A deep learning-based method for predicting the frequency classes of drug side effects based on multi-source similarity fusion.

Motivation: Drug side effects refer to harmful or adverse reactions that occur during drug use, unrelated to the therapeutic purpose. A core issue in drug side effect prediction is determining the frequency of these drug side effects in the population, which can guide patient medication use and drug development. Many computational methods have been developed to predict the frequency of drug side effects as an alternative to clinical trials.

Regulation of PEST-containing nuclear proteins in cancer cells: implications for cancer biology and therapy.

The PEST-containing nuclear protein (PCNP) is a nuclear protein involved in the regulation of cell cycle progression, protein degradation, and tumorigenesis. PCNP contains a PEST sequence, a polypeptide structural motif rich in proline (P), glutamic acid (E), serine (S), and threonine (T), which serves as a proteolytic recognition signal. The degradation of specific proteins via the PEST sequence plays a crucial role in modulating signaling pathways that control cell growth, differentiation, apoptosis, and stress responses.

RIPK1 in necroptosis and recent progress in related pharmaceutics.

Necroptosis is a programmed form of cell death. Receptor-interacting serine/threonine protein kinase l (RIPK1) is a crucial protein kinase that regulates the necroptosis pathway. Increased expression of death receptor family ligands such as tumor necrosis factor (TNF) increases the susceptibility of cells to apoptosis and necroptosis.

Catalytic Regio- and Enantioselective Boracarboxylation of Arylalkenes with CO and Diboron.

Catalytic asymmetric carboxylation of readily available alkenes with CO, an abundant and sustainable one-carbon building block, that gives access to value-added α-stereogenic carboxylic acids in an atom- and step-economic manner is highly attractive. However, it has remained a formidable challenge for the synthetic community. Here, the first example of Cu-catalyzed highly regio- and enantioselective boracarboxylation reaction on various arylalkenes with diboron under an atmospheric pressure of CO is described, which afforded a variety of chiral β-boron-functionalized α-aryl carboxylic acids with up to 87% yield and 97% ee under mild conditions.

TRIM37 promotes the aggressiveness of ovarian cancer cells and increases c-Myc expression by binding to HUWE1.

Tripartite motif containing 37 (TRIM37) was reported to function as a tumor promoter in the development of various cancers. However, the biological role of TRIM37 in ovarian cancer (OC) was still unclear. Expressions of TRIM37 and HUWE1 were detected by qRT-PCR and western blotting in OC cells.

Significance of glutathione peroxidase 4 and intracellular iron level in ovarian cancer cells-"utilization" of ferroptosis mechanism.

Objective And Design: Ovarian cancer is the major cause of death in gynecologic diseases worldwide. Ferroptosis, a nonapoptotic form of cell death, is featured by accumulation of iron-based lipid peroxidation. The elevated iron level and malondialdehyde (MDA) in ovarian cancer cells suggest more vulnerable to ferroptosis, nevertheless, ferroptosis is not observed in ovarian cancer cells.

Asymmetric Synthesis of 1-Benzazepine Derivatives via Copper-Catalyzed Intramolecular Reductive Cyclization.

An asymmetric construction of enantioenriched 2,3-substituted-1-benzazepine derivatives containing a cyclic tertiary amine moiety was developed by copper-catalyzed reductive intramolecular cyclization of ()-dienyl arenes with a tethered ketimine. This protocol involves tandem chemo-, regio-, and enantioselective hydrocupration and asymmetric cyclization in the presence of a chiral bisphosphine-copper catalyst. Under mild conditions, a broad range of 1-benzazepine derivatives was obtained in good to high yields with high degrees of diastereoselectivity and enantioselectivity.

Copper-Catalyzed Regioselective and Diastereoselective Synthesis of Borylated 1-Benzo[ b]azepines.

A practical regioselective and diastereoselective synthesis of functionalized 1-benzo[ b]azepines by copper-catalyzed intramolecular cyclization has been developed. The reaction involves borylcupration of a mixture of ( E/ Z)-1,3-dienes, followed by capture of the generated ( Z)-allylcopper species with an imine to produce 7-membered N-heterocycles as single diastereomers. The reaction is applicable to various ( E/ Z)-dienyl arenes with an imine moiety at the ortho-position, including aryl, alkyl, and heterocyclic aldimines, and ketimines, affording borylated 2,3- cis-substituted 1-benzo[ b]azepines in good yields.

Copper-Catalyzed Asymmetric Synthesis of Borylated cis-Disubstituted Indolines.

A copper-catalyzed, intramolecular borylative cyclization of vinyl arenes with imines is reported, which affords enantio-enriched indolines as a single diastereomer under mild conditions. A benzylcopper species is generated by Cu-Bpin addition to the alkene, which then acts as a nucleophile for intramolecular imine addition. The reaction is applicable to various vinyl arenes with an imine moiety at the ortho-position, including heterocycles, for formation of borylated indolines in good yields and ee values up to 90 %.

Regioselective synthesis of highly functionalized alkenylboronates by Cu-catalyzed borylation of propargylic silylalkynes.

High regioselectivity was achieved in the Cu(i)-catalyzed borylation of internal propargylic alkynes with a silyl substituent to afford multifunctionalized alkenylboron compounds. While both the silyl and propargylic substituents are known to act as directing groups, a N-heterocyclic carbene (NHC)-Cu complex furnished β-vinylboronate products (relative to Si) with high selectivity.

Copper-catalyzed synthesis of 1,1-diborylalkanes through regioselective dihydroboration of terminal alkynes.

The copper-catalyzed sequential hydroboration of terminal alkynes with pinacolborane to prepare 1,1-diborylalkanes directly from alkynes was studied. Protected propargyl amines, propargyl alcohol derivatives, and simple alkynes regioselectively produced the desired 1,1-diborylalkanes in good yields with a copper/xantphos catalyst.