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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]

Val‐Val‐Tyr‐Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride‐induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non‐alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L‐02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine‐choline‐deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non‐esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis‐related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24‐7 and Bacteroidia in high‐fat diet (HFD)‐fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)‐associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut‐liver axis activation. VVYP might be a promising drug candidate for NASH. [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]

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]

Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin‐like growth factor‐1 receptor (IGF‐1R) is highly expressed in UM and has been shown to be associated with hepatic metastases. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells. Pristimerin (PRI) has been demonstrated to inhibit the growth of several cancer cells, but its role and underlying mechanisms in the IGF‐1‐induced UM cell proliferation are largely unknown. The present study examined the anti‐proliferative effect of PRI on UM cells and its possible role in IGF‐1R signalling transduction. MTT and clonogenic assays were used to determine the role of PRI in the proliferation of UM cells. Flow cytometry was performed to detect the effect of PRI on the cell cycle distribution of UM cells. Western blotting was carried out to assess the effects of PRI and IGF‐1 on the IGF‐1R phosphorylation and its downstream targets. The results indicated that IGF‐1 promoted the UM cell proliferation and improved the level of IGF‐1R phosphorylation, whereas PRI attenuated the effect of IGF‐1. Interestingly, PRI could not only induce the G1 phase accumulation and reduce the G2 phase induced by IGF‐1, but also could stimulate the expression of p21 and inhibit the expression of cyclin D1. Besides, PRI could attenuate the phosphorylations of Akt, mTOR and ERK1/2 induced by IGF‐1. Furthermore, the molecular docking study also demonstrated that PRI had potential inhibitory effects on IGF‐1R. Taken together, these results indicated that PRI could inhibit the proliferation of UM cells through down‐regulation of phosphorylated IGF‐1R and its downstream signalling. [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]

Advances in polyoxometalate (POM) self-assembly chemistry are always accompanied by new developments in molecular blocks. The exploration and discovery of uncommon building blocks offer great possibilities for generating unprecedented POM clusters. An intriguing Sb III -W VI -cotemplated antimonotungstate [H 2 N(CH 3 ) 2 ] 11 Na[SbW 9 O 33 ]Er 2 (H 2 O) 2 Sb 2 [SbW VI W 15 O 57 ]·22H 2 O ( 1 ) was synthesized, which comprises a classical trivacant Keggin [SbW 9 O 33 ] 9- ({SbW 9 }) fragment and an unclassical lacunary Dawson-like [SbW VI W 15 O 57 ] 15- ({SbW VI W 15 }) subunit. Notably, the Dawson-like {SbW VI W 15 } subunit is the first example of a [SbO 3 ] 3- and [W VI O 6 ] 6- mixed-heteroatom-directing POM segment. Hexacoordinated [W VI O 6 ] 6- can not only serve as the heteroatom function but its additional oxygen sites can also link to lanthanide, main-group metal, and transition-metal centers to form the innovative structure. {SbW VI W 15 } and {SbW 9 } subunits are joined by the heterometallic [Er 2 (H 2 O) 2 Sb 2 O 17 ] 22- cluster to give rise to an asymmetric sandwich-type architecture. To further realize its potential application in electrochemical sensing, a conductive 1 @rGO composite was obtained by the electrochemical deposition of 1 with graphene oxide (GO). Using a 1 @rGO-modified glassy carbon electrode as the working electrode, an electrochemical biosensor for detecting the antidepressant drug paroxetine (PRX) was successfully constructed. This work can provide a viable strategy for synthesizing mixed-heteroatom-directing POMs and demonstrates the application of POM-based materials for the electrochemical detection of drug molecules.

Template-directed assembly of giant cluster-based nanomaterials is an everlasting theme in cluster science. In this work, ethylenediamine tetramethylphosphonic acid [H 8 EDTPA = (POCH 2 (OH) 2 ) 4 C 2 H 4 N 2 ] and [B-α-SbW 9 O 33 ] 9- were, respectively, used as an organic template and an inorganic template to prepare an organophosphonic acid-regulating P V -Sb III -heteroatom-inserted polyoxotungstate aggregate [H 2 N(CH 3 ) 2 ] 5 Na 11 H 9 [CeW 4 O 10 (HEDTPA)SbW 15 O 50 ][B-α-SbW 9 O 33 ] 2 ·36H 2 O ( 1 ). Noteworthily, organophosphonic acid ligand not only works as an organic template leading to the assembly of a [HEDTPASbW 15 O 50 ] 14- building block but also further bridges the sandwich-type [CeW 4 O 10 (B-α-SbW 9 O 33 ) 2 ] 11- entity. To extend its potential application in electrochemical sensing properties, we prepared a three-dimensional 1 @EGO composite (EGO = reduced graphene oxide functionalized by ethylenediamine) with porous architecture and a prominent conducting ability. Furthermore, the 1 @EGO composite was explored as a modification material for glassy carbon electrodes to build a dual-signal readout electrochemical aptasensor for carcinogens, which shows much better detection performance for aflatoxin B1 compared with traditional single-signal biosensors.

Antimicrobial peptides (AMPs) are promising antibacterial agents often hindered by their undesired hemolytic activity. Inspired by gramicidin S (GS), a well-known cyclodecapeptide, we synthesized a panel of antibacterial cyclopeptidomimetics using β,γ-diamino acids (β,γ-DiAAs). We observed that peptidomimetic CP-2 displays a bactericidal activity similar to that of GS while possessing lower side-effects. Moreover, extensive studies revealed that CP-2 likely kills bacteria through membrane disruption. Altogether, CP-2 is a promising membrane-active antibiotic with therapeutic potential., (© 2020 Wiley-VCH GmbH.)

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 EC 50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC 0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).

Eighteen new Lycopodium alkaloids, lycosquarrines A-R ( 1 - 18 ), and eight known alkaloids were isolated from the aerial parts of Phlegmariurus squarrosus . Compounds 1 - 5 and 19 , identified from natural sources for the first time, are uncommon lycopodine-type alkaloids with β-oriented H-4. Pentacyclic 4 and 5 represent the first examples of 5,12- and 5,11-epoxy Lycopodium alkaloids, respectively, and an epoxide-opening cyclization reaction is suggested to be a key step in their biosynthesis. Compound 18 possesses the same carbon skeleton as carinatine A ( 22 ), which was previously reported as a unique Lycopodium alkaloid with a 5/6/6/6 ring system. X-ray crystallographic data analysis was used to determine the absolute configuration of 18 , leading to the establishment of the absolute configuration of 22 by comparison of the ECD spectra. An anti-acetylcholinesterase activity assay showed that 11 and 20 exhibited inhibitory activities with IC 50 values of 4.2 and 2.1 μM, respectively.

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.

A double-oxalate-bridging tetra-Gd 3+ containing divacant Lindqvist dimeric isopolytungtate Na 10 [Gd 2 (C 2 O 4 )(H 2 O) 4 (OH)W 4 O 16 ] 2 ·30H 2 O ( Gd 4 W 8 ) was obtained based on the reaction of Na 2 WO 4 ·2H 2 O, H 2 C 2 O 4 , and GdCl 3 in aqueous solution. Its dimeric polyoxoanion is established by two divacant Lindqvist [W 4 O 16 ] 8- segments connected by a rectangular tetra-nuclearity [Gd 4 (C 2 O 4 ) 2 (H 2 O) 8 (OH) 2 ] 6+ cluster. Notably, neighboring trinuclear [Na 3 O 4 (H 2 O) 11 ] 5- clusters are interconnected to construct a picturesque 1-D sinusoidal Na-O cluster chain. The most outstanding characteristic is that 1-D sinusoidal Na-O cluster chains combine [Gd 2 (C 2 O 4 )(H 2 O) 4 (OH)W 4 O 16 ] 2 10- polyoxoanions together, giving rise to an intriguing 3-D extended porous framework. The red emitter Eu 3+ ions and green emitter Tb 3+ ions are first codoped into Gd 4 W 8 to substitute Gd 3+ ions for the exploration of the energy transfer (ET) mechanism between Eu 3+ and Tb 3+ ions and the color-tunable PL property in the isopolytungtate system. The PL emission spectra and decay lifetime measurements of the Eu 3+ /Tb 3+ codoped Gd 4 W 8 system illustrate that under excitation at 370 nm, Tb 3+ ions can transfer energy to Eu 3+ ions. When the molar concentration of Tb 3+ ions is fixed at 0.9 and that of the Eu 3+ ions gradually increases from 0.01 to 0.08, the calculated ET efficiency (η ET ) from Tb 3+ to Eu 3+ ions increases from 7.9% for Gd 0.36 Tb 3.6 Eu 0.04 W 8 to 67.3% for Gd 0.08 Tb 3.6 Eu 0.32 W 8 . The energy transfer mechanism (Tb 3+ → Eu 3+ ) is a nonradiative dipole - dipole interaction. Furthermore, upon excitation at 370 nm, Eu 4 W 8 and Tb 4 W 8 show visible red- and green-emitting lights, respectively. When codoping trace amounts of Eu 3+ ions in Tb 4 W 8 , under excitation at 370 nm, Tb 3.92 Eu 0.08 W 8 displays near white-light emission.