Cellular Physiology and Biochemistry最新文献

{"title":"Aging and Infection: Impact of Immunosenescence and Inflammaging in Respiratory Viral Infections.","authors":"Alhussain Alnakhli, Jalnar Albaloshi, Lamin B Cham","doi":"10.33594/000000848","DOIUrl":"10.33594/000000848","url":null,"abstract":"<p><p>A strong yet appropriate immune response is essential for the timely control and clearing of respiratory viral infections. However, as physical condition declines with age, so does immune function. Immunosenescence is an age-related immune dysfunction marked by dysregulation of innate immune pathways, thymic involution, decreased T and B cell numbers and function, altered metabolism, and epigenetic changes. Additionally, older individuals often develop inflammaging, a condition characterized by elevated levels of proinflammatory markers. This deterioration of immune function in older adults significantly impairs viral control and increases disease severity. Studies consistently show a progressive rise in hospitalization and mortality rates with age. This review discusses the complex relationship between aging, immunosenescence, and inflammaging during respiratory viral infections, as well as the underlying mechanisms that increase susceptibility, disease severity, and hospitalization among older adults.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"60 1","pages":"73-88"},"PeriodicalIF":2.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431149","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":"Relationship Between Left Ventricular Remodeling Assessed by Strain Echocardiography and Conventional Echocardiography Before and After Cardiac Resynchronization Therapy in Severe Heart Failure Patients.","authors":"Giang Song Tran, Bang Phu Thi Hoang, Si Dung Chu","doi":"10.33594/000000874","DOIUrl":"10.33594/000000874","url":null,"abstract":"<p><strong>Background/aims: </strong>To assess the relationship between left ventricular remodeling as evaluated by strain echocardiography and conventional echocardiography before and after cardiac resynchronization therapy (CRT) in patients with severe heart failure.</p><p><strong>Methods: </strong>A cross-sectional descriptive study with follow-up comparison before and after CRT. The study included 33 heart failure patients indicated for CRT at the Vietnam National Heart Institute, Bach Mai Hospital from late 2015 to December 2021.</p><p><strong>Results: </strong>Left ventricular end-systolic volume and end-diastolic volume significantly decreased after three months of follow-up (p < 0.001) and showed a strong inverse correlation with QRS recovery (r = 0.65). A positive correlation was observed between changes in left atrial volume index (LAVI) and 4B strain (r = 0.96, p < 0.05). After three months of CRT implantation, positive correlations were observed between isovolumic relaxation time (IVRT) and left atrial volume index (LAVI), and between left atrial volume and E/e' obtained from tissue Doppler imaging (r = 0.53, p < 0.05). No correlation was found between E/e' and total EF, between 2B strain and total EF, or between 2B strain and LAVI.</p><p><strong>Conclusion: </strong>Strain echocardiography represents an important tool for diagnosing, assessing risk factors, and monitoring heart failure. After three months of CRT implantation, significant improvement in left ventricular volume and ejection fraction was observed, indicating improved treatment effectiveness.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"60 1","pages":"63-72"},"PeriodicalIF":2.5,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376172","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":"Evidence For a Fibrogenic Interaction Between the Aryl Hydrocarbon Receptor and the Wnt/β-Catenin Pathways in Human Keratinocytes and Fibroblasts.","authors":"Anna Wajda, Adam Ejma-Multański, Dina Himida, Barbara Stypińska, Gabriela Filipowicz, Andrea Rossi, Inken Hacheney, Thomas Haarmann-Stemmann, Agnieszka Paradowska-Gorycka, Charlotte Esser","doi":"10.33594/000000846","DOIUrl":"10.33594/000000846","url":null,"abstract":"<p><strong>Background/aims: </strong>Systemic sclerosis is a rare autoimmune and fibrotic disease, often manifesting in the skin. The aryl hydrocarbon receptor is critical for skin homeostasis; however, its role in fibrosis is not well understood. We investigated the crosstalk between TGFβ, AHR, and Wnt/β-catenin signaling.</p><p><strong>Methods: </strong>Human dermal fibroblasts and HaCaT keratinocytes, both wild-type and AHR-deficient, were cultured in mono- and co-cultures. Cells were treated with TGFβ and the AHR agonist FICZ. Collagen type I and MMP1 were quantified, Wnt/β-catenin genes analyzed, migration assessed, and proteome profiling performed.</p><p><strong>Results: </strong>AHR deletion reduced Wnt/β-catenin gene expression and abrogated TGFβ-induced collagen production. Co-cultures showed AHR-dependent regulation of immune-related genes, and scratch closure was also AHR-dependent.</p><p><strong>Conclusion: </strong>The study demonstrates a context-dependent role of AHR in skin fibrosis and its interaction with TGFβ and Wnt/β-catenin signaling.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"60 1","pages":"44-62"},"PeriodicalIF":2.5,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156054","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":"Tumor Destructive Mechanical Impulse (TMI) Treatment of Solid Tumors. Part II: Biomechanics, Computational Simulation, Technical Generator and Applicator Design, and Physiological Effect.","authors":"Axel Erich Theuer, Nicolas Schierbaum, Heike Niessner, Tobias W Sinnberg, Tilman E Schäffer, Florian Lang, John David Mullins, Thomas K Eigentler, Gerhard Franz Walter","doi":"10.33594/000000844","DOIUrl":"10.33594/000000844","url":null,"abstract":"<p><strong>Background/aims: </strong>To explore the feasibility and effectiveness of Tumor Destructive Mechanical Impulse (TMI) treatment of solid tumors, biomechanical preconditions for subsequent computational simulation of focused shock wave propagation within cells and tissue are investigated. This innovative \"soft\" approach is different from the FDA-approved high intensity focused ultrasound (HIFU)-based histotripsy, and from electrical Tumor Treating Fields (TTFs).</p><p><strong>Methods: </strong>Atomic force microscopy investigation for cell mechanics, multiple parametric computational simulations for focused shock wave propagation, technical TMI generator and applicator design, light- and electron-microscopic evaluation of treatment effects on tumor cells and tissue.</p><p><strong>Results: </strong>Individual tumor cell evaluation of physical properties as basis for multiple parametric simulations determine the optimal treatment parameters (total energy required, energy flux density, shock wave frequency) and applicator positions; design flexibility of applicator devices for extra- and intracorporeal treatment.</p><p><strong>Conclusion: </strong>The fundamental feasibility, effectiveness and reliability of TMI treatment of solid tumors were proven, providing a reliable theoretical basis for the broadly applicable translation into clinical practice.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"60 1","pages":"30-43"},"PeriodicalIF":2.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017307","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":"Peripheral miRNA-155 Expression and Circulating Inflammatory Cytokines in Patients with Helicobacter pylori-Associated Chronic Gastritis: An Exploratory Case-Control Study.","authors":"Sarah Kassab Shandaway Al-Zamali","doi":"10.33594/000000843","DOIUrl":"10.33594/000000843","url":null,"abstract":"<p><strong>Background/aims: </strong>Infection with Helicobacter pylori is a major cause of chronic gastritis and persistent gastric inflammation. miRNA-155 and inflammatory cytokines play key roles in immune regulation; however, their systemic expression profiles in H. pylori-associated chronic gastritis are not fully characterized.</p><p><strong>Methods: </strong>Twenty-five patients with endoscopically and histologically confirmed H. pylori-associated chronic gastritis and 25 age-matched healthy controls were included. Peripheral miRNA-155 expression was measured by quantitative real-time PCR, and serum IL-6, IFN-γ, and IL-10 levels were quantified by ELISA.</p><p><strong>Results: </strong>Patients exhibited significantly elevated peripheral miRNA-155 expression compared with controls (p < 0.001). Serum IL-6, IFN-γ, and IL-10 concentrations were also significantly higher in patients (all p < 0.001). Logistic regression analyses indicated significant associations between biomarker levels and H. pylori infection status.</p><p><strong>Conclusion: </strong>This exploratory case-control study demonstrates systemic alterations in miRNA-155 expression and inflammatory cytokines in H. pylori-associated chronic gastritis. These findings suggest immune-regulatory changes detectable in peripheral blood, warranting validation in larger independent cohorts.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"60 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324110","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":"The Impact of Aging on Organ Systems in Sickle Cell Disease: a Comparative Review of Physiological Adaptation and Dysfunction.","authors":"Hind A Alzahrani","doi":"10.33594/000000839","DOIUrl":"10.33594/000000839","url":null,"abstract":"<p><p>Sickle cell anemia (SCA) is a progressive, systemic disorder that can lead to multi-organ dysfunction. While it has traditionally been most prevalent in regions where malaria is endemic, recent epidemiological studies have shown an increasing disease prevalence in non-endemic areas, primarily attributed to global human migration patterns. The severity of SCA typically worsens with age. In early childhood, affected individuals may present with renal hyperfiltration, neurocognitive delays, cardiac remodeling, and skeletal fragility. The presence of these early manifestations often predicts the development of chronic complications later in life, including splenic atrophy, neurodegeneration, and impaired cerebral perfusion. Adequate management of SCA begins with universal newborn screening programs, enabling early detection and the initiation of appropriate interventions. Therapeutic advancements, ranging from disease-modifying agents such as hydroxyurea to curative options including gene therapy and stem cell transplantation, have significantly improved clinical outcomes; however, long-term morbidity remains a significant challenge. This review aimed to explore the effect of aging on pathophysiological changes and the onset of organ-specific complications in SCA patients. It highlights the importance of age-tailored monitoring and a multidisciplinary approach to detect early signs of organ damage, prevent irreversible complications, and consequently improve overall quality of life.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"59 6","pages":"930-939"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431232","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":"Lnc-ANRIL Protects Against Myocardial Ischemia-Reperfusion Injury by Suppressing Ferroptosis via the miR-7238-3p/GPX4 Axis.","authors":"Yijun Liu, Binhua Wu, Yunhao Shao, Kui Hu, Jian Mo, Liangqing Zhang, Guixi Mo","doi":"10.33594/000000837","DOIUrl":"https://doi.org/10.33594/000000837","url":null,"abstract":"<p><strong>Background/aims: </strong>Myocardial infarction remains a leading cause of cardiovascular morbidity and mortality. Although reperfusion therapy restores myocardial blood flow, it can induce myocardial ischemia-reperfusion injury (MI/RI). Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid reactive oxygen species, contributes to MI/RI and is characterized by downregulation of GPX4 and upregulation of ACSL4. LncRNA ANRIL is aberrantly expressed in acute myocardial infarction and may provide myocardial protection, but its role in MI/RI-induced ferroptosis is unclear.</p><p><strong>Methods: </strong>A mouse MI/R model was established by ligating the left anterior descending coronary artery in C57BL/6 mice. HL-1 and H9C2 cardiomyocytes underwent hypoxia-reoxygenation to simulate MI/RI in vitro. Lnc-ANRIL was overexpressed using pEGFP-lnc-ANRIL or silenced using siANRIL. Ferroptosis indicators (ROS, malondialdehyde, Fe2+, GPX4, ACSL4) were assessed. Candidate miRNAs targeting lnc-ANRIL and GPX4 were predicted (miRDB) and validated by dual-luciferase assays.</p><p><strong>Results: </strong>Ferroptosis was activated in MI/R tissues and hypoxia-reoxygenation-treated cardiomyocytes, with decreased GPX4, increased ACSL4, and elevated ROS, malondialdehyde, and Fe2+. Lnc-ANRIL expression was reduced. Overexpression of lnc-ANRIL attenuated ferroptosis markers and increased GPX4, whereas lnc-ANRIL silencing exacerbated ferroptosis. Mechanistically, lnc-ANRIL acted as a sponge for miR-7238-3p, which targets the 3'-UTR of GPX4 to suppress expression. Overexpression of miR-7238-3p enhanced ferroptosis and cardiomyocyte damage.</p><p><strong>Conclusion: </strong>MI/RI downregulates lnc-ANRIL, relieving inhibition of miR-7238-3p and suppressing GPX4, thereby triggering ferroptosis in cardiomyocytes. Lnc-ANRIL protects against MI/RI-induced ferroptosis via the miR-7238-3p/GPX4 axis, suggesting a potential therapeutic target.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"59 6","pages":"903-917"},"PeriodicalIF":2.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888160","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":"The Effect of 6-Gingerol on Human AML Cell Lines.","authors":"Tingting Zhang, Chunfang Kong, Anna Li, Hongbo Cheng, Weirong Ding, Bo Ke, Chen Chen, Mei Wu","doi":"10.33594/000000838","DOIUrl":"https://doi.org/10.33594/000000838","url":null,"abstract":"<p><strong>Background/aims: </strong>Acute myeloid leukemia (AML) is a devastating hematological malignancy without a definitive cure. 6-Gingerol, a bioactive compound, has shown promise in treating various cancers, yet its impact on AML remains elusive.</p><p><strong>Methods: </strong>Cell growth and clonogenic capacity were assessed using CCK-8 testing and colony formation assays. Flow cytometry was employed to analyze cell cycle progression and apoptosis. The invasive capability of AML cells was evaluated through the Transwell migration assay. Fluorescent probe staining was used to determine intracellular reactive oxygen species (ROS) concentration, while Western blot was utilized to assess the expression levels of key proteins including Bcl-2, caspase3, MAPK, and p-MAPK in AML cells. Potential targets of 6-gingerol in AML were identified through bioinformatics databases (STP, SEA, STICH, OMIM GeneMap, GeneCards). GO and KEGG enrichment analysis was performed using clusterProfiler (v4.16.0).</p><p><strong>Results: </strong>6-Gingerol inhibited proliferation, colony formation, and invasive capacity of AML cells and induced G1 cell-cycle arrest. 6-Gingerol increased ROS and elevated caspase 3, MAPK, and p-MAPK levels. Sixty-seven overlapping targets between 6-gingerol and AML were identified and enriched in MAPK signaling and ROS-related pathways. NFKB1 emerged as a pivotal hub gene.</p><p><strong>Conclusion: </strong>6-Gingerol may represent a promising Traditional Chinese Medicine-derived agent for AML treatment.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"59 6","pages":"918-929"},"PeriodicalIF":2.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888195","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":"Advances in the Study of Bronchial and Vascular Architecture of Lungs in the Rat's Model: from Morphogenesis to Disease Modelling.","authors":"Aliyarbayova Aygun Aliyar, Aliyeva Sanam Eldar, Shukurova Ayten Sadig, Gasimova Tarana Mubariz, Mustafayeva Nigar Adil, Aliyeva Sabina Aydın","doi":"10.33594/000000834","DOIUrl":"10.33594/000000834","url":null,"abstract":"<p><p>Bronchial and vascular architecture in the rat lung forms an interdependent scaffold that balances ventilation with perfusion and adapts to metabolic demand. Development proceeds through coordinated branching programs that couple epithelial growth with vascular patterning while matrix remodeling and epithelial-mesenchymal crosstalk shape airway caliber and capillary alignment. Quantification has moved from classical design-based stereology to organ-scale µCT, optical clearing, and multiscale computational reconstructions that link structure to function. Across disease models, Chronic Obstructive Pulmonary Disease (COPD) and emphysema show distal airspace enlargement with vascular rarefaction, pulmonary hypertension (PH) features medial thickening and arteriolar muscularization, asthma combines epithelial remodeling with angiogenesis, and fibrosis exhibits collagen deposition with capillary regression. Convergent signaling networks integrate these changes, including VEGF and HIF pathways that govern angiogenesis, Notch and Wnt programs that regulate morphogenesis, and oxidative stress with cytokine and microRNA axes that drive vascular remodeling. Translational alignment is strengthened by single-cell and imaging biomarkers that map rat phenotypes to human pathology, while bioengineered platforms and in silico models provide controllable test beds for hypothesis testing. Predictive frameworks for remodeling across development and disease could be provided by standardized pipelines that combine morphometry, mechanics, and molecular profiles.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"59 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970600","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":"Conifer Essential Oils Modulate Oxidative Stress and Erythrocyte Stability in Human Blood in Vitro.","authors":"Halina Tkaczenko, Tomasz Wróblewski, Dzmitryi Ushakou, Paweł Mochalski, Lyudmyla Buyun, Natalia Kurhaluk","doi":"10.33594/000000835","DOIUrl":"https://doi.org/10.33594/000000835","url":null,"abstract":"<p><strong>Background/aims: </strong>Essential oils (EOs) derived from conifers of the Pinaceae family are complex bioactive mixtures known for their antioxidant and antimicrobial properties. However, their impact on human redox homeostasis, particularly in blood, remains poorly understood. This study aimed to compare the redox-modulating and membrane-stabilising effects of essential oils from Scots pine (PEO), European spruce (SEO), and European silver fir (FEO) using an in vitro human blood model.</p><p><strong>Methods: </strong>The chemical composition of each EO was characterised using gas chromatography-mass spectrometry (GC-MS), proton-transfer-reaction mass spectrometry (PTR-MS), and Fourier-transform infrared spectroscopy (FTIR). Human blood samples were incubated with different EO concentrations, and oxidative stress biomarkers, antioxidant enzyme activities, and erythrocyte membrane stability were evaluated.</p><p><strong>Results: </strong>All EOs exhibited terpene-rich profiles dominated by α-pinene, β-pinene, borneol, and bornyl acetate, with distinct species-specific differences. The oils displayed concentration-dependent biphasic redox effects. At moderate concentrations, PEO and SEO enhanced total antioxidant capacity and increased catalase and ceruloplasmin activities by 15-25% (p < 0.05). In contrast, higher doses-particularly of FEO-induced lipid peroxidation and protein oxidation by 40-60% (p < 0.05), indicating pro-oxidant behaviour. Erythrocyte haemolysis assays revealed that SEO exerted the strongest membrane-stabilising effect (haemolysis reduced by 18%), whereas FEO increased membrane fragility (haemolysis increased by 27%).</p><p><strong>Conclusion: </strong>Pinaceae-derived essential oils exhibit dual antioxidant and pro-oxidant activity dependent on concentration and species. Among them, PEO showed the most balanced redox profile. These findings highlight both the therapeutic potential and the importance of controlled dosing when considering such oils for biomedical applications.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"59 S2","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767303","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}