Caffeic acid hinders the proliferation and migration through inhibition of IL-6 mediated JAK-STAT-3 signaling axis in human prostate cancer

Background:Caffeic acid(CA)is considered a promising phytochemical that has inhibited numerous cancer cell proliferation.Therefore,it is gaining increasing attention due to its safe and pharmacological applications.In this study,we investigated the role of CA in inhibiting the Interleukin-6(IL-6)/Janus kinase(JAK)/Signal transducer and activator of transcription-3(STAT-3)mediated suppression of the proliferation signaling in human prostate cancer cells.Materials and Methods:The role of CA in proliferation and colony formation abilities was studied using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay and colony formation assays.Tumour cell death and cell cycle arrest were identified usingflow cytometry techniques.CA treatment-associated protein expression of mitogen-activated protein kinase(MAPK)families,IL-6/JAK/STAT-3,proliferation,and apoptosis protein expressions in PC-3 and LNCaP cell lines were measured using Western blot investigation.Results:We have obtained that treatment with CA inhibits prostate cancer cells(PC-3 and LNCaP)proliferation and induces reactive oxygen species(ROS),cell cycle arrest,and apoptosis cell death in a concentration-dependent manner.Moreover,CA treatment alleviates the expression phosphorylated form of MAPK families,i.e.,extracellular signal-regulated kinase 1(ERK1),c-Jun N-terminal kinase(JNK),and p38 in PC-3 cells.IL-6 mediated JAK/STAT3 expressions regulate the proliferation and antiapoptosis that leads to prostate cancer metastasis and migration.Therefore,to mitigate the expression of IL-6/JAK/STAT-3 is considered an important target for the treatment of prostate cancer.In this study,we have observed that CA inhibits the expression of IL-6,JAK1,and phosphorylated STAT-3 in both PC-3 and LNCaP cells.Due to the inhibitory effect of IL-6/JAK/STAT-3,it resulted in decreased expression of cyclin-D1,cyclin-D2,and CDK1 in both PC-3 cells.In addition,CA induces apoptosis by enhancing the expression of Bax and caspase-3;and decreased expression of Bcl-2 in prostate cancer cells.Conclusions:Thus,CA might act as a therapeutical application against prostate cancer by targeting the IL-6/JAK/STAT3 signaling axis.

Wenjing Zhitong recipe exhibits potential anti-primary dysmenorrhea properties by inhibiting COX2 and PKC signaling pathway in rats induced by estradiol benzoate and oxytocin

Objective:To explore the effect and mechanism of action of the Wenjing Zhitong recipe(WZR)in primary dysmenorrhea(PD)treatment.Methods:Uterine contractions were induced by estradiol benzoate and oxytocin in a PD model and WZR was administrated.The rate of change in uterine contractility and the writhing test were used to evaluate the effects of WZR.The serum levels of prostaglandin F_(2a)(PGF_(2a))and prostaglandin E_2(PGE_2),and the activity of cyclooxygenase-2(COX2)were detected by enzyme-linked immunosorbent assay(ELISA).The changes in phosphor-phospholipase C(pPLC/PLC),phosphor-protein kinase C(pPKC/PKC),and connexin 43(CX43)expression were detected using immunohistochemistry and western blot.Results:WZR significantly reduced the rate of change in uterine contractility and writhing times in the PD model.WZR treatment inhibited the enzymatic activity of COX2 and reduced the levels of PGF_(2a),PGF_(2a)/PGE2and COX2 in the PD model.WZR also significantly reduced the expression of pPLC/PLC,pPKC/PKC and CX43.Targeting the inhibition of COX2 activity,caffeic acid and 1-acetyl-β-carboline were validated as the active ingredients in WZR responsible for reducing uterine contractions.Conclusion:WZR attenuated PD by inhibiting COX2 activity,downregulating PGF_(2a)/PGE_2 expression,and inhibiting the PKC signaling pathway.

Enhanced efficiency of the Sb_(2)Se_(3)thin-film solar cell by the anode passivation using an organic small molecular of TCTA

Antimony selenide(Sb_(2)Se_(3))is an emerging solar cell material.Here,we demonstrate that an organic small molecule of 4,4',4''-tris(carbazol-9-yl)-triphenylamine(TCTA)can efficiently passivate the anode interface of the Sb_(2)Se_(3)solar cell.We fabricated the device by the vacuum thermal evaporation,and took ITO/TCTA(3.0 nm)/Sb_(2)Se_(3)(50 nm)/C60(5.0 nm)/Alq3(3.0 nm)/Al as the device architecture,where Alq3 is the tris(8-hydroxyquinolinato)aluminum.By introducing a TCTA layer,the open-circuit voltage is raised from 0.36 to 0.42 V,and the power conversion efficiency is significantly improved from 3.2%to 4.3%.The TCTA layer not only inhibits the chemical reaction between the ITO and Sb_(2)Se_(3)during the annealing process but it also blocks the electron diffusion from Sb_(2)Se_(3)to ITO anode.The enhanced performance is mainly attributed to the suppression of the charge recombination at the anode interface.

Exploring the Mechanism of Blumea balsamifera(L.)DC in Preventing and Treating Alzheimer's Disease Based on HPLC-ESI-HRMS and Network Pharmacology

[Objectives]To expose the plausible mechanism of Blumea balsamifera(L.)DC.against Alzheimer s disease via network pharmacology and HPLC-ESI-HRMS technology.[Methods]To begin with,HPLC-ESI-HRMS was employed to identify the components of B.balsamifera.Secondly,the potential targets of the components were identified and predicted based on chemical similarity and online databases.Thirdly,by way of topological analysis of a component-disease target interaction network,the primary candidate targets and potential active components were identified.Lastly,molecular docking analysis was used to confirm the interaction between active components and therapeutic targets.[Results]According to the final results,HPLC-ESI-HRMS identified 70 components.Out of these,20 components were potentially biologically active,and most of them were sesquiterpenoids.According to the molecular docking results,the primary active components were appropriately coordinated with the core targets,indicating a high level of pharmacodynamic activity.Thus,the sesquiterpenes present in B.balsamifera are considered potential active ingredients having multi-target and multi-pathway effects for treating Alzheimer s disease.[Conclusions]This research will provide a scientific reference for the future pharmacological activity and clinical application of B.balsamifera.

“作为方法的儿童视角”:认识困境与实践规范

随着儿童视角研究日趋丰富,儿童视角被作为一种研究方法的反省和自觉认识相继出现。基于方法自觉意识的管窥,呈现出儿童视角的角色定位不准、研究起点模糊不清、研究价值取向不明等基本问题。故需从哲学层面回应“作为方法的儿童视角”的应然逻辑:本体论层面主张回归儿童的生命样态;认识论层面超越现有研究的窠臼;价值观层面关照儿童视角研究。以期使扩大认识的维度,进一步促进实践的规范,为儿童主体性地位的崛起奠定基础,丰富儿童研究的知识图景,激发实践中的行动智慧。

A Design of 220 kV Line Protection Action Deduction System Based on Numerical Simulation

Accurate conditions monitoring and early wrong action warnings of relay protection in the Smart Substation is the basic guarantee to realize the normal operation of primary and secondary system of the power grid.At present,the traditional operation and maintenance monitoring methods of relay protections have poor timeliness,while some automatic monitoring methods have insufficient early warning performance,and lack the online action deduction function independent of the actual device.In this paper,a design method of integrated action deduction system including protection logic reasoning and software and hardware operation condition is proposed.The system can receive real-time operation information of protection online,simulate different types of faults,and output the recording information of sub modules belongs to the action deduction system.It can realize the online monitoring of device faults such as deducing the correctness of setting values at a certain time in the future,giving the wrong action warnings and predicting the probability of them as well,which effectively improves the operation and maintenance efficiency of the secondary system in the intelligent substation.

Experimental study on reactivity and inorganic component transformation of activated fuels in a fluidized bed

The gasification and combustion of activated fuels produced from fluidized beds are beneficial for achieving clean and efficient coal utilization.In this study,a high-calcium coal was used for the activation process,carried out in a high-temperature vertical fluidized bed.The carbon and ash characteristics of activated fuels were studied.The reactivity of activated fuels was characterized using Raman test,and scanning electron microscopy coupled with energy-dispersive spectrometry(SEM-EDS).Inorganic components were characterized using X-ray diffraction(XRD)and X-ray fluorescence spectrometry(XRF).With the increase in temperature and equivalence ratio(ER),the graphitization degree of activated fuels decreases,and a higher proportion of active sites leads to,a better activation effect.The activation effect is optimized at the equivalence ratio of 0.45.As the temperature rises,the calcium-containing minerals in the raw coal are gradually transformed into anorthite(CaAl_(2)SiO_(7)),and the anhydrite(CaSO_(4))reacts with the reducing gas(CO)to produce oldhamite(CaS);Fe_(2)O_(3),as a fluxing agent,is prone to melting with silica-aluminates at high temperature.As the particle size of activated fuel increased,the relative enrichment index(REI)of heavy metals decreased.

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke

Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability,which gravely burdens the global economy.Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy.Even so,patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury.It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies.Regarding the pathogenesis,multiple pathological events trigger the activation of cell death pathways.Particular attention should be devoted to excitotoxicity,oxidative stress,and inflammatory responses.Thus,in this article,we first review the principal mechanisms underlying neuronal death mediated by these significant events,such as intrinsic and extrinsic apoptosis,ferroptosis,parthanatos,pyroptosis,necroptosis,and autophagic cell death.Then,we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.

Cancer-associated fibroblasts in breast cancer:Challenges and opportunities

The tumor microenvironment is proposed to contribute substantially to the progression of cancers,including breast cancer.Cancer-associated fibroblasts(CAFs)are the most abundant components of the tumor microenvironment.Studies have revealed that CAFs in breast cancer originate from several types of cells and promote breast cancer malignancy by secreting factors,generating exosomes,releasing nutrients,reshaping the extracellular matrix,and suppressing the function of immune cells.CAFs are also becoming therapeutic targets for breast cancer due to their specific distribution in tumors and their unique biomarkers.Agents interrupting the effect of CAFs on surrounding cells have been developed and applied in clinical trials.Here,we reviewed studies examining the heterogeneity of CAFs in breast cancer and expression patterns of CAF markers in different subtypes of breast cancer.We hope that summarizing CAFrelated studies from a historical perspective will help to accelerate the development of CAF-targeted therapeutic strategies for breast cancer.

A novel algorithm to identifying vehicle travel path in elevated road area based on GPS trajectory data

In recent years, the increasing development of traffic information collection technology based on floating car data has been recognized, which gives rise to the establishment of real-time traffic information dissemina- tion system in many cities. However, the recent massive construction of urban elevated roads hinders the processing of corresponding GPS data and further extraction of traffic information （e.g., identifying the real travel path）, as a result of the frequent transfer of vehicles between ground and elevated road travel. Consequently, an algorithm for identifying the travel road type （i.e., elevated or ground road） of vehicles is designed based on the vehicle traveling features, geometric and topological characteristics of the elevated road network, and a trajectory model proposed in the present study. To be specific, the proposed algorithm can detect the places where a vehicle enters, leaves or crosses under elevated roads. An experiment of 10 sample taxis in Shanghai, China was conducted, and the comparison of our results and results that are obtained from visual interpretation validates the proposed algo- rithm.