Open Life Sciences最新文献

{"title":"Evaluation and application analysis of animal models of PIPNP based on data mining.","authors":"Jun Yu, Shengbo Jin, Haozhe Piao, Mingzhu Li","doi":"10.1515/biol-2025-1122","DOIUrl":"10.1515/biol-2025-1122","url":null,"abstract":"<p><p>The aim of this study is to systematically retrieve, synthesize, and assess methodologies employed in the development of paclitaxel-induced peripheral neuropathic pain (PIPNP) animal models, with the objective of optimizing protocols for model construction and evaluation. A structured search strategy was implemented using the terms \"Paclitaxel-induced peripheral neuropathic pain\" OR \"Chemotherapy-induced peripheral neuropathic pain\" AND \"animal models\" OR \"rats\" OR \"mice\" OR \"experimental animals\" across the China National Knowledge Infrastructure, Wanfang, and VIP databases. Identical search criteria were applied to the PubMed and Web of Science platforms. The literature search covered publications from database inception through December 31, 2024. A total of 128 articles were reviewed, including 18 in Chinese and 110 in English. All studies employed rodent models, including 16 strains and including both sexes, with ages ranging from 5 weeks to 10 months. In rats, 28 distinct modeling protocols were identified: 4 involving continuous paclitaxel injections, 23 employing alternate-day injections, and 1 using a single administration. For mice, 21 methods were recorded, comprising 6 continuous, 13 alternate-day, and 2 single-injection protocols. Upon successful model induction, six behavioral pain alterations were consistently documented, evaluated using 16 different assessment techniques. Current PIPNP models predominantly utilize 6- to 8-week-old male Sprague-Dawley (SD) rats, with paclitaxel administered at 2 mg/kg on either days 0, 2, 4, and 6 or days 1, 3, 5, and 7. Based on data mining and comparative evaluation of modeling approaches, the use of 6- to 8-week-old male SD rats or 8- to 10-week-old male C57BL/6J mice with paclitaxel administered at 2 mg/kg on days 1, 3, 5, and 7 is recommended for establishing PIPNP models. The translational alignment between PIPNP models and clinical phenotypes remains insufficient and requires further refinement.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251122"},"PeriodicalIF":1.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation.","authors":"Xinmin Tian, Lanying Shi, Xiaozhen Bai, Ze Wang","doi":"10.1515/biol-2025-1128","DOIUrl":"10.1515/biol-2025-1128","url":null,"abstract":"<p><p>The Siberian flying squirrel (<i>Pteromys volans</i>) is an arboreal, nocturnal, and gliding rodent. It is crucial for maintaining ecosystem balance and the dispersal of forest seeds. In Northeast China, the number of Siberian flying squirrels is decreasing and their habitats are shrinking due to logging and habitat loss. To make more targeted and effective measures to protect and manage the population, there is an urgent need to study the genetic changes in the population, particularly looking at genetic diversity and gene flow. In this study, we collected hair samples from 91 Siberian flying squirrels in a way that did not harm them. Then, we analyzed the DNA in these samples, specifically using cytochrome <i>b</i> and microsatellite loci, and examined the genetic diversity and population structure of flying squirrels living in the northern Changbai Mountains of Northeast China. The results indicated that the genetic diversity in the populations was high. However, a high proportion of rare haplotypes and a low frequency of alleles indicated that the genetic diversity might decline in the future. There were significantly low to moderate levels of genetic differentiation among the four populations. According to our STRUCTURE analysis, the four geographical populations belonged to three genetic clusters (Fangzheng, Bin County, and Weihe-Muling). The isolation by distance model could not effectively explain the current pattern of the population genetic structure. The haplotype network showed no clear phylogeographic pattern among the four geographic populations, indicating that the geographic barriers between the flying squirrels might have formed only recently. To better protect the Siberian flying squirrels, conservation methods should be further improved. For example, habitat restoration and ecological corridor construction should be carried out to increase gene exchange and help the population recover and grow faster.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251128"},"PeriodicalIF":1.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications.","authors":"Lina Guan, Jing Chen, Hongqun Jiang","doi":"10.1515/biol-2025-1086","DOIUrl":"10.1515/biol-2025-1086","url":null,"abstract":"<p><p>This study focuses on the critical role of HDAC11 in age-related hearing loss and its underlying mechanisms. Through cellular experiments, we deeply explored the effects of HDAC11 on the proliferation and senescence of HEI-OC1 cells. The results showed that HDAC11 overexpression significantly reduced the acetylation level of α-microtubule protein, which in turn affected the stability of microtubule structure and accelerated the apoptosis and senescence process of HEI-OC1 cells. In addition, the overexpression of HDAC11 inhibited the Pink1/Parkin signaling pathway, which impeded the mitochondrial autophagy process and ultimately led to mitochondrial dysfunction. In animal experiments, we further verified the ameliorative effect of HDAC11 overexpression on hearing loss in aged mice. The experimental results showed that HDAC11 overexpression not only attenuated the histopathological damage of the cochlea in aged mice but also effectively improved their hearing function. Notably, HDAC11 overexpression suppressed the expression of cellular autophagy-related proteins and Pink1 and Parkin proteins. In summary, the present study preliminarily revealed that HDAC11 may regulate mitochondrial autophagy by inhibiting the Pink1/Parkin pathway, thus providing a new theoretical basis for improving hearing loss in the elderly.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251086"},"PeriodicalIF":1.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in \"<i>Harward</i>\" kiwifruit (<i>Actinidia deliciosa</i>).","authors":"Long Ma, Chunming Chi, Shuangqing Lv, Yan'an Tong, Lili Yang","doi":"10.1515/biol-2025-1114","DOIUrl":"10.1515/biol-2025-1114","url":null,"abstract":"<p><p>Potassium plays an important role in improving crop growth, yield, and quality; however, choosing the right potassium fertiliser remains challenging. To determine the optimal potassium fertiliser for kiwifruit, this study investigated the effects of different potassium sources on kiwifruit yield and postharvest quality as well as plant and soil nutrient contents in an orchard in Shaanxi Province, Northwest China. Two types of potassium fertiliser were examined (K₂SO₄ and KCl; total K₂O = 584 kg ha^-1) at two different application stages (basal and topdressing) under the following four treatments: basal K₂SO₄ + KCl topdressing, basal K₂SO₄ + K₂SO₄ topdressing, basal KCl + K₂SO₄ topdressing, and basal KCl + KCl topdressing. The different potassium sources had no significant effect on kiwifruit yield; however, a slight increase in yield and economic gain was observed under combined treatment with K₂SO₄ and KCl compared to single fertiliser treatment. Meanwhile, the single fruit weight and vitamin C content of the fruit were 7.0 and 4.6% higher under treatment with basal K₂SO₄ + KCl topdressing compared with K₂SO₄ treatment alone, and 3.1 and 14.9% higher compared with KCl treatment alone. Moreover, application of KCl promoted potassium and chlorine absorption by both the leaves and fruit. However, no significant differences in the content of sulphate or chloride ions in the surface soil (0-40 cm) were observed between potassium sources. In contrast, in deeper soil, the content of chloride ions was highest after KCl treatment, while that of sulphate ions was highest after K₂SO₄ topdressing. Overall, these findings suggest that the most appropriate potassium source for kiwifruit production is basal application of K₂SO₄ followed by KCl as topdressing in the study region.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251114"},"PeriodicalIF":1.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoassay for pyruvate kinase M1/2 as an Alzheimer's biomarker in CSF.","authors":"Matthijs B de Geus, Pia Kivisäkk, Bianca A Trombetta, Betty M Tijms, Pieter Jelle Visser, Steven E Arnold, Becky C Carlyle","doi":"10.1515/biol-2025-1101","DOIUrl":"10.1515/biol-2025-1101","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by amyloid-beta plaques and tau tangles in the brain, but these markers alone do not predict disease progression. The intersection of these pathologies with other processes including metabolic changes may contribute to disease progression. Brain glucose metabolism changes are among the earliest detectable events in AD. Pyruvate kinase (PKM) has been implicated as a potential biomarker to track these metabolic changes. We have developed an enzyme-linked immunosorbent assay (ELISA) to assess PKM levels in cerebrospinal fluid (CSF). First, we verified the relationship of CSF PKM levels with cognitive decline, revealing a correlation between elevated CSF PKM levels and accelerated cognitive decline in preclinical AD patients in a tau-dependent manner. We developed the ELISA using two PKM-specific antibodies and validated it through quality control steps, indicating robust quantification of PKM. We showed that ELISA measurements of PKM correlate with mass spectrometry values in matching samples. When tested on an independent cohort, the assay confirmed elevation of PKM in AD. These findings support the use of PKM as a potential biomarker for tracking early metabolic changes in AD, offering a novel tool for investigating metabolic alterations and their intersection with other underlying pathologies in AD progression.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251101"},"PeriodicalIF":1.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model.","authors":"Haseeb Ahmad, Irfan Anjum, Halima Usman, Aisha Mobashar, Arham Shabbir, Yousef A Bin Jardan, Amira Metouekel, Musaab Dauelbait, Mohammed Bourhia","doi":"10.1515/biol-2025-1083","DOIUrl":"10.1515/biol-2025-1083","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disease causing joint inflammation, deformity, cartilage deterioration, and pain. Benzimidazole derivatives exhibit various pharmacological properties. This study evaluated the antiarthritic, immunomodulatory, and anti-inflammatory potential of a benzimidazole derivative 2-(2-(benzylthio)-1<i>H</i>-benzo[d]imidazol-1-yl)-<i>N</i>'-(4-nitrobenzylidiene) acetohydrazide (BMZ-AD) in a Freund's complete adjuvant (FCA)-induced arthritic rat model. FCA was administered on day 0, and treatment with BMZ-AD (25 mg/kg, 50 mg/kg, and 75 mg/kg) and piroxicam (10 mg/kg) began on day 7 and continued up to 28 days. Rats were sacrificed on day 28. Arthritis was assessed using an arthritic scoring index, and paw edema was measured with a digital water plethysmometer. Biochemical and hematological parameters were analyzed, reverse transcription polymerase chain reaction measured the mRNA expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and molecular docking evaluated BMZ-AD interactions with these proteins. Enzyme-linked immunosorbent assay determined prostaglandin E2 levels. BMZ-AD treatment reduced inflammation, pannus formation, and pro-inflammatory cytokines (TNF-α and IL-6) and decreased PGE2 levels, comparable to piroxicam. Blood profiles improved with significant reductions in white blood cells and platelets in treatment groups. BMZ-AD demonstrated antiarthritic, anti-inflammatory, and immunomodulatory properties, suggesting that it could be a potential drug for RA treatment with fewer side effects.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251083"},"PeriodicalIF":1.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect.","authors":"Tunde Jurikova, Nela Skowronkova, Magdalena Zvonkova, Jana Orsavova, Sezai Ercisli, Libor Dokoupil, Katarina Fatrcova-Sramkova, Anna Adamkova, Jiri Mlcek","doi":"10.1515/biol-2025-1117","DOIUrl":"10.1515/biol-2025-1117","url":null,"abstract":"<p><p>Although cornelian cherry is an underutilized fruit species, its fruits have a high biological value due to valuable biologically active substances, especially polyphenols. The total content of polyphenols accounts for 37% of all the bioactive substances examined. Flavonols, anthocyanins, flavan-3-ols, and phenolic acids represent the main groups of phenolic compounds present and thanks to these compounds, cornelian cherry fruits possess mainly antioxidant, anti-inflammatory, antimicrobial, metabolic, antidiabetic, cardioprotective, and anticancer effects. This review summarizes new research aimed at popularizing this lesser-known species not only for direct consumption but also for further processing.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251117"},"PeriodicalIF":1.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the regulation of autophagy in cardiovascular diseases by chemokines.","authors":"Jingfeng Ma, Xiaotong Tan, Juling Feng, Zhihui Li, Shuo Tan, Boling Li, Lei Zhao","doi":"10.1515/biol-2022-1026","DOIUrl":"10.1515/biol-2022-1026","url":null,"abstract":"<p><p>Cardiovascular diseases (CVD) are the leading cause of death worldwide. Chemokines are a class of proteins that possess characteristics of both chemoattractants and cytokines. They play a pivotal role in CVD by regulating the recruitment of immune cells and suppressing inflammatory responses. These proteins are crucial for maintaining cardiac function and for managing myocardial cell damage under various stress conditions. Autophagy, a vital intracellular degradation mechanism, is essential for clearing misfolded proteins and damaged organelles, thus promoting cell survival during starvation and other stress conditions. A substantial body of research indicates that chemokines can modulate the development of CVD by influencing the autophagy process. Research has shown that targeting pathways such as CXCR4 and CXCL12, defective CXCL16/CXCR6, and inhibiting CX3CL1 can regulate autophagy and impact CVD. The protective role of chemokines in CVD through the modulation of autophagy may offer new perspectives for treatment.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20221026"},"PeriodicalIF":1.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: <i>In vitro</i> and <i>in vivo</i> evaluations.","authors":"Pan Li, Jing Wang, Huan Wang, Songchun Liu, Qibin Zhang","doi":"10.1515/biol-2022-1032","DOIUrl":"10.1515/biol-2022-1032","url":null,"abstract":"<p><p>This investigation explores the impact of hesperidin and its zinc(ii) complex on osteoblast differentiation and subsequent bone formation. The biocompatibility of synthesized complexes (0-20 μg/mL) was assessed <i>in vitro</i> using mouse mesenchymal stem cells, while <i>in vivo</i> toxicity was evaluated using a chick embryo model. Both hesperidin and its zinc(ii) complex were found to be non-toxic at a concentration of 10 μg/mL. Notably, these compounds significantly increased alkaline phosphatase activity and enhanced calcium deposition. Molecular analyses revealed upregulation of Runx2 and type 1 collagen mRNA expression, along with increased levels of osteonectin and osteocalcin proteins, while negative regulators of osteoblast differentiation (Smad7, Smurf1, HDAC7) were downregulated. A new aspect of this study is demonstrating that the zinc(ii) complex of hesperidin uniquely enhances osteogenic activity compared to hesperidin alone, highlighting its potential to improve bone formation significantly. Additionally, we elucidated the role of miR-143-3p in mediating these effects, achieved through HDAC7 suppression and enhanced Runx2 expression, assessed using the pmirGLO dual luciferase reporter system. Zebrafish studies further demonstrated the complexes' effects on bone formation, revealing increased osteoblastic activity and improved calcium-to-phosphorus ratios in regenerated scales. These findings underscore the potential of hesperidin-Zn(ii) as a promising therapeutic agent for bone tissue engineering.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20221032"},"PeriodicalIF":1.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of <i>Piriformospora indica</i> and arbuscular mycorrhizal fungus on growth and physiology of <i>Moringa oleifera</i> under low-temperature stress.","authors":"Guo Zhou, Sini Wu, Meichun Qiu, Yingtong Long, Qian He, Junjie Zhang","doi":"10.1515/biol-2025-1111","DOIUrl":"10.1515/biol-2025-1111","url":null,"abstract":"<p><p><i>Moringa</i> is a perennial tree with high nutritional value, and it is drought tolerant and barren but has poor cold resistance during the seedling stage. This study selected <i>Piriformospora indica</i> (PI) and arbuscular mycorrhizal fungus (AM) as inoculants, <i>Moringa</i> seedlings were inoculated, and their growth and physiological responses were evaluated under different low-temperature stress times. The research results show that PI and AM can symbiotically associate with <i>Moringa</i> successfully and promote their nutritional growth. At low temperature, Moringa inoculated with PI and AM exhibited better physiological resistance. However, the effect of mixed inoculation of PI and AM is not as significant as that of single inoculation of any strain. Inoculating plant growth-promoting rhizobia (PGPR) reduced the richness of fungal communities and the number of unique operational taxonomic units (OTUs), with PI being the most prominent. Vaccination with PGPR also increased bacterial diversity, richness, and the number of unique OTUs, with AM inoculation showing the most prominent performance. This suggests that <i>Moringa</i> seedling growth and responsiveness to low-temperature stress are significantly influenced by PGPR, and there may be interactions between different bacterial strains. The results suggest that PGPR can improve the yield and quality of <i>Moringa</i> by promoting growth and regulating stress resistance.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"20 1","pages":"20251111"},"PeriodicalIF":1.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}