Rapid and Efficient Extraction and HPLC Analysis of Sesquiterpene Lactones from Aucklandia lappa Root.

The root of Aucklandia lappa Decne, family Asteraceae, is widely used in Asian traditional medicine due to its sesquiterpene lactones. The aim of this study was the development and optimization of the extraction and analysis of these sesquiterpene lactones. The current Chinese Pharmacopoeia reports a monograph for "Aucklandiae Radix", but the extraction method is very long and tedious including maceration overnight and ultrasonication. Different extraction protocols were evaluated with the aim of optimizing the maceration period, solvent, and shaking and sonication times. The optimized method consists of only one hour of shaking plus 30 minutes of sonication using 100% MeOH as solvent. 1H NMR spectroscopy was used as a complementary analytical tool to monitor the residual presence of sesquitepene lactones in the herbal material. A suitable LC-DAD method was set up to quantify the sesquiterpene lactones. Recovery was ca. 97%, but a very high instability of constituents was found after powdering the herbal drug. A loss of about 20% of total sesquiterpenes was found after 15–20 days; as a consequence, it is strongly endorsed to use fresh powdered herbal material to avoid errors in the quantification

Echoes of the past: niche evolution, range dynamics, and their coupling shape the distribution of species in the Chrysanthemum zawadskii species complex

The distribution of species changes over time, and the current distribution of different species could result from distinct eco-evolutionary processes. Thus, investigating the spatiotemporal changes in the niche and geographic range of species is fundamental to understanding those processes and mechanisms shaping the current distributions of species. However, many studies only compared the current distribution and niche of the target species, ignoring the fact that the range shift of species is a dynamic process. Here, we reconstructed niche evolution and range dynamics of species to provide more information on related eco-evolutionary processes. We focused on a monophyletic species complex, Chrysanthemum zawadskii species complex, in which species occupy diverse habitats and exhibit different distribution patterns. Specifically, we investigated the niche breadth and overlap between lineages or species of the complex in geographic and environmental spaces. We then tested the phylogenetic signals for different climatic variables and estimated the niche of ancestral nodes on a time-calibrated phylogeny. Next, we used phyloclimatic modeling to reconstruct the dynamics of range shift for this complex. Our results show that this complex contains both specialist and generalist species, and niche diverges greatly among different species and intraspecific lineages of the complex. The moisture gradient may be the primary driver of the niche divergence of species in the complex. The reconstruction of ancestral distribution shows that this complex originated in the Qinling mountains and surrounding areas during the early Pliocene, and then diverged with the range expansion and niche evolution. Species of the complex have different range dynamics. Based on our findings, we propose that niche evolution, range dynamics, and their coupling shape the distribution of species, which provides insight into the eco-evolutionary processes that formed the current distribution of species in the C. zawadskii complex

Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells

BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, is recommended as the first-line anti-malarial drug with low toxicity. DHA has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways, although the molecular mechanisms are not well understood. METHODS: In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. Collapse of mitochondrial transmembrane potential (ΔΨ(m)) was measured by dynamic detection under a laser scanning confocal microscope and flow cytometry analysis using Rhodamine123. Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. RESULTS: Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨ(m )and the activation of caspase-3. CONCLUSION: These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. Our work may provide evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of lung adenocarcinoma

Ultrahigh Thermoelectric Performance by Electron and Phonon Critical Scattering in Cu 2 Se 1‐x I x

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102251/1/adma201302660.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102251/2/adma201302660-sup-0001-S1.pd

Development and validation of a risk score model for predicting autism based on pre- and perinatal factors

BackgroundThe use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism.MethodsA stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort.ResultsFive factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism.ConclusionThis risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application

Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation

Aim To study the dominant role of parasympathetic inputs at cellular level of baroreflex afferent pathway and underlying mechanism in neurocontrol of blood pressure regulation. Methods Whole‐cell patch‐clamp and animal study were conducted. Results For the first time, we demonstrated the spontaneous activities from resting membrane potential in myelinated A‐ and Ah‐type baroreceptor neurons (BRNs, the 1st‐order), but not in unmyelinated C‐types, using vagus‐nodose slice of adult female rats. These data were further supported by the notion that the spontaneous synaptic currents could only be seen in the pharmacologically and electrophysiologically defined myelinated A‐ and Ah‐type baroreceptive neurons (the 2nd‐order) of NTS using brainstem slice of adult female rats. The greater frequency and the larger amplitude of the spontaneous excitatory postsynaptic currents (EPSCs) compared with the inhibitory postsynaptic currents (IPSCs) were only observed in Ah‐types. The ratio of EPSCs:IPSCs was estimated at 3:1 and higher. These results confirmed that the afferent‐specific spontaneous activities were generated from baroreflex afferent pathway in female‐specific subpopulation of myelinated Ah‐type BRNs in nodose and baroreceptive neurons in NTS, which provided a novel insight into the dominant role of sex‐specific baroreflex‐evoked parasympathetic drives in retaining a stable and lower blood pressure status in healthy subjects, particularly in females. Conclusion The data from current investigations establish a new concept for the role of Ah‐type baroreceptor/baroreceptive neurons in controlling blood pressure stability and provide a new pathway for pharmacological intervention for hypertension and cardiovascular diseases

Structural mechanism for bacterial oxidation of oceanic trimethylamine into trimethylamine N -oxide

Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm (RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm. The catalytic process of Tmm consists of a reductive half-reaction and an oxidative half-reaction. In the reductive half-reaction, FAD is reduced and a C4a-hydroperoxyflavin intermediate forms. In the oxidative half-reaction, this intermediate attracts TMA through electronic interactions. After TMA binding, NADP+ bends and interacts with D317, shutting off the entrance to create a protected micro-environment for catalysis and exposing C4a-hydroperoxyflavin to TMA for oxidation. Sequence analysis suggests that the proposed catalytic mechanism is common for bacterial Tmms. These findings reveal the catalytic process of TMA oxidation by marine bacterial Tmm and first show that NADP+ undergoes a conformational change in the oxidative half-reaction of FMOs