Prostate cancer is a prevalent malignancy, often diagnosed at advanced stages and associated with poor prognosis. Genistein, a soybean isoflavone, has demonstrated antitumor effects against castration-resistant prostate cancer in vivo. Our results indicate that genistein effectively downregulates the expression of key enzymes involved in the de novo synthesis pathway, namely AKR1C3, SRD5A2, CYP11A1, and 3βHSD, thus blocking androgen synthesis in CRPC cells. Additionally, genistein inhibits the activation and nuclear translocation of the AR. Collectively, these findings support the potential of genistein as a therapeutic agent for CRPC, highlighting its role in both inhibiting androgen synthesis and disrupting AR signaling.

Background: Breast cancer is a leading cause of cancer-related mortality among women globally, with triple-negative breast cancer (TNBC) being particularly aggressive. Delphinidin (Dp), an anthocyanin monomer, has shown promising health benefits. Objective: This study investigates the effects of Dp on TNBC and aims to elucidate its specific mechanisms of action. Design: We utilized cell counting kit-8 (CCK-8) assays, colony formation assays, and scratch assays to evaluate the influence of Dp on the proliferation and migration of TNBC cells. Flow cytometry was employed to analyze programmed cell death-ligand 1 (PD-L1) and Cluster of Differentiation 69 expression, while Western blotting assessed the levels of PD-L1, Janus Kinase 2 (JAK2), Signal Transducer and Activator of Transcription 3 (STAT3), p-JAK2, p-STAT3, and exosomal marker proteins. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to measure concentrations of PD-L1, interferon-γ (IFN-γ), and tumor necrosis factor-β (TNF-β). Results: Dp effectively inhibited TNBC cell proliferation and migration, as evidenced by CCK-8, colony formation, and scratch assays. Flow cytometry and Western blot analysis indicated a reduction in PD-L1 expression in TNBC cells. Meanwhile, we successfully isolated TNBC cell-derived exosomes, with ELISA experiments showing a decrease in PD-L1 expression in these exosomes following Dp treatment. In a co-culture system with TNBC and Jurkat cells, Dp enhanced Cluster of Differentiation 69 expression and reactivated Jurkat cells, resulting in increased secretion of IFN-γ and TNF-β. Additionally, Dp significantly reduced the p-JAK2/JAK2 and p-STAT3/STAT3 ratios in TNBC cells. Conclusion: Dp may exert its anti-TNBC effects by downregulating PD-L1 expression in TNBC cells and exosomes through the JAK2/STAT3 signaling pathway, potentially restoring T cell activity and modifying the tumor microenvironment.

Pulmonary arterial hypertension (PAH) is a complex and devastating disease that the underlying cellular and molecular mechanisms are largely remains unknown. This study aimed to elucidate the key hub genes and pathways in PAH by bioinformatics analysis. In the current study, we performed WGCNA analysis to systematically identify the hub genes for PAH using transcriptome microarray data. From the Gene Expression Omnibus (GEO) database, one microarray dataset (GSE113439) was downloaded for this study. There were 26 samples in this data set, including 15 PHA samples and 11 normal controls. Based on weighted correlation network analysis, 11 modules were identified and the MEgreenyellow module showed a significantly positive correlation with PAH (r = 0.93, P = 1e−06). The genes in greenyellow module were mainly significantly enriched in mitophagy related pathways by KEGG analyses. Combined with the protein–protein interaction (PPI) and co-expression networks, ten hub genes were identified as candidate biomarkers for PAH in the greenyellow module, including CTNNB1, NIPBL, ROCK2, ROCK1, SCAF11, JAK1, BIRC6, KIF5B, PPP1R12A and XRN1. These hub genes might be potential targets for clinical therapy against PAH. The molecular mechanisms involved in these genes that affected the prognosis of PAH should be further validated through biological and basic studies.

Background Prostate cancer is the second leading cause of cancer-related death among males in America. The patients’ survival time is significantly reduced after prostate cancer develops into castration-resistant prostate cancer (CRPC). It has been reported that AKR1C3 is involved in this progression, and that its abnormal expression is directly correlated with the degree of CRPC malignancy. Genistein is one of the active components of soy isoflavones, and many studies have suggested that it has a better inhibitory effect on CRPC. Objective This study aimed to investigate the antitumor effect of genistein on CRPC and the potential mechanism of action. Design A xenograft tumor mouse model established with 22RV1 cells was divided into the experimental group and the control group, and the former was given 100 mg/kg.bw/day of genistein, with 22RV1, VCaP, and RWPE-1 cells cultured in a hormone-free serum environment and treated with different concentrations of genistein (0, 12.5, 25, 50, and 100 μmol/L) for 48 h. Molecular docking was used to elucidate the molecular interactions between genistein and AKR1C3. Results Genistein inhibits CRPC cell proliferation and in vivo tumorigenesis. The western blot analysis confirmed that the genistein significantly inhibited prostate-specific antigen production in a dose-dependent manner. In further results, AKR1C3 expression was decreased in both the xenograft tumor tissues and the CRPC cell lines following genistein gavage feeding compared to the control group, with the reduction becoming more obvious as the concentration of genistein was increased. When the genistein was combined with AKR1C3 small interfering ribonucleic acid and an AKR1C3 inhibitor (ASP-9521), the inhibitory effect on the AKR1C3 was more pronounced. In addition, the molecular docking results suggested that the genistein had a strong affinity with the AKR1C3, and that it could be a promising AKR1C3 inhibitor. Conclusion Genistein inhibits the progression of CRPC via the suppression of AKR1C3.

针对视频流图像的目标检测,基于帧间差分理论提出了一种实时多运动目标检测算法.根据视频图像在实时处理中的应用,基于FPGA硬件平台并行处理快与可编程的特性,在FPGA上实现算法,经过MATLAB环境算法验证,并在设计的FPGA视频图像处理系统进行实现.该系统主要由图像采集模块、图像缓存模块、图像处理模块及图像显示模块4部分组成,通过OV5640采集图像数据,再对数据进行差分、滤波、形态学等一系列算法处理,存入DDR3中,最后通过VGA进行显示.实验结果表明,该系统在一定测距范围内可稳定跟踪运动目标,可实时显示,多 目标检测识别率较高,能实时检测视频流图像中的多运动目标.

针对图像传输不稳定的问题,设计了一种基于FPGA的实时视频图像传输系统.采用用户数据报协议(UDP)作为通信协议,图像采集选用OV5640图像传感器,其内部集成了传感器和图像处理单元,更加方便稳定;图像处理选用的是Altera公司的EP4CE10F17C8N系列芯片.当摄像头采集到图像数据后暂存到DDR3 SDRAM中,FPGA再读取暂存的图像信息,对其预处理后将图像数据以以太网帧格式封装,利用板卡自带的千兆以太网芯片RTL8211F实现通过以太网将读取的信息发送给PC机,再通过上位机读取图像信息并实时显示,图像分辨率为1280×720.实验结果表明,该系统实现了实时视频图像传输,图像传输稳定,能有效、稳定地工作.

铁对维持视觉光转导过程有着重要作用.本文从铁的摄取、贮存、利用、输出等方面介绍视网膜铁代谢情况.但过度光照可导致视网膜铁代谢障碍,过量铁会导致有害的氧化应激.本文通过回顾近几年铁代谢紊乱与视网膜光损伤的最新研究进展发现,铁代谢蛋白表达异常引起的铁过载是光诱导视网膜变性的主要原因之一,铁过载与年龄相关性黄斑变性等视网膜疾病密切相关,去铁胺、去铁酮和地拉罗斯等铁螯合剂可以有效结合铁离子,维持细胞内铁代谢稳态,保护视网膜免受铁诱导的氧化损伤.本文从铁代谢角度丰富了视网膜光损伤疾病的病理机制内容,为视网膜光损伤的防护提供一新的选择和研究思路,并进一步指出铁螯合疗法对视网膜变性等眼科疾病的保护作用.

目的 研究黄酮类化合物对三阴性乳腺癌(TNBC)肿瘤微环境(TME)的改善作用.方法 查阅国内外相关文献并归纳总结,综述黄酮类化合物通过影响TME对TNBC产生的作用.结果 黄酮类化合物通过不同机制,使TNBC细胞与TME相互作用,阻滞细胞周期、抑制癌细胞侵袭、转移、新血管生成和诱导细胞凋亡.结论 黄酮类化合物在 TME中具有不同的抗 TNBC活性,将TME作为治疗靶点的进一步研究具有重要意义.

Gestational diabetes mellitus (GDM) , gestational hypertension, macrosomia, low birth weight, and premature delivery can directly affect short- and long-term maternal and infant health. Fasting plasma glucose can be obtained conveniently and rapidly during pregnancy. Numerous studies have verified that early- and mild-pregnancy fasting plasma glucose are associated with GDM, large for gestational age, and neonatal birth weight. But there is still some controversy about whether they associate with gestational hypertension and cesarean section. Furthermore, further studies are needed to examine their long-term influence on related diseases of pregnant women and their offspring in childhood and adulthood. This paper gives a summary of recent advances in the associations of early- and mid-pregnancy fasting plasma glucose with pregnancy outcome, providing a reference for future studies that profoundly explore relevant issues.

Aiming at the problems of poor uniqueness and high resource consumption of slice after the implementation of Arbiter physical unclonable function (Arbiter PUF) on field programmable gate array (FPGA), a new improved scheme of switch component structure is proposed. The switch component structure of the improved scheme adopts the parallel-connected mode to improve the uniqueness of the circuit, which avoids the cross-connected mode unable to achieve symmetrical layout on FPGA. At the same time, the improved scheme uses lookup tables to construct the structure of programmable delay line (PDL) with a multiplexer (MUX), which can reduce the internal resource consumption of slice while receiving the same 64-bit challenges. The improved scheme was tested on FPGA boards, the uniqueness and steadiness of different switch component schemes are compared and analyzed, and the feasibility of the improved scheme is verified. The results show that in the generation of Arbiter PUF, compared with the conventional scheme, the improved scheme reduces the resource consumption and improves the uniqueness by 22.2%; Compared with the MUX + MUX scheme, the improved scheme saves 50% of resource consumption while maintaining good uniqueness.

Delphinidin is a type of anthocyanin monomer with antioxidant, anti-inflammatory, and anti-tumor effects. However, the biological mechanisms underlying its anti-breast cancer activity have not been thoroughly studied. We further studied the effect of delphinidin on breast cancer cells through comprehensive network pharmacology, cellular and molecular experiments. We acquired the know therapeutic targets of delphinidin and obtained differentially expressed genes (DEGs) of breast cancer using RTCGA. We used topological analysis to screen out the 106 core targets of delphinium anti-breast cancer and performed functional analysis. These genes were mainly enriched in the pathways in cancer, Progesterone-mediated oocyte maturation and cell cycle. Then, by taking the intersection of the three analyzed data sets, important core targets (EGFR, TOP2A and PTGS2) were obtained and molecular-docking was performed to validate the result. Additionally, In Vitro experiments, MCF-7 and BT-474 cell proliferation was inhibited in a dose-dependent manner by delphinidin and the expressions of EGFR, TOP2A and PTGS were reduced. Moreover, delphinidin influenced cell cycle, the expressions of cdk1 and cyclin B1 were reduced. Furthermore, delphinidin induced apoptosis by activating the MAPK-Signaling pathway. Collectively, our findings suggested that delphinidin may offer effective approaches in breast cancer prevention and therapy.Supplemental data for this article is available online at http://dx.doi.org/10.1080/01635581.2021.2012582.

乳腺癌是全球常见的女性高发恶性肿瘤,目前居女性癌症发病率首位,也是女性癌症相关死亡的最主要病因[1].饮酒是乳腺癌已知的危险因素之一,近年随着中国经济水平的提高和人们生活方式的改变,中国女性的饮酒率已经达到12.2％[2].中国乳腺癌发病人数和死亡人数近年来也逐渐提高,中国每年新增乳腺癌患者26.9万例,新增死亡患者7万例[3].乳腺癌已然成为我国一项重大公共卫生事件,对乳腺癌的防控值得我们加以重视.本文就与乳腺癌发生发展相关的信号通路和乙醇通过这些信号通路发挥的促进作用作一综述.

In order to meet the high-speed and reliable data transmission requirements in high-speed signal acquisition and playback systems, a high-speed data interaction system based on FPGA-based PCIe interface and Gigabit Ethernet interface is designed. The system combines the high-speed data transmission capabilities of PCIe interface and flexible port expansion capabilities of Gigabit Ethernet. It uses FPGA as the core controller and builds control logic based on the UDP protocol to realize data interaction between PCIe and Gigabit Ethernet. This article mainly introduces PCIe communication block, Gigabit Ethernet communication block and the specific implementation plan of the data transmission process, and proposes a bidirectional dislocation cache transceiver mechanism based on ping-pong operation to ensure the reliability of data transmission and increase the data transmission rate. The test result shows that the data conversion result of this design is accurate and reliable, and has obvious advantages in the transmission rate, which is close to the ideal value of 950Mb/s, which can be applied to various high-speed data transmission occasions.

乳腺癌是女性癌症相关死亡中最常见的恶性肿瘤之一,其影响因素主要包括家族遗传史、膳食因素、社会因素、性激素水平等.其中,膳食因素中膳食脂肪的摄入在乳腺癌的发病过程中发挥着重要作用.不同膳食脂肪酸种类对乳腺癌的影响不同,同时脂肪酸代谢失调也是乳腺癌恶性转化的一个重要原因.本文综述了膳食脂肪的种类与特点,及其对乳腺癌的发生、发展及结局的影响,目的是阐述膳食脂肪对乳腺癌影响的可能机制及评价膳食脂肪在乳腺癌发病过程中的作用,指导人们从膳食途径上防治乳腺癌.

Diabetes mellitus is an important public health problem worldwide. Insulin deficiency caused by pancreatic β cell dysfunction is an important pathogenic factor of diabetes mellitus. This study evaluated whether empagliflozin (EMPA) protects the pancreas from diabetes mellitus-induced injury by downregulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/Gasdermin D (GSDMD) pyroptosis-related inflammasome pathway in vitro and in vivo. In vivo, animals were separated into blank control (control, C57/bl6j wild-type mice), diabetes model (db/db mice, BKS-Leprem2Cd479/Gpt mice), and db/db mice+EMPA (db/db+EMPA) groups. In vitro, pancreatic β cells were separated into low glucose (control), high glucose (HG), and HG+EMPA groups. The db/db+EMPA group were administered empagliflozin at 10 mg/(kg·day) by gavage for six months. Histological changes in the pancreatic tissues were observed by hematoxylin-eosin staining, and levels of the pyroptosis-related inflammatory factors NLPR3, caspase-1, and GSDMD were measured by immunohistochemistry and immunofluorescence staining methods. The Cell Counting Kit-8 assay was used to detect the effect of different concentrations of glucose and empagliflozin on the proliferation of mouse insulinoma islet β (β TC-6) cells. NLRP3/caspase-1/GSDMD expression was assessed by western blotting and immunofluorescent labeling in the β TC-6 cells. The results showed that empagliflozin reduced the pathological changes and inflammatory cell infiltration in the pancreatic tissues of db/db mice. Furthermore, empagliflozin not only reduced the expression levels of NLRP3/caspase-1/GSDMD in vitro, but also reduced their expression levels in vivo. In summary, our data suggested that empagliflozin protects the pancreatic tissues from diabetes mellitus-induced injury by downregulating the NLRP3/caspase-1/GSDMD pyroptosis-related inflammasome pathway.

One of the major reasons for the delayed wound healing in diabetes is the dysfunction of endothelial progenitor cells (EPCs) induced by hyperglycaemia. Improvement of EPC function may be a potential strategy for accelerating wound healing in diabetes. Procyanidin B2 (PCB2) is one of the major components of procyanidins, which exhibits a variety of potent pharmacological activities. However, the effects of PCB2 on EPC function and diabetic wound repair remain elusive. We evaluated the protective effects of PCB2 in EPCs with high glucose (HG) treatment and in a diabetic wound healing model. EPCs derived from human umbilical cord blood were treated with HG. The results showed that PCB2 significantly preserved the angiogenic function, survival and migration abilities of EPCs with HG treatment, and attenuated HG‐induced oxidative stress of EPCs by scavenging excessive reactive oxygen species (ROS). A mechanistic study found the protective role of PCB2 is dependent on activating nuclear factor erythroid 2‐related factor 2 (Nrf2). PCB2 increased the expression of Nrf2 and its downstream antioxidant genes to attenuate the oxidative stress induced by HG in EPCs, which were abolished by knockdown of Nrf2 expression. An in vivo study showed that intraperitoneal administration of PCB2 promoted wound healing and angiogenesis in diabetic mice, which was accompanied by a significant reduction in ROS level and an increase in circulating EPC number. Taken together, our results indicate that PCB2 treatment accelerates wound healing and increases angiogenesis in diabetic mice, which may be mediated by improving the mobilization and function of EPCs.

Adenoviral vectors are superior to plasmid vectors in their gene transport efficiency. The A subunit of the diphtheria toxin (DTA) gene is a popular suicide gene in cancer gene therapy. However, DTA is seldom used in adenoviral therapy due to its great toxicity. The toxicity of DTA is so great that even a single molecule of DTA is enough to kill one cell. To avoid this highly toxic effect on normal cells, DTA should be controlled by tumor-specific promoters. The survivin promoter is a widely used tumor-specific promoter. But genes driven by the survivin promoter show a low level of basal gene expression in non-cancer cells. DTA driven by the survivin promoter in adenoviral vectors may be highly toxic not only to cancer cells but also to normal cells. Therefore, DTA should be attenuated when it is used in adenoviral vectors driven by the survivin promoter. In this study, we compared the three kinds of recombinant adenoviruses that carry DTA or its attenuated forms (DTA176 and DTA197) in the treatment of human lung cancer. The results showed that in comparison with both DTA and DTA176, DTA197 is more suitable for adenoviral cancer therapy controlled by the survivin promoter. In addition, Adsur-DTA197 (DTA197 delivered by an adenoviral vector with the survivin promoter) sensitized human lung cancer cells to cisplatin both in vitro and in vivo. These results indicated that Adsur-DTA197 may be a potential chemosensitizer in cancer therapy.

扩频因其良好的保密性被广泛应用于各领域,在非协作条件下对扩频信号解扩则需要进行参数估计.针对直扩信号在低信噪比情况下采用传统倒谱法估计伪码周期性能陡然下降,以及传统倒谱中周期图谱法会造成频谱泄漏的问题,提出了一种基于延迟相乘与Marple算法的Yule-Walker自回归功率谱的倒谱法.通过MATLAB仿真分析,该方法能够提升伪码周期分量幅度,增强噪声抑制能力,避免频谱泄漏.

目的 探究飞燕草素(Delphinidin)对光诱导661W细胞铁过载的调控作用及机制.方法 将小鼠视网膜感光细胞661 W分为Control组、Light组、Light+铁螯合剂(DFP)组、Light+Delphinidin组、Control+Delphinidin组.以(2000±200)lx白色荧光持续照射661 W细胞48 h建立光损伤模型,采用CCK-8法筛选Delphinidin和DFP的最佳作用浓度.利用CCK-8法测定各组细胞活力,Hoechst-PI荧光观察各组细胞的细胞膜受损程度,流式细胞仪检测各组细胞铁含量及脂质过氧化物水平,Western blot检测各组细胞铁代谢相关蛋白表达水平.结果 CCK-8法检测结果显示,5μmol·L-1 Delphinidin和20μmol·L-1 DFP为最佳作用浓度.与Control组相比,Light组661 W细胞损伤严重,细胞活力下降为(56.69±1.48)％,铁含量增加,脂质过氧化物水平升高,差异均有统计学意义(均为P<0.05);与Light组相比,Light+DFP组和Light+Delphinidin组661W细胞损伤减轻,细胞活力分别升高为(62.85±0.46)％和(63.41±0.68)％,铁含量减少,脂质过氧化物水平降低,差异均有统计学意义(均为P<0.05).Western blot检测结果显示,与Control组相比,Light组细胞二价金属离子转运体1(DMT1)、转铁蛋白受体1(TfR1)、铁蛋白轻链(FTL)、铁蛋白重链1(FTH1)表达水平均升高,膜铁转运蛋白(Fpn)表达水平降低,差异均有统计学意义(均为P<0.05);与Light组相比,Light+DFP组和Light+Delphinidin组细胞TfR1、Fpn蛋白表达水平均升高,DMT1、FTL和FTH1蛋白表达水平均降低,差异均有统计学意义(均为P<0.05).结论 Delphinidin可通过调节铁代谢相关蛋白表达,缓解光诱导的661 W细胞铁过载,进而抑制脂质过氧化反应,减少视网膜氧化损伤.

目的 探讨飞燕草素对光化学损伤661W细胞的保护作用及其机制.方法 取661W细胞进行培养,根据预实验结果采用(2000±200)lux光照强度持续照射细胞48 h作为造模条件,采用5 μmol·L-1飞燕草素、3 mmol·L-1抗氧化剂N-乙酰-L-半胱氨酸(NAC)为最佳用药浓度.细胞分组如下:对照组,常规避光培养48 h;光照组,(2000±200)lux光照培养48 h;光照飞燕草素组,(2000±200)lux光照培养24 h,换含5 μmol.L-1飞燕草素的培养基继续光照培养24 h;避光飞燕草素组,避光培养24 h,换含5 μmol·L-1飞燕草素的培养基继续避光培养24 h;光照NAC组,(2000±200)lux光照培养24 h,换含3 mmol·L-1 NAC的培养基继续光照培养24 h.采用显微镜观察各组细胞状态、CCK-8 检测细胞生存率、DCFH-DA荧光探针染色检测细胞活性氧(ROS)水平、JC-10 染色检测线粒体膜电位、Annexin V-FITC/PI染色检测细胞凋亡率、Western blot检测氧化应激线粒体凋亡通路相关蛋白表达水平.结果 显微镜下可见,对照组细胞生长状态良好;光照组细胞皱缩卷曲,脱落细胞增加.CCK-8检测结果显示:与对照组相比,光照组细胞生存率均明显降低,差异有统计学意义(P＜0.05);避光飞燕草素组细胞生存率无明显变化(P＞0.05).与光照组相比,光照飞燕草素组、光照NA C组和避光飞燕草素组细胞生存率均明显回升,差异均有统计学意义(均为P＜0.05).与对照组相比,光照组ROS含量均明显上升,差异有统计学意义(P＜0.05);避光飞燕草素组RO S含量减少不明显,差异无统计学意义(P＞0.05).与光照组相比,光照飞燕草素组、光照NAC组和避光飞燕草素组ROS含量均明显下降,差异均有统计学意义(均为P＜0.05).与对照组相比,光照组线粒体膜电位均明显下降,差异有统计学意义(P＜0.05);避光飞燕草素组线粒体膜电位变化不明显,差异无统计学意义(P＞0.05).与光照组相比,光照飞燕草素组、光照NAC组和避光飞燕草素组线粒体膜电位明显上升,差异均有统计学意义(均为P＜0.05).与光照组相比,光照飞燕草素组、光照NAC组和避光飞燕草素组细胞凋亡率均明显降低,差异均有统计学意义(均为P＜0.05).与光照组相比,光照飞燕草素组、光照NAC组和避光飞燕草素组的iNOS、Bax、细胞色素C、Cleaved-Caspase-3蛋白表达均下调,Bcl-2蛋白表达均上调,Bcl-2/Bax值均明显上升,差异均有统计学意义(均为P＜0.05).结论 飞燕草素可通过调节氧化应激线粒体凋亡通路相关蛋白表达,对光化学损伤661W细胞产生保护作用.