All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China...All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.展开更多
All the data in this catalog are chosen from the "Preliminary Seismological Report of Chi- nese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near Chi...All the data in this catalog are chosen from the "Preliminary Seismological Report of Chi- nese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.展开更多
All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China...All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geoohysics, China Earthquake Administration.展开更多
Illustration All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in a...Illustration All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled bv the Ninth Section of Institute of Geophysics, China Earthquake Administration.展开更多
[Objective] This study aimed to identify the in vitro antibacterial activity of golden buckwheat extract and investigate the therapeutic effect of its preparation on mycoplasma infection. [Method] Through measuring th...[Objective] This study aimed to identify the in vitro antibacterial activity of golden buckwheat extract and investigate the therapeutic effect of its preparation on mycoplasma infection. [Method] Through measuring the minimum inhibitory concentra-tion, the in vitro antibacterial activity of golden buckwheat water extract was deter-mined; meanwhile, the therapeutic effect of golden buckwheat oral solution on my-coplasma infection was determined by artificial y infecting chickens with Mycoplasma gal isepticum culture. [Results] The golden buckwheat water extract had obvious in-hibitory effects against Pseudomonas aeruginosa and Escherichia coli, and a certain inhibitory effect on Salmonel a and Staphylococcus aureus; administration of golden buckwheat oral solution at the dose of 0.5%-1.0% continuously for 5 d had a good therapeutic effect against mycoplasma infection. [Conclusion] The study provides sci-entific bases for further study on the antibacterial activity of golden buckwheat and its application.展开更多
In the context of Chinese learning English writing to learn and length approach is one of the highlighted concepts and practices. It entails sufficient comprehensible input and active interaction. It is found that the...In the context of Chinese learning English writing to learn and length approach is one of the highlighted concepts and practices. It entails sufficient comprehensible input and active interaction. It is found that the theme-based modules/units, if organized and performed meaningfully and closely related to the learners' life and experiences, will best integrate these three elements in the process of the second language learning, which is geared in some major aspects to the whole language philosophy. 'Writing to learn' is a product of reverse thinking. In a theme-based module/unit, a writing task of the same theme is put at its end with some requirements for language enhancement. It serves as an engine to learn other skills. In reality, it is not writing alone that functions in the SLA, but writing at the final stage that requires comprehended input and good qualitative interaction together to fuel SLA. An experiment of 20 weeks shows the positive results for the model.展开更多
According to the ideas and concepts of systems dynamic of continent structure, using previous information related to the study area, combining analyses on orogenic belt, basin and magmatic rock, the present paper synt...According to the ideas and concepts of systems dynamic of continent structure, using previous information related to the study area, combining analyses on orogenic belt, basin and magmatic rock, the present paper synthesizes the tectono - sedimentary development of southeastern coast region, China, with special emphasis on the mountain making, basining and magmatic activity. The tectonic evolution after Late Caledonian orogeny was dominated by alternating rifting and converging, subsiding and uplifting, mountain making and basining in central and southern parts of southeastern China and the adjacent regions to the east and west. Seventeen geologic events , nine events of plate or terrain convergence , and continental crust accretion , as well as eight events of intracontinental rifting and basin faulting , are closely related to the tectonic and sedimentary evolution of the study area . The accompanied intense and frequent sedimentation , folding , faulting , magmatism and ore- forming process allowed huge coal , multimetal and potential petroleum source rocks to form in local depressions throughout the Caledonian to Himalavan time .展开更多
Fourteen new tricyclohexyltin (Ⅳ)-O,O-diaryldithiophosphates were synthesized and determined by IR, 1H NMR, 13C NMR, 119Sn NMR MS, and elemental analysis. The structures of all the compounds consist of discrete molec...Fourteen new tricyclohexyltin (Ⅳ)-O,O-diaryldithiophosphates were synthesized and determined by IR, 1H NMR, 13C NMR, 119Sn NMR MS, and elemental analysis. The structures of all the compounds consist of discrete molecule containing a four-coordinated tin atom. Results from the preliminary biological test show that these compounds have a high miticidal activity.展开更多
All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China...All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China EarthQuake Administration.展开更多
Illustration All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in ...Illustration All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.展开更多
OBJECTIVE: To investigate the effect of Yiqihuoxue prescription(YQHX) from Traditional Chinese Medicine(TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver ...OBJECTIVE: To investigate the effect of Yiqihuoxue prescription(YQHX) from Traditional Chinese Medicine(TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver kinase B1(LKB1)-dependent Notch1 and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK). YQHX was prepared with substances with properties that benefit, to activate blood circulation based on the TCM theory.METHODS: Animal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The animals were randomly divided into a myocardial infarction(MI) group, a YQHX group, a perindopril group, a γ-secretase inhibitor, Notch signal inhibitor(DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the relevant indexes were examined on weeks 1 and 4.Changes in cardiac structure and function were examined by echocardiography. The glucose and free fatty acids(FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK m RNA was examined by a real-time fluorescence quantitative method. The expression of glucose transporter 4(GLUT4), and the expression of total acetyl-Co A carboxylase(ACC) and its phosphorylation were examined by western blotting.RESULTS: Compared with the sham group, the expression of Notch, LKB1 and AMPK m RNA in the MI group was lower. Compared with the MI group, the expression of these m RNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and p ACC decreased in the MI group. On week 1, the expression of p ACC protein was higher. In the DAPT group, the expression of p ACC protein decreased. Compared with the YQHX group, the expression of p ACC protein in the DAPT + YQHX group was lower. On week 4,compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindo-pril group was higher. The expression of GLUT4 protein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC protein between the groups.CONCLUSION: YQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocardial tissue after myocardial infarction. Furthermore,it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via different mechanisms and protecting the heart.展开更多
GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells.Their importance to basic cell biology,human diseases,and pharma-ceutical interventions is well established.Many crystal st...GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells.Their importance to basic cell biology,human diseases,and pharma-ceutical interventions is well established.Many crystal structures of GPCR proteins have been reported in both active and inactive conformations.These data indicate that agonist binding alone is not suffi cient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins,yet other essential factors re-main elusive.Based on analysis of available GPCR crystal structures,we identifi ed a potential conformational switch around the conserved Asp2.50,which consistently shows distinct conformations between inactive and active states.Combining the structural information with the current literature,we propose an energy-coupling mechanism,in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.展开更多
Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant oss...Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant osseous healing. Early topical insulin treat- ment was recently shown to normalize diabetic bone healing by rectifying impairments in osteoblastic activities. In this study, insulin/poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double-emulsion solvent evaporation method. Microspheres were then incorporated in fibrin gel to develop a local drug delivery system for diabetic patients requiring im- plant treatment. In vitro release of insulin from fibrin gel loaded with these microspheres was assessed, and sustained prolonged insulin release over 21 days ascertained. To assess the bioactivity of released insulin and determine whether slow release might improve impaired diabetic bone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, mineralized nodule formation, and ELISA (enzyme-linked immunosorbent assay) assays were performed. The insulin released from the drug delivery system stimulated cell growth in previously inhibited cells, and ameliorated the impaired bone-forming ability of human MG-63 cells under high glucose conditions. Fibrin gel loaded with insulin/PLGA microspheres shows potential for improving peri-implant bone formation in diabetic patients.展开更多
Hemophilia A is caused by a genetic mutation in coagulation factor VIII (FVIII) gene and gene therapy is considered to be a promising strategy for its treatment. We recently demonstrated that co-delivery of two vect...Hemophilia A is caused by a genetic mutation in coagulation factor VIII (FVIII) gene and gene therapy is considered to be a promising strategy for its treatment. We recently demonstrated that co-delivery of two vectors expressing M662C mutated heavy and D1828C mutated light chain genes of B-domain-deleted coagulation factor VIII (BDD-FVIII) leads to inter-chain disulfide cross-linking and improved heavy chain secretion in vitro. In this study, co-injection of both M662C and D1828C mutated BDD-FVIII gene expression vectors into mice resulted in increased heavy chain secretion and coagulation activity in plasma in vivo. Approximately (239+_56) ng mL-1 above endogenous levels of transgenic FVIII heavy chain was found in mouse plasma using a chain-specific ELISA. For FVIII coagulation activity, approximately (1.09+_0.25) IU mL-1 above en- dogenous levels were detected in co-injected transgenic mouse plasma using a chromogenic assay. These data demonstrate that inter-chain disulfide bonds likely increase heavy chain secretion and coagulation activity in the plasma of transgenic mice with an improved efficacy of a dual-vector delivery of BDD-FVIII gene. These findings support our ongoing efforts to develop a gene therapy for hemophilia A treatment using dual-AAV vectors.展开更多
文摘All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.
文摘All the data in this catalog are chosen from the "Preliminary Seismological Report of Chi- nese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.
文摘All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geoohysics, China Earthquake Administration.
文摘Illustration All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled bv the Ninth Section of Institute of Geophysics, China Earthquake Administration.
基金Supported by the Special Project of Department of Science and Technology of Hebei Province(08820412D)the Special Project of Qinhuangdao Municipal Bureau of Science and Technology[Qinkeji(2003)30-35]+1 种基金the Special Project of Shijiazhuang Municipal Bureau of Science and Technology(07150193A)the Scientific Research Innovation Team Project of Hebei Normal University of Science and Technology(TD201201)~~
文摘[Objective] This study aimed to identify the in vitro antibacterial activity of golden buckwheat extract and investigate the therapeutic effect of its preparation on mycoplasma infection. [Method] Through measuring the minimum inhibitory concentra-tion, the in vitro antibacterial activity of golden buckwheat water extract was deter-mined; meanwhile, the therapeutic effect of golden buckwheat oral solution on my-coplasma infection was determined by artificial y infecting chickens with Mycoplasma gal isepticum culture. [Results] The golden buckwheat water extract had obvious in-hibitory effects against Pseudomonas aeruginosa and Escherichia coli, and a certain inhibitory effect on Salmonel a and Staphylococcus aureus; administration of golden buckwheat oral solution at the dose of 0.5%-1.0% continuously for 5 d had a good therapeutic effect against mycoplasma infection. [Conclusion] The study provides sci-entific bases for further study on the antibacterial activity of golden buckwheat and its application.
基金This paper is in a project sponsored by The Special Fund Construction of Guangdong Higher Education It was alsoselected to beincluded in the presentations at the 4th Asia TEFL Conferencein Fukuoka,Japan
文摘In the context of Chinese learning English writing to learn and length approach is one of the highlighted concepts and practices. It entails sufficient comprehensible input and active interaction. It is found that the theme-based modules/units, if organized and performed meaningfully and closely related to the learners' life and experiences, will best integrate these three elements in the process of the second language learning, which is geared in some major aspects to the whole language philosophy. 'Writing to learn' is a product of reverse thinking. In a theme-based module/unit, a writing task of the same theme is put at its end with some requirements for language enhancement. It serves as an engine to learn other skills. In reality, it is not writing alone that functions in the SLA, but writing at the final stage that requires comprehended input and good qualitative interaction together to fuel SLA. An experiment of 20 weeks shows the positive results for the model.
文摘According to the ideas and concepts of systems dynamic of continent structure, using previous information related to the study area, combining analyses on orogenic belt, basin and magmatic rock, the present paper synthesizes the tectono - sedimentary development of southeastern coast region, China, with special emphasis on the mountain making, basining and magmatic activity. The tectonic evolution after Late Caledonian orogeny was dominated by alternating rifting and converging, subsiding and uplifting, mountain making and basining in central and southern parts of southeastern China and the adjacent regions to the east and west. Seventeen geologic events , nine events of plate or terrain convergence , and continental crust accretion , as well as eight events of intracontinental rifting and basin faulting , are closely related to the tectonic and sedimentary evolution of the study area . The accompanied intense and frequent sedimentation , folding , faulting , magmatism and ore- forming process allowed huge coal , multimetal and potential petroleum source rocks to form in local depressions throughout the Caledonian to Himalavan time .
基金This paper was presented on the Fourth Asian Chemical Congress Beijin (1991)
文摘Fourteen new tricyclohexyltin (Ⅳ)-O,O-diaryldithiophosphates were synthesized and determined by IR, 1H NMR, 13C NMR, 119Sn NMR MS, and elemental analysis. The structures of all the compounds consist of discrete molecule containing a four-coordinated tin atom. Results from the preliminary biological test show that these compounds have a high miticidal activity.
文摘All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China EarthQuake Administration.
文摘Illustration All the data in this catalog are chosen from the "Preliminary Seismological Report of Chinese Seismic Stations" (Its abbreviation is "Monthly Report"). The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The "Monthly Report" is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.
基金Supported by the National Natural Science Foundation of China:Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Microvascular Dysfunction and Related Regulators of Myocardial Infarction Rats(No.81173142)Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Mitochondrial Energy Metabolism and Signal Transduction of Myocardial Ischemia Rats(No.81473552)The Basic Research Program(graduate program)of Beijing university of Chinese Medicine:Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Notch Signal Network of Myocardial Infarction Rats(No.2016-JYB-XS034)
文摘OBJECTIVE: To investigate the effect of Yiqihuoxue prescription(YQHX) from Traditional Chinese Medicine(TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver kinase B1(LKB1)-dependent Notch1 and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK). YQHX was prepared with substances with properties that benefit, to activate blood circulation based on the TCM theory.METHODS: Animal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The animals were randomly divided into a myocardial infarction(MI) group, a YQHX group, a perindopril group, a γ-secretase inhibitor, Notch signal inhibitor(DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the relevant indexes were examined on weeks 1 and 4.Changes in cardiac structure and function were examined by echocardiography. The glucose and free fatty acids(FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK m RNA was examined by a real-time fluorescence quantitative method. The expression of glucose transporter 4(GLUT4), and the expression of total acetyl-Co A carboxylase(ACC) and its phosphorylation were examined by western blotting.RESULTS: Compared with the sham group, the expression of Notch, LKB1 and AMPK m RNA in the MI group was lower. Compared with the MI group, the expression of these m RNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and p ACC decreased in the MI group. On week 1, the expression of p ACC protein was higher. In the DAPT group, the expression of p ACC protein decreased. Compared with the YQHX group, the expression of p ACC protein in the DAPT + YQHX group was lower. On week 4,compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindo-pril group was higher. The expression of GLUT4 protein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC protein between the groups.CONCLUSION: YQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocardial tissue after myocardial infarction. Furthermore,it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via different mechanisms and protecting the heart.
基金the National Basic Research Program(973 Program)to XCZ(Nos.2009CB918803 and 2011CB910301).
文摘GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells.Their importance to basic cell biology,human diseases,and pharma-ceutical interventions is well established.Many crystal structures of GPCR proteins have been reported in both active and inactive conformations.These data indicate that agonist binding alone is not suffi cient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins,yet other essential factors re-main elusive.Based on analysis of available GPCR crystal structures,we identifi ed a potential conformational switch around the conserved Asp2.50,which consistently shows distinct conformations between inactive and active states.Combining the structural information with the current literature,we propose an energy-coupling mechanism,in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.
文摘Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant osseous healing. Early topical insulin treat- ment was recently shown to normalize diabetic bone healing by rectifying impairments in osteoblastic activities. In this study, insulin/poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double-emulsion solvent evaporation method. Microspheres were then incorporated in fibrin gel to develop a local drug delivery system for diabetic patients requiring im- plant treatment. In vitro release of insulin from fibrin gel loaded with these microspheres was assessed, and sustained prolonged insulin release over 21 days ascertained. To assess the bioactivity of released insulin and determine whether slow release might improve impaired diabetic bone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, mineralized nodule formation, and ELISA (enzyme-linked immunosorbent assay) assays were performed. The insulin released from the drug delivery system stimulated cell growth in previously inhibited cells, and ameliorated the impaired bone-forming ability of human MG-63 cells under high glucose conditions. Fibrin gel loaded with insulin/PLGA microspheres shows potential for improving peri-implant bone formation in diabetic patients.
基金supported by the Natural Science Foundation of Shandong Province,China(Grant No.ZR2010CM061)the Scientific Research Foundation from Ministry of Education for Returned Overseas Chinese Scholars(Grant No.20071108)
文摘Hemophilia A is caused by a genetic mutation in coagulation factor VIII (FVIII) gene and gene therapy is considered to be a promising strategy for its treatment. We recently demonstrated that co-delivery of two vectors expressing M662C mutated heavy and D1828C mutated light chain genes of B-domain-deleted coagulation factor VIII (BDD-FVIII) leads to inter-chain disulfide cross-linking and improved heavy chain secretion in vitro. In this study, co-injection of both M662C and D1828C mutated BDD-FVIII gene expression vectors into mice resulted in increased heavy chain secretion and coagulation activity in plasma in vivo. Approximately (239+_56) ng mL-1 above endogenous levels of transgenic FVIII heavy chain was found in mouse plasma using a chain-specific ELISA. For FVIII coagulation activity, approximately (1.09+_0.25) IU mL-1 above en- dogenous levels were detected in co-injected transgenic mouse plasma using a chromogenic assay. These data demonstrate that inter-chain disulfide bonds likely increase heavy chain secretion and coagulation activity in the plasma of transgenic mice with an improved efficacy of a dual-vector delivery of BDD-FVIII gene. These findings support our ongoing efforts to develop a gene therapy for hemophilia A treatment using dual-AAV vectors.