Trilobatin rescues fulminant hepatic failure by targeting COX2: Involvement of ROS/TLR4/NLRP3 signaling.

BACKGROUND: Fulminant hepatic failure (FHF) lacks efficient therapies notwithstanding increased comprehending of the inflammatory response and oxidative stress play crucial roles in the pathogenesis of this type of hepatic damage. Trilobatin (TLB), a naturally occurring food additive, is endowed with anti-inflammation and antioxidant properties. PURPOSE: In current study, we evaluated the effect of TLB on FHF with a mouse model with d-galactosamine/lipopolysaccharide (GalN/LPS)-induced FHF and LPS-stimulated Kupffer cells (KCs) injury. METHODS: Mice were randomly divided into seven groups: control group, TLB 40 mg/kg + control group, GalN/LPS group, TLB 10 mg/kg + GalN/LPS group, TLB 20 mg/kg + GalN/LPS group, TLB 40 mg/kg + GalN/LPS group, bifendate 150 mg/kg + GalN/LPS group. The mice were administered intragastrically TLB (10, 20 and 40 mg/kg) for 7 days (twice a day) prior to injection of GalN (700 mg/kg)/LPS (100 µg/kg). The KCs were pretreated with TLB (2.5, 5, 10 µM) for 2 h or its analogue (10 µM) or COX2 inhibitor (10 µM), and thereafter challenged by LPS (1 µg/ml) for 24 h. RESULTS: TLB effectively rescued GalN/LPS-induced FHF. Furthermore, TLB inhibited TLR 4/NLRP3/pyroptosis pathway, and caspase 3-dependent apoptosis pathway, along with reducing excessive cellular and mitochondrial ROS generation and enhancing mitochondrial biogenesis. Intriguingly, TLB directly bound to COX2 as reflected by transcriptomics, molecular docking technique and surface plasmon resonance assay. Furthermore, TLB failed to attenuate LPS-induced inflammation and oxidative stress in KCs in the absence of COX2. CONCLUSION: Our findings discover a novel pharmacological effect of TLB: protecting against FHF-induced pyroptosis and apoptosis through mediating ROS/TLR4/NLRP3 signaling pathway and reducing inflammation and oxidative stress. TLB may be a promising agent with outstanding safety profile to treat FHF.

2,3-Disubstituted Fluorene Scaffold for Efficient Green Phosphorescent Organic Light-Emitting Diodes.

Fluorene is a classic three-membered polycyclic aromatic hydrocarbon, and it has been widely used in optoelectronic devices. Here we explore a simple and efficient strategy for the derivatization at the 2- and 3- positions in fluorene unit. By introducing different types of substituents, we design two pairs of 2,3-disubstituted fluorene isomers and use them as host materials for phosphorescent organic light-emitting diodes (PHOLEDs). The green PHOLEDs hosted by these fluorene derivatives realize high external quantum efficiencies (EQE) over 20 % with low efficiency roll-off. Particularly, the devices hosted by 2TRz3TPA and 2TPA3TRz achieve nearly 24 % EQE and 104 lm W-1 power efficiency. These results clearly demonstrate that the 2,3-disubstituted fluorene platforms are potentially useful for constructing host materials.

Biomimetic Hybrid Nanozymes with Self-Supplied H+ and Accelerated O2 Generation for Enhanced Starvation and Photodynamic Therapy against Hypoxic Tumors.

Nanozymes as artificial enzymes that mimicked natural enzyme-like activities have received great attention in cancer diagnosis and therapy. Biomimetic nanozymes require more consideration regarding complicated tumor microenvironments to mimic biological enzymes, thus achieving superior nanozyme activity in vivo. Here we report a biomimetic hybrid nanozyme (named rMGB) which integrates natural enzyme glucose oxidase (GOx) with nanozyme manganese dioxide (MnO2) by mutual promotion for maximizing the enzymatic activity of MnO2 and GOx. Under hypoxia environment, we observed that MnO2 could react with endogenous H2O2 to produce O2 for enhancing the catalytic efficiency of GOx for starvation therapy. Meanwhile, we confirmed that glucose oxidation generated gluconic acid and further improved the catalytic efficiency of MnO2 subsequently. The biochemical reaction cycle, consisting of MnO2, O2, GOx, and H+, was triggered by the tumor microenvironment and accelerated each other so as to achieve self-supplied H+ and accelerate O2 generation, enhancing the starvation therapy, alleviating tumor hypoxia and accelerating the reactive oxygen species generation in photodynamic therapy. This biomimetic hybrid nanozyme would further facilitate the development of biological nanozymes for cancer treatment.

Chiral induction in the ionothermal synthesis of a 3D chiral heterometallic metal-organic framework constructed from achiral 1,4-naphthalenedicarboxylate.

A chiral heteometallic compound, [(EMIM)NaCu(1,4-ndc)2]n (1), constructed from the achiral 1,4-naphthalenedicarboxylate (1,4-ndc) ligand has been ionothermally synthesized and structurally and magnetically characterized. The chiral induction effect of the enantiopure 1-ethyl-3-methylimidazolium (EMIM) L-lactate additive in the ionothermal reaction is briefly discussed.

Poly[tetra-µ2-L-lactato-indium(III)sodium(I)].

The asymmetric unit of the title compound, [InNa(C(3)H(5)O(3))(4)](n), consists of one In(III) ion, one Na(I) ion and four crystallographically independent L-lactate monoanions. The coordination of the In(III) ion is composed of five carboxylate O and two hydroxy O atoms in a distorted pentagonal-bipyramidal coordination geometry. The Na(I) ion is six-coordinated by four carboxylate O atoms and two hydroxy O atoms from four L-lactate ligands in a distorted octahedral geometry. Each In(III) ion is coordinated by four surrounding L-lactate ligands to form an [In(L-lactate)(4)](-) unit, which is further linked by Na(I) ions through Na-O bonds to give a two-dimensional layered structure. Hydrogen bonds between the hydroxy groups and carboxylate O atoms are observed between neighbouring layers.