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Abstract Dynamic control transmission and polarization properties of electromagnetic (EM) wave propagation is investigated using chemical reconfigurable all-dielectric metasurface. The metasurface is composed of cross-shaped periodical teflon tubes and inner filled chemical systems (i.e., mixtures and chemical reaction) in aqueous solution. By tuning the complex permittivity of chemical systems, the reconfigurable metasurface can be easily achieved. The transmission properties of different incident polarized waves (i.e., linear and circular polarization) were simulated and experimentally measured for static ethanol solution as volume ratio changed. Both results indicated this metasurface can serve as either tunable FSS (Frequency Selective Surface) or tunable linear-to-circular/cross Polarization Converter at required frequency range. Based on the reconfigurable laws obtained from static solutions, we developed a dynamic dielectric system and researched a typical chemical reaction with time-varying permittivity filled in the tubes experimentally. It provides new ways for realizing automatic reconfiguration of metasurface by chemical reaction system with given variation laws of permittivity.

While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.

T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. Mechanistic experiments showed that siRNA silencing of Tim-3 or soluble Tim-3 treatment interfering with membrane Tim-3-ligand interaction reduced de novo production of IFN-γ and TNF-α by Tim-3-expressing T cells. Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. This study therefore uncovered a previously unknown mechanism for T-cell immune responses regulated by Tim-3, and findings may have implications for potential immune intervention in TB.

Background Expression of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors, but the underlying molecular mechanisms and its clinical significance in renal cell carcinoma (RCC) remain to be elucidated. Methods ETK expression in 90 human RCC and 30 human normal renal tissue samples was examined by immunohistochemistry and compared with several clinicopathologic parameters. To further demonstrate the biological function of ETK in RCC, Western blot was used to test the expression level of ETK protein in RCC cell lines. Subsequent to the downregulation of ETK by small interfering RNA, the effects of ETK on RCC cell growth, apoptosis, migration and invasion were assessed by methyl thiazol tetrazolium assay, flow cytometry and transwell assay. And the varying expression of VEGF, STAT3 and phosphorylated STAT3 (p-STAT3) in RCC were evaluated by Western blot. Results Immunohistochemistry analysis showed that ETK expression was highly increased in RCC and was positively correlated with clinical stage, grade and metastasis. Simultaneously, the overall survival time in patients with higher ETK expression was obviously shorter than that in patients with lower ETK expression. ETK was also detected in RCC cell lines. Moreover, the down-regulating ETK significantly inhibited RCC cell growth, migration, invasion and promoted apoptosis. The expression of VEGF and p-STAT3 were also decreased. Conclusions Our study suggests that the overexpression of ETK is associated with the malignancy and disease progression of RCC. Since ETK is also involved in RCC cell biological function and VEGF-ETK-STAT3 loop, ETK may be used as a potential therapeutic target for RCC. [ABSTRACT FROM AUTHOR]

T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4+ and CD8+ T cells, which preferentially displayed polarized effector memory phenotypes. Consistent with effector phenotypes, Tim-3+ CD4+ and Tim-3+ CD8+ T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3- counterparts, and Tim-3- expressing T cells more apparently limited intracellular Mtb replication in macrophages. The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3+ CD4+ and Tim-3+ CD8+ T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. Mechanistic experiments showed that siRNA silencing of Tim-3 or soluble Tim-3 treatment interfering with membrane Tim-3-ligand interaction reduced de novo production of IFN-γ and TNF-α by Tim-3-expressing T cells. Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4+ and CD8+ T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. This study therefore uncovered a previously unknown mechanism for T-cell immune responses regulated by Tim-3, and findings may have implications for potential immune intervention in TB. [ABSTRACT FROM AUTHOR]

Graft-vs.-host disease (GVHD) remains the major limitation of allogeneic bone marrow transplantation (BMT) and stem cell transplantation, and leukemia recurrence is another important complication in leukemia treatment. Immature CD8 α+ dendritic cells (DC) have good potential in GVHD treatment and immunological tolerance studies. To find a new way to prevent GVHD, not increasing the risk of leukemia recurrence, in this study, predominant CD8 α+ immature DC were induced from murine bone marrow (BM) cells by 5 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF) plus 20-ng/mL interleukin (IL)-4, 100-ng/mL stem cell factor (SCF) and 25-ng/mL Flt3L, and 97.09 of prepared DC were CD8 α+ on day 3. These DC were identified as morphologically and phenotypically immature CD8 α+ DC. The suppressive function was observed in vitro, and then in vivo on allo-BMT leukemia model. The prepared predominant immature CD8 α+ DC were weak syngeneic lymphocyte stimulators and could suppress mixed leukocyte reaction in vitro. In vivo, they prevented the pathological changes of GVHD and prolonged the surviving time of allo-BMT leukemia mice. The effect showed a dose–effect relationship. 86.7% of allo-BMT plus 1 million predominant CD8 α+ DC leukemia mice reached long-term survival. Although predominant immature CD8 α+ DC had the function of GVHD suppression, they did not increase leukemia recurrence. The method and findings may have important potency for GVHD treatment in clinical application. [ABSTRACT FROM AUTHOR]

Background The World Health Organization (WHO) ranks respiratory tract infection (RTI) as the second leading cause of death worldwide for children under 5 years of age. The aim of this work was to evaluate the epidemiology characteristics of respiratory viruses found in children and adults with RTI from July 2009 to June 2012 in southern China. Methods In this work, a total of 14 237 nasopharyngeal swabs (14 237 patients from 25 hospitals) were analyzed, and seven respiratory viruses (influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human metapneumovirus, human coronavirus, human bocavirus) were detected using PCR/RT-PCR from nasopharyngeal swabs. Results The demographic characteristics, viral prevalence, age distribution, seasonal distribution, and pathogen spectrum of the patients with RTIs were analyzed. Co-infection was observed in 483 specimens, but it was more common in male patients, inpatients, children, and young adults. It varied by season, being more prevalent in the spring and summer and less so in the winter. Human coronavirus and human bocavirus were the most common pathogens, tending to occur in co-infection with other respiratory viruses. Conclusions This work adds to our knowledge of the epidemiology characteristics of these seven common respiratory viruses among patients with RTI in southern China. The detection of the specific viral causes of infection provides a useful starting point for an understanding of illness attributable to respiratory infection, and might also provide data relevant to the development of prevention strategies. [ABSTRACT FROM AUTHOR]