Although the deep galleries of natural underground cavities are difficult to access and are sometimes dangerous, they have the potential to preserve trace fossils. Here, we report on the first ...occurrence of sauropod dinosaur tracks inside a karstic cave. Three trackways are preserved on the roof of the Castelbouc cave 500 m under the surface of the Causse Méjean plateau, southern France. The tracks are Bathonian in age (ca. 168–166 Ma), a crucial but still poorly known time interval in sauropod evolution. The three trackways yield sauropod tracks that are up to 1.25 m long and are therefore amongst the largest known dinosaur footprints worldwide. The trackmakers are hypothesized to be titanosauriforms. Some of the tracks are extremely well preserved and show impressions of digits, digital pads, and claws. We erect the new ichnogenus and ichnospecies Occitanopodus gandi, igen. et isp. nov. In order to characterize depositional environments, we conducted sedimentological, petrographic, and mineralogical analyses. The tracks from Castelbouc attest the presence of sauropods in proximal littoral environments during the Middle Jurassic. This discovery demonstrates the great potential of prospecting in deep karst caves that can occasionally offer larger and better-preserved surfaces than outdoor outcrops.
Gandi capsule (GDC) has been used clinically for years for treatment of vascular lesions caused by diabetes. However, its comprehensive ingredients, especially those that can be absorbed, remain ...unclear. In this study, we developed a simple and fast ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOFMS) method to identify the ingredients of GDC extract, as well as those that can permeate the Caco-2 monolayer cell model. Firstly, 52 components were rapidly identified in GDC extract. Then, a total of 17 components were able to pass across Caco-2 cells from the apical side to the basolateral side with the apparent permeability coefficients (
P
app
) > 1.0 × 10
−5
cm/s, which indicate good intestinal permeability and bioavailability. Furthermore, 14 of the 17 penetrative components were definitely detected and identified in rat plasma. These results confirmed that the combination of Caco-2 monolayer cell absorption model and UHPLC–Q-TOFMS is suitable for fast screening of the ingredients entering the blood circulation. Our results will serve as a foundation for further evaluation of the pharmacological efficacy of GDC in the clinical treatment of diabetic vascular disease.
Graphical abstract
Background Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with ...routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. Methods To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. Results Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. Conclusion Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1. Graphical abstract Keywords: Gandi capsule, Network pharmacology; active component UHPLC-QQQ-MS/MS, Surface plasmon resonance, Molecular mechanism; action target
Recent archaeological investigations of the Gomal plain in northwestern Pakistan have revealed important new evidence for the types of regional socio-economic transformations that were taking place ...in the lead up to the development of urban centres on the Indus plain in the third millennium BC. It is now clear that there were several early phases of cultural development in the region, and excavations at the site of Gandi Umar Khan have revealed evidence for a previously unknown transition, between the 'Tochi-Gomal' and 'Kot Diji' phases. This article will present the evidence for this transition and investigate its broader cultural context.
Türk devriminin I. Dünya Savaşı ertesinde anti-emperyalist bir karakterde gerçekleştirilmiş olması,
devrimin ve devrim sonrasında gerçekleştirilen inkılâpların evrensel manada emsal teşkil etmesini
...de beraberinde getirmiştir. Hint ve İran devrimleri, Türk devrimiyle çağdaş olmamalarına rağmen, Türk devriminin sömürgeci güçlere karşı verdiği mücadeleden ve bu mücadeleler sonrası gerçekleştirilen inkılâplardan etkilenmişlerdir. Ancak her iki devrimin de Türk devrimi ile birebir örtüştüğünü söylemek güçtür. Nitekim her bir devrim, içinden çıktığı toplumunun sosyo-ekonomik ve siyasal yapısına uygun olarak, kendine özgü nitelikler taşımaktadır. Bu makalenin amacı da Türk devriminin Hint ve İran devrimleri üzerindeki etkisini bu devrimlerin kendine özgü niteliklerini de hesaba katarak analiz etmektir.
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