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Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages decreased intestinal motility and was sufficient to reverse the GI hypermotility that is associated with chemotherapy treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of prostaglandin E2 and elicited colon contraction in a paracrine manner via prostaglandin E receptor signaling in intestinal smooth muscle cells without input from the enteric nervous system. Collectively, our data identify TRPV4-expressing MMs as an essential component required for maintaining normal GI motility and provide potential drug targets for GI motility disorders.
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Colo/fisiologia , Motilidade Gastrointestinal , Macrófagos/metabolismo , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais , Canais de Cátion TRPV/metabolismo , Animais , Receptor 1 de Quimiocina CX3C/metabolismo , Colo/fisiopatologia , Ciclo-Oxigenase 1/deficiência , Ciclo-Oxigenase 1/metabolismo , Dinoprostona/análise , Dinoprostona/metabolismo , Feminino , Mucosa Gástrica/citologia , Expressão Gênica , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Contração Muscular , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/deficiência , Canais de Cátion TRPV/genéticaRESUMO
Water plays a crucial role in various heterogeneous catalytic reactions, but the atomic-scale characterization of how water participates in these chemical processes remains a significant challenge. Here we directly visualize the promoting role of interfacial water in the deprotonation of formic acid (FA) on a metal surface, using combined scanning tunneling microscopy and qPlus-based noncontact atomic force microscopy. We find the dissociation of FA when coadsorbed with water on the Cu(111) surface, resulting in the formation of hydronium and formate ions. Interestingly, most of the hydrated proton and formate ions exhibit a phase-separated behavior on Cu(111), in which Eigen and Zundel cations assemble into a monolayer hexagonal hydrogen-bonding (H-bonding) network, and bidentate formate ions are solvated with water and aggregate into one-dimensional chains or two-dimensional H-bonding networks. This phase-separated behavior is essential for preventing the proton transfer back from hydronium to formate and the reformation of FA. Density functional theory calculations reveal that the participation of water significantly reduces the deprotonation barrier of FA on Cu(111), in which water catalyzes the decomposition of FA through the Grotthuss proton transfer mechanism. In addition, the separate solvation of hydronium and bidentate formate ions is energetically preferred due to the enhanced interaction with the copper substrate. The promoting role of water in the deprotonation of FA is further confirmed by the temperature-programmed desorption experiment, which shows that the intensity of the H2 desorption peak significantly increases and the desorption of FA declines when water and FA coadsorbed on the Cu(111) surface.
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BACKGROUND: A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. METHODS: Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. RESULTS: Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14-4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93-95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (- 4.30 ± 3.66) and 12 months (- 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001). CONCLUSIONS: The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.
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Veia Femoral , Veia Ilíaca , Stents , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Veia Femoral/cirurgia , Veia Ilíaca/cirurgia , Resultado do Tratamento , Adulto , Idoso , Qualidade de VidaRESUMO
Cellulose foams are in high demand in an era of prioritizing environmental consciousness. Yet, transferring the exceptional mechanical properties of cellulose fibers into a cellulose network remains a significant challenge. To address this challenge, an innovative multiscale design is developed for producing cellulose foam with exceptional network integrity. Specifically, this design relies on a combination of physical cross-linking of the microfibrillated cellulose (MFC) networks by cellulose nanofibril (CNF) and aluminum ion (Al3+), as well as self-densification of the cellulose induced by ice-crystal templating, physical cross-linking, solvent exchange, and evaporation. The resultant cellulose foam demonstrates a low density of 40.7 mg cm-3, a high porosity of 97.3%, and a robust network with high compressive modulus of 1211.5 ± 60.6 kPa and energy absorption of 77.8 ± 1.9 kJ m-3. The introduction of CNF network and Al3+ cross-linking into foam also confers excellent wet stability and flame self-extinguish ability. Furthermore, the foam can be easily biodegraded in natural environments , re-entering the ecosystem's carbon cycle. This strategy yields a cellulose foam with a robust network and outstanding environmental durability, opening new possibilities for the advancement of high-performance foam materials.
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Lignocellulosic nanofibrils (LCNFs) isolation is recognized as an efficient strategy for maximizing biomass utilization. Nevertheless, achieving a 100% yield presents a formidable challenge. Here, an esterification strategy mediated by the equilibrium moisture in biomass is proposed for LCNFs preparation without the use of catalysts, resulting in a yield exceeding 100%. Different from anhydrous chemical thermomechanical pulp (CTMP0%), the presence of moisture (moisture content of 7 wt%, denoted as CTMP7%) introduces a notably distinct process for the pretreatment of CTMP, comprising the initial disintegration and the post-esterification steps. The maleic acid, generated through maleic anhydride (MA) hydrolysis, degrades the recalcitrant lignin-carbohydrate complex (LCC) structures, resulting in esterified CTMP7% (E-CTMP7%). The highly grafted esters compensate for the mass loss resulting from the partial removal of hydrolyzed lignin and hemicellulose, ensuring a high yield. Following microfluidization, favorable LCNF7% with a high yield (114.4 ± 3.0%) and a high charge content (1.74 ± 0.09 mmol g-1) can be easily produced, surpassing most previous records for LCNFs. Additionally, LCNF7% presented highly processability for filaments, films, and 3D honeycomb structures preparation. These findings provide valuable insights and guidance for achieving a high yield in the isolation of LCNFs from biomass through the mediation of equilibrium moisture.
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MAIN CONCLUSION: The SiMBR genes in foxtail millet were identified and studied. Heterologous expression of SiMBR2 in Arabidopsis can improve plant tolerance to drought stress by decreasing the level of reactive oxygen species. Foxtail millet (Setaria italica L.), a C4 crop recognized for its exceptional resistance to drought stress, presents an opportunity to improve the genetic resilience of other crops by examining its unique stress response genes and understanding the underlying molecular mechanisms of drought tolerance. In our previous study, we identified several genes linked to drought stress by transcriptome analysis, including SiMBR2 (Seita.7G226600), a member of the MED25 BINDING RING-H2 PROTEIN (MBR) gene family, which is related to protein ubiquitination. Here, we have identified ten SiMBR genes in foxtail millet and conducted analyses of their structural characteristics, chromosomal locations, cis-acting regulatory elements within their promoters, and predicted transcription patterns specific to various tissues or developmental stages using bioinformatic approaches. Further investigation of the stress response of SiMBR2 revealed that its transcription is induced by treatments with salicylic acid and gibberellic acid, as well as by salt and osmotic stresses, while exposure to high or low temperatures led to a decrease in its transcription levels. Heterologous expression of SiMBR2 in Arabidopsis thaliana enhanced the plant's tolerance to water deficit by reducing the accumulation of reactive oxygen species under drought stress. In summary, this study provides support for exploring the molecular mechanisms associated with drought resistance of SiMBR genes in foxtail millet and contributing to genetic improvement and molecular breeding in other crops.
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Arabidopsis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Setaria (Planta) , Estresse Fisiológico , Setaria (Planta)/genética , Setaria (Planta)/fisiologia , Setaria (Planta)/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/fisiologia , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Secas , Plantas Geneticamente Modificadas , Família Multigênica , Regiões Promotoras Genéticas/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Foot-and-mouth disease virus (FMDV) is a single-stranded picornavirus that causes economically devastating disease in even-hooved animals. There has been little research on the function of host cells during FMDV infection. We aimed to shed light on key host factors associated with FMDV replication during acute infection. We found that HDAC1 overexpression in host cells induced upregulation of FMDV RNA and protein levels. Activation of the AKT-mammalian target of rapamycin (mTOR) signaling pathway using bpV(HOpic) or SC79 also promoted FMDV replication. Furthermore, short hairpin RNA (shRNA)-induced suppression of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), a transcription factor downstream of the AKT-mTOR signaling pathway, resulted in downregulation of FMDV RNA and protein levels. Coimmunoprecipitation assays showed that the ACTase domain of CAD could interact with the FMDV 2C protein, suggesting that the ACTase domain of CAD may be critical in FMDV replication. CAD proteins participate in de novo pyrimidine synthesis. Inhibition of FMDV replication by deletion of the ACTase domain of CAD in host cells could be reversed by supplementation with uracil. These results revealed that the contribution of the CAD ACTase domain to FMDV replication is dependent on de novo pyrimidine synthesis. Our research shows that HDAC1 promotes FMDV replication by regulating de novo pyrimidine synthesis from CAD via the AKT-mTOR signaling pathway. IMPORTANCE Foot-and-mouth disease virus is an animal virus of the Picornaviridae family that seriously harms the development of animal husbandry and foreign trade of related products, and there is still a lack of effective means to control its harm. Replication complexes would generate during FMDV replication to ensure efficient replication cycles. 2C is a common viral protein in the replication complex of Picornaviridae virus, which is thought to be an essential component of membrane rearrangement and viral replication complex formation. The host protein CAD is a key protein in the pyrimidines de novo synthesis. In our research, the interaction of CAD and FMDV 2C was demonstrated in FMDV-infected BHK-21 cells, and it colocalized with 2C in the replication complex. The inhibition of the expression of FMDV 3D protein through interference with CAD and supplementation with exogenous pyrimidines reversed this inhibition, suggesting that FMDV might recruit CAD through the 2C protein to ensure pyrimidine supply during replication. In addition, we also found that FMDV infection decreased the expression of the host protein HDAC1 and ultimately inhibited CAD activity through the AKT-mTOR signaling pathway. These results revealed a unique means of counteracting the virus in BHK-21 cells lacking the interferon (IFN) signaling pathway. In conclusion, our study provides some potential targets for the development of drugs against FMDV.
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Vírus da Febre Aftosa , Febre Aftosa , Animais , Linhagem Celular , Vírus da Febre Aftosa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas , RNA/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Replicação Viral , CricetinaeRESUMO
Environmentally persistent free radicals (EPFRs) can pose exposure risks by inducing the generation of reactive oxygen species. As a new class of pollutants, EPFRs have been frequently detected in atmospheric particulate matters. In this study, the seasonal variations and sources of EPFRs in a severe cold region in Northeastern China were comprehensively investigated, especially for the high pollution events. The geomean concentration of EPFRs in the total suspended particle was 6.58 × 1013 spins/m3 and the mean level in winter was one order of magnitude higher than summer and autumn. The correlation network analysis showed that EPFRs had significantly positive correlation with carbon component, K+ and PAHs, indicating that EPFRs were primarily emitted from combustion and pyrolysis process. The source appointment by the Positive Matrix Factorization (PMF) model indicated that the dominant sources in the heating season were coal combustion (48.4%), vehicle emission (23.1%) and biomass burning (19.4%), while the top three sources in the non-heating season were others (41.4%), coal combustion (23.7%) and vehicle emissions (21.2%). It was found that the high EPFRs in cold season can be ascribed to the extensive use of fossil fuel for heating demand; while the high EPFRs occurred in early spring were caused by the large-scale opening combustion of biomass. In summary, this study provided important basic information for better understanding the pollution characteristics of EPFRs, which suggested that the implementation of energy transformation and straw utilization was benefit for the control of EPFRs in severe cold region.
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Poluentes Atmosféricos , Carvão Mineral , Monitoramento Ambiental , Estações do Ano , Poluentes Atmosféricos/análise , Carvão Mineral/análise , China , Radicais Livres/análise , Biomassa , Material Particulado/análise , Cidades , Poluição do Ar/análiseRESUMO
The Chinese white wax scale insect (CWWSI), Ericerus pela, can secret an amount of wax equivalent to their body weight. Previous studies demonstrated the fatty acyl-CoA reductase (far3) plays a pivotal role in wax secretion of CWWSI. The high expression of far3 is crucial for the massive wax secretion. However, the transcription regulation of far3 was not clear. To identify regulatory factors that control the expression of far3, the assay for transposase-accessible chromatin (ATAC) and yeast one-hybrid (Y1H) were carried out in this study. The ATAC sequencing of the CWWSI at the early wax-secretion stage ATAC-seq resulted in 22.75 GB raw data, generated 75,827,225 clean reads and revealed 142,771 peaks. There was one significant peak in the 3 kb upstream regulation regions. The peak sequence is located between -1000 and -670 bp upstream of the far3 transcription start site, spanning a length of 331 bp. This peak sequence served as bait for creating the pAbAi-peak recombinant vector, used in Y1H screenings to identify proteins interacting with far3 gene. The results indicate a successful CWWSI cDNA library construction with a capacity of 1.2 × 107 colony forming unit, a 95.8% recombination rate, and insert sizes between 1,000 and 2,000 bp. Self-activation tests established that 100 ng/mL of AbA effectively inhibited bait vector self-activation. Finally, a total of 88 positive clones were selected. After sequencing and removal of duplication, 63 unique clones were obtained from these screened colonies. By aligning the clone sequences with full-length transcriptome and genome of CWWSI, the full-length coding sequences of these clones were obtained. BlastX analysis identified a transcription factor, nuclear transcription factor Y beta, and two co-activators, cAMP-response-element-binding-protein-binding protein and WW domain binding protein 2. Reverse transcription quantitative polymerase chain reaction analysis confirmed that their expression patterns were consistent with the developmental stages preceding wax secretion and matched the wax secretion characteristics during ovulation periods. These results are beneficial for further research into the regulatory mechanisms of wax secretion of CWWSI.
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Cromatina , Hemípteros , Feminino , Animais , Saccharomyces cerevisiae/genética , Hemípteros/genética , Aldeído Oxirredutases/genética , Transcriptoma , Fatores de Transcrição/genética , Ácidos Graxos , Acil Coenzima A/genéticaRESUMO
Circular RNA (CircRNA), as a classical noncoding RNA, has been proven to regulate skeletal muscle development (SMD). However, the molecular genetic basis of circRNA regulation in muscle cells remains unclear. In this study, the expression patterns of circRNAs in the longissimus dorsi muscle at embryonic day 75 and postnatal day 1 in DBGs were investigated to identify the key circRNAs that play an important role in SMD in goats. A total of 140 significantly and differentially expressed circRNAs (DEcircRNAs) were identified among the groups at different developmental stages. Among the 116 host genes (HGs) of DEcircRNAs, 76 were significantly and differentially expressed, which was confirmed by previous RNA_seq data. Furthermore, the expression pattern of 10 DEcircRNAs with RT-qPCR was verified, which showed 80% concordance rate with that of RNA_seq datasets. Moreover, the authenticity of seven randomly selected DEcircRNAs was verified by PCR Sanger sequencing. Based on the functional annotation results, among the 76 significantly and differentially expressed HGs, 74 were enriched in 845 GO terms, whereas 35 were annotated to 85 KEGG pathways. The results of this study could provide a comprehensive understanding of the genetic basis of circRNAs involved in SMD and muscle growth.
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MicroRNAs , RNA Circular , Animais , RNA Circular/genética , Cabras/genética , Perfilação da Expressão Gênica/veterinária , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Desenvolvimento Muscular/genéticaRESUMO
Skin cutaneous melanoma (SKCM) is the most life-threatening skin cancer and lacks early detection and effective treatment strategies. Many long noncoding RNAs are associated with the development of tumors and may serve as potential immunotherapeutic targets. In this study, microarray analysis was performed to screen for differentially expressed lncRNAs between SKCM and normal tissues, and SMG7-AS1 was identified as an upregulated lncRNA in SKCM. Subsequently, bioinformatic analysis revealed that dysregulation of SMG7-AS1 influences metastasis and immune infiltration. qRT-PCR of clinical samples demonstrated that the expression of SMG7-AS1 was higher in melanoma tissues. Flow cytometry showed that SMG7-AS1 plays a vital role in the cell cycle. Additionally, SMG7-AS1 was found to be associated with immunotherapy responses. To the best of our knowledge, this study is the first to report that SMG7-AS1 is associated with SKCM and may serve as a prognostic biomarker and predictor of immunotherapy responses in SKCM.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Prognóstico , Linhagem Celular Tumoral , Biomarcadores , Proteínas de Transporte , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Hull colour is an important morphological marker for selection in seed production of foxtail millet. However, the molecular mechanisms underlying hull colour variation remain unknown. RESULTS: An F7 recombinant inbred line (RIL) population containing 215 lines derived from Hongjiugu × Yugu18 was used to analyze inheritance and detect the quantitative trait loci (QTL) for four hull colour traits using major gene plus polygene mixed inheritance analysis and composite interval mapping (CIM) in four environments. Genetic analysis revealed that the hull colour L* value (HCL*) was controlled by two major genes plus additive polygenes, the hull colour a* value (HCa*) was controlled by three major genes, the hull colour b* value (HCb*) was controlled by two major genes plus polygenes, and the hull colour C* value (HCC*) was controlled by four major genes. A high-density genetic linkage map covering 1227.383 cM of the foxtail millet genome, with an average interval of 0.879 cM between adjacent bin markers, was constructed using 1420 bin markers. Based on the genetic linkage map and the phenotypic data, a total of 39 QTL were detected for these four hull colour traits across four environments, each explaining 1.50%-49.20% of the phenotypic variation. Of these, six environmentally stable major QTL were co-localized to regions on chromosomes 1 and 9, playing a major role in hull colour. There were 556 annotated genes within the two QTL regions. Based on the functions of homologous genes in Arabidopsis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) gene annotations, five genes were predicted as candidate genes for further studies. CONCLUSIONS: This is the first study to use an inheritance model and QTL mapping to determine the genetic mechanisms of hull colour trait in foxtail millet. We identified six major environmentally stable QTL and predicted five potential candidate genes to be associated with hull colour. These results advance the current understanding of the genetic mechanisms underlying hull colour traits in foxtail millet and provide additional resources for application in genomics-assisted breeding and potential isolation and functional characterization of the candidate genes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Setaria (Planta) , Locos de Características Quantitativas , Mapeamento Cromossômico/métodos , Setaria (Planta)/genética , Carcinoma Hepatocelular/genética , Cor , Neoplasias Hepáticas/genética , Melhoramento Vegetal , Estudos de Associação GenéticaRESUMO
BACKGROUND AND AIMS: The increasing prevalence of metabolic and cardiovascular diseases poses a significant challenge to global healthcare systems. Regular physical activity (PA) is recognized for its positive impact on cardiovascular risk factors. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA), sedentary behavior (SB), and abdominal aortic calcification (AAC) using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study used data from NHANES participants aged 40 and above during the 2013-2014 cycle. AAC scores were assessed using the Kauppila scoring system, and MVPA and SB were self-reported. Sociodemographic variables were considered, and multivariable linear regression models were used to analyze associations between MVPA, SB, and AAC scores. Subgroup analyses were conducted based on age, sex, BMI, hypertension, and diabetes. RESULTS: The study included 2843 participants. AAC prevalence was higher in older age groups, smokers, and those with diabetes or hypertension. Lower socioeconomic status was associated with higher AAC prevalence. Individuals engaged in any level of MVPA exhibited lower AAC rates compared to inactive individuals. Not engaging in occupational MVPA (ß = 0.46, 95% confidence interval = 0.24â0.67, p < .001) and prolonged SB (ß = 0.28, 95% confidence interval = 0.04â0.52, p = .023) were associated with higher AAC scores. However, no significant associations were found for transportation and leisure time MVPA. Subgroup analysis revealed age and hypertension as effect modifiers in the MVPA-AAC relationship. CONCLUSIONS: This study highlights the potential benefits of engaging in occupational MVPA and reducing SB in mitigating AAC scores, particularly among older individuals and those with hypertension.
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Diabetes Mellitus , Hipertensão , Humanos , Idoso , Exercício Físico , Inquéritos Nutricionais , Comportamento SedentárioRESUMO
Using a murine collagen-induced arthritis model, we characterized the heterogeneity of synovial CD8+ T cells based on the expression of chemokine receptors, cytokines, and nuclear transcription factors. Four subsets, i.e. CXCR3-CCR4- cells, CXCR3+CCR4- cells, CXCR3+CCR4+ cells, and CXCR3-CCR4+ cells, were present in synovial CD8+CD62L-CCR6+IL-23R+CCR10- T cells. CXCR3-CCR4- cells belonged to exhausted CD8+ T cells. CXCR3+CCR4- cells were Tc17.1 cells expressing both IL-17A and IFN-γ. CXCR3+CCR4+ cells were transitional Tc17.1 cells expressing IL-17A but lower IFN-γ, and CXCR3-CCR4+ cells were Tc17 cells expressing IL-17A but no IFN-γ. Transitional Tc17.1 cells can differentiate into Tc17.1 cells in vitro under the instruction of IL-12. Tc17.1 cells and transitional Tc17.1 cells strongly induced the expression of pro-inflammatory mediators in synovial fibroblasts, whereas Tc17 cells were less potent in doing so. IFN-γ was involved in the higher pathogenicity of Tc17.1 cells and transitional Tc17.1 cells on synovial fibroblasts. This study expands the understanding of Tc17 biology by unveiling the phenotypic and functional heterogeneity of synovial IL-17A-expressing CD8+ T cells. These heterogeneous IL-17A-expressing CD8+ T cells could be novel therapeutic targets in future arthritis treatment.
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Artrite Experimental , Linfócitos T CD8-Positivos , Interleucina-17 , Membrana Sinovial , Células Th17 , Animais , Camundongos , Artrite Experimental/imunologia , Artrite Experimental/patologia , Linfócitos T CD8-Positivos/imunologia , Interleucina-17/metabolismo , Membrana Sinovial/imunologia , Células Th17/imunologiaRESUMO
BACKGROUND: Renal excretion is one of the major routes of nanomaterial elimination from the body. Many previous studies have found that graphene oxide nanosheets are excreted in bulk through the kidneys. However, how the lateral size affects GO disposition in the kidneys including glomerular filtration, active tubular secretion and tubular reabsorption is still unknown. RESULTS: The thin, two-dimensional graphene oxide nanosheets (GOs) was observed to excrete in urine through the kidneys, but the lateral dimension of GOs affects their renal clearance pathway and renal injury. The s-GOs could be renal excreted via the glomerular filtration, while the l-GOs were predominately excreted via proximal tubular secretion at a much faster renal clearance rate than the s-GOs. For the tubular secretion of l-GOs, the mRNA level of basolateral organic anion transporters Oat1 and Oat2 in the kidney presented dose dependent increase, while no obvious alterations of the efflux transporters such as Mdr1 and Mrp4 mRNA expression levels were observed, suggesting the accumulation of l-GOs. During the GO renal elimination, mostly the high dose of 15 mg/kg s-GO and l-GO treatment showed obvious kidney injuries but at different renal compartment, i.e., the s-GOs induced obvious glomerular changes in podocytes, while the l-GOs induced more obvious tubular injuries including necrosis of renal tubular epithelial cells, loss of brush border, cast formation and tubular dilatation. The specifically tubular injury biomarkers KIM1 and NGAL were shown slight increase with mRNA levels in l-GO administrated mice. CONCLUSIONS: This study shows that the lateral size of GOs affected their interactions with different renal compartments, renal excretion pathways and potential kidney injuries.
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Nefropatias , Rim , Camundongos , Animais , Rim/metabolismo , Nefropatias/metabolismoRESUMO
PURPOSE: To investigate the relationship between the medial and posteromedial femoral anatomic structures and the femoral tunnel exit produced by different tunnel orientations when creating the femoral tunnel for posterior cruciate ligament reconstruction (PCLR) using the inside-out (IO) technique and to estimate safe tunnel orientations to minimize the risk of iatrogenic injury to these structures. METHODS: Eleven cadaveric knees were used. The medial and posteromedial aspects of each knee joint were dissected to reveal the "safe zone," which is a bony area that avoids the distribution or attachment of at-risk structures (MCL, PMC structures, and articular cartilage), while remaining 10 mm away from the articular cartilage. The hypothesis of this study was that by creating the femoral tunnel at specific angles using the IO technique, the tunnel outlet would be as close to the safe zone as possible, protecting the at-risk structures from damage. Femoral tunnels were drilled at 20 different angle combinations on each specimen: 0°, 15°, 30°, 45°, and 60° relative to a line parallel to the transepicondylar axis in the axial plane, as well as 15°, 30°, 45°, and 60° relative to a line parallel to the femoral axis in the coronal plane. The positional relationship between each tunnel exit and the safe zone was recorded, and the shortest distance between the exit center and the safe zone boundary was measured. RESULTS: The risk of iatrogenic injury differed depending on the drilling orientation (χ2 = 168.880, P < 0.001). Femoral drilling angle combinations of 45/45°, 45/60°, 60/30°, 60/45°, and 60/60° (axial/coronal) were considered relatively safer than other orientations (P < 0.05). The shortest distance between the tunnel exit and the safe zone boundary was negatively correlated with the angle in the axial plane (P < 0.001, r = - 0.810). CONCLUSIONS: When creating the IO femoral tunnel for single-bundle PCL reconstruction, angle combinations of 45/45°, 45/60°, 60/30°, 60/45°, and 60/60° (axial/oblique coronal) could be utilized to prevent at-risk structures from being damaged. The drilling angles and the safe zone can be employed to optimize the femoral tunnel in PCLR.
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Reconstrução do Ligamento Cruzado Posterior , Ligamento Cruzado Posterior , Humanos , Articulação do Joelho/cirurgia , Fêmur/cirurgia , Joelho/cirurgia , Doença Iatrogênica , Cadáver , Ligamento Cruzado Posterior/cirurgiaRESUMO
Health risks from exposure to contaminants are generally estimated by evaluating concentrations of the contaminants in environmental matrixes. However, accurate health risk assessment is difficult because of uncertainties regarding exposures. This study aims to utilize data on the concentrations of organophosphate flame retardants (OPFRs) in surface soil across China coupled with Monte Carlo simulations to compensate for uncertainties in exposure to evaluate the health risks associated with contamination of soil with this class of flame retardants. Results revealed that concentrations of ∑OPFRs were 0.793-406 ng/g dry weight (dw) with an average of 23.2 ng/g dw. In terms of spatial distribution, higher OPFRs concentrations were found in economically developed regions. Although the values of health risk of OPFRs in soil across China were below the threshold, the high concentrations of OPFRs in soil in some regions should attract more attentions in future. Sensitivity analysis revealed that concentrations of OPFRs in soil, skin adherence factor, and exposure duration were the most sensitive parameters in health risk assessment. In summary, the study indicated that the national scale soil measurement could provide unique information on OPFRs exposure and health risk assessment, which was useful for the management of soil in China and for better understanding of the environmental fate of OPFRs in the global perspective.
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Monitoramento Ambiental , Retardadores de Chama , Humanos , China , Retardadores de Chama/análise , Método de Monte Carlo , Organofosfatos/análise , Medição de Risco , SoloRESUMO
BACKGROUND: Starch is a major nutrient in the human diet and has been widely used as an ingredient in many food and non-food applications. However, the research on the quality characteristics of Tartary buckwheat is lagging behind, and there is a lack of high-quality special varieties, which makes it difficult to become a popular food. The physicochemical properties of Tartary buckwheat starch may be affected by different environments and varieties, and the stability of planted varieties in different regions is also an important issue in current research. RESULTS: The average amylose content and pasting properties of Dingxi Tartary buckwheat were lower, while the solubility, transparency, relative crystallinity and gelatinization enthalpy were higher compared with the other two regions, and there were significant differences between different varieties. All samples showed typical A-type structure, and the starch short-range order structure changed slightly. Amylose content, solubility, transparency, granule size distribution, pasting properties and thermal properties were significantly affected by environment and variety. CONCLUSION: When choosing high-quality special varieties and products for processing, it contributes to select different buckwheat varieties and planting areas based on various objectives by understanding the effects of environment and varieties on the physicochemical properties of Tartary buckwheat starch. In this study, the four varieties planted in Dingxi and the two varieties in Zhaojue were easy to digest, and the differences of pasting properties and thermal properties are helpful to improve the application of Tartary buckwheat starch in the food industry. © 2023 Society of Chemical Industry.
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Fagopyrum , Traqueófitas , Humanos , Amido/química , Amilose/química , Fagopyrum/química , SolubilidadeRESUMO
BACKGROUND: "Crisis military deployment" was defined as a situation in which military personnel are suddenly ordered to duty to support an operation away from their home station and in a potentially dangerous environment. As a result of complex changes in the global political and economic landscape, military nurses are assuming an increasing number of crisis military deployment tasks. Moral distress has been widely studied among civilian nurses. However, little is known about the moral distress military nurses experience during military deployments in crisis. AIM: This review discussed the current state of research on the phenomenon, unique factors, specific sources, and measurement tools. METHODS: The scope of the study was defined using a framework developed by Arksey and O'Malley. Following English databases were searched: PubMed, CINAHL, Cochrane Library, Web of Science, and Embase, using MeSH terms and free word combinations; furthermore, Chinese databases: CNKI and CBMDisc, were explored using thematic terms from inception until January 20, 2023. Data were selected and defined by the inclusion and exclusion criteria and independently screened by two researchers. ETHICAL CONSIDERATIONS: The scoping review adhered to sound scientific practice and respected authorship and reference sources. RESULTS: Finally, 21 articles were included in the review. The moral distress of military nurses in crisis military deployments had unique and specific sources and reported positive aspects. The deployment environment and nature of the mission, responsibilities and obligations of military nurses, and the limited rights of patients were unique factors. Specific sources included third-party intervention, military triage, resource allocation, futile care, care of the enemy, and return to the battlefield. Military nurses in deployment reported positive aspects. They grow in their inner strength, build deep friendships and gain a greater sense of professional value. CONCLUSION: It is important to understand the unique factors and specific sources of moral distress faced by military nurses in crisis military deployments and to identify the positive aspects. This research will help prepare military nurses for future deployments in advance by providing useful information to mitigate and eliminate moral distress.
Assuntos
Ética em Enfermagem , Destacamento Militar , Militares , Enfermeiras e Enfermeiros , Humanos , Princípios Morais , Enfermeiras e Enfermeiros/psicologiaRESUMO
CONTEXT: The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms remain unclear. OBJECTIVE: This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR. MATERIALS AND METHODS: We used a myocardial NR rat model to confirm the effect and mechanism of action of TMYX in alleviating NR. Sprague-Dawley (SD) rats were divided into Control (Con), sham, NR, TMYX (4.0 g/kg), and sodium nitroprusside (SNP, 5.0 mg/kg), and received their treatments once a day for one week. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively. RESULTS: TMYX (4.0 g/kg) showed therapeutic effects on NR by improving the cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the expression of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the HIF-1, NF-κB, and TNF signaling pathways. In vivo, TMYX decreased the expression of MPO, NF-κB, and TNF-α and increased the expression of GPER, p-ERK, and HIF-1α. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by G-15, H-89, L-NAME, ODQ and four K+ channel inhibitors. CONCLUSIONS: TMYX exerts its pharmacological effects in the treatment of NR via multiple targets. However, the contribution of each pathway was not detected, and the mechanisms should be further investigated.