Heterodimerization in RTKs is of vital importance in the RTK signaling and cell functions.Heterodimerization between RTKs can result in diversity of downstream signals,increasing the ability of cells to respond to ext...Heterodimerization in RTKs is of vital importance in the RTK signaling and cell functions.Heterodimerization between RTKs can result in diversity of downstream signals,increasing the ability of cells to respond to external experiments.Traditional RTKs heterodimerization always occur in the same families and is lack of agonists to activate the heterodimeric RTKs signaling pathway.Herein,we developed the DNA agonist based on bivalent aptamers for the heterodimerized RTKs of different families,AF/AM-1,which could simultaneously activate FGFR1 and c-Met signaling.It is the first agonist that realizing the heterodimerization and activation of FGFR1 and c-Met,two different RTK families.The activation of FGFR1/c-Met heterodimer result in the down-stream signals transduction,such as the phosphorylation of Akt and Erk,inducing the cell migration and proliferation.The DNA agonist for RTK heterodimer of different families would have potential applications in the fields of biomedicine.展开更多
Artificially induced tetraploid Pacific oyster, Crassostrea gigas Thunberg, produces more aneuploid gametes than nor- mal diploid one, although they showed a comparable fecundity to diploidy. The meiotic chromosome co...Artificially induced tetraploid Pacific oyster, Crassostrea gigas Thunberg, produces more aneuploid gametes than nor- mal diploid one, although they showed a comparable fecundity to diploidy. The meiotic chromosome configuration of 3 tetraploid and 1 tetraploid/triploid mosaic males were analyzed through direct chromosome observation. A majority of metaphase I spermato- cytes contained both bivalents and quadrivalents. The chromosome configuration of these males was characterized by preferential formation of bivalents to quadrivalents. Bivalents appeared in all spermatocytes and consisted of 86% of all chromosome aggregates. In comparison, quadrivalents occurred in 91% spermatocytes and consisted of only 12.6% of all chromosome aggregates. The mean bivalent frequency per spermatocyte varied between 14.4 and 17.2; while that of quadrivalents varied between 2.2 and 2.7. Most quadrivalents were tandemly chained （58%） or circled （39%）. The total number of chromosome aggregates per spermatocyte ranged from 13 to 20 with an average of 17.6; while 18 （16 bivalents and 2 quadrivalents） was the most frequent. Univalents and trivalents appeared in very low frequency. Aneuploid （hypotetraploid） spermatocytes were observed in a low frequency. The chromosome con- figuration of in the mosaic individual was similar to that of tetraploid individuals. The percentage of triploid spermatocytes （2%） of the mosaic individual was significantly lower （2＂2 =30, P〈 0.01） than that of triploid cells （46%） in its somatic tissue.展开更多
Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used forma...Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.展开更多
A-form DNA is one of the biologically active double helical structure.The study of A-DNA structure has an extensive application for developing the field of DNA packaging in biotechnology.In aqueous solution,the A-DNA ...A-form DNA is one of the biologically active double helical structure.The study of A-DNA structure has an extensive application for developing the field of DNA packaging in biotechnology.In aqueous solution,the A-DNA structure will have a free transformation,the A-DNA structure will be translated into B-form structure with the evolution of time,and eventually stabilized in the B-DNA structure.To explore the stability function of the bivalent metal ions on the A-DNA structure,a series of molecular dynamics simulations have been performed on the A-DNA of sequence(CCCGGCCGGG).The results show that bivalent metal ions(Mg^(2+),Zn^(2+),Ca^(2+))generate a great effect on the structural stability of A-DNA in the environment of high concentration.As the interaction between metal ions and electronegative DNA chains,the stability of A-DNA in solution is gradually improved with the increasing solution concentration of ions.In metal salt solution with high concentration,metal ions can be easily distributed in the solvation shells around the phosphate groups and further lead to the formation of shorter and more compact DNA structure.Also,under the condition of the same concentration and valency of the metal ions,the stability of A-DNA structure is different.The calculations indicate that the structure of A-DNA in CaCl_(2)solution is less stable than in MgCl_(2)and ZnCl_(2)solution.展开更多
Well-spread meiotic pachytene bivalents were obtained by using the prolonged hypotonic treatment com-bined with high chloroform Carnory’s fixative solution from cells of the testes of domestic pigs. Comparison in the...Well-spread meiotic pachytene bivalents were obtained by using the prolonged hypotonic treatment com-bined with high chloroform Carnory’s fixative solution from cells of the testes of domestic pigs. Comparison in the division index and length of pachytene bivalents with metaphase chromosomes showed that those of the former are 5 times higher and 3.42(1.87-5.98) times longer than those of the latter. Comparative studies on chromomere maps of bivalents and mitotic chromosomal G-bands were conducted by using the chromo-some 12 as a example. Sex vesicle and various shapes of synaptic sex chromosomes have been observed.Two-color PRimed IN Situ (PRINS) labeling has been conducted successfully on pachytene bivalents of pigs.展开更多
Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myo...Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.展开更多
Huntington’s disease（HD）is a currently incurable,late onset,progressive,ultimately fatal neurological disorder（Bates et al.,2015）.We have recently published the results of comprehensive genetic interaction tests ...Huntington’s disease（HD）is a currently incurable,late onset,progressive,ultimately fatal neurological disorder（Bates et al.,2015）.We have recently published the results of comprehensive genetic interaction tests aimed at identification of histone methyltransferases and demethylases involved in HD pathogenesis in a Drosophila model of the disease（Song et al.,2018）.展开更多
The role of bivalent cations and choline in ATP induced apoptosis via P2Z purinoceptor was investigated in human leukemic lymphocytes. In vitro exposure of leukemic lymphocytes with P2Z rec...The role of bivalent cations and choline in ATP induced apoptosis via P2Z purinoceptor was investigated in human leukemic lymphocytes. In vitro exposure of leukemic lymphocytes with P2Z receptors to 1 mmol/L ATP or 0 1 mmol/L benzoylbenzoic ATP(BzATP) for 8 h in the presence of choline, 1 mmol/L Mg 2+ or other bivalent cations, and ATP induced DNA breaks, associated with apoptosis were quantified by TdT assay. We observed that (1) Extracellular Mg 2+ or Ca 2+ stimulated ATP induced DNA fragmentation in a dose dependent manner, and the compatible evidence was provided by the inhibition of ATP induced DNA fragmentation in the present of EGTA or EDTA; (2) ATP induced DNA fragmentation was completely inhibited by 1 mmol/L Zn 2+ ;(3)ATP induced DNA breaks were not affected by Ba 2+ , Sr 2+ , Co 2+ when they were substituted for extracellular Mg 2+ or Ca 2+ ;(4)Choline, an inhibitor of phospholipase D(PLD) stimulated by ATP through P2Z receptor in human lymphocytes, was also a partial inhibitor of ATP induced DNA fragmentation, and the results were confirmed by flow cytometric analysis (FCA); (5)ATP induced DNA fragmentation was completely obliterated when the temperature was lower than 10℃. These results suggest that the endonuclease and PLD may be involved in ATP induced apoptosis in human lymphocytes via P2Z receptor.展开更多
The relations between catalytic activities and compositions of the systems Mg_xZn_(1-x)Fe_2O_4, Co_xZn_(1-x)Fe_2O_4, Co_xMg_(1-x)Fe_2O_4, Cd_xZn_(1-x)Fe_2O_4 and Mg_xZn_(1-x)Fe_2O_4·0.17Fe_2O_3 have been studied ...The relations between catalytic activities and compositions of the systems Mg_xZn_(1-x)Fe_2O_4, Co_xZn_(1-x)Fe_2O_4, Co_xMg_(1-x)Fe_2O_4, Cd_xZn_(1-x)Fe_2O_4 and Mg_xZn_(1-x)Fe_2O_4·0.17Fe_2O_3 have been studied by flow differential reactor, XRD, and derivative IR techniques. It has been found that the appropriate normal-inverse spinel combination substantially increases the activity for the title raction. The structure of the active site and the role of the bivalent cation in the title catalyst have been inferred.展开更多
Study of physisorbed and chemisorbed carbon dioxide (CO<sub>2</sub>) species was carried out on the NaX zeolite modified by cationic exchanges with bivalent cations (Ca<sup>2+</sup> and Ba<s...Study of physisorbed and chemisorbed carbon dioxide (CO<sub>2</sub>) species was carried out on the NaX zeolite modified by cationic exchanges with bivalent cations (Ca<sup>2+</sup> and Ba<sup>2+</sup>) by temperature-programmed desorption of CO<sub>2</sub> (CO<sub>2</sub>-TPD). Others results were obtained by infrared to complete the study. The results of this research showed, in the physisorption region (213 - 473 K), that the cationic exchanges on NaX zeolite with bivalent cations increase slightly the interactions of CO<sub>2</sub> molecule with adsorbents and/or cationic site. Indeed, the desorption energies of physisorbed CO<sub>2</sub> obtained on the reference zeolite NaX (13.5 kJ·mol<sup>-1</sup>) are lower than that of exchanged zeolites E-CaX and E-BaX (15.77 and 15.17 kJ·mol<sup>-1</sup> respectively). In the chemisorbed CO<sub>2</sub> region (573 - 873 K), the desorption energies related to desorbed species (bidentate carbonates: CO<sub>3</sub>2-</sup>) on the exchanged zeolites E-CaX and E-BaX are about 81 kJ·mol<sup>-1</sup>, higher than the desorbed species (bicarbonates: HCO<sub>3</sub>2-</sup>) on the reference R-NaX (62 kJ·mol<sup>-1</sup>). In addition, the exchanged E-BaX zeolite develops the secondary adsorption sites corresponding to bicarbonates species with desorption energies of 35 kJ·mol<sup>-1</sup> lower to desorption energies of bicarbonates noted on the reference zeolite NaX.展开更多
Objective To evaluate the effectiveness of Hemorrhagic Fever with Renal Syndrome(HFRS) bivalent vaccine in field.Methods The articles on effectiveness of HFRS bivalent vaccine were retrieved from Vip Database,China Jo...Objective To evaluate the effectiveness of Hemorrhagic Fever with Renal Syndrome(HFRS) bivalent vaccine in field.Methods The articles on effectiveness of HFRS bivalent vaccine were retrieved from Vip Database,China Journal Full-text Database,Wanfang database,China Hospital Knowledge Database,Chinese Biomedical Literature Database,MEDLINE and ProQuest.Two persons extracted data and evaluated the quality of data together for meta-analysis.Results Seven articles were included into the analysis,and two articles were random clinical trials,five were quasi-trials.Meta-analysis showed that the overall effectiveness of HFRS bivalent vaccine was 85%(95%confidence interval:53%-95%) within one year after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 87%(95%confidence interval:54%-96%) and 60%,respectively;it was 96%(95%confidence interval:78%-99%) within 2-5 years after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 95%(95%confidence interval:19%-100%) and 96%(95%confidence interval:70%-99%),respectively;it was 100%(only one article included) within 6-9.6 years after vaccination.The effectiveness in two-dose recipients was 88%(95%confidence interval:62%-96%) during 1-2.5 years after vaccination,and that in three-dose recipients was 94%(95%confidence interval:70%-99%) during 1-5 years after vaccination.Conclusions HFRS bivalent vaccine is effective in field,and there is no difference between two-dose recipients and three-dose recipients.We should do some further studies on the long-term effectiveness of HFRS bivalent vaccine and on the age of vaccine reception.展开更多
The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical...The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.展开更多
Osteoarthritis(OA)is the most prevalent joint disorder occurring with articular cartilage degradation.It includes a switch from an articularto a growth plate chondrocyte phenotype.Here,we investigated the histone modi...Osteoarthritis(OA)is the most prevalent joint disorder occurring with articular cartilage degradation.It includes a switch from an articularto a growth plate chondrocyte phenotype.Here,we investigated the histone modification profiles and found significant H3K27me3 loss inOA,which led to disease-associated gene expression.Surprisingly,these genes were occupied by both H3K27me3 and H3K4me3 in normalchondrocytes,showing a poised bivalent state.Furthermore,we observed the derepression of similar bivalent genes in growth platechondrocytes.Finally,a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model.Our resultsreveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy andcontributes to a promising epigenetic therapy for OA.展开更多
Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA...Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.展开更多
Human adenoviruses(HAdvs)are major respiratory pathogens.Specifically,human adenovirus type 4(HAdV4)and human adenovirus type 7(HAdV7)are known for causing fever and pneumonia,with docu-mented cases of fatalities amon...Human adenoviruses(HAdvs)are major respiratory pathogens.Specifically,human adenovirus type 4(HAdV4)and human adenovirus type 7(HAdV7)are known for causing fever and pneumonia,with docu-mented cases of fatalities among the population.In recent years,HAdV4/HAdv7 has been implicated in caus-ing substantial outbreaks,leading to increased morbidity in multiple countries.Most HAdV4 and HAdV7 infections have been reported in North America,Asia,Europe,Africa,South America,Oceania,and the Middle East.Most fatalities occurred in North America(the United States)and Asia(China and Singapore).Engineered recombinant adenoviruses have played a crucial role as vaccine vectors.In this study,we con-structed a recombinant adenovirus,Ad4ITRmut-Ad7E3,and evaluated it in vitro and in vivo.We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain,indicating that the mutation of inverted terminal repeats(ITRs)weakened the replication ability of HAdV4.Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain,administered by intraperitoneal injection and oral gavage,resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdv7.This finding not only pro-vides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vac-cine candidate against HAdV4 and HAdv7 but also against other prevalent adenovirus serotypes such as HAdV3,HAdV11,HAdV14,and HAdv55,from various regions.展开更多
Well spread pachytene bivalents and high resolution G-handing patterns have been obtainedby using the prolonged hypotonic treatment combined with the trypsin-hot salt banding technique in the sper-maries of rice field...Well spread pachytene bivalents and high resolution G-handing patterns have been obtainedby using the prolonged hypotonic treatment combined with the trypsin-hot salt banding technique in the sper-maries of rice field eels(Monopterus albus Zuiew).Each bivalent has been idendified and a total of 310—450 bands on 12 bivalents observed.This might bethe largest number of multiple bands obtained from fish chromosomes so far published.An idiogram of 372G-bands has been set up and detailed descriptions of the landmark systems and the band positions have beengiven.展开更多
Genetic and expressional stability of Bt toxin gene is crucial for the breeding of insect-resistant transgenic cotton varieties and their commercialization. Genomic Southern blot analysis of R3, R4 and R5 generations ...Genetic and expressional stability of Bt toxin gene is crucial for the breeding of insect-resistant transgenic cotton varieties and their commercialization. Genomic Southern blot analysis of R3, R4 and R5 generations of bivalent transgenic insect-resistant cotton plants was done in order to determine the integration, the copy number and the inheritance stability of Bt toxin gene in the transgenic cotton plants. The results indicated that there was a 4.7 kb positive band in the Southern blot when the genomic DNA of the bivalent transgenic insect-resistant cotton plants and the positive control (the plasmid) were digested with HindⅢ respectively. This result proved that the Bt toxin gene had been integrated into the genome of the cotton in full length. There is only one XhoⅠ restriction site in the Bt toxin gene. Southern blot analysis indicated that many copies of Bt toxin gene had been integrated into the genome of the cotton when the genomic DNA of transgenic plants was digested with XhoⅠ. Among them, there were four copies (about 17.7, 8, 5.5 and 4.7 kb in size) existing in all the tested plants of R3, R4 and R5 generations. The preliminary conclusion was that there were more than four copies of Bt toxin gene integrated into the genome of the cotton, among them, more than one copy can express and inherit steadily. This result provides a scientific basis for the breeding of the bivalent insect-resis- tant transgenic cotton plants and its commercialization.展开更多
Haemorrhagic fever with renal syndrome (HFRS) is a worldwide epidemic plaguing over thirty nations. This disease has spread across 26 provinces, cities and autonomous regions of China with an annual onsets number ...Haemorrhagic fever with renal syndrome (HFRS) is a worldwide epidemic plaguing over thirty nations. This disease has spread across 26 provinces, cities and autonomous regions of China with an annual onsets number of more than a hundred thousand and a mortality rate of 5% to 15%, accounting for over 80% of cases in the world, and threatening the safety and health of Chinese people. 1 Analysis of serum samples over recent years indicates that the plagued areas are expanding. Instead of a single type Ⅰ or Ⅱ strain, each area now has a combination with one type predominant. 2 These demographic changes revealed a shortcoming of the monovalent vaccine in use, urging China to develop a purified bivalent vaccine based on monovalent one. This research on clinical observation and immunization effects led to a purified bivalent vaccine manufactured by Changchun Institute of Biological Products, China from primary cultured hamster kidney cells.展开更多
COVID-19 is a disease that disproportionately impacts the Hispanic population,due to the prevalence of certain risk factors and the high number of essential workers in this com-munity.In this work,we analyze the vacci...COVID-19 is a disease that disproportionately impacts the Hispanic population,due to the prevalence of certain risk factors and the high number of essential workers in this com-munity.In this work,we analyze the vaccination strategies that would minimize the COVID-19 health disparities in El Paso County,TX,in the context of the emergence of a new highly transmissible and immune-escaping SARS-CoV-2 variant.We stratify an age-structure stochastic SEIR model that tracks the evolution of immunity derived from in-fections and vaccination according to Hispanic vs non-Hispanic ethnicity and parameterize it to the demographic,health and immunization data of El Paso County,TX.After fitting the model,the results show that increasing vaccination with bivalent boosters by five-fold in anticipation of highly transmissible and immune escaping variants would decrease the cumulative hospital admissions and mortality from Mar 1,2023,to Dec 31,2023,by 62.72%and 61.41%,respectively.Further,our projections reveal that the disproportionate impact on the Hispanic community would be eliminated if approximately half of the doses that are given to the non-Hispanic group according to the equal distribution,would be re-allocated to the Hispanic population.Our findings can guide public health officials in US cities with large Hispanic communities and help them design vaccination strategies that minimize COVID-19 health disparities caused by emerging variants using specific vacci-nation strategies.展开更多
Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiel...Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiella ictaluri are two pathogenic bacteria found in yellow catfish and often infect the fish through mucosal surfaces.Delivery of a bivalent inactivated vaccine by injection has been shown to induce a strong systemic immune response against both bacterial infections.However,mucosal immune responses and protective efficiency induced by this inactivated vaccine administrated via immersion are yet to be investigated.We developed a bivalent vaccine containing formalin-inactivated A.veronii and E.ictaluri and evaluated the immune response in yellow catfish after immersion vaccination using body fluids biochemistry indices,agglutinating antibody titers,and the expression level of immune-related genes in the skin,gills,spleen,and head kidney.The activities of innate immune-related enzymes and specific agglutination antibody titers in body fluids,as well as the expression of innate and adaptive immune-related genes in both the mucosal and systemic tissues of vaccinated fish,were significantly higher than that in control fish.Next,we assessed the protective efficacy by a challenge model of virulent strains of E.ictaluri and A.veronii.The relative survival percent of vaccinated fish was 80%and 87%after challenging fish with E.ictaluri and A.veronii,respectively,which was higher than unvaccinated control fish(43%and 57%).These results confirm that the bivalent inactivated vaccine administered via immersion induces a strong mucosal immune response and confers good protection against both E.ictaluri and A.veronii.Our results also reinforce the notion that immersion vaccination could stimulate both mucosal and systemic immunity contributing to protection against pathogens.展开更多
基金the National Natural Science Foundation of China(Nos.22104158,82174104,U1903211)the Natural Science Foundation of Hunan Province(No.2021JJ40041)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023A1515011346)Shenzhen Science and Technology Program(No.SZBH202130)。
文摘Heterodimerization in RTKs is of vital importance in the RTK signaling and cell functions.Heterodimerization between RTKs can result in diversity of downstream signals,increasing the ability of cells to respond to external experiments.Traditional RTKs heterodimerization always occur in the same families and is lack of agonists to activate the heterodimeric RTKs signaling pathway.Herein,we developed the DNA agonist based on bivalent aptamers for the heterodimerized RTKs of different families,AF/AM-1,which could simultaneously activate FGFR1 and c-Met signaling.It is the first agonist that realizing the heterodimerization and activation of FGFR1 and c-Met,two different RTK families.The activation of FGFR1/c-Met heterodimer result in the down-stream signals transduction,such as the phosphorylation of Akt and Erk,inducing the cell migration and proliferation.The DNA agonist for RTK heterodimer of different families would have potential applications in the fields of biomedicine.
文摘Artificially induced tetraploid Pacific oyster, Crassostrea gigas Thunberg, produces more aneuploid gametes than nor- mal diploid one, although they showed a comparable fecundity to diploidy. The meiotic chromosome configuration of 3 tetraploid and 1 tetraploid/triploid mosaic males were analyzed through direct chromosome observation. A majority of metaphase I spermato- cytes contained both bivalents and quadrivalents. The chromosome configuration of these males was characterized by preferential formation of bivalents to quadrivalents. Bivalents appeared in all spermatocytes and consisted of 86% of all chromosome aggregates. In comparison, quadrivalents occurred in 91% spermatocytes and consisted of only 12.6% of all chromosome aggregates. The mean bivalent frequency per spermatocyte varied between 14.4 and 17.2; while that of quadrivalents varied between 2.2 and 2.7. Most quadrivalents were tandemly chained （58%） or circled （39%）. The total number of chromosome aggregates per spermatocyte ranged from 13 to 20 with an average of 17.6; while 18 （16 bivalents and 2 quadrivalents） was the most frequent. Univalents and trivalents appeared in very low frequency. Aneuploid （hypotetraploid） spermatocytes were observed in a low frequency. The chromosome con- figuration of in the mosaic individual was similar to that of tetraploid individuals. The percentage of triploid spermatocytes （2%） of the mosaic individual was significantly lower （2＂2 =30, P〈 0.01） than that of triploid cells （46%） in its somatic tissue.
基金supported by the Fish Innovation Team of Shandong Agriculture Research System (No. SDAIT-1206)the Aquatic Animal Immunologic Agents Engineering Research Center of Shandong Province, the Qingdao Agricultural University Doctoral Start-Up Fund (6631122030)+5 种基金the National Natural Science Foundation of China (No. 32002421)the Advanced Talents Foundation of QAU (No. 6651118016)the Natural Science Foundation of Shandong Province (No. ZR2019BC009)the ‘First-Class Fishery Discipline’ program of Shandong Province, the special top talent plan ‘One Thing One Decision (Yi Shi Yi Yi)’the Key Research and Development Program in Shandong Province (No. 2018YFJH0703)Breeding Plan of Shandong Provincial Qingchuang Research Team (2019)
文摘Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.
基金supported by the National Natural Science Foundation of China(Grant No.11564015)the Foundation of Educational Committee of Jiangxi Province,China(Grant No.GJJ211112)the Fund for Distinguished Young Scholars of Jiangxi Science&Technology Normal University(Grant No.2015QN-BJRC002)。
文摘A-form DNA is one of the biologically active double helical structure.The study of A-DNA structure has an extensive application for developing the field of DNA packaging in biotechnology.In aqueous solution,the A-DNA structure will have a free transformation,the A-DNA structure will be translated into B-form structure with the evolution of time,and eventually stabilized in the B-DNA structure.To explore the stability function of the bivalent metal ions on the A-DNA structure,a series of molecular dynamics simulations have been performed on the A-DNA of sequence(CCCGGCCGGG).The results show that bivalent metal ions(Mg^(2+),Zn^(2+),Ca^(2+))generate a great effect on the structural stability of A-DNA in the environment of high concentration.As the interaction between metal ions and electronegative DNA chains,the stability of A-DNA in solution is gradually improved with the increasing solution concentration of ions.In metal salt solution with high concentration,metal ions can be easily distributed in the solvation shells around the phosphate groups and further lead to the formation of shorter and more compact DNA structure.Also,under the condition of the same concentration and valency of the metal ions,the stability of A-DNA structure is different.The calculations indicate that the structure of A-DNA in CaCl_(2)solution is less stable than in MgCl_(2)and ZnCl_(2)solution.
基金supported by the Key Project of National Basic Research and Developmental Plan(G2000016103)of Chinathe National Outstanding Youth Science Foundation(39925027)+1 种基金National Natural Science Foundation of China(39570519)the International Foundation for Science(IFS,B/2425-2F).
文摘Well-spread meiotic pachytene bivalents were obtained by using the prolonged hypotonic treatment com-bined with high chloroform Carnory’s fixative solution from cells of the testes of domestic pigs. Comparison in the division index and length of pachytene bivalents with metaphase chromosomes showed that those of the former are 5 times higher and 3.42(1.87-5.98) times longer than those of the latter. Comparative studies on chromomere maps of bivalents and mitotic chromosomal G-bands were conducted by using the chromo-some 12 as a example. Sex vesicle and various shapes of synaptic sex chromosomes have been observed.Two-color PRimed IN Situ (PRINS) labeling has been conducted successfully on pachytene bivalents of pigs.
文摘Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.
基金supported by Hungarian National Research,Development and Innovation Office(NKFIH) grants K-112294GINOP-2.3.2-15-2016-00032 and GINOP-2.3.2-15-2016-00034 to LB
文摘Huntington’s disease（HD）is a currently incurable,late onset,progressive,ultimately fatal neurological disorder（Bates et al.,2015）.We have recently published the results of comprehensive genetic interaction tests aimed at identification of histone methyltransferases and demethylases involved in HD pathogenesis in a Drosophila model of the disease（Song et al.,2018）.
文摘The role of bivalent cations and choline in ATP induced apoptosis via P2Z purinoceptor was investigated in human leukemic lymphocytes. In vitro exposure of leukemic lymphocytes with P2Z receptors to 1 mmol/L ATP or 0 1 mmol/L benzoylbenzoic ATP(BzATP) for 8 h in the presence of choline, 1 mmol/L Mg 2+ or other bivalent cations, and ATP induced DNA breaks, associated with apoptosis were quantified by TdT assay. We observed that (1) Extracellular Mg 2+ or Ca 2+ stimulated ATP induced DNA fragmentation in a dose dependent manner, and the compatible evidence was provided by the inhibition of ATP induced DNA fragmentation in the present of EGTA or EDTA; (2) ATP induced DNA fragmentation was completely inhibited by 1 mmol/L Zn 2+ ;(3)ATP induced DNA breaks were not affected by Ba 2+ , Sr 2+ , Co 2+ when they were substituted for extracellular Mg 2+ or Ca 2+ ;(4)Choline, an inhibitor of phospholipase D(PLD) stimulated by ATP through P2Z receptor in human lymphocytes, was also a partial inhibitor of ATP induced DNA fragmentation, and the results were confirmed by flow cytometric analysis (FCA); (5)ATP induced DNA fragmentation was completely obliterated when the temperature was lower than 10℃. These results suggest that the endonuclease and PLD may be involved in ATP induced apoptosis in human lymphocytes via P2Z receptor.
基金Project supported by National Natural Science Foundation of P. R. China.
文摘The relations between catalytic activities and compositions of the systems Mg_xZn_(1-x)Fe_2O_4, Co_xZn_(1-x)Fe_2O_4, Co_xMg_(1-x)Fe_2O_4, Cd_xZn_(1-x)Fe_2O_4 and Mg_xZn_(1-x)Fe_2O_4·0.17Fe_2O_3 have been studied by flow differential reactor, XRD, and derivative IR techniques. It has been found that the appropriate normal-inverse spinel combination substantially increases the activity for the title raction. The structure of the active site and the role of the bivalent cation in the title catalyst have been inferred.
文摘Study of physisorbed and chemisorbed carbon dioxide (CO<sub>2</sub>) species was carried out on the NaX zeolite modified by cationic exchanges with bivalent cations (Ca<sup>2+</sup> and Ba<sup>2+</sup>) by temperature-programmed desorption of CO<sub>2</sub> (CO<sub>2</sub>-TPD). Others results were obtained by infrared to complete the study. The results of this research showed, in the physisorption region (213 - 473 K), that the cationic exchanges on NaX zeolite with bivalent cations increase slightly the interactions of CO<sub>2</sub> molecule with adsorbents and/or cationic site. Indeed, the desorption energies of physisorbed CO<sub>2</sub> obtained on the reference zeolite NaX (13.5 kJ·mol<sup>-1</sup>) are lower than that of exchanged zeolites E-CaX and E-BaX (15.77 and 15.17 kJ·mol<sup>-1</sup> respectively). In the chemisorbed CO<sub>2</sub> region (573 - 873 K), the desorption energies related to desorbed species (bidentate carbonates: CO<sub>3</sub>2-</sup>) on the exchanged zeolites E-CaX and E-BaX are about 81 kJ·mol<sup>-1</sup>, higher than the desorbed species (bicarbonates: HCO<sub>3</sub>2-</sup>) on the reference R-NaX (62 kJ·mol<sup>-1</sup>). In addition, the exchanged E-BaX zeolite develops the secondary adsorption sites corresponding to bicarbonates species with desorption energies of 35 kJ·mol<sup>-1</sup> lower to desorption energies of bicarbonates noted on the reference zeolite NaX.
文摘Objective To evaluate the effectiveness of Hemorrhagic Fever with Renal Syndrome(HFRS) bivalent vaccine in field.Methods The articles on effectiveness of HFRS bivalent vaccine were retrieved from Vip Database,China Journal Full-text Database,Wanfang database,China Hospital Knowledge Database,Chinese Biomedical Literature Database,MEDLINE and ProQuest.Two persons extracted data and evaluated the quality of data together for meta-analysis.Results Seven articles were included into the analysis,and two articles were random clinical trials,five were quasi-trials.Meta-analysis showed that the overall effectiveness of HFRS bivalent vaccine was 85%(95%confidence interval:53%-95%) within one year after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 87%(95%confidence interval:54%-96%) and 60%,respectively;it was 96%(95%confidence interval:78%-99%) within 2-5 years after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 95%(95%confidence interval:19%-100%) and 96%(95%confidence interval:70%-99%),respectively;it was 100%(only one article included) within 6-9.6 years after vaccination.The effectiveness in two-dose recipients was 88%(95%confidence interval:62%-96%) during 1-2.5 years after vaccination,and that in three-dose recipients was 94%(95%confidence interval:70%-99%) during 1-5 years after vaccination.Conclusions HFRS bivalent vaccine is effective in field,and there is no difference between two-dose recipients and three-dose recipients.We should do some further studies on the long-term effectiveness of HFRS bivalent vaccine and on the age of vaccine reception.
文摘The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.
基金supported by the National Natural Science Foundation of China(U22A20280,81874027)Science&Technology Department of Sichuan Province(2023NSFSC1607,2021YFSY0003,2022YFS0051,2022NSFSC1312)+1 种基金Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(312200102)Clinical Research Incubation project of West China Hospital of Sichuan University(2021HXFH036)。
文摘Osteoarthritis(OA)is the most prevalent joint disorder occurring with articular cartilage degradation.It includes a switch from an articularto a growth plate chondrocyte phenotype.Here,we investigated the histone modification profiles and found significant H3K27me3 loss inOA,which led to disease-associated gene expression.Surprisingly,these genes were occupied by both H3K27me3 and H3K4me3 in normalchondrocytes,showing a poised bivalent state.Furthermore,we observed the derepression of similar bivalent genes in growth platechondrocytes.Finally,a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model.Our resultsreveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy andcontributes to a promising epigenetic therapy for OA.
基金supported by a grant(2023YFC2307600,to Z.J.Z.)from the Na-tional Key Research and Development Program of Chinaa grant(202102AA100051,to Z.J.Z.)from the Yunnan Provincial Sci-ence and Technology Department,China+2 种基金a grant(H-2018102,to J.W.)from the High-level Health Technical Personnel Project of Yunnan Province,Chinaa grant(2022SCP001,to Z.J.Z.)from the Spring City Plan:The High-level Talent Promotion and Training Project of Kunmingand a grant(32371000,to C.M.L.)from the National Natural Science Foundation of China.
文摘Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2018YFA0900800).
文摘Human adenoviruses(HAdvs)are major respiratory pathogens.Specifically,human adenovirus type 4(HAdV4)and human adenovirus type 7(HAdV7)are known for causing fever and pneumonia,with docu-mented cases of fatalities among the population.In recent years,HAdV4/HAdv7 has been implicated in caus-ing substantial outbreaks,leading to increased morbidity in multiple countries.Most HAdV4 and HAdV7 infections have been reported in North America,Asia,Europe,Africa,South America,Oceania,and the Middle East.Most fatalities occurred in North America(the United States)and Asia(China and Singapore).Engineered recombinant adenoviruses have played a crucial role as vaccine vectors.In this study,we con-structed a recombinant adenovirus,Ad4ITRmut-Ad7E3,and evaluated it in vitro and in vivo.We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain,indicating that the mutation of inverted terminal repeats(ITRs)weakened the replication ability of HAdV4.Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain,administered by intraperitoneal injection and oral gavage,resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdv7.This finding not only pro-vides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vac-cine candidate against HAdV4 and HAdv7 but also against other prevalent adenovirus serotypes such as HAdV3,HAdV11,HAdV14,and HAdv55,from various regions.
基金the National Doctorate Research Foundation of Chinathe National Natural Science Foundation of China
文摘Well spread pachytene bivalents and high resolution G-handing patterns have been obtainedby using the prolonged hypotonic treatment combined with the trypsin-hot salt banding technique in the sper-maries of rice field eels(Monopterus albus Zuiew).Each bivalent has been idendified and a total of 310—450 bands on 12 bivalents observed.This might bethe largest number of multiple bands obtained from fish chromosomes so far published.An idiogram of 372G-bands has been set up and detailed descriptions of the landmark systems and the band positions have beengiven.
基金supported by the National"863"High-Tech Program,the Special Foundation of the Ministry of Agriculture for"Developing Cotton Production"and the Chinese Foundation for Agriculture Science and Education.
文摘Genetic and expressional stability of Bt toxin gene is crucial for the breeding of insect-resistant transgenic cotton varieties and their commercialization. Genomic Southern blot analysis of R3, R4 and R5 generations of bivalent transgenic insect-resistant cotton plants was done in order to determine the integration, the copy number and the inheritance stability of Bt toxin gene in the transgenic cotton plants. The results indicated that there was a 4.7 kb positive band in the Southern blot when the genomic DNA of the bivalent transgenic insect-resistant cotton plants and the positive control (the plasmid) were digested with HindⅢ respectively. This result proved that the Bt toxin gene had been integrated into the genome of the cotton in full length. There is only one XhoⅠ restriction site in the Bt toxin gene. Southern blot analysis indicated that many copies of Bt toxin gene had been integrated into the genome of the cotton when the genomic DNA of transgenic plants was digested with XhoⅠ. Among them, there were four copies (about 17.7, 8, 5.5 and 4.7 kb in size) existing in all the tested plants of R3, R4 and R5 generations. The preliminary conclusion was that there were more than four copies of Bt toxin gene integrated into the genome of the cotton, among them, more than one copy can express and inherit steadily. This result provides a scientific basis for the breeding of the bivalent insect-resis- tant transgenic cotton plants and its commercialization.
文摘Haemorrhagic fever with renal syndrome (HFRS) is a worldwide epidemic plaguing over thirty nations. This disease has spread across 26 provinces, cities and autonomous regions of China with an annual onsets number of more than a hundred thousand and a mortality rate of 5% to 15%, accounting for over 80% of cases in the world, and threatening the safety and health of Chinese people. 1 Analysis of serum samples over recent years indicates that the plagued areas are expanding. Instead of a single type Ⅰ or Ⅱ strain, each area now has a combination with one type predominant. 2 These demographic changes revealed a shortcoming of the monovalent vaccine in use, urging China to develop a purified bivalent vaccine based on monovalent one. This research on clinical observation and immunization effects led to a purified bivalent vaccine manufactured by Changchun Institute of Biological Products, China from primary cultured hamster kidney cells.
基金supported by the Counsil of State and Territorial Epidemiologists(grant no.NU38OT000297).
文摘COVID-19 is a disease that disproportionately impacts the Hispanic population,due to the prevalence of certain risk factors and the high number of essential workers in this com-munity.In this work,we analyze the vaccination strategies that would minimize the COVID-19 health disparities in El Paso County,TX,in the context of the emergence of a new highly transmissible and immune-escaping SARS-CoV-2 variant.We stratify an age-structure stochastic SEIR model that tracks the evolution of immunity derived from in-fections and vaccination according to Hispanic vs non-Hispanic ethnicity and parameterize it to the demographic,health and immunization data of El Paso County,TX.After fitting the model,the results show that increasing vaccination with bivalent boosters by five-fold in anticipation of highly transmissible and immune escaping variants would decrease the cumulative hospital admissions and mortality from Mar 1,2023,to Dec 31,2023,by 62.72%and 61.41%,respectively.Further,our projections reveal that the disproportionate impact on the Hispanic community would be eliminated if approximately half of the doses that are given to the non-Hispanic group according to the equal distribution,would be re-allocated to the Hispanic population.Our findings can guide public health officials in US cities with large Hispanic communities and help them design vaccination strategies that minimize COVID-19 health disparities caused by emerging variants using specific vacci-nation strategies.
文摘Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiella ictaluri are two pathogenic bacteria found in yellow catfish and often infect the fish through mucosal surfaces.Delivery of a bivalent inactivated vaccine by injection has been shown to induce a strong systemic immune response against both bacterial infections.However,mucosal immune responses and protective efficiency induced by this inactivated vaccine administrated via immersion are yet to be investigated.We developed a bivalent vaccine containing formalin-inactivated A.veronii and E.ictaluri and evaluated the immune response in yellow catfish after immersion vaccination using body fluids biochemistry indices,agglutinating antibody titers,and the expression level of immune-related genes in the skin,gills,spleen,and head kidney.The activities of innate immune-related enzymes and specific agglutination antibody titers in body fluids,as well as the expression of innate and adaptive immune-related genes in both the mucosal and systemic tissues of vaccinated fish,were significantly higher than that in control fish.Next,we assessed the protective efficacy by a challenge model of virulent strains of E.ictaluri and A.veronii.The relative survival percent of vaccinated fish was 80%and 87%after challenging fish with E.ictaluri and A.veronii,respectively,which was higher than unvaccinated control fish(43%and 57%).These results confirm that the bivalent inactivated vaccine administered via immersion induces a strong mucosal immune response and confers good protection against both E.ictaluri and A.veronii.Our results also reinforce the notion that immersion vaccination could stimulate both mucosal and systemic immunity contributing to protection against pathogens.
