Wild pink bayberry free phenolic extract induces mitochondria-dependent apoptosis and G0/G1 cell cycle arrest through p38/MAPK and PI3K/Akt pathway in MDA-MB-231 cancer cells

Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.

Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.

Exploring the potential of the metaverse medical paradigm in drug addiction treatment: a preliminary discussion and future prospects

INTRODUCTION,Drug addiction is a chronic and recurrent encephalopathy characterised by impulsive behaviour,spiritual cravings,psychological distortion and physical damage!'According to the role of molecular biology mechanisms on the central nervous system,addictive substances can be classified as inhibitors(eg,opioids,etc),stimulants(eg,methamphetamine(MA),nicotine,cocaine,etc)and hallucinogens(eg,cannabis,etc).As published by the World Drug Report 2022,over284million individualsaged 15-64 worldwide have reportedly abused drugs in the past 12 months,emphasising the international challenge of effective detox treatment.

Connectome-based predictive modelling can predict follow-up craving after abstinence in individuals with opioid use disorders

Background Individual differences have been detected in individuals with opioid use disorders(OUD)in rehabilitation following protracted abstinence.Recent studies suggested that prediction models were effective for individual-level prognosis based on neuroimage data in substance use disorders(SUD).Aims This prospective cohort study aimed to assess neuroimaging biomarkers for individual response to protracted abstinence in opioid users using connectome-based predictive modelling(CPM).Methods One hundred and eight inpatients with OUD underwent structural and functional magnetic resonance imaging(fMRI)scans at baseline.The Heroin Craving Questionnaire(HCQ)was used to assess craving levels at baseline and at the 8-month follow-up of abstinence.CPM with leave-one-out cross-validation was used to identify baseline networks that could predict follow-up HCQ scores and changes in HCQ(HCQtolow V-up-HCQpa baseline).Then,the follow-up aseline predictive ability of identified networks was tested in a separate,heterogeneous sample of methamphetamine individuals who underwent MRI scanning before abstinence for SUD.Results CPM could predict craving changes induced by long-term abstinence,as shown by a significant correlation between predicted and actual HCQ fllow-up(r=0.417,p<0.001)and changes in HCQ(negative:r=0.334,p=0.002;positive:r=0.233,p=0.038).Identified craving-related prediction networks included the somato-motor network(SMN),salience network(SALN),default mode network(DMN),medial frontal network,visual network and auditory network.In addition,decreased connectivity of frontal-parietal network(FPN)-SMN,FPN-DMN and FPN-SALN and increased connectivity of subcortical network(SCN)-DMN,SCN-SALNandSCN-SMN were positively correlated with craving levels.Conclusions These findings highlight the potential applications of CPM to predict the craving level of individuals after protracted abstinence,as well as the generalisation ability;the identified brain networks might be the focus of innovative therapies in the future.

Amino acid transporters: Emerging roles in drug delivery for tumor-targeting therapy

Amino acid transporters,which play a vital role in transporting amino acids for the biosynthesis of mammalian cells,are highly expressed in types of tumors.Increasing studies have shown the feasibility of amino acid transporters as a component of tumortargeting therapy.In this review,we focus on tumor-related amino acid transporters and their potential use in tumor-targeting therapy.Firstly,the expression characteristics of amino acid transporters in cancer and their relationship with tumor growth are reviewed.Secondly,the recognition requirements are discussed,focusing on the“acidbase”properties,conformational isomerism and structural analogues.Finally,recent developments in amino acid transporter-targeting drug delivery strategies are highlighted,including prodrugs and nanocarriers,with special attention to the latest findings of molecular mechanisms and targeting efficiency of transporter-mediated endocytosis.We aim to offer related clues that might lead to valuable tumor-targeting strategies by the utilization of amino acid transporters.

角蛋白酶基因gm2886在密旋链霉菌ACT12中的表达及鉴定

通过生物信息学分析,在本实验室分离得到的1株羽毛高效降解菌微白黄链霉菌Fea-10基因组中发现基因gm2886(GenBank Accession Number:KY368946)可能编码一新的角蛋白酶,通过在该基因5'端和3'端分别连接红霉素抗性基因启动子(PermE)和组氨酸标签编码序列并构建在大肠杆菌-链霉菌穿梭质粒pSET152上,接合转入密旋链霉菌Streptomyces pactum ACT12,从而实现了异源表达,蛋白纯化后对其酶学性质进行了研究。实验结果表明,带有组氨酸标签编码序列的gm2886在密旋链霉菌ACT12中可以表达分泌得到1个大小约为36 kDa的蛋白。多种底物检测表明异源表达得到的重组蛋白GM2886-His6具有蛋白酶活性,可以降解水不溶性的天青角蛋白和羽毛粉;其最适温度和pH分别为50℃和pH 10.0。PMSF可抑制GM2886-His6的酶活,而EDTA不能,说明该酶为丝氨酸蛋白酶。本研究为从分子水平上解析羽毛高效降解菌Fea-10的活性机理,从而进一步开发其应用潜力提供了基础,同时可为该类蛋白酶的研究提供借鉴。

MRI扩散张量成像在评估短期戒断甲基苯丙胺成瘾者脑白质改变中的价值

目的探讨MRI扩散张量成像(DTI)在短期戒断甲基苯丙胺(MA)成瘾者脑白质改变中的价值。方法自2017年8月至2018年12月招募55例短期戒断MA成瘾者,男40例,女15例,年龄14~45(37.24±7.31)岁,均来自湖南省长沙市、株洲市和岳阳市强制戒毒所;同期招募52名健康对照者,男40名,女12名,年龄18~59(40.3±9.1)岁。收集受试者的DTI数据、人口统计学特征、成瘾一般信息及冲动性量表第十一版评分(BIS-11)。采用基于纤维束的空间统计分析技术(TBSS)比较两组间DTI指标的差异,然后将差异有统计学意义的指标与首次使用MA的年龄、使用MA时间、每天使用的剂量、BIS-11总分及3个子量表评分进行相关性分析。结果MA组和健康对照组BIS-11总分、BIS动机冲动及BIS注意冲动得分差异具有统计学意义(均P<0.05)。与对照组相比,MA组各向异性分数(FA)(0.58±0.02比0.56±0.02,0.77±0.02比0.75±0.04,0.79±0.04比0.76±0.06;均P<0.05)、轴向扩散系数(AD)(0.57±0.01比0.56±0.02,P=0.001)及平均扩散系数(MD)(0.66±0.02比0.65±0.02,0.52±0.07比0.51±0.06,均P<0.05)值均升高,而两组间径向扩散系数(RD)值差异无统计学意义(P>0.05)。FA值升高的白质区域位于胼胝体膝部及体部、双侧放射冠前部及左侧放射冠上部,AD值升高的区域位于胼胝体膝部、体部、压部,双侧内囊前肢、内囊后肢、放射冠前部,放射冠上部、放射冠后部、外囊及上纵束,MD值升高的区域主要位于右侧上纵束、内囊前肢和内囊后肢,且胼胝体体部的FA值与每天使用MA的剂量呈正相关(r=0.301,P=0.026)。结论短期戒断的MA成瘾者存在白质纤维水肿及损伤,并且胼胝体体部损伤程度与每天使用MA剂量呈正相关。

Glioma stem cells and neural stem cells respond differently to BMP4 signaling

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates,resistance to combined therapy,and dismal prognosis.Glioma stem cells(GSCs)are likely responsible for tumor progression,resistance to therapy,recurrence,and poor prognosis owing to their high self-renewal and tumorigenic potential.As a family member of BMP signaling,bone morphogenetic protein4(BMP4)has been reported to induce the differentiation of GSCs and neural stem cells(NSCs).However,the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear.In this study,we treated hGSCs and hNSCs with BMP4 and com-pared the phenotypic and transcriptional changes between these two cell types.Phenotypically,we found that the growth of hGSCs was greatly inhibited by BMP4,but the same treatment only increased the cell size of hNSCs.While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs,the profiles of differentially expressed genes were distinct between the two groups.A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture.Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation.Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

Video information recovery from EM leakage of computers based on storage oscilloscope

A hardware platform using broadband antenna,oscilloscope,and spectrum analyzer is designed to receive radio frequency(RF)signals from electromagnetic radiation leakage of computers in the office environment.The process of receiving and the processing techniques have also been given.Then,the software radio-based computing models and software algorithms are proposed to demodulate and decode the RF signals.An experimental result shows that the text information can be recovered from electromagnetic(EM)leakage wave of computer by this interception system.This architecture not only reduces the cost of the system’s hardware but also makes interception more flexible.The innovation points of this paper are recovering the video information in EM leakage wave of computers in an ordinary office environment based on public equipments and proposing the process of receiving processing techniques that only use the software radiobased computing models and software algorithms.

Tailoring component incorporation for homogenized perovskite solar cells

Deep-level traps at the buried interface of perovskite and energy mismatch problems between the perovskite layer and heterogeneous interfaces restrict the development of ideal homogenized films and efficient perovskite solar cells(PSCs)using the one-step spin-coating method.Here,we strategically employed sparingly soluble germanium iodide as a homogenized bulk in-situ reconstruction inducing material preferentially aggregated at the perovskite buried interface with gradient doping,markedly reducing deep-level traps and withstanding local lattice strain,while minimizing non-radiative recombination losses and enhancing the charge carrier lifetime over 9μs.Furthermore,this gradient doping assisted in modifying the band diagram at the buried interface into a desirable flattened alignment,substantially mitigating the energy loss of charge carriers within perovskite films and improving the carrier extraction equilibrium.As a result,the optimized device achieved a champion power conversion efficiency of 25.24% with a fill factor of up to 84.65%,and the unencapsulated device also demonstrated excellent light stability and humidity stability.This work provides a straightforward and reliable homogenization strategy of perovskite components for obtaining efficient and stable PSCs.