人白细胞介素－2的两个部分拮抗剂

通过定点诱变技术得到６个生物活性剧烈下降的人白细胞介素－２（ＩＬ－２）突变体,其中两个突变体即１５Ｖａｌ－ＩＬ－２和１２６Ａｓｐ－ＩＬ－２可以在一定浓度范围内使ＩＬ－２的生物效应降低。在对高亲和力ＩＬ－２受体（ＩＬ－２Ｒ）的竞争抑制实验中,１５Ｖａｌ－ＩＬ－２和１２６Ａｓｐ－Ｉｌ－２又表现了一定的竞争能力。这些结果表明１５Ｖａｌ－ＩＬ－２和１２６Ａｓｐ－ＩＬ－２可部分拮抗天然ＩＬ－２的作用。结合Ｉ     

A robust six-miRNA prognostic signature for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) remains a major health problem worldwide. We aimed to identify a robust microRNA (miRNA)-based signature for predicting HNSCC prognosis. The miRNA expression profiles of HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. The TCGA HNSCC cohort was randomly divided into the discovery and validation cohort. A miRNA-based prognostic signature was built up based on TGCA discovery cohort, and then further validated. The downstream targets of prognostic miRNAs were subjected to functional enrichment analyses. The role of miR-1229-3p, a prognosis-related miRNA, in tumorigenesis of HNSCC was further evaluated. A total of 305 significantly differentially expressed miRNAs were found between HNSCC samples and normal tissues. A six-miRNA prognostic signature was constructed, which exhibited a strong association with overall survival (OS) in the TCGA discovery cohort. In addition, these findings were successfully confirmed in TCGA validation cohort and our own independent cohort. The miRNA-based signature was demonstrated as an independent prognostic indicator for HNSCC. A risk signature-based nomogram model was constructed and showed good performance for predicting the OS for HNSCC. The functional analyses revealed that the downstream targets of these prognostic miRNAs were closely linked to cancer progression. Mechanistically, in vitro analysis revealed that miR-1229-3p played a tumor promoting role in HNSCC. In conclusion, our study has developed a robust miRNA-based signature for predicting the prognosis of HNSCC with high accuracy, which will contribute to improve the therapeutic outcome.     

Efficient Plasmonic Au/CdSe Nanodumbbell for Photoelectrochemical Hydrogen Generation beyond Visible Region

In this communication, light harvesting and photoelectrochemical (PEC) hydrogen generation beyond the visible region are realized by an anisotropic plasmonic metal/semiconductor hybrid photocatalyst with precise control of their topology and heterointerface. Controlling the intended configuration of the photocatalytic semiconductor to anisotropic Au nanorods' plasmonic hot spots, through a water phase cation exchange strategy, the site‐selective overgrowth of a CdSe shell evolving from a core/shell to a nanodumbbell is realized successfully. Using this strategy, tip‐preferred efficient photoinduced electron/hole separation and plasmon enhancement can be realized. Thus, the PEC hydrogen generation activity of the Au/CdSe nanodumbbell is 45.29 µmol cm^?2 h^?1 (nearly 4 times than the core/shell structure) beyond vis (λ > 700 nm) illumination and exhibits a high faradic efficiency of 96% and excellent stability with a constant photocurrent for 5 days. Using surface photovoltage microscopy, it is further demonstrated that the efficient plasmonic hot charge spatial separation, which hot electrons can inject into CdSe semiconductors, leads to excellent performance in the Au/CdSe nanodumbbell.     

Exosomes from human-bone-marrow-derived mesenchymal stem cells protect against renal ischemia/reperfusion injury via transferring miR-199a-3p

Renal ischemia/reperfusion (I/R) injury is the main reason for acute kidney injury (AKI) and is closely related to high morbidity and mortality. In this study, we found that exosomes from human-bone-marrow-derived mesenchymal stem cells (hBMSC-Exos) play a protective role in hypoxia/reoxygenation (H/R) injury. hBMSC-Exos were enriched in miR-199a-3p, and hBMSC-Exo treatment increased the expression level of miR-199a-3p in renal cells. We further explored the function of miR-199a-3p on H/R injury. miR-199a-3p was knocked down in hBMSCs with a miR-199a-3p inhibitor. HK-2 cells cocultured with miR-199a-3p-knockdown hBMSCs were more susceptible to H/R injury and showed more apoptosis than those cocultured with hBMSCs or miR-199a-3p-overexpressing hBMSCs. Meanwhile, we found that HK-2 cells exposed to H/R treatment incubated with hBMSC-Exos decreased semaphorin 3A (Sema3A) and activated the protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK) pathways. However, HK-2 cells cocultured with miR-199a-3p-knockdown hBMSCs restored Sema3A expression and blocked the activation of the AKT and ERK pathways. Moreover, knocking down Sema3A could reactivate the AKT and ERK pathways suppressed by a miR-199a-3p inhibitor. In vivo, we injected hBMSC-Exos into mice suffering from I/R injury; this treatment induced functional recovery and histologic protection and reduced cleaved caspase-3 and Sema3A expression levels, as shown by immunohistochemistry. On the whole, this study demonstrated an antiapoptotic effect of hBMSC-Exos, which protected against I/R injury, via delivering miR-199a-3p to renal cells, downregulating Sema3A expression and thereby activating the AKT and ERK pathways. These findings reveal a novel mechanism of AKI treated with hBMSC-Exos and provide a therapeutic method for kidney diseases.     

Treatment and utilization of wastewater in the Beijing Zoo by an aquatic macrophyte system

This paper deals with a nutrient cycling experiment in the Beijing Zoo that uses macrophytes as the added link to make a purification system. The whole system consisted of macrophyte cultivating area and no macrophyte area. By making up the different functional groups of aquatic plants, a multilevel cycling network is formed, which has a rather high purification capability. During the experimental period, the water quality of the Waterfowl Lake and the Peony Pavilion Lake improved significantly, with total nitrogen and total phosphorus reductions of up to 58 and 38%, respectively. Other parameters also confirmed the good purification effect of this system. The economic and social benefits met the requirement of the original design.     

Synthesis, characterization, and in vitro evaluation of long-chain hyperbranched poly(ethylene glycol) as drug carrier

A series of novel long-chain hyperbranched poly(ethylene glycol)s (LHPEGs) with biodegradable connections were designed and synthesized in one pot through proton-transfer polymerization using PEG and commercial glycidyl methacrylate as monomers and potassium hydride as catalyst. The LHPEGs were hydrolyzed at neutral pH resulting in the decrease of molecular weights. In vitro evaluation demonstrated that LHPEGs were biocompatible and displayed negligible hemolytic activity. The efficient cellular uptake of LHPEGs was confirmed by flow cytometry and confocal laser scanning microscopy. Moreover, conjugation of a model hydrophobic anticancer drug methotrexate to LHPEGs inhibited the proliferation of a human cervical carcinoma Hela cell line. MTT assay indicated that the conjugated methotrexate dose required for 50% cellular growth inhibition against Hela cells was 20 μg/mL. By combining the advantages of long-chain hyperbranched structure and PEG, LHPEG provides a promising drug carrier for therapeutic fields.