Melatonin derivative 6a protects Caenorhabditis elegans from formaldehyde neurotoxicity via ADH5.

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD).

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[]indoles.

Herein, a Sc(OTf)-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon.

Cooperative Cu/Pd-Catalyzed 1,5-Boroacylation of Cyclopropyl-Substituted Alkylidenecyclopropanes.

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with Bpin and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

Circulating Exosomal LncRNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities.

Objective: Exosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH).

Methods: We used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls.

Acid-Promoted Cyclization of α-Azidobenzyl Ketones through C═N Bond Formation: Synthesis of 6-Substituted Quinoline Derivatives.

An acid-promoted cyclization of α-azidobenzyl ketones has been developed for the synthesis of 6-substituted quinoline derivatives. A variety of synthetically useful 6-OTf or -OMs quinoline derivatives were obtained in moderate to good yields. The reaction proceeds via C═N bond formation without organophosphine, providing convenient access to structurally interesting and synthetically important 6-substituted quinoline derivatives in moderate to good yields.

Ruthenium-Catalyzed Carbonylation of α-Aminoaryl-Tethered Alkylidenecyclopropanes: Synthesis of Eight-Membered Benzolactams.

The synthesis of medium-sized lactams is a great challenge because of the unfavorable transannular interactions and entropic barriers in the transition state. We have developed a ruthenium-catalyzed carbonylation of α-aminoaryl-tethered alkylidenecyclopropanes (ACPs) that allows for the efficient preparation of valuable eight-membered benzolactams under ligand-free conditions. The amino group served a dual role of both directing group and nucleophile to facilitate the metallacycle formation and the carbonylation.

Photoinduced reductive Reformatsky reaction of α-haloesters and aldehydes or ketones by cooperative dual-metal catalysis.

A photoinduced reductive Reformatsky reaction by cooperative dual-metal catalysis is described. This methodology enables the implementation of this venerable reaction in environmentally friendly conditions, obviating the need for a stoichiometric amount of metals. A broad range of synthetically useful β-hydroxy esters can be efficiently prepared in moderate to high yields using this protocol.

Total Synthesis of (+)-Peniciketal B.

An efficient synthesis of (+)-peniciketal B has been accomplished in 15 steps from the commercially available materials atraric acid, acryloyl chloride, and (+)-homoallylic alcohol. A convergent synthetic approach that is quite concise for constructing either "hemisphere" of (+)-peniciketal B with a common intermediate is employed that relies on a cascade intermolecular FeCl-mediated "inner sphere" Michael-type reaction/double cyclization of an α,β-unsaturated ketone and substituted phenol to build the benzo-fused 2,8-dioxabicyclo[3.3.

Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment.

Background: Exosomal miRNAs play crucial roles in many central nervous system diseases. Cerebral small vessel disease (CVSD) is a small vessel disease that is affected by various factors. This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities.

Molybdenum-Mediated Reductive Hydroamination of Vinylcyclopropanes with Nitroarenes: Synthesis of Homoallylamines.

A molybdenum-mediated reductive hydroamination of vinylcyclopropanes with nitroarenes has been developed. A broad range of substituted homoallylamines were prepared in good to excellent yields from readily available starting materials. No noble metal catalysts were used in this reaction, and Mo(CO) acted as both catalyst and reductant.

Total synthesis of bi-magnolignan.

Bi-magnolignan, isolated from the leaves of officinalis, has shown excellent physiological activity against tumor cells. An efficient strategy for the first total synthesis of bi-magnolignan is reported. The bi-dibenzofuran skeleton was constructed functional group interconversions of commercially available materials 1,2,4-trimethoxybenzene and 4-allylanisole.

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease.

Background: Cerebral small vessel disease (CSVD) with an insidious onset can cause overall neurological dysfunction and dementia, bringing a massive burden to society. However, the pathogenesis of CSVD is complex and reliable non-invasive biomarkers for diagnosis are still not available at present. Our study aimed to investigate abnormal exosomal miRNA patterns via microarray analysis and identify candidate biomarkers for CSVD.

Bismuth(III)-Catalyzed 1,8-Addition/Cyclization/Rearrangement of Propargylic -Quinone Methides with 2-Vinylphenol: Synthesis of Indeno[2,1-]chromenes.

The unique reactivity of generated propargylic quinone methides as a new type of five-carbon synthon has been discovered by a novel bismuth(III)-catalyzed tandem annulation reaction. This 1,8-addition/cyclization/rearrangement cyclization cascade reaction is characterized by unusual structural reconstruction of 2-vinylphenol, involving cleavage of the C1'═C2' bond and formation of four new bonds. This method provides a convenient and mild approach to generate synthetically important functionalized indeno[2,1-]chromenes.

Base-promoted [4 + 2] annulation of pyrrole-2-carbaldehyde derivatives with β,γ-unsaturated α-ketoesters: syntheses of 5,6-dihydroindolizines.

A base-promoted [4 + 2] annulation of pyrrole-2-carbaldehyde derivatives with β,γ-unsaturated α-ketoesters for the syntheses of multisubstituted 5,6-dihydroindolizines was developed. Using DBN as a base, the reaction proceeds smoothly under mild conditions to provide the target products in moderate to high yields, and many useful functional groups can be tolerated.

Studies toward synthesis of the core skeleton of spiroaspertrione A.

Bioassay-guided isolation of spiroaspertrione A from cultures of . TJ23 in 2017 demonstrated potent resensitization of oxacillin against methicillin-resistant by lowering the oxacillin minimal inhibitory concentration up to 32-fold. To construct this unique spiro[bicyclo[3.

Palladium-Catalyzed Nucleophilic Reaction of Alkylidenecyclopropanes with β,γ-Unsaturated α-Ketoesters: Ligand-Controlled Divergent Synthesis.

A palladium-catalyzed ligand-controlled selective 1,4-addition and cycloaddition reaction of β,γ-unsaturated α-ketoesters with alkylidenecyclopropanes (ACPs) has been developed. Using ACPs and β,γ-unsaturated α-ketoesters as starting materials, γ-dienyl-α-ketoesters and dihydro-2-pyrans could be prepared selectively by modulating the ligand. A range of multisubstituted α-ketoesters and dihydro-2-pyrans were obtained in moderate to excellent yields with excellent regioselectivities.

Palladium Catalyzed Dicarbonylation of α-Iodo-Substituted Alkylidenecyclopropanes: Synthesis of Carbamoyl Substituted Indenones.

A palladium catalyzed dicarbonylation of α-iodo-substituted ACPs for the synthesis of carbamoyl substituted indenones has been developed. Two carbonyl groups were incorporated into the product with the cleavage of the proximal C-C bond of the ACPs. A broad range of carbamoyl substituted indenones were efficiently prepared in good to excellent yields.

Palladium-Catalyzed Intramolecular Heck/Aminocarbonylation of Alkene-Tethered Iodobenzenes with Nitro Compounds: Synthesis of Carbamoyl-Substituted Benzoheterocycles.

A palladium-catalyzed intramolecular Heck/aminocarbonylation of alkene-tethered iodobenzenes with nitro compounds has been developed for the synthesis of carbamoyl-substituted benzoheterocycles. Using Mo(CO) as a solid CO source, no external reductant or additives were needed in this procedure. Both nitroarenes and nitroalkanes were well tolerated.

Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson's Disease Models of .

Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson's disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of P-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a-6j).

Palladium-Catalyzed Carbonylative Sonogashira/Annulation Reaction: Synthesis of Indolo[1,2-]isoquinolines.

A palladium-catalyzed carbonylative Sonogashira/annulation reaction for the synthesis of indolo[1,2-]isoquinolines has been developed. Tetracyclic 6/5/6/6 indoline skeletons were synthesized in moderate to good yields from easily available 2-bromo--(2-iodophenyl)benzamides and terminal alkynes. Notably, this efficient methodology established three C-C bonds and a C-N bond through a one-step transformation and provided a new method for the synthesis of indolo[1,2-]isoquinoline derivatives.

Development and Validation of a Plasma FAM19A5 and MRI-Based Radiomics Model for Prediction of Parkinson's Disease and Parkinson's Disease With Depression.

Prediction and early diagnosis of Parkinson's disease (PD) and Parkinson's disease with depression (PDD) are essential for the clinical management of PD. The present study aimed to develop a plasma Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD. The study involved 176 PD patients and 181 healthy controls (HC).

Dearomatization of 2,3-Disubstituted Indoles via 1,8-Addition of Propargylic (Aza)--Quinone Methides.

Dearomatization of indole is a useful strategy to access indolimines: a motif widely exists in biologically active molecules and natural products. Herein, an efficient method for the dearomatization of 2,3-disubstituted indoles to generate diverse indolimines with tetrasubstituted allenes is described. This work accomplishes dearomatization of 2,3-disubstituted indoles through 1,8-addition of (aza)--quinone methides, which are generated in situ from propargylic alcohols.