中国-东盟博览会旅游展暨MICE高峰论坛10月启幕

由国家旅游局、广西壮族自治区人民政府共同主办的2016中国-东盟博览会旅游展，将于10月20日-22日在中国广西桂林举办。

Dietary Nε-(carboxymethyl)lysine affects cardiac glucose metabolism and myocardial remodeling in mice

BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered associated with myocardial remodeling.Nε-(carboxymethyl)lysine(CML)is a representative foodborne toxic product,which can be ingested via daily diet.Therefore,there is a marked need to explore the effects of dietary CML on the myocardium.AIM To explore the effects of dietary CML(dCML)on the heart.METHODS C57 BL/6 mice were divided into a control group and a dCML group.The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk.Body weight and blood glucose were recorded every 4 wk.^(18)F-fluorodeoxyglucose(FDG)was used to trace the glucose uptake in mouse myocardium,followed by visualizing with micro-positron emission tomography(PET).Myocardial remodeling and glucose metabolism were also detected.In vitro,H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h.The effects of exogenous CML on glucose metabolism,collagen I expression,hypertrophy,and apoptosis of cardiomyocytes were analyzed.RESULTS Our results suggest that the levels of fasting blood glucose,fasting insulin,and serum CML were significantly increased after 20 wk of dCML.Micro-PET showed that ^(18)F-FDG accumulated more in the myocardium of the dCML group than in the control group.Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy.The indexes of myocardial fibrosis,apoptosis,and hypertrophy were also increased in the dCML group,whereas the activities of glucose metabolism-related pathways and citrate synthase(CS)were significantly inhibited.In cardiomyocytes,collagen I expression and cellular size were significantly increased after the addition of exogenous CML.CML significantly promoted cellular hypertrophy and apoptosis,while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.CONCLUSION This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.

Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice

AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Myricetin and Hesperidin Inhibit Cerebral Thrombogenesis and Atherogenesis in <i>Apoe^-/-</i>and <i>Ldlr^-/-</i>Mice

Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids, including hesperidin, naringin and nobiletin, inhibited thrombogenesis and hypertension in stroke prone spontaneously hypertensive rats (SHRSP) by protecting the endothelium from the adverse effects of free radical formation. We have now further investigated the protective effects of myricetin and hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E (apoE) and lowdensity lipoprotein receptor (LDLR) deficient (Apoe-/- and Ldlr-/- double knockout) mice. Three groups of mice were fed high fat diet alone and high fat diet mixed with myricetin (100 mg/kg/day and 200 mg/kg/day) or glucosyl hesperidin (G-hesperidin;250 mg/kg/day and 500 mg/kg/day) for 8 weeks. There were no differences in body weight related to administration of the flavonoids. Thrombotic tendency was assessed using a He-Ne laser technique in the murine cerebral pial vessels. In addition, atherogenesis was quantified histologically after dissection of the aorta from each mouse and staining with Oil Red O solution. The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p < 0.001). These findings demonstrated that daily intake of myricetin and hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids.

Distinct effect of potassium 2-(l-hydroxypentyl) - benzoate on hippocampal neurons, synapses and dystrophic axons in APP/PS1 mice

OBJECTIVE To study the protective effect of potassium 2-(l-hydroxypentyl)-benzoate(PHPB) on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice.METHODS Ten-month-old male APP/PS1 transgenic mice and age-matched wild-type mice were randomly divided into three groups:wild-type group(WT Con group,n=10),APP/PS1 group(Tg Con group,n=10) and PHPB treated APP/PS1 group(PHPB group,n=10).PHPB group received 30 mg · kg-1 PHPB by oral gavage once daily for 3 months.WT Con group and Tg Con group received the same volume of water.Three months later,mice were sacrificed for biochemical and pathological testing such as transmission electron microscopy,Golgi staining and Western boltting analysis.RESULTS Under the transmission electron microscope,most hippocampal neurons and subcel ular organel es in WT Con group exhibited normal morphology.However,the degenerative changes were observed in Tg Con group such as nuclear fragmentation,mitochondrial swelling,ribosomes detachment and autophagic vacuoles accumulation.The hippocampal synapses number and the thickness of postsynaptic density(PSD) were significantly decreased in Tg Con group compared with the WT Con group(P<0.05).After PHPB treatment,the degenerative changes in APP/PS1 mice were alleviated to some extent.The synapse number has been elevated significantly(P<0.05) and the PSD has been thickened as well.Golgi staining showed that the spine density of secondary and tertiary apical dendritic branches was significantly decreased in CA1 and DG areas of Tg Con group(P<0.05).Sholl analysis revealed a decrease of dendritic complexity in Tg Con group compared with WT Con group(P<0.05).These abnormalities were alleviated to some extent after PHPB treatment.Western blotting study showed that the protein levels of synaptic marker PSD-95 and synaptophysin were significantly decreased in the hippocampus of Tg Con group(P<0.05).A significant increase of PSD-95(P<0.05) and a slight increase of SYP were observed after the PHPB treatment.Besides,we found a significant increase in the ratio of LC3-Ⅱ/LC3-Ⅰ in Tg Con group compared with the WT Con group(P<0.01) and the relevant improvement after PHPB treatment(P<0.05),which showed the regulatory effect of PHPB on autophagy impairment.CONCLUSION PHPB showed protective effects on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice,which might help explain its role on cognitive improvement in Alzheimer disease treatment.

ESTABLISHMENT OF A MAMMARY CANCER CELL LINE Ca 761-86 AND ITS BIOLOGICAL CHARACTERISTICS IN INBRED 615 MICE

A cell line designated as Ca 761-86 has been established from the solid mouse mammary cancer (Ca 761) by suspension culture. It has been passaged for more than 212 generations. Moderate round cells were predominant and most of them were mononuclear. Some characteristics of malignant cells and A-type viral-like particles were observed by electron microscopy. The results of cytochemical studies (DNA, RNA, SDH, 5' AMPase, ACP etc.) were comparable to the ultramicroscopic results. It multiplied approximately 27.4 fold on day 5 with mitotic index reaching 1.8% on day 3. This cell line was a hyperdiploid with karyotype of 45 or 45, -2X, tril2, tri17, +M1-5. Cell agglutination was observed when treated with ConA (≥7 fig, ml). Spontaneous agglutination might also take place without adding any ConA. After 5×106 cells of Ca 761-86 suspension were transplanted into the normal inbred 615 mice by different ways (subcutan eous, intrafoot-pad or intraperitoneal), the transplan lability rate reached 100%. Spontaneous remission was never observed and its metastatic ability reserved. PPLO were not detected. Ca 761-86 may be of value for practical purposes.

S1-7 Inhibition of Phosphodiesterase-2 Activity in the Amygdala Produces Anxiolytic-Like Effects in Mice

Objective To explore the role of phosphodiesterase-2 activity in the amygdala produces anxiolytic-like effects in mice.Methods:Male ICR mice were implanted with guide cannula targeting the central nucleus of the amygdala bilaterally.Following recovery from surgery,mice were administered either Bay 60-7550 or lentiviral vector/microRNA targeted to PDE2.The effects of pharmacological inhibition were assessed 30 min post-treatment while those of PDE2 knockdown were assessed beginning one week after treatment with the lentiviral vector/microRNA.Behavioral effects were assessed in the elevated plus-maze and the tail-suspension tests;ODQ was used to assess cyclic GMP involvement.Cannula placement and viral vector localization were determined histologically via its GFP tag.Results:Administration of Bay 60-7550 into the central nucleus of the amygdala resulted in anxiolytic-and antidepressant-like effects on behavior of mice in the elevated plus-maze and tail-suspension test,respectively;these effects were blocked by pretreatment with ODQ.Viral vector/microRNA-induced knockdown of PDE2 resulted in similar effects on behavior in these tests,which also were blocked by ODQ.The treatment reduced PDE2 expression by approximately 80%.Conclusion:The present study does provide an additional line of support that reduced PDE2 activity,achieved in this case via lentiviral vector/microRNA-induced knockdown,is associated with such behavioral effects,resulting from treatment with NO donors,which also increase cyclic GMP signaling.

S4B-4 A Novel Allosteric Phosphodiesterase 4D Inhibitor BPN14770 Reverses Cognitive Impairment in Humanized PDE4D Mice

Classical inhibitors of PDE4 lack subtype selectivity due to exact amino acid sequence conservation of the catalytic site,and consequently,development of these drugs has stalled due to dose-limiting side effects of nausea and emesis.While use of subtype-selective inhibitors(i.e.,for PDE4A,B,or D)could overcome this issue,conservation of the catalytic region,to which classical inhibitors bind,limits this approach.The present study examined the effects of BPN14770,an allosteric inhibitor of PDE4D,which binds to a primate-specific,N-terminal region,conferring greater than 260-fold selectivity for PDE4D.BPN14770 was 100-fold more potent for improving memory and cognition in humanized PDE4D(hPDE4D)mice,which expressed the primate-specific binding sequence,compared to wild-type mice;meanwhile,it exhibited low potency in a mouse surrogate model for emesis.The behavioral and matching neurochemical data presented established a relationship between PDE4D target engagement and effects on cognition for BPN14770.Furthermore,BPN14770 reversed memory and cognitive deficits induced byβ-amyloid peptide 1-42(Aβ42)in Morris water maze,Y maze and novel object recognition tests in the humanized PDE4D mice.The morphological analyses suggested that the number of dendrites and the dendritic length in the CA1 of hippocampus were significantly increased after the Aβ42-treated hPDE4D mice were administered of BPN14770 for two weeks.The neurochemical and molecular biological assays suggested that neuroplasticity-related proteins and neurotrophic factor BDNF in the hippocampus of hPDE4D mice were significantly increased after the hPDE4D mice were treated with BPN14770.These findings suggest clinical potential for PDE4D selective inhibitors in disorders with cognitive deficits such as Alzheimer’s disease,which affects approximately 20 million people worldwide and nearly 5 million people in the United States.

T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer's disease mice

Alzheimer＇s disease is closely associated with disorders of neurogenesis in the brain, and growing evidence supports the involvement of immunological mechanisms in the development of the disease. However, at present, the role of T cells in neuronal regeneration in the brain is unknown. We injected amyloid-beta 1-42 peptide into the hippocampus of six BALB/c wild-type mice and six BALB/c-nude mice with T-cell immunodeficiency to establish an animal model of Alzhei- mer＇s disease. A further six mice of each genotype were injected with same volume of normal saline. Immunohistochemistry revealed that the number of regenerated neural progenitor cells in the hippocampus of BALB/c wild-type mice was significantly higher than that in BALB/c-nude mice. Quantitative fluorescence PCR assay showed that the expression levels of peripheral T cell-associated cytokines （interleukin-2, interferon-y） and hippocampal microglia-related cyto- kines （interleukin-113, tumor necrosis factor-a） correlated with the number of regenerated neural progenitor cells in the hippocampus. These results indicate that T cells promote hippocampal neurogenesis in Alzheimer＇s disease and T-cell immunodeficiency restricts neuronal regeneration in the hippocampus. The mechanism underlying the promotion of neuronal regeneration by T cells is mediated by an increased expression of peripheral T cells and central microglial cytokines in Alzheimer＇s disease mice. Our findings provide an experimental basis for understanding the role of T cells in Alzheimer＇s disease.

Investigation of Linarinic acid and one of its derivatives against cerebral ischemia in mice

The study aims to investigate the effects of(-)-Linarinic acid(LA) and one of its derivatives(LAd) on brain injury induced by ischemia. Malonaldehyde(MDA) is determined as an index for lipid peroxidation both in vitro and vivo. Mice were pre-treated with LA and LAd for 3 d.Thereafter, they were induced to have incomplete cerebral ischemia with both bilateral carotid artery occlusion and hypotension(BCAOH). In the first part of the in vivo experiment, mice were divided into four groups: sham(control), ischemia, ischemia + LA(200 mg/kg, i.g.) and ischemia + LAd(200 mg/kg, i.g.). In the second part, the dose-response of LAd was investigated at 100, 200 and 400 mg/kg i.g., respectively. A modified neurological severity score was developed for evaluating behavioral deficits of the mice with ischemia. Brains of the mice were excised in order to determinate MDA after ischemia for 6 h. Survival time, survival rate, neurological injury score and MDA level in brains were observed. Results were: 1) The data in vitro showed that both LA and LAd could inhibit the generation of MDA. IC50 values obtained by Probit analysis were 2.9 mM for LAd and 4.88 mM for LA;2) BCAOH could significantly shorten the survival span, reduce the survival rate and cause neurological deficits,which were associated with high level of lipid hydroperoxide production in cerebral tissues;3) LAd decreased lipid peroxidation and improved the neurological outcome more than LA.It is concluded that LAd offers a better neuroprotection than LA against brain damage caused by cerebral ischemia.

INHIBITORY EFFECT OF DEMO ON THE GROWTH OF TRANSPLANTED HUMAN COLON CANCER IN NUDE MICE

A human colon cancer cell line Hce- 8693 was heterotransplanted in nude mice. Polyamine blosythesis Inhibitor a- dlfiuoromethylomithine (DFMO ) show a marked reproducible inhibition in this model. The size and weight of transplanted tumor In DFMO group were smaller than those of the control group and the average inhibition rate was 72.8% (P < 0.001) . DFMO showed higher tumor inhibitory rate than 5-Fu (35. 4%) (P<0. 001) . Furthermore. DFMO demonstrated less severe bone marrow inhibition in the nude mice than 5-Fu (20. 0% Vs 53. 2%. P<0. 001) .There was no synergistic action in these two drugs at the experimental dose. The concentration of putrescine and spermidine in the plasma and tumor tissue in the DFMO group were 70% lower than those of the control group (P<0. 001) . These results indicate that the anti-tumor effect of DFMO might be explained by the inhibition of polyamine biosynthesis and this study provides an experimental basis for future clinical application of DFMO.

Further Pharmacological Studies Using the Compound （1 z）-2-（Hyd roxym et hyl）-Dodec-1 -E ne-1,3-D iol

The compound （1 z）-2-（hydroxymethyl）-dodec-1-ene-1,3-diol was previously isolated from the integument of the red palm weevil Rhynhophorus ferruginous and found to antagonize calcium chloride induced dysrrhythmia in mice. Further calcium-dependent pharmacological actions performed in this study revealed that it has the ability to inhibit platelets aggregation induced in guinea pigs with either ADP or archegonia acids, and the compound also decreased the arterial pressure in rats in a dose-dependent manner and exerted potential ant consultant activity in mice against pentylene tetrazole-induced seizures. However, no complete protection was observed. Analgesic studies in mice using the hot plate （58 ℃） revealed its potential analgesic activities. Its effective dose 50 （ED50） was 85.7 ± 6.3 mg/kg （N= 5）. The compound seamed to produce all of the above actions via a calcium antagonistic action.

The Thromboxane Receptor Antagonist S18886 influence the stability of atherosclerosis in ApoE Null Mice

Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clopidegrol on the development of atherosclerosis, accumulation of lipid- filled macropha-ges in apoE null mice. Methods All mice were done cuffed common carotid artery and fed a Western-type atherogenic diet for 6 weeks from the day of surgery, at same time the therapy group mice were gavaged S18886 5 mg/Kg/day and clopidegrol respec- tively, the same volume water were gavaged as the placebo group. Results profound inhibition of lesion area growth after cuff of the right common carotid artery in mice with 5 mg/kg of S18886, markdely reduce intima to media ratio and intima to total wall area compare with clopidegrol or blank group; Macrophage infiltration into sites of arterial plaque was also markedly attenuated by ICAM-1 deficiency in the S18886 group, whereas inside the arterial wall plaque of placebo apoE null mice α-smooth muscle actin markedly attenuated. Treatment with 25 mg/kg/day clopidegrol reduced the level of ICAM-1 stai ning, both S18886 and clopidegrol didn't influence the α-smooth muscle actin inside plaque. Conclusions It was considered that the novel anti-thrombotic drug significant reduce macrophage infiltration in the sites of arterial plaque by ICAM-1 deficiency, S18886 not only reduce the size, but also stabilized the plaque.

The adjustment of γ-aminobutyric acid_A tonic subunits in Huntington＇s disease：from transcription to translation to synaptic levels into the neostriatum

γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA activates two kind of membrane receptors known as GABAA and GABAB,the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6,β3,δ,or ρ1-3 subunits,they are located at perisynaptic and/or in extrasynaptic regions.The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation.On this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s disease.Huntington＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as YAC128.In all of them,some key experimental reports are focused on neostriatum.The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures,its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively,they display strong expression of many types of GABAA receptors,including tonic subunits.The studies about of GABAA tonic subunits and Huntington＇s disease into the neostriatum are rising in recent years,suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition,a hallmark of Huntington＇s disease.

Nrf2/ARE signaling protects against oxaliplatin-induced hepatotoxicity in mice

Nuclear factor erythroid 2-related factor 2 （Nrf2） controls the expression of a wide array of antioxidant response element （ARE）-driven genes, which are involved in stress response and metabolism regulation. The role of Nrf2/ARE signaling in resistances of cancer cells to radiotherapy and chemotherapy has been widely accepted. However, much less is known about the relevance of Nrf2 to chemotherapy-associated toxicities, such as hepatotoxicity. In the present study, nine chemotherapeutic agents were firstly tested in embryonic fibroblasts （MEFs） and hepatocytes isolated from Nrf2 deficient or wild-type mice. The results indicate that the cytotoxicity of oxaliplatin in hepatocytes was significantly higher than that in MEFs and enhanced by Nrf2 deficiency. Furthermore, oxaliplatin treatment caused more pronounced steatosis and severer liver injury in Nrf2-/- mice compared with wild-type counterparts, as evidenced by dramatically elevated serum transaminase and bilirubin, increased accumulation of fat, inflammatory infiltration and blood congestion. The increased hepatotoxicity in Nrf2 deficient mice was possibly caused by decreased expression of antioxidant genes and glutathione depletion. Our results demonstrated that oxaliplatin-induced hepatotoxicity was significantly impacted by Nrf2 status, therefore Nrf2 could potentially serve as a biomarker to predict or a target to prevent hepatotoxicity of oxaliplatin.

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China.However,the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown.We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E(ApoE)and LDL receptor(LDLR)dual deficient(ApoE^(–/–)LDLR^(–/–))mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure.CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis.Mechanistically,both Wnt and lysine-specific demethylase 4A(KDM4A)pathways were significantly activated in mice with heart injury.Conversely,CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors.While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity.In addition,CDDP attenuated simvastatin-induced myolysis in skeletal muscle.Taken together,our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Isolation,Characterization,and Phylogenetic Analysis of Two New Crimean-Congo Hemorrhagic Fever Virus Strains from the Northern Region of Xinjiang Province,China

Crimean-Congo hemorrhagic fever(CCHF)caused by the CCHF virus(CCHFV)is a tick-borne natural focal disease with a mortality rate of approximately 50%.CCHFV is widely prevalent in Africa,southern Asia,the Middle East,and southeast Europe.CCHF outbreaks have been reported previously in Xinjiang province,China,especially in its southern region.Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks,rodents,and infected individuals from cities and counties in southern Xinjiang.Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype,based on complete sequences of the S segments of its negative-stranded RNA genome.The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang.Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses;these analyses indicated that the genotype of both strains was different from that of other Chinese strains.Furthermore,previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed.CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years,and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains.Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains.

Transgenic 4-1BBL-engineered vaccine stimulates potent Gag-specific therapeutic and long-term immunity via increased priming of CD44＋CD62Lhigh IL-7R＋ CTLs with up- and downregulation of anti- and pro-apoptosis genes

Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8＋ cytotoxic T lymphocyte （CTL） responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus （AdV）4-1BBL, which expressed mouse 4-1BB ligand （4-1BBL）, and generated transgenic 4-1BBL-engineered OVA-Texo/4.1BSL and Gag-Texo/4.1BSL vaccines by transfecting ovalbumin （OVA）-Texo and Gag-＇rexo cells with AdV4.1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/4.ZSSL vaccine stimulates more efficient OVA-specific CTL responses （3.26%） compared to OVA-Texo-activated responses （1.98%） in wild-type C57BIJ6 mice and the control OVA-TeXO/Nu, vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-1OovA cells. OVA-Texo/4.1BBL-stimulated CTLs, which have a CD44＋CD62Lhigh IL-7R＋ phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-1OovA melanoma. In addition, we demonstrate that OVA-Texo/4_ZBBL-Stimulated CTLs up- and downregulate the expression of anti-apoptosis （Bcl2110, Naipl, No13, Pak7 and Tnfrsfllb） and pro-apoptosis （Casp12, Trp63 and Trp73） genes, respectively, by RT2 Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4.1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B 16 melanoma BL6-1OGag/A2 cells than the control Gag-TeXO/NuH vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-ZBBL vaccine, which is capable of stimulating potent Gag-specific therapeutic and long-term immunity, may represent a new immunotherapeutic vaccine for controlling HIV-1 infection.

Humanized mice are susceptible to Salmonella typhi infection

Salmonella enterica serovar Typhi is a pathogen that only infects humans.Currently,there is no animal model for studying this pathogen.Recently,alymphoid RAG2^(-/-)/γc^(-/-) mice engrafted with human leukocytes,known as humanized mice,have been successfully utilized to develop experimental models for several human-specific viral infections,including HIV,human-like dengue fever and hepatitis C virus.Little is known about the usefulness and feasibility of the humanized mouse model for the study of human-specific bacterial pathogens,such as S.typhi.The aim of this study was to determine if Salmonella enterica serovar Typhi could establish productive infection in humanized mice.Here we report that intravenous inoculation of S.typhi into humanized mice,but not controls,established S.typhi infections.High bacterial loads were found in the liver,spleen,blood and bone marrow of mice reconstituted with human leukocytes,but not in the unreconstituted control mice.Importantly,S.typhi-infected humanized mice lost significant body weight,and some of the infected mice displayed neurological symptoms.Our data suggest,for the first time,that humanized mice are susceptible to S.typhi challenge and that this model can be utilized to study the pathogenesis of S.typhito develop novel therapeutic strategies.