Zhongyi Yang, Ruhai Gong, Yoshiharu Mimata, Shaosong Ye, Wei Ji, Wenxiu Ye
A key tricarboxylic acid cycle metabolite, malate, accumulates in leaves during dehydration and induces stomatal closure by recruiting cytosolic Ca2+, activating a SLOW ANION CHANNEL-ASSOCIATED 1, and promoting reactive oxygen species. However, the effects of malate on stomatal opening and its underlying molecular mechanisms remain poorly understood. Our study revealed that, among TCA cycle metabolites, malate specifically inhibited light-induced stomatal opening in both grapevine and Arabidopsis. We demonstrated that SLAC1 was required for malate's inhibitory effects. The inhibition by malate was disrupted by Ca2+ signaling inhibitors. Additionally, malate signal was mediated by G-proteins, which regulate the production of second messengers. ROS production was abolished when G-proteins were inhibited. These findings show that malate efficiently maintains stomatal closure by not only inducing stomatal closure but also inhibiting stomatal opening. The inhibition of stomatal opening by malate is mediated through the activation of SLAC1 and the G-protein signaling cascade.
{"title":"Malate inhibits light-induced stomatal opening through SLAC1- and G-proteins-mediated pathway in grapevine and Arabidopsis.","authors":"Zhongyi Yang, Ruhai Gong, Yoshiharu Mimata, Shaosong Ye, Wei Ji, Wenxiu Ye","doi":"10.1093/bbb/zbaf011","DOIUrl":"https://doi.org/10.1093/bbb/zbaf011","url":null,"abstract":"<p><p>A key tricarboxylic acid cycle metabolite, malate, accumulates in leaves during dehydration and induces stomatal closure by recruiting cytosolic Ca2+, activating a SLOW ANION CHANNEL-ASSOCIATED 1, and promoting reactive oxygen species. However, the effects of malate on stomatal opening and its underlying molecular mechanisms remain poorly understood. Our study revealed that, among TCA cycle metabolites, malate specifically inhibited light-induced stomatal opening in both grapevine and Arabidopsis. We demonstrated that SLAC1 was required for malate's inhibitory effects. The inhibition by malate was disrupted by Ca2+ signaling inhibitors. Additionally, malate signal was mediated by G-proteins, which regulate the production of second messengers. ROS production was abolished when G-proteins were inhibited. These findings show that malate efficiently maintains stomatal closure by not only inducing stomatal closure but also inhibiting stomatal opening. The inhibition of stomatal opening by malate is mediated through the activation of SLAC1 and the G-protein signaling cascade.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We clarified for the first time the synthesis procedure and characterization of pantetheine trisulfide, a potential new drug. Pantetheine trisulfide is the first supersulfur compound with both thermal stability and water solubility. Its hygroscopicity and deliquescence promote the hydrolysis of trisulfide, but these limitations are overcome by powdered composites of pantetheine trisulfide with silica gel or lactose.
{"title":"Synthesis and characterization of thermally stable and water-soluble pantetheine trisulfide and its composites.","authors":"Shoichiro Tomonaga, Hiroaki Ishimaru, Shizuki Misada, Takahiro Isobe, Etsuo Ohshima, Shinji Kitagaki","doi":"10.1093/bbb/zbaf010","DOIUrl":"https://doi.org/10.1093/bbb/zbaf010","url":null,"abstract":"<p><p>We clarified for the first time the synthesis procedure and characterization of pantetheine trisulfide, a potential new drug. Pantetheine trisulfide is the first supersulfur compound with both thermal stability and water solubility. Its hygroscopicity and deliquescence promote the hydrolysis of trisulfide, but these limitations are overcome by powdered composites of pantetheine trisulfide with silica gel or lactose.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protein kinase C (PKC) is a family of serine/threonine kinases, and PKC ligands have the potential to be therapeutic seeds for cancer, Alzheimer's disease, and human immunodeficiency virus infection. However, in addition to desired therapeutic effects, most PKC ligands also exhibit undesirable pro-inflammatory effects. The discovery of new scaffolds for PKC ligands is important for developing less inflammatory PKC ligands, such as bryostatins. We previously reported that machine learning combined with our knowledge of the pharmacophore yielded 15 PKC ligand candidates, but we did not evaluate their PKC binding affinities fully. In this paper, PKC binding affinities of four candidates were examined to assess their potential as PKC ligands and to validate machine learning-assisted screening. Although compound 3' did not bind to PKC C1 domains, 1a, 2', and 4a exhibited moderate PKC binding affinities, suggesting that machine learning-assisted screening is advantageous in identifying new PKC ligand scaffolds.
{"title":"Validation of Machine Learning-assisted Screening of PKC Ligands: PKC Binding Affinity and Activation.","authors":"Jumpei Maki, Asami Oshimura, Yudai Shiotani, Maki Yamanaka, Sogen Okuda, Ryo C Yanagita, Shigeru Kitani, Yasuhiro Igarashi, Yutaka Saito, Yasubumi Sakakibara, Chihiro Tsukano, Kazuhiro Irie","doi":"10.1093/bbb/zbaf008","DOIUrl":"https://doi.org/10.1093/bbb/zbaf008","url":null,"abstract":"<p><p>Protein kinase C (PKC) is a family of serine/threonine kinases, and PKC ligands have the potential to be therapeutic seeds for cancer, Alzheimer's disease, and human immunodeficiency virus infection. However, in addition to desired therapeutic effects, most PKC ligands also exhibit undesirable pro-inflammatory effects. The discovery of new scaffolds for PKC ligands is important for developing less inflammatory PKC ligands, such as bryostatins. We previously reported that machine learning combined with our knowledge of the pharmacophore yielded 15 PKC ligand candidates, but we did not evaluate their PKC binding affinities fully. In this paper, PKC binding affinities of four candidates were examined to assess their potential as PKC ligands and to validate machine learning-assisted screening. Although compound 3' did not bind to PKC C1 domains, 1a, 2', and 4a exhibited moderate PKC binding affinities, suggesting that machine learning-assisted screening is advantageous in identifying new PKC ligand scaffolds.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Proper diet is crucial for obesity prevention. Food health research primarily focuses on two aspects: the pathogenesis of lifestyle-related diseases caused by obesity and the identification of dietary components that can aid in the prevention and treatment of lifestyle-related diseases. Substantial knowledge has been accumulated regarding these aspects via health function evaluations based on biological experiments. However, the intricate causal relationships and specific biological metabolites or food compounds that affect health remain unclear. To address these issues, my recent studies have incorporated mass spectrometry data, particularly metabolomic data obtained via comprehensive component analysis, to enhance health function evaluation via biological experiments. These studies have revealed various biological and healthy compounds derived from different food materials for the management of obesity-induced metabolic disorders.
{"title":"Application of mass spectrometry data for health evaluation.","authors":"Haruya Takahashi","doi":"10.1093/bbb/zbae182","DOIUrl":"10.1093/bbb/zbae182","url":null,"abstract":"<p><p>Proper diet is crucial for obesity prevention. Food health research primarily focuses on two aspects: the pathogenesis of lifestyle-related diseases caused by obesity and the identification of dietary components that can aid in the prevention and treatment of lifestyle-related diseases. Substantial knowledge has been accumulated regarding these aspects via health function evaluations based on biological experiments. However, the intricate causal relationships and specific biological metabolites or food compounds that affect health remain unclear. To address these issues, my recent studies have incorporated mass spectrometry data, particularly metabolomic data obtained via comprehensive component analysis, to enhance health function evaluation via biological experiments. These studies have revealed various biological and healthy compounds derived from different food materials for the management of obesity-induced metabolic disorders.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"215-223"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Treatments for osteoporosis are typically given postfracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilize the bioactive properties of natural compounds to modify osteoclast and osteoblast activity. d-limonene a well-tolerated, anti-inflammatory monoterpene found in citrus fruits holds promise due to its suppressive effect on NFκB, a key regulator of bone cell activity. We found that limonene promoted osteoblast differentiation and bone nodule formation and inhibited RANKL-induced osteoclast formation and bone resorption in vitro. Limonene also reduced the proresorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix, and osteocalcin) and significantly decreasing osteoclastogenic cytokine production (PTHrP, IL-1β, and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimize bone cell activity to maintain or enhance bone mass.
{"title":"d-limonene suppresses RANKL-induced osteoclast differentiation and promotes osteoblast activity in vitro.","authors":"Lynn McCallum, Simon W Fox","doi":"10.1093/bbb/zbae164","DOIUrl":"10.1093/bbb/zbae164","url":null,"abstract":"<p><p>Treatments for osteoporosis are typically given postfracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilize the bioactive properties of natural compounds to modify osteoclast and osteoblast activity. d-limonene a well-tolerated, anti-inflammatory monoterpene found in citrus fruits holds promise due to its suppressive effect on NFκB, a key regulator of bone cell activity. We found that limonene promoted osteoblast differentiation and bone nodule formation and inhibited RANKL-induced osteoclast formation and bone resorption in vitro. Limonene also reduced the proresorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix, and osteocalcin) and significantly decreasing osteoclastogenic cytokine production (PTHrP, IL-1β, and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimize bone cell activity to maintain or enhance bone mass.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"232-240"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tomoko Sumi, Hirona Kugo, Mayo Higashihara, Tatsuya Moriyama, Nobuhiro Zaima
Abdominal aortic aneurysm (AAA) is a disease in which the abdominal aorta expands irreversibly and ruptures. At present, no preventive methods are available for this disease. Among potential risk factors, certain foods are considered to play important roles in the development of AAA. Epidemiological studies suggest a close relationship between AAA and dietary habits. Experimental studies have clarified potential suppressive or progressive food components for AAA. In this review, a summary of studies related to nutritional science in the fields of AAA and/or aortic degeneration are provided.
{"title":"Food components and abdominal aortic aneurysm.","authors":"Tomoko Sumi, Hirona Kugo, Mayo Higashihara, Tatsuya Moriyama, Nobuhiro Zaima","doi":"10.1093/bbb/zbae141","DOIUrl":"10.1093/bbb/zbae141","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a disease in which the abdominal aorta expands irreversibly and ruptures. At present, no preventive methods are available for this disease. Among potential risk factors, certain foods are considered to play important roles in the development of AAA. Epidemiological studies suggest a close relationship between AAA and dietary habits. Experimental studies have clarified potential suppressive or progressive food components for AAA. In this review, a summary of studies related to nutritional science in the fields of AAA and/or aortic degeneration are provided.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"152-160"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Flavonoids are present in plant foods such as vegetables and fruits and exhibit various physiological effects, including antioxidant and anti-inflammatory properties. Ingested flavonoids are absorbed from the intestinal tract and circulated in the blood. Some studies have indicated the presence of flavonoids in breast milk. However, information on their metabolites and concentrations in breast milk and the subsequent transfer to and physiological functions in infants is limited. Therefore, this review presents a compilation of recent findings on the transfer of flavonoids to infants via breast milk and their bioactivities.
{"title":"Flavonoids in breast milk and their absorption, metabolism, and bioactivity in infants.","authors":"Akari Ishisaka, Nao Fujiwara, Rie Mukai, Miyu Nishikawa, Shinichi Ikushiro, Akira Murakami","doi":"10.1093/bbb/zbae140","DOIUrl":"10.1093/bbb/zbae140","url":null,"abstract":"<p><p>Flavonoids are present in plant foods such as vegetables and fruits and exhibit various physiological effects, including antioxidant and anti-inflammatory properties. Ingested flavonoids are absorbed from the intestinal tract and circulated in the blood. Some studies have indicated the presence of flavonoids in breast milk. However, information on their metabolites and concentrations in breast milk and the subsequent transfer to and physiological functions in infants is limited. Therefore, this review presents a compilation of recent findings on the transfer of flavonoids to infants via breast milk and their bioactivities.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"165-173"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ikuhisa Nishida, Shogo Nishihara, Tomohiro Kaino, Makoto Kawamukai, Dai Hirata
Coenzyme Q (CoQ), a component of the electron transport chain, participates in aerobic respiration to produce ATP. Little is known about the relationship between CoQ and ethanol fermentation. Herein, we revealed that the deficiency or the addition of CoQ in sake yeast led to an increase or a decrease, respectively, in ethanol production rate at the early stage of fermentation.
{"title":"Effect of coenzyme Q deficiency on ethanol fermentation in sake yeast.","authors":"Ikuhisa Nishida, Shogo Nishihara, Tomohiro Kaino, Makoto Kawamukai, Dai Hirata","doi":"10.1093/bbb/zbae167","DOIUrl":"10.1093/bbb/zbae167","url":null,"abstract":"<p><p>Coenzyme Q (CoQ), a component of the electron transport chain, participates in aerobic respiration to produce ATP. Little is known about the relationship between CoQ and ethanol fermentation. Herein, we revealed that the deficiency or the addition of CoQ in sake yeast led to an increase or a decrease, respectively, in ethanol production rate at the early stage of fermentation.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"313-318"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takahiko Kondo, Surachat Sibponkrung, Panlada Tittabutr, Nantakorn Boonkerd, Shu Ishikawa, Neung Teaumroong, Ken-Ichi Yoshida
Bacillus velezensis S141 helps soybean establish specific symbiosis with strains of Bradyrhizobium diazoefficiens to form larger nodules and improve nitrogen fixation efficiency. In this study, we found that the dry weight of soybean roots increased significantly in the presence of S141 alone under drought conditions. Hence, S141 improved the root growth of soybean under limited water supply conditions. S141 can produce some auxin, which might be involved in the improved nodulation. Inactivating IPyAD of S141, which is required for auxin biosynthesis, did not alter the beneficial effects of S141, suggesting that the root growth was independent of auxin produced by S141. Under drought conditions, soybean exhibited some responses to resist osmotic and oxidative stresses; however, S141 was relevant to none of these responses. Although the mechanism remains unclear, S141 might produce some substances that stimulate the root growth of soybean under drought conditions.
{"title":"Bacillus velezensis S141 improves the root growth of soybean under drought conditions.","authors":"Takahiko Kondo, Surachat Sibponkrung, Panlada Tittabutr, Nantakorn Boonkerd, Shu Ishikawa, Neung Teaumroong, Ken-Ichi Yoshida","doi":"10.1093/bbb/zbae168","DOIUrl":"10.1093/bbb/zbae168","url":null,"abstract":"<p><p>Bacillus velezensis S141 helps soybean establish specific symbiosis with strains of Bradyrhizobium diazoefficiens to form larger nodules and improve nitrogen fixation efficiency. In this study, we found that the dry weight of soybean roots increased significantly in the presence of S141 alone under drought conditions. Hence, S141 improved the root growth of soybean under limited water supply conditions. S141 can produce some auxin, which might be involved in the improved nodulation. Inactivating IPyAD of S141, which is required for auxin biosynthesis, did not alter the beneficial effects of S141, suggesting that the root growth was independent of auxin produced by S141. Under drought conditions, soybean exhibited some responses to resist osmotic and oxidative stresses; however, S141 was relevant to none of these responses. Although the mechanism remains unclear, S141 might produce some substances that stimulate the root growth of soybean under drought conditions.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"304-312"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To elucidate the function of the bile acid-binding receptor TGR5 in skeletal muscle, we developed transgenic mice expressing human TGR5 in the skeletal muscle tissue. A significant increase in muscle mass was observed in these transgenic mice, whereas a decrease in muscle mass was observed in the TGR5-deficient mice. Following treadmill exercise, TGR5 gene expression increased in response to ER stress induced in skeletal muscle via an ER stress response motif present in its promoter region. Exercise and rapid postprandial elevation in blood bile acid concentrations can be considered the primary stimuli for the TGR5-mediated increase in skeletal muscle mass. We developed a scoring system to identify food ingredients with TGR5 agonist activity, and identified the citrus limonoid nomilin. Similar effects were observed for other triterpenoids in addition to nomilin. Cell culture and in vivo experiments demonstrated that these food factors increase protein synthesis and muscle mass.
{"title":"Bile acids acting as a feeding signal and functional foods mimicking bile acid function.","authors":"Ryuichiro Sato","doi":"10.1093/bbb/zbae133","DOIUrl":"10.1093/bbb/zbae133","url":null,"abstract":"<p><p>To elucidate the function of the bile acid-binding receptor TGR5 in skeletal muscle, we developed transgenic mice expressing human TGR5 in the skeletal muscle tissue. A significant increase in muscle mass was observed in these transgenic mice, whereas a decrease in muscle mass was observed in the TGR5-deficient mice. Following treadmill exercise, TGR5 gene expression increased in response to ER stress induced in skeletal muscle via an ER stress response motif present in its promoter region. Exercise and rapid postprandial elevation in blood bile acid concentrations can be considered the primary stimuli for the TGR5-mediated increase in skeletal muscle mass. We developed a scoring system to identify food ingredients with TGR5 agonist activity, and identified the citrus limonoid nomilin. Similar effects were observed for other triterpenoids in addition to nomilin. Cell culture and in vivo experiments demonstrated that these food factors increase protein synthesis and muscle mass.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"161-164"},"PeriodicalIF":1.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}