Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification.

CRISPR base editing screens enable analysis of disease-associated variants at scale; however, variable efficiency and precision confounds the assessment of variant-induced phenotypes. Here, we provide an integrated experimental and computational pipeline that improves estimation of variant effects in base editing screens. We use a reporter construct to measure guide RNA (gRNA) editing outcomes alongside their phenotypic consequences and introduce base editor screen analysis with activity normalization (BEAN), a Bayesian network that uses per-guide editing outcomes provided by the reporter and target site chromatin accessibility to estimate variant impacts.

Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification.

CRISPR base editing screens are powerful tools for studying disease-associated variants at scale. However, the efficiency and precision of base editing perturbations vary, confounding the assessment of variant-induced phenotypic effects. Here, we provide an integrated pipeline that improves the estimation of variant impact in base editing screens.

SIMBA: single-cell embedding along with features.

Most current single-cell analysis pipelines are limited to cell embeddings and rely heavily on clustering, while lacking the ability to explicitly model interactions between different feature types. Furthermore, these methods are tailored to specific tasks, as distinct single-cell problems are formulated differently. To address these shortcomings, here we present SIMBA, a graph embedding method that jointly embeds single cells and their defining features, such as genes, chromatin-accessible regions and DNA sequences, into a common latent space.

A new class of constitutively active super-enhancers is associated with fast recovery of 3D chromatin loops.

Background: Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation during development and differentiation. In addition, the enrichment of disease-associated single nucleotide polymorphism in super-enhancers indicates their critical function in disease-specific gene regulation. However, little is known about the function of super-enhancers beyond gene regulation.

Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson's disease.

Moutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson's disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD.

Pharmacokinetics and Brain Distribution of the Active Components of DA-9805, Saikosaponin A, Paeonol, and Imperatorin in Rats.

DA-9805 is a botanical anti-Parkinson's drug candidate formulated from ethanol extracts of the root of , the root cortex of , and the root of . The pharmacokinetics (PKs) and brain distribution of active/representative ingredients of DA-9805, Saikosaponin a (SSa; 1.1⁻4.

Simultaneous determination of saikosaponin a, paeonol, and imperatorin, components of DA-9805, in rat plasma by LC-MS/MS and application to a pharmacokinetic study.

DA-9805 is a new botanical antiparkinson drug candidate formulated using an ethanolic extract of the root of Bupleurum falcatum, the root cortex of Paeonia suffruticosa, and the root of Angelica dahurica. In this study, a sensitive and rapid LC-MS/MS method was developed to simultaneously determine, saikosaponin a, paeonol, and imperatorin, three active/representative ingredients of DA-9805, in rat plasma. Plasma was extracted by mixture of ethyl acetate and methyl tertiary butyl ether.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

Introduction: DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites.

Odisolane, a Novel Oxolane Derivative, and Antiangiogenic Constituents from the Fruits of Mulberry (Morus alba L.).

Mulberry, the fruit of Morus alba L., is known as an edible fruit and commonly used in Chinese medicines as a warming agent and as a sedative, tonic, laxative, odontalgic, expectorant, anthelmintic, and emetic. Systemic investigation of the chemical constituents of M.

Ethanol production from galactose by a newly isolated Saccharomyces cerevisiae KL17.

A wild-type yeast strain with a good galactose-utilization efficiency was newly isolated from the soil, and identified and named Saccharomyces cerevisiae KL17 by 18s RNA sequencing. Its performance of producing ethanol from galactose was investigated in flask cultures with media containing various combination and concentrations of galactose and glucose. When the initial galactose concentration was 20 g/L, it showed 2.