Pflugers Archiv : European journal of physiology最新文献

{"title":"NAPE-PLD: the healthy intersection of N-acylethanolamines and bile acids in physiology and diseases.","authors":"Gianpiero Garau, Lucia Chico, Maico Polzella, Francesco Fornai","doi":"10.1007/s00424-026-03203-x","DOIUrl":"10.1007/s00424-026-03203-x","url":null,"abstract":"<p><p>Linking the distinctive structural and functional properties of lipids belonging to different signaling classes is a frontier of physiology. The present minireview focuses on the endocannabinoidome phospholipase NAPE-PLD, which has bile acids (BAs) as structural cofactors at membrane interface and generates bioactive N-acylethanolamines (NAEs) that promote pleiotropic effects. NAPE-PLD is thus at the crossroads of both their physiological functions, an area of ongoing research. The wide internal channel of NAPE-PLD facilitates the transmembrane transport of pyridoxal 5'-phosphate (PLP) and can support the activity of PLP-dependent enzymes in mitochondria, peroxisome and other subcellular compartments. Recent insights demonstrate that drugs and agents that stabilize NAPE-PLD can control blood pressure, vascular resistance and cardiovascular morbidity in clinics, offering new perspectives on the interaction between NAEs and BAs in cardiometabolic and neurological disorders.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNAs in exercise: the hidden regulators of adaptation.","authors":"Qin Zhang, Zhouren Zhang, Cai Ren, Ping Xiang, Xinhua Li, Ru Ren, Lianting Feng, Jicheng Chen","doi":"10.1007/s00424-026-03204-w","DOIUrl":"10.1007/s00424-026-03204-w","url":null,"abstract":"<p><p>Regular physical activity elicits coordinated molecular adaptations across skeletal muscle, the cardiovascular system, metabolic organs and the brain, underpinning improvements in performance and cardiometabolic health. While classical signaling pathways such as AMPK-PGC‑1α, Ca²⁺/calcineurin, and mTORC1 have been extensively characterized, long non-coding RNAs (lncRNAs) have recently emerged as key regulators of exercise-induced remodeling. Here, we synthesize current evidence on lncRNAs as molecular mediators of exercise adaptations, drawing on mechanistic studies and systems-level transcriptomics. In skeletal muscle, the exercise-induced lncRNAs CYTOR and TUG1 modulate fast-twitch myogenesis, mitochondrial function and fiber-type specification. In the heart, CPhar, lncExACT1 and Mhrt779 discriminate physiological from pathological hypertrophy and encode antihypertrophic \"memory,\" whereas endothelial NEAT1 integrates aerobic training with m⁶A-modulated pyroptosis and atheroprotection. MALAT1 mediates neuroprotection after exercise preconditioning in ischemia/reperfusion models. Omics and network analyses reveal highly modality-, tissue- and cell-type-specific lncRNA programs during human training and across multiple organs. Emerging clinical data support circulating lncRNAs such as MALAT1 and HOTTIP as candidate biomarkers of vascular function and training adaptation. Collectively, lncRNAs constitute a hidden regulatory layer that shapes the quality, magnitude and persistence of exercise-induced adaptations. However, mechanistic evidence is currently limited to a small number of \"flagships\" lncRNAs, and non-muscle tissues and inter-organ communication remain underexplored. Priorities include functional validation of atlas-derived candidates, dissection of exerkine lncRNAs, and integration of lncRNA biology into precision exercise medicine.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid-sensing ion channels as sensors of brain metabolic state.","authors":"Jianyang Du, Qian Ge, Gyeongah Park","doi":"10.1007/s00424-026-03202-y","DOIUrl":"10.1007/s00424-026-03202-y","url":null,"abstract":"<p><p>Acid-sensing ion channels (ASICs) are widely recognized as proton (H⁺)-gated cation channels that respond to extracellular acidification associated with pathological states such as ischemia, inflammation, and epilepsy. However, an emerging body of evidence compels a broader conceptual reframing: ASICs function as dynamic sensors of metabolic state, integrating real-time signals of neural activity, including CO₂-derived H⁺, lactate, and nano-domain pH transients, to regulate neuronal excitability and intercellular communication. Here, we review the mechanisms by which activity-dependent pH shifts arise in the brain, how lactate potentiates ASIC gating through divalent-cation chelation and direct channel modulation, and how the tripartite neuron-astrocyte-vascular unit functions as a spatially organized pH-sensing system. We discuss how astrocytes simultaneously buffer extracellular pH and express ASICs, placing them at the center of a bidirectional metabolic feedback loop, and how ASICs in cerebrovascular cells may link neural metabolic load to vascular tone. Finally, we identify key open questions, including the spatial scale of physiologically relevant pH nano-domains, the role of ASIC tachyphylaxis as a \"use-history\" sensor, and whether ASIC-dependent metabolic signaling shapes circuit-level dynamics during sleep-wake transitions and high-demand cognitive states. This perspective reframes ASICs not merely as damage sensors but as constitutive physiological transducers of brain metabolic activity.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSLP impairs mucociliary transport by inhibiting JAK signaling in both central and peripheral airways.","authors":"Hatsumi Sugiyama, Tsutomu Tamada, Koji Murakami, Hidemi Aritake, Risako Shionoya, Mitsuhiro Yamada, Masayuki Nara, Itsuro Kazama, Takashi Nakahari, Hisatoshi Sugiura","doi":"10.1007/s00424-026-03201-z","DOIUrl":"10.1007/s00424-026-03201-z","url":null,"abstract":"<p><p>Mucociliary transport (MCT) is the dominant mechanical host defense system in human airways. Although the importance of the peripheral airway in the pathophysiology of bronchial asthma has recently attracted attention, the characteristics of MCT in the peripheral airway during asthma remain unclear. This study aimed to investigate MCT velocity in the central and peripheral airways and the effects of thymic stromal lymphopoietin (TSLP) on MCT. Central and peripheral airways were isolated from freshly obtained porcine airways immediately after slaughter. The airway specimens were mounted in a custom-built fluorescence microscopy-based measurement system. MCT velocity and ciliary beat frequency (CBF) were measured under the following conditions: without stimulation, in the presence of a low concentration of acetylcholine (ACh), and after stimulation TSLP, which reflects the pathophysiological condition of bronchial asthma. MCT velocity in the peripheral airways was slower than that in the central airways at less than one tenth (median: 75.40 μm/sec vs. 2.63 μm/sec). Under physiologically low ACh concentrations, MCT velocity was increased in the peripheral airway but not in the central airway. TSLP addition partially inhibited MCT velocity in both the central and peripheral airways by approximately two-thirds to one-half. TSLP also partially inhibited the CBF in both the central and peripheral airways from approximately two-thirds to one-third. Furthermore, TSLP receptor (TSLPR) expression was confirmed in airway tissues by immunohistochemical staining. The inhibitory effects of TSLP on MCT velocity were completely abolished by pre-incubation with a Janus kinase (JAK) inhibitor. In conclusion, TSLP has the potential to reduce MCT velocity, especially in the peripheral airways, by inhibiting TSLPR signaling pathways, resulting in impaired CBF. The characteristics of MCT differ between the central and peripheral airways. Importantly, TSLP-induced MCT impairment may aggravate mucus plug formation in the peripheral airways in patients with bronchial asthma.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The bile acid-sensive ion channel (BASIC) is expressed in pancreatic α-cells and involved in glucagon secretion.","authors":"Jingyu Yang, Stefan Gründer, Dominik Wiemuth","doi":"10.1007/s00424-026-03199-4","DOIUrl":"10.1007/s00424-026-03199-4","url":null,"abstract":"<p><p>Pancreatic α-cells play a key role in glucose homeostasis through glucagon secretion. Here, we discover that the bile acid-sensitive ion channel (BASIC), a Na⁺ channel of the DEG/ENaC family, has a hitherto unrecognized role in α-cell function. We found that BASIC is mainly expressed in glucagon-positive α-cells of mouse islets. Genetic ablation of BASIC in mice reduced α-cell number, glucagon expression, and glucagon serum levels. These dramatic changes were accompanied by disturbed expression of α-cell specific transcription factors. Our findings identify BASIC as a previously unknown regulator of α-cell physiology.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent and compartment-specific macrophage accumulation associates with glomerular injury in BTBR ob/ob mice.","authors":"Mariana Charleaux de Ponte, Victoria Mel Dussan Angulo, Leticia Barreto da Silva, Karina Thieme","doi":"10.1007/s00424-026-03195-8","DOIUrl":"10.1007/s00424-026-03195-8","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and represents a growing global health burden. One of its major complications is diabetic kidney disease (DKD), a progressive condition characterized by declining kidney function accompanied by structural alterations in tissue. Among the multiple pathways involved in DKD progression, inflammation has emerged as a key contributor. In parallel, increasing evidence suggests that biological sex influences disease progression; however, whether and how sex modulates inflammatory mechanisms driving DKD progression remains incompletely understood. In this study, we investigated the interplay between inflammation and biological sex in DKD using the BTBR ob/ob model, which closely recapitulates the human disease. Obese diabetic mice exhibited significant albuminuria regardless of sex; however, podocyte-associated proteins displayed sex-dependent molecular regulation. At the inflammatory level, no changes were detected in whole-kidney analyses based on the selected markers, but a compartment-specific response was observed, characterized by increased macrophage infiltration and upregulation of Ccl2 (MCP-1) gene expression in the glomerular compartment, especially in males. Additionally, the tubular compartment exhibited distinct sex- and metabolism-dependent inflammatory gene expression patterns. Together, these findings indicate that inflammation in this model is spatially compartmentalized and also differentially regulated according to sex. This integrated perspective may contribute to a better understanding of DKD progression and support the development of more precise and targeted therapeutic strategies.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Posttransplant urine ammonium-pH index levels and graft outcomes in kidney transplant recipients.","authors":"Marie B Nielsen, Nicoline V Krogstrup, Mads V Sørensen, Anders M Kristensen, Ina M Schiessl, Jens Leipziger, Henrik Birn, Peder Berg","doi":"10.1007/s00424-026-03198-5","DOIUrl":"10.1007/s00424-026-03198-5","url":null,"abstract":"<p><strong>Introduction: </strong>Functional assessment is essential to quantify kidney graft quality early after kidney transplantation. Kidney transplantation is inherently associated with ischemia-reperfusion-injury, a noxious insult for proximal tubule cells that may not be captured by glomerular function markers. The urine ammonium-pH index (uAPI) is a functional measure of the tubulointerstitial capacity for ammonium excretion. Here, we aimed to investigate the association between the uAPI and graft function in kidney transplant recipients.</p><p><strong>Methods: </strong>In this post-hoc observational analysis of the CONTEXT trial (NCT01395719), kidney transplant recipients with available urine samples were divided into an exploration cohort (n = 112) and a validation cohort (n = 88). The uAPI was assessed at baseline, 90 min after reperfusion, day 1, 2 and 3 posttransplant. Day 6 kidney graft biopsies were stained for VCAM1 as a marker of tubular injury. Outcomes were delayed graft function, estimated time to 50% reduction in plasma creatinine, and measured GFR on day 5 and 12 months posttransplant. Results were adjusted for age, sex, plasma creatinine and albuminuria.</p><p><strong>Results: </strong>In the exploration cohort, a higher uAPI on day 2 and day 3 was associated with lower VCAM1 expression (p < 0.001 and p = 0.002, respectively), lower risk of delayed graft function, and shorter estimated time to 50% reduction in plasma creatinine (p < 0.001). A higher uAPI on day 3 was associated with higher measured GFR on day 5 (p < 0.001) and at 12 months (p < 0.001) posttransplant. These findings were confirmed in the validation cohort and robust to adjustments. Associations between day 3 uAPI and long-term graft function were consistent in subgroup analyses, including in patients with vs. without delayed graft function. Inclusion of day 3 uAPI improved prediction of measured GFR > 60 at 12 months posttransplant.</p><p><strong>Conclusions: </strong>A higher uAPI likely informs about better tubulointerstitial function posttransplant and is associated with better early and 12-month kidney graft function.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards an integrative structural model of the fishnet slit diaphragm: Understanding its physiology through proteomics and structural insight.","authors":"Achilleas S Frangakis, Alexandra N Birtasu, Florian Grahammer","doi":"10.1007/s00424-026-03200-0","DOIUrl":"10.1007/s00424-026-03200-0","url":null,"abstract":"<p><p>The kidney slit diaphragm (SD) connects the foot processes of glomerular podocytes, anatomically forming the outermost part of the three-layered glomerular filtration barrier. The SD is a large molecular polymer that, together with the foot processes, covers the glomerular capillaries and has diverse functions. It establishes a strong yet flexible cell-cell contact between foot processes from neighboring podocytes and additionally acts as a dynamic signaling platform linking structural integrity with cellular responses. Understanding the physiology of the SD has been hampered by limited structural insights and a lack of precise knowledge of protein composition of its building blocks.The recent convergence of the proteomic analyses of the SD with atomically resolved structures and in situ cryo-electron tomography imaging have led to the fishnet SD. The fishnet SD is based on the high-resolution 3D cryo-electron tomographic images of native glomeruli that revealed an unexpected fishnet architecture, observed in mouse, fly and human. This breakthrough has provided a new and markedly different view of how we understand and analyze the SD. It provides important principles for understanding spatial self-organization, assembly, turnover, and force compensation and offers an important basis for functional investigations, including the elucidation of molecular mechanisms of clinically relevant diseases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Klotho revisited: tubular heterogeneity reshapes mineral metabolism, aging, and CKD.","authors":"Ganesh Pathare","doi":"10.1007/s00424-026-03197-6","DOIUrl":"10.1007/s00424-026-03197-6","url":null,"abstract":"<p><p>α-Klotho (hereafter Klotho) was discovered as an aging-suppressor protein whose function is intrinsically dependent on the kidney. Its shed ectodomain, soluble Klotho (sKlotho), is detectable in blood and urine. As an obligate co-receptor for endocrine fibroblast growth factor 23, Klotho operates at the intersection of mineral metabolism and chronic kidney disease (CKD). Within the kidney, Klotho expression is moderate in the proximal tubule but strongly enriched in the distal nephron, although the functional significance of this heterogeneity remains unclear. Recent findings from nephron segment-specific Klotho knockout mice reveal functional specialization of tubular Klotho along the nephron. According to the revised model, distal nephron Klotho regulates calcium reabsorption, bone remodeling, and urinary sKlotho levels. By contrast, proximal tubular Klotho regulates phosphate and vitamin D metabolism and is likely the principal source of circulating sKlotho; its loss recapitulates hyperphosphatemia, FGF23 resistance, and ageing-like phenotypes. This review re-evaluates the long-standing paradigm of renal Klotho biology in light of emerging evidence for functionally distinct proximal and distal nephron Klotho. Together, these insights place the kidney and its tubular Klotho heterogeneity at the center of mineral metabolism, aging and CKD.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological characterization of neuropeptide S-expressing neurons in the periLC: influence of the female estrous cycle on neuronal excitability in mice.","authors":"Nike Leah Laukamp, Kay Jüngling","doi":"10.1007/s00424-026-03192-x","DOIUrl":"10.1007/s00424-026-03192-x","url":null,"abstract":"<p><p>Neuropeptide S (NPS) signaling is critically involved in arousal, sleep-wake regulation, fear and anxiety, and related forms of learning and memory, yet comparatively little is known about whether intrinsic properties of identified NPS neurons differ between sexes or fluctuate across the female estrous cycle. Here, we performed whole-cell patch-clamp recordings from genetically identified NPS-eGFP neurons in acute horizontal brainstem slices containing the peri-locus coeruleus (periLC) region. We show that periLC NPS neurons can be subdivided into two electrophysiologically distinct classes based on their discharge patterns from hyperpolarized membrane potentials: a delayed-onset firing phenotype (type I) and a regular-spiking phenotype (type II). Pharmacological and voltage-clamp analyses indicate that differential contribution of a transient A-type potassium current (I_A), consistent with Kv4 channel function, is a key determinant of these firing phenotypes and provides a mechanism for gain control in type I neurons. Across male and female mice, we did not detect robust sex differences in the relative abundance of these neuronal classes or in overall excitability measures, suggesting that baseline intrinsic properties of periLC NPS neurons are broadly comparable between sexes. In contrast, estrous staging revealed a selective modulation of intrinsic discharge in females: during non-receptive stages (metestrus/diestrus), type I neurons exhibited higher spike output and increased instantaneous firing frequencies compared with receptive stages (proestrus/estrus), whereas type II neurons were comparatively stable across the cycle. These findings provide a cellular mechanism by which ovarian state may tune NPS neuron output and, consequently, the impact of NPS signaling on downstream circuits controlling arousal and stress-related behaviors.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}