Characterization of leachates from drainage asphalt pavement under multi-factor environmental treatments.

Pavement leachates could cause considerable environmental contamination. However, the influence of multiple environmental factors on the compositions of pavement leachates is still ill-understood. Therefore, it is necessary to analyse the variation of bitumen leachates with environmental factors and accordingly clarify the leaching mechanism. For this reason, a multi-environment device was invented to perform single-factor, two-factor and full-climate environmental treatments on open-graded friction courses (OGFC) asphalt mixtures. Subsequently, the acidity and alkalinity (pH) value, metal element composition and conductivity of the bitumen leachates with varying environmental treatments were characterized and analysed. Based on this, the leaching mechanism of bitumen leachates dissolved in water was proposed. The results indicated that the bitumen compositions were influenced by different environmental treatments, inducing the variation of pavement leachates. The primary substances of pavements leachates were composed of the organic acid substances and minor metal element ions. Accordingly, the experiment results demonstrated the increase of conductivity, and partial metal element concentration with the extension of treatment time. In terms of the pH value, an initial increase followed by a progressive decrease was observed.

Serine metabolism orchestrates macrophage polarization by regulating the IGF1-p38 axis.

Serine metabolism is reportedly involved in immune cell functions, but whether and how serine metabolism regulates macrophage polarization remain largely unknown. Here, we show that suppressing serine metabolism, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase in the serine biosynthesis pathway or by exogenous serine and glycine restriction, robustly enhances the polarization of interferon-γ-activated macrophages (M(IFN-γ)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo. Mechanistically, serine metabolism deficiency increases the expression of IGF1 by reducing the promoter abundance of S-adenosyl methionine-dependent histone H3 lysine 27 trimethylation. IGF1 then activates the p38-dependent JAK-STAT1 axis to promote M(IFN-γ) polarization and suppress STAT6-mediated M(IL-4) activation. This study reveals a new mechanism by which serine metabolism orchestrates macrophage polarization and suggests the manipulation of serine metabolism as a therapeutic strategy for macrophage-mediated immune diseases.

A Temperature-Independent Methodology for Polymer Bitumen Modification Evaluation Based on DSR Measurement.

Owing to the continuous increase of traffic loads, bitumen modification has been manifested as an efficient methodology to enhance asphaltic pavement performance. Currently, the modification index, defined as the ratio of mechanical properties (e.g., complex modulus) before and after bitumen modification, is extensively adopted to evaluate the modification degree. However, bituminous materials behave as temperature-dependent, which indicates that the mechanical property varies with measured temperatures. As a result, the calculated modification index also shows temperature-dependent property, which inhibits the use of modification index. For this reason, this study introduced a method to eliminate the temperature-dependency of the modification index. In specific, a mathematical model considering the properties of modifiers was firstly established to predict the modification index-temperature curve (MI-T curve). In what follows, the temperature-dependency of modification index was analyzed to verify the proposed model on three types of modifiers, which were graphene, Styrene-Butadiene-Styrene (SBS), and Ethyl-Vinyl-Acetate (EVA), respectively. The results indicated that the developed model could efficiently predict the MI-T curves. Besides, the effective modification area (EMA) and optimal modification index (OMI) were two reasonable indicators that evaluate the bitumen modification without considering the temperature-dependency.

Proceedings of the 2019 National Toxicology Program Satellite Symposium.

The 2019 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Raleigh, North Carolina, at the Society of Toxicologic Pathology's 38th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included aging mouse lesions from various strains, as well as the following lesions from various rat strains: rete testis sperm granuloma/fibrosis, ovarian cystadenocarcinoma, retro-orbital schwannoma, periductal cholangiofibrosis of the liver and pancreas, pars distalis hypertrophy, chronic progressive nephropathy, and renal tubule regeneration. Other cases included polyovular follicles in young beagle dogs and a fungal blood smear contaminant. One series of cases challenged the audience to consider how immunohistochemistry may improve the diagnosis of some tumors. Interesting retinal lesions from a rhesus macaque emphasized the difficulty in determining the etiology of any particular retinal lesion due to the retina's similar response to vascular injury. Finally, a series of lesions from the International Harmonization of Nomenclature and Diagnostic Criteria Non-Rodent Fish Working Group were presented.

Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Trapping and Impairs Brown Adipose Tissue Thermogenesis.

Growth hormone (GH) binds to its receptor (growth hormone receptor [GHR]) to exert its pleiotropic effects on growth and metabolism. Disrupted GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific Ghr deficiency and clinical observations. Here we constructed an adipose-specific Ghr knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose Ghr accelerated dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing brown adipose tissue burning and white adipose tissue browning induced by cold were slowed in the absence of adipose Ghr but were recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signaling emulates a healthy obesity situation which has metabolic advantages against HFD.

The catalytic role of the M2 metal ion in PP2Cα.

PP2C family phosphatases (the type 2C family of protein phosphatases; or metal-dependent phosphatase, PPM) constitute an important class of signaling enzymes that regulate many fundamental life activities. All PP2C family members have a conserved binuclear metal ion active center that is essential for their catalysis. However, the catalytic role of each metal ion during catalysis remains elusive. In this study, we discovered that mutations in the structurally buried D38 residue of PP2Cα (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding. Using the D38A and D38K mutations of PP2Cα as specific tools in combination with enzymology analysis, our results demonstrated that the M2 metal ion determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding and stabilizes the leaving group after P-O bond cleavage. The newly characterized catalytic role of the M2 metal ion in this family not only provides insight into how the binuclear metal centers of the PP2C phosphatases are organized for efficient catalysis but also helps increase our understanding of the function and substrate specificity of PP2C family members.