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A thorough comprehension of nitrogen biogeochemical processes in the vadose zone is crucial for the effective prevention and remediation of soil-groundwater system contamination. Despite the growing research on this subject, the full scope of nitrogen biogeochemical characterization in different geological environments remains poorly understood. This study addresses this knowledge gap by integrating geochemical, microbiological and numerical simulation approaches to gain a deeper insight into nitrogen biogeochemistry in agriculture. Our findings indicate the biogeochemical behavior of nitrogen in the vadose zone is mediated by microorganisms, driven by hydraulics, influenced by geological conditions and environmental factors. Along the groundwater flow, NH4+-N was found to be heavily accumulated in the topsoil of 0-40 cm, while NO3--N was transported and driven by hydrodynamics from both vertical and horizontal directions. Microbial diversity, species composition and functional microorganisms were significantly influenced by soil depth, rather than geomorphological types. Oxidation-reduction potential (ORP), total organic carbon (TOC), soil moisture (MOI), bicarbonate (HCO3-), and ferrous (Fe2+) were identified as the principal environmental factors that regulate nitrogen metabolism and the dominant biochemical processes, encompassing nitrogen fixation, nitrification, and denitrification. Driven by hydrodynamics, NH4+-N, NO2--N and NO3--N tend to form distinct biochemical reaction zones in the vertical vadose zone. These areas are dynamic and subject to geomorphologies. It should be noted that NO3--N can migrate towards groundwater from the clayey sand in the Alluvial Plain, which presents a potential risk of groundwater contamination. The fissure structure of loess may serve as the major transport pathway for groundwater nitrogen contamination in the Loess Tableland. This finding highlights the importance of integrating microbiology, geochemistry and hydraulics to elucidate the biogeochemical processes of nitrogen in the vadose zone with a dynamic mindset.
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Água Subterrânea , Nitrogênio , Microbiologia do Solo , Nitrogênio/análise , Água Subterrânea/química , Água Subterrânea/microbiologia , Monitoramento Ambiental , Solo/química , Desnitrificação , Poluentes Químicos da Água/análise , NitrificaçãoRESUMO
BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed. CASE SUMMARY: This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient's abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases. CONCLUSION: For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.
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Gaseous carbon exchange at the water-air interface of rivers and lakes is an essential process for regional and global carbon cycle assessments. Many studies have shown that rivers surrounding urban landscapes can be hotspots for greenhouse gas (GHG) emissions. Here we investigated the variability of diffusive GHG (methane [CH4] and carbon dioxide [CO2]) emissions from rivers in different landscapes (i.e., urban, agricultural and mixed) and from lakes in Suzhou, a highly urbanized region in eastern China. GHG emissions in the Suzhou metropolitan water network followed a typical seasonal pattern, with the highest fluxes in summer, and were primarily influenced by temperature and dissolved oxygen concentration. Surprisingly, lakes were emission hotspots, with mean CH4 and CO2 fluxes of 2.80 and 128.89 mg m-2 h-1, respectively, translating to a total CO2-equivalent flux of 0.21 g CO2-eq m-2 d-1. The global warming potential of urban and mixed rivers (0.19 g CO2-eq m-2 d-1) was comparable to that for lakes, but about twice the value for agricultural rivers (0.10 g CO2-eq m-2 d-1). Factors related to the high GHG emissions in lakes included hypoxic water conditions and an adequate nutrient supply. Riverine CH4 emissions were primarily associated with the concentrations of total dissolved solids (TDS), ammonianitrogen and chlorophyll a. CO2 emissions in rivers were mainly closely related to TDS, with suitable conditions allowing rapid organic matter decomposition. Compared with other types of rivers, urban rivers had more available organic matter and therefore higher CO2 emissions. Overall, this study emphasizes the need for a deeper understanding of the impact of GHG emissions from different water types on global warming in rapidly urbanizing regions. Flexible management measures are urgently needed to mitigate CO2 and CH4 emissions more effectively in the context of the shrinking gap between urban and rural areas with growing socio-economic development.
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A new 3D zinc-based metal-organic framework {[Zn7L2(DMF)3(H2O)(OH)2]·5DMF}n (1) (H6L = 5,5',5â³-(methylsilanetriyl) triisophthalic acid) was constructed with an organosilicon-based linker, where H6L is a tetrahedral structure furnished with rich -COO- chelating sites for Zn(II) immobilization. Compound 1 exhibited two types of irregular one-dimensional channels and a three-dimensional skeleton with large specific surface area, making it a promising catalytic platform. Moreover, by incorporation of the second metal ion into the inorganic node of framework 1, isomorphic bimetallic MOF ZnMg-1 was successfully synthesized. ZnMg-1 demonstrated enhanced catalytic activity compared to 1 under identical conditions. Contrast experiments and theoretical calculations indicate that bimetallic active sites play a facilitating role in the chemical fixation of epoxides and CO2. It indicated that efficient chemical fixation of CO2 to cyclic carbonates was obtained over isomorphic MOF catalysts 1 and ZnMg-1.
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OBJECTIVE: To investigate the safety, local ablation efficacy, analgesic effects, and factors influencing the survival of patients with advanced pancreatic cancer treated with high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Patients with advanced pancreatic cancer who underwent HIFU for the first time at the Suining Central Hospital between January 2018 and September 2022 were enrolled. The efficacy of tumor ablation was assessed using enhanced computed tomography (CT) and magnetic resonance imaging (MRI), pain relief was assessed using the visual analog scale (VAS), and complications and survival rates were investigated. The Kaplan-Meier method and a Cox regression model were used to analyze the independent risk factors that may have affected prognosis. RESULTS: Intraoperative ultrasonography showed varying degrees of grayscale changes in all cases. One month after surgery, enhanced computed tomography or magnetic resonance imaging examinations showed complete or partial responses in 85.22% of the patients. Pain relief was achieved in 98.21% of the patients. No postoperative complications of SIR-C grade or higher were observed. The overall median survival time (MST) was 12.1 months. Cox multifactorial analysis showed that the main factors affecting overall survival (OS) were clinical stage, preoperative liver function, and combination chemotherapy. CONCLUSION: HIFU is safe and effective for pancreatic cancer treatment, and has the potential to become an important supplement for the treatment of advanced pancreatic cancer. This approach needs to be further verified by multi-center and large-sample studies.
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Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias , Pâncreas , Dor , Neoplasias PancreáticasRESUMO
The incidence of ampulla of Vater carcinoma, a type of periampullary cancer, has been increasing at an annual percentage rate of 0.9%. However, patients with ampulla of Vater carcinoma have quite different prognoses due to the heterogeneities of the tissue origin of this carcinoma. In addition to TNM staging, histological subtypes and molecular features of ampulla of Vater carcinoma are the key factors for predicting the clinical outcomes of patients. Fortunately, with the development of testing technology, information on the histological subtypes and molecular features of ampulla of Vater carcinoma is increasingly being analyzed in-depth. Patients with the pancreaticobiliary subtype have shorter survival times. In immunohistochemical examination, high cutoff values of positive MUC1 staining can be used to accurately predict the outcome of patients. Mutant KRAS, TP53, negative SMAD4 expression, and microsatellite stability are related to poor prognosis, while the clinical value of BRCA1/BRCA2 mutations is limited for prognosis. Testing the histological subtypes and molecular characteristics of ampulla of Vater carcinoma not only is the key to prognosis analysis but also provides extra information for targeted treatment to improve the clinical outcomes of patients.
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OBJECTIVE: To evaluate the feasibility, safety, and efficacy of high-intensity focused ultrasound (HIFU) and microwave ablation (MWA) for the treatment of small liver metastatic tumors. METHODS: Fifty-eight patients with small liver metastatic tumors who underwent HIFU (n = 28) or MWA (n = 30) at Suining Central Hospital between January 2016 and December 2021 were retrospectively evaluated. Demographic and clinical characteristics were compared between the two groups. RESULTS: Operation times were longer and hospitalization costs were lower in the HIFU group than in the MWA group. Postoperative hospitalization times, tumor ablation rates, and clinical response and control rates did not differ significantly between the two groups 1 month after surgery. Rates of postoperative complications such as fever, liver dysfunction, injury, pain, and biliary leakage did not differ between the two groups. The 1- and 3-year cumulative survival rates were 96.4% and 52.4%, respectively, after HIFU and 93.3% and 51.4%, respectively, after MWA, which did not represent significant differences. CONCLUSIONS: HIFU is a safe and feasible method of treating small liver metastatic tumors. Compared with MWA, HIFU was associated with lower hospitalization costs, reduced trauma, and fewer postoperative complications, making it a promising new local ablative treatment option for liver metastatic tumors.
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Neoplasias Hepáticas , Micro-Ondas , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
Nitrogen pollution in groundwater is an environmental issue of global concern. Identifying nitrogen pollution sources and determining migration and transformation processes are the major ways to prevent and control nitrogen pollution in the groundwater on a regional scale. In this study, groundwater in the lower Wei River was investigated by combining multi-isotope tracing techniques with the SIAR hybrid model (source resolution) to trace the nitrate sources and their contribution rate to nitrogen pollution in groundwater of different geomorphological units, considering types of geomorphology as the units. The multi-isotope tracing technique allows dynamic analysis of nitrate sources, and the combination of this technology can improve the accuracy of nitrogen source traceability. The results indicated that the pH of the water bodies in the study area ranged from 6.83 to 8.01, which is neutral and weakly alkaline. The nitrogen pollution was mainly due to nitrates. The significant factors affecting nitrogen migration in groundwater are the geomorphological type, the chemical characteristics of the groundwater, and the age of the groundwater. Nitrogen migration and transformation processes in the study area were dominated by nitrification, and sources of nitrate pollution were mainly animal manure and domestic sewage (32.6%), followed by atmospheric deposition (26.8%), soil nitrogen (20.9%), and chemical fertilizer (19.7%). The main sources of nitrate in groundwater from river flats, alluvial plains, and loess tableland were animal manure and domestic sewage (43.7%), animal manure and domestic sewage (59.1%), and atmospheric deposition (55.5%), respectively. The result is mainly related to the different structural characteristics of various geomorphic units and the intensity of human activities. This study can provide a theoretical basis for the relevant agencies to develop plans to combat groundwater pollution.
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Água Subterrânea , Poluentes Químicos da Água , Animais , Humanos , Nitrogênio/análise , Nitratos/análise , Isótopos de Nitrogênio/análise , Rios/química , Esterco/análise , Esgotos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Água Subterrânea/química , ChinaRESUMO
Although toluene is a typical in-vehicle pollutant, the impacts of in-vehicle toluene exposure on cognitive functions remain unestablished. Therefore, this study aimed to investigate the effects of short-term toluene exposure in vehicles on working memory based on neural oscillations. In total, 24 healthy adults were recruited. Each subject was exposed to four different concentrations of toluene and divided into 0 ppb, 17.5 ppb, 35 ppb, and 70 ppb groups for self-control studies. After 4 h of exposure to each concentration of toluene, a behavioral test of visual working memory was performed while 19-channel electroencephalogram (EEG) signals were collected. Meanwhile, the power spectral density (PSD) and spatial distribution of working memory encoding, maintenance, and extraction periods were calculated by short-time Fourier transform to clarify the characteristic frequency bands, major brain regions, and characteristic channels of each period. To compare the changes in the characteristic patterns of neural oscillations under the effect of different concentrations of toluene. There was no significant difference in working memory reaction time and correct rate between the groups at different toluene concentrations (p > 0.05). The characteristic frequency band of the working memory neural oscillations in each group was the theta frequency band; the PSD of the theta frequency band was predominantly concentrated in the frontal area, and the characteristic channel was the Fz channel. The whole brain (F = 3.817, p < 0.05; F = 4.758, p < 0.01; F = 3.694, p < 0.05), the frontal area (F = 2.505, p < 0.05; F = 2.839, p < 0.05; F = 6.068, p < 0.05), the Fz channel (F = 3.522, p < 0.05; F = 3.745, p < 0.05; F = 6.526, p < 0.05), and the PSD of working memory in the theta frequency band was significantly increased in the 70 ppb group compared with the other three groups during the coding, maintenance, and retrieval phases of working memory. When the in-vehicle toluene exposure concentration was 70 ppb, the PSD of the characteristic frequency bands of working memory was significantly increased in the whole brain, major brain regions, and characteristic channels.
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Encéfalo , Memória de Curto Prazo , Adulto , Humanos , Eletroencefalografia , CogniçãoRESUMO
To study the inorganic nitrogen in the process of interaction of river and groundwater and the changes in the microbial community, a vertical simulation device was used to simulate groundwater recharge to river water (upwelling) and river water recharge to groundwater (downwelling). The inorganic nitrogen concentrations in the soil and water solution as well as the characteristics of the microbial community were assessed to determine the inorganic nitrogen transformation and microbial community response in the heterogeneous interaction zone under hydrodynamic action, and the interaction mechanism between nitrogen transformation and the microbial community in the interaction zone was revealed. The removal rates of NO3--N in the simulated solution reached 99.1% and 99.3% under the two fluid-groundwater conversion modes, and the prolonged hydraulic retention time (HRT) of the oxidization-reduction layer in the fine clay area and the high organic matter content made the inorganic nitrogen transformation process dominated by microorganisms more complete. The denitrification during upwelling, dominated by denitrifying bacteria in Sphingomonas, Pseudomonas, Bacillus, and Arthrobacter, was stronger than that during downwelling. Dissimilatory nitrate reduction to ammonium (DNRA), controlled by some aerobic bacteria in Pseudomonas, Bacillus, and Desulfovibrio, was more intense in downflow mode than upflow mode.
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Compostos de Amônio , Bacillus , Água Subterrânea , Microbiota , Nitrogênio , Hidrodinâmica , Desnitrificação , Nitratos , ÁguaRESUMO
RATIONALE: Upper gastrointestinal hemorrhage (UGIH) is defined as hemorrhage originating from the gastrointestinal tract proximal to the ligament of Treitz. The causes of UGIH include esophagitis, gastritis, peptic ulcers, Mallory-Weiss syndrome, and cancer. However, a rare cause of UGIH, such as an accessory spleen, may lead to serious complications if left untreated and can sometimes be very difficult to diagnose preoperatively. PATIENT CONCERNS: An 18-year-old man was admitted to the Department of Gastroenterology of our hospital due to "repeated black stool for 2 months with aggravation, accompanied by hematemesis for 9 days." He denied any history of hepatitis, trauma, or surgery. DIAGNOSIS: Laboratory evaluation revealed severe anemia (hemoglobin, 6.4 g/dL). Computed tomography revealed a mass measuring 127 mm in its largest dimension, located in the upper left abdomen, with varicose veins in the gastric fundus. Moreover, distended blue-purple tortuous veins were observed by gastroscopy in the gastric fundus. We believed the mass was likely an abnormally proliferating accessory spleen; however, the causes of severe anemia and gastrointestinal hemorrhage were unknown. INTERVENTIONS: After discussion in a multidisciplinary conference, the mass was completely resected laparoscopically, and the subserosal veins in the gastric fundus were sutured using absorbable threads. OUTCOMES: After the surgery, the patient recovered uneventfully without any complications. Clinicopathological examination showed that the mass was chronic congestive splenomegaly. Gastrointestinal hemorrhage secondary to an abnormally proliferating accessory spleen was confirmed as the diagnosis. Laboratory evaluation revealed hemoglobin at 12.1 g/dL 2 months after surgery. At the 12-month follow-up, the patient showed no recurrence of gastrointestinal hemorrhage. LESSONS: UGIH caused by accessory spleen is extremely rare. This entity should be considered in differential diagnosis of gastrointestinal hemorrhage. Surgical intervention is necessary for timely diagnosis and treatment in case of gastrointestinal hemorrhage in critical clinical situations.
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Anormalidades do Sistema Digestório , Síndrome de Mallory-Weiss , Esplenopatias , Adolescente , Anormalidades do Sistema Digestório/complicações , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hematemese/etiologia , Humanos , Masculino , Síndrome de Mallory-Weiss/complicações , Esplenopatias/complicaçõesRESUMO
The DNA sensor cGAS detects cytosolic DNA and instigates type I interferon (IFN) expression. Recent studies find that cGAS also localizes in the nucleus and binds the chromatin. Despite the mechanism controlling nuclear cGAS activation is well elucidated, whether nuclear cGAS participates in DNA sensing is unclear. Here, we report that herpes simplex virus 1 (HSV-1) infection caused the release of cGAS from the chromatin into the nuclear soluble fraction. Like its cytosolic counterpart, the leaked nuclear soluble cGAS also sensed viral DNA, produced cGAMP, and induced mRNA expression of type I IFN and interferon-stimulated genes. Consistently, the nuclear soluble cGAS limited HSV-1 infection. Furthermore, enzyme-deficient mutation (D307A) or cGAS inhibitor RU.251 abolished nuclear cGAS-mediated innate immune responses, suggesting that enzymatic activity is also required for nuclear soluble cGAS. Taken all together, our study demonstrates that nuclear soluble cGAS acts as a nuclear DNA sensor detecting nuclear-replicating DNA viruses.
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Infecções por Vírus de DNA , Vírus de DNA , Nucleotidiltransferases , Cromatina , DNA/genética , DNA/metabolismo , Infecções por Vírus de DNA/genética , Infecções por Vírus de DNA/metabolismo , Infecções por Vírus de DNA/virologia , Vírus de DNA/genética , Vírus de DNA/metabolismo , Herpes Simples/genética , Humanos , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismoRESUMO
Long-term survivals of patients with hepatocellular carcinoma (HCC) remain unfavorable, which is largely attributed to active carcinogenesis. Growing studies have suggested that the reliable gene signature could act as an independent prognosis factor for HCC patients. We tried to screen the survival-related genes and develop a prognostic prediction model for HCC patients based on the expression profiles of the critical survival-related genes. In this study, we analyzed TCGA datasets and identified 280 genes with differential expressions (125 increased genes and 155 reduced genes). We analyzed the prognosis value of the top 10 dysregulated genes in HCC patients and identified three critical genes, including FCN3, CDC20, and E2F1, which were confirmed to be associated with long-term survival in both TCGA and ICGC datasets. The results of the LASSO model screened CDC20 and FCN3 for the development of the prognostic model. The CDC20 expression was distinctly increased in HCC specimens, while the FCN3 expression was distinctly decreased in HCC. At a suitable cutoff, patients were divided into low-risk and high-risk groups. Survival assays revealed that patients in high-risk groups exhibited a shorter overall survival than those in low-risk groups. Finally, we examine the relationships between risk score and immune infiltration abundance in HCC and observed that risk score was positively correlated with infiltration degree of B cells, T cell CD4+ cells, neutrophil, macrophage, and myeloid dendritic cells. Overall, we identified three critical survival-related genes and used CDC20 and FCN3 to develop a novel model for predicting outcomes and immune landscapes for patients with HCC. The above three genes also have a high potential for targeted cancer therapy of patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas Cdc20/genética , Proteínas de Ciclo Celular , Humanos , Lectinas , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , PrognósticoRESUMO
[This corrects the article DOI: 10.3389/fnhum.2021.770678.].
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The mouse is a common and cost-effective animal model for basic research, and the number of genetically engineered mouse models with cardiac phenotype is increasing. In vivo electrophysiological study in mice is similar to that performed in humans. It is indispensable for acquiring intracardiac electrocardiogram recordings and determining baseline cardiac cycle intervals. Furthermore, the use of programmed electrical stimulation enables determination of parameters such as sinoatrial conduction time, sinus node recovery time, atrioventricular-nodal conduction properties, Wenckebach periodicity, refractory periods and arrhythmia vulnerability. This protocol describes specific procedures for determining these parameters that were adapted from analogous human protocols for use in mice. We include details of ex vivo electrophysiological study, which provides detailed insights into intrinsic cardiac electrophysiology without external influences from humoral and neural factors. In addition, we describe a heart preparation with intact innervation by the vagus nerve that can be used as an ex vivo model for vagal control of the cardiac conduction system. Data acquisition for in vivo and ex vivo electrophysiological study takes ~1 h per mouse, depending on the number of stimulation protocols applied during the procedure. The technique yields highly reliable results and can be used for phenotyping of cardiac disease models, elucidating disease mechanisms and confirming functional improvements in gene therapy approaches as well as for drug and toxicity testing.
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Sistema de Condução Cardíaco , Nó Sinoatrial , Animais , Eletrocardiografia , Sistema de Condução Cardíaco/fisiologia , Frequência Cardíaca/fisiologia , Camundongos , Nó Sinoatrial/fisiologia , Nervo Vago/fisiologiaRESUMO
Situs inversus totalis is a rare congenital anatomical anomaly that causes some difficult problems for surgeons when performing an operation. However, without histopathology specimens from surgery, a misdiagnosis of cancer may be unavoidable, in addition to affecting the improvement of prognosis. This study reports a rare patient with situs inversus totalis who presented with the main complaints of pruritus and vague abdominal pain. She was first misdiagnosed with cholangiocarcinoma and was finally diagnosed with duodenal papilla adenocarcinoma via laparoscopic pancreaticoduodenectomy. Situs inversus totalis was not a contraindication for surgery. Skilled surgeons and complete preparation during the perioperative period are two important keys to successful surgeries. Performing laparoscopic pancreaticoduodenectomy for patients with situs inversus totalis to avoid misdiagnosis of cancer and tailor appropriate therapy plans is cost-effective.
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OBJECTIVE: Although stroke mortality has remained stable over the past decade, the long-term trends of stroke burden are scarce in China, especially in low-income populations. Thus, we aimed to explore the secular trends in the prognosis of stroke in a low-income population in China. METHODS: This was a population-based stroke surveillance study that included all of the participants in the Tianjin Brain Study. Stroke management and outcomes were evaluated for all stroke patients. Trends in the burden of stroke were assessed as annual percentage changes. RESULTS: Overall, 1462 stroke cases occurred from 1992 to 2018, and 58.7% of patients were male. The rates of diagnosis by neuroimaging and of hospitalization increased noticeably across sexes and ages for all stroke types, and the greatest increases were observed among elderly women; diagnosis by neuroimaging increased by 4.7% and the rate of hospitalization increased by 12.4% (all P<0.001). Stroke fatality decreased by 3.7% annually among those aged <65 years and by 3.1% among patients aged ≥65 years; the corresponding rates were 7.4% and 3.5%, respectively, for women. The recurrence rate of ischemic stroke significantly decreased among all men, by 9.6% for those aged <65 years and by 3.1% for those aged ≥65 years; however, for women, this rate only significantly decreased for those aged ≥65 years. CONCLUSION: Our findings suggest that the allocation of medical resources has improved over the past decades. However, it is crucial to enhance secondary stroke prevention for women aged <65 years by controlling risk factors in low-income populations.
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Cytosolic DNA from pathogens activates the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) that produces the second messenger, cGAMP. cGAMP triggers a signal cascade leading to type I IFN expression. Host DNA is normally restricted in the cellular compartments of the nucleus and mitochondria. Recent studies have shown that DNA virus infection triggers mitochondrial stress, leading to the release of mitochondrial DNA to the cytosol and activation of cGAS; however, the regulatory mechanism of mitochondrial DNA-mediated cGAS activation is not well elucidated. In this study, we analyzed cGAS protein interactome in mouse RAW264.7 macrophages and found that cGAS interacted with C1QBP. C1QBP predominantly localized in the mitochondria and leaked into the cytosol during DNA virus infection. The leaked C1QBP bound the NTase domain of cGAS and inhibited cGAS enzymatic activity in cells and in vitro. Overexpression of the cytosolic form of C1QBP inhibited cytosolic DNA-elicited innate immune responses and promoted HSV-1 infection. By contrast, deficiency of C1QBP led to the elevated innate immune responses and impaired HSV-1 infection. Taken together, our study suggests that C1QBP is a novel cGAS inhibitor hidden in the mitochondria.
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DNA , Nucleotidiltransferases , Animais , Citosol/metabolismo , DNA/metabolismo , Imunidade Inata , Camundongos , Mitocôndrias , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismoRESUMO
Stabilities of cellulose Pickering emulsions are of great importance to utilize them effectively, but influenced by their complex compositions, such as, colloidal particles, oil phases and water phases. In this work, solid-liquid controllable polymerization products could obtain by adjusting cellulose nanocrystals (CNCs) concentration and vinyl acetate (VAc)-water ratio. The emulsions in zone Ó (w/o) and II (o/w) of the three-phase diagram were selected for researching. The polymerization emulsions in zone II illustrated the o/w ratio played a more important role than CNCs concentration in the storage stability and practicality of the polymerized emulsion; The polymer in zone Ó showed a large number of porous structures. This is an innovative method that different forms of target products are obtained through the guidance of three-phase diagram, which not only broadens the application field, but also applies to other Pickering emulsion systems.
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Celulose/química , Nanopartículas/química , Polimerização , Compostos de Vinila/química , Emulsões/química , Água/químicaRESUMO
Retinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type I interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain to be fully elucidated. Here we show that the FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates RIG-I activation. FIP200 deficiency impaired RIG-I signaling and increased host susceptibility to RNA virus infection. In vivo studies further demonstrated FIP200 knockout mice were more susceptible to RNA virus infection due to the reduced innate immune response. Mechanistic studies revealed that FIP200 competed with the helicase domain of RIG-I for interaction with the two tandem caspase activation and recruitment domains (2CARD), thereby facilitating the release of 2CARD from the suppression status. Furthermore, FIP200 formed a dimer and facilitated 2CARD oligomerization, thereby promoting RIG-I activation. Taken together, our study defines FIP200 as an innate immune signaling molecule that positively regulates RIG-I activation.