Deleted in liver cancer 1 suppresses the growth of prostate cancer cells through inhibiting Rho-associated protein kinase pathway

Objective:Deleted in liver cancer 1(DLC1)is a GTPase-activating protein that is reported as a suppressor in certain human cancers.However,the detailed biological function of DLC1 is still unclear in human prostate cancer(PCa).In the present study,we aimed to explore the function of DLC1 in PCa cells.Methods:Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line(LNCaP)using RNA interference and lentiviral vector transduction.The Cell Counting Kit-8 assay was performed to determine cell proliferation.The cell cycle was examined by performing a propidium iodide staining assay.Results:Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells.Moreover,DLC1 expression was negatively correlated with Rho-associated protein kinase(ROCK)expression in LNCaP cells.Importantly,this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo.Conclusion:Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.

Non-Cooperative Game of Coordinated Scheduling of Parallel Machine Production and Transportation in Shared Manufacturing

Given the challenges of manufacturing resource sharing and competition in the modern manufacturing industry,the coordinated scheduling problem of parallel machine production and transportation is investigated.The problem takes into account the coordination of production and transportation before production as well as the disparities in machine spatial position and performance.A non-cooperative game model is established,considering the competition and self-interest behavior of jobs from different customers for machine resources.The job from different customers is mapped to the players in the game model,the corresponding optional processing machine and location are mapped to the strategy set,and the makespan of the job is mapped to the payoff.Then the solution of the scheduling model is transformed into the Nash equilibrium of the non-cooperative game model.A Nash equilibrium solution algorithm based on the genetic algorithm(NEGA)is designed,and the effective solution of approximate Nash equilibrium for the game model is realized.The fitness function,single-point crossover operator,and mutation operator are derived from the non-cooperative game model’s characteristics and the definition of Nash equilibrium.Rules are also designed to avoid the generation of invalid offspring chromosomes.The effectiveness of the proposed algorithm is demonstrated through numerical experiments of various sizes.Compared with other algorithms such as heuristic algorithms(FCFS,SPT,and LPT),the simulated annealing algorithm(SA),and the particle swarm optimization algorithm(PSO),experimental results show that the proposed NE-GA algorithm has obvious performance advantages.

Coordinated Scheduling of Two-Agent Production and Transportation Based on Non-Cooperative Game

A two-agent production and transportation coordinated scheduling problem in a single-machine environment is suggested to compete for one machine from different downstream production links or various consumers.The jobs of two agents compete for the processing position on a machine,and after the pro-cessed,they compete for the transport position on a transport vehicle to be trans-ported to two agents.The two agents have different objective functions.The objective function of the first agent is the sum of the makespan and the total trans-portation time,whereas the objective function of the second agent is the sum of the total completion time and the total transportation time.Given the competition between two agents for machine resources and transportation resources,a non-cooperative game model with agents as game players is established.The job pro-cessing position and transportation position corresponding to the two agents are mapped as strategies,and the corresponding objective function is the utility func-tion.To solve the game model,an approximate Nash equilibrium solution algo-rithm based on an improved genetic algorithm(NE-IGA)is proposed.The genetic operation based on processing sequence and transportation sequence,as well as the fitness function based on Nash equilibrium definition,are designed based on the features of the two-agent production and transportation coordination scheduling problem.The effectiveness of the proposed algorithm is demonstrated through numerical experiments of various sizes.When compared to heuristic rules such as the Longest Processing Time first(LPT)and the Shortest Processing Time first(SPT),the objective function values of the two agents are reduced by 4.3%and 2.6% on average.

急性Standford A型主动脉夹层围手术期患者发生低血氧症的危险因素及其预测价值

目的探讨急性Stanford A型主动脉夹层患者手术前后低氧血症的相关危险因素及其预测价值。方法选取2014年9月—2017年10月河南省胸科医院收治的急性Stanford A型主动脉夹层患者128例。根据是否存在术前低氧血症将研究对象分为术前低氧血症组和术前非低氧血症组;根据是否存在术后低氧血症将患者分为术后低氧血症组和术后非低氧血症组。采用回顾性分析的方法,收集患者一般资料及术前动脉血氧饱和度、术后24 h内氧合指数及血红蛋白浓度等临床资料。分析患者的临床资料与低氧血症的关系。结果术前低氧血症组和术前非低氧血症组患者术后24 h内患者氧合指数、体重指数、慢性阻塞性肺疾病史及术前超敏C反应蛋白比较,差异有统计学意义(P<0.05)。术后低氧血症组和术后非低氧血症组患者慢性阻塞性肺疾病史、术中输血总量、术中体外循环转流时间及术后24 h内患者氧合指数比较,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,体重指数[Ol^R=1.306(95%CI:1.038,1.643),P=0.024]、慢性阻塞性肺疾病史[Ol^R=1.278(95%CI:1.024,1.594),P=0.043]及超敏C反应蛋白[Ol^R=1.257(95%CI:1.116,1.417),P=0.039]是影响术前低氧血症的独立危险因素,术中输血总量[Ol^R=1.322(95%CI:1.068,1.637),P=0.008]、术中体外循环转流时间[Ol^R=1.458(95%CI:1.208,1.760),P=0.029]是影响术后低氧血症的独立危险因素。结论超敏C反应蛋白对于术前低氧血症发生有预测价值,而术中输血量、术中体外循环转流时间对于术后低氧血症的发生具有较好的预测价值。

Chemokine ligand 20 enhances progression of hepatocellular carcinoma via epithelial-mesenchymal transition

AIM: To identify the mechanisms of chemokine ligand 20(CCL20)-induced hepatocellular carcinoma(HCC) metastasis and evaluate it as a prognostic marker. METHODS: Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels ofepithelial-mesenchymal transition(EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide(MTT) and Transwell assays. RESULTS: CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level(P = 0.043), tumor size(P = 0.000), tumor number(P = 0.008), vascular invasion(P = 0.014), and tumor differentiation(P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression(both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability(P < 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, β-catenin and vimentin, and decreased E-cadherin expression(P < 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression(13.33%, 4/30), and positively correlated with vimentin(90.0%, 27/30), β-catenin(96.67%, 29/30) and p-AKT(76.67%, 23/30) expression.CONCLUSION: CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/β-catenin pathways.

Combined Application of 5% Natamycin and 0.2% Fluconazole for the Treatment of Fungal Keratitis

Purpose: To observe the clinical efficacy of combined use of 5% natamycin and 0.2% fluconazole for the treatment of fungal keratitis. Methods:A total of 65 cases diagnosed with fungal keratitis by direct smear and/or fungus culture from January 2010 to January 2013 were enrolled in this study.The duration from the onset of symptoms to admission to our ophthalmic center ranged from 9 to 90 d (mean 29.5 ±19.1 d) in the severe group, which significantly differed from the 7 to 36 d (mean 16.6±7.1 d) in the non-severe group (P<0.01). All cases were divided into non-severe and severe groups based on the degree of corneal inflammation. All cases were treated with topical use of 5% natamycin and 0.2% fluconazole once per hour. The same clinical and examination protocols were adopted for both groups. Results:In the non-severe group,23 of the 24 patients (95.8%) were healed, and 1 (4.2%) showed treatment effica cy. In the severe group,12 of 41 patients (29.3%) were healed, 11(26.8%) showed clinical efficacy, and 18(43.9%) showed no efficacy. The patients between two groups significantly differed in terms of efficacy (P<0.01). Conclusion:Combined use of 5% natamycin and 0.2% fluconazole is efficacious in treating fungal keratitis, especially mild or moderate infections.

Engineered Biomimetic Platelet Membrane-Coated Nanoparticles Block Staphylococcus aureus Cytotoxicity and Protect Against Lethal Systemic Infection

Staphylococcus aureus(S.aureus)is a leading human pathogen capable of producing severe invasive infections such as bacteremia,sepsis,and endocarditis with high morbidity and mortality,exacerbated by the increasingly widespread antibiotic resistance exemplified by methicillin-resistant strains(MRSA).S.aureus pathogenesis is fueled by the secretion of toxins—such as the membrane-damaging pore-forming atoxin,which have diverse cellular targets including the epithelium,endothelium,leukocytes,and platelets.Here,we examine the use of human platelet membrane-coated nanoparticles(PNPs)as a biomimetic decoy strategy to neutralize S.aureus toxins and preserve host cell defense functions.The PNPs blocked platelet damage induced by S.aureus secreted toxins,thereby supporting platelet activation and bactericidal activity.Likewise,the PNPs blocked macrophage damage induced by S.aureus secreted toxins,thus supporting macrophage oxidative burst,nitric oxide production,and bactericidal activity,and diminishing MRSA-induced neutrophil extracellular trap release.In a mouse model of MRSA systemic infection,PNP administration reduced bacterial counts in the blood and protected against mortality.Taken together,the results from the present work provide a proof of principle of the therapeutic benefit of PNPs in toxin neutralization,cytoprotection,and increased host resistance to invasive S.aureus infection.

Identification of the keratin-associated protein 13-3 (KAP13-3) gene in sheep

Keratin-associated proteins (KAPs) are a major structural component of hair and wool fibres, and play a critical role in determining the properties of the fibre. To date, forty functional high sulphur KAP genes from fourteen families have been identified in humans, but only six functional high sulphur KAP genes have been identified in sheep. This led us to search for the ovine KAP13-3 gene, a gene encoding a high sulphur KAP. In this study, the notional KAP13- 3 gene (KRTAP13-3) was amplified using primers designed based on a reported bovine KRTAP13-3 se- quence. PCR-single stranded conformational polymorphism (PCR-SSCP) analysis was used to screen amplicons derived from the gene in one hundred and forty seven New Zealand Romney crossbred sheep. Five unique banding patterns were revealed. Either one PCR-SSCP pattern (homozygous) or a combination of two patterns (heterozygous) was observed for each sheep. Sequencing of PCR amplicons representtative of different SSCP patterns revealed five different DNA sequences. The sequences derived from the amplicons showed a low homology to other known ovine KRTAPs, but had a high homology with previous reported KRTAP13-n sequences from human and cattle, with the closest homology being with bovine KRTAP13-3, suggesting the sequences represent the ovine KRTAP13-3 locus. Among the five allele sequences, four nucleotide substitutions were identified within the coding region. Of these substitutions, three were non-synonymous and would result in amino acid changes (p.Arg79Cys, p.Arg81Gln and p.Tyr130His). This variation in the KAP13-3 gene may affect gene expression, the structure and assembly of the protein, and consequently influence wool traits, if KAP13-3 is of importance to wool fibre structure.

LASG Global AGCM with a Two-moment Cloud Microphysics Scheme:Energy Balance and Cloud Radiative Forcing Characteristics

Cloud dominates influence factors of atmospheric radiation, while aerosol–cloud interactions are of vital importance in its spatiotemporal distribution. In this study, a two-moment(mass and number) cloud microphysics scheme, which significantly improved the treatment of the coupled processes of aerosols and clouds, was incorporated into version 1.1 of the IAP/LASG global Finite-volume Atmospheric Model(FAMIL1.1). For illustrative purposes, the characteristics of the energy balance and cloud radiative forcing(CRF) in an AMIP-type simulation with prescribed aerosols were compared with those in observational/reanalysis data. Even within the constraints of the prescribed aerosol mass, the model simulated global mean energy balance at the top of the atmosphere(TOA) and at the Earth’s surface, as well as their seasonal variation, are in good agreement with the observational data. The maximum deviation terms lie in the surface downwelling longwave radiation and surface latent heat flux, which are 3.5 W m-2(1%) and 3 W m-2(3.5%), individually. The spatial correlations of the annual TOA net radiation flux and the net CRF between simulation and observation were around 0.97 and 0.90, respectively. A major weakness is that FAMIL1.1 predicts more liquid water content and less ice water content over most oceans. Detailed comparisons are presented for a number of regions, with a focus on the Asian monsoon region(AMR). The results indicate that FAMIL1.1 well reproduces the summer–winter contrast for both the geographical distribution of the longwave CRF and shortwave CRF over the AMR. Finally, the model bias and possible solutions, as well as further works to develop FAMIL1.1 are discussed.

现代中国监狱研究论纲(上)——基于传统向现代转换及其自主知识体系建构的视角

由清末狱制改良运动开启的中国现代监狱及其监狱学的建构之旅,始终处于进行时,包括在革命根据地监狱基础上建立和发展起来的社会主义中国监狱及其监狱学的建构。尤其随着20世纪80年代改革开放,直至现在进入中国特色社会主义新时代,现代性所带来的机遇与挑战急剧上升,“千年未有之变局”的困惑越发凸显,给中国监狱理论与实践以巨大冲击。但也正是对这种传统向现代转换及其自主知识体系建构的执着,中国式现代化才能成功。以此视角来研究中国监狱,沿着马克思主义社会实践进路,以问题为导向,现代中国自己的社会主义一般监狱学说、原理、方案即现代中国监狱理想图景呼之欲出。

Synthesis and characterization of star-branched polyamide 6 via anionic ring-opening polymerization with N,N',N''-trimesoyltricaprolactam as a multifunctional activator

Star-branched polyamide 6 was prepared via anionic ring-opening polymerization of ε-caprolactam in the presence of a simple benzene-centered trifunctional activator of N,N＇,N＂-trimesoyltricaprolactam. A high polymer yields of above 95% were achieved at 160 ℃ for 15 min utilizing ε-caprolactam magnesium bromide as a catalyst. Compared with its linear counterpart, the resultant star-branched polyamide 6 showed smaller relative viscosity （1.51 ）, decreased melting temperature （218 ℃） and lower crystallinity （24.2%）. The specific properties demonstrated the existence of a star-branched structure and provided potential advantages in engineering applications.

Recent Progress in Capturing and Neutralizing Inflammatory Cytokines

Inflammatory cytokines are key players in modulating immune responses to mount effective host defense.However,excessive production of inflammatory cytokines contributes to the destructive components responsible for various inflammatory disorders.As a result,treatment strategies have been developed to lower the cytokine levels or block their bioactivity.In particular,therapeutic agents that directly capture and neutralize cytokines have gained significant attention as they bypass the interactions with the host cells,and therefore,are less likely to induce immunogenic response and clearance.Among them,“monoplex”platforms such as cytokine-neutralizing antibodies(CNAs)are commonly designed to target a specific cytokine for neutralization.Meanwhile,to address the multiplexity of the cytokine targets in diseases,multiplex platforms such as glycosaminoglycan-containing biomaterials and cell-membrane-coated nanoparticles are emerging.Herein,we have reviewed the recent progress of these cytokine-neutralizing platforms(CNPs)and discussed their applications in treating inflammatory disorders.Overall,understanding the structure–function relationships underlying these CNPs would lead to the design of novel therapeutics toward effective management of inflammatory diseases.