Bjerremclean4780

Local IR (20 Gy) to nude mice bearing HEp-2 tumors significantly reduced tumor burden, while fewer effects on tumor burden in mice carrying CXCL10-KO tumors were observed. We furtherly evaluated the possible roles the chemokine receptor CXCR3 plays in mediating the sensitivity of cultured HEp-2 cells to IR. Altered expression of CXCR3 in HEp-2 cells affected IR-induced killing of HEp-2 cells. Our data suggest the IFNgamma-activated CXCL10/CXCR3 axis may contribute to the effective radiation-induced killing of HEp-2 cells in vitro.Thymic stromal lymphopoietin (TSLP) is associated with fungal keratitis. This work aims to investigate whether TSLP can regulate T helper (Th) 17 and regulatory T cell (Treg) differentiation. We separated dendritic cells (DCs) from peripheral blood of healthy volunteers. DCs were treated with TSLP to activate DCs, and exosomes were obtained. CD+ T cells were incubated with exosomes from TSLP-treated DCs. We found that exosomes from TSLP-treated DCs notably promoted the proportions of Th17 cells and inhibited the proportions of Tregs in the CD4+ T cells. Moreover, exosomes from TSLP-treated DCs enhanced the expression of retinoid-related orphan receptor γt (RORγt) and interleukin 17 (IL-17), and repressed the expression of forkhead box protein P3 (Foxp3) and interleukin 10 (IL-10) in the CD4+ T cells. Furthermore, miR-21 was highly expressed in exosomes from TSLP-treated DCs. Exosomes from TSLP-treated miR-21-silenced DCs promoted Treg differentiation and suppressed Th17 differentiation. Smad7 up-regulation repressed Th17 differentiation and enhanced Treg differentiation, which was abolished by miR-21 overexpression. Smad7 overexpression rescued the effect of exosomes from TSLP-treated DCs on Th17/Treg differentiation. In conclusion, our article confirms that TSLP induces DCs to deliver miR-21 by secreting exosomes, and thus miR-21 regulates Th17/Treg differentiation by inhibiting Smad7. Thus, this work further reveals the biological role of miR-21 in fungal keratitis.Nuclear shape alteration in ocular tissues, which can be used as a metric for overall cell deformation, may also lead to changes in gene expression and protein synthesis that could affect the biomechanics of the tissue extracellular matrix. The biomechanics of iris tissue is of particular interest in the study of primary angle-closure glaucoma. As the first step towards understanding the mutual role of the biomechanics and deformation of the iris on the activity of its constituent stromal cells, we conducted an ex-vivo study in freshly excised porcine eyes. Iris deformation was achieved by activating the constituent smooth muscles of the iris. Pupillary responses were initiated by inducing miosis and mydriasis, and the irides were placed in a fixative, bisected, and sliced into thin sections in a nasal and temporal horizontal orientation. The tissue sections were stained with DAPI for nucleus, and z-stacks were acquired using confocal microscopy. Images were analyzed to determine the nuclear aspect ratio (NARo-environment during their in-vivo physiological function.The iris plays an important role in certain types of glaucoma, including primary angle-closure glaucoma and pigmentary glaucoma. Enitociclib molecular weight Iris mechanics are also important in influencing trabecular meshwork deformation in response to intraocular pressure changes in some animal species. Although mice are widely used to study ocular disease, including glaucoma, the in vivo biomechanical properties of the murine iris are unknown. Thus, the primary objective of this study was to estimate murine iris biomechanical stiffness. We used optical coherence tomography (OCT) images of the anterior segment of living mice (n = 13, age = 7.3 ± 3.2 [mean ± SD] months) at sequentially increasing IOP levels, observing IOP-dependent iris deformations. We then used an inverse finite element model to predict iris deformations under the same conditions, estimating iris stiffness by maximizing agreement between OCT data and numerical simulations. Our results show an in vivo murine iris stiffness of 96.1 ± 54.7 kPa (mean ± SD), which did not correlate with age but was dependent on gender. Our results further showed strong evidence of reverse pupillary block, with mean posterior chamber pressure remaining at approximately 12 mmHg even as anterior chamber pressure was set to much higher levels. Our approach to monitoring iris stiffness in vivo is applicable to study potential changes of iris stiffness in various pathophysiological conditions and thus has significant potential for clinical care of ocular disease involving iris biomechanics.Accumulating evidence indicates time-of-day variations in ischemic neuronal injury. Under ischemic conditions, Zn2+ is massively released from hippocampal glutamatergic neurons, and intracellular Zn2+ accumulation results in neuron death. Notably, excitatory amino acid carrier 1 (EAAC1), known as a cysteine transporter, is involved in Zn2+ homeostasis, and its expressions exhibit a diurnal fluctuation. This study aimed to investigate whether time of day of an ischemic insult affects Zn2+ accumulation and neuronal injury and determine whether altered Zn2+ accumulation is modulated by EAAC1 diurnal fluctuation in the hippocampus in a mouse model of ischemic stroke. Mice subjected to transient global ischemia for 40 min at Zeitgeber time 18 (ZT18) (2300) exhibited reduced Zn2+ accumulation and neuronal death in the hilar region of the hippocampus compared to those at ZT4 (0900). link2 The EAAC1 protein expression in the hippocampus was increased at ZT18 relative to ZT4. Intracerebroventricular injection of a non-selective excitatory amino acid transporter inhibitor, DL-threo-β-benzyloxyaspartate, or a selective EAAC1 inhibitor, L-aspartic acid β-hydroxamate, increased ischemia-induced Zn2+ accumulation and neuronal death in the hilus at ZT18. These findings suggest that ischemia-induced Zn2+ accumulation displays circadian fluctuations through diurnal variations in EAAC1 expressions and affects susceptibility to ischemic neuronal injury in the hippocampal hilar region.Nitrous acid (HONO) is of considerable interest because it is an important precursor of hydroxyl radicals (OH), a key species in atmospheric chemistry. HONO sources are still not well understood, and air quality models fail to predict OH as well as HONO mixing ratios. As there is little knowledge about the potential contribution of plant surfaces to HONO emission, this laboratory work investigated HONO formation by heterogeneous reaction of NO2 on Zea mays. Experiments were carried out in a flow tube reactor; HONO, NO2 and NO were measured online with a Long Path Absorption Photometer (LOPAP) and a NOx analyzer. Tests were performed on leaves under different conditions of relative humidity (5-58%), NO2 mixing ratio representing suburban to urban areas (10-80 ppbv), spectral irradiance (0-20 W m-2) and temperature (288-313 K). Additional tests on plant wax extracts from Zea mays leaves showed that this component can contribute to the observed HONO formation. Temperature and NO2 mixing ratios were the two environmental parameters that showed substantially increased HONO emissions from Zea mays leaves. The highest HONO emission rates on Zea mays leaves were observed at 313 K for 40 ppbv of NO2 and 40% RH and reached values of (5.6 ± 0.8) × 109 molecules cm-2 s-1. Assuming a mixing layer of 300 m, the HONO flux from Zea mays leaves was estimated to be 171 ± 23 pptv h-1 during summertime, which is comparable to what has been reported for soil surfaces.Methanogenic sludge digestion plays a pivotal role in attenuating and hygienizing the massively-produced waste activated sludge (WAS), which is predominantly composed of microbial cells and extracellular polymeric substances (EPS). The efficient sludge digestion requires a variety of functionally active microorganisms working together closely to convert sludge organic matter into biogas. Nonetheless, the digestion efficiency (or digestibility quantified as carbon removal efficiency) of major sludge constituents (i.e., microbial cells and EPS) and associated functionally active microorganisms in sludge digesters remain elusive. In this study, we identified the digestibility of sludge microbial cells and the associated functionally active microorganisms by using Escherichia coli (E. coli)-fed digestion and microbial source tracking. The average carbon removals in four digesters fed with fresh WAS (WAS-AD), thermal pretreated WAS (Thermal-WAS-AD), E. coli cells (E.coli-AD) and thermal pretreated E. coli cells (TAS-AD, respectively. By contrast, feeding WAS-derived microorganisms accounted for 23.2 ± 4.4% and 2.3 ± 1.2% of total microbial communities in the WAS-AD and Thermal-WAS-AD, respectively.The neighborhood effect averaging problem (NEAP) is a major methodological problem that might affect the accuracy of assessments of individual exposure to mobility-dependent environmental factors (e.g., air/noise pollution, green/blue spaces, or healthy food environments). Focusing on outdoor ground-level ozone as a major air pollutant, this paper examines the NEAP in the evaluation of sociodemographic disparities in people's air pollution exposures in Los Angeles using one-day activity-travel diary data of 3790 individuals. link3 It addresses two questions (1) How does the NEAP affect the evaluation of sociodemographic disparities in people's air pollution exposures? (2) Which social groups with high residence-based exposures do not experience neighborhood effect averaging? The results of our spatial regression models indicate that assessments of sociodemographic disparities in people's outdoor ground-level ozone exposures might be erroneous when people's daily mobility is ignored because of the different manifestations of neighborhood effect averaging for different social/racial groups. The results of our spatial autologistic regression model reveal that non-workers (e.g., the unemployed, homemakers, the retired, and students) do not experience downward averaging they have significantly lower odds of experiencing downward averaging that could have attenuated their high exposures experienced in their residential neighborhoods while traveling to other neighborhoods (thus, being doubly disadvantaged). Therefore, to avoid erroneous conclusions in environmental inequality research and ineffective public policies, it would be critical to take the NEAP into account in future studies of sociodemographic disparities related to mobility-dependent environmental factors.The continuous degradation of plastic waste in the environment leads to the generation of micro- and nanoplastic fragments and particles. Due to the ubiquitous presence of plastic particles in natural habitats as well as in food, beverages and tap water, oral exposure of the human population with plastic particles occurs worldwide. We investigated acute toxicological effects of polystyrene (PS) and polyvinyl chloride (PVC) micro- and nanoparticles in an advanced in vitro triple culture model (Caco-2/HT29-MTX-E12/THP-1) mimicking the healthy and inflamed human intestine to study the effect of inflammatory processes on plastic particle toxicity. We monitored barrier integrity, cytotoxicity, cell layer integrity, DNA damage, the release of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and mucus distribution after 24 h of particle exposure. In addition, we investigated cytotoxicity, DNA damage and IL-1β release in monocultures of the three cell lines. Amine-modified polystyrene nanoparticles (PS-NH2) served as a positive control for particle-induced toxicity.