , Técnicas Eletroquímicas/métodos , Carbono/química , Paládio/química , Porosidade , Humanos , Eletrodos , Técnicas Biossensoriais/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease. The aim of this research is to identify new biomarkers and therapeutic targets for the treatment of such deadly diseases. METHODS: Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were used to identify distinct immune cell infiltration types between AAA and normal abdominal aortas. Single-cell RNA sequencing data were used to analyse the hallmark genes of AAA-associated macrophage cell subsets. Six macrophage-related hub genes were identified through weighted gene co-expression network analysis (WGCNA) and validated for expression in clinical samples and AAA mouse models. We screened potential therapeutic drugs for AAA through online Connectivity Map databases (CMap). A network-based approach was used to explore the relationships between the candidate genes and transcription factors (TFs), lncRNAs, and miRNAs. Additionally, we also identified hub genes that can effectively identify AAA and atherosclerosis (AS) through a variety of machine learning algorithms. RESULTS: We obtained six macrophage hub genes (IL-1B, CXCL1, SOCS3, SLC2A3, G0S2, and CCL3) that can effectively diagnose abdominal aortic aneurysm. The ROC curves and decision curve analysis (DCA) were combined to further confirm the good diagnostic efficacy of the hub genes. Further analysis revealed that the expression of the six hub genes mentioned above was significantly increased in AAA patients and mice. We also constructed TF regulatory networks and competing endogenous RNA networks (ceRNA) to reveal potential mechanisms of disease occurrence. We also obtained two key genes (ZNF652 and UBR5) through a variety of machine learning algorithms, which can effectively distinguish abdominal aortic aneurysm and atherosclerosis. CONCLUSION: Our findings depict the molecular pharmaceutical network in AAA, providing new ideas for effective diagnosis and treatment of diseases.
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Aneurisma da Aorta Abdominal , Perfilação da Expressão Gênica , Macrófagos , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/diagnóstico , Humanos , Animais , Macrófagos/metabolismo , Camundongos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Modelos Animais de Doenças , Transcriptoma , Biomarcadores/metabolismoRESUMO
The damage of road base course has the characteristics of strong concealment and difficulty in detecting. For this reason, the impact imaging method has been used for detection of road base course. This paper discussed systematically collection points setting, excitation mode and data processing method. Through the application in testing for highway pavement base before and after grouting maintenance, the results show that the method is simple and accurate. The detection results can be displayed in a two-dimensional image form and it is easy to be used in road maintenance. This method can be used to identify and locate the damages of the pavement base, to judge the uniformity of the pavement base structure. It can also be used to evaluate the effectiveness of internal damage after grouting repairing.
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Tumor-infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion-related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune-promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor-infiltrating CD4+ T cells were identified, and both the immune-promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD-1) and Treg cells in Module 2 (αCTLA-4) in mouse models could help reinvigorate the effector function of Module 1-exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2-exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.
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Depression, which is a disease of heterogeneous etiology, is characterized by high disability and mortality rates. Gut microbiota are associated with the development of depression. To further explore any differences in the mechanisms of depression induced by gut microbiota and traditional stresses, as well as facilitate the development of microbiota-based interventions, a fecal microbiota transplantation (FMT) depression model was made. This was achieved by transplanting feces from major depressive disorder (MDD) patients into germ-free mice. Second, the mechanisms of the depression induced by gut microbiota were analyzed in comparison with those of the depression caused by different forms of stress. It turned out that mice exhibited depressive-like behavior after FMT. Then, PCR array analysis was performed on the hippocampus of the depressed mice to identify differentially expressed genes (DEGs). The KEGG analysis revealed that the pathways of depression induced by gut microbes are closely associated with immuno-inflammation. To determine the pathogenic pathways of physiological stress and psychological stress-induced depression, raw data was extracted from several databases and KEGG analysis was performed. The results from the analysis revealed that the mechanisms of depression induced by physiological and psychological stress are closely related to the regulation of neurotransmitters and energy metabolism. Interestingly, the immunoinflammatory response was distinct across different etiologies that induced depression. The findings showed that gut microbiota dysbiosis-induced depression was mainly associated with adaptive immunity, while physiological stress-induced depression was more linked to innate immunity. This study compared the pathogenesis of depression caused by gut microbiota dysbiosis, and physiological and psychological stress. We explored new intervention methods for depression and laid the foundation for precise treatment.
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Transtorno Depressivo Maior , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Hipocampo , Estresse Psicológico , Animais , Hipocampo/metabolismo , Camundongos , Masculino , Transtorno Depressivo Maior/microbiologia , Transtorno Depressivo Maior/metabolismo , Humanos , Modelos Animais de Doenças , Depressão , Camundongos Endogâmicos C57BL , Disbiose/microbiologia , Perfilação da Expressão Gênica/métodosRESUMO
Six low molecular weight fenugreek polysaccharides (FP) were isolated and purified by ethanol stepwise precipitation (EFP-20, EFP-40, and EFP-60) and DEAE-52 cellulose column method (DFP-0, DFP-0.15, and DFP-0.3), respectively. The effects of different separation and purification techniques on the preliminary properties and biological activities of fenugreek polysaccharides were compared. The results showed that the DEAE-52 cellulose-eluted fractions had a higher total sugar content and displayed a looser structure. The molecular weights of all six fractions were in the range of 4-19â kDa, with significant changes in the ratio of galactose to mannose. All six fractions contained α-D-galactopyranose and ß-D-mannopyranose structures. Activity tests showed that all six fractions possessed antioxidant, hypoglycemic and DNA-protective activities. Among them, the DFP-0 fraction showed the highest activity. Overall, different isolation and purification methods lead to changes in the properties and bioactivities of FP, which provides a theoretical basis for the development and application of FP in functional foods and drugs.
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Background: This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments. Methods: We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1ß, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed. Results: A positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors. Conclusion: O_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.
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3D carbon-based porous sponges are recognized for significant potential in oil absorption and electromagnetic interference (EMI). However, their widespread application is hindered by a common compromise between high performance and affordability of mass production. Herein, a novel approach is introduced that involves laser-assisted micro-zone heating melt-blown spinning (LMHMS) to address this challenge by creating pitch-based submicron carbon fibers (PSCFs) sponge with 3D interconnected structures. These structures bestow the resulting sponge exceptional characteristics including low density (≈20 mg cm-3), high porosity (≈99%), remarkable compressibility (80% maximum strain), and superior conductivity (≈628 S m-1). The resultant PSCF sponges realize an oil/organic solvent sorption capacity over 56 g/g and possess remarkable regenerated ability. In addition to their effectiveness in cleaning up oil/organic solvent spills, they also demonstrated strong electromagnetic shielding capabilities, with a total shielding effectiveness (SE) exceeding 60 dB across the X-band GHz range. In virtue of extreme lightweight of ≈20 mg cm-3, the specific SE of the PSCF sponge reaches as high as ≈1466 dB cm3 g-1, surpassing the performance of numerous carbon-based porous structures. Thus, the unique blend of properties renders these sponges promising for transforming strategies in addressing oil/organic solvent contaminations and providing effective protection against EMI.