Preparation and Application of Microfibrillated Cellulose-modified Ground Calcium Carbonate

Microfibrillated cellulose(MFC) was first prepared by 2,2,6,6-tetramethylpiperidine-1-oxyl(TEMPO) oxidation pretreatment and mechanical grinding in the presence of a certain amount of ground calcium carbonate(GCC).The effects of GCC dosage and grinding concentration on the fibrillation were investigated.The obtained MFC was then added to the bulk GCC to form MFC-modified GCC fillers.The properties of MFCmodified GCC fillers were compared to those of the traditional GCC fillers.Results showed that the resulting fibrils became more uniform when the dosage of GCC was 10%~15% and the concentration of the suspension was 6.97%.Compared to traditional GCC,the average particle size of the MFCmodified GCC fillers was larger.Scanning electron microscopy images showed that GCC and MFC formed a bridge structure in the MFC-modified GCC fillers.In the process of papermaking,the MFC-modified GCC fillers decreased the drainage rate but increased the retention of fillers.The prepared papers filled with MFC-modified GCC fillers had higher tensile strength than those filled with traditional GCC fillers.

Recent progress and challenges in screening and characterization of UGT1A1 inhibitors

Uridine-diphosphate glucuronosyltransferase 1 A1(UGT1 A1) is an important conjugative enzyme in mammals that is responsible for the conjugation and detoxification of both endogenous and xenobiotic compounds. Strong inhibition of UGT1 A1 may trigger adverse drug/herb–drug interactions, or result in metabolic disorders of endobiotic metabolism. Therefore, both the US Food and Drug Administration(FDA)and the European Medicines Agency(EMA) have recommended assaying the inhibitory potential of drugs under development on the human UGT1 A1 prior to approval. This review focuses on the significance,progress and challenges in discovery and characterization of UGT1 A1 inhibitors. Recent advances in the development of UGT1 A1 probes and their application for screening UGT1 A1 inhibitors are summarized and discussed in this review for the first time. Furthermore, a long list of UGT1 A1 inhibitors, including information on their inhibition potency, inhibition mode, and affinity, has been prepared and analyzed. Challenges and future directions in this field are highlighted in the final section. The information and knowledge that are presented in this review provide guidance for rational use of drugs/herbs in order to avoid the occurrence of adverse effects via UGT1 A1 inhibition, as well as presenting methods for rapid screening and characterization of UGT1 A1 inhibitors and for facilitating investigations on UGT1 A1–ligand interactions.

Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1

UDP-glucuronosyltransferase 1A1(UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug–drug interactions(DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risks via UGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The IC_(50) values of icotinib and erlotinib against UGT1A1-mediated NCHN-O-glucuronidation in human liver microsomes(HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with the Kivalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risks via UGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration–time curve(AUC) of NCHN. These findings are helpful for the medicinal chemists todesign and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risks via UGT1A1 inhibition.

In situ monitoring of the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET

Microemulsions are promising drug delivery systems for the oral administration of poorly watersoluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized,especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering(SAXS) and fluorescence resonance energy transfer(FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl_2, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

Research on port ecological suitability evaluation index system and evaluation model

Along with the rapid development of port building, the negative impacts of port＇s construction and operation on the coastline ecosystem are also increasingly strong. Therefore, it＇s urgent to establish a scientific and complete system of port ecological suitability evaluation. This paper pointed out the characteristics of port ecological effects and the principles of selecting evaluation index, and used the ＂pressure-state-response （PSR）＂ model to analysis the various pressures on the environment caused by port construction and operation, and the system＇s response. On this basis, we constructed the port ecological suitability evaluation index. This model used the combination of qualitative and quantitative analytic hierarchy process, to meet the multi-level, multi-objective characteristics of evaluation index system. The evaluation index system and evaluation model can be used to analysis the ecological suitability of port projects comprehensively and have some guiding significance to the port ecological suitability evaluation.

D-cycloserin,a NMDA-agonist may be a treatment option for anti-NMDAR encephalitis

Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is caused by reversible neuron dysfunction associated an autoantibody-mediated decrease of NMDAR in the entire brain.A N-methyl-D-aspartate(NMDA)-agonist treatment for anti-NMDAR encephalitis might have a role considering its specific mechanism.The authors used D-cycloserine,a partial NMDA-agonist in a refractory case with prolonged intensive care unit duration.A 13-year-old female presented with headache,cognitive deterioration,generalized seizures,coma and hypoventilation with required mechanical ventilation.Anti-NMDAR antibodies were identified in cerebrospinal fluid and serum confirming anti-NMDAR encephalitis.The patient was refractory to first-line and second-line immunotherapy and removal of ovary teratoma.D-cycloserine was then administered and her symptoms improved gradually and significantly.This is the first reported case in which D-cycloserine was applied to this disease.D-cycloserine might be a potential option as specific treatment in anti-NMDAR encephalitis.