Objective:The aims of this study were to investigate the clinical applicability of 3D segmentation in measuring cochlear anatomical parameters,explore factors that influence the insertion angle of cochlear implant ele...Objective:The aims of this study were to investigate the clinical applicability of 3D segmentation in measuring cochlear anatomical parameters,explore factors that influence the insertion angle of cochlear implant electrodes in patients with inner ear malformations,and determine the value of 3D segmentation in predicting cochlear implant electrode insertion depth by simulating electrode implantation in a reconstructed 3D model.Methods:Data from 208 temporal bone CT scans of patients with a variety of inner ear malformations(including the CH,IP-Ⅰ,IP-Ⅱ,and IP-Ⅲtypes)who underwent cochlear implantation at our center were retrospectively analyzed.Preoperative temporal bone CT data were subjected to three-dimensional(3D)segmentation of the cochlea with a 3D slicer.Results:Cochlear malformation types,including IP typesⅠ(42 ears),Ⅱ(278ears),Ⅲ(20 ears),and CH(65 ears),were diagnosed and measured in 208 preoperative CT datasets.Cochlear anatomical parameters and electrode length were correlated,which partially explained the variations in electrode insertion angle.The mean angle of implantation among the enrolled patients was 564.33°,and the mean implantation angle prediction error in the 3D segmentation was|23.74|°.Conclusion:Three-dimensional segmentation from temporal bone CT is valuable for surgeons,especially in treating patients with inner ear malformation.Such insights will help surgeons understand overall anatomical variations,predict electrode implantation depth,and complete preoperative imaging assessments for cochlear implant insertion depth in patients with inner ear malformations.展开更多
Opium poppy(Papaver somniferum)is a source of morphine,codeine,and semisynthetic derivatives,including oxycodone and naltrexone.Here,we report the de novo assembly and genomic analysis of P.somniferum traditional land...Opium poppy(Papaver somniferum)is a source of morphine,codeine,and semisynthetic derivatives,including oxycodone and naltrexone.Here,we report the de novo assembly and genomic analysis of P.somniferum traditional landrace‘Chinese Herbal Medicine’.Variations between the 2.62 Gb CHM genome and that of the previously sequenced high noscapine 1(HN1)variety were also explored.Among 79,668 protein-coding genes,we functionally annotated 88.9%,compared to 68.8%reported in the HN1 genome.Gene family and 4DTv comparative analyses with three other Papaveraceae species revealed that opium poppy underwent two whole-genome duplication(WGD)events.The first of these,in ancestral Ranunculales,expanded gene families related to characteristic secondary metabolite production and disease resistance.The more recent species-specific WGD mediated by transposable elements resulted in massive genome expansion.Genes carrying structural variations and large-effect variants associated with agronomically different phenotypes between CHM and HN1 that were identified through our transcriptomic comparison of multiple organs and developmental stages can enable the development of new varieties.These genomic and transcriptomic analyses will provide a valuable resource that informs future basic and agricultural studies of the opium poppy.展开更多
To search for a new eco-friendly therapy for infectious disease caused by Escherichia coli,Staphylococcus aureus or Klebsiella oxytoca,we collected the vaginal swabs from healthy women,screened for Lactobacillus and f...To search for a new eco-friendly therapy for infectious disease caused by Escherichia coli,Staphylococcus aureus or Klebsiella oxytoca,we collected the vaginal swabs from healthy women,screened for Lactobacillus and found a strain repressing the growth of pathogenic bacteria.The new isolate was identified as L.gasseri by the colony morphology,Gram staining,biochemical reactions and confirmed by the 16 S rDNA sequencing.The HMV18 strain inhibited the growth of food-borne pathogens such as E.coli,S.aureus and K.oxytoca.The HMV18 strain was sensitive to penicillin,ampicillin,erythromycin,tetracycline and chloramphenicol.The HMV18 strain producedα-hemolysis.Pathological histology of the mice ileum showed that the mucosa,villi,lamina propria and crypt depth remained intact and there was no inflammation or hyperemia in the L.gasseri HMV18 gavaged group.L.gasseri HMV18 could not up-regulate inflammatory cytokines level of plasma.All the results suggested L.gasseri HMV18 is a candidate probiotic to be an additive for food preservation or drug to prevent food-borne diseases.展开更多
Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of...Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.展开更多
This study conducted a bibliometric and visualization analysis of 265 publications related to Gelsemium elegans Benth.(G.elegans)poisoning in China,retrieved from the China National Knowledge Infrastructure database c...This study conducted a bibliometric and visualization analysis of 265 publications related to Gelsemium elegans Benth.(G.elegans)poisoning in China,retrieved from the China National Knowledge Infrastructure database covering the years 1995–2025.It systematically summarizes the current status,developmental trends,and research hotspots in this field.The results indicate that research on G.elegans poisoning in China has evolved through three distinct phases:An initial stage from 1995 to 2005,rapid growth from 2005 to 2015,and a peak period after 2016,with publication peaks in 2019 and 2022,reflecting growing scientific and public attention to this issue.Key research institutions are primarily concentrated at the Hunan Agricultural University and Fujian University of Traditional Chinese Medicine,representing the core centers in the field.Keyword co-occurrence and clustering analyses revealed“G.elegans,”“poisoning,”and“Gelsemium alkaloids”as central themes,with studies on the toxicological mechanisms of indole alkaloids being particularly prominent.Research directions span toxicological mechanisms,epidemiology,and clinical management.Funding analysis further showed that the National Natural Science Foundation of China has provided substantial support for this field.Overall,research on G.elegans poisoning has advanced considerably,especially regarding alkaloid constituents and their toxic mechanisms.However,translational research,early diagnosis,antidote development,and misuse prevention remain underexplored.Future studies should emphasize multidisciplinary collaboration to promote advances in clinical management,toxicological assessment,and public health prevention strategies related to G.elegans poisoning.展开更多
Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many cancers.Therefore, inhibiting the acti...Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many cancers.Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR.Olmutinib is an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), which has been approved in South Korea for advanced EGFR T790 M-positive non-small cell lung cancer(NSCLC). Here,we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin(DOX) and rhodamine 123(Rho 123) in ABC transporter subfamily G member 2(ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [^(125) I]-iodoarylazidoprazosin(IAAP). However, olmutinib neither altered ABCG2 expression at protein and m RNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly,olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.展开更多
In order to investigate immunogenicity in the induction of humoral and cellular immune responses, severe acute respiratory syndrome associated coronavirus （SARS-CoV）-N gene recombinant replication-defective adenovir...In order to investigate immunogenicity in the induction of humoral and cellular immune responses, severe acute respiratory syndrome associated coronavirus （SARS-CoV）-N gene recombinant replication-defective adenoviral vector, rAd-N, was generated and immunized BALB/c mice in a pcDNA3.1-N prime-rAd-N boost regimen. After humoral and cellular immune response detection, different levels of SARS-CoV N protein specific antibodies and interferon-γ （IFN-γ） secretion are shown compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen. There is a significant difference between heterogeneous and homologous vaccinations. The heterogeneous combinations were all higher than those of the homologous combinations in the induction of anti-N antibody response. Among the three heterogeneous combinations, pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N induced the strongest antibody response. In the induction of IFN-γ production, the homologous combination of rAd-N/rAd-N/rAd-N/rAd-N was significantly stronger than that of pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N, but was relatively weaker than the heterogeneous combination of pcDAN3.1-N/pcDAN3.1-N/pcDAN3.1-N/rAd-N. This combination was a most efficient immunization regimen in induction of SARS-CoV-N-specific （IFN-γ） secretion just as the antibody response. These results suggest that DNA immunization followed by recombinant adenovirns boosting could be used as a potential SARS-CoV vaccine.展开更多
In recent years,benzodiazepines and benzodiazepine-like drugs are the most common substances associated with drug-facilitated sexual assaults(DFSA);however,barbiturates are also detected occasionally.Segmental hair an...In recent years,benzodiazepines and benzodiazepine-like drugs are the most common substances associated with drug-facilitated sexual assaults(DFSA);however,barbiturates are also detected occasionally.Segmental hair analysis provides useful information on the historic pattern of drug use,enabling differentiation between single exposure in DFSA cases and chronic use.However,sensitive and specific methods for barbiturate analysis in hair samples are needed.Herein,we present an ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)method for qualitative and quantitative determination of seven barbiturates in hair samples.Firstly,a hair strand was decontaminated and then freeze-milled in liquid nitrogen.Next,50mg of powdered hair was extracted with methanol in an ultrasonic bath for 10 min in the presence of 10 ng phenobarbital-d5.The supernatant was dried under nitrogen gas,and the pellet was dissolved in 100 μL mobile phase.Afterwards,10 μL of the suspension was injected into the UHPLC-HRMS system.The present method involved two UHPLC conditions for determination of barbiturates(I)and identification of the structural isomers amobarbital and pentobarbital(II).This method showed satisfactory linearity in a range of 0.02–20.00 ng/mg for UHPLC conditions I and II,both with a high determination coefficient(0.9991–0.9999).The selectivity,intra-and interday precision,accuracy and matrix effect of the method were acceptable.Next,the validated method was applied to investigate an authentic DFSA case.Hair samples(black,approximate 25cm long)were collected 3 months after the assault,and the proximal segments(0–5 cm from the root;each segment was 1 cm long)were analysed.Amobarbital was detected at a concentration of<LOQ(limit of quantification)and 0.09 ng/mg in the second and third 1-cm hair segment but not in the other segments.Thus,our method was successful in determining barbiturate concentration in human hair after a single-dose exposure,showing its potential for application in the investigation of DFSA cases.展开更多
基金supported by the National Key Research and Development Program of China(grant no.2022YFC2402705)National Municipal Natural Science Foundation(grant no.82471161)Beijing Municipal Natural Science Foundation(grant no.7244308)。
文摘Objective:The aims of this study were to investigate the clinical applicability of 3D segmentation in measuring cochlear anatomical parameters,explore factors that influence the insertion angle of cochlear implant electrodes in patients with inner ear malformations,and determine the value of 3D segmentation in predicting cochlear implant electrode insertion depth by simulating electrode implantation in a reconstructed 3D model.Methods:Data from 208 temporal bone CT scans of patients with a variety of inner ear malformations(including the CH,IP-Ⅰ,IP-Ⅱ,and IP-Ⅲtypes)who underwent cochlear implantation at our center were retrospectively analyzed.Preoperative temporal bone CT data were subjected to three-dimensional(3D)segmentation of the cochlea with a 3D slicer.Results:Cochlear malformation types,including IP typesⅠ(42 ears),Ⅱ(278ears),Ⅲ(20 ears),and CH(65 ears),were diagnosed and measured in 208 preoperative CT datasets.Cochlear anatomical parameters and electrode length were correlated,which partially explained the variations in electrode insertion angle.The mean angle of implantation among the enrolled patients was 564.33°,and the mean implantation angle prediction error in the 3D segmentation was|23.74|°.Conclusion:Three-dimensional segmentation from temporal bone CT is valuable for surgeons,especially in treating patients with inner ear malformation.Such insights will help surgeons understand overall anatomical variations,predict electrode implantation depth,and complete preoperative imaging assessments for cochlear implant insertion depth in patients with inner ear malformations.
基金the National Science Foundation of China(Grant 81671876)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grant 2016JB024)。
文摘Opium poppy(Papaver somniferum)is a source of morphine,codeine,and semisynthetic derivatives,including oxycodone and naltrexone.Here,we report the de novo assembly and genomic analysis of P.somniferum traditional landrace‘Chinese Herbal Medicine’.Variations between the 2.62 Gb CHM genome and that of the previously sequenced high noscapine 1(HN1)variety were also explored.Among 79,668 protein-coding genes,we functionally annotated 88.9%,compared to 68.8%reported in the HN1 genome.Gene family and 4DTv comparative analyses with three other Papaveraceae species revealed that opium poppy underwent two whole-genome duplication(WGD)events.The first of these,in ancestral Ranunculales,expanded gene families related to characteristic secondary metabolite production and disease resistance.The more recent species-specific WGD mediated by transposable elements resulted in massive genome expansion.Genes carrying structural variations and large-effect variants associated with agronomically different phenotypes between CHM and HN1 that were identified through our transcriptomic comparison of multiple organs and developmental stages can enable the development of new varieties.These genomic and transcriptomic analyses will provide a valuable resource that informs future basic and agricultural studies of the opium poppy.
基金supported by Natural Science Foundation of Hebei Province(H2020206579)S&T Program of Hebei(18277743D)+3 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)Key R&D projects in Hebei Province(20327125D)the Training Plan for Young Innovative Talents in Science and Technology(TJZR202008)Spring rain project of Hebei Medical University(CYCZ201906)。
文摘To search for a new eco-friendly therapy for infectious disease caused by Escherichia coli,Staphylococcus aureus or Klebsiella oxytoca,we collected the vaginal swabs from healthy women,screened for Lactobacillus and found a strain repressing the growth of pathogenic bacteria.The new isolate was identified as L.gasseri by the colony morphology,Gram staining,biochemical reactions and confirmed by the 16 S rDNA sequencing.The HMV18 strain inhibited the growth of food-borne pathogens such as E.coli,S.aureus and K.oxytoca.The HMV18 strain was sensitive to penicillin,ampicillin,erythromycin,tetracycline and chloramphenicol.The HMV18 strain producedα-hemolysis.Pathological histology of the mice ileum showed that the mucosa,villi,lamina propria and crypt depth remained intact and there was no inflammation or hyperemia in the L.gasseri HMV18 gavaged group.L.gasseri HMV18 could not up-regulate inflammatory cytokines level of plasma.All the results suggested L.gasseri HMV18 is a candidate probiotic to be an additive for food preservation or drug to prevent food-borne diseases.
基金financially supported by postdoctoral funding of Hebei Medical UniversityHebei Province Postdoctoral Research Project Funding(B2022003035)+5 种基金Natural Science Foundation of Hebei Province(H2020206579)CAMS Innovation Found for Medical Sciences(2019-I2M-5-055)2023 Scientific Research Projects of Colleges and Universities in Hebei Province(QN2023131)S&T Program of Hebei(18277743D)Undergraduate Innovation Experiment Project from Hebei Medical University(USIP2019008)Spring rain project of Hebei Medical University(CYCZ201906)。
文摘Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.
基金sponsored by the Major Projects of the National Natural Science Foundation of China(No.82293650,82293651)the Natural Science Foundation for Distinguished Young Scholars of Hebei Province,China(No.H2022206026).
文摘This study conducted a bibliometric and visualization analysis of 265 publications related to Gelsemium elegans Benth.(G.elegans)poisoning in China,retrieved from the China National Knowledge Infrastructure database covering the years 1995–2025.It systematically summarizes the current status,developmental trends,and research hotspots in this field.The results indicate that research on G.elegans poisoning in China has evolved through three distinct phases:An initial stage from 1995 to 2005,rapid growth from 2005 to 2015,and a peak period after 2016,with publication peaks in 2019 and 2022,reflecting growing scientific and public attention to this issue.Key research institutions are primarily concentrated at the Hunan Agricultural University and Fujian University of Traditional Chinese Medicine,representing the core centers in the field.Keyword co-occurrence and clustering analyses revealed“G.elegans,”“poisoning,”and“Gelsemium alkaloids”as central themes,with studies on the toxicological mechanisms of indole alkaloids being particularly prominent.Research directions span toxicological mechanisms,epidemiology,and clinical management.Funding analysis further showed that the National Natural Science Foundation of China has provided substantial support for this field.Overall,research on G.elegans poisoning has advanced considerably,especially regarding alkaloid constituents and their toxic mechanisms.However,translational research,early diagnosis,antidote development,and misuse prevention remain underexplored.Future studies should emphasize multidisciplinary collaboration to promote advances in clinical management,toxicological assessment,and public health prevention strategies related to G.elegans poisoning.
基金supported by the National Natural Science Foundation of China (No. 81473233)Guangzhou Technology Program Foundation (No. 201604020079)+1 种基金The Science and Technology Project of Guangdong Province (No. 2016A030312014)The Scientific and Technological Leading Talent Project of Guangdong Province (2015)
文摘Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many cancers.Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR.Olmutinib is an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), which has been approved in South Korea for advanced EGFR T790 M-positive non-small cell lung cancer(NSCLC). Here,we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin(DOX) and rhodamine 123(Rho 123) in ABC transporter subfamily G member 2(ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [^(125) I]-iodoarylazidoprazosin(IAAP). However, olmutinib neither altered ABCG2 expression at protein and m RNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly,olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.
文摘In order to investigate immunogenicity in the induction of humoral and cellular immune responses, severe acute respiratory syndrome associated coronavirus （SARS-CoV）-N gene recombinant replication-defective adenoviral vector, rAd-N, was generated and immunized BALB/c mice in a pcDNA3.1-N prime-rAd-N boost regimen. After humoral and cellular immune response detection, different levels of SARS-CoV N protein specific antibodies and interferon-γ （IFN-γ） secretion are shown compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen. There is a significant difference between heterogeneous and homologous vaccinations. The heterogeneous combinations were all higher than those of the homologous combinations in the induction of anti-N antibody response. Among the three heterogeneous combinations, pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N induced the strongest antibody response. In the induction of IFN-γ production, the homologous combination of rAd-N/rAd-N/rAd-N/rAd-N was significantly stronger than that of pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N, but was relatively weaker than the heterogeneous combination of pcDAN3.1-N/pcDAN3.1-N/pcDAN3.1-N/rAd-N. This combination was a most efficient immunization regimen in induction of SARS-CoV-N-specific （IFN-γ） secretion just as the antibody response. These results suggest that DNA immunization followed by recombinant adenovirns boosting could be used as a potential SARS-CoV vaccine.
基金This study was financially supported in part by the National Key R&D Program of China[grant number 2016YFC0800704]the Natural Science Foundation of China[grant number 81501633].
文摘In recent years,benzodiazepines and benzodiazepine-like drugs are the most common substances associated with drug-facilitated sexual assaults(DFSA);however,barbiturates are also detected occasionally.Segmental hair analysis provides useful information on the historic pattern of drug use,enabling differentiation between single exposure in DFSA cases and chronic use.However,sensitive and specific methods for barbiturate analysis in hair samples are needed.Herein,we present an ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)method for qualitative and quantitative determination of seven barbiturates in hair samples.Firstly,a hair strand was decontaminated and then freeze-milled in liquid nitrogen.Next,50mg of powdered hair was extracted with methanol in an ultrasonic bath for 10 min in the presence of 10 ng phenobarbital-d5.The supernatant was dried under nitrogen gas,and the pellet was dissolved in 100 μL mobile phase.Afterwards,10 μL of the suspension was injected into the UHPLC-HRMS system.The present method involved two UHPLC conditions for determination of barbiturates(I)and identification of the structural isomers amobarbital and pentobarbital(II).This method showed satisfactory linearity in a range of 0.02–20.00 ng/mg for UHPLC conditions I and II,both with a high determination coefficient(0.9991–0.9999).The selectivity,intra-and interday precision,accuracy and matrix effect of the method were acceptable.Next,the validated method was applied to investigate an authentic DFSA case.Hair samples(black,approximate 25cm long)were collected 3 months after the assault,and the proximal segments(0–5 cm from the root;each segment was 1 cm long)were analysed.Amobarbital was detected at a concentration of<LOQ(limit of quantification)and 0.09 ng/mg in the second and third 1-cm hair segment but not in the other segments.Thus,our method was successful in determining barbiturate concentration in human hair after a single-dose exposure,showing its potential for application in the investigation of DFSA cases.
