Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the em...Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.展开更多
The widespread and growing interest in the Internet of Things(IoT)may be attributed to its usefulness in many different fields.Physical settings are probed for data,which is then transferred via linked networks.There ...The widespread and growing interest in the Internet of Things(IoT)may be attributed to its usefulness in many different fields.Physical settings are probed for data,which is then transferred via linked networks.There are several hurdles to overcome when putting IoT into practice,from managing server infrastructure to coordinating the use of tiny sensors.When it comes to deploying IoT,everyone agrees that security is the biggest issue.This is due to the fact that a large number of IoT devices exist in the physicalworld and thatmany of themhave constrained resources such as electricity,memory,processing power,and square footage.This research intends to analyse resource-constrained IoT devices,including RFID tags,sensors,and smart cards,and the issues involved with protecting them in such restricted circumstances.Using lightweight cryptography,the information sent between these gadgets may be secured.In order to provide a holistic picture,this research evaluates and contrasts well-known algorithms based on their implementation cost,hardware/software efficiency,and attack resistance features.We also emphasised how essential lightweight encryption is for striking a good cost-to-performance-to-security ratio.展开更多
Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutic...Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.展开更多
Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Met...Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Methods:Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China.Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week(MET-h/week)according to World Health Organization recommendations:none,below recommendation(>0-7.49 MET-h/week);at recommended level(7.5-14.9 MET-h/week);above recommendation(>15 MET-h/week).Mortality and cardiovascular disease data were obtained from national registries.Results:During a median follow-up of 12.4 and 9.7 years,in the UK and China cohorts,repectively,higher levels of leisure-time PA were inversely associated with all-cause(1571 and 2351 events)and cardiovascular mortality(392 and 1060 events),mostly consistent with a linear dose-response relationship.PA below,at,and above recommendations,compared with no activity,yielded all-cause mortality hazard ratios of0.94(95%confidence interval(95%CI):0.79-1.12),0.90(95%CI:0.74-1.10),and 0.85(95%CI:0.70-1.02)in British adults and 0.87(95%CI:0.68-1.10),0.88(95%CI:0.74-1.03),and 0.77(95%CI:0.70-0.85)in Chinese adults.Associations with cardiovascular mortality were more pronounced in British adults(0.80(95%CI:0.58-1.11),0.75(95%CI:0.52-1.09),and 0.69(95%CI:0.48-0.97))but less pronounced in Chinese adults(1.06(95%CI:0.76-1.47),1.01(95%CI:0.80-1.28),and 0.79(95%CI:0.69-0.92)).PA at recommended levels was not associated with lower rates of major adverse cardiovascular events(2345 and 4458 events).Conclusion:Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes.Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.展开更多
Background:Evidence on the health benefits of occupational physical activity(OPA)is inconclusive.We examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer morta...Background:Evidence on the health benefits of occupational physical activity(OPA)is inconclusive.We examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer mortality and survival times.Methods:This study included prospective and longitudinal data from the MJ Cohort,comprising adults over 18 years recruited in 1998-2016,349,248 adults(177,314 women)with baseline OPA,of whom 105,715(52,503 women)had 2 OPA measures at 6.3±4.2 years(mean±SD)apart.Exposures were baseline OPA,OPA changes,and baseline leisure-time physical activity.Results:Over a mean mortality follow-up of 16.2±5.5 years for men and 16.4±5.4 years for women,11,696 deaths(2033 of CVD and 4631 of cancer causes)in men and 8980 deaths(1475 of CVD and 3689 of cancer causes)in women occurred.Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men(multivariable-adjusted hazard ratio(HR)=0.93,95%confidence interval(95%CI):0.89-0.98 compared to light OPA)and women(HR=0.86,95%CI:0.79-0.93).Over a mean mortality follow-up of 12.5±4.6 years for men and 12.6±4.6 years for women,OPA decreases in men were detrimentally associated(HR=1.16,95%CI:1.01-1.33)with all-cause mortality,while OPA increases in women were beneficially(HR=0.83,95%CI:0.70-0.97)associated with the same outcome.Baseline or changes in OPA showed no associations with CVD or cancer mortality.Conclusion:Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women.Our longitudinal OPA analyses partly confirmed the prospective findings,with some discordance between sex groups.展开更多
Mussels from two sites within the Baltic mussel (Mytilus edulis × M. trossulus) hybrid zone were used in a comparative study on the effects of salinity-changing rates on filtration activity. The acute effect of v...Mussels from two sites within the Baltic mussel (Mytilus edulis × M. trossulus) hybrid zone were used in a comparative study on the effects of salinity-changing rates on filtration activity. The acute effect of varying salinity-changing rates was found to be similar in M. edulis from the brackish Great Belt and in M. trossulus from the low saline Central Baltic Sea, and the relationships could be described by linear regression lines through 0.0 indicating that the acute effect of deteriorating conditions at decreasing salinities is the opposite as for improving conditions when the salinity is subsequently increased. Further, both M. edulis and M. trossulus acclimatized to 20 psu reacted to an acute salinity change to 6.5 psu by immediately closing their valves whereupon the filtration rate gradually increased during the following days, but only M. trossulus had completely acclimatized to 6.5 psu within 5 days which may be explained by different genotypes of M. edulis and M. trossulus which probably reflected an evolutionary adaptation of the latter to survive in the stable low-salinity Baltic Sea.展开更多
The effects of salinities between 10 and 30 psu on the growth of blue mussels, Mytilus edulis, were studied in laboratory feeding experiments and compared to the growth of mussels suspended in net-bags in the brackish...The effects of salinities between 10 and 30 psu on the growth of blue mussels, Mytilus edulis, were studied in laboratory feeding experiments and compared to the growth of mussels suspended in net-bags in the brackish water Great Belt, Denmark. In the laboratory, 3 series of growth experiments were conducted: in Series #1, groups of mussels were exposed to 10, 15, 25 and 30 psu, in Series #2, two groups of mussels were exposed to 10 and 30 psu, respectively, for 15 days (first period) where upon the mussels were exposed to the reversed salinities for another 15 days (second period). In Series #3, two groups of mussels were initially exposed to 15 and 25 psu for 22 days whereupon the mussel groups were exposed to the reversed salinities for another 17 days. In the laboratory experiments there was a tendency towards reduced growth with decreasing salinity, reflected as reduced shell growth rate and decreasing weight specific growth rate with falling salinity. The shell growth rate was relatively low in the first feeding period compared to the second period, and mussels that were initially exposed to 10 psu, where the growth was low, exhibited fast growth when subsequently exposed to 30 psu, and reversed when 30 psu mussels were exposed to 10 psu. The study showed that mussels are able to adjust growth at changing salinities, and the observed effect of salinity could partly be explained by a temporary shell valve closure after a sudden change in salinity. The specific growth rate of mussels measured in laboratory experiments at salinities between 15 to 25 psu (4.2% to 4.8% d–1) were comparable to the growth of mussels in the field experiment (3.2% to 4.0% d–1) where the salinity varied between 24 and 13 psu during the growth period.展开更多
This paper describes the Danish legal framework for district cooling as an example of a model which so far has had limited success. A number of suggestions are analysed and discussed.
Introduction: The incidence of head and neck cancers has increased markedly over the last decade. A Danish study of the costs of head and neck cancers has not been undertaken. Such studies have again become relevant d...Introduction: The incidence of head and neck cancers has increased markedly over the last decade. A Danish study of the costs of head and neck cancers has not been undertaken. Such studies have again become relevant due to the development of the HPV vaccines, as some cases are attributable to high-risk HPV 16 or 18. The objective of study was to estimate the incidence of head and neck cancers and their health care costs. Methods: Data on incidence and health care use related to head and neck cancer were obtained from Danish health care registers. New cancer patients were identified in the Danish National Cancer Register. Resource use per year in the hospital sector was estimated using data from the National Patient Register applying charges as cost estimates. Health care consumption by cancer patients was compared with that by an age- and sex-matched cohort without cancer. Results: We found that nearly 1000 new cases of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancer are diagnosed annually. In total the cost of these cancers to the Danish hospital sector constituted 31.6 million Euros per year, with the majority of costs (74%) occurring in men. The total costs associated with HPV16/18-related head and neck cancers were estimated to be 6.1 million Euros per year. Conclusion: This study provides the first Danish estimates of the costs associated with non-cervical and non-genital HPV-related cancers based on very reliable, individual-based data. It is expected that the current HPV vaccination programme will reduce this burden.展开更多
Background:Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens.However,the lifestyles of children with mental,behavioral,and...Background:Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens.However,the lifestyles of children with mental,behavioral,and developmental disorders(MBDDs)remains under-described within the literature of public health field.This study aimed to examine adherence to 24-hour movement guidelines among children with MBDDs compared to population norms and whether these differences are affected by demographic characteristics.Methods:Data were from the 2016-2020 National Survey of Children’s Health—A national,population-based,cross-sectional study.We used the data of 119,406 children aged 6-17 years,which included 38,571 participants with at least 1 MBDD and 80,835 without.Adherence to the 24-hour movement guidelines was measured using parent-reported physical activity,screen time,and sleep duration.Results:Among children with MBDDs,20.3%,37.0%,60.7%,and 77.3%met the physical activity,screen time,sleep,and at least 1 of the 24-hour movement guidelines.These rates were lower than those in children without MBDDs(22.8%,46.2%,66.7%,and 83.4%,respectively;all p<0.001).Children with MBDDs were less likely to meet these guidelines(odds ratio(OR)=1.21,95%confidence interval(95%CI):1.13-1.30;OR=1.37,95%CI:1.29-1.45;OR=1.29,95%CI:1.21-1.37;OR=1.45,95%CI:1.35-1.56)than children without MBDDs.Children with emotional disorders had the highest odds of not meeting these guidelines(OR=1.43,95%CI:1.29-1.57;OR=1.48,95%CI:1.37-1.60;OR=1.49,95%CI:1.39-1.61;OR=1.72,95%CI:1.57-1.88)in comparison to children with other MBDDs.Among children aged12-17 years,the difference in proportion of meeting physical activity and screen time guidelines for children with vs.children without MBDD was larger than that among children aged 6-11 years.Furthermore,the above difference of meeting physical activity guidelines in ethnic minority children was smaller than that in white children.Conclusion:Children with MBDDs were less likely to meet individual or combined 24-hour movement guidelines than children without MBDDs.In educational and clinical settings,the primary focus should be on increasing physical activity and limiting screen time in children aged 12-17 years who have MBDDs;and specifically for white children who have MBDDs,increasing physical activity may help.展开更多
The number of ureterorenoscopic procedures for upper urinary tract stone management has increased dramatically during recent years worldwide[1].Developments in flexible ureteroscope and laser technology have made it p...The number of ureterorenoscopic procedures for upper urinary tract stone management has increased dramatically during recent years worldwide[1].Developments in flexible ureteroscope and laser technology have made it possible to successfully address larger and more complex stone scenarios retrogradely.On the other hand,this means that more and more patients are exposed to the potential adverse effects of ureteroscopy[2].In general,ureteroscopy is considered a safe procedure.However,serious complications and even deaths do occur,and these events are most likely underreported[3,4].展开更多
Magnetic resonance(MR)imaging is a widely employed medical imaging technique that produces detailed anatomical images of the human body.The segmentation of MR im-ages plays a crucial role in medical image analysis,as ...Magnetic resonance(MR)imaging is a widely employed medical imaging technique that produces detailed anatomical images of the human body.The segmentation of MR im-ages plays a crucial role in medical image analysis,as it enables accurate diagnosis,treatment planning,and monitoring of various diseases and conditions.Due to the lack of sufficient medical images,it is challenging to achieve an accurate segmentation,especially with the application of deep learning networks.The aim of this work is to study transfer learning from T1-weighted(T1-w)to T2-weighted(T2-w)MR sequences to enhance bone segmentation with minimal required computation resources.With the use of an excitation-based convolutional neural networks,four transfer learning mechanisms are proposed:transfer learning without fine tuning,open fine tuning,conservative fine tuning,and hybrid transfer learning.Moreover,a multi-parametric segmentation model is proposed using T2-w MR as an intensity-based augmentation technique.The novelty of this work emerges in the hybrid transfer learning approach that overcomes the overfitting issue and preserves the features of both modalities with minimal computation time and resources.The segmentation results are evaluated using 14 clinical 3D brain MR and CT images.The results reveal that hybrid transfer learning is superior for bone segmentation in terms of performance and computation time with DSCs of 0.5393±0.0007.Although T2-w-based augmentation has no significant impact on the performance of T1-w MR segmentation,it helps in improving T2-w MR segmentation and developing a multi-sequences segmentation model.展开更多
BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported ...BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.展开更多
AIM:To evaluate the agreement between transrectal ultrasound(TRUS) and magnetic resonance imaging(MRI) in classification of ≥ T3 rectal tumors.METHODS:From January 2010 to January 2012,86 consecutive patients with ≥...AIM:To evaluate the agreement between transrectal ultrasound(TRUS) and magnetic resonance imaging(MRI) in classification of ≥ T3 rectal tumors.METHODS:From January 2010 to January 2012,86 consecutive patients with ≥ T3 tumors were included in this study.The mean age of the patients was 66.4 years(range:26-91 years).The tumors were all ≥ T3 on TRUS.The sub-classification was defined by the penetration of the rectal wall:a:0 to 1 mm;b:1-5 mm;c:6-15;d:> 15 mm.Early tumors as ab(≤ 5 mm) and advanced tumors as cd(> 5 mm).All patients underwent TRUS using a 6.5 MHz transrectal transducer.The MRI was performed with a 1.5 T Philips unit.The TRUS findings were blinded to the radiologist performing the interpretation of the MRI images and measuring the depth of extramural tumor spread.RESULTS:TRUS found 51 patients to have an early ≥ T3 tumors and 35 to have an advanced tumor,whereas MRI categorized 48 as early ≥ T3 tumors and 38 as advanced tumors.No patients with tumors classified as advanced by TRUS were found to be early on MRI.The kappa value in classifying early versus advanced T3 rectal tumors was 0.93(95% CI:0.85-1.00).We found a kappa value of 0.74(95% CI:0.63-0.86) for the total sub-classification between the two methods.The mean maximal tumor outgrowth measured by TRUS,5.5 mm ± 5.63 mm and on MRI,6.3 mm ± 6.18 mm,P = 0.004.In 19 of the 86 patients the following CT scan or surgery revealed distant metastases;of the 51 patients in the ultrasound ab group three(5.9%) had metastases,whereas 16(45.7%) of 35 in the cd group harbored distant metastases,P = 0.00002.The odds ratio of having distant metastases in the ultrasound cd group compared to the ab group was 13.5(95% CI:3.5-51.6),P = 0.00002.The mean maximal ultrasound measured outgrowth was 4.3 mm(95% CI:3.2-5.5 mm) in patients without distant metastases,while the mean maximal outgrowth was 9.5 mm(95% CI:6.2-12.8 mm) in the patients with metastases,P = 0.00004.Using the MRI classification three(6.3%) of 48 in the MRI ab group had distant metastases,while 16(42.1%) of the 38 in the MRI cd group,P = 0.00004.The MRI odds ratio was 10.9(95% CI:2.9-41.4),P = 0.00008.The mean maximal MRI measured outgrowth was 4.9 mm(95% CI:3.7-6.1 mm) in patients without distant metastases,while the mean maximal outgrowth was 11.5 mm(95% CI:7.8-15.2 mm) in the patients with metastases,P = 0.000006.CONCLUSION:There is good agreement between TRUS and MRI in the pretreatment sub-classification of ≥ T3 tumors.Distant metastases are more frequent in the advanced group.展开更多
The rapid increase in energy demand,the extensive use of fossil fuels and the urgent need to reduce the carbon dioxide emissions have raised concerns in the transportation sector.Alternate renewable and sustainable so...The rapid increase in energy demand,the extensive use of fossil fuels and the urgent need to reduce the carbon dioxide emissions have raised concerns in the transportation sector.Alternate renewable and sustainable sources have become the ultimate solution to overcome the expected depletion of fossil fuels.The conversion of lignocellulosic biomass to liquid(BtL)transportation fuels seems to be a promising path and presents advantages over first generation biofuels and fossil fuels.Therefore,development of BtL systems is critical to increase the potential of this resource in a sustainable and economic way.Conversion of lignocellulosic BtL transportation fuels,such as,gasoline,diesel and jet fuel can be accomplished through various thermochemical processes and processing routes.The major steps for the production of BtL fuels involve feedstock selection,physical pretreatment,production of bio-oil,upgrading of bio-oil to transportation fuels and recovery of value-added products.The present work is aiming to give a comprehensive review of the current process technologies following these major steps and the current scenarios of biomass to liquid facilities for the production of biofuels.展开更多
AIM: To evaluate ATP-binding cassette(ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer(CRC) development. METHODS: Literature search was conducted on Pub Med using com...AIM: To evaluate ATP-binding cassette(ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer(CRC) development. METHODS: Literature search was conducted on Pub Med using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein(P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2(MRP2) and ABCG2/breast cancer resistance protein(BCRP), Abcb1/Mdr1 a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported thatchanges in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of hostmicrobiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogenfree Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies.展开更多
Purpose: The aims of this study were to(1) investigate the health-related physical fitness profile of untrained adolescent boys in comparison to adolescent soccer players,(2) determine the intensity and enjoyment of 6...Purpose: The aims of this study were to(1) investigate the health-related physical fitness profile of untrained adolescent boys in comparison to adolescent soccer players,(2) determine the intensity and enjoyment of 6 v 6 and 4 v 4 small-sided games, and(3) evaluate the health-related effects of a short-period of soccer training in the untrained group.Methods: Forty-one adolescent boys(untrained, n = 24: age = 15.9 ± 0.6 years; trained, n = 17: age = 15.7 ± 0.7 years) were recruited. For Purpose 1,the players(n = 17) and the untrained(n = 24) boys were tested for speed, jumping power, postural balance, flexibility, and aerobic capacity. After baseline testing, Purposes 2 and 3 were addressed by randomly assigning the untrained boys to either a soccer-training group(small-sided games,2 sessions per week for 8 weeks) or to a control group, followed by identical retesting.Results: At baseline, physical fitness was higher(p < 0.001) in trained players than in untrained for aerobic fitness, sprinting, jumping power, and postural balance. Small-sided games using 6 v 6 or 4 v 4 elicited similar heart rate(HR)(mean: ~ 85% peak heart rate, HR_(peak)), rate of perceived exertion, and enjoyment responses. Over 8 weeks, the between-group analysis revealed that soccer training had a large beneficial effect on postural balance(45%) when compared with control group with unclear effects on other fitness parameters.Conclusion: Adolescent soccer players had markedly higher physical fitness compared with untrained adolescents. Small-sided soccer games practiced by untrained adolescents elicited high exercise intensity. While 8 weeks of twice-weekly soccer training sessions induced significant improvement in postural balance, the short duration of the study was not sufficient to result in between-group differences in sprint and jump performance or aerobic fitness.展开更多
Neuromuscular activity is suppressed during maximal eccentric(ECC)muscle contraction in untrained subjects owing to attenuated levels of central activation and reduced spinal motor neuron(MN)excitability indicated by ...Neuromuscular activity is suppressed during maximal eccentric(ECC)muscle contraction in untrained subjects owing to attenuated levels of central activation and reduced spinal motor neuron(MN)excitability indicated by reduced electromyography signal amplitude,diminished evoked H-reflex responses,increased autogenic MN inhibition,and decreased excitability in descending corticospinal motor pathways.Maximum ECC muscle force recorded during maximal voluntary contraction can be increased by superimposed electrical muscle stimulation only in untrained individuals and not in trained strength athletes,indicating that the suppression in MN activation is modifiable by resistance training.In support of this notion,maximum ECC muscle strength can be increased by use of heavy-load resistance training owing to a removed or diminished suppression in neuromuscular activity.Prolonged(weeks to months)of heavy-load resistance training results in increased H-reflex and V-wave responses during maximal ECC muscle actions along with marked gains in maximal ECC muscle strength,indicating increased excitability of spinal MNs,decreased presynaptic and/or postsynaptic MN inhibition,and elevated descending motor drive.Notably,the use of supramaximal ECC resistance training can lead to selectively elevated V-wave responses during maximal ECC contraction,demonstrating that adaptive changes in spinal circuitry function and/or gains in descending motor drive can be achieved during maximal ECC contraction in response to heavy-load resistance training.展开更多
Purpose: The present study evaluated the effects of regular participation in small-sided team handball training on body composition, osteogenic response, physical performance, and cardiovascular risk factors, as well ...Purpose: The present study evaluated the effects of regular participation in small-sided team handball training on body composition, osteogenic response, physical performance, and cardiovascular risk factors, as well as well-being and motivation, in young untrained women.Methods: Twenty-eight untrained 20- to 30-year-old women were randomized to a handball training group(HG; n = 14, height 170 ± 5 cm, weight 73 ± 11 kg, VO_(2peak) 37.7 ± 4.1 mL/min/kg) that trained 1.7 ± 0.3 times per week over 12 weeks(70 min 4 v 4 handball sessions) or an inactive control group(CG; n = 14, 169 ± 5 cm, 71 ± 12 kg, 38.1 ± 3.7 mL/min/kg). Physiological and psychological and motivational training adaptations were assessed pre-and post-intervention by dual-energy X-ray Absorptiometry(DXA) scans, blood sampling, physical tests, and questionnaires.Results: The average heart rate(HR) over all training sessions was equal to 85% ± 6% HR_(max). Between-group intervention effects were observed in favor of HG for muscle mass(2.1%, p = 0.024), proximal femur bone mineral density(0.8%, p = 0.041), Yo-Yo IE1 intermittent endurance test level 1(IE1) performance(35%, p < 0.001), and incremental treadmill test performance(11.5%, p = 0.003), but not total fat mass(p = 0.176),mean arterial blood pressure(p = 0.328), resting HR(p = 0.219), or blood lipids(p = 0.298—0.854). In CG, no changes were observed in any of the measured physiological variables after the training period. Compared to CG, HG had an increase in intrinsic motivation(p < 0.001) and in the well-being subscale "energy"(p = 0.010).Conclusion: Participation in regular recreational team handball training organized as small-sided games has marked beneficial effects on physical performance, musculoskeletal fitness, well-being, and motivation in untrained young women.展开更多
As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer's disease (AD). Under physiological conditions, the synaptic con- nections between neurons underg...As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer's disease (AD). Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, 'plastic' neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.展开更多
基金supported by the Novo Nordisk Foundation(NNF180C0034936)the Lundbeck Foundation(R380-2021-1262)(to CD and JN)。
文摘Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.
基金supported by project TRANSACT funded under H2020-EU.2.1.1.-INDUSTRIAL LEADERSHIP-Leadership in Enabling and Industrial Technologies-Information and Communication Technologies(Grant Agreement ID:101007260).
文摘The widespread and growing interest in the Internet of Things(IoT)may be attributed to its usefulness in many different fields.Physical settings are probed for data,which is then transferred via linked networks.There are several hurdles to overcome when putting IoT into practice,from managing server infrastructure to coordinating the use of tiny sensors.When it comes to deploying IoT,everyone agrees that security is the biggest issue.This is due to the fact that a large number of IoT devices exist in the physicalworld and thatmany of themhave constrained resources such as electricity,memory,processing power,and square footage.This research intends to analyse resource-constrained IoT devices,including RFID tags,sensors,and smart cards,and the issues involved with protecting them in such restricted circumstances.Using lightweight cryptography,the information sent between these gadgets may be secured.In order to provide a holistic picture,this research evaluates and contrasts well-known algorithms based on their implementation cost,hardware/software efficiency,and attack resistance features.We also emphasised how essential lightweight encryption is for striking a good cost-to-performance-to-security ratio.
基金funded by grants from the Novo Nordisk Foundation (NNF18OC0052699) (M.S.H.) and NNF18OC0055047 (M.F.)the Region of Southern Denmark (ref: 18/17553 (M.S.H.))+3 种基金Odense University Hospital (ref: A3147) (M.F.)a faculty fellowship from the University of Southern Denmark (K.M.), the Lundbeck Foundation (ref: R335-2019-2195) (K.M.and A.R.)an Academy of Medical Sciences Springboard Award supported by the British Heart Foundation, Diabetes UK, the Global Challenges Research Fund, the Government Department of Business, Energy and Industrial Strategy and the Wellcome Trust (ref: SBF004 | 1034, C.M.G)a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 224155/Z/21/Z to C.M.G.).
文摘Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.
文摘Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Methods:Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China.Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week(MET-h/week)according to World Health Organization recommendations:none,below recommendation(>0-7.49 MET-h/week);at recommended level(7.5-14.9 MET-h/week);above recommendation(>15 MET-h/week).Mortality and cardiovascular disease data were obtained from national registries.Results:During a median follow-up of 12.4 and 9.7 years,in the UK and China cohorts,repectively,higher levels of leisure-time PA were inversely associated with all-cause(1571 and 2351 events)and cardiovascular mortality(392 and 1060 events),mostly consistent with a linear dose-response relationship.PA below,at,and above recommendations,compared with no activity,yielded all-cause mortality hazard ratios of0.94(95%confidence interval(95%CI):0.79-1.12),0.90(95%CI:0.74-1.10),and 0.85(95%CI:0.70-1.02)in British adults and 0.87(95%CI:0.68-1.10),0.88(95%CI:0.74-1.03),and 0.77(95%CI:0.70-0.85)in Chinese adults.Associations with cardiovascular mortality were more pronounced in British adults(0.80(95%CI:0.58-1.11),0.75(95%CI:0.52-1.09),and 0.69(95%CI:0.48-0.97))but less pronounced in Chinese adults(1.06(95%CI:0.76-1.47),1.01(95%CI:0.80-1.28),and 0.79(95%CI:0.69-0.92)).PA at recommended levels was not associated with lower rates of major adverse cardiovascular events(2345 and 4458 events).Conclusion:Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes.Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.
基金The authors thank the participants for their participation in the MJ Health Management Institution prospective cohort study.All of the data used in this research were authorized for use by the MJ Health Resource Centre(Authorization code:MJHRF2019013A)the Health and Welfare Data Science Centre.Any interpretations or conclusions described in this paper do not represent the views of the MJ Health Resource CentreThis work was supported by a National Health and Medical Research Council(Australia)Investigator Grant(APP1194510).
文摘Background:Evidence on the health benefits of occupational physical activity(OPA)is inconclusive.We examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer mortality and survival times.Methods:This study included prospective and longitudinal data from the MJ Cohort,comprising adults over 18 years recruited in 1998-2016,349,248 adults(177,314 women)with baseline OPA,of whom 105,715(52,503 women)had 2 OPA measures at 6.3±4.2 years(mean±SD)apart.Exposures were baseline OPA,OPA changes,and baseline leisure-time physical activity.Results:Over a mean mortality follow-up of 16.2±5.5 years for men and 16.4±5.4 years for women,11,696 deaths(2033 of CVD and 4631 of cancer causes)in men and 8980 deaths(1475 of CVD and 3689 of cancer causes)in women occurred.Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men(multivariable-adjusted hazard ratio(HR)=0.93,95%confidence interval(95%CI):0.89-0.98 compared to light OPA)and women(HR=0.86,95%CI:0.79-0.93).Over a mean mortality follow-up of 12.5±4.6 years for men and 12.6±4.6 years for women,OPA decreases in men were detrimentally associated(HR=1.16,95%CI:1.01-1.33)with all-cause mortality,while OPA increases in women were beneficially(HR=0.83,95%CI:0.70-0.97)associated with the same outcome.Baseline or changes in OPA showed no associations with CVD or cancer mortality.Conclusion:Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women.Our longitudinal OPA analyses partly confirmed the prospective findings,with some discordance between sex groups.
文摘Mussels from two sites within the Baltic mussel (Mytilus edulis × M. trossulus) hybrid zone were used in a comparative study on the effects of salinity-changing rates on filtration activity. The acute effect of varying salinity-changing rates was found to be similar in M. edulis from the brackish Great Belt and in M. trossulus from the low saline Central Baltic Sea, and the relationships could be described by linear regression lines through 0.0 indicating that the acute effect of deteriorating conditions at decreasing salinities is the opposite as for improving conditions when the salinity is subsequently increased. Further, both M. edulis and M. trossulus acclimatized to 20 psu reacted to an acute salinity change to 6.5 psu by immediately closing their valves whereupon the filtration rate gradually increased during the following days, but only M. trossulus had completely acclimatized to 6.5 psu within 5 days which may be explained by different genotypes of M. edulis and M. trossulus which probably reflected an evolutionary adaptation of the latter to survive in the stable low-salinity Baltic Sea.
基金formed part of the MarBioShell project supported by the Danish Agency for Science,Technology and Innovation for the period January 2008 to December 2012.
文摘The effects of salinities between 10 and 30 psu on the growth of blue mussels, Mytilus edulis, were studied in laboratory feeding experiments and compared to the growth of mussels suspended in net-bags in the brackish water Great Belt, Denmark. In the laboratory, 3 series of growth experiments were conducted: in Series #1, groups of mussels were exposed to 10, 15, 25 and 30 psu, in Series #2, two groups of mussels were exposed to 10 and 30 psu, respectively, for 15 days (first period) where upon the mussels were exposed to the reversed salinities for another 15 days (second period). In Series #3, two groups of mussels were initially exposed to 15 and 25 psu for 22 days whereupon the mussel groups were exposed to the reversed salinities for another 17 days. In the laboratory experiments there was a tendency towards reduced growth with decreasing salinity, reflected as reduced shell growth rate and decreasing weight specific growth rate with falling salinity. The shell growth rate was relatively low in the first feeding period compared to the second period, and mussels that were initially exposed to 10 psu, where the growth was low, exhibited fast growth when subsequently exposed to 30 psu, and reversed when 30 psu mussels were exposed to 10 psu. The study showed that mussels are able to adjust growth at changing salinities, and the observed effect of salinity could partly be explained by a temporary shell valve closure after a sudden change in salinity. The specific growth rate of mussels measured in laboratory experiments at salinities between 15 to 25 psu (4.2% to 4.8% d–1) were comparable to the growth of mussels in the field experiment (3.2% to 4.0% d–1) where the salinity varied between 24 and 13 psu during the growth period.
文摘This paper describes the Danish legal framework for district cooling as an example of a model which so far has had limited success. A number of suggestions are analysed and discussed.
基金supported by an unrestricted research grant to CAST,University of Southern Denmark,from Sanofi Pasteur MSD.
文摘Introduction: The incidence of head and neck cancers has increased markedly over the last decade. A Danish study of the costs of head and neck cancers has not been undertaken. Such studies have again become relevant due to the development of the HPV vaccines, as some cases are attributable to high-risk HPV 16 or 18. The objective of study was to estimate the incidence of head and neck cancers and their health care costs. Methods: Data on incidence and health care use related to head and neck cancer were obtained from Danish health care registers. New cancer patients were identified in the Danish National Cancer Register. Resource use per year in the hospital sector was estimated using data from the National Patient Register applying charges as cost estimates. Health care consumption by cancer patients was compared with that by an age- and sex-matched cohort without cancer. Results: We found that nearly 1000 new cases of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancer are diagnosed annually. In total the cost of these cancers to the Danish hospital sector constituted 31.6 million Euros per year, with the majority of costs (74%) occurring in men. The total costs associated with HPV16/18-related head and neck cancers were estimated to be 6.1 million Euros per year. Conclusion: This study provides the first Danish estimates of the costs associated with non-cervical and non-genital HPV-related cancers based on very reliable, individual-based data. It is expected that the current HPV vaccination programme will reduce this burden.
基金financial support of the Key-Area Research and Development Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(82103794)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515011757)General Administration of Sport of China and China Institute of Sport Science(19—21)Guangxi Key Research and Development Plan(GUIKEAB18050024)。
文摘Background:Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens.However,the lifestyles of children with mental,behavioral,and developmental disorders(MBDDs)remains under-described within the literature of public health field.This study aimed to examine adherence to 24-hour movement guidelines among children with MBDDs compared to population norms and whether these differences are affected by demographic characteristics.Methods:Data were from the 2016-2020 National Survey of Children’s Health—A national,population-based,cross-sectional study.We used the data of 119,406 children aged 6-17 years,which included 38,571 participants with at least 1 MBDD and 80,835 without.Adherence to the 24-hour movement guidelines was measured using parent-reported physical activity,screen time,and sleep duration.Results:Among children with MBDDs,20.3%,37.0%,60.7%,and 77.3%met the physical activity,screen time,sleep,and at least 1 of the 24-hour movement guidelines.These rates were lower than those in children without MBDDs(22.8%,46.2%,66.7%,and 83.4%,respectively;all p<0.001).Children with MBDDs were less likely to meet these guidelines(odds ratio(OR)=1.21,95%confidence interval(95%CI):1.13-1.30;OR=1.37,95%CI:1.29-1.45;OR=1.29,95%CI:1.21-1.37;OR=1.45,95%CI:1.35-1.56)than children without MBDDs.Children with emotional disorders had the highest odds of not meeting these guidelines(OR=1.43,95%CI:1.29-1.57;OR=1.48,95%CI:1.37-1.60;OR=1.49,95%CI:1.39-1.61;OR=1.72,95%CI:1.57-1.88)in comparison to children with other MBDDs.Among children aged12-17 years,the difference in proportion of meeting physical activity and screen time guidelines for children with vs.children without MBDD was larger than that among children aged 6-11 years.Furthermore,the above difference of meeting physical activity guidelines in ethnic minority children was smaller than that in white children.Conclusion:Children with MBDDs were less likely to meet individual or combined 24-hour movement guidelines than children without MBDDs.In educational and clinical settings,the primary focus should be on increasing physical activity and limiting screen time in children aged 12-17 years who have MBDDs;and specifically for white children who have MBDDs,increasing physical activity may help.
文摘The number of ureterorenoscopic procedures for upper urinary tract stone management has increased dramatically during recent years worldwide[1].Developments in flexible ureteroscope and laser technology have made it possible to successfully address larger and more complex stone scenarios retrogradely.On the other hand,this means that more and more patients are exposed to the potential adverse effects of ureteroscopy[2].In general,ureteroscopy is considered a safe procedure.However,serious complications and even deaths do occur,and these events are most likely underreported[3,4].
基金Swiss National Science Foundation,Grant/Award Number:SNSF 320030_176052Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung,Grant/Award Number:320030_176052。
文摘Magnetic resonance(MR)imaging is a widely employed medical imaging technique that produces detailed anatomical images of the human body.The segmentation of MR im-ages plays a crucial role in medical image analysis,as it enables accurate diagnosis,treatment planning,and monitoring of various diseases and conditions.Due to the lack of sufficient medical images,it is challenging to achieve an accurate segmentation,especially with the application of deep learning networks.The aim of this work is to study transfer learning from T1-weighted(T1-w)to T2-weighted(T2-w)MR sequences to enhance bone segmentation with minimal required computation resources.With the use of an excitation-based convolutional neural networks,four transfer learning mechanisms are proposed:transfer learning without fine tuning,open fine tuning,conservative fine tuning,and hybrid transfer learning.Moreover,a multi-parametric segmentation model is proposed using T2-w MR as an intensity-based augmentation technique.The novelty of this work emerges in the hybrid transfer learning approach that overcomes the overfitting issue and preserves the features of both modalities with minimal computation time and resources.The segmentation results are evaluated using 14 clinical 3D brain MR and CT images.The results reveal that hybrid transfer learning is superior for bone segmentation in terms of performance and computation time with DSCs of 0.5393±0.0007.Although T2-w-based augmentation has no significant impact on the performance of T1-w MR segmentation,it helps in improving T2-w MR segmentation and developing a multi-sequences segmentation model.
基金the Natural Science Foundation of Hainan Province,No.823MS046the Talent Program of Hainan Medical University,No.XRC2022007.
文摘BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.
文摘AIM:To evaluate the agreement between transrectal ultrasound(TRUS) and magnetic resonance imaging(MRI) in classification of ≥ T3 rectal tumors.METHODS:From January 2010 to January 2012,86 consecutive patients with ≥ T3 tumors were included in this study.The mean age of the patients was 66.4 years(range:26-91 years).The tumors were all ≥ T3 on TRUS.The sub-classification was defined by the penetration of the rectal wall:a:0 to 1 mm;b:1-5 mm;c:6-15;d:> 15 mm.Early tumors as ab(≤ 5 mm) and advanced tumors as cd(> 5 mm).All patients underwent TRUS using a 6.5 MHz transrectal transducer.The MRI was performed with a 1.5 T Philips unit.The TRUS findings were blinded to the radiologist performing the interpretation of the MRI images and measuring the depth of extramural tumor spread.RESULTS:TRUS found 51 patients to have an early ≥ T3 tumors and 35 to have an advanced tumor,whereas MRI categorized 48 as early ≥ T3 tumors and 38 as advanced tumors.No patients with tumors classified as advanced by TRUS were found to be early on MRI.The kappa value in classifying early versus advanced T3 rectal tumors was 0.93(95% CI:0.85-1.00).We found a kappa value of 0.74(95% CI:0.63-0.86) for the total sub-classification between the two methods.The mean maximal tumor outgrowth measured by TRUS,5.5 mm ± 5.63 mm and on MRI,6.3 mm ± 6.18 mm,P = 0.004.In 19 of the 86 patients the following CT scan or surgery revealed distant metastases;of the 51 patients in the ultrasound ab group three(5.9%) had metastases,whereas 16(45.7%) of 35 in the cd group harbored distant metastases,P = 0.00002.The odds ratio of having distant metastases in the ultrasound cd group compared to the ab group was 13.5(95% CI:3.5-51.6),P = 0.00002.The mean maximal ultrasound measured outgrowth was 4.3 mm(95% CI:3.2-5.5 mm) in patients without distant metastases,while the mean maximal outgrowth was 9.5 mm(95% CI:6.2-12.8 mm) in the patients with metastases,P = 0.00004.Using the MRI classification three(6.3%) of 48 in the MRI ab group had distant metastases,while 16(42.1%) of the 38 in the MRI cd group,P = 0.00004.The MRI odds ratio was 10.9(95% CI:2.9-41.4),P = 0.00008.The mean maximal MRI measured outgrowth was 4.9 mm(95% CI:3.7-6.1 mm) in patients without distant metastases,while the mean maximal outgrowth was 11.5 mm(95% CI:7.8-15.2 mm) in the patients with metastases,P = 0.000006.CONCLUSION:There is good agreement between TRUS and MRI in the pretreatment sub-classification of ≥ T3 tumors.Distant metastases are more frequent in the advanced group.
基金financial support from CONACYT-The Mexican National Council for Science and Technology (REFERENCE: 326204/439098)the University of Southern Denmark
文摘The rapid increase in energy demand,the extensive use of fossil fuels and the urgent need to reduce the carbon dioxide emissions have raised concerns in the transportation sector.Alternate renewable and sustainable sources have become the ultimate solution to overcome the expected depletion of fossil fuels.The conversion of lignocellulosic biomass to liquid(BtL)transportation fuels seems to be a promising path and presents advantages over first generation biofuels and fossil fuels.Therefore,development of BtL systems is critical to increase the potential of this resource in a sustainable and economic way.Conversion of lignocellulosic BtL transportation fuels,such as,gasoline,diesel and jet fuel can be accomplished through various thermochemical processes and processing routes.The major steps for the production of BtL fuels involve feedstock selection,physical pretreatment,production of bio-oil,upgrading of bio-oil to transportation fuels and recovery of value-added products.The present work is aiming to give a comprehensive review of the current process technologies following these major steps and the current scenarios of biomass to liquid facilities for the production of biofuels.
文摘AIM: To evaluate ATP-binding cassette(ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer(CRC) development. METHODS: Literature search was conducted on Pub Med using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein(P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2(MRP2) and ABCG2/breast cancer resistance protein(BCRP), Abcb1/Mdr1 a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported thatchanges in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of hostmicrobiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogenfree Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies.
文摘Purpose: The aims of this study were to(1) investigate the health-related physical fitness profile of untrained adolescent boys in comparison to adolescent soccer players,(2) determine the intensity and enjoyment of 6 v 6 and 4 v 4 small-sided games, and(3) evaluate the health-related effects of a short-period of soccer training in the untrained group.Methods: Forty-one adolescent boys(untrained, n = 24: age = 15.9 ± 0.6 years; trained, n = 17: age = 15.7 ± 0.7 years) were recruited. For Purpose 1,the players(n = 17) and the untrained(n = 24) boys were tested for speed, jumping power, postural balance, flexibility, and aerobic capacity. After baseline testing, Purposes 2 and 3 were addressed by randomly assigning the untrained boys to either a soccer-training group(small-sided games,2 sessions per week for 8 weeks) or to a control group, followed by identical retesting.Results: At baseline, physical fitness was higher(p < 0.001) in trained players than in untrained for aerobic fitness, sprinting, jumping power, and postural balance. Small-sided games using 6 v 6 or 4 v 4 elicited similar heart rate(HR)(mean: ~ 85% peak heart rate, HR_(peak)), rate of perceived exertion, and enjoyment responses. Over 8 weeks, the between-group analysis revealed that soccer training had a large beneficial effect on postural balance(45%) when compared with control group with unclear effects on other fitness parameters.Conclusion: Adolescent soccer players had markedly higher physical fitness compared with untrained adolescents. Small-sided soccer games practiced by untrained adolescents elicited high exercise intensity. While 8 weeks of twice-weekly soccer training sessions induced significant improvement in postural balance, the short duration of the study was not sufficient to result in between-group differences in sprint and jump performance or aerobic fitness.
文摘Neuromuscular activity is suppressed during maximal eccentric(ECC)muscle contraction in untrained subjects owing to attenuated levels of central activation and reduced spinal motor neuron(MN)excitability indicated by reduced electromyography signal amplitude,diminished evoked H-reflex responses,increased autogenic MN inhibition,and decreased excitability in descending corticospinal motor pathways.Maximum ECC muscle force recorded during maximal voluntary contraction can be increased by superimposed electrical muscle stimulation only in untrained individuals and not in trained strength athletes,indicating that the suppression in MN activation is modifiable by resistance training.In support of this notion,maximum ECC muscle strength can be increased by use of heavy-load resistance training owing to a removed or diminished suppression in neuromuscular activity.Prolonged(weeks to months)of heavy-load resistance training results in increased H-reflex and V-wave responses during maximal ECC muscle actions along with marked gains in maximal ECC muscle strength,indicating increased excitability of spinal MNs,decreased presynaptic and/or postsynaptic MN inhibition,and elevated descending motor drive.Notably,the use of supramaximal ECC resistance training can lead to selectively elevated V-wave responses during maximal ECC contraction,demonstrating that adaptive changes in spinal circuitry function and/or gains in descending motor drive can be achieved during maximal ECC contraction in response to heavy-load resistance training.
基金financial support by TrygFondenNordea-fonden (Nordea-fonden 02-2011-4360)+2 种基金the Danish Handball Federation (Dansk Ha ndbold Forbund, DHF)the European Handball Federation (EHF)funded in part by the Danish and European Handball Federation
文摘Purpose: The present study evaluated the effects of regular participation in small-sided team handball training on body composition, osteogenic response, physical performance, and cardiovascular risk factors, as well as well-being and motivation, in young untrained women.Methods: Twenty-eight untrained 20- to 30-year-old women were randomized to a handball training group(HG; n = 14, height 170 ± 5 cm, weight 73 ± 11 kg, VO_(2peak) 37.7 ± 4.1 mL/min/kg) that trained 1.7 ± 0.3 times per week over 12 weeks(70 min 4 v 4 handball sessions) or an inactive control group(CG; n = 14, 169 ± 5 cm, 71 ± 12 kg, 38.1 ± 3.7 mL/min/kg). Physiological and psychological and motivational training adaptations were assessed pre-and post-intervention by dual-energy X-ray Absorptiometry(DXA) scans, blood sampling, physical tests, and questionnaires.Results: The average heart rate(HR) over all training sessions was equal to 85% ± 6% HR_(max). Between-group intervention effects were observed in favor of HG for muscle mass(2.1%, p = 0.024), proximal femur bone mineral density(0.8%, p = 0.041), Yo-Yo IE1 intermittent endurance test level 1(IE1) performance(35%, p < 0.001), and incremental treadmill test performance(11.5%, p = 0.003), but not total fat mass(p = 0.176),mean arterial blood pressure(p = 0.328), resting HR(p = 0.219), or blood lipids(p = 0.298—0.854). In CG, no changes were observed in any of the measured physiological variables after the training period. Compared to CG, HG had an increase in intrinsic motivation(p < 0.001) and in the well-being subscale "energy"(p = 0.010).Conclusion: Participation in regular recreational team handball training organized as small-sided games has marked beneficial effects on physical performance, musculoskeletal fitness, well-being, and motivation in untrained young women.
基金supported by grant SDU2020 to Prof.Bente Finsen and Prof.Martin R.Larsen(COPING AD–Collaborative Project on the Interaction between Neurons and Glia in Alzheimer’s Disease)
文摘As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer's disease (AD). Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, 'plastic' neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.