Understanding the factors behind apple farmers’willingness to pass on the management of their farms to their descendants is crucial to the continuity of apple production.Due to the high specificity of the human capit...Understanding the factors behind apple farmers’willingness to pass on the management of their farms to their descendants is crucial to the continuity of apple production.Due to the high specificity of the human capital,physical assets,land assets,and geographical location in apple production,this study used a binary logistic regression and a mediating effect model to explore the impact of asset specificity on farmers’intergenerational succession willingness of apple management(FISWAM)and to examine the mediating effects of loss aversion in the impact of asset specificity on the FISWAM.The results showed that about 18.68%of the respondents expressed willingness to transfer their apple business between generations,and the FISWAM was generally weak.In addition to the negative impact of geographical location specificity(GLS),human capital specificity(HCS),physical assets specificity(PAS),and land assets specificity(LAS)can enhance the FISWAM.Loss aversion plays a partial mediating role in the impact of PAS,LAS,and GLS on the FISWAM.展开更多
Domain adaptation(DA) aims to find a subspace,where the discrepancies between the source and target domains are reduced. Based on this subspace, the classifier trained by the labeled source samples can classify unlabe...Domain adaptation(DA) aims to find a subspace,where the discrepancies between the source and target domains are reduced. Based on this subspace, the classifier trained by the labeled source samples can classify unlabeled target samples well.Existing approaches leverage Graph Embedding Learning to explore such a subspace. Unfortunately, due to 1) the interaction of the consistency and specificity between samples, and 2) the joint impact of the degenerated features and incorrect labels in the samples, the existing approaches might assign unsuitable similarity, which restricts their performance. In this paper, we propose an approach called adaptive graph embedding with consistency and specificity(AGE-CS) to cope with these issues. AGE-CS consists of two methods, i.e., graph embedding with consistency and specificity(GECS), and adaptive graph embedding(AGE).GECS jointly learns the similarity of samples under the geometric distance and semantic similarity metrics, while AGE adaptively adjusts the relative importance between the geometric distance and semantic similarity during the iterations. By AGE-CS,the neighborhood samples with the same label are rewarded,while the neighborhood samples with different labels are punished. As a result, compact structures are preserved, and advanced performance is achieved. Extensive experiments on five benchmark datasets demonstrate that the proposed method performs better than other Graph Embedding methods.展开更多
Objectives: The study aimed to determine the most appropriate hearing screening test to identify disabling hearing loss for adults aged 65 years or older.Methods: This study included 577 older adults. Four hearing scr...Objectives: The study aimed to determine the most appropriate hearing screening test to identify disabling hearing loss for adults aged 65 years or older.Methods: This study included 577 older adults. Four hearing screening tests were considered in the study, including the Hearing Handicap Inventory for Elderly Screening(HHIE-s), three single question tests, the whisper test, and the finger rub test. The sensitivity and specificity of these tests referenced to the hearing threshold of disabling hearing loss were estimated.Results: Among all tests, only the single self-perception question(0.7064 for sensitivity;0.7225 for specificity) and whisper test(0.7833 for sensitivity;0.7708 for specificity) could obtain both sensitivity and specificity higher than 70% for adults aged ≥65 years.Conclusion: Overall, we suggest using the whisper test to identify disabling hearing loss(>40 dB HL at the better ear) for adults aged 65 years or older. However, if the conditions do not permit, the single selfperception question is also acceptable. Moreover, HHIE-s might not be a good test to detect disabling hearing loss for adults aged 80 years or older.展开更多
The cerebral cortex is one of the most complex structures of the mammalian central nervous system and accounts for the extraordinary cognitive abilities in primates and humans.Since the 19th century,neur ons have been...The cerebral cortex is one of the most complex structures of the mammalian central nervous system and accounts for the extraordinary cognitive abilities in primates and humans.Since the 19th century,neur ons have been believed to be the main players in the building of the brain,yet astrocytes also play a crucial role as fundamental building blocks of the cerebral cortex complexity.展开更多
Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic expe...Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic experimental colitis in rats through the PI3K/AKT/mTOR signaling pathway.Methods:Sixty pathogen-free SD rats were randomly assigned to six groups:the normal,model,Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)groups,each with 10 rats.Chronic colitis was induced in rats by combining immunization and local stimulation.After model establishment,electrical needle intervention combined with dispersing wave of 2 Hz/50 Hz with a current intensity of 2 mA once daily for 20 min was applied on acupoints of each group.Subsequently,the inflammation of colonic mucosa and serum levels of inflammatory factors(IL-23,IL-17,IL-10)were observed;ELISA was used to detect mRNA expressions of PI3K,Akt and mTOR in colitic tissues by RT-PCR as well as protein content of p-PI3k/PI3K,p-Akt/Akt,and p-mTOR/mTOR in colitic tissues by Western blotting.Result:Compared with the normal group,the model rats showed a poor general condition,serious damage to the colonic mucosa with a large number of inflammatory cells infiltration.The serum IL-23 and IL-17 expressions were significantly increased(P<0.01),while the serum IL-10 expression was significantly decreased(P<0.01);the mRNA and protein expressions of PI3K,Akt,mTOR and p-PI3K,p-Akt and p-mTOR were significantly increased(P<0.05,P<0.01).Compared with the model group,the pathological slices of rats in each acupoints intervention group showed obvious improvement of colitis inflammatory reaction and tissue damage;the serological levels of IL-23 and IL-17 were significantly reduced(P<0.01),while the serology level of IL-10 was significantly increased(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Compared with Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)groups,the recovery degree of mucosa layers in Shang Ju Xu(ST37)group was closer to that of normal group,and the curative effect was relatively the best;in terms of serological levels of IL-23 and IL-17,the Shang Ju Xu(ST37)group was significantly lower(P<0.05),while the level of IL-10 was significantly higher(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Conclusion:Results indicate that electrical acupuncture at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)show similar effects in relieving the colitis-induced damage in the mucosa of chronic colitis rats,as well as inflammatory response.Among them,Shang Ju Xu(ST25)has a superior overall effect in treating chronic colitis compared to Tian Shu(ST25),Da Chang Shu(BL25)and Zu San Li(ST36).The mechanism may be related to inhibition of PI3K/Akt/mTOR signaling pathway.展开更多
Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at rece...Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at receptive field (cheek) were recorded extracellularly with glass mi-cro-electrode. Electroacupuncture (EA ) was applied at bilateral " Xiaguan" (ST 7 on face ) or "Zusanli" (ST 36 on shank) acupoint with Iow (2V) and high (18V) intensity. The noclceptive re-sponse of convergent neurons in TNC could be inhihited by low intensity EA applied at "Xiaguan" butnot "Zusanlil", showing the specificity of acupoints. High intensity EA at either "Xiaguan" or "Zusan-li" also reduced the nociceptive responses, showing the analgesic extensiveness of acupoints. We sug-gest that "the gate of control" mechanism plays a main role in low intensity EA and "diffuse noxiousinhibitory controls" (DNIC) rnechanism does so in high intensity EA.The results suggest that we should pay attention to the location of acupoints,展开更多
The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the th...The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.展开更多
The hemagglutinin (HA) of influenza viruses facilitates receptor binding and membrane fusion, which is the initial step of virus infection. Human influenza viruses preferentially bind to receptors with α2-6 lin- kage...The hemagglutinin (HA) of influenza viruses facilitates receptor binding and membrane fusion, which is the initial step of virus infection. Human influenza viruses preferentially bind to receptors with α2-6 lin- kages to galactose (SAα2,6Gal), whereas avian influenza viruses prefer receptors with α2-3 linkages to galactose (SAα2,3Gal). The current 2009 H1N1 pandemic is caused by a novel influenza A virus that has its genetic materials from birds, humans, and pigs. Its pandemic nature is characterized clearly by its dual binding to the α2-3 as well as α2-6 receptors, because the seasonal human H1N1 virus only binds to the α2-6 receptor. In a previous study, the informational spectrum method (ISM), a bioinformatics technique, was applied to uncover one highly conserved region in the HA protein associated with receptor binding preference in each of various influenza subtypes. In the present study, we extended the previous work by discovering multiple such domains in HA of 2009 H1N1 and avian H5N1 to expand our repertoire of known key regions in HA responsible for receptor binding affinity. Three such domains in HA of 2009 H1N1 were found at residue positions 106 to 130, 150 to 174, and 191 to 221, and another three domains in HA of avian H5N1 were located at residue positions 46 to 65, 136 to 153, and 269 to 286. These identified domains could be utilized as therapeutic and diagnostic targets for the prevention and treatment of influenza infection.展开更多
Visual evoked potentials (VEPs) are a series of signals about visual occipital cortex in response to visual stimuli and can be used as one of ob-jective non-invasive neuro-physiological pa-rameters to reflect the visu...Visual evoked potentials (VEPs) are a series of signals about visual occipital cortex in response to visual stimuli and can be used as one of ob-jective non-invasive neuro-physiological pa-rameters to reflect the visual organs and central visual pathway’s functional integrity. Previous studies have shown that acute and chronic ex-ercise could affect VEPs independent from body temperature and other physiological parameters. VEPs may well be used as neuro-physiological criteria in defining the performances of the ath-letes. Different sports training have different effects on VEPs, but the results are not consis-tent. P100 latency is the representative compo-nent of VEPs and it is of high, steady amplitude and of slight intra- and inter-individual variabil-ity so that the index is most commonly used. The purpose of this study was to investigate the specificity and sensitivity of P100 latency to dif-ferent physical activities. The neural electricity device of NDI-200 was used to measure the pattern reversal VEPs of all subjects, including the values of the resting state before and after different events exercise. Different events exer-cise contained an aerobic cycloergometric ex-ercise (7 subjects were conducted to a Bruce Graded Exercise Test on the Monark Ergomedic 839E cycloergometer, THR (target heart rate) = 85% HRmax, 3 times/week, about 10 minutes once time, 6 weeks), tennis training (16 volun-teers, 2 hours/day, 3 days/week, 8 weeks), aerobic Latin exercise (7 subjects, 1 hour/day, 3 days/week, 6 weeks) and the Baduanjin of Health Qigong training (6 subjects, 1 hour/day, 3 days/week, 6 weeks). The VEPs recordings of the control groups obtained synchronized with the experimental groups. SPSS 11.5 for win-dows was used for statistical analysis. A level of P﹤0.05 was accepted as statistically significant. The VEPs P100 latency of post-exercise of all experimental groups except Baduanjin group became shorter significantly compared with those of pre-exercise (P﹤0.05). No significant difference was found between pre-and post- exercise for the control groups. This study showed that exercise could shorten the P100 la-tency significantly. Moreover, it also indicated that VEPs were sensitive to exercise to a certain extent. We concluded that VEPs might well be used as neuro-physiological criteria in defining the performances of the athletes. It was found that the VEPs P100 latency became shorter after most training programs;furthermore, it demon-strated that P100 latency of VEPs had little specificity to different events.展开更多
The influence of factors on the subst rate-specificity of Pst Ⅰ restric tion endonuclease has been studied with the method of electrophoresis. The resu lts show that, the specificity of Pst Ⅰ almost can not be influ...The influence of factors on the subst rate-specificity of Pst Ⅰ restric tion endonuclease has been studied with the method of electrophoresis. The resu lts show that, the specificity of Pst Ⅰ almost can not be influenced by th e sin gle alteration of the concentration of Tris·HCl, Mg 2+ or Na+ in the rea ction s ystem, but it can be altered by the reduction of any two of them. The specificit y can not be altered by the single alteration of pH or the replacement of Mg 2+ w ith Mn 2+. The addition of glycerol or dimethylsulphoxide (DMSO) to the rea ction system results in the relaxation of the substrate-specificity of Pst Ⅰ , b ut dim ethylmethylformide, glycol and ethyl alcohol can not bring about the alteration of Pst Ⅰ specificity. Through the method of cloning and sequencing, the nuc leot ides of No.1 and 6 in the recognition sequence of Pst Ⅰ have changed (1C→A or 6 G→T). Used with the enzyme analysis of an artificially synthetic DNA segment co ntaining a special sequence, the nucleotides of No.1 and 6 have both changed (1C →A and 6G→T). The recognition sequence of Pst Ⅰ is speculated to be chan ged from CTGCA↓G to TGCA↓.展开更多
Specificity protein(Sp)transcription factors(TFs)Sp1,Sp3 and Sp4,and the orphan nuclear receptor 4A1(NR4A1)are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patien...Specificity protein(Sp)transcription factors(TFs)Sp1,Sp3 and Sp4,and the orphan nuclear receptor 4A1(NR4A1)are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patient survival.Results of knockdown and overexpression of Sp1,Sp3 and Sp4 in pancreatic and other cancer lines show that these TFs are individually pro-oncogenic factors and loss of one Sp TF is not compensated by other members.NR4A1 is also a prooncogenic factor and both NR4A1 and Sp TFs exhibit similar functions in pancreatic cancer cells and regulate cell growth,survival,migration and invasion.There is also evidence that Sp TFs and NR4A1 regulate some of the same genes including survivin,epidermal growth factor receptor,PAX3-FOXO1,α5-andα6-integrins,β1-,β3-andβ4-integrins;this is due to NR4A1 acting as a cofactor and mediating NR4A1/Sp1/4-regulated gene expression through GC-rich gene promoter sites.Several studies show that drugs targeting Sp downregulation or NR4A1 antagonists are highly effective inhibitors of Sp/NR4A1-regulated pathways and genes in pancreatic and other cancer cells,and the triterpenoid celastrol is a novel dual-acting agent that targets both Sp TFs and NR4A1.展开更多
Previous studies on mammals showed that peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)played a prominent role in regulating muscle fiber type transition and composition.However,the role of P...Previous studies on mammals showed that peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)played a prominent role in regulating muscle fiber type transition and composition.However,the role of PGC-1αin chicken muscle has seldom been explored.To investigate the effect of PGC-1αon chicken skeletal muscles in this study,the PGC-1αgene was overexpressed or silenced in chicken primary myoblasts by using lentivirus,and then the effects of the PGC-1αgene overexpression and knockdown on the mRNA expression profile of genes related to myofiber type specificity were examined during fiber formation.The results showed that overexpression of PGC-1αfrom proliferation to differentiation was accompanied by the up-regulated expression of Pax7,MyoD,and CnAα,which was significantly(P<0.01)increased after one day of transfection(1 I).The enhancement of MyoG,MEF2 c,and MyHC SM expression lagged,which was improved significantly(P<0.01)after four days of transfection(1 I3 D).Overexpression of PGC-1αdecreased(P<0.01)the MyHC FWM expression after four days of transfection(1 I3 D),and it had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM during myofiber formation.The effective silence(P<0.01)of PGC-1αby lentivirus mediating short hairpin RNA(shRNA)was detected after four days of transfection(1 I3 D)in cultures,and the lack of its function in chicken primary myoblasts significantly(P<0.01)down-regulated the expression of Pax7,MyoD,CnAα,MyoG,MEF2 c,and MyHC SM,significantly(P<0.01)up-regulated the expression of MyHC FWM,and had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM.These results indicated that the role of PGC-1αin regulating the fiber type specificity of chicken skeletal muscles might be similar to that in mammals,which interplayed with key genes related to myocyte differentiation and calcineurin signaling pathway.展开更多
AIM:To investigate the expression profiles of the transcription factor specificity protein 1(Sp1)and collagenⅠin recurrent pterygial tissues.What is more,to compare the changes of Sp1 and collagen I among primary pte...AIM:To investigate the expression profiles of the transcription factor specificity protein 1(Sp1)and collagenⅠin recurrent pterygial tissues.What is more,to compare the changes of Sp1 and collagen I among primary pterygial tissue,recurrent pterygial tissue and conjunctival tissue.METHODS:In the prospective study,we collected the pterygial tissues of 40 patients who underwent resection of primary pterygial tissue and recurrent pterygial tissue,and the conjunctival tissues of 10 patients with enucleation due to trauma.The relative expression levels of Sp1 and collagen I were analyzed by reverse transcription quantitative-polymerase chain reaction and Western blot.Paired t-test was performed to compare the Sp1 and collagen I of recurrent pterygial tissues,as well as the primary pterygial tissues and conjunctival tissues.In further,Pearson’s hypothesis testing of correlation coefficients was used to compare the correlations of Sp1 and Collagen I.RESULTS:The content of Sp1 and collagen I m RNA and protein was significantly greater in recurrent pterygial tissue than that was in primary and conjunctival tissue(P<0.05).There was a positive correlation between the m RNA and protein levels of Sp1 and collagen I in recurrent pterygial tissues(protein:r=0.913,P<0.05;m RNA:r=0.945,P<0.05).CONCLUSION:Sp1 and collagen I are expressed in normal conjunctival,primary,and recurrent pterygial tissues,but expression is significantly greater in the latter.Sp1 and collagen I may be involved in the regulation of the development of recurrent pterygium.展开更多
Introduction: Reports indicate that fluorescent staining of smears increases sensitivity of direct microscopy;so ZN staining is being replaced with fluorescent microscopy in RNTCP in India. Chemical processing and spu...Introduction: Reports indicate that fluorescent staining of smears increases sensitivity of direct microscopy;so ZN staining is being replaced with fluorescent microscopy in RNTCP in India. Chemical processing and sputum concentration may also improve sensitivity of microscopy. Objective: To compare the sensitivity and specificity of microscopy for AFB using ZN and fluorescent stains in direct and concentrated specimen with culture as gold standard. Methods: Morning sputum specimen of patients, suspected of having pulmonary tuberculosis, over a period of 6 months was subjected to direct microscopy using fluorescent stain;the same slide was over-stained with ZN stain. Same sputum sample was concentrated by Petroff’s method and subjected to fluorescent microscopy followed by ZN microscopy and finally to culture for AFB. Results: Sensitivity of fluorescent stained concentrated sputum samples was maximum and of ZN stained unprocessed sputum samples was minimum. Specificity of three of the methods was equal at 0.96 but of ZN stained concentrated sputum smears was 0.97. Sensitivity of total fluorescent stains was 0.85 (Specificity 0.96) and sensitivity of total ZN stained smears was 0.80 (Specificity 0.96). Discussion: We used same smear for fluorescent and ZN stains, so smear related variability is decreased. Blinding for microscopy was practically complete. Conclusion: The sensitivity of sputum microscopy for AFB can be increased by concentrating the sputum and using fluorescent microscopy. The specificity remains high in all the methods.展开更多
A widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was imprinted on poly (4-vinylpyridine) (4-VP) using (40%) ethyleneglycol dimethacrylate (EGDMA) as crosslinking agent. The classical imprinting technolog...A widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was imprinted on poly (4-vinylpyridine) (4-VP) using (40%) ethyleneglycol dimethacrylate (EGDMA) as crosslinking agent. The classical imprinting technology makes use of a high degree of crosslinking which does not allow the template molecules to move freely. So the binding sites, located in the central area of the three dimensional polymer matrix are hard to be accessed and the template molecules cannot be extracted totally. But here we propose a low crosslinked system with high specificity and selectivity. The imprinted and non-imprinted polymers were characterized by various spectroscopic techniques. The extent of binding was followed by batch equilibration method and compared with the respective non-imprinted polymer. Conditions for maximum specific rebinding were set by altering certain factors like template/monomer ratio, concentration of template solution, rebinding medium, mass of polymer and time of incubation. The selectivity of the imprinted polymer was investigated by comparing the binding with structural analogues of 2,4-D like, phenoxyacetic acid (POA), 4-chlorophenoxyacetic acid (4-CPOA) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The imprinted polymer exhibited high affinity towards the template molecule and was selectively rebound to the specific sites. The binding towards the structural analogues depends on the number of chlorine in the benzene ring.展开更多
After calculation on the fracture angles under various conditions of specific surface energies with different symmetry operations of rotation, the complicated behavior of dependence of fractal dimension on the strudur...After calculation on the fracture angles under various conditions of specific surface energies with different symmetry operations of rotation, the complicated behavior of dependence of fractal dimension on the strudure of crystal is shown. It is found that the crack propagates along the weakest crystal plane no matter what the direction of the maximum stress is if the anisotropy is sufficiently strong; and then, the fractal dimension of the fractured surfaces might be determined by the approximate fractal Structure already existed in the material. Specificity of the fractal dimension of fractured surfaces would be easy to appear in this case. Reversely, the crack propagates along the direction of the maximum stress no matter what direction of the weakest crystal plane is if the anisotropy is sufficiently weak. Universality of the fractal dimension of fractured surfaces would be possible to appear in this case. In many real materials, universality and specificity of the materials are associated. The fractal dimension measured may more or less be influenced by the Structure of materials and it shows its universality through the specificity of materials.展开更多
Recently, a genetic variant of 2009 H1N1 has become the predominant virus circulating in the southern hemisphere, particularly Australia and New Zealand, and in Singapore during the winter of 2010. It was associated w...Recently, a genetic variant of 2009 H1N1 has become the predominant virus circulating in the southern hemisphere, particularly Australia and New Zealand, and in Singapore during the winter of 2010. It was associated with several vaccine breakthroughs and fatal cases. We analyzed three reported mutations D94N, N125D, and V250A in the HA protein of this genetic variant. It appeared that the reason for D94N and V250A to occur in pairs was to maintain the HA binding to human type receptor, so the virus could replicate in humans efficiently. Guided by this interpretation, we discovered a new mutation V30A that could compensate for N125D as V250A did for D94N. We demonstrated that the presence of amino acids 30A and 125N in HA enhanced the binding to human type receptor, while 30V and 125D favored the receptors of avian type and of A/South Carolina/1/18 (H1N1). Furthermore, a combination of 94D, 125D, and 250V made the primary binding preference similar to that of A/South Carolina/1/18 (H1N1) and a combination of 94N, 125D, and 250A resulted in the primary binding affinity for avian type receptor, which clearly differed from that of A/California/07/2009 (H1N1), a strain used in the vaccine for 2009 H1N1. We also re-examined the origin of 2009 H1N1 to refine our knowledge of this important issue. Although the NP, PA, PB1, and PB2 of 2009 H1N1 were closest to North American swine H3N2 in sequence identity, their interaction patterns were closest to swine H1N1 in North America.展开更多
Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly de...Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly demonstrated that only five mutations, fewer than previously estimated, are needed to make avian H5N1 influenza transmissible between ferrets through the air, raising fears that a human pandemic is possible if this virus escapes from the lab. Of the five mutations found, four of them are located in the HA gene that is responsible for the viral entry into the host cells. A crucial step for avian influenza to go across the species boundary to infect humans is the switch of its receptor binding specificity from avian to human types. The first task of this study was to quantify the individual as well as the collective effect of the known HA mutations from the previous research on receptor binding selection. Our second task was to identify new combinations of HA mutations that could change the receptor binding preference of H5N1 from avian to human types. Our findings thus deepened our understanding of the previous research and also extended its results by discovering new combinations of mutations that could enhance the binding of avian H5N1 to human type receptors while reduce that to avian types.展开更多
Avian influenza such as H5N1 could infect humans and cause great health concern due to its high mortality rate. In March 2013, a novel reassortant avian-origin influenza A (H7N9) virus was found in several patients wi...Avian influenza such as H5N1 could infect humans and cause great health concern due to its high mortality rate. In March 2013, a novel reassortant avian-origin influenza A (H7N9) virus was found in several patients with severe respiratory illness in China. Since then, at least 82 people in China have been infected with this new virus and 17 have died from this virus. The question of how these people were infected with this virus and whether this virus will spread among people remains an urgent topic for research. This study took an early investigation of this virus ?by comparing the collected viral genome sequences ?of 2013 H7N9 inChinaagainst those of previous avian H7N9 and examined the receptor binding specificity of this new virus. This virus was found to be very different from the previous avian H7N9 viruses and surprisingly many of the internal proteins of 2013 H7N9 from the avian and human hosts in China were either identical or similar. Our analysis of the HA protein of this virus implied that the current strains of 2013 H7N9 inChina displayed avian type receptors as their primary binding preference and human type receptors as secondary. For pandemic risk assessment, we also detected 23 mutations, including a few well known for host adaptation, in the HA1 domain of the HA protein from this virus. Each mutation was quantified for its impact on the recaptor binding selection using a bioinformatics approach. Collectively these current mutations tended to decrease the HA binding affinity for avian type recaptors and increase that for human type receptors, which could enhance the ability of this virus to infect humans.展开更多
基金supported by the National Natural Science Foundation of China(71573211)the Humanities and Social Sciences Youth Foundation+1 种基金Ministry of Education of China(22YJC790164)the earmarked fund for China Agriculture Research System(CARS-28)。
文摘Understanding the factors behind apple farmers’willingness to pass on the management of their farms to their descendants is crucial to the continuity of apple production.Due to the high specificity of the human capital,physical assets,land assets,and geographical location in apple production,this study used a binary logistic regression and a mediating effect model to explore the impact of asset specificity on farmers’intergenerational succession willingness of apple management(FISWAM)and to examine the mediating effects of loss aversion in the impact of asset specificity on the FISWAM.The results showed that about 18.68%of the respondents expressed willingness to transfer their apple business between generations,and the FISWAM was generally weak.In addition to the negative impact of geographical location specificity(GLS),human capital specificity(HCS),physical assets specificity(PAS),and land assets specificity(LAS)can enhance the FISWAM.Loss aversion plays a partial mediating role in the impact of PAS,LAS,and GLS on the FISWAM.
基金supported in part by the Key-Area Research and Development Program of Guangdong Province (2020B010166006)the National Natural Science Foundation of China (61972102)+2 种基金the Guangzhou Science and Technology Plan Project (023A04J1729)the Science and Technology development fund (FDCT)Macao SAR (015/2020/AMJ)。
文摘Domain adaptation(DA) aims to find a subspace,where the discrepancies between the source and target domains are reduced. Based on this subspace, the classifier trained by the labeled source samples can classify unlabeled target samples well.Existing approaches leverage Graph Embedding Learning to explore such a subspace. Unfortunately, due to 1) the interaction of the consistency and specificity between samples, and 2) the joint impact of the degenerated features and incorrect labels in the samples, the existing approaches might assign unsuitable similarity, which restricts their performance. In this paper, we propose an approach called adaptive graph embedding with consistency and specificity(AGE-CS) to cope with these issues. AGE-CS consists of two methods, i.e., graph embedding with consistency and specificity(GECS), and adaptive graph embedding(AGE).GECS jointly learns the similarity of samples under the geometric distance and semantic similarity metrics, while AGE adaptively adjusts the relative importance between the geometric distance and semantic similarity during the iterations. By AGE-CS,the neighborhood samples with the same label are rewarded,while the neighborhood samples with different labels are punished. As a result, compact structures are preserved, and advanced performance is achieved. Extensive experiments on five benchmark datasets demonstrate that the proposed method performs better than other Graph Embedding methods.
文摘Objectives: The study aimed to determine the most appropriate hearing screening test to identify disabling hearing loss for adults aged 65 years or older.Methods: This study included 577 older adults. Four hearing screening tests were considered in the study, including the Hearing Handicap Inventory for Elderly Screening(HHIE-s), three single question tests, the whisper test, and the finger rub test. The sensitivity and specificity of these tests referenced to the hearing threshold of disabling hearing loss were estimated.Results: Among all tests, only the single self-perception question(0.7064 for sensitivity;0.7225 for specificity) and whisper test(0.7833 for sensitivity;0.7708 for specificity) could obtain both sensitivity and specificity higher than 70% for adults aged ≥65 years.Conclusion: Overall, we suggest using the whisper test to identify disabling hearing loss(>40 dB HL at the better ear) for adults aged 65 years or older. However, if the conditions do not permit, the single selfperception question is also acceptable. Moreover, HHIE-s might not be a good test to detect disabling hearing loss for adults aged 80 years or older.
文摘The cerebral cortex is one of the most complex structures of the mammalian central nervous system and accounts for the extraordinary cognitive abilities in primates and humans.Since the 19th century,neur ons have been believed to be the main players in the building of the brain,yet astrocytes also play a crucial role as fundamental building blocks of the cerebral cortex complexity.
基金Shanxi Province Applied Basic Research Project(No.201801D121358)。
文摘Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic experimental colitis in rats through the PI3K/AKT/mTOR signaling pathway.Methods:Sixty pathogen-free SD rats were randomly assigned to six groups:the normal,model,Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)groups,each with 10 rats.Chronic colitis was induced in rats by combining immunization and local stimulation.After model establishment,electrical needle intervention combined with dispersing wave of 2 Hz/50 Hz with a current intensity of 2 mA once daily for 20 min was applied on acupoints of each group.Subsequently,the inflammation of colonic mucosa and serum levels of inflammatory factors(IL-23,IL-17,IL-10)were observed;ELISA was used to detect mRNA expressions of PI3K,Akt and mTOR in colitic tissues by RT-PCR as well as protein content of p-PI3k/PI3K,p-Akt/Akt,and p-mTOR/mTOR in colitic tissues by Western blotting.Result:Compared with the normal group,the model rats showed a poor general condition,serious damage to the colonic mucosa with a large number of inflammatory cells infiltration.The serum IL-23 and IL-17 expressions were significantly increased(P<0.01),while the serum IL-10 expression was significantly decreased(P<0.01);the mRNA and protein expressions of PI3K,Akt,mTOR and p-PI3K,p-Akt and p-mTOR were significantly increased(P<0.05,P<0.01).Compared with the model group,the pathological slices of rats in each acupoints intervention group showed obvious improvement of colitis inflammatory reaction and tissue damage;the serological levels of IL-23 and IL-17 were significantly reduced(P<0.01),while the serology level of IL-10 was significantly increased(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Compared with Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)groups,the recovery degree of mucosa layers in Shang Ju Xu(ST37)group was closer to that of normal group,and the curative effect was relatively the best;in terms of serological levels of IL-23 and IL-17,the Shang Ju Xu(ST37)group was significantly lower(P<0.05),while the level of IL-10 was significantly higher(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Conclusion:Results indicate that electrical acupuncture at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)show similar effects in relieving the colitis-induced damage in the mucosa of chronic colitis rats,as well as inflammatory response.Among them,Shang Ju Xu(ST25)has a superior overall effect in treating chronic colitis compared to Tian Shu(ST25),Da Chang Shu(BL25)and Zu San Li(ST36).The mechanism may be related to inhibition of PI3K/Akt/mTOR signaling pathway.
文摘Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at receptive field (cheek) were recorded extracellularly with glass mi-cro-electrode. Electroacupuncture (EA ) was applied at bilateral " Xiaguan" (ST 7 on face ) or "Zusanli" (ST 36 on shank) acupoint with Iow (2V) and high (18V) intensity. The noclceptive re-sponse of convergent neurons in TNC could be inhihited by low intensity EA applied at "Xiaguan" butnot "Zusanlil", showing the specificity of acupoints. High intensity EA at either "Xiaguan" or "Zusan-li" also reduced the nociceptive responses, showing the analgesic extensiveness of acupoints. We sug-gest that "the gate of control" mechanism plays a main role in low intensity EA and "diffuse noxiousinhibitory controls" (DNIC) rnechanism does so in high intensity EA.The results suggest that we should pay attention to the location of acupoints,
基金supported by the National Natural Science Foundation of China (Grant No.81622035, 81672610, and 81521002)
文摘The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.
文摘The hemagglutinin (HA) of influenza viruses facilitates receptor binding and membrane fusion, which is the initial step of virus infection. Human influenza viruses preferentially bind to receptors with α2-6 lin- kages to galactose (SAα2,6Gal), whereas avian influenza viruses prefer receptors with α2-3 linkages to galactose (SAα2,3Gal). The current 2009 H1N1 pandemic is caused by a novel influenza A virus that has its genetic materials from birds, humans, and pigs. Its pandemic nature is characterized clearly by its dual binding to the α2-3 as well as α2-6 receptors, because the seasonal human H1N1 virus only binds to the α2-6 receptor. In a previous study, the informational spectrum method (ISM), a bioinformatics technique, was applied to uncover one highly conserved region in the HA protein associated with receptor binding preference in each of various influenza subtypes. In the present study, we extended the previous work by discovering multiple such domains in HA of 2009 H1N1 and avian H5N1 to expand our repertoire of known key regions in HA responsible for receptor binding affinity. Three such domains in HA of 2009 H1N1 were found at residue positions 106 to 130, 150 to 174, and 191 to 221, and another three domains in HA of avian H5N1 were located at residue positions 46 to 65, 136 to 153, and 269 to 286. These identified domains could be utilized as therapeutic and diagnostic targets for the prevention and treatment of influenza infection.
基金supported by the National Natural Scientific Foundation of China(81472924,81620108026)the Fundamental Research Funds for the Central Universities in 2015
文摘Visual evoked potentials (VEPs) are a series of signals about visual occipital cortex in response to visual stimuli and can be used as one of ob-jective non-invasive neuro-physiological pa-rameters to reflect the visual organs and central visual pathway’s functional integrity. Previous studies have shown that acute and chronic ex-ercise could affect VEPs independent from body temperature and other physiological parameters. VEPs may well be used as neuro-physiological criteria in defining the performances of the ath-letes. Different sports training have different effects on VEPs, but the results are not consis-tent. P100 latency is the representative compo-nent of VEPs and it is of high, steady amplitude and of slight intra- and inter-individual variabil-ity so that the index is most commonly used. The purpose of this study was to investigate the specificity and sensitivity of P100 latency to dif-ferent physical activities. The neural electricity device of NDI-200 was used to measure the pattern reversal VEPs of all subjects, including the values of the resting state before and after different events exercise. Different events exer-cise contained an aerobic cycloergometric ex-ercise (7 subjects were conducted to a Bruce Graded Exercise Test on the Monark Ergomedic 839E cycloergometer, THR (target heart rate) = 85% HRmax, 3 times/week, about 10 minutes once time, 6 weeks), tennis training (16 volun-teers, 2 hours/day, 3 days/week, 8 weeks), aerobic Latin exercise (7 subjects, 1 hour/day, 3 days/week, 6 weeks) and the Baduanjin of Health Qigong training (6 subjects, 1 hour/day, 3 days/week, 6 weeks). The VEPs recordings of the control groups obtained synchronized with the experimental groups. SPSS 11.5 for win-dows was used for statistical analysis. A level of P﹤0.05 was accepted as statistically significant. The VEPs P100 latency of post-exercise of all experimental groups except Baduanjin group became shorter significantly compared with those of pre-exercise (P﹤0.05). No significant difference was found between pre-and post- exercise for the control groups. This study showed that exercise could shorten the P100 la-tency significantly. Moreover, it also indicated that VEPs were sensitive to exercise to a certain extent. We concluded that VEPs might well be used as neuro-physiological criteria in defining the performances of the athletes. It was found that the VEPs P100 latency became shorter after most training programs;furthermore, it demon-strated that P100 latency of VEPs had little specificity to different events.
基金Supported by the Research Fund for the Doctoral Program of Higher Education.
文摘The influence of factors on the subst rate-specificity of Pst Ⅰ restric tion endonuclease has been studied with the method of electrophoresis. The resu lts show that, the specificity of Pst Ⅰ almost can not be influenced by th e sin gle alteration of the concentration of Tris·HCl, Mg 2+ or Na+ in the rea ction s ystem, but it can be altered by the reduction of any two of them. The specificit y can not be altered by the single alteration of pH or the replacement of Mg 2+ w ith Mn 2+. The addition of glycerol or dimethylsulphoxide (DMSO) to the rea ction system results in the relaxation of the substrate-specificity of Pst Ⅰ , b ut dim ethylmethylformide, glycol and ethyl alcohol can not bring about the alteration of Pst Ⅰ specificity. Through the method of cloning and sequencing, the nuc leot ides of No.1 and 6 in the recognition sequence of Pst Ⅰ have changed (1C→A or 6 G→T). Used with the enzyme analysis of an artificially synthetic DNA segment co ntaining a special sequence, the nucleotides of No.1 and 6 have both changed (1C →A and 6G→T). The recognition sequence of Pst Ⅰ is speculated to be chan ged from CTGCA↓G to TGCA↓.
基金Supported by Houston Methodist Cancer Center Innovation Award。
文摘Specificity protein(Sp)transcription factors(TFs)Sp1,Sp3 and Sp4,and the orphan nuclear receptor 4A1(NR4A1)are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patient survival.Results of knockdown and overexpression of Sp1,Sp3 and Sp4 in pancreatic and other cancer lines show that these TFs are individually pro-oncogenic factors and loss of one Sp TF is not compensated by other members.NR4A1 is also a prooncogenic factor and both NR4A1 and Sp TFs exhibit similar functions in pancreatic cancer cells and regulate cell growth,survival,migration and invasion.There is also evidence that Sp TFs and NR4A1 regulate some of the same genes including survivin,epidermal growth factor receptor,PAX3-FOXO1,α5-andα6-integrins,β1-,β3-andβ4-integrins;this is due to NR4A1 acting as a cofactor and mediating NR4A1/Sp1/4-regulated gene expression through GC-rich gene promoter sites.Several studies show that drugs targeting Sp downregulation or NR4A1 antagonists are highly effective inhibitors of Sp/NR4A1-regulated pathways and genes in pancreatic and other cancer cells,and the triterpenoid celastrol is a novel dual-acting agent that targets both Sp TFs and NR4A1.
基金supported by the National Natural Science Foundation of China(31301967)the Natural Science Foundation of Jiangsu Province,China(BK20161322)+4 种基金the projects of Key Laboratory for Poultry Genetics and Breeding of Jiangsu Province(JQLAB-ZZ-201703)the Major Breeding Programs in Jiangsu Province,China(PZCZ201728)the earmarked fund for China Agriculture Research System(CARS-41)the Independent Scientific Foundation of Public Welfare Scientific Institutes in Jiangsu Province,China(BM2018026)the Open Projects of Key Laboratory of Chicken Genetics and Breeding,Ministry of Agriculture and Rural Affairs of China(CGB-201704)。
文摘Previous studies on mammals showed that peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)played a prominent role in regulating muscle fiber type transition and composition.However,the role of PGC-1αin chicken muscle has seldom been explored.To investigate the effect of PGC-1αon chicken skeletal muscles in this study,the PGC-1αgene was overexpressed or silenced in chicken primary myoblasts by using lentivirus,and then the effects of the PGC-1αgene overexpression and knockdown on the mRNA expression profile of genes related to myofiber type specificity were examined during fiber formation.The results showed that overexpression of PGC-1αfrom proliferation to differentiation was accompanied by the up-regulated expression of Pax7,MyoD,and CnAα,which was significantly(P<0.01)increased after one day of transfection(1 I).The enhancement of MyoG,MEF2 c,and MyHC SM expression lagged,which was improved significantly(P<0.01)after four days of transfection(1 I3 D).Overexpression of PGC-1αdecreased(P<0.01)the MyHC FWM expression after four days of transfection(1 I3 D),and it had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM during myofiber formation.The effective silence(P<0.01)of PGC-1αby lentivirus mediating short hairpin RNA(shRNA)was detected after four days of transfection(1 I3 D)in cultures,and the lack of its function in chicken primary myoblasts significantly(P<0.01)down-regulated the expression of Pax7,MyoD,CnAα,MyoG,MEF2 c,and MyHC SM,significantly(P<0.01)up-regulated the expression of MyHC FWM,and had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM.These results indicated that the role of PGC-1αin regulating the fiber type specificity of chicken skeletal muscles might be similar to that in mammals,which interplayed with key genes related to myocyte differentiation and calcineurin signaling pathway.
基金Supported by the Key Program of Natural Science Research of Anhui Provincial Education Department(No.KJ2019A1097)Science Foundation of Anhui Provincial Health Bureau(No.2018SEYL025)Natural Science Research of Anhui Provincial Education Department(No.12925KJ2018B11)。
文摘AIM:To investigate the expression profiles of the transcription factor specificity protein 1(Sp1)and collagenⅠin recurrent pterygial tissues.What is more,to compare the changes of Sp1 and collagen I among primary pterygial tissue,recurrent pterygial tissue and conjunctival tissue.METHODS:In the prospective study,we collected the pterygial tissues of 40 patients who underwent resection of primary pterygial tissue and recurrent pterygial tissue,and the conjunctival tissues of 10 patients with enucleation due to trauma.The relative expression levels of Sp1 and collagen I were analyzed by reverse transcription quantitative-polymerase chain reaction and Western blot.Paired t-test was performed to compare the Sp1 and collagen I of recurrent pterygial tissues,as well as the primary pterygial tissues and conjunctival tissues.In further,Pearson’s hypothesis testing of correlation coefficients was used to compare the correlations of Sp1 and Collagen I.RESULTS:The content of Sp1 and collagen I m RNA and protein was significantly greater in recurrent pterygial tissue than that was in primary and conjunctival tissue(P<0.05).There was a positive correlation between the m RNA and protein levels of Sp1 and collagen I in recurrent pterygial tissues(protein:r=0.913,P<0.05;m RNA:r=0.945,P<0.05).CONCLUSION:Sp1 and collagen I are expressed in normal conjunctival,primary,and recurrent pterygial tissues,but expression is significantly greater in the latter.Sp1 and collagen I may be involved in the regulation of the development of recurrent pterygium.
文摘Introduction: Reports indicate that fluorescent staining of smears increases sensitivity of direct microscopy;so ZN staining is being replaced with fluorescent microscopy in RNTCP in India. Chemical processing and sputum concentration may also improve sensitivity of microscopy. Objective: To compare the sensitivity and specificity of microscopy for AFB using ZN and fluorescent stains in direct and concentrated specimen with culture as gold standard. Methods: Morning sputum specimen of patients, suspected of having pulmonary tuberculosis, over a period of 6 months was subjected to direct microscopy using fluorescent stain;the same slide was over-stained with ZN stain. Same sputum sample was concentrated by Petroff’s method and subjected to fluorescent microscopy followed by ZN microscopy and finally to culture for AFB. Results: Sensitivity of fluorescent stained concentrated sputum samples was maximum and of ZN stained unprocessed sputum samples was minimum. Specificity of three of the methods was equal at 0.96 but of ZN stained concentrated sputum smears was 0.97. Sensitivity of total fluorescent stains was 0.85 (Specificity 0.96) and sensitivity of total ZN stained smears was 0.80 (Specificity 0.96). Discussion: We used same smear for fluorescent and ZN stains, so smear related variability is decreased. Blinding for microscopy was practically complete. Conclusion: The sensitivity of sputum microscopy for AFB can be increased by concentrating the sputum and using fluorescent microscopy. The specificity remains high in all the methods.
文摘A widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was imprinted on poly (4-vinylpyridine) (4-VP) using (40%) ethyleneglycol dimethacrylate (EGDMA) as crosslinking agent. The classical imprinting technology makes use of a high degree of crosslinking which does not allow the template molecules to move freely. So the binding sites, located in the central area of the three dimensional polymer matrix are hard to be accessed and the template molecules cannot be extracted totally. But here we propose a low crosslinked system with high specificity and selectivity. The imprinted and non-imprinted polymers were characterized by various spectroscopic techniques. The extent of binding was followed by batch equilibration method and compared with the respective non-imprinted polymer. Conditions for maximum specific rebinding were set by altering certain factors like template/monomer ratio, concentration of template solution, rebinding medium, mass of polymer and time of incubation. The selectivity of the imprinted polymer was investigated by comparing the binding with structural analogues of 2,4-D like, phenoxyacetic acid (POA), 4-chlorophenoxyacetic acid (4-CPOA) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The imprinted polymer exhibited high affinity towards the template molecule and was selectively rebound to the specific sites. The binding towards the structural analogues depends on the number of chlorine in the benzene ring.
基金National Natural Science Foundation of China!59671093 National Natural Science Foundation of China !19874064
文摘After calculation on the fracture angles under various conditions of specific surface energies with different symmetry operations of rotation, the complicated behavior of dependence of fractal dimension on the strudure of crystal is shown. It is found that the crack propagates along the weakest crystal plane no matter what the direction of the maximum stress is if the anisotropy is sufficiently strong; and then, the fractal dimension of the fractured surfaces might be determined by the approximate fractal Structure already existed in the material. Specificity of the fractal dimension of fractured surfaces would be easy to appear in this case. Reversely, the crack propagates along the direction of the maximum stress no matter what direction of the weakest crystal plane is if the anisotropy is sufficiently weak. Universality of the fractal dimension of fractured surfaces would be possible to appear in this case. In many real materials, universality and specificity of the materials are associated. The fractal dimension measured may more or less be influenced by the Structure of materials and it shows its universality through the specificity of materials.
文摘Recently, a genetic variant of 2009 H1N1 has become the predominant virus circulating in the southern hemisphere, particularly Australia and New Zealand, and in Singapore during the winter of 2010. It was associated with several vaccine breakthroughs and fatal cases. We analyzed three reported mutations D94N, N125D, and V250A in the HA protein of this genetic variant. It appeared that the reason for D94N and V250A to occur in pairs was to maintain the HA binding to human type receptor, so the virus could replicate in humans efficiently. Guided by this interpretation, we discovered a new mutation V30A that could compensate for N125D as V250A did for D94N. We demonstrated that the presence of amino acids 30A and 125N in HA enhanced the binding to human type receptor, while 30V and 125D favored the receptors of avian type and of A/South Carolina/1/18 (H1N1). Furthermore, a combination of 94D, 125D, and 250V made the primary binding preference similar to that of A/South Carolina/1/18 (H1N1) and a combination of 94N, 125D, and 250A resulted in the primary binding affinity for avian type receptor, which clearly differed from that of A/California/07/2009 (H1N1), a strain used in the vaccine for 2009 H1N1. We also re-examined the origin of 2009 H1N1 to refine our knowledge of this important issue. Although the NP, PA, PB1, and PB2 of 2009 H1N1 were closest to North American swine H3N2 in sequence identity, their interaction patterns were closest to swine H1N1 in North America.
文摘Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly demonstrated that only five mutations, fewer than previously estimated, are needed to make avian H5N1 influenza transmissible between ferrets through the air, raising fears that a human pandemic is possible if this virus escapes from the lab. Of the five mutations found, four of them are located in the HA gene that is responsible for the viral entry into the host cells. A crucial step for avian influenza to go across the species boundary to infect humans is the switch of its receptor binding specificity from avian to human types. The first task of this study was to quantify the individual as well as the collective effect of the known HA mutations from the previous research on receptor binding selection. Our second task was to identify new combinations of HA mutations that could change the receptor binding preference of H5N1 from avian to human types. Our findings thus deepened our understanding of the previous research and also extended its results by discovering new combinations of mutations that could enhance the binding of avian H5N1 to human type receptors while reduce that to avian types.
文摘Avian influenza such as H5N1 could infect humans and cause great health concern due to its high mortality rate. In March 2013, a novel reassortant avian-origin influenza A (H7N9) virus was found in several patients with severe respiratory illness in China. Since then, at least 82 people in China have been infected with this new virus and 17 have died from this virus. The question of how these people were infected with this virus and whether this virus will spread among people remains an urgent topic for research. This study took an early investigation of this virus ?by comparing the collected viral genome sequences ?of 2013 H7N9 inChinaagainst those of previous avian H7N9 and examined the receptor binding specificity of this new virus. This virus was found to be very different from the previous avian H7N9 viruses and surprisingly many of the internal proteins of 2013 H7N9 from the avian and human hosts in China were either identical or similar. Our analysis of the HA protein of this virus implied that the current strains of 2013 H7N9 inChina displayed avian type receptors as their primary binding preference and human type receptors as secondary. For pandemic risk assessment, we also detected 23 mutations, including a few well known for host adaptation, in the HA1 domain of the HA protein from this virus. Each mutation was quantified for its impact on the recaptor binding selection using a bioinformatics approach. Collectively these current mutations tended to decrease the HA binding affinity for avian type recaptors and increase that for human type receptors, which could enhance the ability of this virus to infect humans.
