Chemico-Biological Interactions最新文献

{"title":"Identification of mechanisms underlying ventilatory dysfunction in organophosphorus chemical warfare agent-exposed mice","authors":"Marilène Trancart ,&nbsp;Nicolas Taudon ,&nbsp;Mylène Penot ,&nbsp;Gwladys Meesemaecker ,&nbsp;Anne-Sophie Hanak ,&nbsp;André-Guilhem Calas","doi":"10.1016/j.cbi.2025.111713","DOIUrl":"10.1016/j.cbi.2025.111713","url":null,"abstract":"<div><div>Chemical warfare nerve agents (CWNA), such as VX, pose significant threats due to their profound impact on vital physiological systems. The primary concern is the risk of respiratory failure resulting from cholinergic dysregulation, a signaling pathway crucial for ventilatory function regulation. This study aims to elucidate the key mechanisms underlying the induction of respiratory failure in mice following sub-lethal VX exposure in order to optimize therapeutic management. We evaluated candidate compounds targeting cholinergic signaling pathways associated with the CWNA poisoning toxidrome or implicated in respiratory disorders with similar symptoms (e.g., asthma or opioid overdose). The efficacy of these compounds in preventing ventilatory abnormalities induced by subcutaneous exposure to 0.9 LD₅₀ of VX was assessed using dual-chamber plethysmography, and survival tests were conducted to confirm their therapeutic effectiveness. Among all the pathways evaluated, only the muscarinic pathway appeared to be involved, with atropine, a standard muscarinic receptor (mAChR) antagonist, which effectively preserved respiratory function by reducing VX-induced bronchoconstriction and preventing respiratory depression. Methylatropine, a peripheral mAChR antagonist that does not cross the blood-brain barrier (BBB), also limited bronchoconstriction but failed to prevent respiratory depression, suggesting that bronchoconstriction is not the primary determinant of this respiratory toxidrome. Surprisingly, tiotropium, a selective M3 mAChR antagonist that also does not cross the BBB, exhibited similar effects to those of atropine. Antagonizing muscarinic pathway overstimulation thus emerges as a key strategy for managing respiratory depression and improving survival outcomes in CWNA-poisoned individuals.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111713"},"PeriodicalIF":5.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitate-induced hepatic insulin resistance as an in vitro model for natural and synthetic drug screening: A scoping review of therapeutic candidates and mechanisms","authors":"Bruno Quintanilha Faria ,&nbsp;Patricia Sthefani Calixto ,&nbsp;Geraldo Picheth ,&nbsp;Luana Mota Ferreira ,&nbsp;F.G.M. Rego ,&nbsp;J.F.C. Guerra ,&nbsp;Marcel Henrique Marcondes Sari","doi":"10.1016/j.cbi.2025.111717","DOIUrl":"10.1016/j.cbi.2025.111717","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance (IR) and β-cell dysfunction, often exacerbated by excessive intake of saturated fatty acids, particularly palmitic acid (PA). As the most abundant saturated fatty acid in Western diets, PA contributes to metabolic dysregulation by inducing mitochondrial dysfunction, enhancing reactive oxygen species (ROS) generation, activating inflammatory pathways, and impairing insulin signaling in hepatocytes. Consequently, PA-induced hepatic IR has become a widely accepted <em>in vitro</em> model for investigating therapeutic strategies to restore insulin sensitivity. This scoping review aims to identify and summarize natural and synthetic compounds evaluated in this model, emphasizing mechanisms of action and highlighting research gaps. A total of 78 eligible studies were selected through a systematic search of PubMed, Scopus, and Web of Science. Most studies employed HepG2 cells and adopted co-incubation or post-treatment protocols to simulate preventive or therapeutic contexts. Natural compounds predominate, particularly polyphenols, flavonoids, alkaloids, and plant extracts. Reported mechanisms involved activation of insulin signaling pathways (phosphoinositide 3-kinase/protein kinase B [PI3K/Akt], adenosine monophosphate-activated protein kinase [AMPK]), attenuation of oxidative stress (reduced ROS and malondialdehyde [MDA], increased superoxide dismutase [SOD] and catalase [CAT]), inhibition of inflammatory mediators (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6], nuclear factor kappa B [NF-κB]), and regulation of apoptosis (caspase-3, Bcl-2-associated X protein/B-cell lymphoma 2 [BAX/Bcl-2]). Overall, this model provides a robust and translationally relevant platform for screening bioactive compounds targeting multiple pathological features of T2DM.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111717"},"PeriodicalIF":5.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The underexplored pulmonary toxicity of pyrrolizidine alkaloids: Emerging hazard from food contamination","authors":"Caibin Zhang ,&nbsp;Zijing Song ,&nbsp;Yuxuan Zhao ,&nbsp;Xiaokai Guo ,&nbsp;Tianyang Huang ,&nbsp;Yihang Guo ,&nbsp;Jiang Ma ,&nbsp;Chengliang Zhang ,&nbsp;Jihang Chen ,&nbsp;Yisheng He","doi":"10.1016/j.cbi.2025.111709","DOIUrl":"10.1016/j.cbi.2025.111709","url":null,"abstract":"<div><div>Pyrrolizidine alkaloids (PAs) are the most widespread plant-derived toxins globally. Humans are frequently exposed to PAs through ingestion of PA-contaminated food products, with chronic dietary exposure estimated at up to 48.4 ng/kg body weight/day, posing a significant global health threat. Aside from the well-documented hepatotoxicity, dietary exposure to PAs is strongly implicated in the development of pulmonary arterial hypertension (PAH), a serious and often fatal disease with limited treatment options. However, the underlying molecular mechanisms remain poorly defined. This review provided updated information of PA contamination in representative food and herbal products. For PAs’ characterized toxic effects on pulmonary vasculature, our review shifts previous focus from downstream pathological processes to the etiological role of dietary PA exposure in PAH development. The activation of pulmonary arterial endothelial cells (PAECs), together with vasoconstriction, inflammation, and vascular remodeling, is recognized as an early event in PAH pathogenesis. Subsequently, activated immune cells, platelets, and dysfunctional PAECs release a complex array of growth factors, inducing pulmonary vascular remodeling and PAH progression. By reviewing intoxication targets and molecular pathways, we propose potentially novel therapeutic targets for dietary PA-related PAH. Given the ubiquitous distribution in the global food chain and their underexplored link to cardiopulmonary disease, we also provide perspectives and outlooks of preventive strategies and targeted interventions.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111709"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comments on “Role of the interleukin-33 (IL-33)/suppressor of tumorigenicity 2 (ST2) signaling in superoxide anion-triggered inflammation and pain behavior in mice”","authors":"Ting Jin","doi":"10.1016/j.cbi.2025.111706","DOIUrl":"10.1016/j.cbi.2025.111706","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111706"},"PeriodicalIF":5.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artemisinin toxicity in HepG2 liver carcinoma cells is linked to protein network in host and molecular interactions with cellular drug targets","authors":"Eena Dodwani,&nbsp;Vishal Trivedi","doi":"10.1016/j.cbi.2025.111707","DOIUrl":"10.1016/j.cbi.2025.111707","url":null,"abstract":"<div><div>Artemisinin treatment at high concentration or prolonged period is exhibiting severe toxicity in liver, kidney and cardio toxicity. Artemisinin is killing HepG2 liver carcinoma cells with an IC₅₀ of 17.33 ± 2.64 μM and cells are showing distorted morphology with appearance of holes on the cell surface. The cells are leaky and releasing the marker enzymes into the culture supernatant. Surprisingly, Artemisinin is inhibiting cell migration potentials in a dose-dependent manner. Drug Bank and Swiss target prediction indicate that the drug molecule is interacting with 118 protein nodes recognizing different pharmacological sites on the molecule. Gene ontology enrichment analysis indicate presence of protein belonging to 266 biological processes, 68 cellular components and 90 molecular functions. KEGG analysis predicts off-target proteins to disrupt cell-cycle, apoptosis, autophagy and other biological pathways. The protein-protein interaction network comprises 104 nodes and 30 edges. Artemisinin is fitting into these proteins and Artermisnin-protein complex is stable under the molecular dynamic simulation. Cells treated with Artemisinin is exhibiting disturbance of cell-cycle, apoptosis following intrinsic pathway and modulation of cyclin D1, activation of MLKL, caspase-8, caspase-3 and degradation of PARP. Artemisinin is curing malaria but current study highlight the importance of off-target effects to understand the liver toxicity in patients.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111707"},"PeriodicalIF":5.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slow binding modulation of paraoxonase 1 activity with terbium ions","authors":"Janez Smerkolj ,&nbsp;Miha Bahun ,&nbsp;Nataša Poklar Ulrih ,&nbsp;Aljoša Bavec ,&nbsp;Miha Pavšič ,&nbsp;Marko Goličnik","doi":"10.1016/j.cbi.2025.111708","DOIUrl":"10.1016/j.cbi.2025.111708","url":null,"abstract":"<div><div>Paraoxonase 1 (PON1) is a metalloenzyme that requires calcium ions at both catalytic and structural binding sites to hydrolyze the substrates. The enzyme is efficiently inhibited by several metal ions, especially transition metals, which tend to bind non-specifically to oxygen, nitrogen, and sulfur ligands of amino acid residues on the PON1 surface. In contrast, several lanthanide ions can specifically replace isomorphous Ca²⁺ ions from many protein binding sites, making them among the most potent metal inhibitors of PON1. However, the exact kinetic effects of lanthanides on PON1 activity are not well understood. Therefore, we investigated the inhibitory effects of Tb³⁺ ions on recombinant PON1 (rePON1) to elucidate how Tb³⁺ binding modulates its enzymatic activity. Our results reveal that Tb³⁺ functions as a slow-binding, reversible inhibitor of rePON1's lactonase activity through a sequential, two-step mechanism involving both metal-binding sites.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111708"},"PeriodicalIF":5.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanodiamond mediated delivery of pyridinium oxime antidotes to central nervous system for potential treatment of exposure to nerve agents","authors":"Denys Bondar ,&nbsp;Olga Smirnova ,&nbsp;Nandish M. Nagappa ,&nbsp;Ivo Heinmaa ,&nbsp;Ondrej Soukup ,&nbsp;Tereza Kobrlova ,&nbsp;Jakub Opravil ,&nbsp;Martina Hrabinova ,&nbsp;Daniel Jun ,&nbsp;Pavel Starkov ,&nbsp;Pirjo Spuul ,&nbsp;Kamil Kuča ,&nbsp;Vadym N. Mochalin ,&nbsp;Yevgen Karpichev","doi":"10.1016/j.cbi.2025.111711","DOIUrl":"10.1016/j.cbi.2025.111711","url":null,"abstract":"<div><div>Currently available antidotes against toxic organophosphorus compounds suffer from poor permeability across the blood-brain barrier (BBB) and due to this, are limited in their ability to restore the inhibited acetylcholinesterase (AChE) in the central nervous system (CNS). We designed functionalized detonation nanodiamond nanocarrier platforms to transport quaternary oxime antidotes into CNS. We showed that the nanodiamonds with covalently attached 4-oximinopyridinium moiety, cross the layer of Madin-Darby Canine Kidney (MDCK) cells, the surrogate BBB model, and demonstrate a dose-independent reactivation <em>in vitro</em> towards human AChE inhibited by nerve agents GB and VX, and pesticide paraoxon. Confocal microscopy visualization of tight junctions and actin cytoskeleton in MDCK and Human Umbilical Vein Endothelial Cells (HUVEC) revealed temporary disruption of tight junctions at higher nanoparticle concentrations without compromising cell viability or cytoskeletal integrity. Although reactivation was modest, the nanodiamond platform showed promise for delivering quaternary oxime to the central nervous system (CNS) <em>in vitro</em>. The results reveal the potential of detonation nanodiamonds as a promising delivery platform for charged therapeutic agents to CNS aimed to enhance treatment outcomes in organophosphorus poisoning.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111711"},"PeriodicalIF":5.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Miconazole activates MAPK-driven oligodendrogenesis to promote myelin regeneration and neurological recovery after subarachnoid hemorrhage","authors":"Gao Mingjun,&nbsp;Xu Ruxiang,&nbsp;Liu Ping,&nbsp;Liu Lingtong,&nbsp;Hu Xiao,&nbsp;Wang Qi,&nbsp;Zou Jiangli,&nbsp;Yin Cheng","doi":"10.1016/j.cbi.2025.111712","DOIUrl":"10.1016/j.cbi.2025.111712","url":null,"abstract":"<div><div>Subarachnoid hemorrhage (SAH) induces multifaceted brain injuries, with white matter injury (WMI) exhibiting dual pathological features resembling traumatic brain injury and cerebral ischemia. Inflammatory responses triggered by SAH lead to extensive axonal and myelin disintegration in white matter, resulting in severe neurological dysfunction. Myelin regeneration post-injury primarily relies on promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). We observed significant alterations in myelin basic protein (MBP) levels in human SAH brain tissues, paralleled by reduced MBP expression in rat brains post-SAH. SAH rats exhibited marked neurological deficits compared to sham group, alongside disrupted myelin integrity. Dynamic changes in OPC and OL populations were identified post-SAH. Miconazole (MCZ), an antifungal medication approved by Food and Drug Administration (FDA), has previously demonstrated neurorestorative properties. Using the mitogen-activated protein kinase (MAPK) pathway inhibitor GSK1120212, it was observed that the MAPK pathway could be effectively reverted, thereby counteracting the effects induced by MCZ. Our findings reveal that MCZ restores MBP expression, enhances OPC-to-OL differentiation, and accelerates myelin regeneration by activating MAPK signaling pathway. This provides a novel therapeutic strategy for mitigating neurological deficits in SAH patients.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111712"},"PeriodicalIF":5.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Permanent modifications in human acetylcholinesterase by acetylthiocholine or acetylcholine modify the hydrolysis of neutral substrates: phenyl acetate and phenyl valerate as examples","authors":"Jorge Estévez,&nbsp;María Ainhoa Poveda,&nbsp;Paula Ruz,&nbsp;Carlos Ami Benalal,&nbsp;Guillermo Gordo,&nbsp;Carmen Estevan,&nbsp;Miguel Ángel Sogorb,&nbsp;Eugenio Vilanova","doi":"10.1016/j.cbi.2025.111710","DOIUrl":"10.1016/j.cbi.2025.111710","url":null,"abstract":"<div><div>Phenyl acetate (PA) and phenyl valerate (PV) are neutral substrates. PV is used to measure PVase activity of neuropathy target esterase (NTE), which is a key molecular event of organophosphorus-induced delayed neuropathy. However, the interaction of acetylthiocholine (AtCh) with the PVase activity of recombinant human acetylcholinesterase (rhAChE) is not competitive reversible inhibition at the same active site. PVase activity increases when thiocholine (tCh) is released at the active site in the presence of AtCh, after AtCh has been completely hydrolyzed. Kinetic behavior suggested that the potentiation effect is caused by thiocholine released at the active site, where AtCh could act as a Trojan horse. Similarly to AtCh, acetylcholine (ACh) interacts with PVase activity. In this study, we demonstrate that AtCh and ACh can also modify PAase activity. Robust kinetic studies of the interactions between the substrates PA and AtCh were performed. The kinetics did not fit classic competitive model between substrates. We demonstrate that the interaction of AtCh or ACh with the active site is permanent, suggesting covalent or noncovalent modifications to the active site. We conclude that products generated directly at the active site could significantly affect the hydrolysis of substrates in living organisms. These findings have important implications for the practical and biotechnological applications of recombinant and purified cholinesterases.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111710"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parasitic infestation biodilutes the summer bioaccumulation of short-chain chlorinated paraffins in endangered South Georgia icefish (Pseudochaenichthys georgianus) in the South Orkney Islands, Antarctic","authors":"Mujia He ,&nbsp;Guoping Zhu","doi":"10.1016/j.cbi.2025.111704","DOIUrl":"10.1016/j.cbi.2025.111704","url":null,"abstract":"<div><div>Short-chain chlorinated paraffins (SCCPs) are emerging persistent organic pollutants (POPs) that are of concern due to their persistence, bioaccumulation potential, and long-range transport capabilities. However, studies on SCCPs in Antarctic organisms have been extremely limited, particularly regarding the interaction between parasites and POPs, including SCCPs, and the bioaccumulation in Antarctic fish. In this study, SCCPs bioaccumulation in the endangered South Georgia icefish (<em>Pseudochaenichthys georgianus</em>) from the South Orkney Islands during austral summer and its interaction with parasite was investigated for the first time. The results revealed that the ∑SCCPs concentration by lipid weight (lw) in fish significantly decreased with increasing fish size. Furthermore, the ∑SCCPs concentration was significantly lower in parasite infested individuals (6.02 ± 7.75 μg/g lw) compared with non-infested individuals (15.27 ± 8.35 μg/g lw). In the muscle of <em>P. georgianus</em>, SCCPs congeners C10 differed significantly from the C11, C12 and C13, both in terms of SCCPs by dry weight (dw) and by lw. The concentration (by dw) of C13 was significantly higher in non-infested individuals than infested ones with concentrations (by lw) of C10 to C13 being significantly higher in non-infested individuals. In non-infested individuals, C10 differed significantly from C11, C12 and C13 (by dw and lw). In infested individuals, C10 (by dw) significantly differed from C11, C12 and C13, whereas, only C10 (by lw) significantly differed from C12 and C13. Additionally, Fulton's Condition Factor, the hepatosomatic index, and habitat depth influenced significantly the bioaccumulation of SCCPs in <em>P. georgianus</em>.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111704"},"PeriodicalIF":5.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}