Metal-organic framework IRMOFs coated with a temperaturesensitive gel delivering norcantharidin to treat liver cancer

BACKGROUND Norcantharidin(NCTD)is suitable for the treatment of primary liver cancer,especially early and middle primary liver cancer.This compound can reduce tumors and improve immune function.However,the side effects of NCTD have limited its application.There is a marked need to reduce the side effects and increase the efficacy of NCTD.AIM To develop a nanomaterial carrier,NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel(NCTD-IRMOF-3-Gel),aiming to improve the anticancer activity of NCTD and reduce the drug dose.METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction.The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated.Cell cytotoxicity assays,flow cytometry,and apoptosis experiments in mouse hepatoma(Hepa1-6)cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm,and the particle size distribution was uniform.The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect.The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation,and the inhibition rate increased with increasing drug concentration.By flow cytometry,NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases,and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest.Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

Fast-speed self-powered PEDOT:PSS/α-Ga_(2)O_(3)nanorod array/FTO photodetector with solar-blind UV/visible dual-band photodetection

Theα-Ga2 O_(3)nanorod array is grown on FTO by hydrothermal and annealing processes.And a self-powered PEDOT:PSS/α-Ga_(2)O_(3)nanorod array/FTO(PGF)photodetector has been demonstrated by spin coating PEDOT:PSS on theα-Ga_(2)O_(3)nanorod array.Successfully,the PGF photodetector shows solar-blind UV/visible dual-band photodetection.Our device possesses comparable solar-blind UV responsivity(0.18 mA/W at 235 nm)and much faster response speed(0.102 s)than most of the reported self-poweredα-Ga_(2)O_(3)nanorod array solar-blind UV photodetectors.And it presents the featured and distinguished visible band photoresponse with a response speed of 0.136 s at 540 nm.The response time is also much faster than the other non-self-poweredβ-Ga_(2)O_(3)DUV/visible dual-band photodetectors due to the fast-speed separation of photogenerated carries by the built-in electric field in the depletion regions of PEDOT:PSS/α-Ga_(2)O_(3)heterojunction.The results herein may prove a promising way to realize fast-speed self-poweredα-Ga_(2)O_(3)photodetectors with solar-blind UV/visible dual-band photodetection by simple processes for the applications of multiple-target tracking,imaging,machine vision and communication.

Anti-inflammatory effect and antihepatoma mechanism of carrimycin

BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin(CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.AIM To obtain a deeper understanding of CAM, its distribution, metabolism and antiinflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.METHODS In this paper, the content of isovaleryl spiramycin Ⅲ was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4(IL-4) levels in the lung and kidney and especially the liver and spleen;moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets,such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.

Formation mechanism and wear behavior of gradient nanostructured Inconel 625 alloy

The formation mechanism and wear behavior of a gradient nanostructured(GNS) Inconel 625 alloy were investigated using SEM, TEM and ball-on-disc sliding wear tester. The results show that surface mechanical grinding treatment(SMGT) induced an approximately 800 μm-deep gradient microstructure, consisting of surface nano-grained,nano-laminated, nano-twined, and severely deformed layers, which resulted in a reduced gradient in micro-hardness from 6.95 GPa(topmost surface) to 2.77 GPa(coarse-grained matrix). The nano-grained layer resulted from the formation of high-density nano-twins and subsequent interaction between nano-twins and dislocations. The width and depth of the wear scar, wear loss volume, and wear rate of the SMGT-treated sample were smaller than those of untreated coarse-grained sample. Moreover, the wear mechanisms for both samples were mainly abrasive wear and adhesive wear, accompanied with mild oxidation wear. The notable wear resistance enhancement of the GNS Inconel 625 alloy was attributed to the high micro-hardness, high residual compressive stress, and high strain capacity of the GNS surface layer.

In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder

BACKGROUND Diabetes is a metabolic disease with a high complication rate.Diabetic foot ulcers(DFUs)seriously affect the quality of life of patients.A total of 15%-20%of diabetic patients develop DFUs,which heal with difficulty over a long time and can result in amputation and disability.Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases.Ruyi Jinhuang powder(RHP)is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice.AIM To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin(HE)staining.The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry(GC-MS),and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism.METHODS Sprague Dawley rats were injected with streptozotocin to establish the DFU model.HE staining was used to observe the wound tissue under an electron microscope.The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction,and then,GC-MS and ultra-performance liquid chromatography–MS were used to separately identify the chemical constituents.In addition,the"herb-component-target"link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information,and the molecular docking of important components and key targets was performed in Discovery Studio software.Cytoscape software was used to visualize and analyze the relationship between the chemical composition,targets and Traditional Chinese Medicine network.RESULTS RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells.A total of 89 chemical components were obtained by GC-MS.Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU,of which the important components were luteolin,trans caryophyllene,ar-turmerone,palmitic acid,methyl palmitate,gallic acid,demethoxycurcumin,berberine,and rheic acid.The key targets were posttranscriptional silencing,topoisomerase II alpha,muscarinic acetylcholine receptor M2,interleukin 6,tumor necrosis factor and retinoic X receptor alpha,and the key pathways were the phosphoinositide 3-kinase-protein kinase B signaling pathway,neuroactive ligand–receptor interactions,and the forkhead box O signaling pathway.CONCLUSION Our results indicated that RHP may play a role in the treatment of DFU through these target pathways by affecting insulin resistance,altering the nervous system and immune system,participating in inflammatory responses and regulating cell proliferation,differentiation and apoptosis through other specific mechanisms.

Effect of Temperature on Topological States of Circular DNA

The different topological states of circular double-stranded DNA can be defined by their linking number. The equilibrium distribution of linking number can be obtained by circularizing a linear DNA into a circle by ligase. Based on the recent experimental results that the DNA bending rigidity and twist rigidity strongly depend on temperature, the reduced bending rigidity can be approximated by g = （3.19 x10-19 - T. 4.14s10-22） erg. cm over the temperature interval （5 ~ 53） ~ C, and the temperature dependence of twist rigidity can be fitted by C （ T） = （4588.89 exp（-T/117.04）- 251.33） nm. The temperature dependence of the linking number distribution of circular DNAs can be predicted by using Monte Carlo simulation. The variance of linking number distribution on temperature is in accordance with the previous experimental results. Compared with the temperature dependence of bending rigidity, the temperature dependence of twist rigidity causes a noticeable fluctuation in linking number distribution and mainly contribute towards the variance change of linking number distribution of circular DNA. The variance of the writhe number and twist number in the equation （（ALk）21 = （（ATw）2） -b （（Wr）2） depends on the length of circular DNA. When the length of circular DNA is less than 230 nm, the variance of twist number （（ATw）2） is dominant over the variance of writhe number （（（wr）2））whereas for the condition that the length of the circular DNA is larger than 370 nm.