Four New Furostanol Saponins from the Rhizomes and Roots of Smilax scobinicaulis and Their Cytotoxicity

Four new furostanol saponins 1–4, along with two known furostanol saponins 5 and 6 and one known spirostanol saponin 7 were isolated from the rhizomes and roots of Smilax scobinicaulis. The structures of the new saponins were elucidated as 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one-3-O-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside (1), 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one (2), 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-20(22)-en-6-one (3), 26-O-β-D-glucopyranoside-3β,23,26-trihydroxy-(23R, 25R)-5α-furostan-20(22)-en-6-one (4) on the basis of spectroscopic analysis. The isolated saponins were evaluated for cytotoxic activity against two human cancer cell lines including Hela (cervical carcinoma) and SMMC-7221 (hepatocellular carcinoma). Compounds 1 and 7 demonstrated cytotoxicity against the tested cell lines

A new flavonoid glycoside from the rhizomes and roots of <i>Smilax scobinicaulis</i>

<div><p>A new flavonoid glycoside, hesperetin-7-<i>O</i>-[β-d-glucopyranosyl-(1 → 3)]-β-d-glucopyranosyl (<b>1</b>), was isolated from the <i>n</i>-BuOH extract of <i>Smilax scobinicaulis</i>, together with four known flavonoid glycosides, clematine (<b>2</b>), ononin (<b>3</b>), daidzin (<b>4</b>) and puerarin (<b>5</b>). All of the five compounds were reported from this material for the first time. Their structures were determined on the basis of spectroscopic and spectrometric methods.</p></div

A new bixanthone derivative from the bark of <i>Garcinia oblongifolia</i>

<div><p>A new bixanthone derivative, garciobioxanthone (<b>1</b>), was isolated from the EtOH extract of the bark of <i>Garcinia oblongifolia</i>, together with 11 known compounds. The structure of <b>1</b> was elucidated on the basis of 1D NMR, 2D NMR and other spectroscopic analysis. The structures of the known compounds were identified by comparison of their spectroscopic data with those reported in the references.</p></div

A dominant variant in the PDE1C gene is associated with nonsyndromic hearing loss

Identification of genes with variants causing non-syndromic hearing loss (NSHL) is challenging due to genetic heterogeneity. The difficulty is compounded by technical limitations that in the past prevented comprehensive gene identification. Recent advances in technology, using targeted capture and next-generation sequencing (NGS), is changing the face of gene identification and making it possible to rapidly and cost-effectively sequence the whole human exome. Here, we characterize a five-generation Chinese family with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining population-specific mutation arrays, targeted deafness genes panel, whole exome sequencing (WES), we identified PDE1C (Phosphodiesterase 1C) c.958G>T (p.A320S) as the disease-associated variant. Structural modeling insights into p.A320S strongly suggest that the sequence alteration will likely affect the substrate-binding pocket of PDE1C. By whole-mount immunofluorescence on postnatal day 3 mouse cochlea, we show its expression in outer (OHC) and inner (IHC) hair cells cytosol co-localizing with Lamp-1 in lysosomes. Furthermore, we provide evidence that the variant alters the PDE1C hydrolytic activity for both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Collectively, our findings indicate that the c.958G>T variant in PDE1C may disrupt the cross talk between cGMP-signaling and cAMP pathways in Ca homeostasis

Association between Serum Vitamin A, Blood Lipid Level and Dyslipidemia among Chinese Children and Adolescents

Background: To study the relationship between serum vitamin A (VA) level and blood lipid profiles in children and adolescents aged 6–18 years, as well as the effect of VA on dyslipidemia. Methods: The project adopted a multistage stratified cluster sampling method. The Food Frequency Questionnaire (FFQ) was used to obtain dietary factors data. Blood samples of subjects were taken via venipuncture. Generalized linear models were used to explore the correlation be-tween VA and biochemical indicators, as well as stratified and inter-actions analysis to explore the influence of confounders on these relationships. Generalized linear models were constructed to explore the association between VA and blood lipids. Restricted cubic splines were used to characterize dose–response associations between serum VA and dyslipidemia based on logistic regression. Results: Serum VA was positively correlated with TC, TG and HDL-C (p p p p < 0.01). Conclusion: Serum VA was positively correlated with blood lipids, but these associations were influenced by age. VA was a risk factor for dyslipidemias, such as hypercholesterolemia, hypertriglyceridemia and mixed hyperlipidemia, but was a protective factor for low high-density lipoprotein cholesterolemia

Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers

CD4+ and CD8+ double-positive (DP) thymocytes play a crucial role in T cell development in the thymus. DP cells rearrange the T cell receptor gene Tcra to generate T cell receptors with TCRβ. DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, regulatory T cells, or invariant nature kill T cells (iNKT) in response to TCR signaling. Chromatin organizer SATB1 is highly expressed in DP cells and is essential in regulating Tcra rearrangement and differentiation of DP cells. Here we explored the mechanism of SATB1 orchestrating gene expression in DP cells. Single-cell RNA sequencing shows that Satb1 deletion changes the cell identity of DP thymocytes and down-regulates genes specifically and highly expressed in DP cells. Super-enhancers regulate the expressions of DP-specific genes, and our Hi-C data show that SATB1 deficiency in thymocytes reduces super-enhancer activity by specifically decreasing interactions among super-enhancers and between super-enhancers and promoters. Our results reveal that SATB1 plays a critical role in thymocyte development to promote the establishment of DP cell identity by globally regulating super-enhancers of DP cells at the chromatin architectural level