{"title":"Synergistic effect of Toll-like receptor 2 ligands and alendronate on proinflammatory cytokine production in mouse macrophage-like RAW-ASC cells is accompanied by upregulation of MyD88 expression","authors":"Reiko Akaho , Yusuke Kiyoura , Riyoko Tamai","doi":"10.1016/j.job.2024.04.003","DOIUrl":"10.1016/j.job.2024.04.003","url":null,"abstract":"<div><h3>Objectives</h3><p>Toll-like receptors (TLRs) recognize whole cells or components of microorganisms. Alendronate (ALN) is an anti-bone-resorptive drug that has inflammatory side effects. The aim in this study was to examine whether ALN augments TLR2 ligand-induced proinflammatory cytokine production using mouse macrophage-like RAW264.7 cells transfected with murine apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) gene (hereafter, referred to as “RAW-ASC cells”).</p></div><div><h3>Methods</h3><p>RAW-ASC cells were pretreated with or without ALN and then incubated with or without TLR2 ligands. The levels of secreted mouse IL-1α, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in culture supernatants and the activation of activator protein-1 (AP-1) or nuclear factor-κB (NF-κB) were measured using enzyme-linked immunosorbent assay (ELISA). The expressions of myeloid differentiation factor 88 (MyD88), caspase-11, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), ASC, NF-κB p65, and actin were analyzed via Western blotting. TLR2 expression was analyzed using flow cytometry.</p></div><div><h3>Results</h3><p>ALN substantially upregulated the Pam<sub>3</sub>CSK<sub>4</sub>-induced release of IL-1α, IL-1β, IL-6, and TNF-α and MyD88 expression in RAW-ASC cells. ST-2825, a MyD88 inhibitor, inhibited the ALN-augmented release of these cytokines. Pretreatment with ALN augmented Pam<sub>3</sub>CSK<sub>4</sub>-induced NF-κB activation in RAW-ASC cells and upregulated AP-1 activation. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein and ALN synergically upregulated the release of IL-1α, IL-1β, IL-6 and TNF-α in RAW-ASC cells.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that ALN augments TLR2 ligand-induced proinflammatory cytokine production via the upregulation of MyD88 expression, and this augmentation is accompanied by the activation of NF-κB and AP-1 in RAW-ASC cells.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 2","pages":"Pages 412-419"},"PeriodicalIF":2.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797509","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}
{"title":"Influence of feeding a soft diet on proteoglycan expression in rat temporomandibular joint discs","authors":"","doi":"10.1016/j.job.2024.05.009","DOIUrl":"10.1016/j.job.2024.05.009","url":null,"abstract":"<div><h3>Objectives</h3><p><span><span>Extracellular matrix<span> components play a significant role in maintaining tissue integrity and pathological processes of the </span></span>temporomandibular joint (TMJ). This study aimed to evaluate the influence of a soft diet on the mRNA expression of </span>proteoglycans<span> and glycosaminoglycans<span><span> (GAGs) linked to proteoglycan core proteins<span> in rat </span></span>TMJ discs.</span></span></p></div><div><h3>Methods</h3><p><span><span>Thirty 4-week-old male Wistar rats<span> were assigned to one of two groups: a control group fed a regular pellet diet and a soft diet group fed a powdered diet for 4 weeks. The mRNA expression levels of 12 </span></span>proteoglycans in TMJ discs were evaluated using real-time polymerase chain reaction (PCR). In addition, histomorphometric and </span>biochemical analyses were performed to evaluate the thickness and deoxyribonucleic acid (DNA), GAG, and water content of the TMJ discs.</p></div><div><h3>Results</h3><p><span>The TMJ disc thickness in the anterior, intermediate, and posterior bands decreased significantly in the soft diet group. The GAG content decreased significantly in the soft-diet group, whereas no significant differences in DNA content or water content ratio were observed between the groups. Real-time PCR indicated that the expression levels of </span>aggrecan<span><span><span><span>, versican, </span>biglycan<span>, decorin, </span></span>fibromodulin, </span>lumican<span>, and chondroadherin decreased in the soft diet group. The expression levels of all versican<span> isoforms decreased in the soft diet group.</span></span></span></p></div><div><h3>Conclusions</h3><p>These results indicate that the biomechanical environment of the TMJ caused by a soft diet is closely related to the expression of proteoglycans in TMJ discs, which may eventually increase the fragility of the TMJ discs.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 3","pages":"Pages 539-545"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238442","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}
{"title":"Spontaneous regeneration after resection of various lengths of hypoglossal nerve in rats","authors":"","doi":"10.1016/j.job.2024.05.010","DOIUrl":"10.1016/j.job.2024.05.010","url":null,"abstract":"<div><h3>Objectives</h3><p>The objective of this study was to investigate spontaneous neural regeneration and functional recovery after resection of various lengths of the hypoglossal (XII) nerve in adult rats.</p></div><div><h3>Methods</h3><p>Twelve weeks after XII nerve resection at lengths ranging from 0.0 to 15.8 mm, the tongue deviation angle of rats was measured to evaluate the severity of paralysis; thereafter, the XII neurons in the XII nucleus were labeled with Fluoro-Gold (FG), which was injected into the tongue to visualize regenerated XII neurons re-innervating the tongue muscles.</p></div><div><h3>Results</h3><p>In the XII nerve-resected rats, the regenerative rates, that is, the percentage of the total number of FG-positive neurons on the injured side relative to that on the uninjured side, were divided into two groups; the regenerative rates were more than 77% and less than 6%, respectively. Upon comparing the two groups, the boundary resection length was approximately 10.0 mm. Moreover, the former and latter groups demonstrated tongue deviation angles less than or greater than 15°, respectively.</p></div><div><h3>Conclusions</h3><p>The critical nerve gap length for spontaneous neural regeneration was approximately 10.0 mm in XII nerve-resected adult rats, and nerve regeneration occurred in both morphological and functional aspects after resection at less than the critical length.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 3","pages":"Pages 582-586"},"PeriodicalIF":2.6,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184539","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}
{"title":"Unraveling the cognitive implications among individuals with co-occurring chronic periodontitis and type 2 diabetes mellitus: A cross-sectional study","authors":"","doi":"10.1016/j.job.2024.05.008","DOIUrl":"10.1016/j.job.2024.05.008","url":null,"abstract":"<div><h3>Objectives</h3><p>Chronic periodontitis and type 2 diabetes mellitus (T2DM) are associated with cognitive decline when examined individually. To gain deeper insight into the combined effects of these conditions on cognitive decline, the present study aimed to examine the cognitive status of individuals with co-occurring T2DM and chronic periodontitis.</p></div><div><h3>Methods</h3><p>We recruited 220 participants categorized into four groups: Group I, healthy subjects; Group II, individuals with chronic periodontitis; Group III, individuals with T2DM; and Group IV, individuals with both T2DM and chronic periodontitis. Medical histories were recorded for all participants, followed by periodontal examination and evaluation of cognitive status using the Montreal Cognitive Assessment (MoCA) scale. Finger dexterity was assessed using the nine-hole peg test.</p></div><div><h3>Results</h3><p>A statistically significant increase in the proportion of mild cognitive impairment (MCI) was observed between groups I and IV (p < 0.001). Logistic regression analysis revealed that, among the parameters assessed in this study, the adjusted odds ratio (OR) was significant for age, finger dexterity scores, and co-occurrence of T2DM and periodontitis.</p></div><div><h3>Conclusions</h3><p>The findings of this study suggest that the co-occurrence of chronic periodontitis and T2DM can have a detrimental effect on the cognitive abilities of an individual. Subsequent research should include longitudinal monitoring of the cognitive status in patients with concurrent conditions during treatment to gain deeper prognostic insights into the relationship between these co-occurring conditions and cognitive decline.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 3","pages":"Pages 605-611"},"PeriodicalIF":2.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1349007924000914/pdfft?md5=36178bf1b8eb15c72788251cf741836d&pid=1-s2.0-S1349007924000914-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epithelial-mesenchymal transition in oral cancer cells induced by prolonged and persistent Fusobacterium nucleatum stimulation","authors":"","doi":"10.1016/j.job.2024.05.006","DOIUrl":"10.1016/j.job.2024.05.006","url":null,"abstract":"<div><h3>Objectives</h3><p>Several studies have reported the effects of <span><span>Fusobacterium nucleatum</span></span><span> stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the </span><em>in vitro</em> studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent <em>Fusobacterium nucleatum</em> infection on oral cancer cells.</p></div><div><h3>Methods</h3><p><span>Human tongue squamous cell carcinoma (SCC) cells were continuously stimulated with </span><em>Fusobacterium nucleatum</em> for two or four weeks, then experimentally evaluated.</p></div><div><h3>Results</h3><p>Prolonged, persistent <em>Fusobacterium nucleatum</em><span> stimulation increased the cells’ proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with </span><em>Fusobacterium nucleatum</em><span> for four weeks in the presence of dexamethasone, </span><em>Fusobacterium nucleatum</em> induced epithelial-mesenchymal transition was inhibited.</p></div><div><h3>Conclusions</h3><p>Epithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent <em>Fusobacterium nucleatum</em><span><span> stimulation and inhibited by dexamethasone. Routine decontamination of the </span>oral cavity may be crucial for controlling tumor invasion and metastasis.</span></p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 3","pages":"Pages 594-604"},"PeriodicalIF":2.6,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088385","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}
{"title":"Periostin regulates integrin expression in gingival epithelial cells","authors":"Reika Hirata , Tomoyuki Iwata , Tsuyoshi Fujita , Takayoshi Nagahara , Shinji Matsuda , Shinya Sasaki , Yuri Taniguchi , Yuta Hamamoto , Kazuhisa Ouhara , Yasusei Kudo , Hidemi Kurihara , Noriyoshi Mizuno","doi":"10.1016/j.job.2023.11.009","DOIUrl":"10.1016/j.job.2023.11.009","url":null,"abstract":"<div><h3>Objective</h3><p>Human gingival epithelial cells (HGECs) function as a mechanical barrier against invasion by pathogenic organisms through epithelial cell–cell junction complexes, which are complex components of integrin. Integrins play an important role in the protective functions of HGECs. Human periodontal ligament (HPL) cells regulate periodontal homeostasis. However, periodontitis results in the loss of HPL cells. Therefore, as replenishment, HPL cells or mesenchymal stem cells (MSCs) can be transplanted. Herein, HPL cells and MSCs were used to elucidate the regulatory mechanisms of HGECs, assuming periodontal tissue homeostasis.</p></div><div><h3>Methods</h3><p>Human gingival fibroblasts (HGFs), HGECs, HPL cells, and MSCs were cultured, and the conditioned medium was collected. With or without silencing periostin mRNA, HGECs were cultured under normal conditions or in a conditioned medium. Integrin and periostin mRNA expression was determined using real-time polymerase chain reaction. Integrin protein expression was analyzed using flow cytometry, and periostin protein expression was determined via western blotting.</p></div><div><h3>Results</h3><p>The conditioned medium affected integrin expression in HGECs. Higher expression of periostin was observed in MSCs and HPL cells than in HGFs. The conditioned medium that contained periostin protein regulated integrin expression in HGECs. After silencing periostin in MSCs and HPL cells, periostin protein was not detected in the conditioned medium, and integrin expression in HGECs remained unaffected.</p></div><div><h3>Conclusions</h3><p>Integrins in HGECs are regulated by periostin secreted from HPL cells and MSCs. This result suggests that periostin maintains gingival cell adhesion and regulates bacterial invasion/infection. Therefore, the functional regulation of periostin-secreting cells is important in preventing periodontitis.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 1","pages":"Pages 170-178"},"PeriodicalIF":2.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1349007923001901/pdfft?md5=eb1ba8f04d82d72f7b412e67ff890979&pid=1-s2.0-S1349007923001901-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138483200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A quantitative study of the development of taste pores in mice","authors":"Atsuko Yamashita, Masato S. Ota","doi":"10.1016/j.job.2024.01.013","DOIUrl":"10.1016/j.job.2024.01.013","url":null,"abstract":"<div><h3>Objectives</h3><p>This study determined the early development of taste buds by observing the changes in the three-dimensional structures of taste pores and microvilli in the circumvallate papillae (CVP) of mice, from pre- and postnatal stages to the adult stages.</p></div><div><h3>Methods</h3><p>Fragments of mouse CVP tissue were collected on embryonic day (E) 18 and postnatal days (P) 0, 3, 6, 7, 14, 21, 28, and 56. The surfaces of the tissue fragments located pore apertures via scanning electron microscopy, and the sizes of the CVP and maximum diameters of the pores were estimated from the recorded images. Likewise, changes in the structures of the epithelium around the pore aperture and microvilli protruding from the pores were examined.</p></div><div><h3>Results</h3><p>The size of the CVP exhibited a linear increase with age from E18 to P56. The epithelium around the pore aperture demonstrated changes to form microridges, indicating a characteristic pattern during CVP development. The size of the pore aperture also increased with age from E18 to P56. Furthermore, an increase in the number of pores with protruding microvilli was observed at the base of the epithelial trench. A significant positive correlation was observed between the maximum diameter of the pore and the size of the CVP.</p></div><div><h3>Conclusions</h3><p>The expansion in the lateral view of the CVP was associated with the developmental stage from E18 to P56, suggesting that the growth of the CVP leads to the opening and enlargement of the taste pores with microvillus projections during these stages.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 1","pages":"Pages 241-248"},"PeriodicalIF":2.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1349007924000136/pdfft?md5=c93310f9bd05684717727b3a3e94cf0c&pid=1-s2.0-S1349007924000136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison between hangeshashinto and dexamethasone for IL-1α and β-defensin 1 production by human oral keratinocytes","authors":"Hiroyuki Hato , Atsushi Kaneko , Chiho Maeda , Ken-ichiro Sakata , Yusuke Ono , Yusuke Mizukami , Toru Kono , Yoshimasa Kitagawa","doi":"10.1016/j.job.2024.01.007","DOIUrl":"10.1016/j.job.2024.01.007","url":null,"abstract":"<div><h3>Objective</h3><p>Human β-defensin 1 (hBD-1) is a antimicrobial peptide that is constantly secreted by oral tissues. Hangeshashinto (HST), a traditional Japanese medicine, has been reported to be effective against stomatitis. This study aimed to clarify the profile of HST by comparing the system of production of interleukin-1α (IL-1α) and hBD-1 in human oral mucosal epithelial cells with dexamethasone (DEX), a steroid used for the treatment of stomatitis.</p></div><div><h3>Methods</h3><p>Human oral keratinocytes (HOK) were treated with HST, DEX, or HST components (baicalein, baicalin, berberine, and glycyrrhizin) for 24 h, and subsequently cultured for 24 h with or without Pam3CSK4 or lipopolysaccharide (LPS). The cell supernatants, total RNA, and intracellular proteins were collected, and changes in IL-1α and hBD-1 protein production and gene expression were evaluated using ELISA and RT-PCR. The phosphorylation of NF-kB and the cell proliferative ability of HOK were evaluated by western blotting and XTT assay, respectively.</p></div><div><h3>Results</h3><p>DEX (0.01–10 μM) significantly suppressed IL-1α and hBD-1 production induced by either Pam3CSK4 or LPS, and also decreased cell growth. In contrast, HST inhibited Pam3CSK4- and LPS-induced IL-1α production at a concentration range of 12.5–100 μg/mL without affecting the cell proliferative capacity and hBD-1 production of HOK. Baicalein and baicalin, which are flavonoid ingredients of HST, showed anti-IL-1α production.</p></div><div><h3>Conclusion</h3><p>HST may be useful as a therapeutic agent for stomatitis and other inflammatory diseases of the oral cavity.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 1","pages":"Pages 188-195"},"PeriodicalIF":2.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1349007924000070/pdfft?md5=02edb1a1d19e8c819ed5827bf8ddcffb&pid=1-s2.0-S1349007924000070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medicinal herbs, especially Hibiscus sabdariffa, inhibit oral pathogenic bacteria","authors":"Kazuya Takada , Shizuki Nakano , Reina Nishio , Daichi Muku , Shinichi Mochizuki , Inori Inui , Kaede Okita , Ayaka Koga , Koji Watanabe , Yoshie Yoshioka , Wataru Ariyoshi , Ryota Yamasaki","doi":"10.1016/j.job.2024.01.006","DOIUrl":"10.1016/j.job.2024.01.006","url":null,"abstract":"<div><h3>Objectives</h3><p>Medicinal herbs are plants with potential medicinal and health benefits. In recent years, they are being increasingly used as a treatment alternative owing to their effectiveness against various diseases. In this study, we investigated the inhibitory effects of 15 medicinal herbs on causative bacteria for dental caries and periodontal disease.</p></div><div><h3>Methods</h3><p>This study evaluated the effects of the extracts of 15 medicinal herbs on growth and biofilm formation in five oral pathogenic bacterial strains. The herbs were processed into extracts, and bacterial strains were cultured. Then, bacterial growth and biofilm formation were assessed using various methods. Finally, the extract of the herb <em>Hibiscus sabdariffa</em> (hibiscus) was analyzed using high-performance liquid chromatography.</p></div><div><h3>Results</h3><p>Incubation of bacteria with the herbal extracts showed that hibiscus exerted a significant inhibitory effect on all the oral pathogenic bacterial strains evaluated in this study. In addition, the pigment delphinidin-3-sambubioside, which is found in hibiscus extract, was identified as a particularly important inhibitory component.</p></div><div><h3>Conclusions</h3><p>These results lay the ground work for the potential development of novel therapeutic or preventive agents against dental caries and periodontal disease, two major oral diseases.</p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"66 1","pages":"Pages 179-187"},"PeriodicalIF":2.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1349007924000069/pdfft?md5=cd7664f50582fee4dbddb0822db16fcb&pid=1-s2.0-S1349007924000069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}