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Traumatic brain injury (TBI) leads to disturbed brain discharge rhythm, elevated excitability, anxiety-like behaviors, and decreased learning and memory capabilities. Cognitive dysfunctions severely affect the quality of life and prognosis of TBI patients, requiring effective rehabilitation treatment. Evidence indicates that moderate exercise after brain injury decreases TBI-induced cognitive decline. However, the underlying mechanism remains unelucidated. Our results demonstrate that TBI causes cognitive impairment behavior abnormalities and overexpression of Nav1.1, Nav1.3 and Nav1.6 proteins inside the hippocampus of mice models. Three weeks of voluntary running wheel (RW) exercise treatments before or/and post-injury effectively redressed the aberrant changes caused by TBI. Additionally, a 10% exercise-conditioned medium helped recover cell viability, neuronal sodium current and expressions of Nav1.1, Nav1.3 and Nav1.6 proteins across cultured neurons after injury. Therefore, the results validate the neuroprotection induced by voluntary RW exercise treatment before or/and post-TBI. The RW exercise-induced improvement in cognitive behaviors and neuronal excitability could be associated with correcting the Nav1.1, Nav1.3, and Nav1.6 expression levels. The current study proves that voluntary exercise is an effective treatment strategy against TBI. The study also highlights novel potential targets for rehabilitating TBI, including the Navs proteins.
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Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Canales de Sodio Activados por Voltaje , Humanos , Ratones , Animales , Calidad de Vida , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/terapia , CogniciónRESUMEN
BACKGROUND: Synaptogyrin-2 (SYNGR2), as a member of synaptogyrin gene family, is overexpressed in several types of cancer. However, the role of SYNGR2 in pan-cancer is largely unexplored. METHODS: From the TCGA and GEO databases, we obtained bulk transcriptomes, and clinical information. We examined the expression patterns, prognostic values, and diagnostic value of SYNGR2 in pan-cancer, and investigated the relationship of SYNGR2 expression with tumor mutation burden (TMB), microsatellite instability (MSI), immune infiltration, and immune checkpoint (ICP) genes. The gene set enrichment analysis (GSEA) software was used to perform pathway analysis. Besides, we built a nomogram of liver hepatocellular carcinoma patients (LIHC) and validated its prediction accuracy. RESULTS: SYNGR2 was highly expressed in most cancers. The high expression of SYNGR2 significantly reduced the overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in multiple types of cancer. Also, receiver operating characteristic (ROC) curve analysis demonstrated that SYNGR2 showed high accuracy in distinguishing cancerous tissues from normal ones. Moreover, SYNGR2 expression was correlated with TMB, MSI, immune scores, and immune cell infiltrations. We also analyzed the association of SYNGR2 with immunotherapy response in LIHC. Finally, a nomogram including SYNGR2 and pathologic T, N, M stage was built and exhibited good predictive power for the OS, DSS, and PFI of LIHC patients. CONCLUSION: Overall, SYNGR2 is a critical oncogene in various tumors. SYNGR2 participates in the carcinogenic progression, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that SYNGR2 can serve as a predictor related to prognosis in pan-cancer, especially LIHC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Sinaptogirinas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Inestabilidad de Microsatélites , Oncogenes , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
The tumor immune microenvironment (TIME) of colon cancer (CC) has been associated with extensive immune cell infiltration (IMI). Increasing evidence demonstrated that plasma cells (PC) have an extremely important role in advance of antitumor immunity. Nonetheless, there is a lack of comprehensive analyses of PC infiltration in clinical prognosis and immunotherapy in CC. This study systematically addressed the gene expression model and clinical information of CC patients. Clinical samples were obtained from the TCGA (The Cancer Genome Atlas) databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), GSVA, and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were employed to research the potential mechanism and pathways. Immunophenoscore (IPS) was obtained to evaluate the immunotherapeutic significance of risk score. Half maximal inhibitory concentration (IC50) of chemotherapeutic medicine was predicted by employing the pRRophetic algorithm. A total of 513 CC samples (including 472 tumor samples and 41 normal samples) were collected from the TCGA-GDC database. Significant black modules and 313 candidate genes were considered PC-related genes by accessing WGCNA. Five pivotal genes were established through multiple analyses, which revealed excellent prognostic. The underlying correlation between risk score with tumor mutation burden (TMB) was further explored. In addition, the risk score was obviously correlated with various tumor immune microenvironment (TIME). Also, risk CC samples showed various signaling pathways activity and different pivotal sensitivities to administering chemotherapy. Finally, the biological roles of the CD177 gene were uncovered in CC.
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Neoplasias del Colon , Medicina , Humanos , Células Plasmáticas , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Inmunoterapia , Algoritmos , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
OBJECTIVE: The predictive biomarkers of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) still need to be further explored. This study aims to establish a new immune prognosis biomarker to predict the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors. METHODS: The subjects of this study were 151 HCC patients receiving ICIs at Harbin Medical University Cancer Hospital from January 2018 to December 2021. This study collected a wide range of blood parameters from patients before treatment and used Cox's regression analysis to identify independent prognostic factors in blood parameters, as well as their ß coefficient. The hepatocellular carcinoma immune prognosis score (HCIPS) was established through Lasso regression analysis and COX multivariate analysis. The cut-off value of HCIPS was calculated from the receiver operating characteristic (ROC) curve. Finally, the prognostic value of HCIPS was validated through survival analysis, stratified analyses, and nomograms. RESULTS: HCIPS was composed of albumin (ALB) and thrombin time (TT), with a cut-off value of 0.64. There were 56 patients with HCIPS < 0.64 and 95 patients with HCIPS ≥ 0.64, patients with low HCIPS were significantly related to shorter progression-free survival (PFS) (13.10 months vs. 1.63 months, P < 0.001) and overall survival (OS) (14.83 months vs. 25.43 months, P < 0.001). HCIPS has also been found to be an independent prognostic factor in this study. In addition, the stratified analysis found a significant correlation between low HCIPS and shorter OS in patients with tumor size ≥ 5 cm (P of interaction = 0.032). The C-index and 95% CI of the nomograms for PFS and OS were 0.730 (0.680-0.779) and 0.758 (0.711-0.804), respectively. CONCLUSIONS: As a new score established based on HCC patients receiving ICIs, HCIPS was significantly correlated with clinical outcomes in patients with ICIs and might serve as a new biomarker to predict HCC patients who cloud benefit from ICIs.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Pronóstico , BiomarcadoresRESUMEN
In this study, an efficient, sensitive, and convenient magnetic solid-phase extraction method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (MSPE-UHPLC-MS/MS) was developed for the simultaneous determination of 19 succinate dehydrogenase inhibitor fungicide residues in six different food matrices The synthesized tetraethylenepentamine magnetic graphene oxide nanocomposite showed the advantages of good dispersibility, large specific surface area (113.93 m2 /g) and large pore volume (0.25 cm3 /g), making it an ideal succinate dehydrogenase inhibitor pretreatment adsorbent. The MSPE-UHPLC-MS/MS method showed linearity in the range of 5.0-800.0 µg/kg, with a correlation coefficient (R2 ) > 0.99, and a limit of quantification of 5 µg/kg. The recovery of succinate dehydrogenase inhibitor fungicides was in the range of 71.2%-119.4%. The MSPE method is simple, rapid, and efficient, making it an ideal alternative to sample pretreatment in the determination of trace succinate dehydrogenase inhibitor fungicides in complex matrices.
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The passive optical network (PON) is widely used in optical fiber communication thanks to its low cost and low resource consumption. However, the passiveness brings about a critical problem that it requires manual work to identify the topology structure, which is costly and prone to bringing noise to the topology logs. In this paper, we provide a base solution firstly introducing neural networks for such problems, and based on that solution we propose a complete methodology (PT-Predictor) for predicting PON topology through representation learning on its optical power data. Specifically, we design useful model ensembles (GCE-Scorer) to extract the features of optical power with noise-tolerant training techniques integrated. We further implement a data-based aggregation algorithm (MaxMeanVoter) and a novel Transformer-based voter (TransVoter) to predict the topology. Compared with previous model-free methods, PT-Predictor is able to improve prediction accuracy by 23.1% in scenarios where data provided by telecom operators is sufficient, and by 14.8% in scenarios where data is temporarily insufficient. Besides, we identify a class of scenarios where PON topology does not follow a strict tree structure, and thus topology prediction cannot be effectively performed by relying on optical power data alone, which will be studied in our future work.
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The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3â ¡/â , Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3â ¡/â and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3â ¡/â and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.
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Aterosclerosis , Placa Aterosclerótica , Animales , Ratones , Apolipoproteínas E , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Beclina-1 , LDL-Colesterol , Molécula 1 de Adhesión Intercelular , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
Birnessite (δ-MnO2) is a layered manganese oxide widely present in the environment and actively participates in the transformation of natural organic matter (NOM) in biogeochemical processes. However, the effect of oxygen on the dynamic interface processes of NOM and δ-MnO2 remains unclear. This study systematically investigated the interactions between δ-MnO2 and fulvic acid (FA) under both aerobic and anaerobic conditions. FA was transformed by δ-MnO2 via direct electron transfer and the generated reactive oxygen species (ROS). During the 32-day reaction, 79.8% of total organic carbon (TOC) in solution was removed under anaerobic conditions, unexpectedly higher than that under aerobic conditions (69.8%), suggesting that oxygen limitation was more conducive to the oxidative transformation of FA by δ-MnO2. The oxygen vacancies (OV) on the surface of δ-MnO2 were more exposed under anaerobic conditions, thus promoting the adsorption and transformation of FA as well as regeneration of the active sites. Additionally, the reaction of FA with δ-MnO2 weakened the strongly bonded lattice oxygen (Olatt), and the released Olatt was an important source of ROS. Interestingly, a part of organic carbon (OC) was preserved by forming MnCO3, which might be a novel mechanism for carbon preservation. These findings contribute to an improved understanding of the dynamic interface processes between MnO2 and NOM and provide new insights into the effects of oxygen limitation on the cycling and preservation of OC.
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Compuestos de Manganeso , Óxidos , Carbono , Dominio Catalítico , Compuestos de Manganeso/química , Óxidos/química , Oxígeno/química , Especies Reactivas de OxígenoRESUMEN
Tracer gas experiments were conducted in a 158 m3 room with overhead supply diffusers to study dispersion of contaminants from simulated speaking in physically distanced meeting and classroom configurations. The room was contained within a 237 m3 cell with open plenum return to the HVAC system. Heated manikins at desks and a researcher operating the tracer release apparatus presented 8-9 thermal plumes. Experiments were conducted under conditions of no forced air and neutral, cooled, or heated air supplied at 980-1100 cmh, and with/out 20% outdoor air. CO2 was released at the head of one manikin in each experiment to simulate small (<5 µm diameter) respiratory aerosols. The metric of exposure relative to perfectly mixed (ERM) is introduced to quantify impacts, based on measurements at manikin heads and at three heights in the center and corners of the room. Chilled or neutral supply air provided good mixing with ERMs close to one. Thermal stratification during heating produced higher ERMs at most manikins: 25% were ≥2.5 and the highest were >5× perfectly mixed conditions. Operation of two within-zone air cleaners together moving ≥400 cmh vertically in the room provided enough mixing to mitigate elevated exposure variations.
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Contaminación del Aire Interior , Ventilación , Aire Acondicionado , Movimientos del Aire , CalefacciónRESUMEN
CD3+CD4-CD8- T cells (double-negative T cells; DNTs) have diverse functions in peripheral immune-related diseases by regulating immunological and inflammatory homeostasis. However, the functions of DNTs in the central nervous system remain unknown. Here, we found that the levels of DNTs were dramatically increased in both the brain and peripheral blood of stroke patients and in a mouse model in a time-dependent manner. The infiltrating DNTs enhanced cerebral immune and inflammatory responses and exacerbated ischemic brain injury by modulating the FasL/PTPN2/TNF-α signaling pathway. Blockade of this pathway limited DNT-mediated neuroinflammation and improved the outcomes of stroke. Our results identified a critical function of DNTs in the ischemic brain, suggesting that this unique population serves as an attractive target for the treatment of ischemic stroke.
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Isquemia Encefálica/inmunología , Complejo CD3/inmunología , Accidente Cerebrovascular/inmunología , Subgrupos de Linfocitos T/inmunología , Anciano de 80 o más Años , Animales , Encéfalo/inmunología , Antígenos CD4/inmunología , Antígenos CD8/inmunología , Modelos Animales de Enfermedad , Femenino , Humanos , Inflamación/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Voltage-gated sodium channel beta 2 (Nav2.2 or Navß2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navß2 in amyloid-ß 1-42- (Aß1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navß2 knockdown restored neuronal viability of Aß1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aß42, sAPPα, and sAPPß, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aß degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navß2 plays crucial roles in the repair of neuronal injury induced by Aß1-42 both in vivo and in vitro.
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Disfunción Cognitiva , Canales de Sodio Activados por Voltaje , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Neuronas/metabolismo , Canales de Sodio Activados por Voltaje/metabolismo , Neprilisina/genética , Neprilisina/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismoRESUMEN
This paper presents pollutant concentrations and performance data for code-required mechanical ventilation equipment in 23 low-income apartments at 4 properties constructed or renovated 2013-2017. All apartments had natural gas cooking burners. Occupants pledged to not use windows for ventilation during the study but several did. Measured airflows of range hoods and bathroom exhaust fans were lower than product specifications. Only eight apartments operationally met all ventilation code requirements. Pollutants measured over one week in each apartment included time-resolved fine particulate matter (PM2.5 ), nitrogen dioxide (NO2 ), formaldehyde and carbon dioxide (CO2 ) and time-integrated formaldehyde, NO2 and nitrogen oxides (NOX ). Compared to a recent study of California houses with code-compliant ventilation, apartments were smaller, had fewer occupants, higher densities, and higher mechanical ventilation rates. Mean PM2.5 , formaldehyde, NO2 , and CO2 were 7.7 µg/m3 , 14.1, 18.8, and 741 ppm in apartments; these are 4% lower, 25% lower, 165% higher, and 18% higher compared to houses with similar cooking frequency. Four apartments had weekly PM2.5 above the California annual outdoor standard of 12 µg/m3 and also discrete days above the World Health Organization 24-hour guideline of 25 µg/m3 . Two apartments had weekly NO2 above the California annual outdoor standard of 30 ppb.
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Contaminación del Aire Interior/estadística & datos numéricos , Gas Natural , Material Particulado , Ventilación , Contaminantes Atmosféricos , California , Culinaria , Monitoreo del Ambiente , Formaldehído , Dióxido de Nitrógeno , Pobreza , Respiración Artificial , Emisiones de VehículosRESUMEN
The synthesis of cyclic carbonates from carbon dioxide (CO2) and epoxides is a 100% atom economical reaction and an attractive pathway for CO2 utilisation. Because CO2 is a thermodynamically stable molecule, the use of catalysts is mandatory in reducing the activation energy of the CO2 conversion. Considering environmental compatibility and the high-efficiency catalytic conversion of CO2, there is the strong need to develop green catalysts. Biomass-based catalysts, a type of renewable resource, have attracted considerable attention due to their unique properties-non-toxic, low-cost, pollution-free, etc. In this review, recent advances in the development of biomass-based catalysts for the synthesis of cyclic carbonates by CO2 and epoxides coupling are summarized and discussed in detail. The effect of biomass-based catalysts, functional groups, reaction conditions, and co-catalysts on the catalytic efficiency and selectivity of synthesizing cyclic carbonates process is discussed. We intend to provide a comprehensive understanding of recent experimental and theoretical progress of CO2 and epoxides coupling reaction and pave the way for both CO2 conversion and biomass unitization.
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Dióxido de Carbono/química , Carbonatos/química , Compuestos Epoxi/química , Biomasa , Dióxido de Carbono/metabolismo , Carbonatos/síntesis química , Catálisis , Ciclización , Teoría Funcional de la Densidad , PorosidadRESUMEN
The metabolic inhibition (MI) test is a classic test for the identification of mycoplasmas, used for measuring the growth-inhibiting antibodies directed against acid-producing mycoplasmas, although their mechanism still remains obscure. To determine the major antigens involved in the immune killing of Mycoplasma bovis, we used a pulldown assay with anti-M. bovis antibodies as bait and identified nine major antigens. Among these antigens, we performed the MI test and determined that the growth of M. bovis could be inhibited effectively in the presence of complement by antibodies against specifically membrane protein P81 or UgpB in the presence of complement. Using a complement killing assay, we demonstrated that M. bovis can be killed directly by complement and that antibody-dependent complement-mediated killing is more effective than that by complement alone. Complement lysis and scanning electron microscopy results revealed M. bovis rupture in the presence of complement. Together, these results suggest that the metabolic inhibition of M. bovis is antibody-dependent complement-mediated killing. This study provides new insights into mycoplasma killing by the complement system and may guide future vaccine development studies for the treatment of mycoplasma infection. Furthermore, our findings also indicate that mycoplasmas may be an appropriate new model for studying the lytic activity of membrane attack complex (MAC).
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Anticuerpos Antibacterianos/inmunología , Proteínas del Sistema Complemento/inmunología , Proteínas de la Membrana/inmunología , Infecciones por Mycoplasma/veterinaria , Mycoplasma bovis/inmunología , Animales , Bovinos , Complejo de Ataque a Membrana del Sistema Complemento/inmunología , Microscopía Electrónica de Rastreo , Infecciones por Mycoplasma/inmunología , ConejosRESUMEN
Much of human exposure to nitrogen oxides (NOx) of ambient origin occurs indoors. Reactions with materials inside building envelopes are expected to influence the amount of ambient NOx that infiltrates indoors. However, envelope penetration factors for ambient NOx constituents have never been measured. Here, we develop and apply methods to measure the penetration factor and indoor loss rates for ambient NOx constituents using time-resolved measurements in an unoccupied apartment unit. Multiple test methods and parameter estimation approaches were tested, including natural and artificial indoor NOx elevation with and without accounting for indoor oxidation reactions. Twelve of 16 tests yielded successful estimates of penetration factors and indoor loss rates. The penetration factor for NO was confirmed to be â¼1 and the mean (±s.d.) NO2 penetration factor was 0.72 ± 0.06 with a mean relative uncertainty of â¼15%. The mean (±s.d.) indoor NO2 loss rate was 0.27 ± 0.12 h-1, ranging 0.06-0.47 h-1, with strong correlations with indoor relative and absolute humidity. Indoor NO loss rates were strongly correlated with the estimated ozone concentration in infiltrating air. Results suggest that envelope penetration factors and loss rates for NOx constituents can be reasonably estimated across a wide range of conditions using these approaches.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Ozono , Monitoreo del Ambiente , Humanos , Óxidos de NitrógenoRESUMEN
The interaction between graphene oxide (GO) and DNA is very sensitive to the environment. For example, under acidic conditions, the affinity of GO for DNA is enhanced, weakening the capability of GO to distinguish DNAs with different conformations. This effect has impeded the development of sensitive pH biosensors based on GO-DNA nanosystems. In this work, we systematically studied the affinity between GO and i-motif forming oligonucleotides (IFOs) at different pH values and developed a herring sperm DNA (HSD) treatment method. Using this method, HSD occupies the surface of GO, compromising the attractive force of GO that is significantly enhanced under acidic conditions. As a result, the ability of GO to distinguish between "open" and "closed" IFOs is successfully generalized to a wider pH range. Finally, a pH-sensitive GO-IFO nanosystem was fabricated that showed excellent sensing ability both in vitro and for intracellular pH detection. Because the interaction between GO and DNA is the basis for constructing GO-DNA biosensors, the strategy developed in this work shows great potential to be applied in a variety of other GO-DNA sensing systems.
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ADN/química , Grafito/química , Microscopía Fluorescente , Línea Celular Tumoral , Humanos , Concentración de Iones de Hidrógeno , Microscopía de Fuerza Atómica , Nanotecnología , Oligonucleótidos/químicaRESUMEN
Recently, smart DNA hydrogels, which are generally formed by the self-assembly of oligonucleotides or through the cross-linking of oligonucleotide-polymer hybrids, have attracted tremendous attention. However, the difficulties of fabricating DNA hydrogels limit their practical applications. We report herein a novel method for producing pH-responsive hydrogels by rolling circle amplification (RCA). In this method, pH-sensitive cross-linking sites were introduced into the polymeric DNA chains during DNA synthesis. As the DNA sequence can be precisely defined by its template, the properties of such hydrogels can be finely tuned in a very facile way through template design. We have investigated the process of hydrogel formation and pH-responsiveness to provide rationales for functional hydrogel design based on the RCA reaction.
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ADN/síntesis química , Hidrogeles/química , Oligonucleótidos/química , Dicroismo Circular/métodos , Electroforesis en Gel de Poliacrilamida/métodos , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo/métodos , Técnicas de Amplificación de Ácido Nucleico , Transición de Fase , Reología/métodosRESUMEN
Using cultured human mast cells (CHMC) the optimization of 2,4-diaminopyrimidine compounds leading to 22, R406 is described. Compound 22 is a potent upstream inhibitor of mast cell degranulation and its mechanism of action is via inhibition of Syk kinase. Compound 22 has significant activity in inhibiting both IgE- and IgG-mediated activation of Fc receptor (FcR) in mast cells and basophils, and in addition inhibits Syk kinase-dependent activity of FcR-mediated activation of monocytes, macrophages, neutrophils, and B cell receptor (BCR)-mediated activation of B lymphocytes. Overall, the biological activity of 22 suggests that it has potential for application as a novel therapeutic for the treatment of an array of autoimmune maladies and hematological malignancies.
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Diseño de Fármacos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Pirimidinas/farmacología , Receptores Fc/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Unsafe behavior among construction personnel poses significant risks in petroleum engineering construction projects. This study addresses this issue through the application of a multi-field coupled homogeneous analysis model. By conducting case analyses of petroleum engineering construction accidents and utilizing the WSR methodology, the influencing factors of unsafe behaviors among construction personnel are systematically categorized into organizational system factors, equipment management factors, and construction personnel factors. Subsequently, employing Risk coupling theory, the study delves into the analysis of these influencing factors, discussing their coupling mechanisms and classifications, and utilizing the N-K model to elucidate the coupling effect among them. Furthermore, a novel approach integrating coupling analysis and multi-agent modeling is employed to establish an evolutionary model of construction personnel's unsafe behavior. The findings reveal that a two-factor control method, concurrently reinforcing equipment and construction personnel management, significantly mitigates unsafe behavior. This study provides valuable insights into the evolution of unsafe behavior among construction personnel and offers a robust theoretical framework for targeted interventions. Significantly, it bears practical implications for guiding safety management practices within petroleum engineering construction enterprises. By effectively controlling unsafe behaviors and implementing targeted safety interventions, it contributes to fostering sustainable development within the petroleum engineering construction industry.
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Industria de la Construcción , Humanos , Modelos Teóricos , Petróleo , Accidentes de Trabajo/prevención & control , Administración de la SeguridadRESUMEN
Pseudorabies virus (PRV), an alphaherpesvirus, is a neglected zoonotic pathogen. Dectin-1 sensing of ß-glucan (BG) induces trained immunity, which can possibly form a new strategy for the prevention of viral infection. However, alphaherpesvirus including PRV have received little to no investigation in the context of trained immunity. Here, we found that BG pretreatment improved the survival rate, weight loss outcomes, alleviated histological injury and decreased PRV copy number of tissues in PRV-infected mice. Type I interferons (IFNs) including IFN-α/ß levels in serum were significantly increased by BG. However, these effects were abrogated in the presence of Dectin-1 antagonist. Dectin-1-mediated effect of BG was also confirmed in porcine and murine macrophages. These results suggested that BG have effects on type I IFNs with antiviral property involved in Dectin-1. In piglets, oral or injected immunization with BG and PRV vaccine could significantly elevated the level of PRV-specific IgG and type I IFNs. And it also increased the antibody levels of porcine reproductive and respiratory syndrome virus vaccine and classical swine fever vaccine that were later immunized, indicating a broad-spectrum effect on improving vaccine immunity. On the premise that the cost was greatly reducing, the immunological effect of oral was better than injection administration. Our findings highlighted that BG induced type I IFNs related antiviral effect against PRV involved in Dectin-1 and potential application value as a feed additive to help control the spread of PRV and future emerging viruses.