Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.

The Enlightenment of ESL Courses at Conestoga College in Canada

Based on one-month observation of ESL courses in Canada, the paper analyzes some characteristics of ESL teaching in Canada, and then further provides enlightenment for our college English teaching in China.

Optimization of Extraction Method of Triterpenoids from Artemisia selengnesis Turcz

[Objectives]The research aimed to optimize the extraction method of triterpenoids from A. selengnesis. [Methods]The ultrasonic extraction of triterpenoids in A. selengnesis was optimized by single factor analysis( including infusion time,ethanol concentration,ultrasonic power,extraction time,and liquid-solid ratio) and response surface method. [Results]The optimum extracting process of triterpenoids was as follows: infusion time of 65 min,ethanol concentration of 80%,ultrasonic power of 275 W,extraction time of 30 min,and liquid-solid ratio of 34 m L/g. Under the optimized condition,the extraction content of triterpenoids reached( 18. 26 ± 0. 10) mg/g. [Conclusions] The optimized extraction had a good modal on practice in developing and utilization.

Degradation of proteins by PROTACs and other strategies

Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera(PROTAC)mechanism have demonstrated clinical efficacy.Recent progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex,extra-terminal domain-4-PROTAC-VonHippel-Lindau(BRD4-PROTAC-VHL),and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019.These discoveries strongly proved the value of the PROTAC strategy.In this review,we summarize recent meaningful research of PROTACs,including the molecular design and optimization strategy as well as clinical application of candidate molecules.We hope to provide useful insights for rational design of PROTACs.

Vitellaria paradoxa nutshells from seven sub-Saharan countries as potential herbal medicines for treating diabetes based on chemical compositions, HPLC fingerprints and bioactivity evaluation

The aim of the study was to determine the feasibility of the Vitellaria paradoxa nutshell as a new medicinal resource for treating diabetes. A total of forty-one compounds were identified by HPLC-DAD-Q-TOF-MS and phytochemical methods in V. paradoxa nutshell methanol extract. Based on HPLC fingerprints, four characteristic constituents were quantified and the origin of twenty-eight V. paradoxa nutshells from seven sub-Saharan countries was compared, which were classified into three groups with chemometric method. Twenty-eight samples contained high total phenolic content, and exhibited moderate-higher antioxidant activity and strong α-glucosidase inhibitory activity. Furthermore, all fractions and isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities, and α-glucosidase inhibitory action mechanism of four characteristic constituents including protocatechuic acid, 3, 5, 7-trihydroxycoumarin,(2 R, 3 R)-(+)-taxifolin and quercetin was investigated via molecular docking method, which were all stabilized by hydrogen bonds with α-glucosidase. The study provided an effective approach to waste utilization of V. paradoxa nutshell, which would help to resolve waste environmental pollution and provide a basis for developing potential herbal resource for treating diabetes.

Promoting performance of lithium-sulfur battery via in situ sulfur reduced graphite oxide coating

Activated graphene/sulfur structure sheathed in a flexible graphene layer is presented as the cathode material of lithium-sulfur battery.The surface coating graphite oxide sheets are reduced by a one-step in situ sulfur reduction method under vacuum at 600℃without any additional reductant.The high reduction degree of in situ sulfur reduced graphite oxide(RGO)coating layer will facilitate the rapid charge transfer at high current rate.The flexible encapsulated RGO structure will retard the diffusion of polysulfides and adjust the volume change of sulfur in cycling.As a result,the electrochemical evaluation of the RGO-activated graphene(AG)/S electrode demonstrates superior capacity,cycling and rate performance.The RGO-AG/S electrode with 60 wt%sulfur loading achieves a stable cyclability over 2000 galvanostatic charge/discharge process(capacity-fade rate of only 0.03%per cycle at1600 mA·g^(-1)).The average Coulombic efficiency remains at~96%with no electrolyte additives(such as LiNO_(3)).The outstanding property of RGO-AG/S electrode is attributed to the distinctive in situ sulfur RGOcoated hierarchical texture.

Systemic lupus erythematosus induced by adjuvants after metal-on-polyethylene total hip arthroplasty

To the Editor:Autoimmune/autoinflammatory syndrome induced by adjuvants(ASIA,Shoenfeld syndrome)has recently been described.Herein,we report a patient with immunoregulatory dysfunction and systemic lupus erythematosis(SLE)after total hip arthroplasty(THA).