Tetrodotoxin (TTX) is well known as the puffer fish toxin. Naturally occurring analogs of TTX have been isolated from puffer fish, newts and frogs, and their structures have been determined by spectroscopic methods. Additionally, TTX analogs have been prepared by chemical modification to investigate its binding site on sodium channels and the structure-activity relationship of TTX. In this article, the NMR data of TTX analogs are listed, and the chemical modification methods for preparation of TTX probes are summarized.
{"title":"CHEMISTRY OF PUFFER FISH TOXIN","authors":"M. Yotsu-Yamashita","doi":"10.1081/TXR-100102536","DOIUrl":"https://doi.org/10.1081/TXR-100102536","url":null,"abstract":"Tetrodotoxin (TTX) is well known as the puffer fish toxin. Naturally occurring analogs of TTX have been isolated from puffer fish, newts and frogs, and their structures have been determined by spectroscopic methods. Additionally, TTX analogs have been prepared by chemical modification to investigate its binding site on sodium channels and the structure-activity relationship of TTX. In this article, the NMR data of TTX analogs are listed, and the chemical modification methods for preparation of TTX probes are summarized.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"14 1","pages":"51 - 66"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76350382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ciguatera is a complex clinical syndrome, caused by a marine bio-toxin, which can affect nearly every system of the human body. The clinical syndrome has characteristic elements in its acute, chronic and recurring forms. The incidence of ciguatera is on the rise, and misdiagnosis is not uncommon. Appropriate identification, management and treatment of ciguatera is dependent on understanding the pathophysiology of the illness, determining the correct form of the illness, and applying the appropriate treatment modalities to that form. More research is necessary to clinically manage ciguatera and the clinical dilemmas it presents.
{"title":"CIGUATERA FISH POISONING: REVIEW OF CLINICAL MANIFESTATIONS","authors":"N. A. Palafox, L. Buenconsejo-Lum","doi":"10.1081/TXR-100105733","DOIUrl":"https://doi.org/10.1081/TXR-100105733","url":null,"abstract":"Ciguatera is a complex clinical syndrome, caused by a marine bio-toxin, which can affect nearly every system of the human body. The clinical syndrome has characteristic elements in its acute, chronic and recurring forms. The incidence of ciguatera is on the rise, and misdiagnosis is not uncommon. Appropriate identification, management and treatment of ciguatera is dependent on understanding the pathophysiology of the illness, determining the correct form of the illness, and applying the appropriate treatment modalities to that form. More research is necessary to clinically manage ciguatera and the clinical dilemmas it presents.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"82 1","pages":"141 - 160"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78708872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The regional distribution and the appearance of astrocytes expressing glial fibrillary acidic protein (GFAP), S100 protein, and proliferating cell nuclear antigen (PCNA) were determined in the cerebral cortex of normal and cobra venom intoxicated rats. Male rats were divided to three groups intramuscularly treated with a single injection of either physiological saline solution or ½ LD50 or LD50 of cobra venom respectively. Formalin-fixed paraffin-embedded brain sections of animals of the three groups were immunohistochemically studied according to avidin-biotin-peroxidase complex method using antibodies against GFAP, S100 protein and PCNA. As biomarkers of cerebral neurotoxicity, dose and time dependent increases in the expression of GFAP and S100 protein were observed. Marked increases in the expression of GFAP and S100 protein were common in high dose (LD50) envenomed rats 72 h after venom injection, whereas in low dose (½ LD50) envenomed rats only moderate increases of these two proteins were detected 72 h post-treatment. Similar pattern of expression was also observed for PCNA in the cerebral cortex layer III but not in layer II or layer I. PCNA, the indicator of cell proliferation, was highly expressed in cerebral cortex of envenomed rats if compared with control animals. These results demonstrate that intramuscular injection of cobra venom produces enhanced cell proliferation as measured by PCNA staining, and reactive astrocytosis as ascertained by increased GFAP and S100 immunoreactivities. This may represent a protective response of the cerebral cortex by which the brain is able to remove injured cells and protect the remaining neurons by PCNA expression. Furthermore, these observations affirm the usefulness of GFAP, S100 and PCNA immunohistochemistry as a sensitive biomarker of neurotoxicity.
{"title":"REACTIVE ASTROCYTIC RESPONSE AND INCREASED PROLIFERATING CELL NUCLEAR ANTIGEN EXPRESSION IN CEREBRAL CORTEX OF ENVENOMED RATS","authors":"I. Hassouna, T. Rahmy","doi":"10.1081/TXR-100108559","DOIUrl":"https://doi.org/10.1081/TXR-100108559","url":null,"abstract":"The regional distribution and the appearance of astrocytes expressing glial fibrillary acidic protein (GFAP), S100 protein, and proliferating cell nuclear antigen (PCNA) were determined in the cerebral cortex of normal and cobra venom intoxicated rats. Male rats were divided to three groups intramuscularly treated with a single injection of either physiological saline solution or ½ LD50 or LD50 of cobra venom respectively. Formalin-fixed paraffin-embedded brain sections of animals of the three groups were immunohistochemically studied according to avidin-biotin-peroxidase complex method using antibodies against GFAP, S100 protein and PCNA. As biomarkers of cerebral neurotoxicity, dose and time dependent increases in the expression of GFAP and S100 protein were observed. Marked increases in the expression of GFAP and S100 protein were common in high dose (LD50) envenomed rats 72 h after venom injection, whereas in low dose (½ LD50) envenomed rats only moderate increases of these two proteins were detected 72 h post-treatment. Similar pattern of expression was also observed for PCNA in the cerebral cortex layer III but not in layer II or layer I. PCNA, the indicator of cell proliferation, was highly expressed in cerebral cortex of envenomed rats if compared with control animals. These results demonstrate that intramuscular injection of cobra venom produces enhanced cell proliferation as measured by PCNA staining, and reactive astrocytosis as ascertained by increased GFAP and S100 immunoreactivities. This may represent a protective response of the cerebral cortex by which the brain is able to remove injured cells and protect the remaining neurons by PCNA expression. Furthermore, these observations affirm the usefulness of GFAP, S100 and PCNA immunohistochemistry as a sensitive biomarker of neurotoxicity.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"120 1","pages":"245 - 259"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77151144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Among the marine toxins relevant for human intoxication, tetrodo-toxin (TTX) has been known as one of the most prejudicial. Puffer fish were originally thought to be the only animal from which TTX could be isolated. Subsequent works determined that TTX also existed in a range of marine organisms of different phylogenic classes and a very few amphibians. The production of TTX is generally accepted to be associated with bacteria. This paper presents the current evidences for the distribution of TTX and its analogs in several vertebrates and invertebrates, along with the probable origin of TTX.
{"title":"DISTRIBUTION AND ORIGIN OF TETRODOTOXIN","authors":"K. Miyazawa, T. Noguchi","doi":"10.1081/TXR-100103081","DOIUrl":"https://doi.org/10.1081/TXR-100103081","url":null,"abstract":"Among the marine toxins relevant for human intoxication, tetrodo-toxin (TTX) has been known as one of the most prejudicial. Puffer fish were originally thought to be the only animal from which TTX could be isolated. Subsequent works determined that TTX also existed in a range of marine organisms of different phylogenic classes and a very few amphibians. The production of TTX is generally accepted to be associated with bacteria. This paper presents the current evidences for the distribution of TTX and its analogs in several vertebrates and invertebrates, along with the probable origin of TTX.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"10 1","pages":"11 - 33"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85156211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tetrodotoxin (TTX) is a potent neurotoxin originally found in the ovary and liver of puffer fish. It has now become abundantly clear that TTX is not synthesized in the puffer fish, and that it is produced by certain bacteria and reaches the fish via the food chain. The pharmacology of TTX had been studied for a long period of time especially in Japan as puffer fish is regarded as the most delicious fish among Japanese. However, since the pioneering discovery of the selective and potent blocking action of TTX on the sodium channel, extensive investigations by a number of scientists into its cellular and molecular mechanism of action have been launched. Equally important is the fact that TTX has since then been used extensively as a chemical tool in the laboratory for the purpose of studying the sodium channel, other ion channels, and various aspects of membrane excitability and synaptic transmission. The highlights of the recent studies of TTX are given in this chapter. Older literature is not discussed as it has been reviewed many times by a number of investigators. Readers are encouraged to consult with these review articles. Thus the present chapter covers the recent developments in the areas of the sources of TTX, the mechanisms of action on sodium channels, TTX-resistant sodium channels, the site of action and binding of TTX, and therapeutic applications of TTX. Saxitotoxin, a paralytic shellfish toxin, which exhibits the same sodium channel blocking action is also described.
{"title":"PHARMACOLOGY OF TETRODOTOXIN","authors":"T. Narahashi","doi":"10.1081/TXR-100102537","DOIUrl":"https://doi.org/10.1081/TXR-100102537","url":null,"abstract":"Tetrodotoxin (TTX) is a potent neurotoxin originally found in the ovary and liver of puffer fish. It has now become abundantly clear that TTX is not synthesized in the puffer fish, and that it is produced by certain bacteria and reaches the fish via the food chain. The pharmacology of TTX had been studied for a long period of time especially in Japan as puffer fish is regarded as the most delicious fish among Japanese. However, since the pioneering discovery of the selective and potent blocking action of TTX on the sodium channel, extensive investigations by a number of scientists into its cellular and molecular mechanism of action have been launched. Equally important is the fact that TTX has since then been used extensively as a chemical tool in the laboratory for the purpose of studying the sodium channel, other ion channels, and various aspects of membrane excitability and synaptic transmission. The highlights of the recent studies of TTX are given in this chapter. Older literature is not discussed as it has been reviewed many times by a number of investigators. Readers are encouraged to consult with these review articles. Thus the present chapter covers the recent developments in the areas of the sources of TTX, the mechanisms of action on sodium channels, TTX-resistant sodium channels, the site of action and binding of TTX, and therapeutic applications of TTX. Saxitotoxin, a paralytic shellfish toxin, which exhibits the same sodium channel blocking action is also described.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"104 1","pages":"67 - 84"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87690260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review is an extensive up-to-date compilation of ciguatera fish poisoning, a food borne disease, which covers all aspects of the problem, with the exception of clinical and therapeutic information. Thus brief accounts of the history, biology, chemistry, pharmacology, epidemiology, detection methods, pathology, and comprehensive references are presented.
{"title":"CIGUATERA FISH POISONING: A FOODBORNE DISEASE","authors":"Yoshitsugi Hokama, J. S. M. Yoshikawa‐Ebesu","doi":"10.1081/TXR-100105732","DOIUrl":"https://doi.org/10.1081/TXR-100105732","url":null,"abstract":"This review is an extensive up-to-date compilation of ciguatera fish poisoning, a food borne disease, which covers all aspects of the problem, with the exception of clinical and therapeutic information. Thus brief accounts of the history, biology, chemistry, pharmacology, epidemiology, detection methods, pathology, and comprehensive references are presented.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"325 1","pages":"139 - 85"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82920130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tetrodotoxin (TTX) intoxication resulting from the ingestion of toxic puffer is relatively common in a number of Asian countries. In Japan, 100 annual human fatality due to ingestion of toxic puffer have been reported until 1960. Poisoning incidents, however, decreased in the recent years by imposing quarantine rule and creating public awareness after extensive study of the toxicity and toxin properties of puffer. Generally, the oral paresthesia is the initial symptom of puffer poisoning. The onset of symptoms is rapid. In spite of long history of TTX intoxication, no antidotes or antitoxins to TTX is invented so far. Treatment is supportive.
{"title":"PUFFER POISONING: EPIDEMIOLOGY AND TREATMENT","authors":"T. Noguchi, J. Ebesu","doi":"10.1081/TXR-100103080","DOIUrl":"https://doi.org/10.1081/TXR-100103080","url":null,"abstract":"Tetrodotoxin (TTX) intoxication resulting from the ingestion of toxic puffer is relatively common in a number of Asian countries. In Japan, 100 annual human fatality due to ingestion of toxic puffer have been reported until 1960. Poisoning incidents, however, decreased in the recent years by imposing quarantine rule and creating public awareness after extensive study of the toxicity and toxin properties of puffer. Generally, the oral paresthesia is the initial symptom of puffer poisoning. The onset of symptoms is rapid. In spite of long history of TTX intoxication, no antidotes or antitoxins to TTX is invented so far. Treatment is supportive.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"16 1","pages":"1 - 10"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82323877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Animal venoms are rich sources of enzymes. Most enzymes found in animal venom are hydrolytic enzymes. A notable exception is L-amino acid oxidase, which is responsible for the yellow color of snake venom. Although a variety of enzymes are present in venom, only a few types have been extensively studied, most notably, proteolytic enzymes and phospholipase A2. There have been relatively few investigations on glycosidases in venom. Practically all studies on venom glycosidases have involved hyaluronidase. In addition, there are a few investigations on nicotinamide adenine nucleotidase (NADase), and polyand disaccharidases. An extensive review of venom glycosidases is presented here in order to provide an overall picture of this class of enzymes. Since hyaluronidase is more extensively investigated than other venom enzymes, it will be discussed in more detail.
{"title":"GLYCOSIDASES IN VENOMS","authors":"A. Tu, K. Kudo","doi":"10.1081/TXR-100108555","DOIUrl":"https://doi.org/10.1081/TXR-100108555","url":null,"abstract":"Animal venoms are rich sources of enzymes. Most enzymes found in animal venom are hydrolytic enzymes. A notable exception is L-amino acid oxidase, which is responsible for the yellow color of snake venom. Although a variety of enzymes are present in venom, only a few types have been extensively studied, most notably, proteolytic enzymes and phospholipase A2. There have been relatively few investigations on glycosidases in venom. Practically all studies on venom glycosidases have involved hyaluronidase. In addition, there are a few investigations on nicotinamide adenine nucleotidase (NADase), and polyand disaccharidases. An extensive review of venom glycosidases is presented here in order to provide an overall picture of this class of enzymes. Since hyaluronidase is more extensively investigated than other venom enzymes, it will be discussed in more detail.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"55 9 1","pages":"161 - 178"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79098808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cottonseed is an economical source of protein and is commonly used in balancing livestock rations; however, its use is typically limited by protein level, fat content, gossypol, and the potential for aflatoxin contamination. There are numerous studies in the literature discussing gossypol and aflatoxin toxicities in livestock and processing methods for reducing gossypol levels in cottonseed. However, there is very limited information in the literature within the last 30 years on how aflatoxin is affected by processing. Evaluation studies were conducted to determine if an extrusion process affected gossypol and aflatoxin levels in cottonseed without negatively impacting the nutritional value of the product, and if these reductions were consistent with the literature. Results from the gossypol study showed a 71 to 78% decrease in free gossypol levels due to the extrusion process, which were lower than some reported methods of processing and consistent with others. Results from the aflatoxin studies showed reductions of 50% when the material was processed by two stages of extrusion at a temperature of 132°C. Similar reductions have been reported on roasting corn at temperatures of 140 to 143°C. The extrusion temperatures used in the evaluation studies did not significantly alter most of the nutritional values analyzed in the study. However, soluble protein was decreased at the higher temperatures. There were no significant differences in analyzed nutritional values based on multiple stages of processing. Results from the evaluation study indicate that extruding cottonseed to reduce gossypol and aflatoxin levels is an area of research that should be further explored, primarily due to the advances made in the aflatoxin and gossypol testing methods during the last 30 years.
{"title":"MECHANICALLY PROCESSING COTTONSEED TO REDUCE GOSSYPOL AND AFLATOXIN LEVELS","authors":"M. Buser, H. Abbas","doi":"10.1081/TXR-100108556","DOIUrl":"https://doi.org/10.1081/TXR-100108556","url":null,"abstract":"Cottonseed is an economical source of protein and is commonly used in balancing livestock rations; however, its use is typically limited by protein level, fat content, gossypol, and the potential for aflatoxin contamination. There are numerous studies in the literature discussing gossypol and aflatoxin toxicities in livestock and processing methods for reducing gossypol levels in cottonseed. However, there is very limited information in the literature within the last 30 years on how aflatoxin is affected by processing. Evaluation studies were conducted to determine if an extrusion process affected gossypol and aflatoxin levels in cottonseed without negatively impacting the nutritional value of the product, and if these reductions were consistent with the literature. Results from the gossypol study showed a 71 to 78% decrease in free gossypol levels due to the extrusion process, which were lower than some reported methods of processing and consistent with others. Results from the aflatoxin studies showed reductions of 50% when the material was processed by two stages of extrusion at a temperature of 132°C. Similar reductions have been reported on roasting corn at temperatures of 140 to 143°C. The extrusion temperatures used in the evaluation studies did not significantly alter most of the nutritional values analyzed in the study. However, soluble protein was decreased at the higher temperatures. There were no significant differences in analyzed nutritional values based on multiple stages of processing. Results from the evaluation study indicate that extruding cottonseed to reduce gossypol and aflatoxin levels is an area of research that should be further explored, primarily due to the advances made in the aflatoxin and gossypol testing methods during the last 30 years.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"29 1","pages":"179 - 208"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86892672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In attempt to protect the consumers from TTX-intoxication, the mouse bioassay has historically been the most universally applied tool to determine the toxicity level in monitoring programs. This bioassay, however, shows low precision and requires a continuous supply of a particular size of mice. These potential drawbacks and the world-wide pressure of refraining from the killing of the live animals subsequently led the scientists for developing alternative chemical methods to the mouse bioassay for TTX detection and quantification. Among them, high-performance liquid chromatog-raphy (HPLC) has largely been used in routine work.
{"title":"CURRENT METHODOLOGIES FOR DETECTION OF TETRODOTOXIN","authors":"T. Noguchi, Y. Mahmud","doi":"10.1081/TXR-100102535","DOIUrl":"https://doi.org/10.1081/TXR-100102535","url":null,"abstract":"In attempt to protect the consumers from TTX-intoxication, the mouse bioassay has historically been the most universally applied tool to determine the toxicity level in monitoring programs. This bioassay, however, shows low precision and requires a continuous supply of a particular size of mice. These potential drawbacks and the world-wide pressure of refraining from the killing of the live animals subsequently led the scientists for developing alternative chemical methods to the mouse bioassay for TTX detection and quantification. Among them, high-performance liquid chromatog-raphy (HPLC) has largely been used in routine work.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"27 1","pages":"35 - 50"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74602341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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