Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At pre...Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At present,many commercial IBV vaccines have been used for the prevention and control of IB;however,IB outbreaks occur frequently.In this study,two new strains of IBV,SX/2106 and SX/2204,were isolated from two flocks which were immunized with IBV H120 vaccine in central China.Phylogenetic and recombination analysis indicated that SX/2106,which was clustered into the GI-19 lineage,may be derived from recombination events of the GI-19 and GI-7 strains and the LDT3-A vaccine.Genetic analysis showed that SX/2204 belongs to the GVI-1 lineage,which may have originated from the recombination of the GI-13 and GVI-1 strains and the H120 vaccine.The virus cross-neutralization test showed that the antigenicity of SX/2106 and SX/2204 was different from H120.Animal experiments found that both SX/2106 and SX/2204 could replicate effectively in the lungs and kidneys of chickens and cause disease and death,and H120 immunization could not provide effective protection against the two IBV isolates.It is noteworthy that the pathogenicity of SX/2204 has significantly increased compared to the GVI-1 strains isolated previously,with a mortality rate up to 60%.Considering the continuous mutation and recombination of the IBV genome to produce new variant strains,it is important to continuously monitor epidemic strains and develop new vaccines for the prevention and control of IBV epidemics.展开更多
The H9N2 subtype of avian influenza virus(AIV)is widely prevalent in poultry and wild birds globally,and has become the predominant subtype circulating in poultry in China.The H9N2 AIV can directly or indirectly(by se...The H9N2 subtype of avian influenza virus(AIV)is widely prevalent in poultry and wild birds globally,and has become the predominant subtype circulating in poultry in China.The H9N2 AIV can directly or indirectly(by serving as a"donor virus")infect humans,posing a significant threat to public health.Currently,there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province,central China.In this study,we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province,and genetic analysis revealed that these viruses belonged to 7 different genotypes.Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations,and exhibited diverse replication abilities within these birds.These viruses could replicate efficiently in the lungs of mice,with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys.At the cellular level,the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays,revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level.The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters.Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China.It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.展开更多
Due to low solubility and bioavailability, atorvastatin calcium is confronted with challenge in conceiving appropriate formulation. Solid dispersion of atorvastatin calcium was prepared through the solvent evaporation...Due to low solubility and bioavailability, atorvastatin calcium is confronted with challenge in conceiving appropriate formulation. Solid dispersion of atorvastatin calcium was prepared through the solvent evaporation method, with Poloxamer 188 as hydrophilic carriers. This formulation was then characterized by scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction and fourier transform infrared spectroscopy. Moreover, all these studies suggested the conversion of crystalline atorvastatin calcium. In addition, the drug solubility studies as well as dissolution rates compared with bulk drug and market tablets Lipitor were also examined. Furthermore, the study investigated the pharmacokinetics after oral administration of Lipitor and solid dispersion. And the AUC 0–8 h and C max increased after taking ATC-P188 solid dispersion orally compared with that of Lipitor. All these could be demonstrated that ATC-P188 solid dispersions would be prospective means for enhancing higher oral bioavailability of ATC.展开更多
A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of A...A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.展开更多
The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles(docetaxel-loaded mixed micelles...The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles(docetaxel-loaded mixed micelles) are able to increase the solubility of DTX inwater, and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles) can accelerate the formation of a depot of this drug-loaded system at the siteof administration. Therefore, the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection. An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety. In conclusion, theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem, with higher tumor inhibition effects and are less toxic to normal tissues.展开更多
Coptis chinensis Franch, a widely used Traditional Chinese Medicine, shows various kinds of bioactivity. The major active components of the herb are considered to be alkaloids. Thus, preparative separation of these al...Coptis chinensis Franch, a widely used Traditional Chinese Medicine, shows various kinds of bioactivity. The major active components of the herb are considered to be alkaloids. Thus, preparative separation of these alkaloids is critical important for further pharmacology and mechanism studies. In the paper, five alkaloids from C. chinensis were purified by HSCCC using the solvent system composed of chloro-form-metha- nol-water (2:1:1, v/v/v) single prepared. The content of each solvent in solvent system were determined by gas chromatography (GC), then according the ratios of solvents in each phase to prepare the mobile and stationary phase respectively. And a comparative study was carried out between together preparation and single preparation of the solvent system. The purities and recoveries of all the products were over 98.5% and 92%. However, 134 mL chloroform, 336 mL methanol and 452 mL water were saved when the two phase were singled by GC. Our research showed an economical method for separating alkaloids from C. chinensis by HSCCC using the solvent system single prepared by GC.展开更多
School-age children are in a specific development stage corresponding to juvenility,when the white matter of the brain experiences ongoing maturation.Dffusion-weighted magnetic resonance imaging(DWI),especially diffus...School-age children are in a specific development stage corresponding to juvenility,when the white matter of the brain experiences ongoing maturation.Dffusion-weighted magnetic resonance imaging(DWI),especially diffusion tensor imaging(DTI),is extensively used to characterize the maturation by assessing white matter properties in vivo.In the analysis of DWI data,spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space.Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization.However,there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development.Here,we established the school-age children diffusion tensor(SACT)template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years.With an age-balanced design,the SACT template represented the entire age range well by showing high similarity to the age-specific templates.Compared with the tensor template of adults,the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of schoolage children.A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template.Although similar spatial patterns were found,the SACT template showed significant effects on the distributions of the statistical results,which may be related to the performance of spatial normalization.Looking forward,the SACT template could contribute to future studies of white matter development in both healthy and clinical populations.The SACT template is publicly available now(tp://igshare com/aricles/dataseu'SACT_.template/14071283).展开更多
Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) resi...Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes ( P = 0.046 and P = 0.048). Pa- tients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs ( P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mu- tations with pre-treatment CTCs compared with post-treatment CTCs. Conclusions: Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.展开更多
基金supported by the National Natural Science Foundation of China(32202788)the Special Research Fund of Shanxi Agricultural University for High-level Talents,China(2021XG004)+3 种基金the Fund for Shanxi“1331 Project”,China(20211331-13)the Shanxi Province Excellent Doctoral Work Award-Scientific Research Project,China(SXBYKY2021063,SXBYKY2021005,and SXBYKY 2022014)the earmarked fund for Modern Agro-industry Technology Research System of Shanxi Province,China(2023CYJSTX15-13)the Fundamental Research Program of Shanxi Province,China(202103021224156)。
文摘Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At present,many commercial IBV vaccines have been used for the prevention and control of IB;however,IB outbreaks occur frequently.In this study,two new strains of IBV,SX/2106 and SX/2204,were isolated from two flocks which were immunized with IBV H120 vaccine in central China.Phylogenetic and recombination analysis indicated that SX/2106,which was clustered into the GI-19 lineage,may be derived from recombination events of the GI-19 and GI-7 strains and the LDT3-A vaccine.Genetic analysis showed that SX/2204 belongs to the GVI-1 lineage,which may have originated from the recombination of the GI-13 and GVI-1 strains and the H120 vaccine.The virus cross-neutralization test showed that the antigenicity of SX/2106 and SX/2204 was different from H120.Animal experiments found that both SX/2106 and SX/2204 could replicate effectively in the lungs and kidneys of chickens and cause disease and death,and H120 immunization could not provide effective protection against the two IBV isolates.It is noteworthy that the pathogenicity of SX/2204 has significantly increased compared to the GVI-1 strains isolated previously,with a mortality rate up to 60%.Considering the continuous mutation and recombination of the IBV genome to produce new variant strains,it is important to continuously monitor epidemic strains and develop new vaccines for the prevention and control of IBV epidemics.
基金Fundamental Research Program of Shanxi Province,China(202103021224156)National Natural Science Foundation of China(32202788)+5 种基金Special Research Fund of Shanxi Agricultural University for High-level Talents,China(2021XG004)Science and Technology Innovation Program of Shanxi Agricultural University,China(2021BQ78)special fund for Science and Technology Innovation Teams of Shanxi Province,China(202304051001041)?Shanxi Province Excellent Doctoral Work Award-Scientific Research Project,China(SXBYKY2021005,SXBYKY2021063,SXBYKY2022014)the Fund for Shanxi“1331 Project”,China(20211331-13)earmarked fund for Modern Agro-industry Technology Research System of Shanxi Province,China.
文摘The H9N2 subtype of avian influenza virus(AIV)is widely prevalent in poultry and wild birds globally,and has become the predominant subtype circulating in poultry in China.The H9N2 AIV can directly or indirectly(by serving as a"donor virus")infect humans,posing a significant threat to public health.Currently,there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province,central China.In this study,we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province,and genetic analysis revealed that these viruses belonged to 7 different genotypes.Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations,and exhibited diverse replication abilities within these birds.These viruses could replicate efficiently in the lungs of mice,with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys.At the cellular level,the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays,revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level.The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters.Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China.It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.
文摘Due to low solubility and bioavailability, atorvastatin calcium is confronted with challenge in conceiving appropriate formulation. Solid dispersion of atorvastatin calcium was prepared through the solvent evaporation method, with Poloxamer 188 as hydrophilic carriers. This formulation was then characterized by scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction and fourier transform infrared spectroscopy. Moreover, all these studies suggested the conversion of crystalline atorvastatin calcium. In addition, the drug solubility studies as well as dissolution rates compared with bulk drug and market tablets Lipitor were also examined. Furthermore, the study investigated the pharmacokinetics after oral administration of Lipitor and solid dispersion. And the AUC 0–8 h and C max increased after taking ATC-P188 solid dispersion orally compared with that of Lipitor. All these could be demonstrated that ATC-P188 solid dispersions would be prospective means for enhancing higher oral bioavailability of ATC.
基金financially supported by the Science and Technology Research Project of Liaoning Provincial Education Department L2013390
文摘A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.
基金financial support to the National Natural Science Foundation of China (81202480,81302723 )the Natural Science Foundation of Liaoning Province (2015020749)+1 种基金the Innovative training program for college students (201710163000080)support of the Pharmacology Laboratory Centre and the Animal Centre of Shenyang Pharmaceutical University
文摘The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles(docetaxel-loaded mixed micelles) are able to increase the solubility of DTX inwater, and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles) can accelerate the formation of a depot of this drug-loaded system at the siteof administration. Therefore, the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection. An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety. In conclusion, theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem, with higher tumor inhibition effects and are less toxic to normal tissues.
文摘Coptis chinensis Franch, a widely used Traditional Chinese Medicine, shows various kinds of bioactivity. The major active components of the herb are considered to be alkaloids. Thus, preparative separation of these alkaloids is critical important for further pharmacology and mechanism studies. In the paper, five alkaloids from C. chinensis were purified by HSCCC using the solvent system composed of chloro-form-metha- nol-water (2:1:1, v/v/v) single prepared. The content of each solvent in solvent system were determined by gas chromatography (GC), then according the ratios of solvents in each phase to prepare the mobile and stationary phase respectively. And a comparative study was carried out between together preparation and single preparation of the solvent system. The purities and recoveries of all the products were over 98.5% and 92%. However, 134 mL chloroform, 336 mL methanol and 452 mL water were saved when the two phase were singled by GC. Our research showed an economical method for separating alkaloids from C. chinensis by HSCCC using the solvent system single prepared by GC.
基金supported by the Beijing Brain Initiative of Beijing Municipal Science&Technology Commission(Z1811001518003)the National Natural Science Foundation of China(31521063)All the authors thank the National Center for Protein Sciences at Peking University for assistance_with brain scanning.The authors thank the"2019 Helmholtz-OCPC-Program for the involvement of postdocs in bilateral collaboration projects"for financial support that enabled this important study,Allthe authors are grateful for the contribution of the participants to the CBD project and the open access to the NKI-Rockiand sample.
文摘School-age children are in a specific development stage corresponding to juvenility,when the white matter of the brain experiences ongoing maturation.Dffusion-weighted magnetic resonance imaging(DWI),especially diffusion tensor imaging(DTI),is extensively used to characterize the maturation by assessing white matter properties in vivo.In the analysis of DWI data,spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space.Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization.However,there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development.Here,we established the school-age children diffusion tensor(SACT)template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years.With an age-balanced design,the SACT template represented the entire age range well by showing high similarity to the age-specific templates.Compared with the tensor template of adults,the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of schoolage children.A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template.Although similar spatial patterns were found,the SACT template showed significant effects on the distributions of the statistical results,which may be related to the performance of spatial normalization.Looking forward,the SACT template could contribute to future studies of white matter development in both healthy and clinical populations.The SACT template is publicly available now(tp://igshare com/aricles/dataseu'SACT_.template/14071283).
基金Beijing Municipal Science and Technol-ogy Commission(grant number Z211100002921013)Tongzhou Liang-gao Talents Project(grant number YH201920)+2 种基金Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research In-stitutes(grant number JYY2024-14)Beijing Municipal Public Wel-fare Development and Reform Pilot Project for Medical Research Insti-tutes(grant number JYY2023-15)We thank all participants and their families for supporting this study.
文摘Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes ( P = 0.046 and P = 0.048). Pa- tients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs ( P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mu- tations with pre-treatment CTCs compared with post-treatment CTCs. Conclusions: Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.