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Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract infections (LRTIs) among infants and young children worldwide and is also a major cause of morbidity in children under 1 year of age (2). Bronchiolitis and pneumonia, which are attributed to HRSV infection, are observed most frequently during the first few months of life (7). Almost all children are infected with HRSV by 2 years of age, and half of all children experience two infections (8, 13).Based on genetic and antigenic variations in structural proteins, HRSV isolates have been subdivided into two major antigenic groups (i.e., A and B), and both subgroups are associated with different severities of infection (15,18,(22)(23)(24). The nucleotide and deduced amino acid sequence similarities are 67% and 53% between group A and group B strains, respectively (11, 19). Antigenic variability is thought to contribute to the capacity of the virus to infect people repeatedly and cause yearly outbreaks. These characteristics may pose a challenge for vaccine design and development (27). The G protein, a surface-expressed glycoprotein that is associated with attachment of the virus, shows the largest antigenic and genetic differences between the two antigenic HRSV subgroups and is one of the targets for neutralization and protective antibody responses (1, 19). The G protein contains two hypervariable regions; the second variable region, which corresponds to the C-terminal region of the G protein (HVR2), reflects overall G protein gene variability and has been analyzed in molecular epidemiological studies (9,(25)(26)(27)(28).Although HRSV has been recognized as an important agent, no effective vaccine is currently available for prophylaxis and there is no effective antiviral treatment against current HRSV infections. The importance of strain differences in relation to clinical features and vaccine development has not been fully elucidated (8,22). In the present study, 894 children with acute respiratory tract infections (ARTIs) were examined over three consecutive seasons for the presence of HRSV, and HRSV strains were genotyped by sequencing HVR2. Demographic and clinical information was collected from all patients. The prevalence and clinical and molecular characterization of HRSV genotypes were further analyzed. MATERIALS AND METHODSPatients and specimens. From December 2006 to March 2009, 894 nasopharyngeal aspirates (NPAs) were collected from children with ARTIs on Tuesday every week in the First Hospital of Lanzhou University, China. ARTIs were classified according to WHO definitions (38). Informed consent was obtained from the parents of all children who provided specimens. The study protocol was approved by the hospital ethics committee. All NPA specimens were collected and transported immediately to the laboratory at the National Institute for Viral

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Background: Hypoxia is crucial in the initiation and progression of tumor metastasis. Circular RNAs (CircRNAs) comprise a novel group of non-coding, RNase R resistant and regulatory RNAs which are generated by 'back-splicing' processes. However, the characterization and function of circRNAs in hypoxic cancer cells remain unknown.Methods: High throughput RNA-seq assay was performed in lung adenocarcinoma cells (A549) under either normoxic or hypoxic conditions. Bioinformatic analysis of differentially expressed circRNAs was conducted and their target genes were predicted and partially confirmed.Results: Hypoxia increased the expression of hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream genes in A549 cells and enhanced cell migration ability. Comprehensive analysis of global circRNAs expression profiles of A549 identified a total of 558 circRNAs candidates, among which 65 circRNAs were differentially expressed (35 upregulated and 30 downregulated) in hypoxic cancer cells. The difference in their circRNA expressions were compared by computational analysis and circRNA-miRNA networks were constructed. We further characterized one circRNA (hsa_circ_0008193) derived from the FAM120A gene and renamed it as circFAM120A. The expression of circFAM120A, as validated by reverse transcription polymerase chain reaction, was significantly downregulated in both hypoxic A549 and lung cancer tissue from patients with lymph node metastasis. Gene ontology (GO) enrichment analysis and KEGG pathway analysis revealed that circFAM120A may participate in lung cancer development.Conclusions: CircRNAs profiles were altered in lung adenocarcinoma under hypoxia and circFAM120A may have the potential to be a new biomarker of lung adenocarcinoma hypoxia.

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Background Age-associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age-associated sarcopenia and metabolic dysfunction. Methods The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2-and 24-month-old mice or human subjects were analysed using qRT-PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14-month-old) for 4 months or in aged mice (22-month-old) for 1 month to systematically investigate irisin's effects on age-associated sarcopenia and metabolic performances, including grip strength, body weights, body composition, insulin sensitivity, energy expenditure, serum parameters and phenotypical and molecular changes in fat and liver. Results We showed that the expression levels of irisin, as well as its precursor Fndc5, were reduced at mRNA and protein expression levels in muscle during ageing. In addition, via phenotypic analysis of FNDC5/irisin knockout mice, we found that FNDC5/irisin deficiency in aged mice exhibited aggravated muscle atrophy including smaller grip strength (À3.23%, P < 0.05), muscle weights (quadriceps femoris [QU]: À20.05%; gastrocnemius [GAS]: À17.91%; tibialis anterior [TA]: À19.51%, all P < 0.05), fibre size (QU: P < 0.01) and worse molecular phenotypes compared with wild-type mice. We then delivered recombinant irisin protein intraperitoneally into ageing or aged mice and found that it could improve sarcopenia with grip strength (+18.42%, P < 0.01 or +13.88%, P < 0.01), muscle weights (QU: +9.02%, P < 0.01 or +16.39%, P < 0.05), fibre size (QU: both P < 0.05) and molecular phenotypes and alleviated age-associated fat tissues expansion, insulin resistance and hepatic steatosis (all P < 0.05), accompanied with altered gene signatures. Conclusions Together, this study revealed the importance of irisin in the maintenance of muscle physiology and systematic energy homeostasis during ageing and suggested a potent therapeutic strategy against age-associated metabolic diseases via irisin administration.

INTRODUCTION An increase in life expectancy in modern world brings an 'aged society', in which a substantial aging population poses challenges both medically and financially [1, 2]. Thus, more and more research interests are piqued toward the combat against aging. Generally, aging is defined as the age-dependent physiological decline that affects all living organisms. Aging undermines multiple major organs and plays a profound role in the onset of neurodegenerative diseases, cardiovascular diseases, metabolic disorders, as well as a loss in muscle and bone mass [3-7]. Recently, metabolic fitness emerges as a novel player in the arena of combating aging. For instance, the prevalence www.aging-us.com