Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with...Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.展开更多
Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as o...Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.展开更多
The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell...The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell type.In the cardiovascular system,Ca2+ is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction pathways.A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure in these systems to maintain normal Ca2+homeostasis has been linked to both heart failure and hypertension.This article focuses on the functions of PMCA,in particular isoform 4(PMCA4) ,in the heart and vasculature and the reported links between PMCAs and contractile function,cardiac hypertrophy,cardiac rhythm and sudden cardiac death,and blood pressure control and hypertension.It is becoming clear that this family of calcium extrusion pumps have essential roles in both cardiovascular health and disease.展开更多
气化是实现化学利用碳资源(尤其是煤)生产化学品和燃料的关键工艺。目前,全球拥有超过272套气化装置,主要应用于煤化工,尤其在中国。由于在一个化工厂通过技术集成达到工业规模的集中生产可实现减少二氧化碳排放并促进碳密集型行业的循...气化是实现化学利用碳资源(尤其是煤)生产化学品和燃料的关键工艺。目前,全球拥有超过272套气化装置,主要应用于煤化工,尤其在中国。由于在一个化工厂通过技术集成达到工业规模的集中生产可实现减少二氧化碳排放并促进碳密集型行业的循环经济,如废物管理、化学和交通行业,因此,近年来全球对垃圾气化的兴趣日益浓厚,尤其是那些在煤气化技术方面积累了丰富的人力资本和运营经验以及拥有完整Coal-to-X产品价值链的国家,如中国,在挖掘通过垃圾气化实现Waste-to-X的潜力方面处于独特的地位。具体而言,废弃物可用于补充煤气化生产如下产品:(1)具有较低或零碳足迹的化学品,具体取决于废物是来源于化石资源还是生物资源。(2)来自生物废弃物的零碳足迹的绿色“氢”,以补充或替代来自煤气化或蒸汽重整得到的“灰色”氢,以供给氢能汽车,并推动工业脱碳。(3)来自生物废弃物的CO_(2)中性合成液体燃料,用于交通工具,以补充或替代石油燃料和合成煤制液体燃料。然而,迄今为止,利用垃圾作为气化原料的操作经验有限,并且文献中也很少涉及以前和当前的工业垃圾气化经验。为了填补这些空白,本研究介绍了1980年代至2000年代德国的两项开创性技术发展—贝伦拉特(Berrenrath)和SVZ黑水泵(即Sekundärrohstoff-Verwertungszentrum:黑水泵二次原料回收中心),并分享了以下三种垃圾与煤共气化技术(即Waste&Coal-to-X)的相关认识和经验教训:固定床气化:鲁奇干法排渣技术以及BGL熔渣气化技术。流化床气化:高温温克勒(HTW-High Temperature Winkler)气化工艺。气流床气化:GSP(Gaskombinat Schwarze Pumpe),即西门子气化工艺。此外,本研究也总结了目前全球100%垃圾气化技术的发展,即Waste-to-X。在气化技术的三种类型中,研发领域和工业界均对流化床与气流床(作为后期气化)技术的结合产�展开更多
The severity of the hot and humid conditions to which miners are exposed increases as the depth of the work site increases.This can cause heat stress that can greatly affect the health and safety of workers.To resolve...The severity of the hot and humid conditions to which miners are exposed increases as the depth of the work site increases.This can cause heat stress that can greatly affect the health and safety of workers.To resolve this,a cooling garment has been developed that uses an atmospheric discharge of liquid CO2 to create a cool microclimate with an average temperature of 12.5(±0.4)℃ beneath the garment.To evaluate the garment's cooling efficiency,19 male subjects participated in an experimental procedure.The two modes,cooling on and off,were compared.Significant physiological differences were found between the two modes after minute 27(p<0.05)until the end of the recovery phase for the heart rate(maximum difference of 10 beats per minute)and the internal body temperature(maximum difference of 0.33℃).It was found that the modes also affected the subjects'perceptions.The ON-mode was associated with better well-being and thermal comfort,and reduced humidity sensation.Perceptions of exertion were lower in the ON-mode condition from minute 2.The findings provide strong evidence of the ability of this cooling garment to reduce heat stress in hot and humid conditions similar to those encountered in deep mines.展开更多
Ghrelin causes interdigestive contractions of the stom- ach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted ...Ghrelin causes interdigestive contractions of the stom- ach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted on the antrum, duodenum, proximal and distal jejunum. After an overnight fast, gastrointestinal (GI) contrac- tions were recorded in freely moving conscious rats. Spontaneous phase m-like contractions were observed at every 13-16 min in rat GI tract. The fasted motor patterns were replaced by the fed motor pattern imme- diately after food intake. Two minutes after finishing the spontaneous phase Ill-like contractions in the antrum, acyl ghrelin (0.8, 2.4 and 8.0 μg/kg per min) was con- tinuously infused for 30 min. Three-five minutes after the starting ghrelin infusion, augmented phase Ⅲ-like contractions were observed at the antrum, duodenum, and jejunum. Ghrelin infusion (0.8, 2.4 and 8.0μg/kg per min) significantly increased motility index of phase Ⅲ-like contractions at the antrum and jejunum in a dose dependent manner, compared to that of saline in- jection. Thus, it is likely that exogenously administered ghrelin causes phase Ⅲ-like contraction at the antrum, which migrates to the duodenum and jejunum. The possible role of 5-HT, in addition to ghrelin, in mediating intestinal migrating motor complex (MMC), is discussed.展开更多
Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be ...Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are展开更多
Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared t...Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P 〈 0.05), including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P - 2.3 × 10 -5). We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.展开更多
Rapid technological improvements in biomaterials,computer-aided design(CAD)and manufacturing(CAM)have endorsed clear aligner therapy(CAT)as a mainstay of orthodontic treatment,and the materials employed for aligner fa...Rapid technological improvements in biomaterials,computer-aided design(CAD)and manufacturing(CAM)have endorsed clear aligner therapy(CAT)as a mainstay of orthodontic treatment,and the materials employed for aligner fabrication play an all-important role in determining the clinical performance of clear aligners.This narrative review has attempted to comprehensively encompass the entire gamut of materials currently used for the fabrication of clear aligners and elucidate their characteristics that are crucial in determining their performance in an oral environment.Historical developments and current protocols in aligner fabrication,features of contemporary bioactive materials,and emerging trends related to CAT are discussed.Advances in aligner material chemistry and engineering possess the potential to bring about radical transformations in the therapeutic applications of CAT;in the absence of which,clear aligners would continue to underperform clinically,due to their inherent biomechanical constraints.Finally,while innovations in aligner materials such as shape memory polymers,direct three-dimensional(3D)printed clear aligners and bioactive materials combined with clear aligner materials are essential to further advance the applications of CAT;increased awareness of environmental responsibilities among aligner manufacturers,aligner prescribing clinicians and aligner users is essential for better alignment of our climate change goals towards a sustainable planet.展开更多
Workers exposed to hot and humid conditions suffer from heat stress that affects their concentration and can potentially lead to an increase in workplace accidents. To minimize heat stress, protective equipment may be...Workers exposed to hot and humid conditions suffer from heat stress that affects their concentration and can potentially lead to an increase in workplace accidents. To minimize heat stress, protective equipment may be worn, such as personal cooling garments. This paper presents and discusses the performances, advantages and disadvantages of existing personal cooling garments, namely air-cooled, liquid-cooled, phase change, hybrid, gas expansion and vacuum desiccant cooling garments, and a thermoelectric cooling technology. The main objective is to identify the cooling technique that would be most suitable for deep mining workers. It appears that no cooling technology currently on the market is perfectly compatible with this type of mining environment. However, combining two or more cooling technologies into a single hybrid system could be the solution to an optimized cooling garment for deep mines.展开更多
文摘Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.
文摘Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.
文摘The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell type.In the cardiovascular system,Ca2+ is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction pathways.A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure in these systems to maintain normal Ca2+homeostasis has been linked to both heart failure and hypertension.This article focuses on the functions of PMCA,in particular isoform 4(PMCA4) ,in the heart and vasculature and the reported links between PMCAs and contractile function,cardiac hypertrophy,cardiac rhythm and sudden cardiac death,and blood pressure control and hypertension.It is becoming clear that this family of calcium extrusion pumps have essential roles in both cardiovascular health and disease.
基金The project was supported by the German Federal Ministry of Education(BMBF)(01LN1713A).
文摘气化是实现化学利用碳资源(尤其是煤)生产化学品和燃料的关键工艺。目前,全球拥有超过272套气化装置,主要应用于煤化工,尤其在中国。由于在一个化工厂通过技术集成达到工业规模的集中生产可实现减少二氧化碳排放并促进碳密集型行业的循环经济,如废物管理、化学和交通行业,因此,近年来全球对垃圾气化的兴趣日益浓厚,尤其是那些在煤气化技术方面积累了丰富的人力资本和运营经验以及拥有完整Coal-to-X产品价值链的国家,如中国,在挖掘通过垃圾气化实现Waste-to-X的潜力方面处于独特的地位。具体而言,废弃物可用于补充煤气化生产如下产品:(1)具有较低或零碳足迹的化学品,具体取决于废物是来源于化石资源还是生物资源。(2)来自生物废弃物的零碳足迹的绿色“氢”,以补充或替代来自煤气化或蒸汽重整得到的“灰色”氢,以供给氢能汽车,并推动工业脱碳。(3)来自生物废弃物的CO_(2)中性合成液体燃料,用于交通工具,以补充或替代石油燃料和合成煤制液体燃料。然而,迄今为止,利用垃圾作为气化原料的操作经验有限,并且文献中也很少涉及以前和当前的工业垃圾气化经验。为了填补这些空白,本研究介绍了1980年代至2000年代德国的两项开创性技术发展—贝伦拉特(Berrenrath)和SVZ黑水泵(即Sekundärrohstoff-Verwertungszentrum:黑水泵二次原料回收中心),并分享了以下三种垃圾与煤共气化技术(即Waste&Coal-to-X)的相关认识和经验教训:固定床气化:鲁奇干法排渣技术以及BGL熔渣气化技术。流化床气化:高温温克勒(HTW-High Temperature Winkler)气化工艺。气流床气化:GSP(Gaskombinat Schwarze Pumpe),即西门子气化工艺。此外,本研究也总结了目前全球100%垃圾气化技术的发展,即Waste-to-X。在气化技术的三种类型中,研发领域和工业界均对流化床与气流床(作为后期气化)技术的结合产�
基金funded by the Fonds de Recherche du QuébecNature et Technologies (FRQNT)
文摘The severity of the hot and humid conditions to which miners are exposed increases as the depth of the work site increases.This can cause heat stress that can greatly affect the health and safety of workers.To resolve this,a cooling garment has been developed that uses an atmospheric discharge of liquid CO2 to create a cool microclimate with an average temperature of 12.5(±0.4)℃ beneath the garment.To evaluate the garment's cooling efficiency,19 male subjects participated in an experimental procedure.The two modes,cooling on and off,were compared.Significant physiological differences were found between the two modes after minute 27(p<0.05)until the end of the recovery phase for the heart rate(maximum difference of 10 beats per minute)and the internal body temperature(maximum difference of 0.33℃).It was found that the modes also affected the subjects'perceptions.The ON-mode was associated with better well-being and thermal comfort,and reduced humidity sensation.Perceptions of exertion were lower in the ON-mode condition from minute 2.The findings provide strong evidence of the ability of this cooling garment to reduce heat stress in hot and humid conditions similar to those encountered in deep mines.
文摘Ghrelin causes interdigestive contractions of the stom- ach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted on the antrum, duodenum, proximal and distal jejunum. After an overnight fast, gastrointestinal (GI) contrac- tions were recorded in freely moving conscious rats. Spontaneous phase m-like contractions were observed at every 13-16 min in rat GI tract. The fasted motor patterns were replaced by the fed motor pattern imme- diately after food intake. Two minutes after finishing the spontaneous phase Ill-like contractions in the antrum, acyl ghrelin (0.8, 2.4 and 8.0 μg/kg per min) was con- tinuously infused for 30 min. Three-five minutes after the starting ghrelin infusion, augmented phase Ⅲ-like contractions were observed at the antrum, duodenum, and jejunum. Ghrelin infusion (0.8, 2.4 and 8.0μg/kg per min) significantly increased motility index of phase Ⅲ-like contractions at the antrum and jejunum in a dose dependent manner, compared to that of saline in- jection. Thus, it is likely that exogenously administered ghrelin causes phase Ⅲ-like contraction at the antrum, which migrates to the duodenum and jejunum. The possible role of 5-HT, in addition to ghrelin, in mediating intestinal migrating motor complex (MMC), is discussed.
文摘Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are
基金funded by the Deutsche Krebshilfe (Grant No. 111450)financially supported by the Competence Network Asthma/COPD that is funded by the German Federal Ministry of Education and Research (Grant No. FKZ 01GI1001)
文摘Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P 〈 0.05), including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P - 2.3 × 10 -5). We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.
文摘Rapid technological improvements in biomaterials,computer-aided design(CAD)and manufacturing(CAM)have endorsed clear aligner therapy(CAT)as a mainstay of orthodontic treatment,and the materials employed for aligner fabrication play an all-important role in determining the clinical performance of clear aligners.This narrative review has attempted to comprehensively encompass the entire gamut of materials currently used for the fabrication of clear aligners and elucidate their characteristics that are crucial in determining their performance in an oral environment.Historical developments and current protocols in aligner fabrication,features of contemporary bioactive materials,and emerging trends related to CAT are discussed.Advances in aligner material chemistry and engineering possess the potential to bring about radical transformations in the therapeutic applications of CAT;in the absence of which,clear aligners would continue to underperform clinically,due to their inherent biomechanical constraints.Finally,while innovations in aligner materials such as shape memory polymers,direct three-dimensional(3D)printed clear aligners and bioactive materials combined with clear aligner materials are essential to further advance the applications of CAT;increased awareness of environmental responsibilities among aligner manufacturers,aligner prescribing clinicians and aligner users is essential for better alignment of our climate change goals towards a sustainable planet.
文摘Workers exposed to hot and humid conditions suffer from heat stress that affects their concentration and can potentially lead to an increase in workplace accidents. To minimize heat stress, protective equipment may be worn, such as personal cooling garments. This paper presents and discusses the performances, advantages and disadvantages of existing personal cooling garments, namely air-cooled, liquid-cooled, phase change, hybrid, gas expansion and vacuum desiccant cooling garments, and a thermoelectric cooling technology. The main objective is to identify the cooling technique that would be most suitable for deep mining workers. It appears that no cooling technology currently on the market is perfectly compatible with this type of mining environment. However, combining two or more cooling technologies into a single hybrid system could be the solution to an optimized cooling garment for deep mines.