Pharmaceutical Science Advances最新文献

{"title":"The effect of particle size on drug bioavailability in various parts of the body","authors":"Zi Hong Mok","doi":"10.1016/j.pscia.2023.100031","DOIUrl":"10.1016/j.pscia.2023.100031","url":null,"abstract":"<div><p>Multiple mechanisms are involved in driving the efficacy of drug delivery. Drug particle size is one of the challenges as particles need to be delivered from the external environment, into the circulation or interstitial fluid and transiting the cell membranes for cellular internalisation. Small particles are presumably easier to be internalised, yet they are not easy to retain as they are subject to fast clearance. Big particles do not cross biological barriers as easily, but their size distribution is easier to be controlled. Because of the various routes of administration, the size range of these particles will also need to be catered for the anatomical, biological, and dynamic barriers involved. This review hopes to provide an insight into the range of particle size that has been engineered for drug delivery via various routes of administration of the body, such as to cross the epithelium of gastrointestinal tract, lungs, skin, blood-brain barrier, kidney and liver, the eye, nose, and ear, the cancer tumour matrix and into the muscles. While successful drug delivery also depends on the material properties of the delivery systems and the bio/nano interface related properties, this review focuses on the importance of particle size for enhancing bioavailability at the various organs of the body.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000296/pdfft?md5=761880ad90cf562b5af20fa305e56c9a&pid=1-s2.0-S2773216923000296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296707","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":"Fuel-propelled nanomotors for acute kidney injury applications","authors":"Weixin Wang ,&nbsp;Rui Gao ,&nbsp;Lin Zhang ,&nbsp;Zhongchao Wang ,&nbsp;Jiahui Sun ,&nbsp;Lei Luo ,&nbsp;Min Pan ,&nbsp;Miaofang Hong ,&nbsp;Jianming Wu ,&nbsp;Qibing Mei ,&nbsp;Ke Tong ,&nbsp;Yini Wang ,&nbsp;Lingyan Qiao ,&nbsp;Fei Tong","doi":"10.1016/j.pscia.2024.100044","DOIUrl":"https://doi.org/10.1016/j.pscia.2024.100044","url":null,"abstract":"<div><p>Acute kidney injury (AKI) is characterized by a rapid loss of renal metabolic function and a high mortality rate. Although significant progress has been made in developing targeted drugs for AKI treatment, issues such as inadequate antioxidant effects and poor renal enrichment efficiency remain. Nanomotors can enhance drug delivery efficiency in AKI treatments through self-propulsion in the microenvironment or via external stimuli. We reviewed recent progress in the targeted treatment of AKI with nanomotors, focusing on their contribution to targeted drug delivery at different stages and combined treatments. Current limitations and future development directions are also discussed.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000102/pdfft?md5=4504c164042e6d4a1599cfcc3339045c&pid=1-s2.0-S2773216924000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594752","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":"Quercetin inhibits malignant progression of high metastatic advanced colon cancer in hypoxia via suppressing ROS and PI3K/AKT pathway","authors":"Pengfei Shang ,&nbsp;Jiawei Yang ,&nbsp;Lijun Shao ,&nbsp;Chao Sun ,&nbsp;Jianbo Ji ,&nbsp;Xiaoyan Wang ,&nbsp;Zongxue Zheng ,&nbsp;Xiuli Guo","doi":"10.1016/j.pscia.2024.100057","DOIUrl":"10.1016/j.pscia.2024.100057","url":null,"abstract":"<div><div>Advanced metastatic colon cancer is difficult to treat with existing chemotherapy medicines, and hypoxic microenvironment is closely related to angiogenesis and distant metastasis of colon cancer. Quercetin, a natural flavonoid, has been shown anti-tumor effects. The aim of this study is to investigate the effect of quercetin alone or combined with 5-FU on the invasion and metastasis of advanced metastatic or primary colorectal cancer in hypoxic environment. The cytotoxicity of quercetin or/and 5-FU on colon cancer cells using CCK8 assay, Hoechst 33342, flow cytometry and AO staining. The effects of quercetin or/and 5-FU on the migration and invasion were determined by transwell, cell scratching method and murine xenograft models. The potential mechanism was explored by Western blot and immunofluorescent assay. The results revealed quercetin effectively inhibited the invasion and migration of high metastatic advanced colon cancer LOVO cells under hypoxia through the inhibition of ROS and the expression of HIF-1α and PI3K/AKT pathway. Combination of quercetin and 5-FU could promote the inhibition of 5-FU on the invasion and migration of LOVO cells. Moreover, quercetin also significantly inhibited the proliferation of either LOVO cells or HT-29 ​cells under hypoxia by inducing apoptosis and autophagy, particularly, showing stronger inhibition on HT-29 ​cells than LOVO cells. In conclusion, quercetin inhibited the invasion and migration of advanced metastatic colon cancer LOVO cells under hypoxia through inhibition of ROS and HIF-1α expression and the downregulation of PI3K/AKT pathway. Moreover, quercetin alone or in combination with 5-FU can effectively inhibit the invasion and migration of high metastatic advanced colon cancer. Quercetin has the potential to be used as an effective anti-colon cancer drug alone or in combination for the clinical treatment of advanced colon cancer.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654966","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":"Intracellularly driven chemical modifications of antimicrobial secondary metabolites: Potent mechanisms of self-resistance","authors":"Xiaohua Li ,&nbsp;Jianhua Ju","doi":"10.1016/j.pscia.2023.100032","DOIUrl":"10.1016/j.pscia.2023.100032","url":null,"abstract":"<div><p>Natural products (NPs), especially antibiotics, exhibit diverse bioactivities and often play critically important roles in dictating and/or driving medical, health, agricultural, animal husbandry, and cosmetic industry initiatives. An important realization in the field of NP applications is that both targeted pathogens and the antibiotic-producing hosts themselves have usually evolved a host of resistance strategies by which to protect themselves. Although the former class of microbes (pathogens) has come to be associated with the global antibiotic resistance crisis, mechanisms by which producing organisms become resistant or tolerant to the ill effects of their bioactive metabolites have begun to attract a great deal of attention. Studies aimed at understanding antibiotic resistance have shown that producer-bourne mechanisms of self-resistance are possible prototypes by which to understand corresponding resistance elements in antibiotic-resistant bacteria. Historically speaking, the most efficient and potent chemistries employed by pathogens to evade harm from antimicrobial NPs have evoked enzymatically-driven transformations. We summarize herein the primary chemical modifications known to impart upon bioactive NP-producing microbes a means of self-defense against their own antimicrobial secondary metabolites; in understanding these chemistries we expect to gain new insights into how antibiotic resistance mechanisms in targeted pathogens might be circumvented or prevented. Such a translation of knowledge has a high likelihood of advancing humanity's ability to counter drug-resistant pathogens.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000302/pdfft?md5=9b7368c90310b0814596be32a9a53382&pid=1-s2.0-S2773216923000302-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139292184","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":"Possible hemoglobin enhancing effect of phytol in methotrexate-induced folate deficient Swiss albino mice: In vivo and in silico studies","authors":"Muhammad Torequl Islam ,&nbsp;Raihan Chowdhury ,&nbsp;Md Sakib Al Hasan ,&nbsp;Salehin Sheikh ,&nbsp;Md Shimul Bhuia ,&nbsp;Sumaya Akter Bithi ,&nbsp;Most Israt Jahan Oni ,&nbsp;Mehedi Hasan Bappi ,&nbsp;Siddique Akber Ansari ,&nbsp;Elaine C.P. Lucetti ,&nbsp;Catarina M. Tahim ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Irfan Aamer Ansari","doi":"10.1016/j.pscia.2024.100043","DOIUrl":"10.1016/j.pscia.2024.100043","url":null,"abstract":"<div><p>The diterpenoid phytol is evidently acting against anemia in experimental animals. However, the molecular mechanisms behind this issue are yet to be discovered. This study aimed to evaluate phytol's effect on methotrexate-induced folate-deficient animals through in vivo and in silico studies. For this, a total of thirty adult male Swiss albino mice were randomly divided into six different groups, namely the normal control (vehicle), the negative control (folate deficiency inducer, methotrexate 3 ​mg/kg), the standard (folic acid 1.5 ​mg/kg), two test groups comprising phytol 25 and 50 ​mg/kg, and a combined group composed of the standard and highest test doses of phytol. Except for the vehicle, all groups were treated with methotrexate for the first 3 days (once/day) to induce folate deficiency. Then followed by the respective treatment once a day for 3 days. Hemoglobin (Hb) level was measured from the peripheral blood (by tail cutting) on days 1st (before treatment), 4th (after methotrexate treatment), and 7th (after treatment). On the other hand, the computational studies were performed by PyMol, PyRex, Discovery Studio, and other complementary tools. Findings suggest that phytol significantly (<em>p</em> ​&lt; ​0.05) augmented Hb levels that are altered by methotrexate-induced reduction of Hb levels in animals dose-dependently. The combination also augmented Hb levels in animals; however, its effect was slightly lower than the individual groups (standard and test). In the in silico study, phytol showed good binding capacity (binding energy: −7.0 ​kcal/mol) with dihydrofolate reductase (DHFR). In conclusion, phytol may act against folate deficiency by altering methotrexate's impacts in animals, possibly through interacting with DHFR. Further validated research is necessary to develop phytol as an anti-anemia drug in the near future.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000096/pdfft?md5=bfaea545e629e34b31944f3178097e2e&pid=1-s2.0-S2773216924000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407753","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":"Protective effect of lycorine hydrochloride against diabetic nephropathy in high-fat diet and streptozotocin-induced diabetic mice","authors":"Kai-Li Fang ,&nbsp;Xin-Yu Qi ,&nbsp;Qing-Tong Han ,&nbsp;Lu-Zhou Chen ,&nbsp;Xiao-Ning Wang ,&nbsp;Zhen-Peng Xu ,&nbsp;Lu-Qing Shang ,&nbsp;Tao Shen","doi":"10.1016/j.pscia.2024.100035","DOIUrl":"https://doi.org/10.1016/j.pscia.2024.100035","url":null,"abstract":"<div><p>Diabetic nephropathy (DN) poses a significant risk to individuals with diabetes. Inflammation plays a crucial role in DN pathogenesis. Lycorine hydrochloride (LH) is derived from <em>Lycoris radiata</em> (L'Hér.). This herb has been identified as a potent anti-inflammatory molecule. Further studies indicated that LH displayed therapeutic potential against metabolic disorders, renal dysfunction, and fibrosis in a high-fat diet and streptozotocin-induced (HFD/STZ)-induced DN mouse model. Mechanistically, LH mitigated renal inflammation in DN mice by targeting NF-κB pathways and the NLRP3 inflammasome verified by <em>in vivo</em> study. <em>In vitro</em>, LH inhibited NLRP3 inflammasome activation induced by nigericin (Ng), monosodium urate (MSU), and ATP, reduced caspase-1 activation, and IL-1β release. Additionally, LH suppressed the NF-κB IS-induced activation, prevented nuclear translocation of NF-κB, and subsequently reduced the expression of downstream proteins COX2 and iNOS. Collectively, these results indicated that LH primarily improved hyperglycemia-induced renal function by reducing inflammation by targeting NF-κB and NLRP3 inflammasome, implying it is a promising therapeutic agent for DN.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000011/pdfft?md5=e5fb7692c1c50492d880fd4f179372d7&pid=1-s2.0-S2773216924000011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051643","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":"Natural product databases for drug discovery: Features and applications","authors":"Tao Zeng,&nbsp;Jiahao Li,&nbsp;Ruibo Wu","doi":"10.1016/j.pscia.2024.100050","DOIUrl":"10.1016/j.pscia.2024.100050","url":null,"abstract":"<div><p>Natural products (NPs) exhibit diverse chemical structures and biological activities that make them valuable sources for drug discovery. With advancements in computational technology, computation-enabled natural drug discovery is gaining increasing significance, with NP databases playing a pivotal role. In light of this, we first summarize the key features of NP databases, including structural data, property annotations, biological sources, biosynthetic pathways, and web interfaces. Subsequently, the wide applications of these databases in drug discovery, such as virtual screening, knowledge graph construction, and molecular generation, are reviewed. We further discuss the puzzle of database development, focusing on data quality and updating. Finally, we emphasize the pivotal role of team collaboration and toolkit innovation in harnessing the immense potential of NP-related databases to accelerate bioactivity mining, structure modification, and manufacturing. This review aims to elucidate the key features and applications of NP databases, with the goal of aiding researchers in developing and maintaining high-quality NP databases for drug discovery.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000163/pdfft?md5=d93f2dd8732dd7264d746b01693aaec6&pid=1-s2.0-S2773216924000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168004","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":"Blockage of HSP90 and IDO1 pathway by α-MSH modified nanoelicitor to dual-facilitate mild photothermal therapy","authors":"Shunli Fu,&nbsp;Qingping Ma,&nbsp;Jiangnan Li,&nbsp;Yifan Wang,&nbsp;Chunyan Yang,&nbsp;Panpan Gu,&nbsp;Weihan Zhang,&nbsp;Yongjun Liu,&nbsp;Na Zhang","doi":"10.1016/j.pscia.2023.100009","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100009","url":null,"abstract":"<div><p>Mild photothermal therapy (PTT) kills tumors at low temperatures (&lt;45 ​°C) with less non-specific thermal diffusion through adjacent normal tissues, making it a promising antitumor strategy. Although mild PTT can directly convert light energy into heat to kill tumors and indirectly induce immune cell death to prime the immune response, it simultaneously induces negative regulatory factors in the body to resist antitumor functions. In particular, the direct killing effects were reversed by the upregulation of heat shock protein 90 (HSP90) induced by mild PTT. The antitumor effects of T-cell-based immunotherapy counter indoleamine 2,3-dioxygenase1 (IDO1)-catalyzed kynurenine accumulation. Current studies have mainly focused on promoting direct killing effects or utilizing the priming immune response to strengthen the immunotherapy of mild PTT. Therefore, it is necessary to investigate whether the simultaneous promotion of direct killing and indirect immune activation would synergistically maximize mild PTT efficacy. This study reports on the development of a tumor-targeting nanoelicitor, α-<strong>M</strong>SH-<strong>G</strong>A/<strong>I</strong>R780/1-<strong>M</strong>T-<strong>Lip</strong>osome (M-GIM-Lip), by co-loading the photothermal agent IR780, HSP90 inhibitor geldanamycin, and IDO1 inhibitor 1-MT into liposomes with a melanoma-specific target ligand α-MSH modification. After accumulating in the tumor, the M-GIM-Lip could significantly inhibit tumor progress by combinate blockage of HSP90 and IDO1 pathways at 41 ​°C treatment of mild PTT. The study offers an innovative co-regulation strategy for enhancing the antitumor effects of mild PTT.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190382","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":"Structure, functions, and recent advances in the development of SIRT2 inhibitors","authors":"Junxin Xue,&nbsp;Xuben Hou,&nbsp;Hao Fang","doi":"10.1016/j.pscia.2023.100010","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100010","url":null,"abstract":"<div><p>Silent information regulators (sirtuins) are highly evolutionarily conserved and participate in many biological processes in the human body. Unlike classical histone deacetylases, the biological activity of sirtuins depends on nicotinamide adenine dinucleotide (NAD⁺). Among the seven human sirtuins, sirtuin 2 (SIRT2) is one of the most studied and plays important roles in cell aging, energy metabolism, and genome stability. SIRT2 dysregulation is closely associated with the development of cancer and neurodegenerative diseases. In this review, we summarize the structure, function, and recent developments in small-molecule inhibitors of SIRT2. We hope this review will aid the future development of new SIRT2 inhibitors.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190383","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":"Controlled release of bilayer tablet comprising vitamin B6 rapid-release layer and melatonin sustained-release layer","authors":"Yan Wang ,&nbsp;Jiaqi Xu ,&nbsp;Nan Gao ,&nbsp;Hongqian Lv ,&nbsp;Minge Sun ,&nbsp;Peng Zhang","doi":"10.1016/j.pscia.2023.100008","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100008","url":null,"abstract":"<div><p>Here, the formulation of a novel bilayer tablet comprising a vitamin B₆ rapid-release layer and a melatonin sustained-release layer is described. The effects of viscosity and concentration of the sustained-release matrix material, amount of diluent, and melatonin particle size on the release characteristics of melatonin were examined. In addition, the drug-release behavior of the prepared bilayer tablets was examined in different dissolution media. Further, drug-release kinetics and melatonin behavior in the sustained-release layer were evaluated based on dissolution profiles and changes in tablet weight during dissolution. Furthermore, the stability of the bilayer tablet was established. The <em>in vitro</em> release test revealed that vitamin B₆ was completely released within 10–15 ​min, with melatonin demonstrating ∼90% cumulative release within 8 ​h. Based on kinetic model fitting results, melatonin release was well fitted to the Ritger-Peppas model; the release mechanism was non-Fick diffusion with both diffusion and erosion. The drug-release study confirmed that the melatonin sustained-release layer predominantly underwent polymer swelling rather than polymer erosion. The stability test results showed that the bilayer tablets had good stability under high temperature, high humidity, and light conditions. The bilayer tablets offer an alternative for the controlled-release oral administration of melatonin, although their <em>in vivo</em> effects need to be investigated in human studies.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190387","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}