BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
Partial substitution of chemical fertilizers by organic amendments is adopted widely for promoting the availability of soil phosphorus(P)in agricultural production.However,few studies have comprehensively evaluated th...Partial substitution of chemical fertilizers by organic amendments is adopted widely for promoting the availability of soil phosphorus(P)in agricultural production.However,few studies have comprehensively evaluated the effects of longterm organic substitution on soil P availability and microbial activity in greenhouse vegetable fields.A 10-year(2009–2019)field experiment was carried out to investigate the impacts of organic fertilizer substitution on soil P pools,phosphatase activities and the microbial community,and identify factors that regulate these soil P transformation characteristics.Four treatments included 100%chemical N fertilizer(4 CN),50%substitution of chemical N by manure(2 CN+2 MN),straw(2 CN+2 SN),and combined manure with straw(2 CN+1 MN+1 SN).Compared with the 4 CN treatment,organic substitution treatments increased celery and tomato yields by 6.9-13.8%and 8.6-18.1%,respectively,with the highest yields being in the 2 CN+1 MN+1 SN treatment.After 10 years of fertilization,organic substitution treatments reduced total P and inorganic P accumulation,increased the concentrations of available P,organic P,and microbial biomass P,and promoted phosphatase activities(alkaline and acid phosphomonoesterase,phosphodiesterase,and phytase)and microbial growth in comparison with the 4 CN treatment.Further,organic substitution treatments significantly increased soil C/P,and the partial least squares path model(PLS-PM)revealed that the soil C/P ratio directly and significantly affected phosphatase activities and the microbial biomass and positively influenced soil P pools and vegetable yield.Partial least squares(PLS)regression demonstrated that arbuscular mycorrhizal fungi positively affected phosphatase activities.Our results suggest that organic fertilizer substitution can promote soil P transformation and availability.Combining manure with straw was more effective than applying these materials separately for developing sustainable P management practices.展开更多
To assess the effects of savanna afforestation on soil phosphorus （P） transformations in eastern Horqin Sandy Land, China, P fractions and phosphomonoesterase activities were examined in two soil horizons （0-5 cm a...To assess the effects of savanna afforestation on soil phosphorus （P） transformations in eastern Horqin Sandy Land, China, P fractions and phosphomonoesterase activities were examined in two soil horizons （0-5 cm and 5-20 cm） under a savanna and an adjacent 30-year-old Mongolian pine （Pinus sylvestris L. vat. mongolica Litv.） plantation on a P-deficient semi arid sandy soil. The results showed that all soil P fractions and phosphomonoestcrase activities decreased with soil depth at both sites except that labile organic P under the plantation was constant with soil depth, In contrast to savanna, soils trader Mongolian pine plantation had lower phosphomonoesterase activities and concentrations of all P fractions （with an exception of Al-P）, lower proportions of organic P and Ca-P in total P, and higher proportions of labile P, Al-P and Fe-P in total P. These results suggested that P transformations mainly occurred in surface soils, and P recycled through litterfall was the most important source of plant available P. Mongolian pine afforestation enhanced the bioavailability of both organic P and Ca-P. simultaneously reduced soil P pools. indicating that protection of forest floor and P fertilization are necessary to maintain the sustainable functioning of Mongolian pine plantations.展开更多
[ Objective ] The paper was to screen the better extraction method for herbicidal active substances of Eupatorium adenophorum. [ Method ] Three com- mon extraction methods, Soxhlet extraction, ultrasonic extraction an...[ Objective ] The paper was to screen the better extraction method for herbicidal active substances of Eupatorium adenophorum. [ Method ] Three com- mon extraction methods, Soxhlet extraction, ultrasonic extraction and conventional extraction method, were used to prepare E. adenophorum extracts, and the herblcidal activity of E. adenophorum extracts extracted by 3 methods was studied by seed germination method. [ Result] The extraction rate of Soxhlet extraction was the highest of （22.54 ± 0.48 ）%, and the herbicidal activities of E. adenophorum extracted by Soxhlet extraction was relatively stronger. [ Conclusion] Soxhlet extraction was the better extraction method for herbicidal active substances of E. adenophorum.展开更多
Background:Whether or not there is targeted pharmacotherapy for dementia,an active and healthy lifestyle that includes physical activity(PA)may be a better option than medication for preventing dementia.We examined th...Background:Whether or not there is targeted pharmacotherapy for dementia,an active and healthy lifestyle that includes physical activity(PA)may be a better option than medication for preventing dementia.We examined the association between leisure-time sedentary behavior(SB)and the risk of dementia incidence and mortality.We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities.Methods:In the UK Biobank,484,169 participants(mean age=56.5 years;45.2%men)free of dementia were followed from baseline(2006-2010)through July 30,2021.A standard questionnaire measured individual leisure-time SB(watching TV,computer use,and driving)and PA(walking for pleasure,light and heavy do-it-yourself activity,strenuous sports,and other exercise)frequency and duration in the 4 weeks prior to evaluation.Apolipoprotein E(APOE)genotype data were available for a subset of 397,519(82.1%)individuals.A Cox proportional hazard model and an isotemporal substitution model were used in this study.Results:During a median 12.4 years of follow-up,6904 all-cause dementia cases and 2115 deaths from dementia were recorded.In comparison to participants with leisure-time SB<5 h/day,the hazard ratio((HR),95%confidence interval(95%CI))of dementia incidence was 1.07(1.02-1.13)for 5-8 h/day and 1.25(1.13-1.38)for>8 h/day,and the HR of dementia mortality was 1.35(1.12-1.61)for>8 h/day.A 1 standard deviation increment of sedentary time(2.33 h/day)was strongly associated with a higher incidence of dementia and mortality(HR=1.06,95%CI:1.03-1.08 and HR=1.07,95%CI:1.03-1.12,respectively).The association between sedentary time and the risk of developing dementia was more profound in subjects<60 years than in those>60 years(HR=1.26,95%CI:1.00-1.58 vs.HR=1.21,95%CI:1.08-1.35 in>8 h/day,p for interaction=0.013).Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a6%decreased risk and 9%decreased mortality from dementia,with exercise(e.g.,swimming,cycling,aerobics,bowling)showing the strongest benefit(HR=0.82,95%CI:0.78-0.86 and HR=0.79,95%CI:0.72-0.86).Compared with APOEε4 noncarriers,APOEε4 carriers are more likely to see a decrease in Alzheimer’s disease incidence and mortality when PA is substituted for SB.Conclusion:Leisure-time SB was positively associated with the risk of dementia incidence and mortality.Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.展开更多
Alpine tundra ecosystems have specific vegetation and environmental conditions that may affect soil phosphorus （P） composition and phosphatase activities. However, these effects are poody understood. This study used...Alpine tundra ecosystems have specific vegetation and environmental conditions that may affect soil phosphorus （P） composition and phosphatase activities. However, these effects are poody understood. This study used NaOH-EDTA extraction and solution ^31P nuclear magnetic resonance （NMR） spectroscopy to determine soil P composition and phosphatase activities, including acid phosphomonoesterase （AcP）, phosphodiesterase （PD） and inorganic pyrophosphatase （IPP）, in the alpine tundra of the Changbai Mountains at seven different altitudinal gradients （i.e., 2000 m, 2100 m, 2200 m, 2300 m, 2400 m, 2500 m, and 2600 m）. The results show that total P （TP）, organic P （OP）, OP/TP, NaOH-EDTA extracted P and AcP, PD, and IPP activities over the altitude range of 2500-2600 m are significantly lower than those below 2400 m. The dominant extracted form of P is OP （73%0-83%） with a large proportion of monoesters （65%0-72%）, whereas inorganic P is present in lower proportions （17%-27%）. The activity of AcP is significantly positively correlated with the contents of soil OP, total carbon （TC）, total nitrogen （TN）, and TP （P 〈 0.05）, indicating that the AcP is a more sensitive index for responding P nutrient storage than PD and IPP. Soil properties, P composition, and phosphatase activities decrease with increased altitude and soil pH. Our results indicate that the distribution of soil P composition and phosphatase activities along altitude and AcP may play an important role in P hydrolysis as well as have the potential to be an indicator of soil quality.展开更多
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
基金supported by the China Agriculture Research System of MOF and MARA(CARS-23-B04)the National Key Research and Development Program of China(2016YFD0201001)。
文摘Partial substitution of chemical fertilizers by organic amendments is adopted widely for promoting the availability of soil phosphorus(P)in agricultural production.However,few studies have comprehensively evaluated the effects of longterm organic substitution on soil P availability and microbial activity in greenhouse vegetable fields.A 10-year(2009–2019)field experiment was carried out to investigate the impacts of organic fertilizer substitution on soil P pools,phosphatase activities and the microbial community,and identify factors that regulate these soil P transformation characteristics.Four treatments included 100%chemical N fertilizer(4 CN),50%substitution of chemical N by manure(2 CN+2 MN),straw(2 CN+2 SN),and combined manure with straw(2 CN+1 MN+1 SN).Compared with the 4 CN treatment,organic substitution treatments increased celery and tomato yields by 6.9-13.8%and 8.6-18.1%,respectively,with the highest yields being in the 2 CN+1 MN+1 SN treatment.After 10 years of fertilization,organic substitution treatments reduced total P and inorganic P accumulation,increased the concentrations of available P,organic P,and microbial biomass P,and promoted phosphatase activities(alkaline and acid phosphomonoesterase,phosphodiesterase,and phytase)and microbial growth in comparison with the 4 CN treatment.Further,organic substitution treatments significantly increased soil C/P,and the partial least squares path model(PLS-PM)revealed that the soil C/P ratio directly and significantly affected phosphatase activities and the microbial biomass and positively influenced soil P pools and vegetable yield.Partial least squares(PLS)regression demonstrated that arbuscular mycorrhizal fungi positively affected phosphatase activities.Our results suggest that organic fertilizer substitution can promote soil P transformation and availability.Combining manure with straw was more effective than applying these materials separately for developing sustainable P management practices.
基金This work was supported by Innovation Research Project of Chinese Academy of Sciences （KZCX3-SW-418）, National Natural Science Foundation of China （30471377） and sustentation project of the Institute of Applied Ecology of Chinese Academy of Sciences （SLYQY0409）.
文摘To assess the effects of savanna afforestation on soil phosphorus （P） transformations in eastern Horqin Sandy Land, China, P fractions and phosphomonoesterase activities were examined in two soil horizons （0-5 cm and 5-20 cm） under a savanna and an adjacent 30-year-old Mongolian pine （Pinus sylvestris L. vat. mongolica Litv.） plantation on a P-deficient semi arid sandy soil. The results showed that all soil P fractions and phosphomonoestcrase activities decreased with soil depth at both sites except that labile organic P under the plantation was constant with soil depth, In contrast to savanna, soils trader Mongolian pine plantation had lower phosphomonoesterase activities and concentrations of all P fractions （with an exception of Al-P）, lower proportions of organic P and Ca-P in total P, and higher proportions of labile P, Al-P and Fe-P in total P. These results suggested that P transformations mainly occurred in surface soils, and P recycled through litterfall was the most important source of plant available P. Mongolian pine afforestation enhanced the bioavailability of both organic P and Ca-P. simultaneously reduced soil P pools. indicating that protection of forest floor and P fertilization are necessary to maintain the sustainable functioning of Mongolian pine plantations.
基金Supported by Youth Fund Project of Yunnan Agricultural University
文摘[ Objective ] The paper was to screen the better extraction method for herbicidal active substances of Eupatorium adenophorum. [ Method ] Three com- mon extraction methods, Soxhlet extraction, ultrasonic extraction and conventional extraction method, were used to prepare E. adenophorum extracts, and the herblcidal activity of E. adenophorum extracts extracted by 3 methods was studied by seed germination method. [ Result] The extraction rate of Soxhlet extraction was the highest of （22.54 ± 0.48 ）%, and the herbicidal activities of E. adenophorum extracted by Soxhlet extraction was relatively stronger. [ Conclusion] Soxhlet extraction was the better extraction method for herbicidal active substances of E. adenophorum.
基金supported by Shanghai Municipal Human Resources and Social Security Bureau(2020074)Clinical Research Plan of SHDC(SHDC2020CR4006)+2 种基金Shanghai Ninth People’s Hospital(YBKA201909)Innovative research team of high-level local universities in Shanghai(SHSMU-ZDCX20212501)Shanghai Municipal Health Commission(2022XD017)。
文摘Background:Whether or not there is targeted pharmacotherapy for dementia,an active and healthy lifestyle that includes physical activity(PA)may be a better option than medication for preventing dementia.We examined the association between leisure-time sedentary behavior(SB)and the risk of dementia incidence and mortality.We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities.Methods:In the UK Biobank,484,169 participants(mean age=56.5 years;45.2%men)free of dementia were followed from baseline(2006-2010)through July 30,2021.A standard questionnaire measured individual leisure-time SB(watching TV,computer use,and driving)and PA(walking for pleasure,light and heavy do-it-yourself activity,strenuous sports,and other exercise)frequency and duration in the 4 weeks prior to evaluation.Apolipoprotein E(APOE)genotype data were available for a subset of 397,519(82.1%)individuals.A Cox proportional hazard model and an isotemporal substitution model were used in this study.Results:During a median 12.4 years of follow-up,6904 all-cause dementia cases and 2115 deaths from dementia were recorded.In comparison to participants with leisure-time SB<5 h/day,the hazard ratio((HR),95%confidence interval(95%CI))of dementia incidence was 1.07(1.02-1.13)for 5-8 h/day and 1.25(1.13-1.38)for>8 h/day,and the HR of dementia mortality was 1.35(1.12-1.61)for>8 h/day.A 1 standard deviation increment of sedentary time(2.33 h/day)was strongly associated with a higher incidence of dementia and mortality(HR=1.06,95%CI:1.03-1.08 and HR=1.07,95%CI:1.03-1.12,respectively).The association between sedentary time and the risk of developing dementia was more profound in subjects<60 years than in those>60 years(HR=1.26,95%CI:1.00-1.58 vs.HR=1.21,95%CI:1.08-1.35 in>8 h/day,p for interaction=0.013).Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a6%decreased risk and 9%decreased mortality from dementia,with exercise(e.g.,swimming,cycling,aerobics,bowling)showing the strongest benefit(HR=0.82,95%CI:0.78-0.86 and HR=0.79,95%CI:0.72-0.86).Compared with APOEε4 noncarriers,APOEε4 carriers are more likely to see a decrease in Alzheimer’s disease incidence and mortality when PA is substituted for SB.Conclusion:Leisure-time SB was positively associated with the risk of dementia incidence and mortality.Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.
基金National Natural Science Foundation of China(No.41171241)
文摘Alpine tundra ecosystems have specific vegetation and environmental conditions that may affect soil phosphorus （P） composition and phosphatase activities. However, these effects are poody understood. This study used NaOH-EDTA extraction and solution ^31P nuclear magnetic resonance （NMR） spectroscopy to determine soil P composition and phosphatase activities, including acid phosphomonoesterase （AcP）, phosphodiesterase （PD） and inorganic pyrophosphatase （IPP）, in the alpine tundra of the Changbai Mountains at seven different altitudinal gradients （i.e., 2000 m, 2100 m, 2200 m, 2300 m, 2400 m, 2500 m, and 2600 m）. The results show that total P （TP）, organic P （OP）, OP/TP, NaOH-EDTA extracted P and AcP, PD, and IPP activities over the altitude range of 2500-2600 m are significantly lower than those below 2400 m. The dominant extracted form of P is OP （73%0-83%） with a large proportion of monoesters （65%0-72%）, whereas inorganic P is present in lower proportions （17%-27%）. The activity of AcP is significantly positively correlated with the contents of soil OP, total carbon （TC）, total nitrogen （TN）, and TP （P 〈 0.05）, indicating that the AcP is a more sensitive index for responding P nutrient storage than PD and IPP. Soil properties, P composition, and phosphatase activities decrease with increased altitude and soil pH. Our results indicate that the distribution of soil P composition and phosphatase activities along altitude and AcP may play an important role in P hydrolysis as well as have the potential to be an indicator of soil quality.
