HPLC Fingerprint Combined with Chemometrics and Network Pharmacology for Q-Markers Prediction Analysis of Saposhnikovia divaricata

Saposhnikovia divaricata(SD)has high medicinal and edible value,but relatively little research has been done on its qual-ity markers(Q-markers).To further clarify the Q-markers of SD with their corresponding pharmacodynamic targets.In this experiment,14 batches of SD were identified and screened for Q-marker candidate components using a combination of HPLC fingerprint with similarity analysis,principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis.Then,network pharmacology was used to predict Q-markers and core targets.The results showed that 5-O-methylvisammioside,cimifugin,and prim-O-glucosylcimifugin could be used as Q-markers of SD;while,MAPK1,MAPK3,PIK3CA,JUN,and MAPK8 were the core targets of SD for drug efficacy.To further evaluate the bind-ing efficiency of Q-markers,molecular docking of the main active ingredients of SD to the core targets was performed.The results showed that the compounds bind well to their targets,and binding energies were all less than-5 kcal/mol.The Q-markers obtained from the screening were closely related to the core target genes,which could achieve therapeutic effects by modulating the relevant signaling pathways.This study offers a reference for the establishment of a set of quality control evaluation system for SD potential Q-markers prediction analysis,and lays the foundation for elucidating the mechanism of actionunderlying itspharmacodynamic substance.

An Early Cretaceous gold mineralization event in the Triassic West Qinling orogen revealed from U-Pb titanite dating of the Ma'anqiao gold deposit

The West Qinling orogen in central China,formed from continental collision between the North China and Yangtze cratons in the Late Triassic,hosts numerous gold deposits with a total Au endowment of about 2000 t.Most deposits were emplaced at ca.250-195 Ma and are genetically associated with the Triassic orogenesis.Here in situ U-Pb titanite dating with laser ablation inductively coupled plasma mass spectrometry indicates the Ma’anqiao gold deposit in the northern portion of this orogen has a distinctive age and under a contrasting tectonic regime.This structurally controlled gold deposit is hosted in Late Ordovician to Early Silurian sub-greenschist facies metasedimentary rocks.The gold mineralization is hosted in quartz-pyritepyrrhotite veins and pyrite-pyrrhotite disseminations in hydrothermally altered rocks,which are crosscut by K-feldspar-calcitechlorite±pyrite veins.Titanite,present both in the disseminated sulfide ores and later veins,was used for in situ U-Pb dating.Titanite from three disseminated sulfide ore samples with Th and U averaging 27.46 and 39.31 ppm(1 ppm=1μg g^(-1)),respectively,yielded lower-intercept ages of 121.1±3.1 to 120.7±3.5 Ma(2σ)in the Tera-Wasserburg diagram.Titanite from three later vein samples with much lower Th and U concentrations averaging 2.74 and 16.21 ppm,respectively,yielded overlapping ages of 120.8±3.2 to 120.3±5.8 Ma(2σ).These new titanite U-Pb ages tightly constrain the formation of the Ma’anqiao gold deposit at ca.121-120 Ma and,when combined with independent geological data,indicate it is not related to the Triassic Qinling orogeny.Rather,its formation is attributed to lithospheric thinning and destruction of the North China craton during the Late Jurassic to Early Cretaceous which has generated numerous gold deposits along the southern margin of this craton.This catastrophic event caused extensive magmatism in large areas of the North Qinling terrane and northern edge of the West Qinling orogen immediately to the south of the North China craton.The heat flux and elevated geothermal gradients associated with this magmatism could have induced prograde metamorphism of the Paleozoic sedimentary infrastructure in and beneath these areas with the derived fluids ascending along pre-existing crustal-scale regional structures to form the Ma’anqiao gold deposit.We suggest that areas in the North Qinling terrane that have been affected by the Late Mesozoic magmatism are potential targets for future exploration of the decratonization-related gold deposits.Additionally,this study highlights the use of titanite U-Pb dating as a robust geochronometer for metasedimentary rock-hosted gold deposits in Phanerozoic orogens,which has previously not been utilized.