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Sarcandra glabra | Molecular networks | Natural products | Structural elucidation | Peroxides Sarcaglarols AD (1-4), two pairs of lindenane−monoterpene heterodimers fused by a 1,2-dioxane moiety, were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy. Their planar structures, absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS, NMR spectroscopic data, ECD spectrum, and the X-ray diffraction study of isopropylidene derivatives. An intermolecular [2+2+2] cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane−monoterpene heterodimer skeleton, which can be recognized as the biogenetic precursors of our previous reported lindenane−normonoterpene conjugates. In addition, compounds 1, 3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.

Glycogen synthase kinase-3 (GSK-3) dysregulation has been implicated in nigral dopaminergic neurodegeneration, one of the main pathological features of Parkinson's disease (PD). The two isoforms, GSK-3α and GSK-3β, have both been suggested to play a detrimental role in neuronal death. To date, several studies have focused on the role of GSK-3β on PD pathogenesis, while the role of GSK-3α has been largely overlooked. Here, we report in situ observations that both GSK-3α and GSK-3β are dephosphorylated at a negatively acting regulatory serine, indicating kinase activation, selectively in nigral dopaminergic neurons following exposure of mice to 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP). To identify whether GSK-3α and GSK-3β display functional redundancy in regulating parkinsonian dopaminergic cell death, we analysed dopaminergic neuron-specific Gsk3a null (Gsk3a Dat ) and Gsk3b null (Gsk3b Dat ) mice, respectively. We found that Gsk3b Dat , but not Gsk3a Dat , showed significant resistance to MPTP insult, revealing non-redundancy of GSK-3α and GSK-3β in PD pathogenesis. In addition, we tested the neuroprotective effect of tideglusib, the most clinically advanced inhibitor of GSK-3, in the MPTP model of PD. Administration of higher doses (200 mg/kg and 500 mg/kg) of tideglusib exhibited significant neuroprotection, whereas 50 mg/kg tideglusib failed to prevent dopaminergic neurodegeneration from MPTP toxicity. Administration of 200 mg/kg tideglusib improved motor symptoms of MPTP-treated mice. Together, these data demonstrate GSK-3β and not GSK-3α is critical for parkinsonian neurodegeneration. Our data support the view that GSK-3β acts as a potential therapeutic target in PD and tideglusib would be a candidate drug for PD neuroprotective therapy.

Clastic sediments, particularly shale, exhibit transverse isotropic properties with the symmetric axis perpendicular to bedding (VTI). These anisotropic rock properties are important in seismic imaging, prestack seismic analysis, and reservoir characterization. Laboratory tests are the main techniques used in measuring rock anisotropic properties. Vertical seismic profiling (VSP) and seismic refraction are the in-situ techniques used to determine anisotropic parameters. All of these methods provide significant insight to the anisotropic properties of the subsurface. However, limitations exist in the applications of these methods because of cost issues and restrictions on the number of measurements that can be conducted. Therefore, new techniques that are cost effective, easy to use, and able to measure continuous anisotropic profiles are desirable. This paper describes a methodology which involves the use of conventional rock properties to derive anisotropic rock properties.The commonly accepted cause of anisotropy in clastic rocks is the alignment of minerals. Hornby et al. (1994) confirmed this theory with evidence of the alignment of platy clay minerals using the SEM (scanning electron microscope) image technique. Johnston and Christensen (1995) performed a quantitative investigation of the alignment of clay minerals using the orientation index determined by X-ray diffraction patterns. They found a linear relationship between the orientation index (a measure of the degree of alignment of platy clay minerals in a given direction) and clay content. They also found that variation in seismic velocity due to anisotropy is proportional to the orientation index or clay content. These observations and findings provide the motivation to explore the physical linkage and quantitative relationship between conventional and anisotropic rock properties (Li, 2002). Because conventional rock properties are determined directly or indirectly from well logging, lab measurements, and insitu seismic measurements, anisotropic rock properties can be estimated after a quantitative relationship between conventional and anisotropic rock properties has been established. In this paper an empirical method is devised to establish this relationship and thus estimate anisotropy. The method is validated by comparing the estimated anisotropy values with those derived from VSP and seismic refraction data. In addition, anisotropy values inverted from prestack depth migration (PSDM) are compared. The potential for application of this method to anisotropic synthetic seismograms, and anisotropic parameter inversion from prestack seismic data is also explored.Physical background. Clay and quartz are two principal mineral constituents of clastic rocks. In general, two basic factors-the volume fraction of clay and the degree of compaction-determine the anisotropic properties of rocks. The first factor constitutes the physical basis for anisotropy, i.e., the platy clay minerals. The second factor forces clay minerals to align in a preferred direction wh...

The relationship between the shapes of drilling-induced core fractures and the in situ state of stress is developed. The stress concentrations at the well bore bottom are first determined using a complete three-dimensional finite element analysis. Existing in situ compressional stresses generate large tensions in the immediate vicinity of the bottom hole which are sufficient to rupture the rock. Tensile fracture trajectories within these concentrated stress fields are predicted using a simple model of fracture propagation. These modeled fracture trajectories resemble well the observed shapes of drilling-induced core disking, petal, and petal-centerline fractures. Further, this agreement suggests that both the shape of the drilling-induced fracture and the location at which it initiates depends on the in situ stress state existing in the rock mass prior to drilling; the core fractures contain substantial information on in situ stress conditions. In all faulting regimes the coring-induced fractures initiate near the bit cut except for most cases under thrust faulting regime where the fracture initiates on the well bore axis. Further, under thrust faulting conditions only disk fractures appear possible. Both petal and disking fractures can be produced in strike-slip and' normal faulting regimes depending upon the relative magnitudes between the least compressive horizontal principal stress and the vertical overburden stress. The predicted fracture shapes are in good qualitative agreement with observations of drilling-induced fractures described in the literature from laboratory experiments and field programs in which in situ stresses are measured by other means. The relationship of the morphology of coring induced fractures and in situ stresses suggests that the fractures can be used as independent complementary indicators in identifying stress regimes.

Hydraulic overpressure can induce fractures and increase permeability in a range of geological settings, including volcanological, glacial and petroleum reservoirs. Here we consider an example of induced hydraulic fracture stimulation in a tight-gas sandstone. Successful exploitation of tight-gas reservoirs requires fracture networks, either naturally occurring, or generated through hydraulic stimulation. The study of seismic anisotropy provides a means to infer properties of fracture networks, such as the dominant orientation of fracture sets and fracture compliances. Shear wave splitting from microseismic data acquired during hydraulic fracture stimulation allows us to not only estimate anisotropy and fracture properties, but also to monitor their evolution through time. Here, we analyse shear wave splitting using microseismic events recorded during a multistage hydraulic fracture stimulation in a tight-gas sandstone reservoir. A substantial rotation in the dominant fast polarization direction (ψ) is observed between the events of stage 1 and those from later stages. Although large changes in ψ have often been linked to stress-induced changes in crack orientation, here we argue that it can better be explained by a smaller fracture rotation coupled with an increase in the ratio of normal to tangential compliance (Z N /Z T) from 0.3 to 0.6. Z N /Z T is sensitive to elements of the internal architecture of the fracture, as well as fracture connectivity and permeability. Thus, monitoring Z N /Z T with shear wave splitting can potentially allow us to remotely detect changes in permeability caused by hydraulic stimulation in a range of geological settings.

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