Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is essential in lipopolysaccharide (LPS)-induced fibroblast activation and collagen secretion in vitro. However, its effects on the process of lung fibroblast activation and fibrosis initiation during LPS induced acute lung injury (ALI) remain unknown. The goal of the present study was to determine the effect of inhibiting TLR4 on LPS-induced ALI and fibrosis in vivo.</p> <p>Methods</p> <p>The ALI model was established by intraperitoneal injection of LPS in mice. TLR4-small hairpin RNA (shRNA) lentivirus was injected intravenously into the mice to inhibit TLR4 expression. mRNA and protein levels were detected by real-time PCR and Western-blot analysis, respectively. The contents of the C-terminal propeptide of type I procollagen (PICP) in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the degree of fibrosis was detected by van Gieson collagen staining, the hydroxyproline assay, and alpha smooth muscle actin (α-SMA) immunohistochemical staining.</p> <p>Results</p> <p>Overexpression of TLR4, type I procollagen, alpha-SMA, and p-AKT in murine pulmonary tissue after intraperitoneal injection of LPS at 72 hours and 28 days were detected. Moreover, the degree of fibrosis was shown to increase by ELISA analysis of PICP in BALF, van Gieson collagen staining, the hydroxyproline assay, and α-SMA immunohistochemical staining. All of these changes were alleviated by intravenous infection with TLR4-shRNA lentivirus.</p> <p>Conclusions</p> <p>Inhibiting TLR4 signaling could ameliorate fibrosis at the early stage of ALI induced by LPS.</p

A Dual-Window DC Bus Interacting Method for DC Microgrids Hierarchical Control Scheme

Hierarchical control schemes have been commonly employed in dc microgrid controls, which combine local control, dc bus voltage coordination, and communication links to guarantee smart operation of dc microgrids. Conventional dc bus voltage regulation cannot conduct signal exchange. Therefore, external communication links are usually needed for hierarchical control schemes. However, once the communication link fails, the hierarchical control system will lose its ability to coordinate the distributed power smartly. This paper proposed a dual-window dc bus interacting (DBI) method to exchange information between the distributed energy sources, for the situations where communication link fails or is not available. A small-scale dc microgrid experimental system was set up, and a simple master-slave control scheme was implemented without communication link to demonstrate the feasibility of the proposed DBI method for dc microgrid controls. The expandability and immunity of the proposed DBI method were also evaluated

Evaluation of electroacupuncture as a non-pharmacological therapy for astrocytic structural aberrations and behavioral deficits in a post-ischemic depression model in mice

BackgroundAscending clinical evidence supports that electroacupuncture (EA) is effective in treating post-ischemic depression (PID), but little is known about how it works at the cellular level. Astrocytes are exquisitely sensitive to their extracellular environment, and under stressful conditions, they may experience aberrant structural remodeling that can potentially cause neuroplastic disturbances and contribute to subsequent changes in mood or behavior.ObjectivesThis study aimed to investigate the effect of EA on behavioral deficits associated with PID in mice and verify the hypothesis that astrocytic morphology may be involved in this impact.MethodsWe established a PID animal model induced by transient bilateral common carotid artery occlusion (BCCAO, 20 min) and chronic restraint stress (CRS, 21 days). EA treatment (GV20 + ST36) was performed for 3 weeks, from Monday to Friday each week. Depressive- and anxiety-like behaviors and sociability were evaluated using SPT, FST, EPM, and SIT. Immunohistochemistry combined with Sholl and cell morphological analysis was utilized to assess the process morphology of GFAP+ astrocytes in mood-related regions. The potential relationship between morphological changes in astrocytes and behavioral output was detected by correlation analysis.ResultsBehavioral assays demonstrated that EA treatment induced an overall reduction in behavioral deficits, as measured by the behavioral Z-score. Sholl and morphological analyses revealed that EA prevented the decline in cell complexity of astrocytes in the prefrontal cortex (PFC) and the CA1 region of the hippocampus, where astrocytes displayed evident deramification and atrophy of the branches. Eventually, the correlation analysis showed there was a relationship between behavioral emotionality and morphological changes.ConclusionOur findings imply that EA prevents both behavioral deficits and structural abnormalities in astrocytes in the PID model. The strong correlation between behavioral Z-scores and the observed morphological changes confirms the notion that the weakening of astrocytic processes may play a crucial role in depressive symptoms, and astrocytes could be a potential target of EA in the treatment of PID

Physics-driven Deep Learning Inversion for Direct Current Resistivity Survey Data

The direct-current (DC) resistivity method is a commonly used geophysical technique for surveying adverse geological conditions. Inversion can reconstruct the resistivity model from data, which is an important step in the geophysical survey. However, the inverse problem is a serious ill-posed problem that makes it easy to obtain incorrect inversion results. Deep learning (DL) provides new avenues for solving inverse problems, and has been widely studied. Currently, most DL inversion methods for resistivity are purely data-driven and depend heavily on labels (real resistivity models). However, real resistivity models are difficult to obtain through field surveys. An inversion network may not be effectively trained without labels. In this study, we built an unsupervised learning resistivity inversion scheme based on the physical law of electric field propagation. First, a forward modeling process was embedded into the network training, which converted the predicted model to predicted data and formed a data misfit to the observation data. Unsupervised training independent of the real model was realized using the data misfit as a loss function. Moreover, a dynamic smoothing constraint was imposed on the loss function to alleviate the ill-posed inverse problem. Finally, a transfer learning scheme was applied to adapt the trained network with simulated data to field data. Numerical simulations and field tests showed that the proposed method can accurately locate and depict geological targets

Last Century Warming Over the Canadian Atlantic Shelves Linked to Weak Atlantic Meridional Overturning Circulation

The Atlantic meridional overturning circulation (AMOC) is a key component of the global climate system. Recent studies suggested a twentieth‐century weakening of the AMOC of unprecedented amplitude (~15%) over the last millennium. Here we present a record of δ18O in benthic foraminifera from sediment cores retrieved from the Laurentian Channel and demonstrate that the δ18O trend is linked to the strength of the AMOC. In this 100‐year record, the AMOC signal decreased steadily to reach its minimum value in the late 1970s, where the weakest AMOC signal then remains constant until 2000. We also present a longer δ18O record of 1,500 years and highlight the uniqueness of the last century δ18O trend. Moreover, the Little Ice Age period is characterized by statistically heavier δ18O, suggesting a relatively weak AMOC. Implications for understanding the mechanisms driving the intensity of AMOC under global warming and high‐latitude freshwater input are discussed.Plain Language SummaryOceanic circulation in the North Atlantic transports huge amounts of water, heat, salt, carbon, and nutrients around the globe. As such, changes in the strength of oceanic currents can yield profound changes in both North American and European climate, in addition to affecting the African and Indian summer monsoon rainfall. In this study, we used geochemical evidence to highlight a slowdown in the North Atlantic Ocean circulation over the last century. This change appears to be unique over the last 1,500 years and could be related to global warming and freshwater input from ice sheet melt. Based on our data, we also suggest that the period often called “The Little Ice Age” was characterized by a slowdown, of less amplitude than the modern weakening, in the North Atlantic Ocean circulation. Thus, our results contribute to ongoing investigations of the state of the circulation in the North Atlantic by providing a robust reconstruction of its variability over the last 1,500 years.Key PointsThe oxygen isotope in the Laurentian Channel can trace variations in the subsurface western North Atlantic circulationThe twentieth century is characterized by the weakest Atlantic meridional overturning circulation of the last 1,500 yearsThe Little Ice Age is also characterized by relatively higher oxygen isotope, which can be linked to a weaker AMOCPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146944/1/grl58240_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146944/2/grl58240.pd

The role of North Brazil Current transport in the paleoclimate of the Brazilian Nordeste margin and paleoceanography of the western tropical Atlantic during the late Quaternary

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Palaeogeography, Palaeoclimatology, Palaeoecology 415 (2014): 3-13, doi:10.1016/j.palaeo.2014.05.030.Reconstructions of surface paleoceanographic conditions of the western equatorial Atlantic and past climates of the adjacent Northeast Brazilian (the "Nordeste") continental margin were undertaken by analyzing sediments from a piston core and associated gravity and box cores recovered from 3107 meter water depth at 0° 20’ N on the equatorial Brazilian continental slope. The record is dated by radiocarbon analysis and oxygen isotopic stratigraphy of planktonic foraminifers and spans from near- modern to approximately 110 Ka. High-resolution XRF analysis provides insight into the paleoclimate history of the Nordeste during the last glacial interval. Several large-amplitude and abrupt peaks are observed in the time series of Ti/Ca and are usually accompanied by peaks of Fe/K. Together these record periods of increased precipitation and intense weathering on the adjacent continent and increased terrestrial sediment discharge from Nordeste rivers into the Atlantic. Within the limits of dating accuracy, most Ti/Ca peaks correlate with Heinrich events in the North Atlantic. This record thus corroborates, and extends back in time, the previous record of Arz et al (1998) determined on sediment cores from farther southeast along the Nordeste margin. Stable oxygen isotopic analysis and Mg/Ca paleothermometry on the near- surface-dwelling planktonic foraminiferal species Globierinoides ruber find that mean sea-surface temperature (SST) during glacial time (20 to 55 Ka, n = 97) was 23.89 ± 0.79 °C and the mean SST during the late Holocene (0 to 5 Ka, n = 14) was 26.89 ± 0.33 °C. SSTs were 0.5 to 2 °C higher and inferred sea-surface salinities were lower during most of the periods of elevated Ti/Ca, thus, as observed in previous studies, the western equatorial Atlantic was warm (at least locally) and the adjacent southern tropical continent was wet at the same time that the high-latitude North Atlantic was cold. Using the SYNTRACE-CCSM3 fully coupled climate model with transient forcing for the period 22 Ka to present, we find that decreased transport of the North Brazil Current co-occurs with reduced Atlantic meridional overturning circulation, and colder-than-normal SSTs in the North Atlantic region. These simulated conditions are invariably associated with significantly increased precipitation in the Nordeste region.Funding for the cruise and post-cruise science was provided to PAB by NSF-OCE-0823650

Investigating the Direct Meltwater Effect in Terrestrial Oxygenâ Isotope Paleoclimate Records Using an Isotopeâ Enabled Earth System Model

Variations in terrestrial oxygenâ isotope reconstructions from ice cores and speleothems have been primarily attributed to climatic changes of surface air temperature, precipitation amount, or atmospheric circulation. Here we demonstrate with the fully coupled isotopeâ enabled Community Earth System Model an additional process contributing to the oxygenâ isotope variations during glacial meltwater events. This process, termed â the direct meltwater effect,â involves propagating large amounts of isotopically depleted meltwater throughout the hydrological cycle and is independent of climatic changes. We find that the direct meltwater effect can make up 15â 35% of the δ18O signals in precipitation over Greenland and eastern Brazil for large freshwater forcings (0.25â 0.50 sverdrup (106 m3/s)). Model simulations further demonstrate that the direct meltwater effect increases with the magnitude and duration of the freshwater forcing and is sensitive to both the location and shape of the meltwater. These new modeling results have important implications for past climate interpretations of δ18O.Key PointsA portion of the δ18O signal in landâ based paleoclimate proxies can be attributed to the direct meltwater effect instead of climatic changesThe direct meltwater effect can make up 15â 35% of the δ18O signals in precipitation in Greenland and eastern Brazil for large meltwater eventsThe direct meltwater effect increases with the magnitude and duration of the freshwater forcing and is sensitive to location and shape dependentPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141374/1/grl56782_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141374/2/grl56782-sup-0001-Supporting_Information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141374/3/grl56782.pd

Secretory Defense Response in the Bird’s Gastro-Intestinal Tract and Nutritional Strategies to Modulate It

The Gastrointestinal tract (GIT) is a very complex environment which converges a lot of players including nutrients, microorganisms, pathogens, cells, and peptides which determine the type of outcome against threats affecting feed efficiency and body weight gain. Traditionally, GIT is examined as a selective barrier which permit or deny the entrance of molecules, but beyond of that, it is a crucial place to produce important proteins for the host which, at least in part, determine the outcome for a threat such as microorganisms, toxins, anti-nutritional factors, among others. During the non-antibiotic promotants time, there is a necessity to understand how this system works and how we can modulate through nutrition, in part to take advantage of this, and support a better immune response and nutrient absorption in challenged poultry environments. The goal of this chapter is to review the different mechanism of immunity in the GIT emphasizing on secretory defense response and the nutritional strategies including fiber and fatty acids to improve it