Biochimie最新文献

{"title":"AhR signaling in joint homeostasis and disease.","authors":"Priyanka Brahmachary, Emelia A Keim, Seth T Walk, Meghan E McGee-Lawrence, Ronald K June","doi":"10.1016/j.biochi.2026.03.003","DOIUrl":"10.1016/j.biochi.2026.03.003","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that integrates environmental, microbial, and metabolic signals to regulate gene expression across diverse tissues. Recent studies highlight AhR's role in skeletal homeostasis and joint biology, particularly through its interactions with microbiome-derived tryptophan metabolites and the Wnt/β-catenin signaling pathway. This review synthesizes current knowledge on AhR signaling mechanisms, including canonical and non-canonical pathways, and explores the impact of exogenous toxicants and microbiome-derived compounds and endogenous host metabolites that activate AhR. We discuss emerging evidence linking AhR activity to cartilage development, inflammation, and osteoarthritis progression, and highlight the utility of gnotobiotic mouse models in dissecting microbiome-AhR interactions. Finally, we examine the therapeutic potential of AhR modulation in joint disease, emphasizing its relevance as a pharmaceutical target for osteoarthritis and age-related musculoskeletal decline.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576911","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":"Ancestral origin of the CXCL17-GPR25 system traced to the lobe-finned fish Latimeria chalumnae.","authors":"Jie Yu, Juan-Juan Wang, Wen-Feng Hu, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo","doi":"10.1016/j.biochi.2026.03.011","DOIUrl":"10.1016/j.biochi.2026.03.011","url":null,"abstract":"<p><p>The roles of C-X-C motif chemokine ligand 17 (CXCL17) and its receptor, G protein-coupled receptor 25 (GPR25), in immune regulation are gaining recognition, but their evolutionary origins and phylogenetic distributions have yet to be determined. In this study, we identified a CXCL17 gene in the lobe-finned fish Latimeria chalumnae (coelacanth), a close living fish relative of tetrapods. This gene produces two alternatively spliced secretory proteins, designated Lc-CXCL17a and Lc-CXCL17b, which display limited sequence similarity to known CXCL17s from mammals or ray-finned fishes. Recombinant forms of Lc-CXCL17a and Lc-CXCL17b were generated via bacterial overexpression, purification, and enzymatic processing. Functional assays, including NanoLuc Binary Technology (NanoBiT)-based β-arrestin recruitment, NanoBiT-based ligand-receptor binding, and chemotaxis assays, demonstrated that both proteins tightly bound to and potently activated coelacanth GPR25 in a manner dependent on their C-terminal residues, because removal of these residues markedly diminished activities. These findings provide the first evidence that a functional CXCL17-GPR25 system exists in lobe-finned fishes, supporting the hypothesis that this ligand-receptor pair originated in ancient fishes and was transmitted to tetrapods through lobe-finned fish ancestors. This work broadens understanding of CXCL17 evolution and highlights the coelacanth as a valuable model for tracing conserved immune signaling pathways.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522936","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":"Inhibition of urease by urea/thiourea-derived heterocycles: IC₅₀ profiling and structure-activity relationship.","authors":"Ali Bağ, Orhan Uluçay","doi":"10.1016/j.biochi.2026.03.009","DOIUrl":"10.1016/j.biochi.2026.03.009","url":null,"abstract":"<p><p>The urease enzyme catalyzes the hydrolysis of urea and plays a critical role in both agricultural and clinical contexts, contributing to nitrogen loss from urea-based fertilizers and promoting the survival and virulence of urease-positive pathogens such as Helicobacter pylori. Therefore, urease inhibitors are considered valuable targets for environmental and therapeutic applications. In this study, the in vitro urease inhibition potentials of five-membered heterocyclic compounds derived from thiourea were investigated. A comparative evaluation was performed using thiourea as the standard inhibitor. Using the Weatherburn indophenol method, IC₅₀ values were calculated from concentration-dependent inhibition curves. The results revealed that all compounds exhibited significant inhibition at low micromolar levels. Specifically, 2-thiohydantoin (IC₅₀ = 2.47 μM) and hydantoin (IC₅₀ = 2.62 μM) were identified as the most potent inhibitors, while rhodanine (IC₅₀ = 3.46 μM) and creatinine (IC₅₀ = 3.63 μM) exhibited moderate effects. 2,4-thiazolidinedione (IC₅₀ = 3.77 μM) was found to be relatively weaker. Compared to the standard inhibitor thiourea (IC₅₀ = 3.67 μM), most of the tested compounds showed similar or higher activity. The results indicate that replacing the CO group with CS can enhance inhibitory activity. Structural differences were also found to play a decisive role in enzyme ligand interactions. This study demonstrates the potential of thiourea-derived heterocyclic scaffolds as effective urease inhibitors.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517547","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":"A single intra-articular injection of IDO-Gal3 shifts synovial fluid metabolic profiles for up to six weeks in male rats with knee instability.","authors":"Folly M Patterson, Carlos J Cruz, Brittany D Partain, Hope Welhaven, Estefania Urrego Hernández, Austen Breland, Jacob L Griffith, Arun Wanchoo, Jonathan O Cooper, Joshua F Yarrow, Ronald K June, Benjamin G Keselowsky, Gregory A Hudalla, Kyle D Allen","doi":"10.1016/j.biochi.2026.03.004","DOIUrl":"10.1016/j.biochi.2026.03.004","url":null,"abstract":"<p><p>Joint metabolism is a potential therapeutic target space for osteoarthritis. We have previously developed a fusion protein of indoleamine 2,3-dioxygenase and galectin-3 (IDO-Gal3) to shift tryptophan metabolism toward the kynurenine pathway in the joint. Here, we hypothesized intra-articular IDO-Gal3 would prevent osteoarthritis progression in male rats as assessed via measures of pain-like behavior, synovial fluid metabolite profile, and joint structure. Joint degeneration was induced by medial collateral ligament transection and full or partial transection of the medial meniscus. IDO-Gal3 was delivered by a single intra-articular injection 3-4 days later. In the first cohort of Sprague Dawley rats, medial tibial plateau cartilage area increased following IDO-Gal3 treatment compared to saline (vehicle) treatment at four weeks. Hind paw withdrawal threshold was increased compared to vehicle control for four weeks. In the second cohort of Lewis rats, synovial fluid metabolomic profiles measured by LC-MS were altered in IDO-Gal3-treated rats at one week and six weeks. At one week, tryptophan metabolism pathway was altered in IDO-Gal3-treated animals. Amino acid pathways involved in collagen turnover, such as arginine and proline, were downregulated at six weeks in injured rats treated with IDO-Gal3. Energy metabolism pathways followed a similar trend. There was no change in medial tibial plateau cartilage area or percent trabecular bone area at six weeks, nor were there differences in bone microstructure, likely related to the partial medial meniscus transection. In conclusion, a single intra-articular injection of IDO-Gal3 improved tactile sensitivity and resulted in short- and long-term shifts in synovial fluid metabolic profiles.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492295","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":"Aryl hydrocarbon receptor signaling in osteosarcopenia: an integrative framework for musculoskeletal aging.","authors":"Hassan Rammal, Alex M Noonan, Daniel Rivas, Dany S Sibai, Vincent Marcangeli, Gustavo Duque","doi":"10.1016/j.biochi.2026.02.016","DOIUrl":"10.1016/j.biochi.2026.02.016","url":null,"abstract":"<p><p>Aging is accompanied by a progressive decline in tissue integrity and functional capacity and is a major risk factor for chronic disease. Osteosarcopenia, defined as the concurrent loss of bone and skeletal muscle mass and function, is a major contributor to frailty, fractures, disability, and reduced quality of life in older adults. While musculoskeletal aging has traditionally been attributed to endocrine and mechanical factors, growing evidence highlights an important role for environmental, microbial, and dietary signals in influencing tissue homeostasis across the lifespan. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that integrates these diverse cues and has emerged as a critical regulator of musculoskeletal homeostasis. In this review, we examine the emerging role of AhR signaling in the regulation of bone and skeletal muscle biology and discuss how context-dependent AhR signaling contributes to key hallmarks of aging, including oxidative stress, mitochondrial dysfunction, chronic inflammation, altered tryptophan metabolism, and gut dysbiosis. We propose that sustained or dysregulated AhR activation provides a mechanistic link between aging-related systemic stressors and the development of osteosarcopenia, highlighting AhR signaling as a potential target for preserving musculoskeletal health during aging.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260321","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 Drosophila aryl hydrocarbon receptor ortholog, spineless, modulates survival and reproduction.","authors":"Shelton G Swint, Shengshuai Shan, Jessica M Hoffman","doi":"10.1016/j.biochi.2026.02.011","DOIUrl":"10.1016/j.biochi.2026.02.011","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a highly conserved, ligand-activated transcription factor in mammals involved in multiple physiological processes, including development, xenobiotic detoxification, and potentially aging, and some of the most potent activators of AhR are tryptophan metabolites. AhR manipulation across species has been shown to have conflicting results on aging phenotypes that are often tissue specific. To expand our understanding of AhR and aging, we studied AhR affects survival and reproduction in Drosophila melanogaster, whose genome contains an ortholog of AhR, spineless (ss). Our findings indicate that ss-deficient flies have a shorter lifespan than wildtype flies but interestingly exhibit reduced mortality until approximately 40 days of age. Similarly, ss-deficient flies are more stress resistant than wildtype at young ages, but this reverses in later age. Negative lifespan-shortening effects of tryptophan metabolites were mitigated in ss-deficient flies, suggesting that the effects of these metabolites are ss-reliant, similar to AhR in mammals. Overall, our preliminary work demonstrates an evolutionarily conserved role for AhR in the aging process and increases our knowledge of the role of AhR/ss on aging phenotypes.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198278","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":"High oral doses of vitamin B₁₂ in early pregnancy improve B₁₂ status of mother and child irrespective of subsequent supplementation a longitudinal study in B₁₂ insufficient Indian women supplemented with either milk, vitamin pills, or placebo.","authors":"Sadanand Naik, Sergey N Fedosov, Namita Mahalle, Sharwari Narawade, Ebba Nexo, Christian W Heegaard","doi":"10.1016/j.biochi.2026.01.014","DOIUrl":"10.1016/j.biochi.2026.01.014","url":null,"abstract":"<p><p>B₁₂ deficiency during pregnancy has been associated with shunted growth, neural tube defects, anemia, and neuro-cognitive disorders. The optimal prevention strategy remains to be found. Here we explore the effect of high doses of oral B₁₂ in early pregnancy followed by physiological doses of B₁₂ or placebo. The women (B₁₂ < 146 pmol/l) were recruited before week 17 and divided into three groups, all primed for 14 days with oral B₁₂ = 5 mg/day. Then onwards, the participants daily received 400 ml of milk (HO-B₁₂ = 1.6 μg; n = 31), B₁₂-pills (CN-B₁₂ = 1.6 μg; n = 32), or placebo (n = 13) until 4 months postpartum. Blood was drawn at baseline, ½ - 6 months after baseline; on the day of delivery (including cord blood); and at 4-month postpartum (child and mother). B₁₂ status was assessed by measuring plasma B₁₂, holotranscobalamin (holoTC), and homocysteine (Hcy). Birth parameters were recorded. Comparable changes were achieved following high dose administration of both B₁₂-forms. Plasma total B₁₂ and holoTC increased 2-3 and 6-10 times, respectively; while total Hcy decreased ≈2-fold. No clear difference was observed during and after interventions with milk, pills and placebo (including newborns). At the end of the study ⅞ of mothers and ⅔ of babies had adequate B₁₂ status despite its steady downward drift. Our study demonstrates the benefit of an early-stage supplementation to pregnant women with high oral B₁₂. A continuous low dose supplementation adds only minor advantages. The results may impact future strategies of ensuring a sufficient B₁₂ supply during pregnancy.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101250","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 aryl hydrocarbon receptor: A modulator of skeletal muscle health and aging.","authors":"Keon Wimberly, Terence E Ryan","doi":"10.1016/j.biochi.2025.12.012","DOIUrl":"10.1016/j.biochi.2025.12.012","url":null,"abstract":"<p><p>Skeletal muscle is fundamental to human health, serving as the primary effector of movement and a central regulator of systemic metabolism. Age-related declines in muscle mass and mitochondrial function contribute to frailty, metabolic dysfunction, and loss of independence in older adults. While these changes are often attributed to reduced physical activity, chronic inflammation, and impaired regenerative capacity, emerging evidence implicates environmental and metabolic sensing pathways in muscle degeneration. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor best known for mediating responses to environmental pollutants such as dioxins, has recently been recognized as a key regulator of endogenous metabolic and redox processes. AHR activation occurs not only through xenobiotic exposure but also via endogenous ligands derived from tryptophan metabolism-including kynurenine and indole derivatives-whose levels rise in aging, chronic kidney disease (CKD), and other pollutant exposures. Sustained AHR activation in skeletal muscle has been shown to impair mitochondrial oxidative phosphorylation, promote proteolysis, and disrupt neuromuscular junction integrity, linking AHR signaling to muscle pathology. Experimental studies in rodent models demonstrate that pharmacologic or genetic inhibition of AHR can preserve muscle mass, mitochondrial function, and regenerative capacity. This review summarizes the molecular biology of the AHR, its emerging roles in skeletal muscle physiology and pathology, and the growing experimental toolkit for interrogating its function. Understanding how AHR signaling integrates environmental, metabolic, and aging cues may reveal new therapeutic opportunities to preserve skeletal muscle health and physical function across the lifespan.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antiretroviral drug emtricitabine increases kynurenine: tryptophan ratio, aryl hydrocarbon receptor activation, and cellular senescence in female mice.","authors":"Alok Tripathi, Shabiha Sultana, Sagar Vyavahare, Jie Chen, Arindam Paul, Huidong Shi, Wenbo Zhi, Rafal Pacholczyk, Bharati Mendhe, Apeksha Anand, Anthony Carrillo, Jaeshia Lindsay, Dima W Alhamad, Husam Bensreti, Christopher L Yearwood, Dylan Taylor, Colby Gross, Maribeth Johnson, Eric J Belin de Chantemele, Mark W Hamrick, Meghan E McGee-Lawrence","doi":"10.1016/j.biochi.2025.12.009","DOIUrl":"10.1016/j.biochi.2025.12.009","url":null,"abstract":"<p><p>HIV-associated mortality has been reduced by antiretroviral therapies (ART), but prolonged ART usage by people living with HIV (PLWH) is associated with frailty and poor healthspan. Mechanisms driving this phenomenon are not fully known, but clinical and preclinical studies suggest that HIV and ART may drive aberrant activation of the aryl hydrocarbon receptor (AhR) by kynurenine (KYN), an endogenous metabolite of tryptophan. Therefore, we investigated whether the combination of an HIV-like phenotype (Tg26 mice) and treatment with ART (emtricitabine; FTC) in female mice alters skeletal muscle homeostasis in an AhR-dependent manner to promote premature muscle aging phenotypes. Short-term FTC treatment increased serum KYN:tryptophan ratio and activated AhR signaling in skeletal muscle of Tg26 mice, although the study duration was not sufficient to induce significant FTC-related functional decline. FTC, alone or in combination with other ART (tenofovir alafenamide and tenofovir disproxil fumarate), activated AhR and induced senescence of female myoblasts in a manner comparable to KYN. Sequencing-based studies revealed targets and pathways related to the impacts of an HIV phenotype and ART in female skeletal muscle, including Gnas (encoding Gsα protein, critical for muscle glucose metabolism), inflammatory pathways, and lipid metabolism. Our studies suggest that the combined presence of HIV viral proteins and exposure to ART induced activation of AhR-mediated signaling in female muscle, as well as widespread changes across the skeletal muscle transcriptome and methylation landscape that may contribute to development of muscle dysfunction. This suggests AhR may represent a novel target for addressing persistent disparities in healthspan for PLWH.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866702","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 uptake of ingested vitamin B12 and its total body balance: a mathematical model suggests the optimal supplementation strategy.","authors":"Sergey N Fedosov","doi":"10.1016/j.biochi.2025.12.002","DOIUrl":"10.1016/j.biochi.2025.12.002","url":null,"abstract":"<p><p>Impaired or insufficient uptake of vitamin B₁₂ causes neurological disorders, anemia, and various diffuse symptoms, all historically called pernicious anemia (PA). Maintenance of adequate B₁₂ body store (B) is important, but the recommended doses and duration of peroral B₁₂-supplementation are usually half-empirical. The current work suggests physiologically realistic algebraic equations to express the changes in B via the daily B₁₂-uptake. The data from literature were used to estimate the relevant parameters of the equations. The modeled values of B showed that the daily ingestion of B₁₂ = 3 × 2.0 μg maintains the steady state value of B = 1316/1858/2683 μg in healthy individuals with low/mean/high types of B₁₂-uptake. The \"classical\" PA-patients have a highly decreased intrinsic factor (falling from 30 μg of B₁₂-equivalents to below 0.2 μg), giving B = 47/81/123 μg for the low/mean/high B₁₂-uptakes and the aforementioned doses. Alignment of B with the combined index of B₁₂-status (cB12) in a heterogeneous cohort indicated that B > 1250 μg provides the safe B₁₂-status for >84 % of the subjects. The risk of PA is associated with B < 400 μg. Repletion of a low body store from B = 400 μg to ≈1250 μg would require a prolonged supplementation of healthy individuals with B₁₂-pills, if they receive 1 × 5 μg/day or 1 × 50 μg/day. These schemes are expected to raise B after the time intervals of (not possible)/2200/780 days or 2330/860/480 days, respectively. Only a pill with high B₁₂ = 5000 μg/day would raise B to 1250 μg in 24/16/10 days.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710466","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}