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In this paper we study a semiconductor laser system excited by multiplicative Ornstein-Uhlenbeck (OU) noise and additive sine-Wiener (SW) noise with a related real part and imaginary part. The two-dimensional Langevin equation (LE) with cross-correlating complex OU noise and complex SW noise is equivalent to the six-dimensional LE. Based on functional methods and spatial dimension extension methods, the six-dimensional Fokker-Planck equation (FPE) is achieved. Through Taylor expansion approximation and linear transformation, the dimensionality of FPE is reduced, and the exact expression of the probability distribution (SPD) in steady state is obtained. The impacts of noise parameters on laser intensity on SPD are further analyzed. Moreover, based on the reduced FPE, the information entropy of the system is obtained. This calculation is useful for us to understand further the influence of system parameters and noise correlation coefficient on the system. The main work lies in obtaining an alternative method for deriving a FPE corresponding to the two-dimensional stochastic semiconductor laser model, which is more applicable than methods in previous literature. An equivalent expression for cross-correlated OU noise and cross-correlated SW noise as well as a method for approximate solutions of a high-dimensional FPE are also provided.
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A diastereoselective 1,3-dipolar cycloaddition reaction between trifluoroethyl amine-derived isatin ketimines and chalcones was successfully achieved in the presence of DBU. A series of 5'-CF3-substituted 3,2'-pyrrolidinyl spirooxindoles were efficiently synthesized with high yields and excellent diastereoselectivities (up to 89% yield, and >99 : 1 dr). The in vitro anticancer activities of these highly functionalized spiro[pyrrolidin-3,2'-oxindole] derivatives were evaluated.
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BACKGROUND: Primary hepatic Burkitt lymphoma (PHBL) in children is an extremely rare hepatic malignancy with a dismal prognosis, unless it is detected and treated promptly. An 11-year-old child with abdominal pain was admitted to our hospital. No notable abnormalities were found during his physical examination or laboratory workup, but the abdominal computed tomography and magnetic resonance imaging both indicated a malignant hepatic mass measuring 9.2 × 7.1 × 7.5 cm in size. His postoperative pathology revealed an unexpected primary hepatic Burkitt lymphoma following a laparoscopic liver lobectomy. He then received rituximab and intense multi-agent chemotherapy as treatment. Despite post-chemotherapy bone marrow suppression, the patient eventually made a full recovery and had a good overall state. CONCLUSION: In this study, we describe a rare case of pediatric primary hepatic Burkitt lymphoma and review the literature on clinical features, diagnosis, and treatment for primary hepatic Burkitt lymphoma in children. We stress that this diagnosis should be taken into account in the absence of other single hepatic lesions or primary tumors of hematological disorders, particularly when there is a normal AFP level.
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Linfoma de Burkitt , Masculino , Humanos , Niño , Linfoma de Burkitt/cirugía , Linfoma de Burkitt/diagnóstico , Pronóstico , Dolor Abdominal , Rituximab/uso terapéutico , Abdomen/patologíaRESUMEN
PURPOSE: Thymectomy is an important treatment for myasthenia gravis (MG). We conducted this study to compare the clinical outcomes of the recently introduced subxiphoid and subcostal arch thymectomy (SASAT) approach with those of the standard unilateral video-assisted thoracoscopic surgery (VATS). METHODS: We analyzed, retrospectively, the perioperative, and long-term outcomes of 179 consecutive MG patients (age 18-65 years), who underwent SASAT or unilateral VATS-extended thymectomy between July, 2012 and May, 2019. RESULTS: All demographic and clinical characteristics were comparable in the two groups. The median surgical time, estimated blood loss, thoracotomy conversion rate, total and chest drainage, and complications did not differ significantly between the groups. The visual analog scale (VAS) score was significantly lower in the SASAT group. Complete stable remission (CSR) was achieved in a significantly larger proportion of the SASAT group patients and was significantly higher in women than in men. The Quantitative MG score was significantly lower in the SASAT group. Patients in the MG Foundation of America Clinical Classification groups I and II achieved better remission rates than those in groups III-V. CONCLUSIONS: SASAT is a safe and feasible MG treatment, which may yield better outcomes than unilateral VATS and improve the quality of treatment.
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Miastenia Gravis , Cirugía Torácica Asistida por Video , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Cirugía Torácica Asistida por Video/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Tiempo de Internación , Timectomía , Miastenia Gravis/cirugíaRESUMEN
"Candidatus Liberibacter asiaticus" (CLas) is a phloem-restricted α-proteobacterium that is associated with citrus huanglongbing (HLB), which is the most destructive disease that affects all varieties of citrus. Although midrib is usually used as a material for CLas detection, we recently found that the bacterium was enriched in fruits, especially in the fruit pith. However, no study has revealed the molecular basis of these two parts in responding to CLas infection. Therefore, we performed transcriptome and UHPLC-MS-based targeted and untargeted metabolomics analyses in order to organize the essential genes and metabolites that are involved. Transcriptome and metabolome characterized 4834 differentially expressed genes (DEGs) and 383 differentially accumulated metabolites (DAMs) between the two materials, wherein 179 DEGs and 44 DAMs were affected by HLB in both of the tissues, involving the pathways of phenylpropanoid biosynthesis, phytohormone signaling transduction, starch and sucrose metabolism, and photosynthesis. Notably, we discovered that the gene expression that is related to beta-glucosidase and endoglucanase was up-regulated in fruits. In addition, defense-related gene expression and metabolite accumulation were significantly down-regulated in infected fruits. Taken together, the decreased amount of jasmonic acid, coupled with the reduced accumulation of phenylpropanoid and the increased proliferation of indole-3-acetic acid, salicylic acid, and abscisic acid, compared to leaf midribs, may contribute largely to the enrichment of CLas in fruit piths, resulting in disorders of photosynthesis and starch and sucrose metabolism.
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Citrus , Rhizobiaceae , Citrus/metabolismo , Liberibacter/genética , Transcriptoma , Reguladores del Crecimiento de las Plantas/metabolismo , Rhizobiaceae/genética , Metaboloma , Sacarosa/metabolismo , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiologíaRESUMEN
Background: Paragangliomas are rare neuroendocrine tumors that could secret catecholamines. Hypertension and heart failure caused by the catecholamine crisis are fatal cardiovascular events. However, silent paragangliomas that lack typical symptoms of catecholamine pose a significant diagnostic challenge. Case summary: A 45-year-old woman who presented with more than 1-year history of abdominal discomfort was suspected of having a gastrointestinal stromal tumor by a local hospital since a vast metastatic mass occupied her left abdomen. Thus, she was recommended to our hospital. After completing the gastroscopy, she unexpectedly developed acute heart failure and was transferred to the Intensive Care Unit (ICU) where the initial diagnosis of paraganglioma was considered through path. However, a second catecholamine crisis due to constipation led to acute heart failure again. After anti-heart failure therapy and rigorous preoperative preparation, surgery was arranged to remove the tumor. Postoperative pathology conï¬rmed the paraganglioma, and the patient was discharged from the hospital in good condition. Conclusion: We reported a rare case of huge retro-peritoneal paraganglioma with successive catecholamine crises and acute heart failure. This was probably the largest retro-peritoneal paraganglioma since the 1980s. Besides, we were the first to use surgical drawing to illustrate its complex anatomical adjacent relationship of retro-peritoneal paraganglioma. Our case emphasizes the inclusion of extra-adrenal paraganglioma in the differential diagnosis of retroperitoneal tumors. In suspected paragangliomas, catecholamine testing is preferable to invasive procedures including gastroscopy and biopsy to avoid triggering a catecholamine crisis. Surgical resection is the primary treatment. We highlight the priority of dealing with the venous reflux branches of the tumor to prevent the release of catecholamines into the blood. In particular, preoperative preparation plays a vital role in managing paraganglioma. Moreover, it is necessary to schedule genetic testing and clinical follow-up due to the metastatic potential of paragangliomas.
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In the context of the global pandemic, the development of tourism in the Yellow River Basin is constrained by the dual mechanisms of the decline in the quality of public service and the deterioration of the ecological environment. In order to promote the high-quality development of the ecological environment in the Yellow River Basin, this paper studies the coordinated development of tourism, the ecological environment and public service in the Yellow River Basin by treating tourism, the ecological environment and public service as a whole. Based on the coupling coordination function GM (1,1) grey prediction method and PVAR model, we discuss the characteristics of spatio-temporal differences, evolutionary trends and the interaction mechanism of the coupling coordination degree (CCD) of tourism-ecological environment-public service in nine provinces along the Yellow River Basin in China from 2008 to 2019. The results show that tourism and public service in the Yellow River Basin are closely related, and the protection of the ecological environment and tourism development are not contradictory. In terms of time, the overall trend is stable and upward from the perspective of the CCD of the three systems; in terms of space, Henan, Shandong, and Sichuan provinces have a relatively high level of CCD. While Qinghai, Gansu, Ningxia, Inner Mongolia, Shaanxi and Shanxi provinces have a lower level of CCD, which shows an upward trend from upstream to downstream in the space. The evolutionary trend of the CCD of the three systems in the basin will be upward in all provinces except for the Shandong province in the next five years. Tourism can promote both the ecological environment and public service from the perspective of the mutual influence mechanism.
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Ríos , Turismo , Evolución Biológica , ChinaRESUMEN
The dual problems of the public crisis from the global epidemic and the deterioration of the ecological environment constrain the economic development in the Yellow River Basin. To promote the sustainable and balanced development in the Yellow River Basin, this paper takes public health, ecological environment, and economic development, as a whole, to study the coordinated development of the Yellow River Basin. Based on coupling coordinated theory, we use the SMI-P method to evaluate the coordinated development index of public health, the ecological environment, and economic development in the Yellow River Basin. Moreover, we use the coordinated regulation and obstacle factor diagnosis to identify the main influencing factors and design regulation methods to optimize the coordinated development index. The results found that (1), during the research period, there is spatiotemporal heterogeneity in the coordinated development level in the Yellow River Basin. From 2009 to 2019, the overall development index increased steadily, while the regional disparity in the coordinated development level was obvious. (2) The ecological environment indicators contribute more to the relevance and obstacle factors, such as the average concentration of fine particulate matter, per capita arable land area, afforestation area, etc. (3) After regulating the overall development level of the Yellow River Basin, we prove that Path 4, which comprehensively considers the relevance and obstacle factors, performs better.
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Salud Pública , Ríos , China , Desarrollo EconómicoRESUMEN
BACKGROUND AND OBJECTIVE: Myocardial infarction (MI) leads to pathological cardiac remodeling and heart failure. Sodium tanshinone IIA sulfonate (STS) shows to possess therapeutic potential. The present study aimed to explore the potential role of STS in ventricular remodeling post-MI. METHODS: Mice were randomly divided into sham, MI + normal saline (NS) and MI + STS (20.8 mg/kg/day intraperitoneally) groups. MI was established following left anterior descending artery ligation. Cardiac function was evaluated using echocardiography. Scar size and myocardial fibrosis-associated markers were detected using Masson's trichrome staining and western blot analysis (WB). Necrosis and inflammation were assessed using H&E staining, lactate dehydrogenase (LDH) detection, ELISA, immunohistochemical staining, and WB. Furthermore, angiogenesis markers and associated proteins were detected using immunohistochemical staining and WB. RESULTS: Mice treated with STS exhibited significant improvements in cardiac function, smaller scar size, and low expression levels of α-smooth muscle actin and collagen I and III at 28 days following surgery, compared with the NS-treated group. Moreover, treatment with STS reduced eosinophil necrosis, the infiltration of inflammatory cells, plasma levels of LDH, high mobility group protein B1, interleukin-1ß and tumor necrosis factor- α, and protein expression of these cytokines at 3 days. Macrophage infiltration was also decreased in the STS group in the early phase. Additionally, CD31+ vascular density, protein levels of hypoxia-inducible factor- 1α, and vascular endothelial growth factor were elevated in the STS-treated mice at 28 days. CONCLUSION: STS improved pathological remodeling post-MI, and the associated therapeutic effects may be a result of a decrease in myocardial necrosis, modulation of inflammation, and an increase in angiogenesis.
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Infarto del Miocardio , Remodelación Ventricular , Animales , Cicatriz/patología , Modelos Animales de Enfermedad , Humanos , Inflamación/metabolismo , Ratones , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Neovascularización Patológica/metabolismo , Fenantrenos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Purposes: To set up an easy-handled and precise delineation of resection plane for hepatic anatomical resection (AR). Methods: Cases of AR using ultrasonography-guided needle insertion to trace the target hepatic vein for delineation of resection planes [new technique (NT) group, n = 22] were retrospectively compared with those without implementation of this surgical technique [traditional technique (TT) group, n = 29] in terms of perioperative courses and surgical outcomes. Results: The target hepatic vein was successfully exposed in all patients of the NT group, compared with a success rate of 79.3% in the TT group (P < 0.05). The average operation time and intraoperative blood loss were 280 ± 32â min and 550 ± 65â ml, respectively, in the NT group. No blood transfusion was required in either group. The postoperative morbidities (bile leakage and peritoneal effusion) were similar between groups. No mortality within 90 days was observed. Conclusions: Ultrasonography-guided needle insertion is a convenient, safe and efficient surgical approach to define a resection plane for conducting AR.
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BACKGROUND: Previous studies reported that there were associations between physical activity (PA), sedentary behavior (SB), triglycerides (TG) and depression. However, it is unclear whether there is an interaction and/or mediation effect of TG in the associations between PA, SB and depression. This study was to explore the effects of TG in the associations between PA, SB and depression, respectively. METHODS: Our study included 7,728 adults (aged ≥20 years) participating in the 2009-2018 National Health and Nutrition Examination Survey (NHANES), which was a nationally representative survey. With higher TG as a mediator, a four-way decomposition method was used to decompose the total effects of insufficient PA and prolonged SB on depression, respectively. RESULTS: There were statistically significant associations between moderate-to-vigorous recreational activity (MVRA), SB, TG and depression (all P < 0.05), respectively. With higher TG as a mediator, there were interaction and mediation effects in the association between SB and depression, and the excess relative risk (95% CI) of reference interaction effect (INTref) and the total mediation effect were 0.15(0.01,0.29) and 0.03(0.00,0.06), respectively. While insufficient MVRA attributed a proportion of 80.42% for the controlled direct effect (CDE) and 6.28% for total mediation effect. In addition, similar findings were observed in those with hypertension, overweight/obesity, dyslipidemia, and metabolic syndromes. LIMITATION: This was a cross-sectional study, and the ability to make causal inference was limited. CONCLUSION: The controlled direct effect of MVRA, the mediation of TG, and the interaction between SB and TG played the vital roles in increasing the risk of depression.
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Depresión , Conducta Sedentaria , Adulto , Estudios Transversales , Depresión/epidemiología , Ejercicio Físico , Humanos , Análisis de Mediación , Encuestas Nutricionales , TriglicéridosRESUMEN
AIMS: Sufficient physical activity (PA) and less sedentary behavior (SB) have antidepressant effects, however the amount of PA varies according to weight status in adults with diabetes. Given that depression is a common complication of diabetes, we aimed to quantify to what extent the effects of diabetes on the risk of depression were explained by SB or insufficient PA in adults with and without obesity. METHODS: Data were collected from the 2007-2016 National Health and Nutrition Examination Survey (NHANES), which included 22,304 participants aged 20â¯years or older. The mediation and interaction were evaluated by the four-way effect decomposition method. RESULTS: In individuals suffering from obesity, diabetes, SB, and insufficient moderate and vigorous intensity recreational activity were associated with an increased risk of depression. The increased relative risk of diabetes on depression could be decomposed into a reference interaction (96.78%), a mediated interaction (5.07%), and a pure indirect effect (2.48%), with insufficient moderate-intensity recreational activity as a potential mediator. SB attributed a proportion of 89.21% for the controlled direct effect and 3.64% for pure indirect effect. CONCLUSION: Adults with obesity and diabetes are encouraged to increase moderate-intensity recreational activity and reduce SB, which can greatly prevent the occurrence of depression.
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Depresión , Diabetes Mellitus , Conducta Sedentaria , Depresión/complicaciones , Depresión/epidemiología , Diabetes Mellitus/epidemiología , Ejercicio Físico , Humanos , Encuestas Nutricionales , Obesidad/complicaciones , Obesidad/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Objective@#To investigate the smartphone addiction among college students during the Coronavirus Disease 2019 (COVID-19) pandemic and its association with daily behaviors and mental health,and to provide reference for heath education and psychological counseling for college students.@*Methods@#An observational study using online quyestionnaire was conducted among 10 357 college students of two provincial medical schools in Guangdong and Shanxi Province from February 24th to March 4th in 2020. Participants were investigated on demographic information, smartphone addiction, daily routine, physical activity, weight status, anxiety, and other health information. Logistic regression with inverse probability treatment weighting (IPTW) based on propensity score was used to analyze the association between smartphone addiction with daily behavior and mental health.@*Results@#The prevalence of smartphone addiction was 59.42%. The prevalence of phone addiction was higher in postgraduates, senior undergraduates, students with non-medical major, students living in GuangDong and those without regular exercise habit before vacation(χ 2=47.91,17.78,42.75,138.58,P<0.05). With IPTW, there were significant associations between smartphone addiction and late bedtimes (OR=1.82, 95%CI=1.66-1.98) and wake-up times (OR=1.55, 95%CI=1.44-1.68), more sedentary behaviors (OR=1.21, 95%CI=1.12-1.31), less moderate to vigorous physical activity (OR=1.33, 95%CI=1.22-1.44), anxiety (OR=2.98, 95%CI=2.52-3.40), weight gain(OR=1.27,95%CI=1.17-1.37) and other detrimental daily behavior and feelings.@*Conclusion@#High prevalence of smartphone addiction has been observed during the COVID-19 pandemic, with impaired daily behavior and mental health.
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BACKGROUND: Negative effects of cardiovascular diseases (CVDs) on depression have been reported, but the relative contribution of physical activity (PA) and sedentary behavior (SB) to such effects remains unclear. Our objective was to precisely quantify the effects modified or mediated by PA and SB using the recently developed four-way effect decomposition. METHODS: Our analysis included 22,117 adults (aged≥20 years) participating in the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Depression was assessed by the Patient Health Questionnaire-9. Moderate recreational activity (MRA), moderate work activity (MWA), and walk or bicycle for transportation, were measured by the Global Physical Activity Questionnaire (GPAQ). A four-way decomposition was applied with PA and SB as mediator to decompose the total effects of CVDs on depression into four components: controlled direct effect (CDE), pure indirect effect (PIE), reference interaction (INTref), and mediated interaction effect (INTmed). RESULTS: There were statistically significant associations between CVDs, MRA, and depression, with the adjusted odds ratios (95% confidence intervals) of being 1.73 (1.42~2.30), 1.81 (1.42~2.30), respectively. With MRA as a mediator, there were interaction and mediation effects in the associations between CVDs and depression, and the proportions attributable of INTref, INTmed, and PIE were 94.08% (P<0.001), 3.92% (P = 0.007), and 1.68% (P = 0.006), respectively. Furthermore, the mediation effect was statistically significant in females rather than males. CONCLUSIONS: MRA strongly modified and mediated the effects of CVDs on depression, especially in females. Our results suggested that sufficient MRA (at least 150 min per week) was considered as requirement for preventing depression in CVDs patients in females.
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Enfermedades Cardiovasculares , Encuestas Nutricionales , Adulto , Enfermedades Cardiovasculares/epidemiología , Depresión/epidemiología , Ejercicio Físico , Femenino , Humanos , Masculino , Conducta SedentariaRESUMEN
BACKGROUND: Although varicocele is considered to be one of the leading causes of male infertility, the precise mechanism underlying how varicocele leads to male infertility is not completely understood. We found the lactate concentration on the varicocele side of the patients was decreased compare with peripheral venous blood. In the testicles, the lactate produced by the sertoli cells through the glycolysis pathway provides most of the energy needed for spermatogenesis, the reduction of lactate will affect spermatogenesis. The objective of this study was to investigate the mechanism of this abnormal energy metabolism phenomenon in varicocele. METHODS: In this study, we collected the testicular tissue from patients with varicocele, the glycolysis related proteins PHGDH was identified by iTRAQ proteomics technology. Experimental rat varicocele model was constructed according to our new clip technique, the mRNA and protein expression levels of PHGDH were examined with qRT-PCR and Western blotting. We constructed a sertoli cell of PHGDH down-regulation model, and then detected the glucose consumption, LDH activities and lactate production in the sertoli cells. Western blot was conducted to investigate the effects of PHGDH on the expression of phosphoserine phosphatase (PSPH) and Pyruvate kinase M2 (PKM2). Flow cytometry was used to detect the cell apoptosis and cell cycle in sertoli cells. RESULTS: The results showed that testicular protein PHGDH was down-regulated in patients with varicocele and in experimental rat varicocele model. Down-regulation of PHGDH in sertoli cells significantly decreased the glucose consumption, LDH activities and lactate production in the sertoli cells, indicating that the low expression of PHGDH ultimately led to a decrease in lactate production by affecting the glycolysis. The Western blot results showed that the down-regulation of PHGDH significantly reduced the expression of pathway protein PSPH and PKM2, leading to the reduction of lactate production. Moreover, PHGDH knockdown can promote apoptosis and inhibit cell cycle to affect cell growth. CONCLUSIONS: Overall, we conformed that varicocele lead to the decreasing of testis lactate production. Down-regulation of PHGDH in sertoli cells may mediate the process of abnormal glucose metabolism. Our study provide new insight into the mechanisms underlying metabolism-associated male infertility and suggests a novel therapeutic target for male infertility.
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Ácido Láctico/metabolismo , Fosfoglicerato-Deshidrogenasa/genética , Células de Sertoli/metabolismo , Varicocele/genética , Varicocele/metabolismo , Animales , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucólisis/efectos de los fármacos , Glucólisis/genética , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Infertilidad Masculina/patología , Masculino , Fosfoglicerato-Deshidrogenasa/antagonistas & inhibidores , Fosfoglicerato-Deshidrogenasa/metabolismo , ARN Interferente Pequeño/farmacología , Ratas , Ratas Sprague-Dawley , Células de Sertoli/efectos de los fármacos , Células de Sertoli/patología , Espermatogénesis/efectos de los fármacos , Espermatogénesis/genética , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Varicocele/patologíaRESUMEN
NB-3 (contactin-6) is a member of the contactin family and has a wide range of roles during central nervous system development and disease. Here, we found that NB-3 was simultaneously induced in the serotonergic raphespinal tract (sRST) axons and in the scar-forming cells after spinal cord injury (SCI). Regrowth of sRST axons was promoted in vivo by blocking NB-3 expression in either sRST axons or scar-forming cells when post-traumatic axons of the sRST tried to penetrate the glial scar. NB-3 deficiency promoted synapse reformation between sRST regenerative axons and motor neurons and enhanced the potential for electrical activity of muscle contraction and motor coordination. In vivo evidence also suggested that NB-3 induction in both sRST axons and scar-forming cells was required to mediate NB-3 signaling inhibition of sRST axon regeneration after SCI. Our findings suggest that NB-3 protein is a potential molecular target for future SCI treatments.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Regeneración Nerviosa/fisiología , Neuronas Serotoninérgicas/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Animales , Axones/metabolismo , Axones/patología , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Moléculas de Adhesión Celular Neuronal/genética , Modelos Animales de Enfermedad , Electromiografía , Técnicas de Silenciamiento del Gen , Ratones , Actividad Motora/fisiología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Vías Nerviosas/metabolismo , Vías Nerviosas/patología , Recuperación de la Función/fisiología , Neuronas Serotoninérgicas/patología , Médula Espinal/metabolismo , Médula Espinal/patología , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/patologíaRESUMEN
Little is known about the molecules mediating the cross-talk between post-traumatic axons and scar-forming cells after spinal cord injury. We found that a sustained NB-3 induction was simultaneously present in the terminations of post-traumatic corticospinal axons and scar-forming cells at the spinal lesion site, where they were in direct contact when axons tried to penetrate the glial scar. The regrowth of corticospinal axons was enhanced in vivo with NB-3 deficiency or interruption of NB-3 trans-homophilic interactions. Biochemical, in vitro and in vivo evidence demonstrated that NB-3 homophilically interacted in trans to initiate a growth inhibitory signal transduction from scar-forming cells to neurons by modulating mTOR activity via CHL1 and PTPσ. NB-3 deficiency promoted BMS scores, electrophysiological transmission, and synapse reformation between regenerative axons and neurons. Our findings demonstrate that NB-3 trans-homophilic interactions mediate the cross-talk between post-traumatic axons and scar-forming cells and impair the intrinsic growth ability of injured axons.
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Axones/fisiología , Moléculas de Adhesión Celular Neuronal/metabolismo , Comunicación Celular , Cicatriz/patología , Neuroglía/fisiología , Transducción de Señal , Traumatismos de la Médula Espinal/patología , Animales , Ratones , Ratones Noqueados , Modelos BiológicosRESUMEN
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Neural recognition molecule NB-3 is involved in neural development and synapse formation. However, its role in axon tract formation is unclear. In this study, we found that the temporal expression of NB-3 in the deep layers of the motor cortex in mice was coincident with the development of the corticospinal tract (CST). Clear NB-3 immunoreactivity in the CST trajectory strongly suggested that NB-3 was expressed specifically in projecting CST axons. By tracing CST axons in NB-3−/− mice at different developmental stages, we found that these axons were capable of projecting and forming a normal trajectory. However, the projection was greatly delayed in NB-3−/− mice compared with wild-type (WT) mice from the embryonic to postnatal stages, a period that is coincident with the completion of the CST projection in mice. Subsequently, although their projection was delayed, CST axons in NB-3−/− mice gradually completed a normal projection. By stage P21, the characteristics of CST projections in NB-3−/− mice were not statistically different from those in WT mice. In addition, we found that the branching of CST axons into spinal gray matter also was delayed in NB-3−/− mice. The CST innervation area in the spinal gray matter of NB-3−/− mice was greatly reduced in comparison with WT mice until P30 and gradually became normal by P45. These data suggest that NB-3 is involved in the normal projection and terminal branching of developing CST axons.