Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D ...Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D response element-binding protein （VDRE-BP）. hnRNPC acts a tetramer of hnRNPC1 （huC1） and hnRNPC2 （huC2）, and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25（OH）2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25（OH）2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a ＂self-cleaving＂ 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25（OH）2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.展开更多
Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is b...Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is believed to facilitate the transport of lipids,particularly cholesterol,from late endosomes/lysosomes to the Golgi apparatus,endoplasmic reticulum and plasma membrane.NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes.Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments,which results in lysosomal storage of a complex mixture of lipids,primarily cholesterol and glycosphingolipids.The NPC proteins regulate sterol homeostasis through production of LDL cholesterol-derived oxysterols.Oxysterols are endogenous ligands for the liver X receptors(LXRs),which can upregulate ATP binding cassette transporter A1(ABCA1) expression.ABCA1 may have antiatherogenic effects through the efflux of it-mediated cholesterol.Meanwhile,NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis.Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.展开更多
The authors report a new case of spine tuberculosis of C1-C2 occurred in a 58-year-old negative HIV patient that was responsible of inflammatory cervical pain with multidirectional stiffness and complicated by spastic...The authors report a new case of spine tuberculosis of C1-C2 occurred in a 58-year-old negative HIV patient that was responsible of inflammatory cervical pain with multidirectional stiffness and complicated by spastic quadriplegia. The diagnosis was made on the basis of presumptive elements, including cervical spinal CT scan, which showed atlan-to-axial subluxation (C1-C2) with destruction of the odontoid apophysis and lateral mass of the atlas and favorable evolution under specific antibiotic treatment with ethambutol, isoniazid, rifampicin, pyrazinamide and immobilization with brace cast, despite the absence of bacteriological and anatomo-pathological evidence of certainty. The evolution has been favorable, with the disappearance of cervical pain, progressive motor recovery and resumption of autonomy of walking.展开更多
Objective: The aim of this study is to evaluate clinical and radiological outcomes in subjects of atlantoaxial instability which were operated using C1 lateral mass and C2 pedicle screw (Harmes technique). Materials a...Objective: The aim of this study is to evaluate clinical and radiological outcomes in subjects of atlantoaxial instability which were operated using C1 lateral mass and C2 pedicle screw (Harmes technique). Materials and Methods: Twenty patients with atlantoaxial instability were scheduled at our clinic for atlantoaxial fusion using polyaxial C1 lateral mass and C2 pedicle screw between January 2008 and March 2014. Results: Trauma was the most common cause of atlantoaxial instability, seen in 18 (90%) patients. Modes of trauma were road traffic accident (75%) and falling (15%). Osteoarthritis was observed in 10% of cases. Patients were followed up with radiographs and clinical examinations. Satisfactory screw placement and reduction were achieved in all patients with the average union time of 3.5 months. There were no implant failures, nonunions, vertebral artery injuries or C2 nerve root injuries. Only, surgical site infections occur in 20% of cases that are improved with medical treatment. Conclusions: C1 lateral mass and C2 pedicle polyaxial screw fixation is an effective technique for the fusion of the atlantoaxial complex. It provides the highest fusion rates without any risk of vertebral injury.展开更多
Objective: Short historical description of the evolution of C1-C2 fixation methods, anatomical tricks and free hand fixation technique description. Method: five patients were operated on using free hand technique, X-r...Objective: Short historical description of the evolution of C1-C2 fixation methods, anatomical tricks and free hand fixation technique description. Method: five patients were operated on using free hand technique, X-rays were only used after the positioning of the patient in the ventral position with Mayfield and at the end before locking the lateral rods. Results: no complications documented, in all the cases CT scans revealed good screw position. Conclusion: Using these landmarks and with a good preoperative planning, it is easy for experienced surgeons to perform the technique in a free hand manner, that avoids X-ray exposure for the whole team and the patient. This technique is not recommended for common use, especially for surgeons with few experiences in this field.展开更多
A subsidiary role of electrochemical neutralization energy(ENE)stored in waste acid/base presents a sustainable and economically viable solution for the production of value-added chemicals and saving energy.Here we de...A subsidiary role of electrochemical neutralization energy(ENE)stored in waste acid/base presents a sustainable and economically viable solution for the production of value-added chemicals and saving energy.Here we demonstrate a pH-asymmetric electrolyzer with a bipolar membrane to realize sustainable and efficient electrocatalytic methane oxidation coupling with hydrogen production at a low energy cost.This approach affords a C1/molecule production rate of up to 2.6 mmol g_(NiO) ^(-1) h^(-1)with simultaneous H_(2) production at a potential as low as 1.4 V.Furthermore,the electrocatalyst achieves sustained catalysis at 1 mA for over 24 h with lower operation voltage by 700 mV under auxiliary ENE supply,which means the cell electricity manner would enable an energy elimination of 36.9%energy saving comparing with state-of-the-art electrolyzers.In situ Raman spectroscopy and density functional theory calculation reveal the catalytic mechanism of the important role of Ni^(III)–O∙–Ni^(III)–O–for the electrochemical methane oxidation(EOM).Meanwhile,the pH-asymmetric integrated cell with simulated and complex waste acid-base solutions showcases a lower voltage of 1.62 V at 1 mA applied current with the same catalysts.Additionally,the device demonstrates negligible degradation at 10 mA cm^(−2),suggesting high overall durability for EOM.Techno-economic evaluation is also conducted to present the energy-saving and profit advantages with less oxygen evolution reaction(OER)competition.This work opens a pathway for prospective applications for the production of commodity chemicals simultaneously in one electrolyzer,which can even turn waste acid and base into resources.展开更多
目的观察厄贝沙坦对脉压(PP)≥60 mm Hg(1 mm Hg=0．133 kPa)高血压患者的动脉弹性功能、反射波及PP的影响。方法选取符合入选条件的原发性高血压患者30例,男13例、女17例,平均年龄为(65．2±8．5)岁(51～83岁),随机分成治疗组和对...目的观察厄贝沙坦对脉压(PP)≥60 mm Hg(1 mm Hg=0．133 kPa)高血压患者的动脉弹性功能、反射波及PP的影响。方法选取符合入选条件的原发性高血压患者30例,男13例、女17例,平均年龄为(65．2±8．5)岁(51～83岁),随机分成治疗组和对照组,分别给予厄贝沙坦(150 mg/d)和安慰剂治疗3个月。结果与治疗前相比,对照组治疗后中心和肱动脉收缩压、舒张压及PP轻度下降,但差异无显著性(P＞0．05)；而治疗组显著下降(P＜0．05),治疗组的降幅均显著高于对照组(P值分别＜0．05和0．01)。治疗后,治疗组的反射波增强压(AP)和增强指数(A1)明显下降(P＜0．01),颈-股动脉脉搏波传导速度(CF-PWV)显著变慢(P＜0．01),降幅显著高于对照组；大、小动脉弹性功能指数(Cl、C_2)值均显著增加(P值分别＜0．05和0．01),增幅显著高于对照组。分别以C_1和CF-PWV变化为应变量,收缩压、舒张压降幅为自变量行多元线形回归分析,决定系数(R2)为0．486及0．384(P＜0．05)。结论厄贝沙坦可明显改善PP≥60mm Hg高血压患者的大、小动脉弹性,减弱外周波反射,缩小PP。展开更多
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 5R01AR037399the UCLA Vector Core (Emmanuelle Faure and Kip Hermann) for vector and viral preparations supported by JCCC/P30 CA016042 and CURE/P30 DK41301
文摘Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D response element-binding protein （VDRE-BP）. hnRNPC acts a tetramer of hnRNPC1 （huC1） and hnRNPC2 （huC2）, and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25（OH）2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25（OH）2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a ＂self-cleaving＂ 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25（OH）2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.
文摘Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is believed to facilitate the transport of lipids,particularly cholesterol,from late endosomes/lysosomes to the Golgi apparatus,endoplasmic reticulum and plasma membrane.NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes.Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments,which results in lysosomal storage of a complex mixture of lipids,primarily cholesterol and glycosphingolipids.The NPC proteins regulate sterol homeostasis through production of LDL cholesterol-derived oxysterols.Oxysterols are endogenous ligands for the liver X receptors(LXRs),which can upregulate ATP binding cassette transporter A1(ABCA1) expression.ABCA1 may have antiatherogenic effects through the efflux of it-mediated cholesterol.Meanwhile,NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis.Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.
文摘The authors report a new case of spine tuberculosis of C1-C2 occurred in a 58-year-old negative HIV patient that was responsible of inflammatory cervical pain with multidirectional stiffness and complicated by spastic quadriplegia. The diagnosis was made on the basis of presumptive elements, including cervical spinal CT scan, which showed atlan-to-axial subluxation (C1-C2) with destruction of the odontoid apophysis and lateral mass of the atlas and favorable evolution under specific antibiotic treatment with ethambutol, isoniazid, rifampicin, pyrazinamide and immobilization with brace cast, despite the absence of bacteriological and anatomo-pathological evidence of certainty. The evolution has been favorable, with the disappearance of cervical pain, progressive motor recovery and resumption of autonomy of walking.
文摘Objective: The aim of this study is to evaluate clinical and radiological outcomes in subjects of atlantoaxial instability which were operated using C1 lateral mass and C2 pedicle screw (Harmes technique). Materials and Methods: Twenty patients with atlantoaxial instability were scheduled at our clinic for atlantoaxial fusion using polyaxial C1 lateral mass and C2 pedicle screw between January 2008 and March 2014. Results: Trauma was the most common cause of atlantoaxial instability, seen in 18 (90%) patients. Modes of trauma were road traffic accident (75%) and falling (15%). Osteoarthritis was observed in 10% of cases. Patients were followed up with radiographs and clinical examinations. Satisfactory screw placement and reduction were achieved in all patients with the average union time of 3.5 months. There were no implant failures, nonunions, vertebral artery injuries or C2 nerve root injuries. Only, surgical site infections occur in 20% of cases that are improved with medical treatment. Conclusions: C1 lateral mass and C2 pedicle polyaxial screw fixation is an effective technique for the fusion of the atlantoaxial complex. It provides the highest fusion rates without any risk of vertebral injury.
文摘Objective: Short historical description of the evolution of C1-C2 fixation methods, anatomical tricks and free hand fixation technique description. Method: five patients were operated on using free hand technique, X-rays were only used after the positioning of the patient in the ventral position with Mayfield and at the end before locking the lateral rods. Results: no complications documented, in all the cases CT scans revealed good screw position. Conclusion: Using these landmarks and with a good preoperative planning, it is easy for experienced surgeons to perform the technique in a free hand manner, that avoids X-ray exposure for the whole team and the patient. This technique is not recommended for common use, especially for surgeons with few experiences in this field.
基金supported by the Shanghai Key Laboratory of Hydrogen Science&Center of Hydrogen Science of Shanghai Jiao Tong University and the Shanghai High-Level Oversea Talents Award.
文摘A subsidiary role of electrochemical neutralization energy(ENE)stored in waste acid/base presents a sustainable and economically viable solution for the production of value-added chemicals and saving energy.Here we demonstrate a pH-asymmetric electrolyzer with a bipolar membrane to realize sustainable and efficient electrocatalytic methane oxidation coupling with hydrogen production at a low energy cost.This approach affords a C1/molecule production rate of up to 2.6 mmol g_(NiO) ^(-1) h^(-1)with simultaneous H_(2) production at a potential as low as 1.4 V.Furthermore,the electrocatalyst achieves sustained catalysis at 1 mA for over 24 h with lower operation voltage by 700 mV under auxiliary ENE supply,which means the cell electricity manner would enable an energy elimination of 36.9%energy saving comparing with state-of-the-art electrolyzers.In situ Raman spectroscopy and density functional theory calculation reveal the catalytic mechanism of the important role of Ni^(III)–O∙–Ni^(III)–O–for the electrochemical methane oxidation(EOM).Meanwhile,the pH-asymmetric integrated cell with simulated and complex waste acid-base solutions showcases a lower voltage of 1.62 V at 1 mA applied current with the same catalysts.Additionally,the device demonstrates negligible degradation at 10 mA cm^(−2),suggesting high overall durability for EOM.Techno-economic evaluation is also conducted to present the energy-saving and profit advantages with less oxygen evolution reaction(OER)competition.This work opens a pathway for prospective applications for the production of commodity chemicals simultaneously in one electrolyzer,which can even turn waste acid and base into resources.
文摘目的观察厄贝沙坦对脉压(PP)≥60 mm Hg(1 mm Hg=0．133 kPa)高血压患者的动脉弹性功能、反射波及PP的影响。方法选取符合入选条件的原发性高血压患者30例,男13例、女17例,平均年龄为(65．2±8．5)岁(51～83岁),随机分成治疗组和对照组,分别给予厄贝沙坦(150 mg/d)和安慰剂治疗3个月。结果与治疗前相比,对照组治疗后中心和肱动脉收缩压、舒张压及PP轻度下降,但差异无显著性(P＞0．05)；而治疗组显著下降(P＜0．05),治疗组的降幅均显著高于对照组(P值分别＜0．05和0．01)。治疗后,治疗组的反射波增强压(AP)和增强指数(A1)明显下降(P＜0．01),颈-股动脉脉搏波传导速度(CF-PWV)显著变慢(P＜0．01),降幅显著高于对照组；大、小动脉弹性功能指数(Cl、C_2)值均显著增加(P值分别＜0．05和0．01),增幅显著高于对照组。分别以C_1和CF-PWV变化为应变量,收缩压、舒张压降幅为自变量行多元线形回归分析,决定系数(R2)为0．486及0．384(P＜0．05)。结论厄贝沙坦可明显改善PP≥60mm Hg高血压患者的大、小动脉弹性,减弱外周波反射,缩小PP。
