An EHBP-1-SID-3-DYN-1 axis promotes membranous tubule fission during endocytic recycling.

The ACK family tyrosine kinase SID-3 is involved in the endocytic uptake of double-stranded RNA. Here we identified SID-3 as a previously unappreciated recycling regulator in the Caenorhabditis elegans intestine. The RAB-10 effector EHBP-1 is required for the endosomal localization of SID-3. Accordingly, animals with loss of SID-3 phenocopied the recycling defects observed in ehbp-1 and rab-10 single mutants. Moreover, we detected sequential protein interactions between EHBP-1, SID-3, NCK-1, and DYN-1. In the absence of SID-3, DYN-1 failed to localize at tubular recycling endosomes, and membrane tubules breaking away from endosomes were mostly absent, suggesting that SID-3 acts synergistically with the downstream DYN-1 to promote endosomal tubule fission. In agreement with these observations, overexpression of DYN-1 significantly increased recycling transport in SID-3-deficient cells. Finally, we noticed that loss of RAB-10 or EHBP-1 compromised feeding RNAi efficiency in multiple tissues, implicating basolateral recycling in the transport of RNA silencing signals. Taken together, our study demonstrated that in C. elegans intestinal epithelia, SID-3 acts downstream of EHBP-1 to direct fission of recycling endosomal tubules in concert with NCK-1 and DYN-1.

Targeted therapy for the treatment of gliomas with multifunctional orange emissive carbon dots.

As a nano-material, carbon dots have been extensively studied and applied in many ways. Herein, iron-doped orange emissive carbon dots (ICDs) were easily synthesized using the hydrothermal method and coupled with Trf and glucose oxidase (GOD) simply by virtue of the abundant functional groups on their surface. The resulting carbon dots were named IGTCDs. The obtained IGTCDs possessed targeting, therapeutic and imaging functions, achieving the enzymolysis of glucose, the decomposition of H2O2 and the release of reactive oxygen species (ROS) sequentially in gliomas as a multifunctional nano-catalyst, and achieving an efficient glioma targeted killing effect. On the basis of the ideal biocompatibility of the IGTCDs with a cell survival rate of over 85%, even at a high concentration (500 µg ml-1), the IGTCDs, which were coupled substances present within the organism, glucose oxidase and transferrins, showed an obvious inhibitory effect on the growth of tumor cells, and the survival rate of the C6 cells was only 28.10% at 300 µg ml-1. The highly efficient anti-tumor effect was further demonstrated in the treatment of mice suffering from glioma, and the tumor inhibition rate was increased to 56.21-98.32%. This safe and effective multifunctional tumor inhibitor could be conveniently synthesized in large quantities, verifying the feasibility of the anti-tumor therapy based on the tumor microenvironment (TME), creating a novel method for the application of carbon dots in tumor treatment and providing a novel, reasonable and effective method for the treatment of cancer and gliomas.

Construction of photo-induced zinc-doped carbon dots based on drug-resistant bactericides and their application for local treatment.

In this project, we propose a highly effective photosensitizer that breaks through drug-resistant bacterial infections with zinc-doped carbon dots. By passing through the membrane of drug-resistant bacteria, the photosensitizers produce ROS in bacteria under the action of blue light to directly kill bacteria, so as to realize the antibacterial local treatment of drug-resistant bacteria. The experiment firstly uses an efficient one-step hydrothermal method to prepare zinc-doped red-light CDs as photosensitizers, in which zinc metal was doped to improve the optical properties of the CDs. Then we try first to use EDTA as a second-step attenuator for preparing CDs to obtain photosensitizers with high-efficiency and low toxicity. In vitro cytotoxicity tests, bacterial effect tests, and in vivo animal experiments have also demonstrated that this antibacterial method has great potential for clinical translation, with a bactericidal efficiency of up to 90%. More notably, we used this antibacterial regimen seven times repeatedly to simulate the bacterial resistance process, with a bactericidal efficiency of up to 90% every time. The result indicated that S. aureus did not develop resistance to our method, showing that our method has the potential to break through drug-resistant bacterial infections as an alternative to antibiotic candidates.

In vivo study of a novel, safe, rapid, and targeted red carbon dot probe for recognition of tumors with high expression of folate enzyme.

Carbon dots (CDS) have been proved to be a type of ideal biological imaging probe. They have the advantages of spontaneous fluorescence, anti-photobleaching, good biocompatibility and easy surface decoration, and are receiving special attention from researchers. The early imaging diagnosis of tumors has always been a practical means of clinical diagnosis. Finding an efficient and low-toxicity tumor probe is the continuous goal of tumor clinical diagnosis and treatment. Therefore, this article uses the modifiable properties of the surface structure of carbon dots, and at the same time, uses the characteristics of tumors with high expression of folate receptors (FR) that can specifically take up folic acid (FA) to construct folic acid carbon dot conjugates (FA-CDs) to achieve targeted tumor uptake. Firstly, CCK8 toxicity tests proved that FA-DCCDs had good biocompatibility and were almost non-toxic. Further, confocal cell imaging experiments, microplate quantitative experiments and flow cytometry experiments proved that FA-CDs were selective and more easily absorbed by tumor cells with high expression of folate receptors, and bare carbon dots could be absorbed into cells without selectivity. Through in vivo experiments, the law of injection of bare CDs into the body was explored, which proved that they had no obvious accumulation and had high distribution in the liver and kidneys. FA-CDs was applied to the targeted imaging of a mouse tumor model in vivo for the first time, which proved again that the carbon point coupled with folic acid had selectivity for tumor cells with high expression of FR receptors, which provided a basis for tumor drug research and early clinical diagnosis of tumors.

Two-photon fluorescence and fluorescence imaging of two styryl heterocyclic dyes combined with DNA.

Two new styryl heterocyclic two-photon (TP) materials, 4-[4-(N-methyl)styrene]-imidazo [4,5-f][1,10] phenanthroline-benzene iodated salt (probe-1) and 4,4-[4-(N-methyl)styrene]-benzene iodated salt (probe-2) were successfully synthesized and studied as potential fluorescent probes of DNA detection. The linear and nonlinear photophysical properties of two compounds in different solvents were investigated. The absorption, one- and two-photon fluorescent spectra of the free dye and dye-DNA complex were also examined to evaluate their photophysical properties. The binding constants of dye-DNA were obtained according to Scatchard equation with good values. The results showed that two probes could be used as fluorescent DNA probes by two-photon excitation, and TP fluorescent properties of probe-1 are superior to that of probe-2. The fluorescent method date indicated that the mechanisms of dye-DNA complex interaction may be groove binding for probe-1 and electrostatic interaction for probe-2, respectively. The MTT assay experiments showed two probes are low toxicity. Moreover, the TP fluorescence imaging of DNA detection in living cells at 800 nm indicated that the ability to locate in cell nuclei of probe-1 is better than that of probe-2.

[Study on the geographic information system databases regarding the control of schistosomiasis in Zhongxiang, Hubei province, China].

OBJECTIVE: Using geographic information system (GIS) and the remote sensing techniques (RS), we developed a schistosomiasis database and geographic distribution map in Zhongxiang city,Hubei province in order to display and analyze the endemic situation longitudinally after the water conservancy project is completed. METHODS: Epidemiological data of schistosomiasis and the correlated climate and hydrology data for the last 30 years were collected and the relevant GIS databases were established under Artificial Neural Networks(ANN) and network training of Landsat TM images. RESULTS: GIS database of schistosomiasis in Zhongxiang city, Hubei province and its vicinity areas were developed including 1 maps regarding the epidemic situation of schistosomiasis. The areas of snail distributing were 4.4 hm2, 8.2 hm2, 24 hm2, 130.4 hm2, 8.13 hm2 and 7.53 hm2, respectively. CONCLUSION: The maps created by GIS database and RS techniques supported the complicated query on space and property, providing a new way in keeping,updating and analyzing available data. The techniques used should be able to provide evidence for the control of schistosomiasis to this water conservancy project.