Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to preven...Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent HFMD.This study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs.The neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune pathways.The immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)mice.Immunological protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice models.Serum‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐YN2015.Furthermore,these levels were significantly higher with abdominal injection than intramuscular injection.The immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,respectively.For ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to survive.Overall,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.展开更多
Previous studies on the behavioral implications of recommender systems suggest that consumer preferences after consumption are malleable and tend to shift towards the ratings presented by a recommender system because ...Previous studies on the behavioral implications of recommender systems suggest that consumer preferences after consumption are malleable and tend to shift towards the ratings presented by a recommender system because of the anchoring effects.Drawing upon the literature on consumer satisfaction,we show that such a view on the anchoring effects of recommender systems is incomplete.Apart from the assimilation effects that pull the consumers’preferences towards the anchor,the contrast effects may shift their preferences in the other direction.Therefore,we theoretically hypothesize that the impacts of recommendations on consumers’constructed preferences are dependent on the level of deviation of the presented rating.The hypotheses are validated through a laboratory experiment.Our findings extend the existing literature on behavioral implications of recommender systems and provide a more comprehensive theoretical lens for understanding the anchoring effects,which may offer helpful insights for improving the design and use of recommender systems.展开更多
Enteroviruses(EVs)are human pathogens commonly observed in children aged 0–5 years and adults.EV infections usually cause the common cold and hand-foot-and-mouth disease;however,more severe infections can result in m...Enteroviruses(EVs)are human pathogens commonly observed in children aged 0–5 years and adults.EV infections usually cause the common cold and hand-foot-and-mouth disease;however,more severe infections can result in multiorgan complications,such as polio,aseptic meningitis,and myocarditis.The molecular mechanisms by which enteroviruses cause these diseases are still poorly understood,but accumulating evidence points to two enterovirus proteases,2Apro and 3Cpro,as the key players in pathogenesis.The 2Apro performs post-translational proteolytic processing of viral polyproteins and cleaves several host factors to evade antiviral immune responses and promote viral replication.It was also discovered that coxsackievirus-induced cardiomyopathy was caused by 2Apro-mediated cleavage of dystrophin in cardiomyocytes,indicating that cellular protein proteolysis may play a key role in enterovirus-associated diseases.Therefore,studies of 2Apro could reveal additional substrates that may be associated with specific diseases.Here,we discuss the genetic and structural properties of 2Apro and review how the protease antagonizes innate immune responses to promote viral replication,as well as novel substrates and mechanisms for 2Apro.We also summarize the current approaches for identifying the substrates of 2Apro to discover novel mechanisms relating to certain diseases.展开更多
Enteroviruses (EVs) are classified into 15 species according to their sequence diversity. They include four human EV (A, B, C, and D) and three rhinoviruses (A, B, and C), and cause diseases in millions of people worl...Enteroviruses (EVs) are classified into 15 species according to their sequence diversity. They include four human EV (A, B, C, and D) and three rhinoviruses (A, B, and C), and cause diseases in millions of people worldwide. Generally, individuals with enteroviral infections have mild clinical symptoms, including respiratory illness, vomiting, diarrhea, dizziness, and fever. More importantly, some members of the human EV family are neurotropic pathogens that may cause a wide range of clinical diseases, such as aseptic meningitis and encephalitis. Previously, the EV that caused the most severe neurotropic symptoms was poliovirus (PV), a member of the EV C group. Poliovirus has been eliminated in most countries through a global vaccination campaign. Non-PV EVs infect the central nervous system (CNS) and are the major EVs causing neurological diseases. These human non-PV EVs include EV A (e.g., EV-A71, CVA6, and CVA16), B (e.g., CVA9 and CVB3, CVB5, echovirus 11 [E11], E30, and E7), C (e.g., CVA24), and D (e.g., EV-D68). Here, we review the relationship between EV infection and CNS diseases and advance in the use of cellular receptors and host immune responses during viral infection.展开更多
In October 2017,a small outbreak of echovirus 30(E30)associated with aseptic meningitis in nine cases occurred at a primary school in the Ningxia Hui Autonomous Region.That year,we observed a significant increase in E...In October 2017,a small outbreak of echovirus 30(E30)associated with aseptic meningitis in nine cases occurred at a primary school in the Ningxia Hui Autonomous Region.That year,we observed a significant increase in E30 levels in an acute flaccid paralysis(AFP)case surveillance system.To investigate their phylogenetic relationships,we determined the whole genomic sequences of 12 strains isolated from aseptic meningitis cases,AFP cases,and healthy children.We found that the E30 strains circulating in Ningxia belong to two lineages(H and J).The strains isolated in 2010,2012,and 2016 belonged to the H lineage.In 2017,a new lineage,J,emerged as the dominant lineage.Phylogenetic trees were constructed based on the whole genome andP1,P2,andP3 regions;clustering with other types of enterovirus species B was found,suggesting that recombination events had occurred.The recombination sites were mainly in regions2B,2C,and3D.This study confirmed that the E30 strains in Ningxia in 2010,2012,and 2016 had different recombination patterns and were recombined with different enteroviruses.The 2017 epidemic E30 originated from another new lineage with a complex recombination pattern and formed an independent transmission chain in Ningxia.展开更多
基金supported by the National Key Researchand Development Programof China (Project No.2021YFC2302003).
文摘Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent HFMD.This study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs.The neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune pathways.The immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)mice.Immunological protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice models.Serum‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐YN2015.Furthermore,these levels were significantly higher with abdominal injection than intramuscular injection.The immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,respectively.For ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to survive.Overall,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.
基金the TsinghuaUniversity Initiative Scientific Research Program under Grant No.2019THZWYX08the MOE Project of Key Research Institute of Humanities and Social Sciences at Universities No.17JJD630006the Research Center for Interactive Technology Industry TsinghuaUniversity under Grant No.RCITI2022T002.
文摘Previous studies on the behavioral implications of recommender systems suggest that consumer preferences after consumption are malleable and tend to shift towards the ratings presented by a recommender system because of the anchoring effects.Drawing upon the literature on consumer satisfaction,we show that such a view on the anchoring effects of recommender systems is incomplete.Apart from the assimilation effects that pull the consumers’preferences towards the anchor,the contrast effects may shift their preferences in the other direction.Therefore,we theoretically hypothesize that the impacts of recommendations on consumers’constructed preferences are dependent on the level of deviation of the presented rating.The hypotheses are validated through a laboratory experiment.Our findings extend the existing literature on behavioral implications of recommender systems and provide a more comprehensive theoretical lens for understanding the anchoring effects,which may offer helpful insights for improving the design and use of recommender systems.
基金supported by the National Key Research and Development Program of China (Project No.2021YFC2302003).
文摘Enteroviruses(EVs)are human pathogens commonly observed in children aged 0–5 years and adults.EV infections usually cause the common cold and hand-foot-and-mouth disease;however,more severe infections can result in multiorgan complications,such as polio,aseptic meningitis,and myocarditis.The molecular mechanisms by which enteroviruses cause these diseases are still poorly understood,but accumulating evidence points to two enterovirus proteases,2Apro and 3Cpro,as the key players in pathogenesis.The 2Apro performs post-translational proteolytic processing of viral polyproteins and cleaves several host factors to evade antiviral immune responses and promote viral replication.It was also discovered that coxsackievirus-induced cardiomyopathy was caused by 2Apro-mediated cleavage of dystrophin in cardiomyocytes,indicating that cellular protein proteolysis may play a key role in enterovirus-associated diseases.Therefore,studies of 2Apro could reveal additional substrates that may be associated with specific diseases.Here,we discuss the genetic and structural properties of 2Apro and review how the protease antagonizes innate immune responses to promote viral replication,as well as novel substrates and mechanisms for 2Apro.We also summarize the current approaches for identifying the substrates of 2Apro to discover novel mechanisms relating to certain diseases.
基金supported by the National Key Research and Development Program of China(Project No.2021YFC2302003)Natural Science Foundation of Beijing(Project No.L192014)。
文摘Enteroviruses (EVs) are classified into 15 species according to their sequence diversity. They include four human EV (A, B, C, and D) and three rhinoviruses (A, B, and C), and cause diseases in millions of people worldwide. Generally, individuals with enteroviral infections have mild clinical symptoms, including respiratory illness, vomiting, diarrhea, dizziness, and fever. More importantly, some members of the human EV family are neurotropic pathogens that may cause a wide range of clinical diseases, such as aseptic meningitis and encephalitis. Previously, the EV that caused the most severe neurotropic symptoms was poliovirus (PV), a member of the EV C group. Poliovirus has been eliminated in most countries through a global vaccination campaign. Non-PV EVs infect the central nervous system (CNS) and are the major EVs causing neurological diseases. These human non-PV EVs include EV A (e.g., EV-A71, CVA6, and CVA16), B (e.g., CVA9 and CVB3, CVB5, echovirus 11 [E11], E30, and E7), C (e.g., CVA24), and D (e.g., EV-D68). Here, we review the relationship between EV infection and CNS diseases and advance in the use of cellular receptors and host immune responses during viral infection.
基金supported by the Science and Natural Science of Ningxia (Grant No.2021AAC03415)the Science and Natural Science of China (Grant No.81960607)+1 种基金Science and Natural Science of Ningxia (Grant No.2022AAC03708)the National Key Research and Development Program of China (Project No.2021YFC2302003).
文摘In October 2017,a small outbreak of echovirus 30(E30)associated with aseptic meningitis in nine cases occurred at a primary school in the Ningxia Hui Autonomous Region.That year,we observed a significant increase in E30 levels in an acute flaccid paralysis(AFP)case surveillance system.To investigate their phylogenetic relationships,we determined the whole genomic sequences of 12 strains isolated from aseptic meningitis cases,AFP cases,and healthy children.We found that the E30 strains circulating in Ningxia belong to two lineages(H and J).The strains isolated in 2010,2012,and 2016 belonged to the H lineage.In 2017,a new lineage,J,emerged as the dominant lineage.Phylogenetic trees were constructed based on the whole genome andP1,P2,andP3 regions;clustering with other types of enterovirus species B was found,suggesting that recombination events had occurred.The recombination sites were mainly in regions2B,2C,and3D.This study confirmed that the E30 strains in Ningxia in 2010,2012,and 2016 had different recombination patterns and were recombined with different enteroviruses.The 2017 epidemic E30 originated from another new lineage with a complex recombination pattern and formed an independent transmission chain in Ningxia.
