DataSheet1_Detection of copy number variations based on a local distance using next-generation sequencing data.docx

As one of the main types of structural variation in the human genome, copy number variation (CNV) plays an important role in the occurrence and development of human cancers. Next-generation sequencing (NGS) technology can provide base-level resolution, which provides favorable conditions for the accurate detection of CNVs. However, it is still a very challenging task to accurately detect CNVs from cancer samples with different purity and low sequencing coverage. Local distance-based CNV detection (LDCNV), an innovative computational approach to predict CNVs using NGS data, is proposed in this work. LDCNV calculates the average distance between each read depth (RD) and its k nearest neighbors (KNNs) to define the distance of KNNs of each RD, and the average distance between the KNNs for each RD to define their internal distance. Based on the above definitions, a local distance score is constructed using the ratio between the distance of KNNs and the internal distance of KNNs for each RD. The local distance scores are used to fit a normal distribution to evaluate the significance level of each RDS, and then use the hypothesis test method to predict the CNVs. The performance of the proposed method is verified with simulated and real data and compared with several popular methods. The experimental results show that the proposed method is superior to various other techniques. Therefore, the proposed method can be helpful for cancer diagnosis and targeted drug development.</p

Biomimetic Syntheses of Rubialatins A, B and Related Congeners

The first total syntheses of rubialatins A and B, two newly discovered naphtho­hydro­quinone dimers, were achieved with high efficiency and elegancy through rationally designed biomimetic approaches. The tandem ring contraction/Michael addition/aldol reaction followed by oxidation enabled the rapid access of prerubialatin from readily available precursors, which then diverted into rubialatins A and B via epoxidation and photoinduced skeletal rearrangement, respectively. Moreover, several new rubialatin congeners were also obtained along the synthetic tour, some of which were proved to be authentic natural products

MOESM1 of Metabolic regulations of a decoction of Hedyotis diffusa in acute liver injury of mouse models

Additional file 1. The minimum standards checklist

MOESM2 of Metabolic regulations of a decoction of Hedyotis diffusa in acute liver injury of mouse models

Additional file 2. The up-regulated and down-regulated metabolites in different categories among control, LPS/GALN group and LPS/GALN + HD group

Chiral Bisphosphine-Catalyzed Asymmetric Staudinger/aza-Wittig Reaction: An Enantioselective Desymmetrizing Approach to Crinine-Type <i>Amaryllidaceae</i> Alkaloids

An unprecedented chiral bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction of 2,2-disubstituted cyclohexane-1,3-diones is reported, enabling the facile access of a broad range of cis-3a-arylhydroindoles in high yields with excellent enantioselectivities. The key to the success of this work relies on the first application of chiral bisphosphine DuanPhos to the asymmetric Staudinger/aza-Wittig reaction. An effective reductive system has been established to address the challenging PVO/PIII redox cycle associated with the chiral bisphosphine catalyst. In addition, comprehensive experimental and computational investigations were carried out to elucidate the mechanism of the asymmetric reaction. Leveraging the newly developed chemistry, the enantioselective total syntheses of several crinine-type Amaryllidaceae alkaloids, including (+)-powelline, (+)-buphanamine, (+)-vittatine, and (+)-crinane, have been accomplished with remarkable conciseness and efficiency

Zebrafish on a Chip: A Novel Platform for Real-Time Monitoring of Drug-Induced Developmental Toxicity

<div><p>Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (<i>Danio rerio</i>) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.</p></div

Apl induced abnormal morphology, developmental retardation, and mortality of zebrafish embryos.

<p>(A) Hatched rate and (B) mortality of zebrafish embryos exposed to gradient Apl every 12 hpf in the microfluidic chip for 96 h. (C) Typical morphological abnormalities of embryos exposed to Apl. Red arrows indicate tail malformation, delayed yolk absorption, pericardial edema, and bent trunk, respectively (from upper left-right to bottom left-right). (D) Mean body length of hatched embryos treated with Apl in the chip compared with the controls (C1) at 72 hpf (n = 6), there are no date at C6 and C7 for the fish are not hatched. The asterisks indicate significant differences from control group (chamber 1) * at <i>p</i><0.05.</p

Apl induced convulsion and mortality of larvae zebrafish aged 72 hpf.

<p>The convulsion rate (A) and mortality (B) of larvae fish after treatment by gradient Apl. The asterisks indicate significant differences from control group (chamber 1) * at <i>p</i><0.05.</p

The heart rates of treated embryos from 48 to 84 hpf by measuring every 12 hpf, the heart rate of the embryos in chamber 7 is zero at 84 hpf.

<p>The asterisks indicate significant differences from control group (chamber 1) * at <i>p</i><0.05.</p

Total Synthesis of Incarvilleatone and Incarviditone: Insight into Their Biosynthetic Pathways and Structure Determination

A concise biomimetic total synthesis of incarvilleatone and incarviditone is achieved in one pot via the highly stereoselective hetero- and homodimerization of (±)-rengyolone, respectively. The structure of incarviditone is revised on the basis of spectroscopic and computational evidence