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Flexible sensors play a crucial role in intelligent electronic devices, while strain-sensing is the fundamental feature for these sensors of different fields. Therefore, developing high-performance flexible strain sensors is essential for building the next generation of smart electronics. Here, a self-powered ultrasensitive strain sensor based on graphene-based thermoelectric composite threads through a simple 3D extrusion method is reported. The optimized thermoelectric composite threads show a large stretchable strain of over 800%. After 1000 cycles of bending, the threads still maintain excellent thermoelectric stability. The thermoelectric effect-induced electricity can realize ultrasensitive strain and temperature detection with high resolution. As wearable devices, the thermoelectric threads can also realize self-powered physiological signals monitoring, including the opening degree of mouth, occlusal frequency, and force of the tooth during the eating process. It provides significant judgment and guidance for promoting oral healthcare and developing good eating habits.
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Grafite , Dispositivos Eletrônicos Vestíveis , Saúde Bucal , Temperatura , EletrônicaRESUMO
OBJECTIVES: Oral squamous cell carcinoma (OSCC) is often diagnosed with cervical lymph node metastasis. Mesenchymal stem cells (MSCs) and interleukin-6 (IL-6) signalling are considered to play important roles in promoting tumour malignancy. The detailed biological interaction of MSCs and IL-6 and the subsequent effect on OSCC metastasis remain largely unclear. This study aimed to determine the effects and molecular mechanism of MSCs-derived IL-6 on tumour invasion and metastasis. SUBJECTS AND METHODS: The effects of MSC-derived IL-6 and tocilizumab on the proliferation, mobility, and epithelial-mesenchymal transition (EMT) of OSCC cells and potential pathways were detected in vitro. In addition, a murine xenograft model was generated to verify the biological mechanism in vivo. RESULTS: The results showed that the expression of MSCs and EMT-related signals was increased in poorly differentiated OSCC tissues. MSCs released a higher level of IL-6 and promoted the proliferation, invasion, and metastasis of OSCC cells and solid neoplasms, which were activated by the downstream molecules JAK and STAT3. CONCLUSIONS: The results indicated that MSCs-derived IL-6-promoted tumour invasion and metastasis via JAK-STAT3 signalling. Blockade of this pathway by tocilizumab may be a potential treatment to improve the prognosis and survival rate of patients with OSCC.
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Acoustic dyadic sensors (ADSs) are a new type of acoustic sensor with higher directivity than microphones and acoustic vector sensors, which has great application potential in the fields of sound source localization and noise cancellation. However, the high directivity of an ADS is seriously affected by the mismatches between its sensitive units. In this article, (1) a theoretical model of mixed mismatches was established based on the finite-difference approximation model of uniaxial acoustic particle velocity gradient and its ability to reflect the actual mismatches was proven by the comparison of theoretical and experimental directivity beam patterns of an actual ADS based on MEMS thermal particle velocity sensors. (2) Additionally, a quantitative analysis method based on directivity beam pattern was proposed to easily estimate the specific magnitude of the mismatches, which was proven to be useful for the design of ADSs to estimate the magnitudes of different mismatches of an actual ADS. (3) Moreover, a correction algorithm based on the theoretical model of mixed mismatches and quantitative analysis method was successfully demonstrated to correct several groups of simulated and measured beam patterns with mixed mismatches.
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Acústica , Localização de Som , Modelos Teóricos , Ruído , AlgoritmosRESUMO
Vascular smooth muscle cells (VSMCs) in the normal arterial media continually express contractile phenotypic markers which are reduced dramatically in response to injury. Tripartite motif-containing proteins are a family of scaffold proteins shown to regulate gene silencing, cell growth, and differentiation. We here investigated the biological role of tripartite motif-containing 28 (TRIM28) and tripartite motif-containing 27 (TRIM27) in VSMCs. We observed that siRNA-mediated knockdown of TRIM28 and TRIM27 inhibited platelet-derived growth factor (PDGF)-induced migration in human VSMCs. Both TRIM28 and TRIM27 can regulate serum response element activity and were required for maintaining the contractile gene expression in human VSMCs. At the same time, TRIM28 and TRIM27 knockdown reduced the expression of PDGF receptor-ß (PDGFRß) and the phosphorylation of its downstream signaling components. Immunoprecipitation showed that TRIM28 formed complexes with TRIM27 through its N-terminal RING-B boxes-Coiled-Coil domain. Furthermore, TRIM28 and TRIM27 were shown to be upregulated and mediate the VSMC contractile marker gene and PDGFRß expression in differentiating human bone marrow mesenchymal stem cells. In conclusion, we identified that TRIM28 and TRIM27 cooperatively maintain the endogenous expression of PDGFRß and contractile phenotype of human VSMCs.
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Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Contração Muscular , Músculo Liso Vascular/fisiologia , Proteínas Nucleares/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteína 28 com Motivo Tripartido/metabolismo , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Proteínas de Ligação a DNA/genética , Humanos , Células-Tronco Mesenquimais/metabolismo , Músculo Liso Vascular/citologia , Proteínas Nucleares/genética , Fenótipo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Elemento de Resposta Sérica , Transdução de Sinais , Proteína 28 com Motivo Tripartido/genéticaRESUMO
In this paper, small-sized acoustic horns, the sensitivity enhancement package for the MEMS-based thermal acoustic particle velocity sensor, have been designed and optimized. Four kinds of acoustic horns, including tube horn, double cone horn, double paradox horn, and exponential horn, were analyzed through numerical calculation. Considering both the amplification factor and effective length of amplification zone, a small-sized double cone horn with middle tube is designed and further optimized. A three-wire thermal acoustic particle velocity sensor was fabricated and packaged in the 3D printed double cone tube (DCT) horn. Experiment results show that an amplification factor of 6.63 at 600 Hz and 6.93 at 1 kHz was achieved. A good 8-shape directivity pattern was also obtained for the optimized DCT horn with the lateral inhibition ratio of 50.3 dB. No additional noise was introduced, demonstrating the DCT horn's potential in improving the sensitivity of acoustic particle velocity sensors.
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Sistemas Microeletromecânicos , Acústica , Animais , Desenho de Equipamento , RuídoRESUMO
Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease with unclear etiology. Autoimmune thyroid diseases (AITD) is a type of autoimmune disease characterized by increased thyroid-specific antibodies. In recent years, more and more studies have found that the incidence of AITD is increased in OLP patients. The occurrence and development of OLP and AITD may be related to the expression of thyroid autoantigen in oral keratinocytes, the imbalance of thyroid hormone ï¼Thï¼1/Th2 and Th17/Treg cell subsets, the abnormal quantity and function of follicular helper T cells and chemokines and the specific killing ability of CD8 T cells to target cells. In this article, the possible immune mechanisms involved in the coexistence of OLP and AITD are reviewed to provide insights for the diagnosis, treatment and prevention of these two diseases from the perspective of immunology.
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Doenças Autoimunes , Doença de Hashimoto , Líquen Plano Bucal , Doenças Autoimunes/complicações , Humanos , Líquen Plano Bucal/complicações , Mucosa Bucal , Células Th17RESUMO
Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knockdown of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs. Knockdown of MTUS1 disturbed the elongated mitochondrial network and induced the formation of perinuclear clusters of mitochondria. Importantly, mitochondrial motility and fusion were suppressed, whereas generation of reactive oxygen species was increased in MTUS1 knockdown ECs. Mechanistically, we showed that the N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins, mitofusin-1 and mitofusin-2, to maintain mitochondrial morphology in ECs. This study illustrated a novel role of MTUS1 in mitochondrial morphology and EC angiogenic responses.-Wang, Y., Huang, Y., Liu, Y., Li, J., Hao, Y., Yin, P., Liu, Z., Chen, J., Wang, Y., Wang, N., Zhang, P. Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.
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Células Endoteliais/metabolismo , Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Linhagem Celular , Movimento Celular/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Lipogenesis is required for the optimal growth of many types of cancer cells, it is shown to control the biosynthesis of the lipid bilayer membrane during rapid proliferation and metastasis, provides cancer cells with signaling lipid molecules to support cancer development and make cancer cells more resistant to oxidative stress-induced cell death. Though multiple lipogenic enzymes have been identified to mediate this metabolic change, how the expression of these lipogenic enzymes are transcriptionally regulated remains unclear. METHODS: Gain- and loss-of-function experiments were conducted to assess the role of transcriptional repressor, nuclear receptor sub-family 6, group A, member 1 (NR6A1) in HepG2 cells. RT-qPCR method was performed to investigate target gene of NR6A1. Western blot was employed to determine the mechanisms by which NR6A1 regulates lipid accumulation in HepG2 cells. RESULTS: We provide evidence that NR6A1 is a novel regulator of lipid metabolism in HepG2 cells. NR6A1 knockdown can increase lipid accumulation as well as insulin-induced proliferation and migration of HepG2 cells. The lipogenic effect correlated well with the expression of lipogenic genes, including fatty acid synthase (FAS), diglyceride acyltransferase-2 (DGAT2), malic enzyme 1 (ME1), microsomal triglyceride transfer protein (MTTP) and phosphoenolpyruvate carboxykinase (PEPCK). NR6A1 knockdown also increased the expression of carnitine palmitoyltransferase 1A (CPT1a), the rate-limiting enzyme in fatty acid oxidation. Furthermore, NR6A1 knockdown induced lipid accumulation through mammalian target of rapamycin complex 1 (mTORC1), but not mTORC2. Moreover, siRNA-mediated knockdown of NR6A1 increased expression of insulin receptor (INSR) and potentitated insulin-induced phosphorylation of mTOR and AKT partly via miR-205-5p in HepG2 cells. CONCLUSIONS: These findings provide important new insights into the role of NR6A1 in the lipogenesis in HepG2 cells. .
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Metabolismo dos Lipídeos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Membro 1 do Grupo A da Subfamília 6 de Receptores Nucleares/metabolismo , Animais , Movimento Celular , Proliferação de Células , Regulação da Expressão Gênica , Inativação Gênica , Células HEK293 , Células Hep G2 , Humanos , Insulina/metabolismo , Lipogênese , MicroRNAs/genética , Membro 1 do Grupo A da Subfamília 6 de Receptores Nucleares/deficiência , Membro 1 do Grupo A da Subfamília 6 de Receptores Nucleares/genética , Receptor de Insulina/genética , Transdução de SinaisRESUMO
A series of studies are dedicated to research the clinical outcomes of oral leukoplakia (OLK) treated with carbon dioxide laser (CO2 laser); however, the results vary from studies especially related to recurrence and malignant transformation. Hence, we performed this meta-analysis to precisely evaluate the malignant transformation of OLK dealt with CO2 laser and investigate the association between its malignant transformation and kinds of related risk factors, such as gender, clinical classification, long duration of leukoplakia, and degree of epithelial dysplasia and lesion regions. We performed a systematic search of the Cochrane Library, EMBASE, Pubmed, Web of Science, and SCOPUS. Single-arm rate of the overall risk of malignant transformation in OLK treated with CO2 laser was calculated using the Der-Simonian Liard method. We applied subgroup analysis to compare the risk of malignant transformation according to the degree of epithelial dysplasia, clinical type, and region of OLK. Moreover, a pooled odds ratio (OR) is calculated, along with its 95% confidence interval (CI), to compare the risk of malignant transformation according to patients' gender, tobacco, and alcohol consumption. We used the meta package of R software for quantitative data synthesis and analysis. The rate of malignant transformation of OLK treated with carbon dioxide laser ranged from 0 to 15.38% in included studies. The overall rate of malignant transformation of OLK treated with CO2 laser is 4.50% under the random effect model [95% CI 0.0305-0.0659]. A systematic review of observational studies of OLK reported that the estimated overall (mean) malignant transformation rate was 3.5%, with a wide range between 0.13 and 34.0%. Interestingly, our result revealed that it was the male, homogeneous type, no tobacco consumption, and without alcohol-use who had a higher tendency of malignancy after laser surgery. However, this result lack statistically significant data. Generally speaking, whether oral leukoplakia patients underwent laser surgical treatment or not, it may have little effect on malignant transformation. In addition, we strongly advise that it had better not to perform CO2 laser intervention on OLK patients with the following clinical characteristics: homogeneous type, male, no tobacco consumption, and without alcohol-use. Evidence is still lacking in terms of relationship between malignant transformation and risk factors among OLK patients managed with CO2 laser. Thus, these associations should be further investigated.
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Transformação Celular Neoplásica/patologia , Lasers de Gás/uso terapêutico , Leucoplasia Oral/patologia , Leucoplasia Oral/cirurgia , Transformação Celular Neoplásica/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Razão de Chances , Viés de Publicação , Fatores de RiscoRESUMO
Fibroblast growth factor receptors (FGFR) play a significant role in both embryonic development and in adults. Upon binding with ligands, FGFR signaling is activated and triggers various downstream signal cascades that are implicated in diverse biological processes. Aberrant regulations of FGFR signaling are detected in numerous cancers. Although FGFR4 was discovered later than other FGFR, information on the involvement of FGFR4 in cancers has significantly increased in recent years. In this review, the recent findings in FGFR4 structure, signaling transduction, physiological function, aberrant regulations, and effects in cancers as well as its potential applications as an anticancer therapeutic target are summarized.
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Antineoplásicos/uso terapêutico , Fatores de Crescimento de Fibroblastos/metabolismo , Neoplasias/patologia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Processamento Alternativo , Antineoplásicos/farmacologia , Carcinogênese/genética , Carcinogênese/patologia , Humanos , Ligantes , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Domínios Proteicos , RNA Interferente Pequeno/uso terapêutico , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/química , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Transdução de Sinais/genéticaRESUMO
Rising instances of flash droughts are contributing to notable variability in soil moisture across terrestrial ecosystems. These phenomena challenge urban ecosystem services, yet the reaction of soil ecological functions (SEFs) to such events is poorly understood. This study investigates the responses of SEFs (about nutrient metabolism capacity and potential) and the microbiome under two specific scenarios: a flooding-drought sequence and a direct drought condition. Using quantitative microbial element cycling analysis, high-throughput sequencing, and enzyme activity measurements, we found that unlike in forests, the microbial composition in urban soils remained unchanged during flash drought conditions. However, SEFs were affected in both settings. Correlation analysis and Mantel test showed that forest soils exhibited more complex interactions among soil moisture, properties, and microbial communities. Positive linear correlation revealed that bacteria were the sole drivers of SEFs. Interestingly, while multi-threshold results suggested bacterial α diversity impeded the maximization of SEFs in urban soils, fungi and protists had a beneficial impact. Cross-domain network of urban soils had higher number of nodes and edges, but lower average degree and robustness than forest soils. Mantel test revealed that fungi and protist had significant correlations with bacterial composition in forest soils, but not in urban soils. In the urban network, the degree and eigenvector centrality of bacterial, fungal and protistan ASVs were significantly lower compared to those in the forest. These results suggest that the lower robustness of the microbial network in urban soils is attributed to limited interactions among fungi, consumer protists, and bacteria, contributing to the failure of microbial-driven ecological functions. Overall, our findings emphasize the critical role of fungi and protists in shielding urban soils from drought-induced disturbances and in enhancing the resistance of urban ecological functions amidst environmental changes.
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Urban green spaces provide multiple ecosystem services and have great influences on human health. However, the compositions and properties of urban soil are not well understood yet. In this study, soil samples were collected from 45 parks in Ningbo to investigate the relationships among soil physicochemical properties, heavy metals and bacterial communities. The results showed that soil dissolved organic matter (DOM) was of high molecular weight, high aromaticity, and low degree of humification. The contents of heavy metals were all below the China's national standard safety limit (GB 3660-2018). The bioavailability of heavy metals highly correlated with soil pH, the content of DOC, the fluorescent component, the degree of humification and the source of DOM. The most abundant genera were Gemmatimonadaceae_uncultured, Xanthobacteraceae_uncultured, and Acidothermus in all samples, which were related to nitrogen cycle and bioavailability of heavy metals. Soil pH, bioavailability of Zn, Cd, and Pb (CaCl2 extracted) were the main edaphic factors influencing bacterial community composition. It should be noted that there was no significant impact of urbanization on soil physicochemical properties and bacterial composition, but they were determined by the source of soil in urban green spaces. However, with the passage of time, the effect of urbanization on urban green spaces cannot be ignored. Overall, this study provided new insight for understanding the linkage among soil physicochemical properties, heavy metals, and bacterial communities in urban green spaces.
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Metais Pesados , Microbiologia do Solo , Poluentes do Solo , Solo , Urbanização , Solo/química , China , Metais Pesados/análise , Poluentes do Solo/análise , Monitoramento Ambiental , BactériasRESUMO
Rapid urbanization in the Asia-Pacific region is expected to place two-thirds of its population in concrete-dominated urban landscapes by 2050. While diverse architectural facades define the unique appearance of these urban systems. There remains a significant gap in our understanding of the composition, assembly, and ecological potential of microbial communities on building exteriors. Here, we examined bacterial and protistan communities on building surfaces along an urbanization gradient (urban, suburban and rural regions), investigating their spatial patterns and the driving factors behind their presence. A total of 55 bacterial and protist phyla were identified. The bacterial community was predominantly composed of Proteobacteria (33.7% to 67.5%). The protistan community exhibited a prevalence of Opisthokonta and Archaeplastida (17.5% to 82.1% and 1.8% to 61.2%, respectively). The composition and functionality of bacterial communities exhibited spatial patterns correlated with urbanization. In urban buildings, factors such as facade type, light exposure, and building height had comparatively less impact on bacterial composition compared to suburban and rural areas. The highest bacterial diversity and lowest Weighted Average Community Identity (WACI) were observed on suburban buildings, followed by rural buildings. In contrast, protists did not show spatial distribution characteristics related to facade type, light exposure, building height and urbanization level. The distinct spatial patterns of protists were primarily shaped by community diffusion and the bottom-up regulation exerted by bacterial communities. Together, our findings suggest that building exteriors serve as attachment points for local microbial metacommunities, offering unique habitats where bacteria and protists exhibit independent adaptive strategies closely tied to the overall ecological potential of the community.
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Bactérias , Urbanização , Bactérias/classificação , MicrobiotaRESUMO
Background/purpose: The application of artificial intelligence diagnosis based on deep learning in the medical field has been widely accepted. We aimed to evaluate convolutional neural networks (CNNs) for automated classification and detection of recurrent aphthous ulcerations (RAU), normal oral mucosa, and other common oral mucosal diseases in clinical oral photographs. Materials and methods: The study included 785 clinical oral photographs, which was divided into 251 images of RAU, 271 images of the normal oral mucosa, and 263 images of other common oral mucosal diseases. Four and three CNN models were used for the classification and detection tasks, respectively. 628 images were randomly selected as training data. In addition, 78 and 79 images were assigned as validating and testing data. Main outcome measures included precision, recall, F1, specificity, sensitivity and area under the receiver operating characteristics curve (AUC). Results: In the classification task, the Pretrained ResNet50 model had the best performance with a precision of 92.86%, a recall of 91.84%, an F1 score of 92.24%, a specificity of 96.41%, a sensitivity of 91.84% and an AUC of 98.95%. In the detection task, the Pretrained YOLOV5 model had the best performance with a precision of 98.70%, a recall of 79.51%, an F1 score of 88.07% and an AUC of Precision-Recall curve 90.89%. Conclusion: The Pretrained ResNet50 and the Pretrained YOLOV5 algorithms were shown to have superior performance and acceptable potential in the classification and detection of RAU lesions based on non-invasive oral images, which may prove useful in clinical practice.
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PbSn solders are used in semiconductor devices for aerospace or military purposes with high levels of reliability requirements. Microalloying has been widely adopted to improve the reliability for Pb-free solders, but its application in PbSn solders is scarce. In this article, the optimization of PbSn solder reliability with Ge microalloying was investigated using both experimental and calculation methods. Intermetallic compounds (IMC) growth and morphologies evolution during reliability tests were considered to be the main factors of device failure. Through first-principle calculation, the growth mechanism of interfacial Ni3Sn4 was discussed, including the formation of vacancies, the Ni-vacancies exchange diffusion and the dominant Ni diffusion along the [1 0 0] direction. The doping of Ge in the cell increased the exchange energy barrier and thus inhibited the IMC development and coarsening trend. In three reliability tests, only 0.013 wt% Ge microalloying in Pb60Sn40 was able to reduce IMC thickness by an increment of 22.6~38.7%. The proposed Ge microalloying method in traditional PbSn solder could yield a prospective candidate for highly reliable applications.
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Arsenic and cadmium in rice grain are of growing concern in the global food supply chain. Paradoxically, the two elements have contrasting behaviors in soils, making it difficult to develop a strategy that can concurrently reduce their uptake and accumulation by rice plant. This study examined the combined impacts of watering (irrigation) schemes, different fertilizers and microbial populations on the bioaccumulation of arsenic and cadmium by rice as well as on rice grain yield. Compared to drain-flood and flood-drain treatments, continuously flooded condition significantly reduced the accumulation of cadmium in rice plant but the level of arsenic in rice grain remained above 0.2 mg/kg, which exceeded the China national food safety standard. Application of different fertilizers under continuously flooded condition showed that compared to inorganic fertilizer and biochar, manure addition effectively reduced the accumulation of arsenic over three to four times in rice grain and both elements were below the food safety standard (0.2 mg/kg) while significantly increasing the rice yield. Soil Eh was the critical factor in the bioavailability of cadmium, while the behavior of arsenic in rhizosphere was associated with the iron cycle. The results of the multi-parametric experiments can be used as a roadmap for low-cost and in-situ approach for producing safe rice without compromising the yield.
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Arsênio , Oryza , Poluentes do Solo , Arsênio/análise , Cádmio/análise , Fertilizantes , Poluentes do Solo/análise , SoloRESUMO
Introduction: Sepsis is a common but serious disease in intensive care units, which may induce multiple organ dysfunctions such as liver injury. Previous studies have demonstrated that gamma delta (γδ) T cells play a protective role in sepsis. However, the function and mechanism of γδ T cells in sepsis-induced liver injury have not been fully elucidated. IL-17A-producing γδ T cells are a newly identified cell subtype. Methods: We utilized IL-17A-deficient mice to investigate the role of IL-17A-producing γδ T cells in sepsis using the cecum ligation and puncture (CLP) model. Results: Our findings suggested that these cells were the major source of IL-17A and protected against sepsis-induced liver injury. Flow cytometry analysis revealed that these γδ T cells expressed Vγ4 TCR and migrated into liver from peripheral post CLP, in a CCR6-dependent manner. When CLP mice were treated with anti-CCR6 antibody to block CCR6-CCL20 axis, the recruitment of Vγ4+ γδ T cells was abolished, indicating a CCR6-dependent manner of migration. Interestingly, pseudo germ-free CLP mice treated with antibiotics showed that hepatic IL-17A+ γδ T cells were regulated by gut commensal microbes. E. coli alone were able to restore the protective effect in pseudo germ-free mice by rescuing hepatic IL-17A+ γδ T cell population. Conclusion: Our research has shown that Vγ4+ IL-17A+ γδ T cells infiltrating into the liver play a crucial role in protecting against sepsis-induced liver injury. This protection was contingent upon the recruitment of CCR6 and regulated by gut commensal microbes.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Linfócitos Intraepiteliais , Sepse , Animais , Camundongos , Escherichia coli , Interleucina-17 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Antígenos de Linfócitos T gama-delta , Sepse/complicaçõesRESUMO
Exposure to ionizing radiation leads to oxidative damages in living cells. NADPH provides the indispensable reducing power to regenerate the reduced glutathione to maintain cellular redox equilibria. In mammalian cells, pentose phosphate pathway (PPP) is the major route to produce NADPH by using glycolytic intermediates, and the rate-limiting step of PPP is controlled by glucose-6-phosphate dehydrogenase (G6PD). Nevertheless, whether G6PD is timely co-opted under ionizing radiation to cope with oxidative stress remains elusive. Here we show that cellular G6PD activity is induced 30 min after ionizing radiation, while its protein expression is mostly unchanged. Mechanistically, casein kinase 2 (CK2) phosphorylates G6PD T145 under ionizing radiation, which consolidates the enzymatic activity of G6PD by facilitating G6PD binding with its substrate NADP+. Further, CK2-dependent G6PD T145 phosphorylation promotes NADPH production, decreases ROS level and supports cell proliferation under ionizing radiation. Our findings report a new anti-oxidative signaling route under ionizing radiation, by which CK2-mediated rapid activation of G6PD orchestrates NADPH synthesis to maintain redox homeostasis, thereby highlighting its potential value in the early treatment of ionizing radiation-induced injuries.