Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal herbs.Conversely,the OA that impacts colon cancer(CC)cells and its underlying mechanisms remain poorly understood.Methods:The cytotoxic effect of OA alone or OA-5-Fluorouracil(5-FU)combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide(MTT).Then,the impact of OA on CC cell lines(LoVo and HT-29)proliferation and stemness were measured using colon formation and tumorsphere formation assays.Octamer-binding transcription factor 4(Oct4),Prominin-1(CD133),Nanog,and transcription factor SOX-2(SOX2)are cell stemness-related indicators whose expression was assessed usingfluorescence qPCR assay,Western blotting,and immunohistochemistry.The effect of OA on the proliferative potency of CC cells was evaluated using an in vivo model.Results:The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU.Moreover,OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers(CD133,Nanog,SOX2,and Oct4)expression levels both in vitro and in vivo,as well as by inactivating the activator of transcription 3(STAT3 signaling)and Janus kinase 2/signal transducer(JAK2).Conclusion:Thesefindings imply that oleanolic acid,both in vitro and in vivo,suppresses the JAK2/STAT3 pathway,which in turn reverses chemoresistance and decreases colon cancer cell stemness.Therefore,by reducing the recommended amount of 5-FU,this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.

Transmissive multifocal laser speckle contrast imaging through thick tissue

Laser speckle contrast imaging(LSCI)is a powerful tool for monitoring blood flow changes in tissue or vessels in vivo,but its applications are limited by shallow penetration depth under reflective imaging configuration.The traditional LSCI setup has been used in transmissive imaging for depth extension up to 2l_(t)–3l_(t)(l_(t)is the transport mean free path),but the blood flow estimation is biased due to the depth uncertainty in large depth of field(DOF)images.In this study,we propose a transmissive multifocal LSCI for depth-resolved blood flow in thick tissue,further extending the transmissive LSCI for tissue thickness up to 12lt.The limited-DOF imaging system is applied to the multifocal acquisition,and the depth of the vessel is estimated using a robust visibility parameter V_(r)in the coherent domain.The accuracy and linearity of depth estimation are tested by Monte Carlo simulations.Based on the proposed method,the model of contrast analysis resolving the depth information is established and verified in a phantom experiment.We demonstrated its effectiveness in acquiring depth-resolved vessel structures and flow dynamics in in vivo imaging of chick embryos.

RNA interference in insects:the link between antiviral defense and pest control

RNA interference(RNAi)is a form of gene silencing triggered by double-stranded RNA(dsRNA)that operates in all eukaryotic cells.RNAi has been widely investigated in insects to determine the underlying molecular mechanism,to investigate its role in systemic antiviral defense,and to develop strategies for pest control.When insect cells are infected by viruses,viral dsRNA signatures trigger a local RNAi response to block viral replication and generate virus-derived DNA that confers systemic immunity.RNAi-based insect pest control involves the application of exogenous dsRNA targeting genes essential for insect development or survival,but the efficacy of this approach has limited potency in many pests through a combination of rapid dsRNA degradation,inefficient dsRNA uptake/processing,and ineffective RNAi machinery.This could be addressed by dsRNA screening and evaluation,focusing on dsRNA design and off-target management,as well as dsRNA production and delivery.This review summarizes recent progress to determine the role of RNAi in antiviral defense and as a pest control strategy in insects,addressing gaps between our fundamental understanding of the RNAi mechanism and the exploitation of RNAi-based pest control strategies.

Synergistic Co-doping effect of CNTs and PVP in Na_(4)MnCr(PO_(4))3 cathode as a strategy for improving the electrochemical performance of SIBs

In order to solve the contradiction between the rapidly growing energy demand and the excessive exploitation of fossil fuels,it is urgent to research and develops more environmentally friendly and efficient energy storage technologies.Therefore,the development of high-performance cathode materials to enhance the energy density of SIB is currently one of the most important topics of scientific research.Advanced high-voltage and low-cost cathode material for SIBs,a composite of carbon-coated Na_(4)MnCr(PO_(4))_(3)(NASICON-type),polyvinylpyrrolidone(PVP),and modified carbon nanotubes(CNTs)is prepared by sol-gel and freeze-drying method.Due to the high conductivity of CNTs,the conductivity of the composite is significantly improved,and its initial capacity is increased to 114 mAh/g at 0.5 C and 96 mAh/g at 5 C(Mn^(2+)/Mn^(4+)conversion for voltage windows 1.4-4.3 V).Moreover,the multi-electrons transfer of Cr^(3+)/Cr^(4+) and Mn^(2+)/Mn^(4+) can provide a high capacity of 165 mAh/g at 0.1 C and 102 mAh/g at 5 C in the high voltage window of 1.4-4.6 V.Furthermore,PVP can effectively inhibit the Jahn-Teller effect caused by Mn ion,making the composite have more excellent high-rate performance and stability.In addition,GITT,EIS and CV curves were drawn to better reveal the excellent kinetic properties of Na_(4)MnCr(PO_(4))_(3)@C@PVP@CNT cathode,and the mechanism of its performance improvement is deeply studied and discussed.Accordingly,the co-doping of CNTs and PVP is a simple way to high conductivity and fast charging of cathode materials for SIBs.

SiOx/C-Ag nanosheets derived from Zintl phase CaSi_(2) via a facile redox reaction for high performance lithium storage

As one of the high-capacity anodes in lithium-ion batteries(LIBs),silicon oxide(SiOx)has attracted wide attention due to its high theoretical capacity,low cost,and proper working voltage.However,the huge volume change and the intrinsic poor conductivity of SiOx still hinder the practical applications.How to address the issues is the focus of current research.In this work,firstly,hydrogen passivated Si nanosheets(Si6H6)were prepared from Zintl phase CaSi2,then,two-dimensional Ag nanoparticle modified SiOVC nanocomposite was prepared via a facile complex redox reaction between SieH6 and AgN03-aniline complexing agent.In this design,aniline was served as carbon sources,and Si6H6could be transformed to SiOx by AgN03 in mild solution condition.The obtained Ag modified SiOVC(SiOx/C-Ag)electrode exhibited high specific capacity(550 mAh·g^(-1)at 0.6 A·g^(-1)),superior rate,and cycling performance when served as anode for LIBs.