Pflugers Archiv : European journal of physiology最新文献

{"title":"The NFAT5 chronicles: a transcription factor's tale of hypoxia, pulmonary drama, and endothelial resilience to hypoxia.","authors":"Dörthe M Katschinski","doi":"10.1007/s00424-025-03080-w","DOIUrl":"https://doi.org/10.1007/s00424-025-03080-w","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736122","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":"Intracellular pH regulates the strength of the intrinsic inward rectification of Kir4.1/Kir5.1 channels.","authors":"Iván A Aréchiga-Figueroa, Leticia G Marmolejo-Murillo, Mayra Delgado-Ramírez, Rodrigo Zamora-Cárdenas, Eloy G Moreno-Galindo, Tania Ferrer, Ricardo A Navarro-Polanco, José A Sánchez-Chapula, Aldo A Rodríguez-Menchaca","doi":"10.1007/s00424-025-03079-3","DOIUrl":"https://doi.org/10.1007/s00424-025-03079-3","url":null,"abstract":"<p><p>Kir4.1/Kir5.1 channels play a crucial role in important physiological functions, notably in the kidneys and brain. A hallmark of these channels is the coexistence of two mechanisms of inward rectification: the classical \"extrinsic\" inward rectification induced by polyamines and Mg²⁺ blocking the pore, and a novel \"intrinsic\" voltage-dependent mechanism driven by K⁺ flux. Previous studies have shown that Kir4.1/Kir5.1 channels are modulated by the intracellular pH in the physiological range. Here, we investigated the influence of the intracellular pH on the extent of the intrinsic inward rectification of Kir4.1/Kir5.1 channels expressed in HEK-293 cells and recorded using the inside-out configuration of the patch-clamp technique. We found that mutations that are known to modulate the pH sensitivity of Kir4.1/Kir5.1 channels attenuated inward rectification. The combination of these mutations in the triple mutant channel Kir4.1(K67M)/Kir5.1(N161E-R230E) virtually abolished inward rectification at pH 7.4; however, this property was re-established at acidic pH values. Consistently, the strong inward rectification of wild-type Kir4.1/Kir5.1 channels was reduced by intracellular alkalinization and further enhanced by acidification. Altogether, these experiments indicate that the intracellular pH strongly regulates the strength of the intrinsic inward rectification. Furthermore, triple mutant channels retained the extrinsic mechanism of inward rectification at pH 7.4, as can be blocked by spermine, but lost the ability to respond to elevated levels of PIP_2, unlike wild-type channels. Interestingly, whole-cell recordings of wild-type and triple mutant channels imply that the mechanism of intrinsic inward rectification is an important contributor to the overall rectification of Kir4.1/Kir5.1 channels in basal conditions.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710810","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":"Intrinsic responses to hypoxia and hypercapnia of neurons in the cardiorespiratory center of the ventral medulla of newborn rats.","authors":"Hiroshi Onimaru, Yui Koyanagi, Kamon Iigaya, Keiko Ikeda, Masahiko Izumizaki","doi":"10.1007/s00424-025-03077-5","DOIUrl":"https://doi.org/10.1007/s00424-025-03077-5","url":null,"abstract":"<p><p>The rostral ventrolateral medulla (RVLM) includes a variety of neurons essential for cardiorespiratory control. Although some of these neurons are thought to be intrinsically sensitive to hypercapnia and/or hypoxia, relationships between types of neurons and responses to hypoxia and/or hypercapnia are not well understood. Tyrosine hydroxylase (TH) is one of the cell-type markers of the RVLM neurons. Here, we report effects of hypoxia and hypercapnia on TH-positive or -negative neurons in the RVLM of newborn rats. Brainstem-spinal cord preparations were isolated from 0-3-day-old Wistar rats and superfused with artificial cerebrospinal fluid equilibrated with 95% O₂ and 5% CO₂, pH 7.4 at 25-26 °C. Membrane potential responses to hypoxia (95% → 0% O₂) and/or hypercapnia (2% → 8% CO₂) were examined in the presence of tetrodotoxin (TTX) after identification of the firing pattern. We found that TH-positive C1 neurons in the RVLM were sensitive to hypoxia with membrane depolarization but less sensitive to hypercapnia. TH-negative neurons in the C1 area showed responses similar to those of C1 neurons. Moreover, C1 area neurons remained depolarized by hypoxia in the presence of TTX plus gliotransmitter blockers. In contrast, Phox2b-positive and TH-negative neurons in the parafacial respiratory group were intrinsically sensitive to CO₂ but not sensitive to hypoxia. Respiratory-related neurons (Phox2b and TH negative) showed a variable response to hypoxia: unchanging, depolarizing, or hyperpolarizing. Our findings suggest that C1 area neurons in the RVLM are intrinsically sensitive to hypoxia and belong to one of the elements constituting central hypoxic sensors.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693043","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":"Reproducibility of smooth muscle mechanical properties in consecutive stretch and activation protocols.","authors":"Simon Kiem, Stefan Papenkort, Mischa Borsdorf, Markus Böl, Tobias Siebert","doi":"10.1007/s00424-025-03075-7","DOIUrl":"https://doi.org/10.1007/s00424-025-03075-7","url":null,"abstract":"<p><p>Mechanical organ models are crucial for understanding organ function and clinical applications. These models rely on input data regarding smooth muscle properties, typically gathered from experiments involving stimulations at different muscle lengths. However, reproducibility of these experimental results is a major challenge due to rapid changes in active and passive smooth muscle properties during the measurement period. Usually, preconditioning of the tissue is employed to ensure reproducible behavior in subsequent experiments, but this process itself alters the tissue's mechanical properties. To address this issue, three protocols (P1, P2, P3) without preconditioning were developed and compared to preserve the initial mechanical properties of smooth muscle tissue. Each protocol included five repetitive experimental cycles with stimulations at a long muscle length, varying in the number of stimulations at a short muscle length (P1: 0, P2: 1, P3: 2 stimulations). Results showed that P2 and P3 successfully reproduced the initial active force at a long length over five cycles, but failed to maintain the initial passive forces. Conversely, P1 was most effective in maintaining constant passive forces over the cycles. These findings are supported by existing adaptation models. Active force changes are primarily due to the addition or removal of contractile units in the contractile apparatus, while passive force changes mainly result from actin polymerization induced by contractions, leading to cytoskeletal stiffening. This study introduces a new method for obtaining reproducible smooth muscle parameters, offering a foundation for future research to replicate the mechanical properties of smooth muscle tissue without preconditioning.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676925","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":"Microbiota, mitochondria, and epigenetics in health and disease: converging pathways to solve the puzzle.","authors":"Natalia Lucia Rukavina Mikusic, Paula Denise Prince, Marcelo Roberto Choi, Luiz Gustavo A Chuffa, Vinícius Augusto Simão, Claudia Castro, Walter Manucha, Isabel Quesada","doi":"10.1007/s00424-025-03072-w","DOIUrl":"https://doi.org/10.1007/s00424-025-03072-w","url":null,"abstract":"<p><p>Dysbiosis, which refers to an imbalance in the composition of the gut microbiome, has been associated with a range of metabolic disorders, including type 2 diabetes, obesity, and metabolic syndrome. Although the exact mechanisms connecting gut dysbiosis to these conditions are not fully understood, various lines of evidence strongly suggest a substantial role for the interaction between the gut microbiome, mitochondria, and epigenetics. Current studies suggest that the gut microbiome has the potential to affect mitochondrial function and biogenesis through the production of metabolites. A well-balanced microbiota plays a pivotal role in supporting normal mitochondrial and cellular functions by providing metabolites that are essential for mitochondrial bioenergetics and signaling pathways. Conversely, in the context of illnesses, an unbalanced microbiota can impact mitochondrial function, leading to increased aerobic glycolysis, reduced oxidative phosphorylation and fatty acid oxidation, alterations in mitochondrial membrane permeability, and heightened resistance to cellular apoptosis. Mitochondrial activity can also influence the composition and function of the gut microbiota. Because of the intricate interplay between nuclear and mitochondrial communication, the nuclear epigenome can regulate mitochondrial function, and conversely, mitochondria can produce metabolic signals that initiate epigenetic changes within the nucleus. Given the epigenetic modifications triggered by metabolic signals from mitochondria in response to stress or damage, targeting an imbalanced microbiota through interventions could offer a promising strategy to alleviate the epigenetic alterations arising from disrupted mitochondrial signaling.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670557","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":"Neuronal subtype-dependent kinetics of EPSCs induced by thalamocortical projections from the ventroposteromedial thalamic nucleus to the insular cortex in rats.","authors":"Yuko Koyanagi, Kiyofumi Yamamoto, Kouhei Kitano, Mie Kajiwara, Masayuki Kobayashi","doi":"10.1007/s00424-025-03074-8","DOIUrl":"https://doi.org/10.1007/s00424-025-03074-8","url":null,"abstract":"<p><p>Cerebrocortical neurons receive glutamatergic inputs via thalamocortical projections, and their activities are simultaneously controlled by GABAergic interneurons. Few studies have demonstrated the difference in the amplitude of evoked excitatory postsynaptic currents (EPSCs) via thalamocortical projections onto glutamatergic excitatory (ENs) and GABAergic inhibitory neurons (INs); the strength of excitation among neural subtypes varies among sensory cortices. The present study aimed to reveal the profile of thalamocortical inputs to ENs and inhibitory neurons in the insular cortex (IC) by evaluating the amplitude and latency of EPSCs evoked in the connection from the ventroposteromedial (VPM) thalamic nucleus to the IC. Whole-cell patch-clamp recordings were prepared from ENs, fast-spiking neurons (FSNs), and non-fast-spiking neurons (NFSNs) in the middle layers (layer 4 and adjacent layers) of the IC. Photostimulation-induced EPSCs (pEPSCs) were evoked via the selective activation of thalamocortical axons via optogenetics. All the neuronal subtypes received direct excitatory inputs from the VPM, and pEPSCs recorded from FSNs had the greatest amplitude and shortest latency compared with those recorded from ENs and NFSNs. Under current-clamp conditions, FSNs almost invariably exhibited action potentials responding to photostimulation, whereas ENs and NFSNs often showed the failure of action potential induction. In addition to excitatory inputs, some neurons exhibited pEPSCs followed by outward GABA_A receptor-mediated currents, which curtailed the pEPSC peak and aligned the timing of the action potential to photostimulation. These results suggested that FSNs play a role in the feedforward inhibition of EN activity in the upper layer of the IC. (244 words).</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630869","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":"Competing effects of activation history on force and cytosolic Ca²⁺ in intact single mice myofibers.","authors":"Alexander M Zero, Charles L Rice, Leonardo Nogueira","doi":"10.1007/s00424-024-03061-5","DOIUrl":"10.1007/s00424-024-03061-5","url":null,"abstract":"<p><p>The purpose was to investigate the changes in cytosolic Ca²⁺ and force output during post-tetanic potentiation (PTP) during pre-fatigue and during prolonged low-frequency force depression (PLFFD) following fatigue. Intact single myofibers from the flexor digitorum brevis of mice were electrically stimulated to record force (n = 8) and free cytosolic Ca²⁺ concentration ([Ca²⁺]_c) with FURA-2 (n = 6) at 32 °C. Initially, force and [Ca²⁺]_c were measured during brief (350 ms) trains of stimuli at 30, 50, 70, and 200 Hz at ~ 2 s intervals (Force-frequency protocol, FFP). Then, a conditioning stimulus (CS) of six 120 Hz stimuli, separated by ~ 3 s, was used to induce PTP, immediately followed by an FFP. Myofiber fatigue was produced by 150 Hz trains every 3 s until peak force decayed 70% of the initial. Thirty minutes after the fatigue, the CS was repeated to assess the effect of PTP on force and [Ca²⁺]_c during PLFFD. The CS in unfatigued myofibers induced PTP as the submaximal force was enhanced and accompanied by increased peak [Ca²⁺]_c with no change in myofilament Ca²⁺ sensitivity. After fatigue, PLFFD was due to lowered peak [Ca²⁺]_c. Inducing PTP during PLFFD enhanced submaximal force primarily through greater peak [Ca²⁺]_c, mitigating the submaximal force deficits. Despite the impaired force during PLFFD, myofibers remained sensitive to PTP, and this mitigated the submaximal force deficits through increased peak [Ca²⁺]_c without a change in myofilament Ca²⁺ sensitivity. Therefore, force adjustments of intact single myofibers due to activation history are principally accomplished by opposing adjustments in [Ca²⁺]_c.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"407-419"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910059","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":"Impact of the estrous cycle on brain monoamines and behavioral and respiratory responses to CO₂ in mice.","authors":"Beatriz Dominiquini-Moraes, Mariana Bernardes-Ribeiro, Luis Gustavo A Patrone, Elisa M Fonseca, Alana T Frias, Kaoma S Costa Silva, Roberta Araujo-Lopes, Raphael E Szawka, Kênia C Bícego, Hélio Zangrossi, Luciane H Gargaglioni","doi":"10.1007/s00424-024-03040-w","DOIUrl":"10.1007/s00424-024-03040-w","url":null,"abstract":"<p><p>The prevalence of panic disorder is two to four times higher in women compared to that in men, and hormonal changes during the menstrual cycle play a role in the occurrence of panic attacks. Here, we investigated the effect of the estrous cycle on the ventilatory and behavioral responses to CO₂ in mice. Female mice in proestrus, estrus, metestrus, or diestrus were exposed to 20% CO₂, and their escape behaviors, brain monoamines, and plasma levels of 17β-estradiol (E₂) and progesterone (P₄) were measured. Pulmonary ventilation (V̇_E), oxygen consumption (V̇O₂), and body core temperature (T_B) were also measured during normocapnia followed by CO₂. Females exposed to 20% CO₂ exhibited an escape behavior, but the estrous cycle did not affect this response. Females in all phases of the estrous cycle showed higher V̇_E and lower T_B during hypercapnia. In diestrus, there was an attenuation of CO₂-induced hyperventilation with no change in V̇O₂, whereas in estrus, this response was accompanied by a reduction in V̇O₂. Hypercapnia also increased the concentration of plasma P₄ and central DOPAC, the main dopamine metabolite, in all females. There was an estrous cycle effect on brainstem serotonin, with females in estrus showing a higher concentration than females in the metestrus and diestrus phases. Therefore, our data suggest that hypercapnia induces panic-related behaviors and ventilatory changes that lead to an increase in P₄ secretion in female mice, likely originating from the adrenals. The estrous cycle does not affect the behavioral response but interferes in the ventilatory and metabolic responses to CO₂ in mice.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"349-369"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731789","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":"Hyperosmolality activates polycystin-2 and TRPM4 in renal primary cilium.","authors":"Steven J Kleene","doi":"10.1007/s00424-024-03050-8","DOIUrl":"10.1007/s00424-024-03050-8","url":null,"abstract":"<p><p>Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating disease characterized by renal cysts. It arises from mutations in proteins expressed in part in the primary cilia of renal epithelial cells. One of these, polycystin-2 (PC2), is an ion-conducting channel. To date, ion channels in the cilium have only been characterized in standard normosmolar external solutions, but the osmolality of the renal filtrate bathing the cilia varies widely. Here I report that urine, which better represents the filtrate, activates a large cation-conducting current in the cilia. With defined external solutions, hyperosmolality through addition of urea, NaCl, or D-mannitol activates a similar current. Most but not all of this current is conducted through TRPM4 channels. It is greatly reduced by internal MgATP or 9-phenanthrol, which inhibit TRPM4, or by shRNA knockdown of TRPM4. However, part of the current activated by urea conducts Ca²⁺ through channels that remain to be identified. External hyperosmolality also greatly increases the activity of ciliary PC2 channels; this is the first physiological stimulus identified for these channels. Possibilities are discussed for the mechanisms of channel activation and the roles for these activities in regulatory volume increase and cystogenesis.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"479-494"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837744","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":"Combined exercise-induced modulation of Notch pathway and muscle quality in senescence-accelerated mice.","authors":"Ana P Pinto, Ângelo Augusto J Sarni, Maria Eduarda A Tavares, Alisson L da Rocha, Ruither O Gomes Carolino, Ivo V de Sousa Neto, Driele C Da Silva Ferreira, Vitor R Munoz, Giovana R Teixeira, Fernando M Simabuco, José R Pauli, Dennys E Cintra, Eduardo R Ropelle, Ellen C de Freitas, Adelino S R da Silva","doi":"10.1007/s00424-024-03048-2","DOIUrl":"10.1007/s00424-024-03048-2","url":null,"abstract":"<p><p>The Notch signaling pathway is crucial for skeletal muscle development, regeneration, inflammation, and aging. This study investigated the association between interleukin-10 (IL-10) and the Notch pathway in C2C12 cells, as well as explored the effects of combined endurance and resistance exercise on the Notch and autophagy pathways in the skeletal muscle of senescence-accelerated mouse-resistant 1 Sedentary (SAMR1 CT), SAMR1 exercised (SAMR1 EX), senescence-accelerated prone mouse 8 Sedentary (SAMP8 CT), and SAMP8 exercised (SAMP8 EX). C2C12 myoblasts were transfected with siIL-10. Histological analysis, reverse transcription-quantitative polymerase chain reaction, and immunoblotting were performed on the quadriceps and tibialis anterior muscles. A publicly available dataset was analyzed to assess the Notch pathway in older men. In summary, IL-10 knockdown in myoblasts reduced the Notch pathway gene and protein expression. In SAMP8 mice, combined exercise improved muscle fiber organization, enhanced balance and coordination, and increased Notch2 and Hes1 mRNA levels. NOTCH2 mRNA levels were also higher in older men compared to young subjects with similar physical activity levels. These findings suggest that combined physical exercise enhances muscle regeneration via the Notch pathway in aged muscle.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"393-405"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971896","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}