Abstract:Adoptive cell transfer (ACT) of tumor infiltrating or genetically engineered T cells is an effective immunotherapy in patients with metastatic cancer, but without additional therapies such as chemotherapy or radiotherapy, the effect was diminished and the tumor regression was also transient. To develop more effective adoptive T cell transfer therapy, central memory T cell (TCM) was expanded in vitro using IL-15 followed by transferring them into mice with B16-OVA melanoma. We found that TCM conferred a prolonged suppression of tumor growth whereas effector T cell (TEFF) cultured by IL-2 showed shorter suppression for tumor growth, which was correlated with sustained high number of tumor-specific CD8 T cells in spleen from IL-15 group. Interestingly, the expression of MHC-Ⅰ in the tumor from IL-15 group was upregulated which suggested that the cross presentation in IL-15 group was efficient. These data collectively suggested that IL-15 treated CD8 T cells elicit more effective anti-tumor response than IL-2 treated CD8 T cells owing to sustained tumor-specific CD8 T cells in spleen. Furthermore, expression of MHC-Ⅰwas upregulated in tumor in response to IL-15 mediated adoptive T cell transfer, suggesting that antigen presenting cells (APCs) were involved in adoptive T cell transfer. Our research may have implications for developing more effective tumor immunotherapy.

Abstract:Lipoproteomics is the proteomic analysis of lipoproteins. Recent lipoproteomics research revealed that lipoprotein-associated proteins have more functions rather than simply being structural molecules and parts of lipid metabolism. Firstly, we summarized the biological functions and categorization of lipoproteins, as well as methods for lipoprotein isolation and discovery proteomics that were recently applied in lipoproteomics. In addition, we analyzed the lipoproteome datasets of high density lipoproteins, low density lipoproteins and very low density lipoproteins. Lastly, we reviewed in the contributions of lipoproteomics in our understanding of coronary artery disease, diabetes and rheumatoid arthritis. Given the extensive description of lipoproteomics technical methods and the application for lipoproteome datasets, we believe that this review will be beneficial to researchers intent to contribute to the field of lipoproteomics.

Abstract:The deposition of senile plaques and neurofibrillary tangles in the brain are the prominent pathophysiology symptom of Alzheimer's disease (AD), in addition to diffuse brain atrophy. Several lines of evidence suggested a strong relationship between the degeneration of forebrain cholinergic neurons and pathogenesis of AD. AD is characterized by the disturbance of forebrain cholinergic system and by the dramatic decrease of acetylcholine (ACh), choline acetyltransferase, and a severe loss of cholinergic neurons. ACh is the only neurotransmitter released in the cholinergic synapses. Choline uptake via choline transporters is essential for ACh re-synthesis. Three types of transporters have been implicated in choline transporter family: high-affinity, Na⁺-dependent choline transporters (CHTs); intermediate-affinity, Na -independent choline transporter-like proteins (CTLs) and polyspecific organic cation transporters (OCTs) with low affinity for choline. It has been shown that abnormal choline transporters are involved in a number of neurodegenerative disorders, including AD. The article aims to summarize the physiological role of choline transporter in the cholinergic system and pathological alterations in AD, providing new insight into the therapeutic treatment of AD.

Abstract:Eukaryotic high-affinity glutamate transporters (also called excitatory amino acid transporters, EAATs) contain five isoforms, GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4 and EAAT5. Structural analysis reveal the membrane topology of glutamate transporters, the structural differences between the eukaryotic and prokaryotic glutamate transporters, and the binding sites for substrate and coupled ions during the transport cycle. Functional studies indicate that EAATs are involved in synaptic transmission, and EAATs play key roles in avoiding glutamate excitotoxicity. Besides, EAATs also participate in regulating learning, memory and motor behavior. In this review, combined with our previous work, we summarize the progress in the research of the structure and function of high-affinity glutamate transporters recently.

Abstract:Electromagnetic radiation is a kind of composite electromagnetic wave and human body contains a series of bioelectrical activities which are sensitive to the environmental electromagnetic wave. Therefore, the electromagnetic radiation may do harm to our human body. Although there are numbers of studies on biological effects induced by electromagnetic radiation, the mechanisms are still unclear. Recently, some researchers have revealed that nicotinamide adenine dinucleotide phosphate oxidase(NADPH oxidase, also known as the respiratory burst oxidase homologue) played an important role in biological effects induced by electromagnetic radiation. Electromagnetic radiation can activate NADPH oxidase complex in direct or indirect ways, then NADPH oxidase can transfer electrons of NADPH and the reactive oxygen species are formed or through some inflammatory factors, correlated matrix metalloproteinase in cells which may lead to inflammation, cell defense, tissue repair and the other processes of life. So, we review recent observations correlated with the mechanisms of it here.

Abstract:PIWI-interacting RNAs(piRNA) are endogenous small RNAs(sRNA), which play roles in resisting exogenous gene invasion and transposon mobility. More than 16 000 piRNAs are found in Caenorhabditis elegans, and the piRNA loci share a conserved upstream sequence. New piRNAs can be predicted based on its conserved upstream sequence. C. elegans are synchronized and small RNAs from wild type and prg-1 strains at L4 developmental period are sequenced through illumina technology. Basing on piRNA conserved uptream sequence, we find 967 new piRNAs expressed at L4 period, and the expressions of new piRNAs disappear in prg-1 mutant. Most of new piRNAs are mapped into two piRNA clusters of Chromosome Ⅳ, and have an overwhelming bias for a 5' uracil. Compared to the published co-immunoprecipitation data from adult worms, over 100 new piRNAs can interact with PRG-1. However, some non-21nt long sRNAs, which also share the same loci with piRNAs, are also found in wide type worms. These non-21nt long sRNA may be co-products of piRNA precursors. Together, these results indicate that our sRNA sequencing identified many new piRNAs in C. elegans.

Abstract:In order to investigate the role of inferior colliculus (IC) neurons in Pratt's roundleaf bats' Doppler-shift compensation (DSC)，we recorded the responses of IC neurons to the echoes by using simulated pulse-echo pairs of bats' DSC. According to the recovery rate of neural responses to echo signals at different frequency shifts of DSC, neurons were classified into two types: selective neurons (S neurons) whose recovery rate was more than 70% at some specific frequency shifts of DSC and non-selective neurons (NS neurons) whose recovery rate was less than 70% at any frequency shifts of DSC. Further analysis revealed that the proportion of S neurons of harmonic neurons (68%) was greater than the non-harmonic neurons (39%), and firing patterns of most harmonic S neurons was phasic (44.3%). Although the intensity-latency curves were similar in S and NS neurons，the harmonic neuron's best amplitude (BA) of the functions in S neurons (95.3 ± 14.0 dB SPL) were notably lower than NS neurons (104.1 ± 10.2 dB SPL) (P < 0.01) ，and there was a very significant difference in BA between the S neurons of harmonic and non-harmonic neurons (95.3 ± 14.0 vs 109.7 ± 7.9 dB SPL, P < 0.01). These results suggested that there is a clear division of labour in IC neurons processing and analyzing echo information during the DSC. S neurons which concentrated in the harmonics can effectively encode the echo information and avoid disturbances of other clutter information by increasing the recovery rate of responses to echo under specific frequency shifts of DSC. And the characteristics of firing patterns and intensity-latency functions of S neurons of harmonic neurons were different than other neurons，which met the need in precise acoustic imaging at complex environments.

Abstract:To research the role of the Dicer and miRNA in vascular smooth muscle cell (VSMC), the conditional gene targeting method, sequential biopsy pregnancy mice, histopathology, immunofluorescence, PCR, Western blot and Real time PCR were used to examine carefully the vasculopathy, the changes of Dicer, miRNAs and proteins of signal transduction pathway in conditional knock out the Dicer (Dicer cKO) embryos. Results indicated that three types of mice with different genotype that was wild type mice, heterozygotic type mice and homozygotic type mice were generated during breeding Dicer cKO mice. In them, wild type mice and heterozygotic mice were able to born, and no evident clinical abnormal showed when they were born, but homozygotic mice was not able to born and died in mother's abdomen. The development delay of Dicer cKO embryos was found in embryonic growth 12.5days (E12.5), the obvious vessels expansion, blood stasis and far-ranging diffuse hemorrhage in E14.5 and death in E15.5. The lesions of Dicer cKO embryos' vessel walls appeared as early as at E13.5, mainly showed irregular arrangement and lower proliferative cells; the pathologic changes of vessel walls thinning, collapse and irregular lumen appeared at E14.5. All destroyed structure of vessel wall, few cell proliferation, damaged barrier function of vessel wall, permeability enhancement and exudation of red blood cell occured at E15.5. The expression of VSMC marker genes, most detected miRNAs and phosphorylated signal transduction pathway proteins that were extracellular signal-regulated kinase and protein kinase showed distinct down regulation at E14.5. This experiment proves that the Dicer is necessary gene for vessel development. The Dicer regulates the expression of VSMC marker genes through commanding miRNA generation and maturation, so as to promote proliferation and differentiation of VSMC and guarantee the integrity of vessel wall structure.

Abstract:Our previous study prepared loading 10,11-methylenedioxy camptothecin (MD-CPT) hyaluronic acid nanocarriers (HANs) as a transdermal delivery system. The further study targets to value the cellular uptake and pharmacokinetic analysis of MD-CPT-loaded HA nanoemulsion as transdermal delivery carriers. A sustained-release dosage formulation was obtained with good skin permeability by optimizing the preparation conditions. The cellular-uptake of keloid fibroblast for nanoemulsion was observed with CLSM, drug eventually into the nucleus. Phagocytosis was time dependence, and different cell lines include HSF, HUVES, MCF-7 and KF were slightly different. Rhodanmine B labeled HANs performed desirable skin permeable capacity across stratum corneum, and the drug was transferred to the dermis by fluorescence microscopy. The optimized HANs formulation was verified with the highest effective drug permeability. The plasma concentration of MD-CPT was analyzed by HPLC, showed an almost 3.6 and 1.6 times increase T_1/2 respectively compared with intravenous and intramuscular injection; moreover, the curve of transdermal delivery was smooth continuous. In vivo imaging system intuitively reflected the distribution of transdermal drug in mice and the drug content of various organs/tissues. The rest of MD-CPT and HANs entered into the blood circulation, eventually excreted through metabolism without body burden. The longer drug residence at topical area with treatment could provide a continuous and controllable, extended efficacy, which was beneficial to superficial lesions therapy.