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Potassic alteration is a common feature in hydrothermal ore systems, and both its occurrence and degree can be important features applicable to ore deposit exploration. Here we report results from optical cathodoluminescence (CL) and chemical composition investigations on K-feldspar of different origins in and around the Early Cretaceous lode gold deposits in the Xiaoqinling area, located along the southern margin of the North China Craton. We focus on K-feldspars from an Early Cretaceous biotite monzogranite (G-Kfs), a Paleoproterozoic migmatite (M-Kfs), and a hydrothermal alteration zone of Early Cretaceous gold deposits (H-Kfs). The grain size of G-Kfs ranges from 1 to 4 mm, usually exhibits tartan twinning, and occasionally shows evidence of exsolution. Part of the M-Kfs exhibits tartan twinning, and the grain size shows wide variation (from tens of microns to several centimeters), while the H-Kfs shows no twinning, and the grain size is generally less than 0.5 mm. Optical CL analyses show that the G-Kfs exhibits two emission bands at around 466–472 and 708–713 nm which occur in multiple, alternating dark red and blue zones. The M-Kfs exhibits blue, red, and/or violet-red luminescence resulting from two emission bands at 446–465 and 694–701 nm. The H-Kfs displays a distinct greenish-yellow luminescence resulting from an emission band at 545–550 nm. Electron probe microanalyses show that among the three K-feldspar types, the G-Kfs contains higher Na2O (average: 0.71 wt.%) and Al2O3 (average: 18.79 wt.%) and lower K2O (average: 15.62 wt.%), whereas the H-Kfs shows higher K2O (average: 16.31 wt.%) and lower Na2O (average: 0.45 wt.%) and Al2O3 (average: 18.61 wt.%). The K2O, Na2O, and Al2O3 contents of the M-Kfs are intermediate between those of the G-Kfs and H-Kfs. In transitioning from the G-Kfs, M-Kfs, to H-Kfs, it is noted that the concentrations of Sr, Ba, and Pb decrease progressively, whereas W, V, Zn, Mn, Sc, Ge, and Ga gradually increase. Concentrations of La, Ce, and Eu in the H-Kfs are lower than in the G-Kfs and M-Kfs, and the Cr and Cu concentrations in the G-Kfs are the lowest. Scatter diagrams constructed with Sr, Ba, Pb, and Rb concentrations show that the three types of K-feldspars fall into different fields. These, as well as the CL and spectral properties of K-feldspar, can clearly distinguish the K-feldspars of magmatic, metamorphic, and hydrothermal origin in the study area.

Cyperi rhizoma (CR) is widely used in gynecology and is a general medicine for treating women's diseases in China. Since the analgesic effect of CR is enhanced after processing with vinegar, CR processed with vinegar (CRV) is generally used clinically. However, the mechanism by which the analgesic effect is enhanced by vinegar processing is unclear. In this study, the ultra-high pressure liquid chromatographytandem mass spectrometry (UPLC-MS/MS) technique was used to examine changes in the blood levels of the exogenous constituents and metabolites between CR-treated and CRV-treated rats with dysmenorrhea. The results revealed differing levels of 15 constituents and two metabolites in the blood of these rats. Among them, the levels of (-)-myrtenol and [(1R,2S,3R,4R)-3-hydroxy-1,4,7,7-tetramethylbicyclo[2.2.1]hept-2-yl]acetic acid in the CRV group were considerably higher than in the CR group. CRV reduced the level of 2-series prostanoids and 4-series leukotrienes with proinflammatory, platelet aggregation, and vasoconstriction activities and provided analgesic effects by modulating arachidonic acid and linoleic acid metabolism and the biosynthesis of unsaturated fatty acids. This study revealed that vinegar processing enhances the analgesic effect of CR and contributes to our understanding of the mechanism of action of CRV.

Signal transducer and activator of transcription 3 (STAT3) is known to be activated in numerous cancer types, including more than 40% of breast cancers. STAT3 ’s downstream gene cMyc serves as an important target in cancer treatment. However, the clinical availability of small-molecule inhibitors that can target cMyc are lacking.Cinnamic aldehyde (CA) has been reported to inhibit the proliferation of a variety of cancer cells, including those in breast cancer; however, its molecular mechanism remains unclear. This study examined CA induction of apoptosis in breast cancer cells via STAT3/cMyc pathway. The corresponding findings demonstrated that CA significantly inhibited the proliferation and migration of MDA-MB-231 cells, MCF-7 cells, and 4T1 cells in both a time and concentration-dependent manner. CA was also shown to enhance the effect of cMyc inhibitor 10074-G5 and was observed to be better than 10074-G5 in the same concentration. CA also inhibited the proliferation and migration of breast cancer cells, which may be related to the induction of breast cancer cells’ mitochondral apoptosis through the down-regulation of apoptosis-related proteins via STAT3/cMyc pathway. Accordingly, this study suggests that CA may serve as a novel cMyc inhibitor in breast cancer cells and should be further studied.

Covalent inhibitors with an electrophilic warhead have received considerable attention due to their remarkable pharmacological properties. However, the electrophilic warhead in covalent drugs is often an α, β-unsaturated amide, and the targets are mainly cysteine or lysine residues. Thus, the development of novel electrophiles that can target other amino acids is highly desirable. Ynamide, a useful and versatile building block, is commonly employed in the construction of various compounds in organic synthesis. The performance of this functional group in a proteome-wide environment has been studied here for the first time, and it has been shown that it can efficiently modify carboxyl residues in situ and in vitro. Upon incorporation of this ynamide warhead into the pharmacophores of kinase inhibitors, the resulting compound showed moderate inhibition against the EGFR L858R mutant but not against EGFR WT. This novel electrophilic group can be used in the development of new types of covalent inhibitors.

Toxin EsaD secreted by some S. aureus strains through the type VII secretion system (T7SS) specifically kills those strains lacking the antitoxin EsaG. Here we report the structures of EsaG, the nuclease domain of EsaD and their complex, which together reveal an inhibition mechanism that relies on significant conformational change of the toxin. To inhibit EsaD, EsaG breaks the nuclease domain of EsaD protein into two independent fragments that, in turn, sandwich EsaG. The originally well-folded ββα-metal finger connecting the two fragments is stretched to become a disordered loop, leading to disruption of the catalytic site of EsaD and loss of nuclease activity. This mechanism is distinct from that of the other Type II toxin-antitoxin systems, which utilize an intrinsically disordered region on the antitoxins to cover the active site of the toxins. This study paves the way for developing therapeutic approaches targeting this antagonism.

Altered expression of Urea Cycle (UC) enzymes occurs in many tumors, resulting a metabolic hallmark termed as UC dysregulation. Polyamines are synthesized from ornithine, and polyamine synthetic genes are elevated in various tumors. However, the underlying deregulations of UC/ polyamine synthesis in cancer remain elusive. Here, we characterized a hypoxia-induced lncRNA LVBU (lncRNA regulation via BCL6/urea cycle) that is highly expressed in colorectal cancer (CRC) and correlates with poor cancer prognosis. Increased LVBU expression promoted CRC cells proliferation, foci formation and tumorigenesis. Further, LVBU regulates urea cycle and polyamine synthesis through BCL6, a negative regulator of p53. Mechanistically, overexpression of LVBU competitively bound miR-10a/miR-34c to protect BCL6 from miR-10a/34c-mediated degradation, which in turn allows BCL6 to block p53-mediated suppression of genes (arginase1 ARG1, ornithine transcarbamylase OTC, ornithine decarboxylase 1 ODC1) involved in UC/polyamine synthesis. Significantly, ODC1 inhibitor attenuated the growth of patient derived xenografts (PDX) that sustain high LVBU levels. Taken together, elevated LVBU can regulate BCL6-p53 signaling axis for systemic UC/polyamine synthesis reprogramming and confers a predilection toward CRC development. Our data demonstrates that further drug development and clinical evaluation of inhibiting UC/polyamine synthesis are warranted for CRC patients with high expression of LVBU.

Lipid bilayers of different phospholipid compositions have been prepared, in the form of vesicles, or of supported lipid bilayers, and doped with Aurora™ at 0.1 mol%. Aurora™ consists of an Au55 gold nanoparticle (about 1.4 nm in diameter) capped with triphenylphosphine ligands and a single diglyceride (distearoyl glycerol) ligand. Gold nanoparticles have been incorporated in the past inside liposomes, or grafted onto their surfaces, with diagnostic or therapeutic aims. Including the gold nanoparticles in a stable form within the lipid bilayers has serious technical difficulties. We have tested the hypothesis that, because of the diglyceride ligand, Aurora™ would allow the easy incorporation of gold nanoclusters into cell membranes or lipid bilayers. Our results show that Aurora™ readily incorporates into lipid bilayers, particularly when they are in the fluid phase, i.e. the state in which cell membranes exist. Calorimetric, fluorescence polarization or fluorescence confocal microscopy concur in showing that bilayer-embedded Aurora™hardly changes the physical properties of the bilayers, nor does it perturb the phase equilibrium in lipid mixtures giving rise to lateral phase separation in the plane of the membrane. Atomic force microscopy shows, in fluid bilayers, well-resolved particles, 1.2–2.9 nm in height, that are interpreted as single Aurora™conjugates. Cryo-transmission electron microscopy allows the clear observation of lipid bilayers with an enhanced contrast due to the Aurora™ gold nanoparticles; the single particles can be resolved at high magnification. Our studies support the applicability of Aurora™ as a membrane-friendly form of nano-gold particles for biological research or clinical applications.

After over 20 years of development in Daqingzijiang Oilfield, isolated sand bodies under the delta front and pro-delta in the Qingshankou Formation(qn)have become important oil and gas reservoir bodies. However, the cause for large amounts of isolated bar sand bodies in the lake-basin delta sediment system has not been reported in China. This article, through core observation, reveals plenty of evidence that there storm waves once existed. Combined with paleogeography and hydrodynamic force analysis, it describes the transformation effect of waves on delta sand bodies and on the formation mechanism of bar sand bodies. Based on a study on paleogeomorphology and the statistics of sand body distribution, we consider &lsquo, Storm waves conveying sand&rsquo, and &lsquo, landform controlling sand&rsquo, as the cause and distribution model of the delta&rsquo, s isolated bar sand body formation. We also think that the superposition of multiple bar sand bodies is the direct cause of the strong anisotropy in reservoirs and the complex relationship between oil and water in reservoirs. Most of these sand bodies have formed into lenticular lithologic hydrocarbon accumulations. On the basis of this integrated study on hydrocarbon accumulation, we set up an accumulation model of lenticular hydrocarbon accumulation involving the variables &lsquo, Surrounded by source rocks to generate hydrocarbon&rsquo, &lsquo, Driven by pressure difference&rsquo, Migration through multi pathways&rsquo, Accumulation by filtering water&rsquo

Rhombohedron-like and fusiform calcium carbonate nanoparticles were fabricated using a new method. Their geometry was controlled by varying the mixing speed and ratio of ethanol versus water in reaction system. The calcium carbonate nanoparticles (CCNPs) have slight effect on viability of human bone-marrow mesenchymal stem cells (hBMSCs) with dose-dependent and shape-dependent, but they can significantly promote osteogenic differentiation of hBMSCs in vitro by 10–37% increase of alkaline phosphatase (ALP) activity, 9–36% growth of collagen secretion and 1.13–1.83 folds upregulation of osteogenesis-related genes, even at lower dose ranges (5–20 μg/ml). The efficacity of promoting osteogenesis depends on the shape and dose of CCNPs. Furthermore, adipogenesis was inhibited by less accumulation of lipid droplets, lower triglyceride (TG) secretion and downregulation of adipogenesis-related genes. These findings improve the understanding of effects CCNPs on hBMSCs fate towards osteoblasts or adipocytes and have meaningful impact for combining use of CCNPs and hBMSCs in tissue engineering and regenerative medicine fields. Keywords: Human bone-marrow mesenchymal stem cells, Calcium carbonate nanoparticles, Osteogenesis, Adipogenesis

Lipid bilayers of different phospholipid compositions have been prepared, in the form of vesicles, or of supported lipid bilayers, and doped with Aurora

The zebrafish larva is a powerful tool for the study of dietary triglyceride (TG) digestion and how fatty acids (FA) derived from dietary lipids are absorbed, metabolized and distributed to the body. While fluorescent FA analogues have enabled visualization of FA metabolism, methods for specifically assaying TG digestion are badly needed. Here we present a novel High Performance Liquid Chromatography (HPLC) method that quantitatively differentiates TG and phospholipid (PL) molecules with one or two fluorescent FA analogues. We show how this tool may be used to discriminate between undigested and digested TG or phosphatidylcholine (PC), and also the products of TG or PC that have been digested, absorbed and re-synthesized into new lipid molecules. Using this approach, we explored the dietary requirement of zebrafish larvae for phospholipids. Here we demonstrate that dietary TG is digested and absorbed in the intestinal epithelium, but without dietary PC, TG accumulates and is not transported out of the enterocytes. Consequently, intestinal ER stress increases and the ingested lipid is not available support the energy and metabolic needs of other tissues. In TG diets with PC, TG is readily transported from the intestine and subsequently metabolized.

The North China craton (NCC) hosts numerous gold deposits and is known as the most gold-productive region of China. The gold deposits were mostly formed within a few million years in the Early Cretaceous (130-120 Ma), coeval with widespread occurrences of bimodal magmatism, rift basins and metamorphic core complexes that marked the peak of lithospheric thinning and destruction of the NCC. Stable isotope data and geological evidence indicate that ore-forming fluids and other components were largely exsolved from cooling magma and/or derived from mantle degassing during the period of lithospheric extension. Gold mineralization in the NCC contrasts strikingly with that of other cratons where gold ore-forming fluids were sourced mostly from metamorphic devolatization in compressional or transpressional regimes. In this paper, we present a summary and discussion on time-space distribution and ore genesis of gold deposits in the NCC in the context of the timing, spatial variation, and decratonic processes. Compared with orogenic gold deposits in other cratonic blocks, the Early Cretaceous gold deposits in the NCC are quite distinct in that they were deposited from magma-derived fluids under extensional settings and associated closely with destruction of cratonic lithosphere. We argue that Early Cretaceous gold deposits in the NCC cannot be classified as orogenic gold deposits as previously suggested, rather, they are a new type of gold deposits, termed as “decratonic gold deposits” in this study. The westward subduction of the paleo-West Pacific plate (the Izanagi plate) beneath the eastern China continent gave rise to an optimal tectonic setting for large-scale gold mineralization in the Early Cretaceous. Dehydration of the subducted and stagnant slab in the mantle transition zone led to continuous hydration and considerable metasomatism of the mantle wedge beneath the NCC. As a consequence, the refractory mantle became oxidized and highly enriched in large ion lithophile elements and chalcophile elements (e.g., Cu, Au, Ag and Te). Partial melting of such a mantle would have produced voluminous hydrous, Au- and S-bearing basaltic magma, which, together with crust-derived melts induced by underplating of basaltic magma, served as an important source for ore-forming fluids. It is suggested that the Eocene Carlin-type gold deposits in Nevada, occurring geologically in the deformed western margin of the North America craton, are comparable with the Early Cretaceous gold deposits of the NCC because they share similar tectonic settings and auriferous fluids. The NCC gold deposits are characterized by gold-bearing quartz veins in the Archean amphibolite facies rocks, whereas the Nevada gold deposits are featured by fine-grained sulfide dissemination in Paleozoic marine sedimentary rocks. Their main differences in gold mineralization are the different host rocks, ore-controlling structures, and ore-forming depth. The similar tectonic setting and ore-forming fluid source, however, indicate that the Carlin-type gold deposits in Nevada are actually analogous to decratonic gold deposits in the NCC. Gold deposits in both the NCC and Nevada were formed in a relatively short time interval (

Liver fatty-acid-binding protein (FABP1, L-FABP) is the major cytosolic binding/chaperone protein for both precursor arachidonic acid (ARA) and the endocannabinoid (EC) products N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). Although FABP1 regulates hepatic uptake and metabolism of ARA, almost nothing is known regarding FABP1's impact on AEA and 2-AG uptake, intracellular distribution, and targeting of AEA and 2-AG to degradative hepatic enzymes. In vitro assays revealed that FABP1 considerably enhanced monoacylglycerol lipase hydrolysis of 2-AG but only modestly enhanced AEA hydrolysis by fatty-acid amide hydrolase. Conversely, liquid chromatography-mass spectrometry of lipids from Fabp1 gene-ablated (LKO) hepatocytes confirmed that loss of FABP1 markedly diminished hydrolysis of 2-AG. Furthermore, the real-time imaging of novel fluorescent NBD-labeled probes (NBD-AEA, NBD-2-AG, and NBD-ARA) resolved FABP1's impact on uptake vs intracellular targeting/hydrolysis. FABP1 bound NBD-ARA with 2:1 stoichiometry analogous to ARA, but bound NBD-2-AG and NBD-AEA with 1:1 stoichiometry-apparently at different sites in FABP1's binding cavity. All three probes were taken up, but NBD-2-AG and NBD-AEA were targeted to lipid droplets. LKO reduced the uptake of NBD-ARA as expected, significantly enhanced that of NBD-AEA, but had little effect on NBD-2-AG. These data indicated that FABP1 impacts hepatocyte EC levels by binding EC and differentially impacts their intracellular hydrolysis (2-AG) and uptake (AEA).

The development and utilization of outstanding germplasm in breeding programs can expedite breeding process. The high yielding variety Mianmai 37, grown widely in southwestern China, has been used widely in breeding programs. Comparisons between Mianmai 37 and its derivatives for yield and yield components were conducted. Simple sequence repeat (SSR) markers were used to test the frequency of specific alleles transferred from Mianmai 37 to its derivative culti-var Mianmai 367. The results indicated that the yield of the derivative cultivars was significantly higher than Mianmai 37, due to an increased grain number per spike. Favorable traits from Mianmai 37 such as resistance to stripe rust, were trans-ferred to its derivatives. At molecular level, 78.9% loci in Mianmai 367 were derived from Mianmai 37 with 75.0, 83.6 and 74.2% from A, B and D genomes, respectively. Mianmai 367 shared common loci with its parent Mianmai 37, such as re-gions Xgwm374-Xbarc167-Xbarc128-Xgwm129-Xgwm388-Xbarc101 on chromosome 2B and Xwmc446-Xwmc366- Xwmc533-Xbarc164-Xwmc418 on chromosome 3B, these regions were associated with grain number, 1000-kernel weight and resistance. The preferred transmission of alleles from Mianmai 37 to its derivatives probably can be explained by the strong selection pressures because of its favorable agronomic traits and the disease resistance.

This paper reports the variation rules for the typomorphic parameters of the pyrite and the gold enrichment rules of the Denggezhuang quartz vein gold deposit at a large-depth scale, providing the mineral signs for deep prospecting prediction through detailed study of the characteristics of crystal’ habits, chemical composition, the thermoelectricity of pyrites, and mineralogical mapping. This paper primarily discusses the correlation between the mineralization intensity and the space-time evolution of the mineralogical parameters, clarifies the physicochemical conditions during gold mineralization, and provides information useful for deep mineralization prediction. We demonstrate that the crystal habits of the pyrites are very complex, primarily occurring as {100}, {210}, and their combinate form. {210} and {100}+{210} have positive correlations with gold mineralization, and {100}+{210} therefore can be useful for locating rich ore segments. The composition of pyrites is characteristically poor in S and rich in As. Their typical trace elements are composed of Mo, As, Pb, Cu, Bi, Zn, Au, Co, Se, Sb, Ag, Ni, Cr, and Te. The average contents of trace elements in pyrites from various stages show that the crystallizing temperature gradually decreased from an early stage to the metallogenic episodes. The precipitation and accumulation of Au and Ag occur primarily in the quartz-pyrite stage (III) and the polymetal minerals stage (IV). The occurrence rate of P-type pyrites (P(%)) is 83.52%. There is a larger dispersion of the thermoelectrical coefficient of pyrite (α) in the Denggezhuang gold deposit than in other deposits in the Jiaodong Peninsula. The electrical conductivity assemblage of pyrites from I to V is characterized by P⩾N→P>N→P≫N→P≫N→P⩾N, which is usually considered beneficial for mineralization. The relative contents of As+Sb+Se+Te and Co+Ni are closely correlated to P-type and N-type average values and their occurrence rates. According to the crystallizing temperature of pyrite, the mineralization intensity, and the denudation degree, the mineralization temperature of the Denggezhuang gold deposit is in the range of 150–322°C and is of a medium-low temperature. The orebody has already become denuded to the top-middle of the orebody, and the size of the orebody is larger than 900 m. Based on the vertical zoning of the thermoelectrical coefficients of pyrites and P-type pyrite mapping, it is suggested that the segment between −425 and −800 m may have exploration potential to the northeast of line 94 of the No. I2-2 orebody.

The climate of the South China Sea is dominated by the East Asian monsoon (EAM) system. Existing paleoclimate reconstructions offered an excellent insight into longer-term EAM variations. However, due to a lack of appropriate high-resolution paleoclimate data, relatively little is known about the frequency and strength of EAM extremes during the Holocene. To evaluate and establish a potential proxy archive for past variations of the EAM on shorter time-scales, we have carried out a calibration study on shells of the bivalve mollusk, Paphia undulata (Born 1778) from Daya Bay, China. This species has a short lifespan (3 years). Shells grow uninterruptedly between February/March and mid-November and are formed near oxygen isotopic (delta O-18) equilibrium with the ambient environment. Shell growth patterns, delta O-18(shell) and delta C-13(shell) values, can be used to estimate the relative amount of precipitation and terrestrial runoff. Therefore, shells of this species can provide reliable, sub-seasonally resolved data on past East Asian summer monsoon strengths. The feasibility of this method has been tested with two Holocene shells from sediment cores taken from the nearby Beibu Gulf. A rather peculiar finding is that shell growth of P. undulata seems to be largely uncoupled to measured local environmental variables. Growth rates are negatively correlated to seawater temperature and chlorophyll a levels and positively to salinity. It is hypothesized here that extraordinary fast shell growth in early spring (February/March; low temperature and primary productivity) are facilitated by preserved energy resources, ensuring that the bivalve quickly reaches the predation window and the required size for reproduction.

Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone.

Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, -5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG). Indeed, FABP1 bound ECs with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA-containing ECs, FABP1 inhibitors, EC uptake/hydrolysis inhibitors, and phytocannabinoids and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists. The physiological impact was examined with liver from wild-type (WT) versus FABP1 gene-ablated (LKO) male mice. As shown by liquid chromatography and mass spectrometry, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD and DAGL) or a decreased level of EC degradative enzyme (FAAH) but correlated with complete loss of FABP1, a decreased level of SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and a decreased level of degradative enzymes (NAAA and MAGL). These data indicated that FABP1 not only is the most prominent endocannabinoid and cannabinoid binding protein but also impacts hepatic endocannabinoid levels.

The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine, and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear—especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human single nucleotide polymorphism (SNP) (26–38 % minor allele frequency and 8.3 ± 1.9 % homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant’s impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system in hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.

Land disposal of fly ash (FA) and sewage sludge (SS) is a major problem due largely to their potentially harmful constituents. In this paper, a potting experiment was performed to evaluate the effects on the plant growth and to discuss in particular the potential hazard to soils and plants according to the characteristics of heavy metal accumulation and migration when FA and SS are used as the amendments of calcific soil in a limestone mining area. The results showed that the application of FA-SS mixture is capable of accelerating the growth of plants and improving the biomass production at either 1:1 or 1:2 FA-SS mixture: soil (w/w). The highest yields were obtained at 1:1 (w/w) mixing ratio. When compared with the Element Background Values of Soils in China, the analysis on heavy metals indicated that the contents of Pb, Cr, Hg, Cd, As, Ni, Cu and Zn in the amended soils came up to the second-class environmental quality standards, only Hg and Cd showed significant accumulation. At the same time, though the metal concentrations in roots were higher than those for the control, the concentrations except Cu, Zn in shoots were lower. And all the heavy metal contents in the plants were substantially lower than the toxicity limits. The results indicated that the combined use of FA and SS at a rational rate of application should pose no danger to both soil and food chain based on the characteristics of the FS and SS, heavy metals and calcific soil.