{"title":"Centrally administered prostaglandin E2 suppresses the micturition reflex in rats","authors":"Takahiro Shimizu , Nobutaka Shimizu , Shun Tsubouchi , Mio Togo , Youichirou Higashi , Motoaki Saito","doi":"10.1016/j.jphs.2025.05.005","DOIUrl":"10.1016/j.jphs.2025.05.005","url":null,"abstract":"<div><div>Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) facilitates the micturition reflex at the lower urinary tract and spinal cord levels. However, the roles of brain PGE<sub>2</sub> in reflex regulation remain unclear. Therefore, we aimed to investigate the effects of intracerebroventricularly administered PGE<sub>2</sub> on the micturition reflex. We further investigated whether the PGE<sub>2</sub>-induced responses were dependent on the sympathetic nervous system (SNS) and identified the brain E-prostanoid receptor subtypes (EP<sub>1</sub>–EP<sub>4</sub>) involved in PGE<sub>2</sub>-induced effects. Intracerebroventricularly administered PGE<sub>2</sub> (0.1, 0.3, or 1 nmol/rat) dose-dependently increased the intercontraction intervals (ICI) and threshold pressure required to induce micturition (TP) without altering maximal voiding pressure in urethane-anesthetized (0.8 g/kg, ip) male rats. PGE<sub>2</sub> (1 nmol/rat) significantly increased the mean blood pressure; 6-hydroxydopamine-induced chemical sympathectomy ameliorated this increase. In contrast, chemical sympathectomy had no significant effect on the PGE<sub>2</sub>-induced increases in ICI and TP. Intracerebroventricularly pretreated SC51322 (EP<sub>1</sub> receptor antagonist, 100 nmol/rat) and PF04418948 (EP<sub>2</sub> receptor antagonist, 100 nmol/rat), but not L-798106 (EP<sub>3</sub> receptor antagonist, 100 nmol/rat) or L-161982 (EP<sub>4</sub> receptor antagonist, 100 nmol/rat), significantly attenuated the PGE<sub>2</sub> (1 nmol/rat)-induced changes in ICI and TP. These results suggest that centrally administered PGE<sub>2</sub> suppresses the rat micturition reflex through brain EP<sub>1</sub> and EP<sub>2</sub> receptors, independent of SNS activation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 231-237"},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early neuromyelitis optica antibody-induced molecular changes in aquaporin 4 and associated proteins at astrocyte endfeet in murine brain tissues","authors":"Yumi Yoshikawa , Masaki Tomioka , Yoichiro Abe , Masato Yasui , Mutsuo Nuriya","doi":"10.1016/j.jphs.2025.05.007","DOIUrl":"10.1016/j.jphs.2025.05.007","url":null,"abstract":"<div><div>Neuromyelitis optica spectrum disorder (NMOSD) is characterized by the production of autoantibodies against aquaporin 4 (AQP4). Because NMOSD progressively causes irreversible and severe neurological damages, understanding the initial molecular changes induced by anti-AQP4 antibody binding is crucial for designing early interventions. However, knowledge about the effects of the antibodies before AQP4 loss in brain tissues is limited. Using acutely prepared mouse brain slices, we aimed to investigate the initial molecular impact of NMO model antibodies on AQP4 and its associated proteins. We employed two different types of NMO model antibodies, E5415A and E5415B; E5415A recognizes both M1 and M23 isoforms, whereas E5415B exclusively binds to M23. We found that E5415A but not E5415B disrupted the uniform perivascular localization of AQP4, leading to fragmentation. We further addressed the impact of these changes on AQP4-associated proteins and found that strong colocalizations between AQP4 and dystrophin-glycoprotein complex (DGC) components were preserved, even after AQP4 localization pattern became fragmented. Thus, our study reveals the initial molecular changes in the AQP4 channel at the astrocytic endfeet in response to NMO model antibodies and highlights the early pathological events occurring in NMOSD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 212-218"},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei She , Wenji Ma , Tongtong Zhang , Xunian Wu , Jianfu Li , Xingyong Li
{"title":"Ginkgolide B inhibits ferroptosis in PC12 cells and ameliorates the oxidative stress in spinal cord injury through activating Nrf2 signaling pathway","authors":"Wei She , Wenji Ma , Tongtong Zhang , Xunian Wu , Jianfu Li , Xingyong Li","doi":"10.1016/j.jphs.2025.05.004","DOIUrl":"10.1016/j.jphs.2025.05.004","url":null,"abstract":"<div><div>Spinal cord injury (SCI) commonly leads to loss of motor and sensory function and results in huge socioeconomic burden, and it triggers numerous secondary pathological events, including oxidative stress and ferroptosis. This study investigates the therapeutic potential of Ginkgolide B (GB), a neuroprotective compound derived from <em>Ginkgo biloba</em>, in mitigating SCI by targeting on ferroptosis. By using Erastin-induced ferroptosis in PC12 cells and a rat contusion SCI model, the present study demonstrated that GB significantly improved locomotor recovery, reduced neuronal loss, and attenuated histopathological damage. Mechanistically, GB suppressed ferroptosis markers, including elevated iron content, lipid peroxidation, and ACSL4, while restoring the expression of GPX4 and xCT. Crucially, GB enhanced nuclear translocation of Nrf2, upregulating downstream antioxidants and ferroptosis-related genes (HO-1 and NQO1). Notably, the functions of GB were abolished after utilization of Nrf2 signaling inhibitor ML385 which revealed the role of GB on recovery of SCI was highly related to the activation of Nrf2 signaling. These findings reveal that GB alleviates SCI by inhibiting ferroptosis through Nrf2 activation, positioning it as a promising therapeutic agent. This study elucidates a novel mechanism linking Nrf2 signaling to ferroptosis suppression in SCI and provides a translational framework for repurposing GB in SCI treatment.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 199-206"},"PeriodicalIF":3.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A novel role of celecoxib in the inhibition of calcium-activated chloride channel ANO1","authors":"Ping Zhou , Qinqin Li , Xiangyu Li , Yani Liu","doi":"10.1016/j.jphs.2025.05.003","DOIUrl":"10.1016/j.jphs.2025.05.003","url":null,"abstract":"<div><div>Celecoxib, a non-steroidal anti-inflammatory drug, is widely used in the clinic for its analgesic and anti-inflammatory effects by inhibiting COX-2. Celecoxib also modulates many ion channels including Nav1.5, Kv7 and Kv2.1 channels. Here we show a novel role of celecoxib in inhibiting calcium-activated chloride channel ANO1 that is involved in pain sensation. Celecoxib results in a concentration-dependent inhibition of ANO1 current with an IC<sub>50</sub> value of 20.3 ± 1.9 μM, and the residue P701 in the S7 is important for celecoxib-mediated ANO1 inhibition. These results suggest that ANO1 inhibition may contribute to celecoxib's analgesic and anti-inflammatory effects.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 207-211"},"PeriodicalIF":3.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Zhao , Zhiwei Liu , Yong Wang , Tan Li , Juan Wang , Yaozhao Li , Chengliang Li , Chuntao Zhai , Christos C. Zouboulis , Xiaolei Ding , Qiang Ju , Zhenlin Hu
{"title":"Nerol enhances lipid synthesis in human sebocytes via cannabinoid receptor-2-mediated MAPK signaling","authors":"Qi Zhao , Zhiwei Liu , Yong Wang , Tan Li , Juan Wang , Yaozhao Li , Chengliang Li , Chuntao Zhai , Christos C. Zouboulis , Xiaolei Ding , Qiang Ju , Zhenlin Hu","doi":"10.1016/j.jphs.2025.04.008","DOIUrl":"10.1016/j.jphs.2025.04.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Nerol, a natural monoterpene, is commonly used as a fragrance additive in perfumes and cosmetics due to its pleasant rose-like aromas. Nerol application possesses diverse pharmacological properties, including anti-microbial, antioxidant, antinociceptive and anti-inflammatory activities, but its effects on sebum production and the consequent skin barrier function remain elusive. Here, we explored the effect of nerol on the lipogenesis of sebocytes.</div></div><div><h3>Patients and methods</h3><div>Immortalized human SZ95 sebocytes were used. The intracellular lipids were quantitatively measured by western blotting or fluorescent Nile Red staining followed by fluorometric analysis, semiquantitative detection or flow cytometry. The cell proliferation and differentiation were detected with CCK8 and flow cytometry, respectively. Moreover, RT-qPCR and immunocytochemistry were used to determine the expression levels of olfactory receptor OR2W3 and cannabinoid receptor-2 (CB2) receptors in SZ95 sebocytes.The mechanism was investigated by RNA interference and Western blotting.</div></div><div><h3>Results</h3><div>Our findings revealed that nerol induced lipid production in SZ95 sebocytes, together with the upregulation of multiple genes related to lipid synthesis, including PPARγ, SREBP-1, and FAS. Nerol also induced sebocyte differentiation, as evidenced by elevated cellular granulation and upregulated differentiation marker genes. Mechanistically, the lipogenic effect of nerol was mediated via CB2, rather than OR2W3 and TRP channels. Moreover, MAPK signaling was involved in neurol's effect.</div></div><div><h3>Conclusion</h3><div>Collectively, our findings show that nerol exerts a lipogenic effect on human sebocytes in a CB2-dependent manner through the activation of MAPK pathway, suggesting the therapeutic potential of this monoterpene in controlling cutaneous disorders involving sebaceous gland dysfunction and reduced sebum production, such as atopic dermatitis, skin dryness and aging.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 219-230"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diurnal variations of neurokinin-1 receptor defines dosing time-dependent differences in antitumor effects of aprepitant in mice","authors":"Yoshihiro Seto , Shun Tokeshi , Daisuke Inoue , Fumiyasu Okazaki , Hideto To","doi":"10.1016/j.jphs.2025.04.007","DOIUrl":"10.1016/j.jphs.2025.04.007","url":null,"abstract":"<div><div>Aprepitant, a neurokinin-1 receptor (NK1R) antagonist, has the potential as a novel anticancer agent. This study explored the impact of chronotherapy on the antitumor effect of aprepitant in a mouse model of colorectal carcinoma. Aprepitant inhibited the proliferation of Colon-26 cells <em>in vitro</em> in a concentration-dependent manner and reduced the expression of cell cycle-related genes. Diurnal variations in NK1R mRNA and protein levels were observed in Colon-26 tumors, peaking at zeitgeber time (ZT) 2 and ZT 10, respectively. Administration of aprepitant at ZT 6, achieving peak plasma concentration at ZT 10, significantly reduced the tumor volume compared with administration at ZT 18. Despite the lower plasma concentrations and AUC<sub>0–12 h</sub> in the ZT 6 group, superior antitumor effect suggests a dosing time-dependent efficacy due to variations in NK1R expression rather than its pharmacokinetics. These findings indicate that the antitumor activity of aprepitant against colorectal cancer can be enhanced by aligning its administration with NK1R expression rhythms, warranting further exploration of aprepitant chronotherapy in cancer chemotherapy.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 193-198"},"PeriodicalIF":3.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibitory effects of ferulic acid on the contraction responses of porcine coronary arteries: a comparison with diltiazem","authors":"Kento Yoshioka , Keisuke Obara , Yilin Luo, Qianghaodi Hong, Ayaka Fujiwara, Wakaba Kinami, Hideaki Ozawa, Yoshio Tanaka","doi":"10.1016/j.jphs.2025.04.006","DOIUrl":"10.1016/j.jphs.2025.04.006","url":null,"abstract":"<div><div>Ferulic acid (FA) exerts protective effects against cardiovascular-related diseases; however, its role in coronary artery dilation is unclear. Here, we examined the effects and underlying mechanisms of FA in response to contractions induced by spasmogenic candidates in porcine coronary arteries (PCAs). FA (3 × 10<sup>−4</sup>–3 × 10<sup>−3</sup> M) inhibited high-KCl-induced contractions in a concentration-dependent manner, and FA (3 × 10<sup>−4</sup>–10<sup>−3</sup> M) inhibited high-KCl-induced increases in intracellular Ca<sup>2+</sup> concentrations in A7r5 cells. FA (3 × 10<sup>−3</sup> M) showed greater inhibition than diltiazem (3 × 10<sup>−5</sup> M) against chemical-induced contractions but weaker inhibition against high-KCl-induced contractions. FA (3 × 10<sup>−4</sup>–3 × 10<sup>−3</sup> M) inhibited contractions induced by endothelin-1 (10<sup>−8</sup> M) and NaF (10<sup>−2</sup> M) under Ca<sup>2+</sup>-free conditions in a concentration-dependent manner; these contractions were fully suppressed by ML-7 (10<sup>−4</sup> M, a myosin light chain kinase inhibitor). FA (3 × 10<sup>−3</sup> M) also inhibited myosin light chain phosphorylation induced by NaF (10<sup>−2</sup> M) in A7r5 cells regardless of extracellular Ca<sup>2+</sup> conditions. These findings indicate that FA inhibits PCA contractions induced by coronary spasmogens by inhibiting L-type Ca<sup>2+</sup> channels and intracellular routes responsible for extracellular Ca<sup>2+</sup> influx-independent contractions. The latter mechanism may involve the inhibition of myosin light chain phosphorylation-related processes.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 172-181"},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of the single-molecule transport kinetics of OATP1B1 genetic variants","authors":"Kazunari Tsujii , Kodai Yajima , Takeshi Akiyoshi , Kazuho Sakamoto , Yoshiaki Suzuki , Takayuki Oka , Ayuko Imaoka , Hisao Yamamura , Junko Kurokawa , Hisakazu Ohtani","doi":"10.1016/j.jphs.2025.04.005","DOIUrl":"10.1016/j.jphs.2025.04.005","url":null,"abstract":"<div><div>Several genetic variants of OATP1B1, a hepatic uptake transporter, increase the blood concentrations of substrate drugs, e.g., ∗15 carriers exhibit higher blood substrate concentrations than ∗1b carriers. It remains unclear whether these differences are due to changes in expression or intrinsic activity (transport activity per OATP1B1 molecule). This study compared the intrinsic activity of four OATP1B1 variants, ∗1a, ∗1b, ∗5, and ∗15, using HEK293 cell lines that co-expressed large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK) channels and one of the OATP1B1 variants. To estimate the kinetic parameters <em>K</em><sub>m</sub> and <em>V</em><sub>max</sub>, 2′, 7′-dichlorofluorescein uptake was evaluated. The number of OATP molecules per cell (Q<sub>T</sub>) was calculated from BK channel-mediated whole-cell conductance and the OATP1B1/BK channel expression ratio (ρ) (determined by LC-MS/MS). <em>V</em><sub>max,int</sub> (maximum intrinsic transport velocity) was obtained by dividing <em>V</em><sub>max</sub> by Q<sub>T</sub>, and intrinsic clearance (<em>CL</em><sub>int</sub>) was calculated as <em>V</em><sub>max,int</sub>/<em>K</em><sub>m</sub>. The <em>K</em><sub>m</sub> values of ∗1a, ∗1b, ∗5, and ∗15 were 12.5, 9.19, 7.53, and 10.4 μM, and their <em>V</em><sub>max,int</sub> values were 3.0, 7.0, 1.5, and 1.2 × 10<sup>−21</sup> mol/OATP molecule/min, respectively. Accordingly, the <em>CL</em><sub>int</sub> value for OATP1B1∗15 was 15 % lower than that for OATP1B1∗1b, suggesting that the increased blood substrate concentrations observed in OATP1B1∗15 carriers may be due to the decreased intrinsic activity of OATP1B1∗15.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 166-171"},"PeriodicalIF":3.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dane Tregeagle , Catherine Doherty , Timothy Callis, Michael Kassiou
{"title":"Non-peptidic natural products that target and modulate oxytocin and arginine vasopressin receptors: Opportunities and challenges","authors":"Dane Tregeagle , Catherine Doherty , Timothy Callis, Michael Kassiou","doi":"10.1016/j.jphs.2025.04.004","DOIUrl":"10.1016/j.jphs.2025.04.004","url":null,"abstract":"<div><div>The ability to target the oxytocin and vasopressin receptors is of high therapeutic value due to their clinical relevance in wide range of neuropsychiatric conditions spanning from anxiety to schizophrenia. Despite the massive therapeutic potential in modulating this system, the only clinically approved small molecule-based therapeutics (Mozavaptan, Conivaptan and Tolvaptan) are for use in the periphery. Cyclotide mimetics of the native neuropeptides are well explored in the literature although these scaffolds are unsuitable for application to the central nervous system. This work highlights non-peptidic natural products that are active within the neurohypophysial system that may be used to inspire future drug discovery endeavours.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 238-258"},"PeriodicalIF":3.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model","authors":"Hiroyuki Neyama , Naoki Dozono , Yasuka Sahara , Kenji Nishikawa , Hiroshi Ueda","doi":"10.1016/j.jphs.2025.03.012","DOIUrl":"10.1016/j.jphs.2025.03.012","url":null,"abstract":"<div><div>Lysophosphatidic acid receptor 1 (LPA<sub>1</sub>) plays a pivotal role in the pathophysiology of various diseases, especially chronic pain. In this study, we assessed the biochemical properties of Compound A, a novel LPA<sub>1</sub> antagonist and its beneficial effects in the fibromyalgia (FM)-like pain model. Compound A was found to be a high-affinity and selective LPA<sub>1</sub> antagonist and have high brain penetrability. Repeated oral administrations of Compound A reversed the hyperalgesia as late as 9 days after the treatments, suggesting this compound has a curative effect in the FM model.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 139-142"},"PeriodicalIF":3.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}