Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.

Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways

Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.

Phosphorylated protein chip combined with artificial intelligence tools for precise drug screening

We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.According to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions.In addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample.The Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors.

Glioblastoma multiforme:Diagnosis, treatment, and invasion

Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.

Effect of grape proanthocyanidins on tumor growth and angiogenesis in H22 liver cancer xenograft model

Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.

A Proton Nuclear Magnetic Resonance (¹H NMR) Investigation of NaCl-Induced Phase Separation of Acetonitrile-Water Mixtures

The microscopic properties of NaCl-induced phase separation of acetonitrile (ACN)-water mixtures have been studied by proton nuclear magnetic resonance (1H NMR). Acetonitrile-rich phase increases with increasing NaCl concentration (cNaCl) at xACN ≈ 0.25. 1H chemical shift of water for acetonitrile-rich phase rapidly decreases with decreasing NaCl mole concentration and that for water-rich phase quickly increases with increasing cNaCl. However, 1H chemical shift of acetonitrile has nothing to do with the molar concentration of NaCl, and it keeps relatively stable for all solutions (±0.002). These results reveal that Na+ and Cl- are rapidly hydrated by water, not by acetonitrile. The change of 1H chemical shift of water has shown that the number of hydrogen bond increases or hydrogen bond strengths with increasing NaCl molarity in mixtures. But hydrogen bond is broken or weaken with the temperature rising. 1H chemical shifts of pure water and the water in acetonitrile-rich phase have been investigated at 293 K, 298 K and 303 K. The hydration number of Na+ (6.05) in water-rich phase is determined by an empirical equation involving 1H chemical shift, temperature and NaCl molarity, which is in good agreement with the literatures.

“娓娓道来”抑或“语惊四座”:股权再融资需求与自愿性业绩预告

本文运用“娓娓道来”和“语惊四座”描述了公司自愿性业绩预告的两种典型方式,从传播学的“铺垫效果”和“期望违背”两个理论视角对业绩预告的动机进行了剖析,利用2010~2015年中国A股上市公司数据,检验了公司股权再融资与自愿性业绩预告之间的关系。结果发现,公司股权再融资促使公司进行了更高可能性和更高频次的自愿性业绩预告,而且投资机会和盈亏状态分别会放大和抑制上述关系。结果揭示,“娓娓道来”式的业绩预告是企业融资需求动机下的多数行为选择,这种具有“铺垫效果”的披露行为契合了传播学的理论认知。

Research progress on rare earth up-conversion and near-infrared Ⅱ luminescence in biological applications

Rare earth luminescence has attracted widespread attention for several decades, among which nearinfrared(NIR) light-related up-conversion luminescence and NIR-Ⅱ luminescence are widely used in the biomedical field. The NIR-related luminescence is widely studied due to the excellent performance, such as good biocompatibility, deep tissue penetration depth, low self-fluorescence and minimal light damage to organisms. In this review, we mainly introduce the mechanism for rare earth up-conversion luminescence, NIR-Ⅱ luminescence and conclude their advantages compared with traditional luminescence.These excellent priorities provide the basis for NIR-related luminescence bioimaging in vivo. Additionally,we hilglight the scheme for the sensitive detection of substances in organisms and various methods for biological therapy. In spite of the existing research, it is outlined that NIR-related luminescence has great potential to be applied in different aspects, expanding perspectives and future challenges of research in related fields. Based on the current scientific achievements, this review can provide reference for research in the areas mentioned above, expand the research direction and arouse a broad interest in different disciplines to pay attention to rare earth luminescence.

Exercise and nutrition benefit skeletal muscle:From influence factor and intervention strategy to molecular mechanism

Sarcopenia is a progressive systemic skeletal muscle disease induced by various physiological and pathological factors,including aging,malnutrition,denervation,and cardiovascular diseases,manifesting as the decline of skeletal muscle mass and function.Both exercise and nutrition produce beneficial effects on skeletal muscle growth and are viewed as feasible strategies to prevent sarcopenia.Mechanisms involve regulating blood flow,oxidative stress,inflammation,apoptosis,protein synthesis and degradation,and satellite cell activation through exerkines and gut microbiomes.In this review,we summarized and discussed the latest progress and future development of the above mechanisms for providing a theoretical basis and ideas for the prevention and treatment of sarcopenia.

Enhanced removal of estrogens from simulated wastewater by biochar supported nanoscale zero-valent iron:performance and mechanism

The intensification of estrogen non-point source pollution has drawn global attention due to their contribution to ecological environment problems worldwide,and it is critical to develop effective,economic and eco-friendly methods for reducing estrogens pollution.To address the agglomeration and oxidation of nano zero-valent iron(nZVI),biochar-nanoscale zero-valent iron composite(nZVI-biochar)could be a feasible choice for estrogens removal.This study summarized biochar and nZVI-biochar preparation,characterization,and unusual applications for estrone(E1),17β-estradiol(E2),and estriol(E3)removal.The properties of biochar and nZVI-biochar in characterization,effects of influencing factors on the removal efficiency,adsorption kinetics,isotherm and thermodynamics were investigated.The experiment results showed that nZVI-biochar exhibited the superior removal performance for estrogens pollutants compared to biochar.Based on the quasi-second-order model,estrogens adsorption kinetics were observed,which supported the mechanism that chemical and physical adsorption existed simultaneously on estrogens removal.The adsorption isotherm of estrogens could be well presented by the Freundlich model and thermodynamics studies explained that nZVI-biochar could spontaneously remove estrogens pollutants and the main mechanisms involvedπ-πinteraction,hydrophobic interaction,hydrogen bonding and degradation through ring rupture.The products analyzed by GC-MS showed that estrogens degradation was primarily attributed to the benzene ring broken,and Fe^(3+)promoted the production of free radicals,which further proved that nZVI-biochar had the excellent adsorption performances.Generally,nZVI-biochar could be employed as a potential material for removing estrogens from wastewater.

Multilevel regulation of N^(6)-methyladenosine RNA modifications: Implications in tumorigenesis and therapeutic opportunities

N^(6)-methyladenosine(m^(6)A)RNA modification is widely perceived as the most abundant and common modification in transcripts.This modification is dynamically regulated by specific m^(6)A“writers”,“erasers”and“readers”and is reportedly involved in the occurrence and development of many diseases.Since m^(6)A RNA modification was discovered in the 1970s,with the progress of relevant research technologies,an increasing number of functions of m^(6)A have been reported,and a preliminary understanding of m^(6)A has been obtained.In this review,we summarize the mechanisms through which m^(6)A RNA modification is regulated from the perspectives of expression,posttranslational modification and protein interaction.In addition,we also summarize how external and internal environmental factors affect m^(6)A RNA modification and its functions in tumors.The mechanisms through which m^(6)A methylases,m^(6)A demethylases and m^(6)A-binding proteins are regulated are complicated and have not been fully elucidated.Therefore,we hope to promote further research in this field by summarizing these mechanisms and look forward to the future application of m^(6)A in tumors.

基于红外隐身及多波段兼容隐身材料

随着探测系统的快速发展和探测精度的提高,隐身技术的需求日益迫切。由于传统的红外隐身材料面临着多途径目标探测的严峻挑战,因此开发既能满足红外隐身要求又能满足雷达隐身、可见光隐身、激光隐身要求的新型兼容隐身材料具有重要意义。红外隐身材料主要针对目标的红外辐射特征进行材料、结构设计,降低目标在背景中热红外辐射信号的突出性以及被热红外制导武器命中的概率。本综述概述了红外隐身及兼容材料的工作原理、制备方法及最新研究进展。首先介绍了最具有发展前景的红外隐身材料包括光子晶体、掺杂半导体、相变材料和纳米材料的结构特性、隐身机理和研究成果,重点关注了实现红外隐身的材料以及具体的隐身特性,讨论了红外兼容雷达、红外兼容可见光、红外兼容激光以及多波段兼容等材料的兼容隐身条件,并对其最新研究进展进行了系统的总结。最后,梳理了目前红外隐身材料以及各兼容材料所存在的不足及面临的困难,并对未来的研究方向进行了展望。

质子交换膜燃料电池金属双极板表面改性研究进展

双极板是质子交换膜燃料电池(PEMFC)的核心组件之一,其质量的好坏直接决定电池堆输出功率的大小和使用寿命的长短.金属双极板因具有优异的力学性能和导电性能,成为当前PEMFC双极板研究中关注的焦点.但是,纯金属双极板在质子交换膜燃料电池环境中易受腐蚀,金属板腐蚀后,释放出可能毒害催化剂的金属离子,或形成可增加界面接触电阻的致密氧化膜,影响燃料电池的输出功率和使用寿命,对金属双极板进行表面改性可以有效解决上述问题.本文首先概述了双极板的种类、优缺点;然后,系统总结了金属双极板表面改性涂层的制备方法、性能与最新研究进展,主要涉及金属基涂层、碳基涂层和导电聚合物涂层;最后分析了改性涂层国产商业化面临的挑战及国内外产业化现状,从成本和寿命出发展望了金属双极板表面改性的发展方向.

钠电池失效研究进展

钠电池因原料钠储量丰富、成本低廉、电极材料来源多样等优点,持续受到人们的关注.但是,在没有外部因素的影响下,钠电池正常运行时会发生一定概率的失效,以电化学性能变化与电池零部件发生破坏的失效模式表现出来,产生电池热失控、短路、起火等失效后果.本文依据失效模式与影响分析(FMEA)技术的理论失效链模型,分别对不同种类钠电池的正极、负极、电解质、隔膜、集流体和外壳等构件进行失效原因分析,基于钠电池构件概述了钠电池失效研究的进展,并提出了钠电池失效分析流程,最后对钠电池失效分析体系的构建进行了展望,旨在为钠电池的失效研究、安全使用与设计制造提供参考.

形态工程在生物基化学品生产中的应用进展

合成生物学和代谢工程是构建微生物细胞工厂、实现化学品绿色生物制造的重要方法,目前主要集中在微生物代谢网络的改造及调控上,很少考虑到微生物细胞特性的影响。形态工程通过改造微生物细胞形态相关蛋白,有目的地对微生物细胞形态及分裂方式进行合理调控,从而优化微生物细胞的特性,是降低生物炼制成本的一种新兴生物工程技术。文中首先介绍了与微生物细胞形态相关的各类蛋白,并重点总结了形态工程在生物基化学品合成方面的应用进展,包括调控细胞体积以提高胞内产物积累量、改善细胞通透性以促进胞外产物分泌、实现高密度发酵以降低生产成本、控制产物水解程度以提高产品性能。最后,提出了形态工程面临的主要问题并展望了其未来的发展趋势。

A review of rare-earth oxide films as high k dielectrics in MOS devices——Commemorating the 100th anniversary of the birth of Academician Guangxian Xu

Recently,rare-earth oxide films have attracted more and more attention as gate dielectrics in metaloxide-semiconductor(MOS)devices,showing the advantages of high dielectric constant(k value),large band gap(Eg)and outstanding physical and chemical stability in contact with silicon substrates.This paper reviews the recent development of rare earth oxide-based gate dielectric films.Aiming at the problem that k value of rare earth oxides(REOs)is generally inversely proportio nal to the band gap value,one of the biggest technical obstacles of high k films,we reviewed three strategies reported in recent papers,namely doping modification,nitriding treatment and multilayer composite,which can provide some insights for long-term development of MOS devices in integrated circuit(IC).

Epidermal growth factor receptor stabilizes programmed death ligand 1 by glycosylation in colorectal cancer with microstatellite instability status

Programmed death ligand-1(PD-L1)is involved in inhibiting of T lymphocyte proliferation,producing cytokine,cytolytic activity,and suppressing of the immune response.Genes with molecular alterations involved in DNA mismatch repair promote cancer initiation and tumor progression.Clinical studies show that colorectal cancer(CRC)patients harboring microsatellite instability(MSI)have a higher anti-programmed cell death protein 1/PD-L1 immunotherapy response ratio compared with microsatellite stable subgroup patients.The underlying mechanism has however remained unclear.Here,we found that compared with microsatellite stable samples,PD-L1 was glycosylated and highly expressed both in MSI CRC cell lines and tissue samples.Specifically,PD-L1 was Nglycosylated at its N35,N192,N200,and N219 sites,and the four glycosylation sites were all responsible for PD-L1 degradation.Additionally,non-glycosylated PD-L1 underwent rapid degradation compared with glycosylated PD-L1 through the 26S proteasome pathway.The faster degradation of the non-glycosylated PD-L1 was ascribed to its binding to glycogen synthase kinase 3b via ubiquitination.This degradation phenotype was,however,not observed for glycosylated PD-L1.Significantly,glycosylated PD-L1 was up-regulated by activated epidermal growth factor receptor in MSI CRC cells.Together,our results indicate that epidermal growth factor receptor stabilized PD-L1 via glycosylation in MSI CRC cells,uncovering a novel role of PD-L1 in MSI CRC immunosuppression and disease progression.The study was approved by the Clinical Ethics Review Committee at the Six Affiliated Hospital of Sun Yat-sen University,China(Approval No.2019ZSLYEC-005).