A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late ...presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.
While most strains of Salmonella enterica serotype Typhi, the etiologic agent of typhoid fever, have only a phase 1 flagellar antigen, H1-d, variations of the flagellar antigen have been observed. ...Although H1-j strains (one of the flagellar antigen variants) account for 10 to 50% of S. enterica serotype Typhi strains found in Indonesia, there have been no published data to suggest its existence in other parts of the world. We describe a case of typhoid fever associated with acute appendicitis caused by an S. enterica serotype Typhi H1-j strain in a Chinese woman in Hong Kong. A gram-negative, motile rod was recovered from her blood and stool cultures. Conventional biochemical tests and the Vitek system (GNI+) showed that the bacterium was S. enterica serotype Typhi. The isolate agglutinated with poly(O), 9O, Vi and H1-j Salmonella antisera but not with poly(H) antisera. The patient developed antibodies against only S. enterica serotype Typhi O antigens but not against H1-d antigen by the Widal test. Flagellin C gene (fliC) sequencing showed a 261-bp deletion in the fliC gene of the isolate, confirming that the isolate possessed the H1-j antigen. The patient had no past history of travel to Indonesia or personal contact with any Indonesian. She recovered with appendectomy and antibiotic treatment. Further studies should be performed to determine the prevalence of this unusual S. enterica serotype Typhi strain in our locality.
Severe pandemic influenza A H1N1 (2009) infection, especially in the lower respiratory tract, is often associated with the virus carrying a D222G substitution in the hemagglutinin (HA) protein of the ...virus. The mechanism for this association has not been fully explored. In the in vitro binding assay, it was found that clinical isolates carrying D222G substitution exhibit higher binding avidity to 2,3-linked sialic acids than the wild-type virus. The receptor binding pocket of the pandemic influenza (H1N1) HA was found to be smaller than those of other influenza A strains, allowing tighter binding of the virus with the receptor, yet also inducing steric stress for the binding. Our homology modeling and molecular docking calculations implicated that residue 222 may affect the positioning of the conserved Q223 residue, hence modulating flexibility of the binding pocket and steric hindrance during receptor binding. The molecular property of residue 222 can also directly influence the 'lysine fence' via the polarity of the amino acid residue where D222G substitution will enhance the electrostatic interactions between the receptor and the protein. The potential importance of residue 222 was illustrated by evolutionary analysis, which showed that this site is under intense selection pressure during adaptation of the virus to human host. Our findings provide a useful reference for follow-up studies in monitoring the ongoing evolution of the pandemic influenza A H1N1 (2009) virus.
A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late ...presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vdelta2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-gamma secreted from human Vdelta2-T cells. Meanwhile, human Vdelta2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.
ABSTRACT
While most strains of
Salmonella enterica
serotype Typhi, the etiologic agent of typhoid fever, have only a phase 1 flagellar antigen, H1-d, variations of the flagellar antigen have been ...observed. Although H1-j strains (one of the flagellar antigen variants) account for 10 to 50% of
S. enterica
serotype Typhi strains found in Indonesia, there have been no published data to suggest its existence in other parts of the world. We describe a case of typhoid fever associated with acute appendicitis caused by an
S. enterica
serotype Typhi H1-j strain in a Chinese woman in Hong Kong. A gram-negative, motile rod was recovered from her blood and stool cultures. Conventional biochemical tests and the Vitek system (GNI+) showed that the bacterium was
S. enterica
serotype Typhi. The isolate agglutinated with poly(O), 9O, Vi and H1-j
Salmonella
antisera but not with poly(H) antisera. The patient developed antibodies against only
S. enterica
serotype Typhi O antigens but not against H1-d antigen by the Widal test. Flagellin C gene (
fliC
) sequencing showed a 261-bp deletion in the
fliC
gene of the isolate, confirming that the isolate possessed the H1-j antigen. The patient had no past history of travel to Indonesia or personal contact with any Indonesian. She recovered with appendectomy and antibiotic treatment. Further studies should be performed to determine the prevalence of this unusual
S. enterica
serotype Typhi strain in our locality.
The aim of this study is to deepen our understanding of psychological processes involved in learning an additional language, particularly the associations between ideal L2 self and L2 willingness to ...communicate (L2 WTC). For this purpose, a moderated mediation model is proposed that incorporates grit and psychological shyness. Drawing on the L2 Motivational Self System framework, this study proposes that ideal L2 self would be positively related to L2 WTC and that grit would mediate the association between the two constructs. We also posit that this mediated association would be moderated by psychological shyness. The data for this multi-university study were collected across three cities in China from 842 (N = 842) undergraduate students majoring in Business English and English for Educational Purposes. Robust analytical techniques were employed to analyze the data. The findings suggested that ideal L2 self was positively related to L2 WTC and that grit mediated the relationship between these two constructs. Additionally, the link between ideal L2 self and grit was found to be moderated by psychological shyness. Furthermore, the strength of this mediated effect increased alongside the level of shyness. These findings hold some notable pedagogical implications.
•a moderated mediation relationship between L2 Ideal Self and Willingness to Communicate in English (L2 WTC) was examined.•Grit was a mediating variable and psychological shyness was a moderator variable in the model (Ideal L2 Self → Grit → L2 WTC)•Grit was found to mediate the relationship between L2 Ideal Self and L2 WTC.•The Ideal L2 Self–Grit nexus was moderated by psychological shyness.•The strength of the mediated effect increased in tandem with the level of shyness.
Psychological factors involved in learning a second language (L2) present a considerable interest for applied linguistics researchers and language educators. This study adopted the L2 Motivational ...Self System (L2MSS) framework to examine links between L2 motivation, willingness to communicate in the target language (L2WTC), classroom environment (L2CE) and psychological shyness of Chinese learners of English. The study posited that L2 motivation would be positively associated with L2WTC and that L2CE would mediate this relationship. It was further proposed that the L2MSS → L2CE → L2WTC nexus would be moderated by the language learners’ psychological shyness. Data were collected from 846 (
= 846) learners of English as a foreign language in three large state universities in China and analysed using rigorous statistical methods. The findings indicated that L2MSS was positively associated with L2WTC and that L2CE mediated the association between the two constructs. Furthermore, psychological shyness moderated the first and the second links in the L2MSS → L2CE → L2WTC nexus. These findings have notable pedagogical implications, such as the need to help students generate a positive self-image as an L2 user, to provide encouragement to the shy students and to create an inclusive and supportive classroom environment.
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