The goal of this work was to analyze the phenological and physiological responses of Brassica rupestris Raf. subsp. hispida Raimondo & Mazzola and Brassica rupestris Raf. subsp. rupestris to environmental factors ...The goal of this work was to analyze the phenological and physiological responses of Brassica rupestris Raf. subsp. hispida Raimondo & Mazzola and Brassica rupestris Raf. subsp. rupestris to environmental factors also in consideration of global change. We used seedlings of the two subspecies originated from wild plants from the natural habitats in Sicily and cultivated in the Botanical Garden of Rome. Leaf morphological and physiological traits and growth dynamic were analyzed as well as the response to an imposed water stress experiment. The results underlined a higher relative growth rate in plant height (RGRH, cm·cm-1·d-1) in B. rupestris subsp. rupestris also attested by the highest plant height (H, cm), leaf area (LA, cm2), specific leaf area (SLA, cm·g-1), total leaf area per plant (TLA, cm2) and total plant dry mass (PDM, g plant-1). Moreover, the significantly highest net photosynthetic rates (A, μmol CO2 m-2·s-1) during the study period of this subspecies was related to the high Chlorophyll content (Chl, SPAD units). B. rupestris subsp. rupestris was also the most tolerant subspecies to imposed water stress showing the highest relative water content (RWC, %), A and water use efficiency (WUE, μmol·mmol-1).展开更多
Lucetta,a cultivar of Eustoma grandiflorum( Raf.) Shinners,was subjected to treatments of different light intensities( 100%,85%,70% and 55% of natural light intensity) and different light durations( 10-h natural light...Lucetta,a cultivar of Eustoma grandiflorum( Raf.) Shinners,was subjected to treatments of different light intensities( 100%,85%,70% and 55% of natural light intensity) and different light durations( 10-h natural lighting,12-h natural lighting,12-h natural lighting+ 2-h LED lighting,12-h natural lighting + 4-h LED lighting),and then its plant height,crown width,stem thickness,stalk thickness,total flower number,flowering period and growth situation were analyzed. The results show that E. grandiflorum( Raf.) Shinners is sensitive to the changes in light intensity. Under 85% of natural light intensity( 40 000-50 000 lux),E. grandiflorum( Raf.) Shinners grew faster,bloomed earlier with more flowers,and was taller,thicker,more robust,higher in yield,larger in pedicel length,and better in cut flower quality,without rosette phenomenon. Long-term exposure to low-intensity light would led to slow growth,thin stalk,delayed flowering,low yield and reduced cut flower quality in E. grandiflorum( Raf.) Shinners. The illumination duration of more than 12 h could promote the differentiation of flower buds,increase the plant height,increase the length of pedicels of E. grandiflorum( Raf.) Shinners. Extending the light duration by 2-4 h at night,that is,14-16 h of illumination was the most ideal illumination time for the growth of E. grandiflorum( Raf.)Shinners. A longer photoperiod could promote the growth and bring forward the blooming of E. grandiflorum( Raf.) Shinners. The longer the illumination time,the higher the plant. The optimum illumination time was between 14 and 16 h. When the illumination duration was shorter than 12 h,the growth of E. grandiflorum( Raf.) Shinners was retarded,and its flowering was also delayed.展开更多
V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating ene...V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.展开更多
BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically...BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically associated with hypertrophic cardiomyopathy(HCM).However,in this case,the patient exhibited atrial and ventricular septal defects(VSDs).CASE SUMMARY This case report describes an 11-year-old boy diagnosed with Noonan syndrome,in whom genetic testing revealed a c.770C>T(p.Ser257 Leu)mutation in RAF1.The patient presented with intermittent chest discomfort and shortness of breath,symptoms that significantly worsened after physical activity.Clinical evaluation revealed marked growth retardation and multiple physical abnormalities.Electrocardiographic and echocardiographic assessments revealed VSDs,atrial septal defects,and left ventricular outflow tract obstruction.Following multidisciplinary consultation,the patient underwent cardiac surgical intervention,which led to clinical improvement;however,they subsequently developed a third-degree atrioventricular block,necessitating the implantation of a permanent pacemaker.During follow-up,echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa,significant improvement in left ventricular outflow tract obstruction,and notable reduction in ventricular septal thickness.A genetic mutation at the c.770C>T(p.Ser257 Leu)locus of RAF1 is typically associated with HCM and pulmonary hypertension.However,this patient’s clinical phenotype manifested as HCM,atrial septal defect,and VSD,suggesting that this mutation may involve a different pathophysiological mechanism.CONCLUSION This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of RAF1 mutation-associated cardiac pathologies.Early surgical intervention can ameliorate structural defects,but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.展开更多
Background:Glioma is the most common tumor of the central nervous system with a poor prognosis.This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ(CAMK2B)in regulating the malignant...Background:Glioma is the most common tumor of the central nervous system with a poor prognosis.This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ(CAMK2B)in regulating the malignant progression of glioma cells,as well as the molecular mechanisms underlying these malignant behaviors.Methods:The correlation between CAMK2B expression in gliomas and patient prognosis was analyzed using immunohistochemistry,quantitative reverse transcription polymerase chain reaction(qRT-PCR),and western blot.Furthermore,the study explored the role of CAMK2B in glioma cell proliferation,invasion,and migration using cell counting kit-8(CCK-8),5-Ethynyl-2′-deoxyuridine(EdU),wound healing,transwell,and in vivo tumor xenograft assays.Result:Patients with high CAMK2B expression exhibited significantly better prognostic outcomes compared to those with low expression levels.Furthermore,CAMK2B expression was significantly lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines.Notably,overexpression of CAMK2B in glioma cells led to an approximate 40%reduction in proliferative capacity and a 60–70%decrease in invasive and migratory abilities,compared to control glioma cells.These differences were statistically significant at p<0.05.Conversely,knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative,invasive,and migratory capabilities of glioma cells in both in vitro and in vivo settings,enhancing these abilities by 1.5 to 3 times.Notably,these effects were reversed through the application of the Rat Sarcoma viral oncogene homolog(Ras)pathway inhibitor,Salirasib.Western blot analysis revealed that knockdown of CAMK2B led to activation of the Ras/Rapidly Accelerated Fibrosarcoma(Raf)/Mitogen-activated protein kinase kinase(MEK)/Extracellular signal-regulated kinase(ERK)signaling pathway in glioma cell lines,whereas overexpression of CAMK2B resulted in the suppression of this pathway.Conclusion:CAMK2B inhibits glioma proliferation,invasion,andmigration through the Ras/Raf/MEK/ERK signaling pathway.展开更多
文摘The goal of this work was to analyze the phenological and physiological responses of Brassica rupestris Raf. subsp. hispida Raimondo & Mazzola and Brassica rupestris Raf. subsp. rupestris to environmental factors also in consideration of global change. We used seedlings of the two subspecies originated from wild plants from the natural habitats in Sicily and cultivated in the Botanical Garden of Rome. Leaf morphological and physiological traits and growth dynamic were analyzed as well as the response to an imposed water stress experiment. The results underlined a higher relative growth rate in plant height (RGRH, cm·cm-1·d-1) in B. rupestris subsp. rupestris also attested by the highest plant height (H, cm), leaf area (LA, cm2), specific leaf area (SLA, cm·g-1), total leaf area per plant (TLA, cm2) and total plant dry mass (PDM, g plant-1). Moreover, the significantly highest net photosynthetic rates (A, μmol CO2 m-2·s-1) during the study period of this subspecies was related to the high Chlorophyll content (Chl, SPAD units). B. rupestris subsp. rupestris was also the most tolerant subspecies to imposed water stress showing the highest relative water content (RWC, %), A and water use efficiency (WUE, μmol·mmol-1).
文摘Lucetta,a cultivar of Eustoma grandiflorum( Raf.) Shinners,was subjected to treatments of different light intensities( 100%,85%,70% and 55% of natural light intensity) and different light durations( 10-h natural lighting,12-h natural lighting,12-h natural lighting+ 2-h LED lighting,12-h natural lighting + 4-h LED lighting),and then its plant height,crown width,stem thickness,stalk thickness,total flower number,flowering period and growth situation were analyzed. The results show that E. grandiflorum( Raf.) Shinners is sensitive to the changes in light intensity. Under 85% of natural light intensity( 40 000-50 000 lux),E. grandiflorum( Raf.) Shinners grew faster,bloomed earlier with more flowers,and was taller,thicker,more robust,higher in yield,larger in pedicel length,and better in cut flower quality,without rosette phenomenon. Long-term exposure to low-intensity light would led to slow growth,thin stalk,delayed flowering,low yield and reduced cut flower quality in E. grandiflorum( Raf.) Shinners. The illumination duration of more than 12 h could promote the differentiation of flower buds,increase the plant height,increase the length of pedicels of E. grandiflorum( Raf.) Shinners. Extending the light duration by 2-4 h at night,that is,14-16 h of illumination was the most ideal illumination time for the growth of E. grandiflorum( Raf.)Shinners. A longer photoperiod could promote the growth and bring forward the blooming of E. grandiflorum( Raf.) Shinners. The longer the illumination time,the higher the plant. The optimum illumination time was between 14 and 16 h. When the illumination duration was shorter than 12 h,the growth of E. grandiflorum( Raf.) Shinners was retarded,and its flowering was also delayed.
基金support from various sources,including the National Natural Science Foundation of China(Grant Nos.81570774,82070872,92049118,and 82370854)the Junior Thousand Talents Program of China,and the Nanjing Medical University Startup Fund(All awarded to J.L.)support provided by Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(Grant No.JSSCTD2021)(All awarded to J.L.).
文摘V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.
基金Supported by the Gansu Provincial Science and Technology Plan Project,No.24JRRA886 and No.23JRRA1287Gansu Provincial People’s Hospital:Excellent Doctoral Student Cultivation Program,No.22GSSYD-14.
文摘BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically associated with hypertrophic cardiomyopathy(HCM).However,in this case,the patient exhibited atrial and ventricular septal defects(VSDs).CASE SUMMARY This case report describes an 11-year-old boy diagnosed with Noonan syndrome,in whom genetic testing revealed a c.770C>T(p.Ser257 Leu)mutation in RAF1.The patient presented with intermittent chest discomfort and shortness of breath,symptoms that significantly worsened after physical activity.Clinical evaluation revealed marked growth retardation and multiple physical abnormalities.Electrocardiographic and echocardiographic assessments revealed VSDs,atrial septal defects,and left ventricular outflow tract obstruction.Following multidisciplinary consultation,the patient underwent cardiac surgical intervention,which led to clinical improvement;however,they subsequently developed a third-degree atrioventricular block,necessitating the implantation of a permanent pacemaker.During follow-up,echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa,significant improvement in left ventricular outflow tract obstruction,and notable reduction in ventricular septal thickness.A genetic mutation at the c.770C>T(p.Ser257 Leu)locus of RAF1 is typically associated with HCM and pulmonary hypertension.However,this patient’s clinical phenotype manifested as HCM,atrial septal defect,and VSD,suggesting that this mutation may involve a different pathophysiological mechanism.CONCLUSION This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of RAF1 mutation-associated cardiac pathologies.Early surgical intervention can ameliorate structural defects,but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.
基金supported by the Natural Science Foundation of Hebei Province(H2021206037)the Government-funded Project on Training of Outstanding Clinical Medical Personnel of Hebei Province in the year 2021(303-16-20-06)the Medical Research Project of Hebei Provincial Health Commission(20230031).
文摘Background:Glioma is the most common tumor of the central nervous system with a poor prognosis.This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ(CAMK2B)in regulating the malignant progression of glioma cells,as well as the molecular mechanisms underlying these malignant behaviors.Methods:The correlation between CAMK2B expression in gliomas and patient prognosis was analyzed using immunohistochemistry,quantitative reverse transcription polymerase chain reaction(qRT-PCR),and western blot.Furthermore,the study explored the role of CAMK2B in glioma cell proliferation,invasion,and migration using cell counting kit-8(CCK-8),5-Ethynyl-2′-deoxyuridine(EdU),wound healing,transwell,and in vivo tumor xenograft assays.Result:Patients with high CAMK2B expression exhibited significantly better prognostic outcomes compared to those with low expression levels.Furthermore,CAMK2B expression was significantly lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines.Notably,overexpression of CAMK2B in glioma cells led to an approximate 40%reduction in proliferative capacity and a 60–70%decrease in invasive and migratory abilities,compared to control glioma cells.These differences were statistically significant at p<0.05.Conversely,knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative,invasive,and migratory capabilities of glioma cells in both in vitro and in vivo settings,enhancing these abilities by 1.5 to 3 times.Notably,these effects were reversed through the application of the Rat Sarcoma viral oncogene homolog(Ras)pathway inhibitor,Salirasib.Western blot analysis revealed that knockdown of CAMK2B led to activation of the Ras/Rapidly Accelerated Fibrosarcoma(Raf)/Mitogen-activated protein kinase kinase(MEK)/Extracellular signal-regulated kinase(ERK)signaling pathway in glioma cell lines,whereas overexpression of CAMK2B resulted in the suppression of this pathway.Conclusion:CAMK2B inhibits glioma proliferation,invasion,andmigration through the Ras/Raf/MEK/ERK signaling pathway.
