LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral

Background:Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Recently,Laminin Gamma 2(LAMC2)has been shown to be abnormally expressed in OSCC;however,how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored.This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC.Methods:To explore the mechanism by which LAMC2 is highly expressed in OSCC,we used small interfering RNA(siRNA)to knock down LAMC2 to further observe the changes in the signaling pathway.Furthermore,we used cell proliferation assays,Transwell invasion assays,and wound-healing assays to observe the changes in OSCC proliferation,invasion,and metastasis.RFP-LC3 was used to detect the level of autophagy intensity.A cell line-derived xenograft(CDX)model was used to detect the effect of LAMC2 on tumor growth in vivo.Results:This study found that the level of autophagy was correlated with the biological behavior of OSCC.The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation,invasion,and metastasis via inhibiting the PI3K/AKT/mTOR pathway.Moreover,autophagy has a dual effect on OSCC,and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.Conclusions:LAMC2 interacts with autophagy to regulate OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration,invasion,and proliferation.

Higher alcohol synthesis over Cu-Fe composite oxides with high selectivity to C_(2+)OH

Cu-Fe composite oxides were prepared by co-precipitation method and tested for higher alcohol synthesis from syngas. The selectivity to C2＋OH and C6＋OH in alcohol distribution was very high while the methane product fraction in hydrocarbon distribution was rather low, demonstrating a promising potential in higher alcohols synthesis from syngas. The distribution of alcohols and hydrocarbons approximately obeyed Anderson-Schulz-Flory distribution with similar chain growth probability, indicating alcohols and hydrocarbons derived from the same intermediates. The effects of Cu/Fe molar ratio, reaction temperature and gas hourly space velocity （GHSV） on catalytic performance were studied in detail. The sample with a Cu/Fe molar ratio of 10/1 exhibited the best catalytic performance. Higher reaction temperature accelerated water-gas-shift reaction and led to lower total alcohols selectivity. GHSV showed great effect on catalytic performance and higher GHSV increased the total alcohol selectivity, indicating there existed visible dehydration reaction of alcohol into hydrocarbon.

Effect of the support on cobalt carbide catalysts for sustainable production of olefins from syngas

Co2C‐based catalysts with SiO2,γ‐Al2O3,and carbon nanotubes(CNTs)as support materials were prepared and evaluated for the Fischer‐Tropsch to olefin(FTO)reaction.The combination of catalytic performance and structure characterization indicates that the cobalt‐support interaction has a great influence on the Co2C morphology and catalytic performance.The CNT support facilitates the formation of a CoMn composite oxide during calcination,and Co2C nanoprisms were observed in the spent catalysts,resulting in a product distribution that greatly deviates from the classical Anderson‐Schulz‐Flory(ASF)distribution,where only 2.4 C%methane was generated.The Co3O4 phase for SiO2‐andγ‐Al2O3‐supported catalysts was observed in the calcined sample.After reduction,CoO,MnO,and low‐valence CoMn composite oxide were generated in theγ‐Al2O3‐supported sample,and both Co2C nanospheres and nanoprisms were identified in the corresponding spent catalyst.However,only separated phases of CoO and MnO were found in the reduced sample supported by SiO2,and Co2C nanospheres were detected in the spent catalyst without the evidence of any Co2C nanoprisms.The Co2C nanospheres led to a relatively high methane selectivity of 5.8 C%and 12.0 C%of theγ‐Al2O3‐and SiO2‐supported catalysts,respectively.These results suggest that a relatively weak cobalt‐support interaction is necessary for the formation of the CoMn composite oxide during calcination,which benefits the formation of Co2C nanoprisms with promising catalytic performance for the sustainable production of olefins via syngas.

重组人角质细胞生长因子-2工程菌的发酵条件研究

人角质细胞生长因子-2对烧伤、割伤等造成的皮肤损伤具有良好的促进修复和愈合功能,在临床、化妆品等方面具有极大的应用潜力。为此,人角质细胞生长因子-2的规模化生产和制备成为开发应用的一项重要前提。本文利用正交实验设计,在摇瓶条件下优化了培养基组分和pH等培养条件对大肠杆菌工程菌细胞生长和重组人角质细胞生长因子-2重组表达的影响。结果表明工程菌生长及表达的最优培养基组分和条件确定为葡萄糖10g/L、蛋白胨20g/L、酵母提取物10g/L、pH7.5及IPTG诱导时间5~6h。最后,在100升的BLBIO-15SIA发酵罐中以优化的发酵条件进行了3个独立批次的发酵实验,工程菌的生物量达到100g/L(DCW)、重组人角质细胞生长因子-2表达量占全细胞总蛋白约为30%。这些结果为进一步中试开发奠定了基础。

达芬奇机器人辅助Swenson-like巨结肠根治术

目的探讨达芬奇机器人辅助Swenson-like巨结肠根治术治疗8个月以内婴儿先天性常见型巨结肠的安全性、可行性、治疗效果和并发症。方法以广州医科大学附属妇女儿童医疗中心胃肠外科40例先天性常见型巨结肠患儿为研究对象,由同一外科医师实施手术,术式为三臂法机器人辅助Swenson-like巨结肠根治术。回顾性收集患儿术前、术中和术后临床资料进行分析,术后随访10~18个月。结果40例(男30例,女10例)先天性病患儿巨结肠(Hirschsprung disease,HSCR),平均手术月龄6±2个月,全部顺利完成手术,均无需中转开放及增加辅助孔,平均手术时间为152±17 min,其中机器人手术操作时间43±16 min,肛门部直肠分离时间6±2 min,术中出血量为2±1 ml,平均切除肠管长度25±7 cm,肠功能恢复时间为8±2 h,住院时间为6±1 d,术后疼痛评分为2±1分;40例术后6例(15%)需行肛门扩张;全部患儿均痊愈出院,围术期内均无手术并发症发生,术后主要并发症为肛周皮炎(7.5%)和小肠结肠炎(7.5%)。结论达芬奇机器人辅助Swenson-like巨结肠根治术适用于婴儿期先天性常见型巨结肠的治疗,近期效果良好。

4T1 cell membrane-derived biodegradable nanosystem for comprehensive interruption of cancer cell metabolism

Glycolysis inhibition can effectively block the energy supply and interrupt tumorigenesis in many types of cancers.However,when glycolysis is inhibited,tumor cells will break down glutamine as the raw material for the replenishment pathway to maintain the tricarboxylic acid cycle ensuring energy supply,therefore inducing ineffective interruption of metabolic.Herein,we designed glutamine transporter antagonist L-γ-glutamyl-p-nitroanilide(GPNA)loaded and 4T1 cancer cell membrane coated iridium oxide nanoparticles(IrO_(2)-GPNA@CCM)to realize a comprehensive inhibition of tumor energy supply which synergistically mediated by glycolysis and glutamine cycle.IrO_(2)NPs were used to catalyze the O_(2)generation by facilitating the decomposition of endogenous H_(2)O_(2)in tumor cells,which further downregulated the expression of HIF-1αand PI3K/pAKT to interrupt the generation of lactate.Meanwhile,the loaded GPNA was released under NIR irradiation to bind to alanine-serine-cysteine transporter(ASCT2)for glutamine uptake suppression,therefore realizing the comprehensive dysfunction of cell metabolism.Moreover,both in vitro and in vivo results convinced the thorough energy inhibition effect based on Ir O_(2)-GPNA@CCM NPs,which provided an inspiring strategy for future construction of tumor therapeutic regimen.

Rod-shape inorganic biomimetic mutual-reinforcing MnO2-Au nanozymes for catalysis-enhanced hypoxic tumor therapy

Biomimetic nanozymes possessing natural enzyme-mimetic activities have been extensively applied in nanocatalytic tumor therapy.However,engineering hybrid biomimetic nanozymes to achieve superior nanozyme activity remained to be an intractable challenge in hypoxic tumors.Herein,a rod-like biomimetic hybrid inorganic MnO2-Au nanozymes are developed,where MnO2 and ultrasmall Au nanoparticles(NPs)are successively deposited on the mesoporous silica nanorod to cooperatively improve the O2 content and thermal sensitivity of hypoxic solid tumors guided by multi-modal imaging.Under the catalyzing of MnO2,the intratumoral H2O2 is decomposed to greatly accelerate O2 generation,which could boost the curative effect of radiation therapy(RT)and further enhance the Au-catalyzed glucose oxidation.Mutually,the Au NPs can steadily and efficiently catalyze the oxidation of glucose in harsh tumor microenvironment,thus sensitizing tumor cells to thermal ablation for mild photothermal therapy and further promoting the catalytic efficiency of MnO2 with the self-supplied H2O2/H+.As a result,this mutual-reinforcing cycle can endow the nanoplatform with accelerated O2 generation,thus alleviating hypoxic environment and further boosting RT effect.Furthermore,acute glucose consuming can induce downregulation expression of heat shock protein(HSP),achieving starvation-promoted mild photothermal therapy.This synthesized hybrid nanozymes proves to be a versatile theranostic agent for nanocatalytic cancer therapy.

Distributed cache replacement method for geospatial data using spatiotemporal localitybased sequence

Specific features of tile access patterns can be applied in a cache replacement strategy to a limited distributed high-speed cache for the cloud-based networked geographic information services(NGISs),aiming to adapt to changes in the access distribution of hotspots.By taking advantage of the spatiotemporal locality,the sequential features in tile access patterns,and the cache reading performance in the burst mode,this article proposes a tile sequence replacement method,which involves structuring a Least Recently Used(LRU)stack into three portions for the different functions in cache replacement and deriving an expression for the temporal locality and popularity of the relevant tile to facilitate the replacement process.Based on the spatial characteristics of both the tiles and the cache burst mode with regard to reading data,the proposed method generates multiple tile sequences to reflect spatiotemporal locality in tile access patterns.Then,we measure the caching value by a technique based on a weighted-based method.This technique draws on the recent access popularity and low caching costs of tile sequences,with the aim of balancing the temporal and spatial localities in tile access.It ranks tile sequences in a replacement queue to adapt to the changes in accessed hotspots while reducing the replacement frequency.Experimental results show that the proposed method effectively improves the hit rate and utilization rate for a limited distributed cache while achieving satisfactory response performance and high throughput for users in an NGIS.Therefore,it can be adapted to handle numerous data access requests in NGISs in a cloud-based environment.