Jorgensenmeier4345

As an environmental toxicant, arsenic causes damage to various organs and systems of the body and has attracted worldwide attention. It is well-known that exposure to arsenic can induce pulmonary fibrosis, but the molecular mechanisms are elusive. Glycolysis is involved in the process of various diseases, including pulmonary fibrosis. Extracellular vehicles (EVs) are mediators of cell communication through transporting miRNAs. The potential of miRNAs in EVs as liquid biopsy biomarkers for various diseases has been reported, and they have been applied in clinical diagnoses. In the present investigation, we focused on the roles and mechanisms of miR-21 in EVs on arsenic-induced glycolysis and pulmonary fibrosis through experiments with human populations, experimental animals, and cells. The results for arsenicosis populations showed that the serum levels of hydroxyproline, lactate, and EVs-miRNAs were elevated and that EVs-miR-21 levels were positively related to the levels of hydroxyproline and lactate. For mice, chronic exposure to arsenite led to high levels of miR-21, AKT activation, elevated glycolysis, and pulmonary fibrosis; however, these effects were blocked by the depletion of miR-21 in miR-21 knockout (miR-21KO) mice. After MRC-5 cells were co-cultured with arsenite-treated HBE cells, the levels of miR-21, AKT activation, glycolysis, and myofibroblast differentiation were enhanced, effects that were blocked by reducing miR-21 and by inhibiting the EVs in HBE cells. The down-regulation of PTEN in MRC-5 cells and primary lung fibroblasts (PLFs) reversed the blocking effect of inhibiting miR-21 in HBE cells. Torkinib Thus, miR-21 down-regulates PTEN and promotes glycolysis via activating AKT, which is associated with arsenite-induced myofibroblast differentiation and pulmonary fibrosis. Our results provide a new approach for the construction of clinical diagnosis technology based on analysis of the mechanism of arsenite-induced pulmonary fibrosis.Depth-related variations in the activities, abundances, and community composition of denitrification and anaerobic ammonia oxidation (anammox) bacteria in coastal sediment cores remain poorly understood. In this study, we used 15N-labelled incubation, quantitative polymerase chain reaction (qPCR), and high-throughput sequencing techniques to reveal the structure and function of denitrifiers and anammox bacteria in sediment cores (almost 100 cm depth) collected in winter and summer from four locations in Daya Bay. The results indicated that the activities and abundances of both denitrifiers and anammox bacteria were detected even in deeper sediments with low concentrations of dissolved inorganic nitrogen (DIN). The potential rates, abundances, and community compositions of denitrifiers and anammox bacteria only varied spatially. In the surface sediment (top 2 cm), denitrifiers had significantly higher activities and abundances than anammox bacteria, but the relative contribution of anammox bacteria to nitrogen loss increased to >60% in the subsurface sediments. Phylogenetic analysis revealed that nirS-type denitrifiers were affiliated to 10 different clusters and Candidatus Scalindua dominated the anammox community in the whole sediments. Furthermore, both denitrification and anammox bacterial communities in the subsurface sediments were distinct from those in the surface sediments. Coupled nitrification and denitrification or anammox may play significant roles in removing fixed N, and the availability of electronic acceptors (e.g. nitrite and nitrate) strongly influenced the N loss activities in the subsurface sediment, emphasising its role as a sink for buried N.We describe the androgen receptor (AR) agonistic/antagonistic effects of 140 veterinary drugs regulated in Republic of Korea, by setting maximum residue limits. It was conducted using two in vitro test guidelines of the Organization for Economic Cooperation and Development (OECD)-the AR-EcoScreen AR transactivation (TA) assay and the 22Rv1/MMTV_GR-KO AR TA assay. These were performed alongside the AR binding affinity assay to confirm whether their AR agonistic/antagonistic effects are based on the binding affinity to AR. Prior to conducting the AR TA assay, the proficiency test was passed the proficiency performance criterion for the AR agonist and AR antagonist assays. Among the veterinary drugs tested, four veterinary drugs (dexamethasone, trenbolone, altrenogest, and nandrolone) and six veterinary drugs (cymiazole, dexamethasone, zeranol, phenothiazine, bromopropylate, and isoeugenol) were determined as AR agonist and AR antagonist, respectively in both in vitro AR TA assays. Zeranol exhibited weak AR agonistic effects with a PC10 value only in the 22Rv1/MMTV_GR-KO AR TA assay. Regarding changing the AR agonistic/antagonistic effects through metabolism, the AR antagonistic activities of zeranol, phenothiazine, and isoeugenol decreased significantly in the presence of phase I + II enzymes. These data indicate that various veterinary drugs could have the potential to disrupt AR-mediated human endocrine system. Furthermore, this is the first report providing information on AR agonistic/antagonistic effects of veterinary drugs using in vitro OECD AR TA assays.The accuracy of the nitrogen (N) budget is of great importance for evidence-based decision-making to address both food security and environmental protection challenges. This study attempts to advance understanding of uncertainties in China's N budget using the Coupled Human And Natural Systems (CHANS) model and Monte Carlo simulation from 1980 to 2018. Results show that the spatial and temporal variations in agricultural and industrial activities and insufficient knowledge on N cycling parameterization are the two dominant causes of uncertainties in the N budget in China. Uncertainties of N inputs generally are 30% for N accumulations. Uncertainty of nitrogen oxides emission is more sensitive to energy consumption due to the large contributions from industry and transportation. While the uncertainty of ammonia emission is predominantly affected by agricultural activity. Combining surface measurements, satellite observations, and atmospheric simulation models enables cross-check of N fluxes in multiple systems and reduces uncertainties of N budget.Hydrodynamic cavitation (HC) coupled with persulfate (PS)-based that resulted in the synergistic degradation of polycyclic aromatic hydrocarbons (PAHs) in contaminated marine sediments. The effects of HC injection pressure and Σ[PAH] [PS] on the rate and extent of PAH degradation were studied in the pressure range of 0.5-2.0 bar, PS concentration rage of 2 × 10-4 to 2 × 10-2 M or Σ[PAH] [PS] of 110-1000, and reaction time of 20-60 min. A pseudo-first-order rate law fitted PAHs removal kinetics well. The degradation rate constant increased with injection pressure, reaching the maximum level at 0.5 bar, then decreased at injection pressure became greater than 0.5 bar. The results showed that PAH removal was 84% by the combined HC and PS process, whereas, HC alone only achieved a 43% removal of PAHs in marine sediments under the optimal inlet pressure of 0.5 bar at PS concentration of 2 × 10-2 M in 60 min. The HC‒PS system effectively removed PH, PY, FLU, BaA, and CH at 91, 99, 91, 84, and 90%, respectively. The maximum removal of 6-, 5-, 4-, 3-, and 2-ring PAHs was 89, 87, 84, 76, and 34%, respectively. Major reactive oxygen species (ROSs), namely, SO4-• and HO•, were responsible for PAHs degradation. Results clearly highlighted the feasibility of HC-PS system for the clean-up of PAHs-laden sediments in particular and other recalcitrant organic contaminants in general.Natural inorganic/organic nanohybrids are a fascinating model in biomaterials design due to their ultra-microstructure and extraordinary properties. Here, we report unique-structured nanohybrids through self-assembly of biomedical inorganic/organic nanounits, composed of bioactive inorganic nanoparticle core (hydroxyapatite, bioactive glass, or mesoporous silica) and chitosan shell - namely Chit@IOC. The inorganic core thin-shelled with chitosan could constitute as high as 90%, strikingly contrasted with the conventional composites. The Chit@IOC nanohybrids were highly resilient under cyclic load and resisted external stress almost an order of magnitude effectively than the conventional composites. The nanohybrids, with the nano-roughened surface topography, could accelerate the cellular responses through stimulated integrin-mediated focal adhesions. The nanohybrids were also able to load multiple therapeutic molecules in the core and shell compartment and then release sequentially, demonstrating controlled delivery systems. The nanohybrids compartmentally-loaded with therapeutic molecules (dexamethasone, fibroblast growth factor 2, and phenamil) were shown to stimulate the anti-inflammatory, pro-angiogenic and osteogenic events of relevant cells. When implanted in the in vivo calvarium defect model with 3D-printed scaffold forms, the therapeutic nanohybrids were proven to accelerate new bone formation. Overall, the nanohybrids self-assembled from Chit@IOC nanounits, with their unique properties (ultrahigh inorganic content, nano-topography, high resilience, multiple-therapeutics delivery, and cellular activation), can be considered as promising 3D tissue regenerative platforms.The next-generation closure device for interventional treatment of congenital heart disease is regarded to be biodegradable, yet the corresponding biomaterial technique is still challenging. Herein, we report the first fully biodegradable atrial septal defect (ASD) occluder finally coming into clinical use, which is made of biodegradable poly(l-lactic acid) (PLLA). We characterized the physico-chemical properties of PLLA fibers as well as the raw polymer and the operability of the as-fabricated occluders. Cell behaviors on material were observed, and in vivo fiber degradation and inflammatory responses were examined. ASD models in piglets were created, and 44 PLLA ASD occluders were implanted via catheter successfully. After 36 months, the PLLA ASD occluders almost degraded without any complications. The mechanical properties and thickness between newborn and normal atrial septum showed no significant difference. We further accomplished the first clinical implantation of the PLLA ASD occluder in a four-year boy, and the two-year follow-up up to date preliminarily indicated safety and feasibility of such new-generation fully biodegradable occluder made of synthetic polymers.Nanomedicine has made significant advances in clinical applications since the late-20th century, in part due to its distinct advantages in biocompatibility, potency, and novel therapeutic applications. Many nanoparticle (NP) therapies have been approved for clinical use, including as imaging agents or as platforms for drug delivery and gene therapy. However, there are remaining challenges that hinder translation, such as non-scalable production methods and the inefficiency of current NP formulations in delivering their cargo to their target. To address challenges with existing formulation methods that have batch-to-batch variability and produce particles with high dispersity, microfluidics-devices that manipulate fluids on a micrometer scale-have demonstrated enormous potential to generate reproducible NP formulations for therapeutic, diagnostic, and preventative applications. Microfluidic-generated NP formulations have been shown to have enhanced properties for biomedical applications by formulating NPs with more controlled physical properties than is possible with bulk techniques-such as size, size distribution, and loading efficiency.