Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications

Lanthanide (Ln)-doped upconversion nanoparticles (UCNPs) with appropriate surface modification can be used for a wide range of biomedical applications such as bio-detection, cancer therapy, bio-labeling, fluorescence imaging, magnetic resonance imaging and drug delivery. The upconversion phenomenon exhibited by Ln-doped UCNPs renders them tremendous advantages in biological applications over other types of fluorescent materials (e.g., organic dyes, fluorescent proteins, gold nanoparticles, quantum dots, and luminescent transition metal complexes) for: (i) enhanced tissue penetration depths achieved by near-infrared (NIR) excitation; (ii) improved stability against photobleaching, photoblinking and photochemical degradation; (iii) non-photodamaging to DNA/RNA due to lower excitation light energy; (iv) lower cytotoxicity; and (v) higher detection sensitivity. Ln-doped UCNPs are therefore attracting increasing attentions in recent years. In this review, we present recent advances in the synthesis of Ln-doped UCNPs and their surface modification, as well as their emerging applications in biomedicine. The future prospects of Ln-doped UCNPs for biomedical applications are also discussed.     

Neighborhood Regularized Logistic Matrix Factorization for Drug-Target Interaction Prediction

In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches.     

Interleukin-33/ST2 signaling promotes production of interleukin-6 and interleukin-8 in systemic inflammation in cigarette smoke-induced chronic obstructive pulmonary disease mice

Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice.     

甘露糖受体的结构特征和免疫功能

甘露糖受体可以通过其胞外3个结合区域使组分内化。它可以介导糖蛋白递呈和蛋白糖基化。甘露糖在维持内环境稳定方面发挥作用,同时还有识别病原体和抗原递呈功能。     

Heparan sulfate proteoglycans regulate autophagy in Drosophila

Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of signaling and molecular recognition at the cell surface and in the extracellular space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have profound effects on growth, patterning, and cell survival. The Drosophila neuromuscular junction provides a tractable model for understanding the activities of HSPGs at a synapse that displays developmental and activity-dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted the organization of a specialized postsynaptic membrane, the subsynaptic reticulum (SSR), and affected the number and morphology of mitochondria. We provide evidence that these changes result from a dysregulation of macroautophagy (hereafter referred to as autophagy). Cellular and molecular markers of autophagy are all consistent with an increase in the levels of autophagy in the absence of normal HS-chain biosynthesis and modification. HS production is also required for normal levels of autophagy in the fat body, the central energy storage and nutritional sensing organ in Drosophila. Genetic mosaic analysis indicates that HS-dependent regulation of autophagy occurs non-cell autonomously, consistent with HSPGs influencing this cellular process via signaling in the extracellular space. These findings demonstrate that HS biosynthesis has important regulatory effects on autophagy and that autophagy is critical for normal assembly of postsynaptic membrane specializations.     

Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD.     

Characterization of the transient species generated by the photoexcitation of C-phycocyanin from Spirulina platensis: a laser photolysis and pulse radiolysis study

Nanosecond laser flash photolysis and pulse radiolysis were used to generate and characterize the triplet state and cation radical of C-phycocyanin (C-PC) from Spirulina platensis. The transient absorption spectra of C-PC were measured from direct excitation and acetone sensitization in aqueous solution at room temperature by KrF (248 nm) laser flash photolysis. Laser-induced transient species have been characterized by the method of acetone sensitization and one-electron oxidation. In nitrous oxide-saturated phosphate buffer saline (pH = 7.0) of C-PC, the produced intermediates are assigned to the excited triplet state and the radical cation. Using acetone as photosensitizer, the C-PC excited triplet states produced via triplet-triplet energy transfer and the C-PC radical cation from electron transfer reaction were further confirmed. Furthermore, the corresponding kinetic parameters were determined. To our knowledge, the transient absorption spectra of C-PC have been reported for the first time.     

QF-PCR在染色体异常男性不育症诊断中的应用

为评估定量荧光PCR(QF-PCR)方法在男性不育遗传学诊断中的应用价值,文章对78例非梗阻性男性不育患者,采用精液常规检测精子情况,并检测患者性激素水平;采用QF-PCR方法对患者性染色体多态性STR位点及特异性位点进行检测;采用常规染色体G显带方法进行核型分析;PCR检测AZF微缺失。结果显示78例非梗阻性男性不育患者中发现无精子症患者18例,少精子症患者20例,总检出率为48.72%。采用QF-PCR方法检出3例47,XXY患者,2例46,XX(SRY+)性反转患者,1例AZFc区微缺失患者,与细胞培养染色体分析和AZF微缺失PCR检测结果相符。与传统方法相比,QF-PCR技术能更迅速、直接、可靠地检测到男性不育患者的染色体异常区域,及早发现染色体细微结构异常,有助于染色体异常造成的男性不育症的鉴别诊断。     

MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma

Abnormal angiogenesis is critically involved in tumor progression and metastasis including endometrial cancer and is regulated by microRNAs such as microRNA-101 (miR-101). We hypothesize that miR-101 expression is disrupted in endometrial cancer and modulation of miR-101 levels is sufficient to regulate tumor growth through angiogenesis. We examined the expression levels of miR-101 and factors involved in angiogenesis in the patients with endometrial cancer. We also overexpressed or inhibited miR-101 in RL-95-2 cells and examined their effects on cell toxicity and tumor growth. Finally, we determined if miR-101 regulated tumorigenesis through cyclooxygenase-2 (COX-2). We found that miR-101 levels were significantly reduced. Factors involved in angiogenesis included vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and aromatase (P450arom), which were increased in endometrial carcinoma. Modulation of miR-101 level was sufficient to affect tumor growth. Finally, we found that the effects of miR-101 inhibition on tumor growth were suppressed by COX-2 inhibition. Our results suggest that modulating miR-101 and COX-2 levels or their activity may be a potential therapeutic strategy for endometrial cancer.     

嗜水气单胞菌溶血素基因的克隆表达及其类毒素的免疫原性分析

根据嗜水气单胞菌溶血素保护性抗原基因序列(GenBank Accession No. AF539467)设计一对引物, 以嗜水气单胞菌河北分离株基因组为模板, 经PCR扩增得到hly基因。序列分析表明, 该基因产物大小为1485 bp, 经测序与GenBank报道的多个嗜水气单胞菌hly基因序列一致性高于99%。将得到的hly基因定向克隆到原核表达载体pET-28a中构建原核重组质粒pET-28a- hly, 转化大肠杆菌 BL21(DE3)中, 得到重组菌株BL21(DE3)(pET-28a-hly), 经IPTG诱导后, SDS-PAGE分析可见一条56 kD的特异条带。Western blotting分析结果显示表达的Hly蛋白能与抗体发生特异性结合,说明其具有较好的免疫原性。将表达的溶血素蛋白制成类毒素疫苗免疫小鼠后, 具有较高的保护效力, 表明该类毒素疫苗有望作为预防由嗜水气单胞菌引起疾病的基因工程类毒素疫苗。