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A tetrahedral {HPO 3 } and {WO 4 } group simultaneously directing acetate-decorated tri-Tb(III)-containing antimonotungstate was prepared and characterized. • Inorganic-organic hybrid trimer antimonotungstate. • Tetrahedral {HPO 3 } and tetrahedral {WO 4 } group directing tri-Tb(III)-containing antimonotungstate. • Photoluminescence properties. A tetrahedral {HPO 3 } and {WO 4 } group simultaneously directing tri-Tb(III)-containing antimonotungstate (AT) K 3 Na 21 H[Tb 3 (Ac) 3 (HPO 3)(WO 4)][B- α -SbW 9 O 33 ] 3 ·36H 2 O (1) has been triumphantly isolated by the aqueous reaction of Na 9 [B- α -SbW 9 O 33 ]·19·.5H 2 O, Na 2 WO 4 ·2H 2 O, H 3 PO 3 and Tb(NO 3) 3 ·6H 2 O. Notably, tetrahedral {HPO 3 } and {WO 4 } groups may play the template-directing function in the formation of polyoxoanion of 1. Under the excitation at 380 nm, the emission spectrum and the decay lifetime curve of 1 have been measured. Upon the O → W LMCT excitation at 260 nm, energy transfer from AT fragments to Tb3+ ions has occurred because Tb3+ ions can absorb energy from the O → W LMCT emission of AT fragments. By switching the excitation wavelength from 250 to 390 nm, it's available to tune the emission color of 1 from blue to green. [ABSTRACT FROM AUTHOR]

A trimeric tri-Tb3+-including antimonotungstate (AMT) hybrid Na17{(WO4)[Tb(H2O)(Ac)(B-α-SbW9O31(OH)2)]3}·50H2O (Tb3W28) was successfully synthesized, in which the capped tetrahedral {WO4} group plays a significant template role in directing the aggregation of three [B-α-SbW9O33]9− fragments and three Tb3+ ions. Eu3+/Tb3+/Dy3+/Gd3+-codoped AMT materials based on Tb3W28 were firstly prepared and their luminescence properties were investigated. The red emitter Eu3+, yellow emitter Dy3+, and nonluminous Gd3+ ions were codoped into Tb3W28 to substitute Tb3+ ions for investigating the energy transfer (ET) mechanism among Eu3+, Tb3+, and Dy3+ ions. Upon the 6H15/2 → 4I13/2 excitation at 389 nm of the Dy3+ ion, the ET1 mechanism (Dy3+ → Tb3+) was confirmed as a non-radiative dipole–dipole interaction. Under the 7F6 → 5L10 excitation at 370 nm of the Tb3+ ion, the ET2 mechanism (Tb3+ → Eu3+) was identified as a non-radiative quadrupole–quadrupole interaction. Under excitation at 389 nm, the two-step successive Dy3+ → Tb3+ → Eu3+ ET3 process was proved in Dy1.2Tb3zEu0.03Gd1.77−3zW28. Through changing the excitation wavelengths, the emission color of Dy1.2Tb1.2Eu0.03Gd0.57W28 can vary from blue to yellow, in which a near-white-light emission case was observed upon excitation at 378 nm. This work not only provides a systematic ET mechanism study of hetero-Ln-codoped AMTs, but also offers some useful guidance for designing novel performance-oriented Ln-codoped polyoxometalate-based materials. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Gardenia jasminoides Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction. Meanwhile, the chemical components of GFE were performed by UPLC-QTOF-MS/MS. GFE significantly decreased DAI scores and ameliorated macroscopic and histologic damage. It also reduced the levels of MPO, NO, MDA, IL-1β, TNF-α, and IL-6, while increasing the level of SOD. Moreover, 56 components were identified in GFE using a UPLC-QTOF-MS/MS method, which can be categorized into six structural groups. Our results indicated that GFE has an ameliorative effect on TNBS-induced colitis in rats, which may further verify its anti-inflammatory and antioxidative properties. Therefore, GFE can be a promising protective agent of colitis that deserves further investigation. [ABSTRACT FROM AUTHOR]

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0–2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction). [ABSTRACT FROM AUTHOR]

Background: Chondrogenic progenitor cells (CPCs) have high self-renewal capacity and chondrogenic potential. Intra-articular delivery of purified mesenchymal stem cells (MSCs) from MRL/MpJ "superhealer" mice increased bone volume during repair and prevents post-traumatic arthritis. Recently, although extracellular vesicles released from MSCs have been used widely for treating OA, the application of extracellular vesicles secreted by CPCs from MRL/MpJ mice in OA therapy has never been reported. In this study, we evaluated the effects of extracellular vesicles secreted by CPCs from control CBA (CBA-EVs) and MRL/MpJ mice (MRL-EVs) on proliferation and migration of murine chondrocytes. We also determined here if weekly intra-articular injections of CBA-EVs and MRL-EVs would repair and regenerate surgically induced model in mice. Methods: CPC surface markers were detected by flow cytometry. CBA-EVs and MRL-EVs were isolated using an ultrafiltration method. Nanoparticle tracking analysis, transmission electron microscopy, and western blots were used to identify extracellular vesicles. CBA-EVs and MRL-EVs were injected intra-articularly in a mouse model of surgical destabilization of the medial meniscus (DMM)-induced OA, and histological and immunohistochemistry analyses were used to assess the efficacy of exosome injections. We used miRNA-seq analysis to analyze the expression profiles of exosomal miRNAs derived from CBA-EVs as well as MRL-EVs. Cell-counting and scratch assays were used to evaluate the effects of CBA-EVs and MRL-EVs on proliferation and migration of murine chondrocytes, respectively. Meanwhile, a specific RNA inhibitor assesses the roles of the candidate miRNAs in CPC-EV-induced regulation of function of chondrocytes. Results: Both CBA-EVs and MRL-EVs stimulated chondrocyte proliferation and migration, but MRL-EVs exerted a stronger effect than CBA-EVs. The similar result was also observed in in vivo study, which indicated that injecting either CBA-EVs or MRL-EVs attenuated OA, but MRL-EVs showed a superior therapeutic effect in comparison with CBA-EVs. The results of bioinformatics analyses revealed that the differentially expressed exosomal miRNAs participated in multiple biological processes. We identified 80 significantly upregulated and 100 downregulated miRNAs. Moreover, we found that the top 20 differentially expressed exosomal miRNAs connected OA repair to processes such as AMPK signaling, regulation of autophagy, and insulin signaling. Notably, miRNA 221-3p were highly enriched in MRL-Exos and treatment with miR 221-3p inhibitor markedly decreased chondrocyte proliferation and migration induced by CBA-EVs or MRL-EVs in vitro. Conclusions: This is the first study to demonstrate MRL-EVs had a greater therapeutic effect on the treatment of OA than CBA-EVs. This study will hopefully provide new insight into the pathogenesis, prevention, and treatment of OA. [ABSTRACT FROM AUTHOR]

• The authors designed novel GPR119 agonists bearing various core moiety from lipophilic cycloolefin fused pyrimidines to polar tetrahydropyridopyrimidines and found that the less polar cyclohexene fused compounds displayed the most potent activity. A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16 , 19 , 26 , 28 , 42) bearing endo - N -Boc-nortropane amine and fluoro-substituted aniline exhibited better EC 50 values (0.27–1.2 μM) though they appeared to be partial agonists. [ABSTRACT FROM AUTHOR]

We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activities with single digit EC 50 values (2.2 nM and 8.1 nM, respectively). Therefore, 15a and 21e were evaluated for their oral glucose tolerance test (oGTT) in C57BL/6N mice. Compound 15a reduced the blood glucose area of under curve from 0 to 2 h (AUC 0–2h ) to 13.5% at the dose of 15 mg/kg comparing with Metformin reduced 18% of AUC 0–2h at the dose of 300 mg/kg. [ABSTRACT FROM AUTHOR]

A class of senkyunolide analogues bearing benzofuranone fragment were designed, synthesized and evaluated for their neuroprotective effect in models of oxygen glucose deprivation (OGD) and oxidative stress. All tested compounds showed neuroprotection profile based on the cell viability assay. In particular, derivatives 1f – 1i possessing furoxan-based nitric oxide releasing functionality exhibited significant biological activities in OGD models. More importantly, compound 1g containing short linker with furoxan displayed the most potent neuroprotection at the concentration of 100 μM (cell survival up to 145.2%). Besides, 1g also showed the middle level neuroprotective effect in model of oxidative stress. [ABSTRACT FROM AUTHOR]

Naturally occurring cyclic antimicrobial peptides (AMPs) such as tyrocidine A (Tyrc A) and gramicidin S (GS) are appealing targets for the development of novel antibiotics. However, their therapeutic potentials are limited by undesired hemolytic activity and relatively poor activity against Gram-negative bacteria. Inspired by polycationic lipopeptide polymyxin B (PMB), the so called 'last-resort' antibiotic for the treatment of infections caused by multidrug-resistant Gram-negative bacteria, we synthesized and biologically evaluated a series of polycationic analogues derived from Tyrc A. We were able to obtain peptide 8 that possesses 5 positive charges exhibiting potent activities against both Gram-negative and Gram-positive bacteria along with totally diminished hemolytic activity. Intriguingly, antibacterial mechanism studies revealed that, rather than the 'pore forming' model that possessed by Tyrc A, peptide 8 likely diffuses membrane in a 'detergent-like' manner. Furthermore, when treating mice with peritonitis–sepsis, peptide 8 showed excellent antibacterial and anti-inflammatory activities in vivo. [Display omitted] • Totally ten polycationic cyclopeptides derived for Tyrocidine A were synthesized. • Several peptides display broad antibacterial spectrum and very low hemolysis. • Peptide 8 shows excellent antibacterial and anti-inflammatory activities in vivo. • Peptide 8 likely diffuses membrane in a 'detergent-like' manner. [ABSTRACT FROM AUTHOR]

A terbium-antimony-oxo-cluster bridging antimonotungstate comprising divacant and tetravacant Keggin segments was prepared and characterized. • Tetramer bridging antimonotungstate. • Terbium-antimony-oxo-cluster bridging antimonotungstate. • Photoluminescence properties. • Energy transfer. A terbium-antimony-oxo-cluster bridging antimonotungstate (AT) [H 2 N(CH 3) 2 ] 8 Na 6 H 8 {[Tb 4 (H 2 O) 6 Sb 6 O 4 ](SbW 10 O 37) 2 (B- α -SbW 8 O 31) 2 }·24H 2 O (1) was successfully prepared by reaction of Na 9 [B- α -SbW 9 O 33 ]·19·.5H 2 O, SbCl 3 , Tb(NO 3) 3 ·6H 2 O and dimethylamine hydrochloride (DMA·HCl) in acidic aqueous solution. Its tetramer polyanion consists of two divacant [SbW 10 O 37 ]11− and two tetravacant [B- α -SbW 8 O 31 ]11− fragments linked by two [Tb 2 (H 2 O) 3 Sb 3 O 2 ]11+ clusters. The photoluminescence emission spectra and lifetime decay curves of 1 are collected respectively under the most f−f excitation at 368 nm and O → W LMCT excitation at 268 nm. The sensitization of AT fragments can enhance the f−f transition emission intensity of Tb3+ ions and prolong the lifetime of Tb3+ ions. The time-resolved emission spectrum of 1 reveals that the decay rate of characteristic emission peaks of Tb3+ ions has been inhibited because of the sensitization effect of AT fragments to Tb3+ ions. The emission spectra under different excitation wavelengths indicate that the excitation at 268 nm from O → W LMCT is the most suitable excitation and can obtain the strongest emission spectrum of 1. Their corresponding CIE coordinates demonstrate that the emission colors of 1 can be tuned by changing different excitation wavelengths. [ABSTRACT FROM AUTHOR]