AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched fo...AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention.展开更多
Mitogen-activated protein kinase （MAPK） and leucine-rich repeat receptor-like kinase （LRR-RLK） signaling pathways have been shown to regulate diverse aspects of plant growth and development. In Arabidopsis, proper...Mitogen-activated protein kinase （MAPK） and leucine-rich repeat receptor-like kinase （LRR-RLK） signaling pathways have been shown to regulate diverse aspects of plant growth and development. In Arabidopsis, proper anther development relies on intercellular communication to coordinate cell proliferation and differentiation. Two closely related genes encoding MAPKs, MPK3 and MPK6, function redundantly in regulating stomatal patterning. Although the mpk6 mutant has reduced fertility, the function of MPK3 and MPK6 in anther development has not been characterized. Similarly, the ERECTA （ER）, ERECTA-LIKE1 （ERL1） and ERL2 genes encoding LRR-RLKs function together to direct stomatal cell fate specification and the er-105 erll-2 erl2-1 triple mutant is sterile. Because the mpk3 rnpk6 double null mutant is embryo lethal, anther development was characterized in the viable mpk3/＋ mpk6/- and er-105 erll-2 erl2-1 mutants. We found that both mutant anthers usually fail to form one or more of the four anther lobes, with the er-105 erl1-2 erl2-1 triple mutant exhibiting more severe phenotypes than those of the mpk3/＋ mpk6/- mutant. The somatic cell layers of the differentiated mutant lobes appeared larger and more disorganized than that of wild-type. In addition, the er-105 erll-2 erl2ol triple mutant has a reduced number of stamens, the majority of which possess completely undifferentiated or under-differentiated anthers. Furthermore, sometimes, the mpk3/＋ mpk6/- mutant anthers do not dehisce, and the er-105 erl1-2 erl2-1 anthers were not observed to dehisce. Therefore, our results indicate that both ER/ERL 1/ERL2 and MPK3/MPK6 play important roles in normal anther lobe formation and anther cell differentiation. The close functional relationship between these genes in other developmental processes and the similarities in anther developmental phenotypes of the two types of mutants reported here further suggest the possibility that these genes might also function in the same pathway to regulate anther cell di展开更多
AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shangh...AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shanghai,China. After surgery,patients were randomized to receive acupuncture(once daily,starting on postoperative day 1, for up to six consecutive days)or usual care.PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery.The main outcomes were time to first flatus,time to first bowel movement, and electrogastroenterography.Secondary outcomes were quality of life(QOL)measures,including pain, nausea,insomnia,abdominal distension/fullness,and sense of well-being. RESULTS:No significant differences in PPOI on day 4 (P=0.71)or QOL measures were found between the groups.There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5(P=0.69)or day 6(P= 0.88).No adverse events related to acupuncture were reported. CONCLUSION:Acupuncture did not prevent PPOI andwas not useful for treating PPOI once it had developed in this population.展开更多
The Ca2+-sensing receptor(the Ca SR),a G-protein-coupled receptor,regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+([Ca2+]o) and responding to a diverse array of stimuli.Mutations in th...The Ca2+-sensing receptor(the Ca SR),a G-protein-coupled receptor,regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+([Ca2+]o) and responding to a diverse array of stimuli.Mutations in the Ca2+-sensing receptor result in hypercalcemic or hypocalcemic disorders,such as familial hypocalciuric hypercalcemia,neonatal severe primary hyperparathyroidism,and autosomal dominant hypocalcemic hypercalciuria.Compelling evidence suggests that the Ca SR plays multiple roles extending well beyond not only regulating the level of extracellular Ca2+ in the human body,but also controlling a diverse range of biological processes.In this review,we focus on the structural biology of the Ca SR,the ligand interaction sites as well as their relevance to the disease associated mutations.This systematic summary will provide a comprehensive exploration of how the Ca SR integrates extracellular Ca2+ into intracellular Ca2+ signaling.展开更多
The term “physical literacy” is gaining traction in many countries and institutions as a goal for physical education. This paper explores the concept of physical literacy and highlights the foundational work in this...The term “physical literacy” is gaining traction in many countries and institutions as a goal for physical education. This paper explores the concept of physical literacy and highlights the foundational work in this area, particularly that of Margaret Whitehead. The relationship of physical literacy to physical education is also discussed with potential ramifications for teachers and learners who adopt physical literacy as the goal of the subject area.展开更多
The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates ...The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. Metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. Many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have been used singly or in combination and include: phy展开更多
Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein ...Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and XPCdefective human fibroblasts identified 861 XPC-responsive genes in the cisplatin treatment (with minimum fold change≥1.5).The cell cycle and cell proliferation-related genes are the most affected genes by the XPC defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the XPC defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an RT-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of the microarray data. To further validate the microarray data, the cisplatin treatment-mediated caspase-3 activation was also determined. The Western blot hybridization results indicate that the XPC defect greatly attenuates the cisplatin treatment-mediated Caspase-3 activation. We elucidated the role of p53 protein in the XPC protein DNA damage recognition-mediated signaling process. The XPC defect reduces the cisplatin treatment-mediated p53 response. These results suggest that the XPC protein plays an important role in the cisplatin treatment-mediated cellular response. It may also suggest a possible mechanism of cancer cell drug resistance.展开更多
The three largest earthquakes in northern California since 1849 were preceded by increased decadal activity for moderate-size shocks along surrounding nearby faults. Increased seismicity, double-difference precise loc...The three largest earthquakes in northern California since 1849 were preceded by increased decadal activity for moderate-size shocks along surrounding nearby faults. Increased seismicity, double-difference precise locations of earthquakes since 1968, geodetic data and fault offsets for the 1906 great shock are used to re-examine the timing and locations of possible future large earthquakes. The physical mechanisms of regional faults like the Calaveras, Hayward and Sargent, which exhibit creep, differ from those of the northern San Andreas, which is currently locked and is not creeping. Much decadal forerunning activity occurred on creeping faults. Moderate-size earthquakes along those faults became more frequent as stresses in the region increased in the latter part of the cycle of stress restoration for major and great earthquakes along the San Andreas. They may be useful for decadal forecasts. Yearly to decadal forecasts, however, are based on only a few major to great events. Activity along closer faults like that in the two years prior to the 1989 Loma Prieta shock needs to be examined for possible yearly forerunning changes to large plate boundary earthquakes. Geodetic observations are needed to focus on identifying creeping faults close to the San Andreas. The distribution of moderate-size earthquakes increased significantly since 1990 along the Hayward fault but not adjacent to the San Andreas fault to the south of San Francisco compared to what took place in the decades prior to the three major historic earthquakes in the region. It is now clear from a re-examination of the 1989 mainshock that the increased level of moderate-size shocks in the one to two preceding decades occurred on nearby East Bay faults. Double-difference locations of small earthquakes provide structural information about faults in the region, especially their depths. The northern San Andreas fault is divided into several strongly coupled segments based on differences in seismicity.展开更多
文摘AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention.
文摘Mitogen-activated protein kinase （MAPK） and leucine-rich repeat receptor-like kinase （LRR-RLK） signaling pathways have been shown to regulate diverse aspects of plant growth and development. In Arabidopsis, proper anther development relies on intercellular communication to coordinate cell proliferation and differentiation. Two closely related genes encoding MAPKs, MPK3 and MPK6, function redundantly in regulating stomatal patterning. Although the mpk6 mutant has reduced fertility, the function of MPK3 and MPK6 in anther development has not been characterized. Similarly, the ERECTA （ER）, ERECTA-LIKE1 （ERL1） and ERL2 genes encoding LRR-RLKs function together to direct stomatal cell fate specification and the er-105 erll-2 erl2-1 triple mutant is sterile. Because the mpk3 rnpk6 double null mutant is embryo lethal, anther development was characterized in the viable mpk3/＋ mpk6/- and er-105 erll-2 erl2-1 mutants. We found that both mutant anthers usually fail to form one or more of the four anther lobes, with the er-105 erl1-2 erl2-1 triple mutant exhibiting more severe phenotypes than those of the mpk3/＋ mpk6/- mutant. The somatic cell layers of the differentiated mutant lobes appeared larger and more disorganized than that of wild-type. In addition, the er-105 erll-2 erl2ol triple mutant has a reduced number of stamens, the majority of which possess completely undifferentiated or under-differentiated anthers. Furthermore, sometimes, the mpk3/＋ mpk6/- mutant anthers do not dehisce, and the er-105 erl1-2 erl2-1 anthers were not observed to dehisce. Therefore, our results indicate that both ER/ERL 1/ERL2 and MPK3/MPK6 play important roles in normal anther lobe formation and anther cell differentiation. The close functional relationship between these genes in other developmental processes and the similarities in anther developmental phenotypes of the two types of mutants reported here further suggest the possibility that these genes might also function in the same pathway to regulate anther cell di
基金Supported by US National Cancer Institute (NCI) grants CA108084 and CA12153031
文摘AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shanghai,China. After surgery,patients were randomized to receive acupuncture(once daily,starting on postoperative day 1, for up to six consecutive days)or usual care.PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery.The main outcomes were time to first flatus,time to first bowel movement, and electrogastroenterography.Secondary outcomes were quality of life(QOL)measures,including pain, nausea,insomnia,abdominal distension/fullness,and sense of well-being. RESULTS:No significant differences in PPOI on day 4 (P=0.71)or QOL measures were found between the groups.There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5(P=0.69)or day 6(P= 0.88).No adverse events related to acupuncture were reported. CONCLUSION:Acupuncture did not prevent PPOI andwas not useful for treating PPOI once it had developed in this population.
基金supported by the US National Institutes of Health(GM081749 and EB007268)a Center for Diagnostics and Therapeutics fellowship(to Zhang Chen)funds from the Georgia Research Alliance
文摘The Ca2+-sensing receptor(the Ca SR),a G-protein-coupled receptor,regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+([Ca2+]o) and responding to a diverse array of stimuli.Mutations in the Ca2+-sensing receptor result in hypercalcemic or hypocalcemic disorders,such as familial hypocalciuric hypercalcemia,neonatal severe primary hyperparathyroidism,and autosomal dominant hypocalcemic hypercalciuria.Compelling evidence suggests that the Ca SR plays multiple roles extending well beyond not only regulating the level of extracellular Ca2+ in the human body,but also controlling a diverse range of biological processes.In this review,we focus on the structural biology of the Ca SR,the ligand interaction sites as well as their relevance to the disease associated mutations.This systematic summary will provide a comprehensive exploration of how the Ca SR integrates extracellular Ca2+ into intracellular Ca2+ signaling.
文摘The term “physical literacy” is gaining traction in many countries and institutions as a goal for physical education. This paper explores the concept of physical literacy and highlights the foundational work in this area, particularly that of Margaret Whitehead. The relationship of physical literacy to physical education is also discussed with potential ramifications for teachers and learners who adopt physical literacy as the goal of the subject area.
文摘The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. Metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. Many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have been used singly or in combination and include: phy
文摘Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and XPCdefective human fibroblasts identified 861 XPC-responsive genes in the cisplatin treatment (with minimum fold change≥1.5).The cell cycle and cell proliferation-related genes are the most affected genes by the XPC defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the XPC defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an RT-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of the microarray data. To further validate the microarray data, the cisplatin treatment-mediated caspase-3 activation was also determined. The Western blot hybridization results indicate that the XPC defect greatly attenuates the cisplatin treatment-mediated Caspase-3 activation. We elucidated the role of p53 protein in the XPC protein DNA damage recognition-mediated signaling process. The XPC defect reduces the cisplatin treatment-mediated p53 response. These results suggest that the XPC protein plays an important role in the cisplatin treatment-mediated cellular response. It may also suggest a possible mechanism of cancer cell drug resistance.
文摘The three largest earthquakes in northern California since 1849 were preceded by increased decadal activity for moderate-size shocks along surrounding nearby faults. Increased seismicity, double-difference precise locations of earthquakes since 1968, geodetic data and fault offsets for the 1906 great shock are used to re-examine the timing and locations of possible future large earthquakes. The physical mechanisms of regional faults like the Calaveras, Hayward and Sargent, which exhibit creep, differ from those of the northern San Andreas, which is currently locked and is not creeping. Much decadal forerunning activity occurred on creeping faults. Moderate-size earthquakes along those faults became more frequent as stresses in the region increased in the latter part of the cycle of stress restoration for major and great earthquakes along the San Andreas. They may be useful for decadal forecasts. Yearly to decadal forecasts, however, are based on only a few major to great events. Activity along closer faults like that in the two years prior to the 1989 Loma Prieta shock needs to be examined for possible yearly forerunning changes to large plate boundary earthquakes. Geodetic observations are needed to focus on identifying creeping faults close to the San Andreas. The distribution of moderate-size earthquakes increased significantly since 1990 along the Hayward fault but not adjacent to the San Andreas fault to the south of San Francisco compared to what took place in the decades prior to the three major historic earthquakes in the region. It is now clear from a re-examination of the 1989 mainshock that the increased level of moderate-size shocks in the one to two preceding decades occurred on nearby East Bay faults. Double-difference locations of small earthquakes provide structural information about faults in the region, especially their depths. The northern San Andreas fault is divided into several strongly coupled segments based on differences in seismicity.
