Pharmaceuticals最新文献

{"title":"Modified Liuwei Dihuang Decoction Ameliorates Oligoasthenozoospermia in Mice via Modulation of the PI3K/AKT/Nrf2 Signaling Pathway.","authors":"Mingzhu Li, Linhuang Chen, Haotian Xu, Junlin Li, Yatian Liu, Xiuyun Chen, Minyi Luo, Xinyuan Xie, Mingyu Yin, Jinyang He","doi":"10.3390/ph18091363","DOIUrl":"10.3390/ph18091363","url":null,"abstract":"<p><p><b>Background</b>: Oligoasthenozoospermia (OA) is a common cause of male infertility. Modified Liuwei Dihuang Decoction (MLWDH) is an improved version of Liuwei Dihuang Decoction (LWDH), a traditional Chinese medicine prescription, which has demonstrated significant therapeutic effects against OA. This study aims to evaluate the protective effects of MLWDH against OA and elucidate its underlying molecular mechanisms. <b>Methods</b>: The constituents of MLWDH were identified via UPLC-HRMS and compound databases (TCMSP, HERB). Network pharmacology analysis was conducted to predict potential therapeutic targets and associated signaling pathways. In vivo, a CP-induced mouse model of OA was established to evaluate the therapeutic efficacy of MWDH by assessing testicular and epididymal indices, sperm quality, histopathological changes and serum hormone levels. Oxidative stress markers, including MDA, SOD, GSH and NO, were measured using commercial assay kits. The underlying molecular mechanisms, particularly those related to oxidative stress and inflammation (PI3K, Akt, Nrf2, Keap1, HO-1, NQO1, NF-κB, TNF-α, IL-6), were further elucidated by RT-qPCR, Western blot, and immunofluorescence. <b>Results</b>: A total of 345 major bioactive compounds were identified in MLWDH. Network pharmacology and molecular docking analyses indicated that MLWDH exerts its effects primarily through the PI3K/AKT signaling pathway. MLWDH administration in vivo significantly improved sperm count, motility, and morphology, while also increasing serum levels of testosterone, FSH, and LH. Moreover, MLWDH significantly mitigated oxidative damage, as evidenced by decreased MDA concentrations and elevated levels of GSH, NO and SOD. Mechanistic investigations further substantiated that MLWDH enhanced PI3K/AKT/Nrf2 signaling while inhibiting NF-κB signaling in OA mice. <b>Conclusions</b>: Our findings suggest that MLWDH ameliorates OA in a preclinical mouse model by improving sperm quality and testicular function, potentially via activation of the PI3K/AKT/Nrf2 signaling pathway and the inhibition of NF-κB signaling, thereby alleviating oxidative stress and inflammatory responses.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Tan et al. FOXO3-Activated circFGFBP1 Inhibits Extracellular Matrix Degradation and Nucleus Pulposus Cell Death via miR-9-5p/BMP2 Axis in Intervertebral Disc Degeneration In Vivo and In Vitro. <i>Pharmaceuticals</i> 2023, <i>16</i>, 473.","authors":"Yanlin Tan, Xiaobin Wang, Yi Zhang, Zhehao Dai, Jing Li, Chuning Dong, Xingwang Yao, Chang Lu, Fei Chen","doi":"10.3390/ph18091367","DOIUrl":"10.3390/ph18091367","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Non-Coding Regions in Breast Cancer: From Gene Regulation to Therapeutic Implications.","authors":"Hussein Sabit, Sara Sobhy, Shaimaa Abdel-Ghany, Al-Hassan Soliman Wadan, Olubukola Ayodele, Yasser Albrahim, Hirendra N Banerjee, Ahmed Elhashash, Borros Arneth","doi":"10.3390/ph18091370","DOIUrl":"10.3390/ph18091370","url":null,"abstract":"<p><p>Breast cancer (BC) remains one of the most prevalent cancers worldwide and a significant cause of cancer-related mortality among women. Despite significant advancements in understanding the genetic foundations of BC, numerous research initiatives have historically focused on protein-coding genes, which constitute merely about 2% of the human genome. This focus has produced significant insights into oncogenes such as HER2, TP53, and BRCA1, along with tumor suppressor genes. Nonetheless, it has led to the non-coding portions of the genome garnering relatively less focus. Recent studies illuminate the crucial significance of non-coding DNA in cancer biology, highlighting its regulatory roles and influence on tumor formation, metastasis, and treatment resistance. This review examines the importance of non-coding DNA in BC. It provides an in-depth analysis of essential non-coding regions, their functions in gene regulation and chromatin structure, and their implications for various BC subtypes. Examining these facets, we seek to reveal the potential of non-coding DNA as a viable source of novel diagnostic markers and treatment approaches.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Adding GLP-1 Receptor Agonists to Insulin Therapy on Cardiovascular and Microvascular Outcomes in Type 2 Diabetes: A Nationwide Cohort Study from Taiwan.","authors":"Fu-Shun Yen, James Cheng-Chung Wei, Chen-Yu Sung, Pei-Yun Li, Fuu-Jen Tsai, Chih-Cheng Hsu, Chii-Min Hwu","doi":"10.3390/ph18091368","DOIUrl":"10.3390/ph18091368","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Selecting appropriate non-insulin hypoglycemic agents to complement insulin therapy is essential for achieving optimal glycemic control. This study aimed to evaluate the impact of glucagon-like peptide-1 receptor agonist (GLP-1 RA) plus insulin therapy on long-term cardiovascular and microvascular outcomes in patients with type 2 diabetes (T2D), with the goal of optimizing treatment strategies. <b>Methods:</b> Using Taiwan's National Health Insurance Research Database (2008-2021), we conducted a retrospective cohort study and identified 6779 propensity score-matched pairs of insulin-treated patients with T2D who initiated either GLP-1 RAs or dipeptidyl peptidase-4 (DPP-4) inhibitors. Cox proportional hazard models were applied to compare outcome risks between the two groups. <b>Results:</b> The mean follow-up was 3.45 years. Compared with DPP-4 inhibitor use, GLP-1 RA use was significantly associated with a reduced risk of major adverse cardiovascular events (aHR 0.52, 95% CI 0.46-0.58), including hospitalizations for coronary artery disease (aHR 0.64, 95% CI 0.54-0.75), stroke (aHR 0.48, 95% CI 0.40-0.56), and heart failure (aHR 0.33, 95% CI 0.25-0.42). GLP-1 RA use was also linked to lower risks of major microvascular complications (aHR 0.42, 95% CI 0.35-0.50), end-stage kidney disease (aHR 0.08, 95% CI 0.04-0.14), sight-threatening retinopathy (aHR 0.62, 95% CI 0.50-0.76), leg amputation (aHR 0.16, 95% CI 0.05-0.57), and all-cause mortality (aHR 0.38, 95% CI 0.32-0.44). <b>Conclusions:</b> In this nationwide cohort, adding GLP-1 RAs to insulin therapy in patients with T2D was associated with significantly lower risks of cardiovascular events, major microvascular complications, and all-cause mortality compared with adding DPP-4 inhibitors. These findings suggest that incorporating GLP-1 RAs into insulin regimens may optimize treatment, lessen disease burden, and improve survival.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Covalently Functionalized Halloysite-Calixarene Nanotubes for Injectable Hydrogels: A Multicavity Platform for Hydrophobic Drug Delivery.","authors":"Giuseppe Cinà, Marina Massaro, Andrea Pappalardo, Carmela Bonaccorso, Cosimo G Fortuna, Placido G Mineo, Angelo Nicosia, Paola Poma, Rita Sánchez-Espejo, Caterina Testa, César Viseras, Serena Riela","doi":"10.3390/ph18091356","DOIUrl":"10.3390/ph18091356","url":null,"abstract":"<p><p><b>Background</b>: Poor water solubility is a major limitation for the therapeutic use of many anticancer drugs. In this study, we report the design and development of two halloysite-based hybrid nanomaterials for the encapsulation and delivery of hydrophobic and positively charged drugs. <b>Methods</b>: A novel multicavity platform was obtained by covalently grafting calix[5]arene macrocycles onto the external surface of halloysite nanotubes (HNTs), combining lumen encapsulation with supramolecular host-guest recognition. PB4, a planar and hydrophobic pyridinium salt with significant antiproliferative activity, was selected as a model compound. Both PB4-loaded HNTs (HNTs/PB4) and calixarene-functionalized HNTs (HNTs-Calix/PB4) were incorporated into Laponite^®-based thixotropic hydrogels to obtain injectable and biocompatible systems. <b>Results</b>: The nanomaterials were thoroughly characterized, and their loading efficiency, release behavior, and aqueous dispersibility were evaluated. Antiproliferative tests on MCF-7 cells demonstrated that both hydrogels retained PB4 activity, with distinct release profiles: the pristine HNTs allowed faster drug availability, while calix[5]arene-functionalized systems promoted sustained release. <b>Conclusions</b>: This work introduces the first example of covalently calixarene-functionalized halloysite and presents a versatile drug delivery platform adaptable to different therapeutic contexts and combination strategies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Pharmacological Properties, Molecular Mechanisms, and Bioavailability Strategies of Chlorogenic Acid in Cardiovascular Diseases Therapy.","authors":"Kai Huang, Duosu Zhang, Ruting Wang, Jiahao Duan, Long Hu, Fan Huang, Wei Liu, Jia Gu, Songlin Li, Chun Yang, Ling Yang","doi":"10.3390/ph18091357","DOIUrl":"10.3390/ph18091357","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs), a group of global diseases, are characterized by high morbidity and mortality, imposing a significant burden on clinical practice. Chlorogenic acid (CGA), a natural compound composed of caffeic acid and quinic acid, is widely found in and extracted from plants such as <i>Lonicera japonica</i> (honeysuckle), <i>Eucommia ulmoides</i> (hardy rubber tree), tea leaves, and coffee beans. In recent years, increasing attention has been directed towards the pharmacological mechanisms of CGA in the treatment of CVDs. This review comprehensively summarizes the current knowledge on the preparation, metabolic pathways, pharmacological effects, and safety profile of CGA. Furthermore, it systematically analyzes the biological effects and molecular targets of CGA in the cardiovascular therapy and highlights strategies to enhance its bioavailability. These insights aim to provide a scientific basis for future basic research and clinical applications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetics and the Response to Antidepressants in Major Depressive Disorder.","authors":"Amanda Gollo Bertollo, Ricieri Mocelin, Zuleide Maria Ignácio","doi":"10.3390/ph18091360","DOIUrl":"10.3390/ph18091360","url":null,"abstract":"<p><p><b>Purpose:</b> Genetic polymorphisms within specific genes play a role in both the genetic predisposition to Major Depressive Disorder (MDD) and the variation observed in responses to antidepressant treatments. Pharmacogenetics examines how these polymorphisms affect medication response. This review highlights significant disparities in the pharmacogenetic influences on antidepressant response, with a focus on ethnic and sex-based differences. <b>Methods:</b> This review synthesizes findings from a comprehensive literature search conducted between 2000 and 2025. It utilized databases such as PubMed, Scopus, and Web of Science, using search terms including \"pharmacogenetics\", \"antidepressants\", \"Major Depressive Disorder\", \"CYP450\", \"neuroplasticity\", and \"genetic variations\". This review integrates pharmacogenetics with neurotransmitters and their transporters, neuroplasticity, growth factors, and the cytochrome P450 family, providing promising insights for personalized MDD treatment strategies. We analyzed and synthesized findings from over 50 relevant studies, focusing on those with a clear emphasis on genetic associations with antidepressant efficacy and adverse effects. <b>Results:</b> Pharmacogenetic analysis facilitates personalized antidepressant prescriptions by identifying key genetic variants that influence treatment outcomes. Specifically, variations in CYP2D6 and CYP2C19 can significantly impact drug metabolism and tolerability. A high percentage of patients with non-normal metabolizer phenotypes are predisposed to adverse drug reactions or ineffective responses. Furthermore, this review identifies significant ethnic and sex-based disparities in treatment response. For example, the L allele of the 5-HTTLPR polymorphism confers a higher likelihood of response and remission following SSRI treatment in white people compared to Asians. Additionally, in women, specific 5-HTTLPR polymorphisms have a more pronounced influence on mood and MDD pathophysiology, with a significant reduction in mood in response to tryptophan depletion. <b>Conclusions:</b> Integrating pharmacogenetic insights, encompassing genetic factors, neurotransmitter pathways, neuroplasticity, and the influence of ethnicity and sex, is crucial for developing personalized antidepressant treatment strategies. This will ultimately optimize patient recovery and minimize adverse effects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Activity and Potential of Olive Leaf Extract as a Topical Agent to Combat <i>Staphylococcus aureus</i> and MRSA Strains: An In Vitro Evaluation.","authors":"Laura Clusa, Miriam Latorre-Millán, Ana María Milagro, Alexander Tristancho-Baró, Ana Isabel López-Calleja, Juan Manuel García-Lechuz, Blanca Fortuño, Nuno Del Villar, Mario Asensio, Olga Martín-Belloso, Isabel Odriozola-Serrano, Roberto Martínez-Beamonte, Jesús Osada, Antonio Rezusta, Yolanda Gilaberte","doi":"10.3390/ph18091358","DOIUrl":"10.3390/ph18091358","url":null,"abstract":"<p><p><b>Background</b>: <i>Staphylococcus aureus</i> is one of the most prevalent bacteria in skin and soft tissue infections (SSTIs). Multidrug-resistant strain emergence, particularly methicillin-resistant <i>S. aureus</i> (MRSA), highlights the need for alternative treatments. <b>Objectives</b>: This study investigates the antimicrobial properties of olive leaf extract (OLE) and describes an epidemiological profiling of patients with SSTI who may benefit from it. <b>Methods</b>: OLE was tested in two reference strains, methicillin-susceptible <i>S. aureus</i> (MSSA) ATCC 29213 and MRSA ATCC 700699, and in 126 clinical isolates from patients with SSTIs according to Clinical Laboratory Standards Institute guidelines. <b>Results</b>: The minimum bactericidal concentration (MBC) ranged from 3.12% to 6.25% <i>w</i>/<i>v</i> for MSSA and 1.56% to 3.12% for MRSA. The lethal curve showed a reduction of 6 log₁₀CFU/mL after two hours of incubation. Most of the 126 clinical samples (103 MSSA and 23 MRSA) came from skin lesions, surgical wounds, and ulcers. Over 90% of MSSA strains were resistant to less than five antibiotics, while 82% of MRSA strains were resistant to more than six. Penicillins demonstrated the lowest susceptibility rate (19.8%), whereas linezolid, daptomycin, pristinamycin, trimethoprim-sulfamethoxazole, teicoplanin, vancomycin, and OLE exhibited 100% susceptibility. No growth was observed for all clinical strains with OLE at ≥6.25% <i>w</i>/<i>v</i>. <b>Conclusions</b>: The findings suggest that OLE could become a promising alternative treatment for skin infections, particularly in the context of increasing antibiotic resistance.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances and Challenges in the Development of New and Novel Treatment Strategies for Eosinophilic Esophagitis (EoE).","authors":"Ivna Olic, Piero Marin Zivkovic, Ivan Zaja, Nikola Pavlovic, Marko Kumric, Josko Bozic","doi":"10.3390/ph18091359","DOIUrl":"10.3390/ph18091359","url":null,"abstract":"<p><p>Eosinophilic esophagitis (EoE) is a long-term, immune-driven condition of the esophagus, which can lead to severe fibrostenosis of the esophagus, and the aim is to control clinical, endoscopic, and histopathologic disorder activity. Currently, treatment options include the use of proton pump inhibitors, topical steroids, and dietary elimination as basic treatments; however, the introduction of dupilumab has provided an additional therapeutic approach. Numerous biologic agents target specific immune pathways, which are promising pharmacologic options in managing this progressive disease. The final goal is to treat the target, with complete resolution as the final objective. To accomplish this, however, effective agents capable of modifying the disease process are required. In this review, we aimed to provide an overall review of EoE therapeutics options, as well as the benefits and safety of new treatment strategies for EoE.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Hou et al. S-72, a Novel Orally Available Tubulin Inhibitor, Overcomes Paclitaxel Resistance via Inactivation of the STING Pathway in Breast Cancer. <i>Pharmaceuticals</i> 2023, <i>16</i>, 749.","authors":"Zhenyan Hou, Songwen Lin, Tingting Du, Mingjin Wang, Weida Wang, Shen You, Nina Xue, Yichen Liu, Ming Ji, Heng Xu, Xiaoguang Chen","doi":"10.3390/ph18091355","DOIUrl":"10.3390/ph18091355","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}