Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early d...Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.展开更多
Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance...Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance to insulin’stissue-acting effects, or a combination of both. Over the last 30 years, the globalprevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure isfound, this amount might climb to 430 million in the coming years. The major fact-ors of the disease’s deterioration include age, obesity, and a sedentary lifestyle.Finding new therapies to manage diabetes safely and effectively without jeopardizingpatient compliance has always been essential. Among the medicationsavailable to manage DM on this journey are glucagon-like peptide-1 agonists,thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targetingreceptors discovered more than 10 years ago. Despite the extensive preliminarystudies, a few clinical observations suggest this process is still in its early stages.The present review focuses on targets that contribute to insulin regulation andmay be employed as targets in treating diabetes since they may be more efficientand secure than current and traditional treatments.展开更多
A new type of x-ray lens composed of multi-square polycapillary slices(ASPXRL)used in focusing parallel x-ray beam was presented in this paper.Compared with conventional x-ray polycapillary lens,ASPXRL can provide sma...A new type of x-ray lens composed of multi-square polycapillary slices(ASPXRL)used in focusing parallel x-ray beam was presented in this paper.Compared with conventional x-ray polycapillary lens,ASPXRL can provide smaller and brighter focus.The effects of the manufacturing imperfections on focusing quality of ASPXRL were evaluated with the values of transmission efficiency and discussed.It is suggested that ASPXRL has application prospects as a condenser lens for x-ray microscopy and flux collectors for x-ray analytical instruments.展开更多
Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels t...Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor developnaent and chemosensitivity of lung adenocarcinoma （ADC）. Methods： We retrospectively investigated the expression and significance ofNEDD4-1, PTEN, and p-Akt proteins in 135 paired A DC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthemaore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- （4,5-dimethylthiazol-2-yl） -5-（3-carboxymethoxyphenyl） -2-（4-sulfophenyl）- 2H-tetrazoliunl method. The ability of migration and invasion ofA549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase （PI3K）/Akt activity, and its downstream target proteins. Results： NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression ofNEDD4-1 in ADC （78.5%, 106/135） was significantly much higher than that in adjacent normal lung tissue （ 13.3%, 29/135, P 〈 0.01）, and it was associated with lymph node metastasis, tumor-node-metastasis （TNM） stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC （60.7% vs. 100.0% in noncancerous specimens, P - 0.007）, and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues （71.1% 96/135） was much higher than that in adjacent lung epithelial cells （6.7%, 9/135, P 〈 0.01 ）. Kaplan-Meier and multivariate analysis demonstrated that expressions ofNEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins. Conclusions： NEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the P13K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.展开更多
文摘Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.
文摘Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance to insulin’stissue-acting effects, or a combination of both. Over the last 30 years, the globalprevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure isfound, this amount might climb to 430 million in the coming years. The major fact-ors of the disease’s deterioration include age, obesity, and a sedentary lifestyle.Finding new therapies to manage diabetes safely and effectively without jeopardizingpatient compliance has always been essential. Among the medicationsavailable to manage DM on this journey are glucagon-like peptide-1 agonists,thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targetingreceptors discovered more than 10 years ago. Despite the extensive preliminarystudies, a few clinical observations suggest this process is still in its early stages.The present review focuses on targets that contribute to insulin regulation andmay be employed as targets in treating diabetes since they may be more efficientand secure than current and traditional treatments.
基金supported by the National Natural Science Foundation of China(Grant No.11875087)。
文摘A new type of x-ray lens composed of multi-square polycapillary slices(ASPXRL)used in focusing parallel x-ray beam was presented in this paper.Compared with conventional x-ray polycapillary lens,ASPXRL can provide smaller and brighter focus.The effects of the manufacturing imperfections on focusing quality of ASPXRL were evaluated with the values of transmission efficiency and discussed.It is suggested that ASPXRL has application prospects as a condenser lens for x-ray microscopy and flux collectors for x-ray analytical instruments.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81402185）.
文摘Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor developnaent and chemosensitivity of lung adenocarcinoma （ADC）. Methods： We retrospectively investigated the expression and significance ofNEDD4-1, PTEN, and p-Akt proteins in 135 paired A DC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthemaore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- （4,5-dimethylthiazol-2-yl） -5-（3-carboxymethoxyphenyl） -2-（4-sulfophenyl）- 2H-tetrazoliunl method. The ability of migration and invasion ofA549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase （PI3K）/Akt activity, and its downstream target proteins. Results： NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression ofNEDD4-1 in ADC （78.5%, 106/135） was significantly much higher than that in adjacent normal lung tissue （ 13.3%, 29/135, P 〈 0.01）, and it was associated with lymph node metastasis, tumor-node-metastasis （TNM） stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC （60.7% vs. 100.0% in noncancerous specimens, P - 0.007）, and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues （71.1% 96/135） was much higher than that in adjacent lung epithelial cells （6.7%, 9/135, P 〈 0.01 ）. Kaplan-Meier and multivariate analysis demonstrated that expressions ofNEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins. Conclusions： NEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the P13K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.
