Structure-Activity Relationship Studies of Substituted 2-Phenyl-1,2,4-triazine-3,5(2,4)-dione Analogues: Development of Potent eEF2K Degraders against Triple-Negative Breast Cancer.

eEF2K, an atypical alpha-kinase, is responsible for regulating protein synthesis and energy homeostasis. Aberrant eEF2K function has been linked to various human cancers, including triple-negative breast cancer (TNBC). However, limited cellular activity of current eEF2K modulators impedes their clinical application.

Identification of Spiro[chromene-2,4'-piperidine]s as Potent, Selective, and G-Biased 5-HT Receptor Partial Agonists.

A series of spiropiperidines was designed and synthesized by structural modifications based on our previous lead compound and evaluated with cellular signaling assays for the discovery of 5-HT receptor (5-HTR) selective agonists with a G bias. Structure-activity relationship (SAR) studies of spiropiperidines uncovered spiro[chromene-2,4'-piperidine]s as a novel chemotype of 5-HTR selective agonists. Among this new series, the 7-chloro analogue was identified as the most potent and selective 5-HTR partial agonist ( = 71.

Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its Significance.

Objective: Depressive disorders constitute a series of debilitating diseases. This study investigated the therapeutic effect of agomelatine (AG) combined with aerobic exercise (AE) on patients with moderate-severe depression (MSD) and the changes of the serum C-reactive protein (CRP) level in patients after treatment as well as its significance.

Methods: A total of 178 MSD patients were randomly assigned to the AG group (N = 90) and AG + AE group (N = 88).

Protective Effect of the Eluting Fraction of Da-Yuan-Yin Decoction on Acute Lung Injury.

Context: The Da-yuan-yin (DYY) decoction is a classical prescription of traditional Chinese medicine that has antipyretic and anti-inflammatory effects. Network Pharmacology (NP) is an emerging discipline based on system-biology theory and biosystem network analysis that researchers can use to predict drug-action targets and mechanisms.

Objective: The study intended to use NP evaluate the protective effects of the fifth eluting fraction of the supernatant of the DYY decoction (DYY-5) for mice induced with acute lung injury (ALI) using lipopolysaccharide (LPS) and to explore DYY-5's mechanisms.

Highly Luminescent and Stable Organic-Inorganic Hybrid Films for Transparent Luminescent Solar Concentrators.

Here, a highly luminescent, stable, and visible-transparent organic-inorganic hybrid film was synthesized in a siloxane-polyether (di-ureasil) sol-gel process by dissolving a 4-hydroxy-2-methyl-1,5-naphthyridine-3-carbonitrile (2mCND) ligand and a europium(III) ion. Doping a europium(III) complex into di-ureasil achieves an boost in photoluminescence quantum efficiency (PLQY) from 23.25 to 68.

Association of lipoproteins and thyroid hormones with cognitive dysfunction in patients with systemic lupus erythematosus.

Background: Neuropsychiatric manifestations occur in up to 75% of adult systemic lupus erythematosus (SLE) patients and are one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of neuropsychiatric SLE (NPSLE), which seriously affects the quality of life of patients. Dyslipidaemia and thyroid symptoms, which are prevalent in SLE patients, have both been related to neuropsychiatric disturbances, including significant psychiatric and cognitive disturbances.

Hippocampal microglia CD40 mediates NPSLE cognitive dysfunction in mice.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the most serious and complicated clinical manifestation of lupus erythematosus. Cognitive dysfunction is the most common symptom of NPSLE. A variety of potential mechanisms or mediators related to the pathogenesis of NPSLE cognitive dysfunction have been proposed.

Synthesis and anticancer activities of biotinylated derivatives of glaucocalyxin A and oridonin.

Fourteen glaucocalyxin A biotinylated derivatives, one glaucocalyxin C biotinylated derivative, and two oridonin biotinylated derivatives were designed and synthesized. Their structures were confirmed from H NMR, C NMR and HRMS data. The derivatives were evaluated for cytotoxic activities against lung (A549), cervical cancer cell line HeLa derivative (KB), multidrug-resistant KB subline (KB-VIN), triple-negative breast (MDA-MB-231), and estrogen receptor-positive breast (MCF-7) cancer cell lines.

Hybrid molecules of scutellarein and tertramethylpyrazine's active metabolites for ischemic stroke.

A series of hybrid molecules of scutellarein and tertramethylpyrazine's active metabolites have been synthesized. Compared to the original compound, these prepared compounds exhibited higher water solubility, more appropriate logP and better stability. Importantly, compounds 11b, 11d and 11e showed improved neuroprotective activity against the HO-induced cell death in PC12 cells, and better antithrombosis activity.

N-Arylsulfonylsubstituted-1H indole derivatives as small molecule dual inhibitors of signal transducer and activator of transcription 3 (STAT3) and tubulin.

Signal transducer and activator of transcription (STAT3) is a proposed therapeutic target for the development of anti-cancer agents. In this report, a series of N-arylsulfonylsubstituted-1H indole derivatives were designed and synthesized as STAT3 inhibitors, their anti-proliferative activities were evaluated against a number of tumor cells, some potent compounds exhibited IC values less than 10 μM. The most potent compound 4a was further confirmed to inhibit STAT3 phosphorylation at Tyr705.

Inversion Domain Boundary Induced Stacking and Bandstructure Diversity in Bilayer MoSe.

Interlayer rotation and stacking were recently demonstrated as effective strategies for tuning physical properties of various two-dimensional materials. The latter strategy was mostly realized in heterostructures with continuously varied stacking orders, which obscure the revelation of the intrinsic role of a certain stacking order in its physical properties. Here, we introduce inversion-domain-boundaries into molecular-beam-epitaxy grown MoSe homobilayers, which induce uncommon fractional lattice translations to their surrounding domains, accounting for the observed diversity of large-area and uniform stacking sequences.

Ultrathin β-tellurium layers grown on highly oriented pyrolytic graphite by molecular-beam epitaxy.

Monolayer tellurium (Te) or tellurene has been suggested by a recent theory as a new two-dimensional (2D) system with great electronic and optoelectronic promises. Here we present an experimental study of epitaxial Te deposited on highly oriented pyrolytic graphite (HOPG) by molecular-beam epitaxy. Scanning tunneling microscopy of ultrathin layers of Te reveals rectangular surface cells with the cell size consistent with the theoretically predicted β-tellurene, whereas for thicker films, the cell size is more consistent with that of the [101[combining macron]0] surface of the bulk Te crystal.

Multivalency-Driven Formation of Te-Based Monolayer Materials: A Combined First-Principles and Experimental study.

Contemporary science is witnessing a rapid expansion of the two-dimensional (2D) materials family, each member possessing intriguing emergent properties of fundamental and practical importance. Using the particle-swarm optimization method in combination with first-principles density functional theory calculations, here we predict a new category of 2D monolayers named tellurene, composed of the metalloid element Te, with stable 1T-MoS_{2}-like (α-Te), and metastable tetragonal (β-Te) and 2H-MoS_{2}-like (γ-Te) structures. The underlying formation mechanism is inherently rooted in the multivalent nature of Te, with the central-layer Te behaving more metal-like (e.

Quantum Effects and Phase Tuning in Epitaxial Hexagonal and Monoclinic MoTe Monolayers.

Monolayer (ML) transition-metal dichalcogenides exist in different phases, such as hexagonal (2H) and monoclinic (1T') structures. They show very different properties: semiconducting for 2H-MoTe and semimetallic for 1T'-MoTe. The formation energy difference between 2H- and 1T'-phase MoTe is small, so there is a high chance of tuning the structures of MoTe and thereby introducing applications of phase-change electronics.

Eupatorium lindleyanum DC. flavonoids fraction attenuates lipopolysaccharide-induced acute lung injury in mice.

Eupatorium lindleyanum DC., "Ye-Ma-Zhui" called by local residents in China, showed anti-inflammatory activity and is used to treat tracheitis. We had isolated and identified the flavonoids, diterpenoids and sesquiterpenes compounds from the herb.

Antischistosomal activity of N,N'-arylurea analogs against Schistosoma japonicum.

Although the antischistosomal activities of N,N'-arylurea analogs were reported, systematic structure-activity relationships have not been conducted. In this Letter, we reported the design, synthesis and evaluation of 45 N,N'-arylurea analogs. Among these prepared compounds, 13 compounds were urea linker modified and 32 were N,N'-arylurea derivatives.

Palladium-Catalyzed Carbonylative Annulation Reactions Using Aryl Formate as a CO Source: Synthesis of 2-Substituted Indene-1,3(2H)-dione Derivatives.

An efficient synthesis of 2-substituted indene-1,3(2H)-diones from stable and readily available 1-(2-halophenyl)-1,3-diones by employing phenyl formate as a CO source has been developed. The reaction occurred via palladium-catalyzed intramolecular carbonylative annulation using K3PO4 as a base and DMSO as a solvent at 95 °C. In this protocol, the reaction showed a broad substrate scope with good to excellent yields.

Observation of intervalley quantum interference in epitaxial monolayer tungsten diselenide.

The extraordinary electronic structures of monolayer transition metal dichalcogenides, such as the spin-valley-coupled band edges, have sparked great interest for potential spintronic and valleytronic applications based on these two-dimensional materials. In this work, we report the experimental observation of quasi-particle interference patterns in monolayer WSe2 using low-temperature scanning tunnelling spectroscopy. We observe intervalley quantum interference involving the Q valleys in the conduction band due to spin-conserving scattering processes, while spin-flipping intervalley scattering is absent.

Line and Point Defects in MoSe2 Bilayer Studied by Scanning Tunneling Microscopy and Spectroscopy.

Bilayer (BL) MoSe2 films grown by molecular-beam epitaxy (MBE) are studied by scanning tunneling microscopy and spectroscopy (STM/S). Similar to monolayer (ML) films, networks of inversion domain boundary (DB) defects are observed both in the top and bottom layers of BL MoSe2, and often they are seen spatially correlated such that one is on top of the other. There are also isolated ones in the bottom layer without companion in the top-layer and are detected by STM/S through quantum tunneling of the defect states through the barrier of the MoSe2 ML.

Design, synthesis and biological evaluation of praziquantel and endoperoxide conjugates as antischistosomal agents.

Background: The widespread use of praziquantel for the treatment of schistosomiasis has led to concerns over the potential development of drug resistance. Therefore, the discovery of novel antischistosomal agents is imperative. In this study, a series of praziquantel and endoperoxide conjugates were synthesized and evaluated as potential antischistosomal agents.

An artemisinin derivative of praziquantel as an orally active antischistosomal agent.

Background: Schistosomiasis is a major health problem in tropical and sub-tropical areas caused by species of trematode belonging to the genus Schistosoma. The treatment and control of this disease has been relying on the use of a single drug praziquantel. However, the drug resistance concern urged the development of new drugs against schistosoma.

Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase.

The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with β-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate.

Development of a novel class of pyrrolo-[1,2,5]benzothiadiazepine derivatives as potential anti-schistosomal agents.

Analogues of pyrrolo-[1,2,5]benzothiadiazepine were prepared and evaluated against Schistosoma japonica. The biological data revealed that most benzothiazepine derivatives show anti-schistosomal activity to some extent, while α-chloronation of the title compound and another bioisosteric derivative pyrrolo-[1,2,5]benzodiazepine displayed the most distinct worm killing activity. This study proved that benzodiazepine may serve as a novel structural skeleton for the development of anti-schistosomal agents.

Praziquantel derivatives with antischistosomal activity: aromatic ring modification.

A series of aromatic ring-modified praziquantel derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin. Several analogs comparable in activity to the drug praziquantel have been identified based on in vitro and in vivo japonuicum schistosomes worm viability assay. Structure and activity relationship of these praziquantel aromatic ring-modified compounds was revealed.