The effect of resistance training on patients with knee osteoarthritis: a systematic review and meta-analysis.

The objective of this study is to investigate the beneficial effects of resistance training (RT) on individuals suffering from knee osteoarthritis (KOA). In order to gather relevant studies from the beginning of various databases until January 2023, a comprehensive search was conducted on PubMed, Embase, Scopus, Web of Science, and The Cochrane Library. Additionally, manual searches were performed on the reference lists.

Design, synthesis and biological evaluation of 1-aryldonepezil analogues as anti-Alzheimer's disease agents.

To design and synthesize a novel series of 1-aryldonepezil analogues. The 1-aryldonepezil analogues were synthesized through palladium/PCy-catalyzed Suzuki reaction and were evaluated for cholinesterase inhibitory activities and neuroprotective effects. docking of the most effective compound was conducted.

Missing WD40 Repeats in ATG16L1 Delays Canonical Autophagy and Inhibits Noncanonical Autophagy.

Canonical autophagy is an evolutionarily conserved process that forms double-membrane structures and mediates the degradation of long-lived proteins (LLPs). Noncanonical autophagy (NCA) is an important alternative pathway involving the formation of microtubule-associated protein 1 light chain 3 (LC3)-positive structures that are independent of partial core autophagy proteins. NCA has been defined by the conjugation of ATG8s to single membranes (CASM).

Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation.

STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only canonical autophagy but also non-canonical autophagy (NCA) which is independent of the ULK1 or BECN1 complexes to form MAP1LC3/LC3-positive structures. Whether STING1-induced NCA has similar characters and physiological functions to canonical autophagy is totally unknown.

Enantioselective Cu-Catalyzed Nucleophilic Substitutions of Polyfluoroarenes: Synthesis of Chiral Polyfluoroaryl Diarylmethanes.

Optically pure diarylmethanes are frequently presented in pharmaceuticals and bioactive molecules. However, minor efforts have been devoted to chiral polyfluoroarene-containing diarylmethanes, and their synthesis is still challenging. Herein, we describe an enantioselective Cu/sulfoxide phosphine () catalyzed nucleophilic substitution reaction by using polyfluoroarenes as the polyfluoroaryl reagent.

Synthesis of Sulfilimines via Selective S-C Bond Formation in Water.

Sulfilimines are valuable compounds both in organic synthesis and in pharmaceuticals. Here we developed a mild and simplified method for preparation of sulfilimines via selective S-C bond formation rather than traditional S-N bond formation. The method is both attractive and useful for the following reasons: it uses a readily available alkylation reagent such alkyl bromide or alkyl iodide, it uses water as solvent, it is easy to perform, and it is convenient for late-stage diversification of drugs.

Enantioselective Double Carbonylation Enabled by High-Valent Palladium Catalysis.

Palladium-catalyzed carbonylation reactions are efficient methods for synthesizing valuable molecules. However, realizing a carbonylation with excellent yield and chemo-, regio-, and enantioselectivities by classical low-valent palladium catalysis is highly challenging. Herein, we describe an enantioselective carbonylation reaction using a high-valent palladium catalysis strategy and employing a chiral sulfoxide phosphine (SOP) ligand.

Cyclopiazonic Acid and Okaramine Analogues, Including Chlorinated Compounds, from YT-1.

Eight new cyclopiazonic acid (-) and five new okaramine (-) alkaloids together with 13 known compounds were isolated from the fungus YT-1. Compounds , , , , , , and were chlorinated indole alkaloids. The structures of compounds - were elucidated by HRESIMS and NMR spectroscopic data.

Discovery of an autophagy inducer J3 to lower mutant huntingtin and alleviate Huntington's disease-related phenotype.

Huntington's disease (HD) is a neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein encoded from extra tracts of CAG repeats in exon 1 of the HTT gene. mHTT proteins are neurotoxic to render the death of neurons and a series of disease-associated phenotypes. The mHTT is degraded through autophagy pathway and ubiquitin-proteasome system (UPS).

Suppression of ATG4B by copper inhibits autophagy and involves in Mallory body formation.

Autophagy is an evolutionarily conserved self-protecting mechanism implicated in cellular homeostasis. ATG4B plays a vital role in autophagy process via undertaking priming and delipidation of LC3. Chemical inhibitors and regulative modifications such as oxidation of ATG4B have been demonstrated to modulate autophagy function.

Enantioselective Cu-Catalyzed Nucleophilic Addition of Fluorinated Reagents: C-C Bond Formation for the Synthesis of Chiral Vicinal Difluorides.

Herein we described the first enantioselective Cu/sulfoxide phosphine (SOP) complex catalyzed nucleophilic addition of fluorinated enolates to -difluoroalkenes. The enantioenriched vicinal difluorides, containing a chiral tertiary fluoride and a fluoroalkene, were successfully afforded via C-C bond formation in good yields (up to 94% yield), high /-selectivity (5:1 → 50:1 for -isomer), and excellent enantioselectivities (up to 98.5:1.

An Insight on the Pathways Involved in Crizotinib and Sunitinib Induced Hepatotoxicity in HepG2 Cells and Animal Model.

Both crizotinib and sunitinib, novel orally-active multikinase inhibitors, exhibit antitumor activity and extend the survival of patients with a malignant tumor. However, some patients may suffer liver injury that can further limit the clinical use of these drugs, however the mechanisms underlying hepatotoxicity are still to be elucidated. Thus, our study was designed to use HepG2 cells and the ICR mice model to investigate the mechanisms of hepatotoxicity induced by crizotinib and sunitinib.

Clinical study on polycystic ovary syndrome treated with Diane-35 and Pioglitazone.

Objective: To observe the effects of Diane-35 and pioglitazone on endocrine, blood lipid, and blood glucose metabolism in patients with polycystic ovary syndrome (PCOS).

Methods: 70 PCOS patients were selected as subjects between January 2019 and January 2020 and were randomized into two groups. The control group was provided with Diane-35 for 1 tablet/day.

Enantioselective Copper-Catalyzed Electrophilic Sulfenylation of Cyclic Imino Esters.

Herein we report an enantioselective sulfenylation of cyclic imino esters with the efficient and versatile sulfenylation reagent -alkyl 4-methylbenzenesulfonothioates. By utilizing the Cu/Bu-Phosferrox catalytic system, we can assemble diverse -alkyl groups into the cyclic imino esters under mild conditions in good yields and with excellent enantioselectivities. Remarkably, this method demonstrates a high tolerance of diverse functional groups and proves to be applicable in the late-stage functionalization of pharmaceuticals.

Binding Features and Functions of ATG3.

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related () genes are indispensable for autophagosome formation. is one of the key genes involved in autophagy, and its homologs are common in eukaryotes.

Halogenated salt assisted Cu-catalyzed asymmetric 1,4-borylstannation of 1,3-enynes: enantioselective synthesis of allenylstannes.

An enantioselective 1,4-borylstannation of 1,3-enynes employed a chiral sulfoxide phosphine ()/Cu complex as a catalyst, and the desired products, chiral allenylstannes, were first synthesized by asymmetric catalysis with satisfactory yields and enantioselectivies. In this protocol, a catalytic amount of additive, a halogenated salt, plays a crucial role in the success. Control experiments and theoretical studies disclosed that the four-membered ring transmetallation transition states which were stabilized by a halide anion are the key to yields and stereochemical outcomes.

Synthesis of Tribenzo[,,]azepines via Palladium-Catalyzed Annulation Reaction of 2-Iodobiphenyls with 2-Halogenoanilines.

A palladium-catalyzed annulation reaction of 2-iodobiphenyls with 2-halogenoanilines has been developed. A variety of 2-iodobiphenyls and 2-halogenoanilines can undergo this transformation. Diversified tribenzo[,,]azepine derivatives can be synthesized in moderate to excellent yields according to this method.

Palladium-Catalyzed Linear Hydrothiocarbonylation of Unactivated Terminal Alkenes: Synthesis of Aliphatic Thioesters.

A Pd-catalyzed hydrothiocarbonylation of unactivated terminal alkenes is presented. According to this protocol, aliphatic thioesters were synthesized with exclusive linear selectivity under mild reaction conditions. Good to excellent yields (up to 91% yield), broad substrate scope, broad functional group tolerance, and utility of the method demonstrated the advantages of this protocol.

Diterpenoids caryopterisoids D - Q and iridoid glucoside derivatives caryopterisides F - H from Caryopteris glutinosa.

Fourteen undescribed diterpenoids caryopterisoids D - Q, three undescribed iridoid glucoside derivatives caryopterisides F - H, and 8 known diterpenoids were isolated from the 95% aqueous ethanolic extract of Caryopteris glutinosa. Their structures were elucidated on the basis of spectroscopic data analysis and chemical derivation studies. The structure and absolute configuration of caryopterisoid D were confirmed by X-ray crystallographic analysis.

Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics.

As a nonaddictive analgesic widely used in clinics, the LD of bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C-diterpenoid alkaloids (-, -, , , and ) were designed and synthesized from bulleyaconitine A to develop nonaddictive analgesics with low toxicity.

Copper(I)-Catalyzed Ketenimine Formation/Aza-Claisen Rearrangement Cascade for Stereoselective Synthesis of α-Allylic Amidines.

A copper-catalyzed three-component reaction of terminal alkynes, TsN, and tertiary allylic amines is developed toward the one-pot synthesis of α-allylic amidines. The product was synthesized on gram scale under 1 mol % of catalyst loading. Transformations of products into alkenyl amine and other nitrogen-containing compounds are demonstrated without any loss of stereochemical information.

Palladium-Catalyzed Synthesis and Anticancer Activity of Paclitaxel-Dehydroepiandrosterone Hybrids.

According to the activity-structure relationship of the C-13 side chain in paclitaxel or docetaxel, eighteen novel paclitaxel-dehydroepiandrosterone (DHEA) hybrids were designed and synthesized by Pd(II)-catalyzed Suzuki-Miyaura cross-coupling of 17-trifluoromethanesulfonic enolate-DHEA with different aryl boronic acids. The in vitro anticancer activity of the hybrids against a human liver cancer cell line (HepG-2) was evaluated by MTT assay, showing that most of these hybrids possessed moderate antiproliferative activity against the HepG-2 cancer cell line. Among these hybrids, three ones (, , and ) with ortho-substituents in the phenyl group of the D-ring of DHEA analogues exhibited moderate anticancer activity.

Enantioselective Synthesis of Multisubstituted Allenes by Cooperative Cu/Pd-Catalyzed 1,4-Arylboration of 1,3-Enynes.

A cooperative Cu/Pd-catalyzed enantioselective synthesis of multisubstituted allenes is established. By employing chiral sulfoxide phosphine (SOP)/Cu and PdCl (dppf) complexes as catalysts, the 1,4-arylboration of 1,3-enynes provides an efficient approach to trisubstituted chiral allenes with up to 92 % yield and 97:3 er. Furthermore, by using 2-substituted 1,3-enynes as substrates, the tetrasubstituted chiral allenes were successfully generated using this strategy.

Natural products as important tyrosine kinase inhibitors.

As an important source of drugs, natural products play an important role in the discovery and development of new drugs. More than 60% of anti-tumor drugs are closely related to natural products. At the same time, as the main cause of tumors, the abnormal activity of tyrosine kinase has become an important target for clinical treatment.