Today, most people know that physical activity(PA) is beneficial for their health ^(1,2)and aspire to engage in regular PA.^(3,4)However, despite their awareness of the importance of PA, it is evident that the transit...Today, most people know that physical activity(PA) is beneficial for their health ^(1,2)and aspire to engage in regular PA.^(3,4)However, despite their awareness of the importance of PA, it is evident that the transition from intention to action is challenging-a situation that has important public health implications. According to the World Health Organization,^(5)1 person dies every 6 s worldwide from causes related to physical inactivity, which underscores the urgency of addressing this situation.展开更多
Background There is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy.The purpose of the study was to investigate the interplay between...Background There is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy.The purpose of the study was to investigate the interplay between objectively measured PA volume and intensity profiles with modeled life expectancy in women and men within the UK Biobank cohort study and interpret findings in relation to brisk walking.Methods Individuals from UK Biobank with wrist-worn accelerometer data were included.The average acceleration and intensity gradient were extracted to describe the physical activity volume and intensity profile.Mortality data were obtained from national registries.Adjusted life expectancies were estimated using parametric flexible survival models.Results 40,953(57.1%)women(median age=61.9 years)and 30,820(42.9%)men(63.1 years)were included.Over a median follow-up of 6.9 years,there were 1719(2.4%)deaths(733 in women;986 in men).At 60 years,life expectancy was progressively longer for higher physical activity volume and intensity profiles,reaching 95.6 years in women and 94.5 years in men at the 90th centile for both volume and intensity,corresponding to 3.4 additional years(95%confidence interval(95%CI):2.4-4.4)in women and 4.6 additional years(95%CI:3.6-5.6)in men compared to those at the 10th centiles.An additional 10-min or 30-min daily brisk walk was associated with 0.9(95%CI:0.5-1.3)and 1.4 years(95%CI:0.9-1.9)longer life expectancy,respectively,in inactive women;and 1.4 years(95%CI:1.0-1.8)and 2.5(95%CI:1.9-3.1)in inactive men.Conclusion Higher physical activity volumes were associated with longer life expectancy,with a higher physical activity intensity profile further adding to a longer life.Adding as little as a 10-min brisk walk to daily activity patterns may result in a meaningful benefit to life expectancy.展开更多
An electronic circular dichroism(ECD)-based chiroptical sensing method has been developed forβ-andγ-chiral primary amines via a C-H activation reaction.With the addition of Pd(OAc)_(2),the flexible remote chiral pri...An electronic circular dichroism(ECD)-based chiroptical sensing method has been developed forβ-andγ-chiral primary amines via a C-H activation reaction.With the addition of Pd(OAc)_(2),the flexible remote chiral primary amine fragment in the bidentate ligand intermediate was fixed to form a cyclopalladium complex,producing an intense ECD response.The correlation between the sign of Cotton effects and the absolute configuration of substrates was proposed,together with theoretical verification using timedependent density functional theory(TDDFT).Chiroptical sensing of an important drug raw material was performed to provide rapid and accurate information on the absolute optical purity.This work introduces an alternative perspective of C-H activation reaction as well as a feasible chiroptical sensing method of remote chiral amines.展开更多
Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)im...Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity;(b)inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity.Methods 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included.Average acceleration and intensity gradient were derived as proxies for PA volume and intensity.We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape(GAMLSS)and modeled the effect of adding moderate(walking)or vigorous(running)activity on the combined change in the volume and intensity centiles(change in PA profile).Results In men,volume was lower as age increased while intensity was lower after age 55;in women,both volume and intensity were lower as age increased.Adding 150 min of moderate PA weekly(5×30 min walking)increased the PA profile by 4 percentage points.Defining moderate PA as brisk walking approximately doubled the increase(9 percentage points)while 75 min of vigorous PA weekly(5×15 min running)trebled the increase(13 percentage points).Conclusion These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data.Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile(volume and intensity)than longer duration moderate activity.展开更多
Device-based measurements are recommended to improve population-based physical activity(PA)surveillance.1,2However,implementation remains challenging due to lack of consensus on analytical methods,and the most widely ...Device-based measurements are recommended to improve population-based physical activity(PA)surveillance.1,2However,implementation remains challenging due to lack of consensus on analytical methods,and the most widely used“generic”(absolute intensity)cut-point approach has limited generalisability to population-level free-living data.Further,current methods generally fail to account for differences in people's physical capacity.展开更多
Background:A shift from self-reports to wearable sensors for global physical activity(PA)surveillance has been recommended.The conventional use of a generic cut-point to assess moderate-to-vigorous PA(MVPA)is problema...Background:A shift from self-reports to wearable sensors for global physical activity(PA)surveillance has been recommended.The conventional use of a generic cut-point to assess moderate-to-vigorous PA(MVPA)is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions.This study aimed to develop age-and sex-(age-sex)specific cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality.Methods:A total of 7601 participants(20-85+years)were drawn from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys(NHANES).Minutes per week of MVPA were assessed with a hip-worn accelerometer.Counts per minute(CPM)were used to define an age-sex specific target intensity,representing the intensity each person should be able to reach based on their age and sex.Age-sex specific MVPA cut-points were defined as any activity above 40%of the target intensity.These population-and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach.For comparison,we also calculated MVPA with a generic cut-point of 1952 CPM.Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with allcause mortality(ascertained through December 2015).Results:Both approaches indicated that 37%of the sample met the 150+min/week guideline.The generic cut-point approach showed a trend to inactivity with age,which was less pronounced using the age-sex specific cut-points.Overall mortality rates were comparable using generic cutpoint(hazard ratio(HR)=0.61,95%confidence interval(95%CI):0.50-0.73)or age-sex specific cut-points(HR=0.57,95%CI:0.50-0.66)for the entire sample.The generic cut-point method revealed an age-and sex-related gap in the benefits of achieving 150+min/week of MVPA,with older adults showing an 18%greater reduction in mortality rates than younger adults,and a larger difference in women than in men.This disparity disappeared when using age-sex specific cut-points.Conclusion:Our findings underscore the value of age-sex specific cut-points for global PA surveillance.MVPA defined with age-sex specific thresholds was associated with all-cause mortality and the dose-response was similar for all ages and sexes.This aligns with the single recommendation of accumulating 150+min/week MVPA for all adults,irrespective of age and sex.This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts.展开更多
Background:High adiposity and low physical activity are associated with cancer risk.Whether different amounts and intensities of physical activity can mitigate this association is unclear.We aimed to examine the indep...Background:High adiposity and low physical activity are associated with cancer risk.Whether different amounts and intensities of physical activity can mitigate this association is unclear.We aimed to examine the independent and combined associations of adiposity and devicemeasured physical activity levels of different intensities with cancer incidence and mortality.Methods:This prospective cohort study included data from 70,747 UK Biobank participants(mean age=61.6±7.9 years,mean±SD;56.4%women)with wrist-worn accelerometer measurements of physical activity and without chronic diseases or mobility limitations.Physical activity exposures included min per week of light intensity physical activity(LPA),moderate-to-vigorous intensity physical activity(MVPA),and vigorous intensity physical activity(VPA),along with total weekly volume.Body mass index(BMI)was calculated from anthropometric measurements.Participants were categorized into 9 groups based on joint tertiles of physical activity and BMI categories(normal weight,overweight,and obesity).Secondary analyses included adiposity using bio-impedance and waist circumference measurements.The outcome was incidence and death from cancer retrieved from national registries.Associations between adiposity,physical activity,and cancer hazard were calculated as subdistribution hazard ratios.A secondary analysis focused on cancer types strongly associated with physical activity.Results:We observed 2625 events(2572 non-fatal and 53 fatal)during a median follow-up of 6.1 years.Compared with the referent(normal weight and high physical activity),overweight and obesity were associated with a 6%to 36%higher cancer hazard across physical activity intensities.However,high MVPA and VPA(approximately 500 min and 32 min per week in the top tertiles,respectively)attenuated the hazard associated with overweight and obesity.Being normal weight was not associated with a higher cancer hazard regardless of physical activity level.The results were similar,although more pronounced,when modeling cancer types strongly associated with physical activity as the outcome.Conclusion:High MVPA and VPA levels may attenuate the association of overweight and obesity with cancer hazard,but maintaining a normal weight seems comparatively more important than physical activity to reduce the hazard.Maintaining a healthy body weight and engaging in physical activity is needed to minimize risk of some cancer types.展开更多
Objective To evaluate the in vitro anti-diabetic effects of Bryonia dioica roots extracts,in-cluding water-acetone extracts and their ethyl acetate and butanol fractions,and chloroform-methanol extracts.Methods The to...Objective To evaluate the in vitro anti-diabetic effects of Bryonia dioica roots extracts,in-cluding water-acetone extracts and their ethyl acetate and butanol fractions,and chloroform-methanol extracts.Methods The total phenolic,flavonoid,flavonol,and saponin contents in the Bryonia dioica root extracts(chloroform-methanol extracts,water-acetone extracts and their ethyl acetate and butanol fractions)were determined using colorimetric methods with Folin-Ciocalteu,aluminum trichloride,and vanillin reagents,respectively.The in vitro anti-diabetic activity was evaluated by measuring the half-maximal inhibitory concentration(IC_(50))values of these root extracts againstα-amylase andα-glucosidase activities,evaluating their effects onα-amy-lase kinetics,quantifying the inhibition of bovine serum albumin(BSA)glycation using fluo-rometry to assess advanced glycation end products(AGE)production,and determining glu-cose uptake by isolated rat hemidiaphragm.Additionally,molecular docking analysis was conducted to investigate the binding affinity and interaction types between Bryonia dioica lig-ands(cucurbitacin B,bryogénin,vitexin,and isovitexin)and target enzymes,and a phyto-chemical-targets interaction network was constructed.Results Forα-amylase inhibition,ethyl acetate fraction demonstrated the most potent activi-ty(IC_(50)=145.95μg/mL),followed by chloroform-methanol extract(IC_(50)=300.86μg/mL).Water-acetone root extracts and their ethyl acetate and butanol fractions inhibited theα-glucosidase activity with IC50 values ranging from 562.88 to 583.90μg/mL.Both ethyl acetate and butanol fractions strongly inhibited non-enzymatic BSA glycation(IC_(50)=318.26 and 323.12μg/mL,respectively).The incubation of isolated rat hemidiaphragms with the ethyl acetate fraction(5 mg/mL)significantly increased glucose uptake(35.16%;P<0.0001),exceeding the effects of insulin(29.27%),chloroform-methanol extract(24.07%),and catechin(15.27%).Molecular docking revealed that cucurbitacin B exhibited the strongest docking scores againstα-amylase(-16.4 kcal/mol),andα-glucosidase(-14.2 kcal/mol).Compared with other ligands,isovitexin formed the maximum number of hydrogen bonds with theα-amylase active site residues(Asp300,Asp197,and Glu233),α-glucosidase residues(Ser13,Arg44,Met86,Gly10,Asp39,and Tyr131)and other residues(Arg195,Trp59,His299,and Tyr62).Network analysis identified 36 overlapping targets between Bryonia dioica phyto-chemicals and type 2 diabetes mellitus-associated genes,with cucurbitacins and polyphenols interacting withα-amylase,α-glucosidase,and Glut4 translocation pathway targets.Conclusion Bryonia dioica root extracts demonstrated promising in vitro anti-diabetic activi-ty through multiple mechanisms,including the inhibitory effect on digestive enzymes,pro-tein antiglycation potential,and enhancement of glucose uptake,suggesting their potential as a source for anti-diabetic drugs development.展开更多
The 1605 M7½ Earthquake is the only earthquake in the history of China that has caused large-scale land subsidence into the sea,with the total area of land subsidence exceeding 100 km2.The disaster has led to the...The 1605 M7½ Earthquake is the only earthquake in the history of China that has caused large-scale land subsidence into the sea,with the total area of land subsidence exceeding 100 km2.The disaster has led to the sinking of 72 villages.There is still no clear understanding of the source seismogenic fault of this earthquake.In this work,we conducted a detailed study of the middle segment of the Maniao-Puqian fault(MPF),which is the epicenter area,through geomorphological survey,data collection,shallow seismic exploration,cross-section drilling,and chronological dating.The results showed that the middle segment of the MPF zone is composed of three nearly parallel normal faults with a dextral strike-slip:“Macun-Luodou fault(F2-1),Haixiu-Dongyuan fault(F2-2),and ChangliuZhuxihe fault(F2-3)”.And F2-2 is composed of two secondary faults,namely F2-2′and F2-2″,with a flower-shaped structure buried under the ground.It is distributed nearly east-west,dipping to the north and has experienced at least five stages of activities since the Miocene.The vertical activity rates of F2-2′and F2-2″are~2.32 and~2.5 mm/a,since the Holocene,respectively.There were eight cycles of transgression and regression since the Miocene.The fault activity resulted in the thickening of the Holocene strata with a slight dip to the south,on the hanging wall,showing V-shaped characteristics.The MPF is likely the source seismogenic fault of the M7½ earthquake that hit Qiongshan in 1605.展开更多
Background:The Compendium of Physical Activities was published in 1993 to improve the comparability of energy expenditure values assigned to self-reported physical activity(PA)across studies.The original version was u...Background:The Compendium of Physical Activities was published in 1993 to improve the comparability of energy expenditure values assigned to self-reported physical activity(PA)across studies.The original version was updated in 2000,and again in 2011,and has been widely used to support PA research,practice,and public health guidelines.Methods:This 2024 update was tailored for adults 19-59 years of age by removing data from those≥60 years.Using a systematic review and supplementary searches,we identified new activities and their associated measured metabolic equivalent(MET)values(using indirect calorimetry)published since 2011.We replaced estimated METs with measured values when possible.Results:We screened 32,173 abstracts and 1507 full-text papers and extracted 2356 PA energy expenditure values from 701 papers.We added303 new PAs and adjusted 176 existing MET values and descriptions to reflect the addition of new data and removal of METs for older adults.We added a Major Heading(Video Games).The 2024 Adult Compendium includes 1114 PAs(912 with measured and 202 with estimated values)across 22 Major Headings.Conclusion:This comprehensive update and refinement led to the creation of The 2024 Adult Compendium,which has utility across research,public health,education,and healthcare domains,as well as in the development of consumer health technologies.The new website with the complete lists of PAs and supporting resources is available at https://pacompendium.com.展开更多
Background:Prolonged sitting and reduced physical activity lead to low energy expenditures.However,little is known about the joint impact of daily sitting time and physical activity on body fat distribution.We investi...Background:Prolonged sitting and reduced physical activity lead to low energy expenditures.However,little is known about the joint impact of daily sitting time and physical activity on body fat distribution.We investigated the independent and joint associations of daily sitting time and physical activity with body fat among adults.Methods:This was a cross-sectional analysis of U.S.nationally representative data from the National Health and Nutrition Examination Survey2011-2018 among adults aged 20 years or older.Daily sitting time and leisure-time physical activity(LTPA)were self-reported using the Global Physical Activity Questionnaire.Body fat(total and trunk fat percentage)was determined via dual X-ray absorptiometry.Results:Among 10,808 adults,about 54.6%spent 6 h/day or more sitting;more than one-half reported no LTPA(inactive)or less than 150 min/week LTPA(insufficiently active)with only 43.3%reported 150 min/week or more LTPA(active)in the past week.After fully adjusting for sociodemographic data,lifestyle behaviors,and chronic conditions,prolonged sitting time and low levels of LTPA were associated with higher total and trunk fat percentages in both sexes.When stratifying by LTPA,the association between daily sitting time and body fat appeared to be stronger in those who were inactive/insuufficiently active.In the joint analyses,inactive/insuufficiently active adults who reported sitting more than 8 h/day had the highest total(female:3.99%(95%confidence interval(95%CI):3.09%-4.88%);male:3.79%(95%CI:2.75%-4.82%))and trunk body fat percentages(female:4.21%(95%CI:3.09%-5.32%);male:4.07%(95%CI:2.95%-5.19%))when compared with those who were active and sitting less than 4 h/day.Conclusion:Prolonged daily sitting time was associated with increased body fat among U.S.adults.The higher body fat associated with 6 h/day sitting may not be offset by achieving recommended levels of physical activity.展开更多
Physical activity(PA)is fundamentally linked to public health,^(1)providing benefits including chronic disease prevention and treatment,^(2)mental health,^(3)musculoskeletal health,^(4)and healthy aging,^(5)along with...Physical activity(PA)is fundamentally linked to public health,^(1)providing benefits including chronic disease prevention and treatment,^(2)mental health,^(3)musculoskeletal health,^(4)and healthy aging,^(5)along with socioeconomic advantages.^(6)These benefits highlight the importance of promoting PA for all populations.The recent publication of the Compendium of Physical Activities(Compendium)serves as a valuable resource,^(7)offering an updated and expanded guide for adults(ages 19-59)with tailored energy cost values for diverse populations.展开更多
Deformed soft-sediment deformation structures(SSDS)can indicate polyphase deformation events and provide valuable insights into the inversion process of a basin.Herein,we present the Miocene–Quaternary deformation in...Deformed soft-sediment deformation structures(SSDS)can indicate polyphase deformation events and provide valuable insights into the inversion process of a basin.Herein,we present the Miocene–Quaternary deformation inversion history of the Bomun sub-basin in the Gyeongju area of SE Korea.The inferred ENE compression direction(σHmax)based on paleostress analysis of the fault system,displacing Miocene sediments and SSDS,corresponds to the current stress field.The widespread occurrence of clear liquefaction structures and the vertical repetition of SSDS indicate substantial seismic activity during the basin opening stage.Brittle deformation features observed at both outcrop-and microstructural-scale along the faults suggest a reactivation as reverse faulting associated with a tilting process.The tectonic history of the study area is distinguished by SSDS associated with seismic activity,and reverse faulting associated with inversion process under ENE orientedσHmax.The Environmental Seismic Intensity Scale(ESI-07)based on the SSDS indicates seismic intensity of IX-X,which might be related with the opening of the Bomun sub-basin.Therefore,detailed analyses of SSDS could provide valuable insights on the dynamics of local geology and contribute to further extensive research on seismic hazards and basin inversion.展开更多
1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to ...1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to achieve health benefits.1-3 Absent from these guidelines are recommendations for light intensity PA(LPA,e.g.,walking at a leisurely pace of 3 km/h or less,equivalent to 1.5-2.9 metabolic equivalents).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
Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Hunting...Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.展开更多
1.Legacy matters The withdrawal of Australia as hosts for the Commonwealth Games in 2026 demonstrates that large international sporting events are more than just sporting mastery,medals,and memories.Money also matters...1.Legacy matters The withdrawal of Australia as hosts for the Commonwealth Games in 2026 demonstrates that large international sporting events are more than just sporting mastery,medals,and memories.Money also matters.1 The cost of hosting a major international tournament is eye-wateringly high.Host governments need to show that the billions of dollars of investment deliver a return beyond sporting glory to justify the resources that are spent.展开更多
The Guxiang-Tongmai segment of the Jiali fault is situated northeast of the Namche Barwa Syntaxis in northeastern Xizang.It is one of the most active strike-slip faults near the syntaxis and plays a pivotal role in th...The Guxiang-Tongmai segment of the Jiali fault is situated northeast of the Namche Barwa Syntaxis in northeastern Xizang.It is one of the most active strike-slip faults near the syntaxis and plays a pivotal role in the examination of seismic activity within the eastern Himalayan Syntaxis.New study in the research region has yielded a 1:200000 gravity dataset covering an area 1500 km^(2).Using wavelet transform multiscale decomposition,scratch analysis techniques,and 3D gravity inversion methods,gravity anomalies,fault distributions,and density structures were determined across various scales.Through the integration of our new gravity data with other geophysical and geological information,our findings demonstrate substantial variations in the overall crustal density within the region,with the fault distribution closely linked to these density fluctuations.Disparities in stratigraphic density are important causes of variations in the capacity of geological formations to endure regional tectonic stress.Earthquakes are predominantly concentrated within the density transition zone and are primarily situated in regions of elevated density.The hanging wall stress within the Guxiang-Tongmai segment of the Jiali fault exhibits a notable concentration,marked by pronounced anisotropy,and is positioned within the density differential zone,which is prone to earthquakes.展开更多
Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values ...Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older adults.MET values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older adults.Results:We identified 68 articles and extracted energy expenditure data on 427 PAs.From these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older adults.We developed a website to present the OA Compendium MET_(60+)values:https://pacompendium.com.Conclusion:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older adults.It is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.展开更多
Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non...Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads.Hence,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology.Herein,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2,4-triazole.Interestingly,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif.This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom.The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping.Importantly,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect.Interestingly,one pair of regioisomers(19S and 19X)induced distinct modes of cell death.Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis.Together,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.展开更多
基金supported by The Shenzhen Educational Research Funding(zdzb2014)The Shenzhen Science and Technology Innovation Commission(202307313000096)+4 种基金The Social Science Foundation from the China's Ministry of Education(23YJA880093)The Post-Doctoral Fellowship(2022M711174)The National Center for Mental Health(Z014)BC is supported by the Chaires de recherche Rennes Métropole(23C 0909)SM is supported by the National Insti-tutes of Health(R01AG72445).
文摘Today, most people know that physical activity(PA) is beneficial for their health ^(1,2)and aspire to engage in regular PA.^(3,4)However, despite their awareness of the importance of PA, it is evident that the transition from intention to action is challenging-a situation that has important public health implications. According to the World Health Organization,^(5)1 person dies every 6 s worldwide from causes related to physical inactivity, which underscores the urgency of addressing this situation.
基金funded by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (BRC)the Applied Research Collaborations East Midlands (ARC-EM)supported by a UKRI project grant (MR/T031816/1)。
文摘Background There is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy.The purpose of the study was to investigate the interplay between objectively measured PA volume and intensity profiles with modeled life expectancy in women and men within the UK Biobank cohort study and interpret findings in relation to brisk walking.Methods Individuals from UK Biobank with wrist-worn accelerometer data were included.The average acceleration and intensity gradient were extracted to describe the physical activity volume and intensity profile.Mortality data were obtained from national registries.Adjusted life expectancies were estimated using parametric flexible survival models.Results 40,953(57.1%)women(median age=61.9 years)and 30,820(42.9%)men(63.1 years)were included.Over a median follow-up of 6.9 years,there were 1719(2.4%)deaths(733 in women;986 in men).At 60 years,life expectancy was progressively longer for higher physical activity volume and intensity profiles,reaching 95.6 years in women and 94.5 years in men at the 90th centile for both volume and intensity,corresponding to 3.4 additional years(95%confidence interval(95%CI):2.4-4.4)in women and 4.6 additional years(95%CI:3.6-5.6)in men compared to those at the 10th centiles.An additional 10-min or 30-min daily brisk walk was associated with 0.9(95%CI:0.5-1.3)and 1.4 years(95%CI:0.9-1.9)longer life expectancy,respectively,in inactive women;and 1.4 years(95%CI:1.0-1.8)and 2.5(95%CI:1.9-3.1)in inactive men.Conclusion Higher physical activity volumes were associated with longer life expectancy,with a higher physical activity intensity profile further adding to a longer life.Adding as little as a 10-min brisk walk to daily activity patterns may result in a meaningful benefit to life expectancy.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2023-I2M-2-009).
文摘An electronic circular dichroism(ECD)-based chiroptical sensing method has been developed forβ-andγ-chiral primary amines via a C-H activation reaction.With the addition of Pd(OAc)_(2),the flexible remote chiral primary amine fragment in the bidentate ligand intermediate was fixed to form a cyclopalladium complex,producing an intense ECD response.The correlation between the sign of Cotton effects and the absolute configuration of substrates was proposed,together with theoretical verification using timedependent density functional theory(TDDFT).Chiroptical sensing of an important drug raw material was performed to provide rapid and accurate information on the absolute optical purity.This work introduces an alternative perspective of C-H activation reaction as well as a feasible chiroptical sensing method of remote chiral amines.
基金supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre and NIHR Applied Research Collaboration East Midlands (ARC EM, (IS-BRC-1215-20010))funded by the National Institute for Health and Care Research Bristol Biomedical Research Centre (IS-BRC-1215-20011)supported by a UKRI research grant (EP/X042464/1)。
文摘Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity;(b)inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity.Methods 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included.Average acceleration and intensity gradient were derived as proxies for PA volume and intensity.We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape(GAMLSS)and modeled the effect of adding moderate(walking)or vigorous(running)activity on the combined change in the volume and intensity centiles(change in PA profile).Results In men,volume was lower as age increased while intensity was lower after age 55;in women,both volume and intensity were lower as age increased.Adding 150 min of moderate PA weekly(5×30 min walking)increased the PA profile by 4 percentage points.Defining moderate PA as brisk walking approximately doubled the increase(9 percentage points)while 75 min of vigorous PA weekly(5×15 min running)trebled the increase(13 percentage points).Conclusion These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data.Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile(volume and intensity)than longer duration moderate activity.
文摘Device-based measurements are recommended to improve population-based physical activity(PA)surveillance.1,2However,implementation remains challenging due to lack of consensus on analytical methods,and the most widely used“generic”(absolute intensity)cut-point approach has limited generalisability to population-level free-living data.Further,current methods generally fail to account for differences in people's physical capacity.
基金supported in part by the intramural research programs at the National Institute on Aging and National Cancer Institute(USA)supported by the Spanish Ministry of Science,Innovation and Universities under Beatriz Galindo's 2022 fellowship program(BG22/00075).
文摘Background:A shift from self-reports to wearable sensors for global physical activity(PA)surveillance has been recommended.The conventional use of a generic cut-point to assess moderate-to-vigorous PA(MVPA)is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions.This study aimed to develop age-and sex-(age-sex)specific cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality.Methods:A total of 7601 participants(20-85+years)were drawn from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys(NHANES).Minutes per week of MVPA were assessed with a hip-worn accelerometer.Counts per minute(CPM)were used to define an age-sex specific target intensity,representing the intensity each person should be able to reach based on their age and sex.Age-sex specific MVPA cut-points were defined as any activity above 40%of the target intensity.These population-and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach.For comparison,we also calculated MVPA with a generic cut-point of 1952 CPM.Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with allcause mortality(ascertained through December 2015).Results:Both approaches indicated that 37%of the sample met the 150+min/week guideline.The generic cut-point approach showed a trend to inactivity with age,which was less pronounced using the age-sex specific cut-points.Overall mortality rates were comparable using generic cutpoint(hazard ratio(HR)=0.61,95%confidence interval(95%CI):0.50-0.73)or age-sex specific cut-points(HR=0.57,95%CI:0.50-0.66)for the entire sample.The generic cut-point method revealed an age-and sex-related gap in the benefits of achieving 150+min/week of MVPA,with older adults showing an 18%greater reduction in mortality rates than younger adults,and a larger difference in women than in men.This disparity disappeared when using age-sex specific cut-points.Conclusion:Our findings underscore the value of age-sex specific cut-points for global PA surveillance.MVPA defined with age-sex specific thresholds was associated with all-cause mortality and the dose-response was similar for all ages and sexes.This aligns with the single recommendation of accumulating 150+min/week MVPA for all adults,irrespective of age and sex.This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts.
基金funded by the Spanish Ministry of Universities under application 33.50.460A.752by the European Union Next Generation EU/PRTR through a Margarita Salas contract of the University of Vigosupported by the Government of Andalusia, Research Talent Recruitment Programme (EMERGIA 2020/00158)。
文摘Background:High adiposity and low physical activity are associated with cancer risk.Whether different amounts and intensities of physical activity can mitigate this association is unclear.We aimed to examine the independent and combined associations of adiposity and devicemeasured physical activity levels of different intensities with cancer incidence and mortality.Methods:This prospective cohort study included data from 70,747 UK Biobank participants(mean age=61.6±7.9 years,mean±SD;56.4%women)with wrist-worn accelerometer measurements of physical activity and without chronic diseases or mobility limitations.Physical activity exposures included min per week of light intensity physical activity(LPA),moderate-to-vigorous intensity physical activity(MVPA),and vigorous intensity physical activity(VPA),along with total weekly volume.Body mass index(BMI)was calculated from anthropometric measurements.Participants were categorized into 9 groups based on joint tertiles of physical activity and BMI categories(normal weight,overweight,and obesity).Secondary analyses included adiposity using bio-impedance and waist circumference measurements.The outcome was incidence and death from cancer retrieved from national registries.Associations between adiposity,physical activity,and cancer hazard were calculated as subdistribution hazard ratios.A secondary analysis focused on cancer types strongly associated with physical activity.Results:We observed 2625 events(2572 non-fatal and 53 fatal)during a median follow-up of 6.1 years.Compared with the referent(normal weight and high physical activity),overweight and obesity were associated with a 6%to 36%higher cancer hazard across physical activity intensities.However,high MVPA and VPA(approximately 500 min and 32 min per week in the top tertiles,respectively)attenuated the hazard associated with overweight and obesity.Being normal weight was not associated with a higher cancer hazard regardless of physical activity level.The results were similar,although more pronounced,when modeling cancer types strongly associated with physical activity as the outcome.Conclusion:High MVPA and VPA levels may attenuate the association of overweight and obesity with cancer hazard,but maintaining a normal weight seems comparatively more important than physical activity to reduce the hazard.Maintaining a healthy body weight and engaging in physical activity is needed to minimize risk of some cancer types.
文摘Objective To evaluate the in vitro anti-diabetic effects of Bryonia dioica roots extracts,in-cluding water-acetone extracts and their ethyl acetate and butanol fractions,and chloroform-methanol extracts.Methods The total phenolic,flavonoid,flavonol,and saponin contents in the Bryonia dioica root extracts(chloroform-methanol extracts,water-acetone extracts and their ethyl acetate and butanol fractions)were determined using colorimetric methods with Folin-Ciocalteu,aluminum trichloride,and vanillin reagents,respectively.The in vitro anti-diabetic activity was evaluated by measuring the half-maximal inhibitory concentration(IC_(50))values of these root extracts againstα-amylase andα-glucosidase activities,evaluating their effects onα-amy-lase kinetics,quantifying the inhibition of bovine serum albumin(BSA)glycation using fluo-rometry to assess advanced glycation end products(AGE)production,and determining glu-cose uptake by isolated rat hemidiaphragm.Additionally,molecular docking analysis was conducted to investigate the binding affinity and interaction types between Bryonia dioica lig-ands(cucurbitacin B,bryogénin,vitexin,and isovitexin)and target enzymes,and a phyto-chemical-targets interaction network was constructed.Results Forα-amylase inhibition,ethyl acetate fraction demonstrated the most potent activi-ty(IC_(50)=145.95μg/mL),followed by chloroform-methanol extract(IC_(50)=300.86μg/mL).Water-acetone root extracts and their ethyl acetate and butanol fractions inhibited theα-glucosidase activity with IC50 values ranging from 562.88 to 583.90μg/mL.Both ethyl acetate and butanol fractions strongly inhibited non-enzymatic BSA glycation(IC_(50)=318.26 and 323.12μg/mL,respectively).The incubation of isolated rat hemidiaphragms with the ethyl acetate fraction(5 mg/mL)significantly increased glucose uptake(35.16%;P<0.0001),exceeding the effects of insulin(29.27%),chloroform-methanol extract(24.07%),and catechin(15.27%).Molecular docking revealed that cucurbitacin B exhibited the strongest docking scores againstα-amylase(-16.4 kcal/mol),andα-glucosidase(-14.2 kcal/mol).Compared with other ligands,isovitexin formed the maximum number of hydrogen bonds with theα-amylase active site residues(Asp300,Asp197,and Glu233),α-glucosidase residues(Ser13,Arg44,Met86,Gly10,Asp39,and Tyr131)and other residues(Arg195,Trp59,His299,and Tyr62).Network analysis identified 36 overlapping targets between Bryonia dioica phyto-chemicals and type 2 diabetes mellitus-associated genes,with cucurbitacins and polyphenols interacting withα-amylase,α-glucosidase,and Glut4 translocation pathway targets.Conclusion Bryonia dioica root extracts demonstrated promising in vitro anti-diabetic activi-ty through multiple mechanisms,including the inhibitory effect on digestive enzymes,pro-tein antiglycation potential,and enhancement of glucose uptake,suggesting their potential as a source for anti-diabetic drugs development.
基金supported by the National Natural Science Foundation of China(No.42272222)the Basic Research Funds of Institute of Geomechanics,Chinese Academy of Geological Sciences(No.DZLXJK202211)China Geological Survey(Nos.DD20190306,DD20190546,DD20160269,DD20230249)。
文摘The 1605 M7½ Earthquake is the only earthquake in the history of China that has caused large-scale land subsidence into the sea,with the total area of land subsidence exceeding 100 km2.The disaster has led to the sinking of 72 villages.There is still no clear understanding of the source seismogenic fault of this earthquake.In this work,we conducted a detailed study of the middle segment of the Maniao-Puqian fault(MPF),which is the epicenter area,through geomorphological survey,data collection,shallow seismic exploration,cross-section drilling,and chronological dating.The results showed that the middle segment of the MPF zone is composed of three nearly parallel normal faults with a dextral strike-slip:“Macun-Luodou fault(F2-1),Haixiu-Dongyuan fault(F2-2),and ChangliuZhuxihe fault(F2-3)”.And F2-2 is composed of two secondary faults,namely F2-2′and F2-2″,with a flower-shaped structure buried under the ground.It is distributed nearly east-west,dipping to the north and has experienced at least five stages of activities since the Miocene.The vertical activity rates of F2-2′and F2-2″are~2.32 and~2.5 mm/a,since the Holocene,respectively.There were eight cycles of transgression and regression since the Miocene.The fault activity resulted in the thickening of the Holocene strata with a slight dip to the south,on the hanging wall,showing V-shaped characteristics.The MPF is likely the source seismogenic fault of the M7½ earthquake that hit Qiongshan in 1605.
文摘Background:The Compendium of Physical Activities was published in 1993 to improve the comparability of energy expenditure values assigned to self-reported physical activity(PA)across studies.The original version was updated in 2000,and again in 2011,and has been widely used to support PA research,practice,and public health guidelines.Methods:This 2024 update was tailored for adults 19-59 years of age by removing data from those≥60 years.Using a systematic review and supplementary searches,we identified new activities and their associated measured metabolic equivalent(MET)values(using indirect calorimetry)published since 2011.We replaced estimated METs with measured values when possible.Results:We screened 32,173 abstracts and 1507 full-text papers and extracted 2356 PA energy expenditure values from 701 papers.We added303 new PAs and adjusted 176 existing MET values and descriptions to reflect the addition of new data and removal of METs for older adults.We added a Major Heading(Video Games).The 2024 Adult Compendium includes 1114 PAs(912 with measured and 202 with estimated values)across 22 Major Headings.Conclusion:This comprehensive update and refinement led to the creation of The 2024 Adult Compendium,which has utility across research,public health,education,and healthcare domains,as well as in the development of consumer health technologies.The new website with the complete lists of PAs and supporting resources is available at https://pacompendium.com.
文摘Background:Prolonged sitting and reduced physical activity lead to low energy expenditures.However,little is known about the joint impact of daily sitting time and physical activity on body fat distribution.We investigated the independent and joint associations of daily sitting time and physical activity with body fat among adults.Methods:This was a cross-sectional analysis of U.S.nationally representative data from the National Health and Nutrition Examination Survey2011-2018 among adults aged 20 years or older.Daily sitting time and leisure-time physical activity(LTPA)were self-reported using the Global Physical Activity Questionnaire.Body fat(total and trunk fat percentage)was determined via dual X-ray absorptiometry.Results:Among 10,808 adults,about 54.6%spent 6 h/day or more sitting;more than one-half reported no LTPA(inactive)or less than 150 min/week LTPA(insufficiently active)with only 43.3%reported 150 min/week or more LTPA(active)in the past week.After fully adjusting for sociodemographic data,lifestyle behaviors,and chronic conditions,prolonged sitting time and low levels of LTPA were associated with higher total and trunk fat percentages in both sexes.When stratifying by LTPA,the association between daily sitting time and body fat appeared to be stronger in those who were inactive/insuufficiently active.In the joint analyses,inactive/insuufficiently active adults who reported sitting more than 8 h/day had the highest total(female:3.99%(95%confidence interval(95%CI):3.09%-4.88%);male:3.79%(95%CI:2.75%-4.82%))and trunk body fat percentages(female:4.21%(95%CI:3.09%-5.32%);male:4.07%(95%CI:2.95%-5.19%))when compared with those who were active and sitting less than 4 h/day.Conclusion:Prolonged daily sitting time was associated with increased body fat among U.S.adults.The higher body fat associated with 6 h/day sitting may not be offset by achieving recommended levels of physical activity.
文摘Physical activity(PA)is fundamentally linked to public health,^(1)providing benefits including chronic disease prevention and treatment,^(2)mental health,^(3)musculoskeletal health,^(4)and healthy aging,^(5)along with socioeconomic advantages.^(6)These benefits highlight the importance of promoting PA for all populations.The recent publication of the Compendium of Physical Activities(Compendium)serves as a valuable resource,^(7)offering an updated and expanded guide for adults(ages 19-59)with tailored energy cost values for diverse populations.
基金supported by a grant(2022-MOIS62-001(RS-2022-ND640011))from the National Disaster Risk AnalysisManagement Technology in Earthquake funded by the Ministry of Interior and Safety(MOIS,Korea).
文摘Deformed soft-sediment deformation structures(SSDS)can indicate polyphase deformation events and provide valuable insights into the inversion process of a basin.Herein,we present the Miocene–Quaternary deformation inversion history of the Bomun sub-basin in the Gyeongju area of SE Korea.The inferred ENE compression direction(σHmax)based on paleostress analysis of the fault system,displacing Miocene sediments and SSDS,corresponds to the current stress field.The widespread occurrence of clear liquefaction structures and the vertical repetition of SSDS indicate substantial seismic activity during the basin opening stage.Brittle deformation features observed at both outcrop-and microstructural-scale along the faults suggest a reactivation as reverse faulting associated with a tilting process.The tectonic history of the study area is distinguished by SSDS associated with seismic activity,and reverse faulting associated with inversion process under ENE orientedσHmax.The Environmental Seismic Intensity Scale(ESI-07)based on the SSDS indicates seismic intensity of IX-X,which might be related with the opening of the Bomun sub-basin.Therefore,detailed analyses of SSDS could provide valuable insights on the dynamics of local geology and contribute to further extensive research on seismic hazards and basin inversion.
文摘1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to achieve health benefits.1-3 Absent from these guidelines are recommendations for light intensity PA(LPA,e.g.,walking at a leisurely pace of 3 km/h or less,equivalent to 1.5-2.9 metabolic equivalents).
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supported by FDCT grants from the Macao Science and Technology Development Fund,China,No.002/2023/ALC(to BYKL)Foshan Medicine Dengfeng Project of China 2019-2021(to BYKL)+3 种基金the Science and Technology Program of Sichuan Province,Nos.2022YFS0620(to DQ)and MZGC20230041(to XFW)the TCMs Commission of Sichuan Province,No.2021MS469(to YT)the Science and Technology Program of Luzhou,No.2022-WGR-194(to YT)the Southwest Medical University Science and Technology Program,No.2021NJXNYD04(to DQ).
文摘Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.
文摘1.Legacy matters The withdrawal of Australia as hosts for the Commonwealth Games in 2026 demonstrates that large international sporting events are more than just sporting mastery,medals,and memories.Money also matters.1 The cost of hosting a major international tournament is eye-wateringly high.Host governments need to show that the billions of dollars of investment deliver a return beyond sporting glory to justify the resources that are spent.
基金supported by the National Foundation of China(Grant Nos.41941016 and 42174123)China Geological Survey(Grant No.DD20221630).
文摘The Guxiang-Tongmai segment of the Jiali fault is situated northeast of the Namche Barwa Syntaxis in northeastern Xizang.It is one of the most active strike-slip faults near the syntaxis and plays a pivotal role in the examination of seismic activity within the eastern Himalayan Syntaxis.New study in the research region has yielded a 1:200000 gravity dataset covering an area 1500 km^(2).Using wavelet transform multiscale decomposition,scratch analysis techniques,and 3D gravity inversion methods,gravity anomalies,fault distributions,and density structures were determined across various scales.Through the integration of our new gravity data with other geophysical and geological information,our findings demonstrate substantial variations in the overall crustal density within the region,with the fault distribution closely linked to these density fluctuations.Disparities in stratigraphic density are important causes of variations in the capacity of geological formations to endure regional tectonic stress.Earthquakes are predominantly concentrated within the density transition zone and are primarily situated in regions of elevated density.The hanging wall stress within the Guxiang-Tongmai segment of the Jiali fault exhibits a notable concentration,marked by pronounced anisotropy,and is positioned within the density differential zone,which is prone to earthquakes.
文摘Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older adults.MET values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older adults.Results:We identified 68 articles and extracted energy expenditure data on 427 PAs.From these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older adults.We developed a website to present the OA Compendium MET_(60+)values:https://pacompendium.com.Conclusion:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older adults.It is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.
基金The National Natural Science Foundation of China(No.22177136)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.CIFMS-2021-I2M-1-007,2022-I2M-2-002)。
文摘Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads.Hence,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology.Herein,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2,4-triazole.Interestingly,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif.This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom.The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping.Importantly,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect.Interestingly,one pair of regioisomers(19S and 19X)induced distinct modes of cell death.Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis.Together,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.
