Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.Thi...Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.This study featured the combined supplementation of soy lecithin(SL)and soy isoflavones(SIF),using in vivo animal models,in vitro vascular ring preparation,and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives.The results show that Aβcan significantly induce learning and memory impairment in rats,as well as pathological changes in brain blood vessels,exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain.The above-mentioned phenomena induced by Aβcan be significantly improved by the combined intervention of SL and SIF.Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβin rat brain vascular tissues and bEND.3 cells.Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared.Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/e NOS pathway within cerebral vascular.This activation improves cerebrovascular vasodilation,offering potential protective effects for both cerebral vascular health and cognitive function.展开更多
The present study examined the role of emotional balance and the moderating role of rumination in the relationship between psychological inflexibility and sleep quality among college students.Participants were 837 Chi...The present study examined the role of emotional balance and the moderating role of rumination in the relationship between psychological inflexibility and sleep quality among college students.Participants were 837 Chinese college students(females=52%,mean age=18.89,SD=0.93 years).They completed the Multidimensional Psychological Inflexibility Scale(MPIS),Affect Balance Scale(ABS),Ruminative Response Scale(RRS),Pittsburgh Sleep Quality Index(PSQI).We utilized moderated-mediation analysis to explore the mechanism of action among variables.Emotional balance mediated the relationship between psychological inflexibility and sleep quality,and rumination moderated the direct effect of psychological inflexibility on sleep quality and the mediating effect of emotional balance.Specifically,the direct effect of psychological inflexibility on sleep quality and the mediating effect of emotional balance increased with the increase in rumination level.High levels of rumination in individuals exacerbate the negative effects of psychological inflexibility on sleep quality.It also enhances the disruption of psychological inflexibility on the individual’s emotional balance ability,which leads to poorer sleep quality.The results contribute to the evidence of how psychological inflexibility explains the sleep quality of college students and how sleep quality can be improved by psychological inflexibility interventions,rumination interventions,and emotional balance interventions.Student development services should provide targeted students’sleep quality counseling for the promotion and maintenance of college students’physical and mental health.展开更多
Background:The aging global population necessitates innovative strategies to enhance older adults’health and quality of life.Physical activity(PA)is crucial for healthy aging,yet many older adults struggle to exercis...Background:The aging global population necessitates innovative strategies to enhance older adults’health and quality of life.Physical activity(PA)is crucial for healthy aging,yet many older adults struggle to exercise regularly.Artificial intelligence(AI)-powered social robots offer an interactive,engaging,and personalized solution to promote PA among this demographic.This systematic review investigated the role of AI-powered social robots in encouraging PA in older adults.Methods:We conducted a systematic literature search in databases including PubMed,IEEE Xplore,Scopus,Cochrane Library,and Web of Science,focusing on studies published until February 2024.We included peer-reviewed articles reporting empiricalfindings on designing,implementing,and evaluating AI-enabled social robots to promote PA among older adults.Studies were conducted in nursing homes,rehabilita-tion centers,community centers,and home environments.Results:A total of 19 studies were included in the review.Analysis reveals that AI-powered social robots effectively motivate older adults to engage in PAs,leading to increased exercise adherence,higher engagement levels,and extended training durations.Social robots have demon-strated effectiveness across various environments,including nursing homes,rehabilitation centers,community centers,home environments,and elder care facilities.In structured environments like nursing homes and rehabilitation centers,robots help maintain regular exercise routines,improving adherence and recovery outcomes.In community and elder care centers,robots promote PA and social engagement by facilitating group exercises and enhancing participation.In home environments,robots provide personalized support for daily activities,offering reminders and engagement,which fosters long-term activity engagement.User acceptance and satisfaction are high,with participantsfinding the robots engaging and enjoyable.Additionally,several studies indicate potential health benefits,such as improved medication adherence,better sleep patterns,and enhanced overall well-being.Nevertheless,additional research is imperative to address unresolved issues concerning the technolog-ical maintenance costs,design constraints,and adaptability of AI-powered social robots to specific user demographics.Conclusion:AI-powered social robots play a promising role in promoting PA among older adults,enhancing their health,well-being,and inde-pendence.This review provides insights for researchers,designers,and healthcare professionals developing AI-enabled social robotic systems for older adults.展开更多
Background: Neighborhood built environment may profoundly influence children's physical activity(PA) and body weight. This study systematically reviewed scientific evidence regarding the impact of built environmen...Background: Neighborhood built environment may profoundly influence children's physical activity(PA) and body weight. This study systematically reviewed scientific evidence regarding the impact of built environment on PA and obesity among children and adolescents in China.Methods: A keyword and reference search was conducted in Active Living Research, Cochrane Library, PubMed, and Web of Science. Studies that met all of the following criteria were included in the review:(1) study designs—experimental studies, observational studies, and qualitative studies;(2) study subjects—Chinese children and/or adolescents aged 17 years;(3) exposures—neighborhood built environment;(4)outcomes—PA and/or body weight status;(5) article type—peer-reviewed publications;(6) time window of search—from the inception of an electronic bibliographic database to May 31, 2018;(7) country—China; and(8) language—articles written in English.Results: A total of 20 studies, including 16 cross-sectional studies, 3 longitudinal studies, and 1 descriptive study, met the predetermined selection criteria and were included in the review. A total of 13 studies adopted subjective built environment measures reported by parents and/or children, 2 adopted objective measures(e.g., geographical information system, field observations), and 5 adopted both objective and subjective measures. PA behaviors included PA, physical inactivity, sedentary behavior, active/passive commuting from/to school, and park visits. Among the 16 studies that provided some quantitative estimates of the influence of built environment on PA and body weight status, all reported a statistically significant relationship in the expected direction. Availability and accessibility in proximity to greenspaces, parks, recreational facilities,and sidewalks were found to be associated with increased PA levels, reduced sedentary behaviors, and/or active commuting among Chinese children and adolescents. In contrast, the absence of bike lanes and living in higher density residential areas were associated with increased likelihood of childhood overweight and obesity.Conclusion: Neighborhood built environment plays an important role in Chinese children's PA engagement and weight outcomes. Building new exercise facilities and enhancing the accessibility of existing facilities hold the potential to enhance PA engagement among Chinese children and adolescents. In addition, urban designs that incorporate sidewalks, bike lanes, walking paths, less motorized traffic, and lower residential density are likely to promote PA and prevent childhood obesity in China.展开更多
Background:Starch is an important substance that supplies energy to ruminants.To provide sufficient energy for high-yielding dairy ruminants,they are typically fed starch-enriched diets.However,starch-enriched diets h...Background:Starch is an important substance that supplies energy to ruminants.To provide sufficient energy for high-yielding dairy ruminants,they are typically fed starch-enriched diets.However,starch-enriched diets have been proven to increase the risk of milk fat depression(MFD)in dairy cows.The starch present in ruminant diets could be divided into rumen-degradable starch(RDS)and rumen escaped starch(RES)according to their different degradation sites(rumen or intestine).Goats and cows have different sensitivities to MFD.Data regarding the potential roles of RDS in milk fat synthesis in the mammary tissue of dairy goats and in regulating the occurrence of MFD are limited.Results:Eighteen Guanzhong dairy goats(day in milk=185±12 d)with similar parity,weight,and milk yield were selected and randomly assigned to one of three groups(n=6),which were fed an LRDS diet(Low RDS=20.52%),MRDS diet(Medium RDS=22.15%),or HRDS diet(High RDS=24.88%)for 5 weeks.Compared with that of the LRDS group,the milk fat contents in the MRDS and HRDS groups significantly decreased.The yields of short-,mediumand long-chain fatty acids decreased in the HRDS group.Furthermore,increased RDS significantly decreased ruminal B.fibrisolvens and Pseudobutyrivibrio abundances and increased the trans-10,cis-12 conjugated linoleic acid(CLA)and trans-10 C18:1 contents in the rumen fluid.A multiomics study revealed that the HRDS diet affected mammary lipid metabolism down-regulation of ACSS2,MVD,AGPS,SCD5,FADS2,CERCAM,SC5D,HSD17B7,HSD17B12,ATM,TP53RK,GDF1 and LOC102177400.Remarkably,the significant decrease of INSIG1,whose expression was depressed by trans-10,cis-12 CLA,could reduce the activity of SREBP and,consequently,downregulate the downstream gene expression of SREBF1.Conclusions:HRDS-induced goat MFD resulted from the downregulation of genes involved in lipogenesis,particularly,INSIG1.Specifically,even though the total starch content and the concentrate-to-fiber ratio were the same as those of the high-RDS diet,the low and medium RDS diets did not cause MFD in lactating goats.展开更多
Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral...Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.展开更多
As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of ...As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.展开更多
AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles...AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicated in additional prospective studies.展开更多
AIM： To explore the interaction models of the cytochrome P-450 （CYP） 1A1 Valvariant and glutathione S-transferase （GST） M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. M...AIM： To explore the interaction models of the cytochrome P-450 （CYP） 1A1 Valvariant and glutathione S-transferase （GST） M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS： A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblingsin-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS： The frequency of the CYPIA1 Valvariant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 （95% confidence interval [95%CI]： 1.2-3.1, P〈0.01）. It showed a significant type 2 form of interaction model when both CYPIA1 Valvariant allele and former tobacco smoking existed （i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYPIA1 variant alone）. The interaction index y was 2.8, and OReg （95%CI） was 5.0 （1.9-13.4）. GSTM1 null genctype and former tobacco smoking were significant in a type 4 interaction model （i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects）. The interaction index y and OReg （95%CI） were 3.4 and 8.4 （3.4-20.9）, respectively.CONCLUSION： Different interaction models of CYPIA1 Valvariant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.展开更多
Purpose This scoping review aimed to offer researchers and practitioners an understanding of artificial intelligence(AI)applications in physical activity(PA)interventions;introduce them to prevalent machine learning(M...Purpose This scoping review aimed to offer researchers and practitioners an understanding of artificial intelligence(AI)applications in physical activity(PA)interventions;introduce them to prevalent machine learning(ML),deep learning(DL),and reinforcement learning(RL)algorithms;and encourage the adoption of AI methodologies.Methods A scoping review was performed in PubMed,Web of Science,Cochrane Library,and EBSCO focusing on AI applications for promoting PA or predicting related behavioral or health outcomes.AI methodologies were summarized and categorized to identify synergies,patterns,and trends informing future research.Additionally,a concise primer on predominant AI methodologies within the realm of PA was provided to bolster understanding and broader application.Results The review included 24 studies that met the predetermined eligibility criteria.AI models were found effective in detecting significant patterns of PA behavior and associations between specific factors and intervention outcomes.Most studies comparing AI models to traditional statistical approaches reported higher prediction accuracy for AI models on test data.Comparisons of different AI models yielded mixed results,likely due to model performance being highly dependent on the dataset and task.An increasing trend of adopting state-of-the-art DL and RL models over standard ML was observed,addressing complex human–machine communication,behavior modification,and decision-making tasks.Six key areas for future AI adoption in PA interventions emerged:personalized PA interventions,real-time monitoring and adaptation,integration of multimodal data sources,evaluation of intervention effectiveness,expanding access to PA interventions,and predicting and preventing injuries.Conclusion The scoping review highlights the potential of AI methodologies for advancing PA interventions.As the field progresses,staying informed and exploring emerging AI-driven strategies is essential for achieving significant improvements in PA interventions and fostering overall well-being.展开更多
基金supported by the National Natural Science Foundation of China(82273620,81302427)。
文摘Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.This study featured the combined supplementation of soy lecithin(SL)and soy isoflavones(SIF),using in vivo animal models,in vitro vascular ring preparation,and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives.The results show that Aβcan significantly induce learning and memory impairment in rats,as well as pathological changes in brain blood vessels,exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain.The above-mentioned phenomena induced by Aβcan be significantly improved by the combined intervention of SL and SIF.Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβin rat brain vascular tissues and bEND.3 cells.Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared.Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/e NOS pathway within cerebral vascular.This activation improves cerebrovascular vasodilation,offering potential protective effects for both cerebral vascular health and cognitive function.
基金the projects funded by the Anhui Business College(Project for School level Counselors of Anhui Business College in 2023:“Research on the Influencing Factors and Intervention Mechanisms of Sleep Disorders in College Students”Grant No.2023KYF08).
文摘The present study examined the role of emotional balance and the moderating role of rumination in the relationship between psychological inflexibility and sleep quality among college students.Participants were 837 Chinese college students(females=52%,mean age=18.89,SD=0.93 years).They completed the Multidimensional Psychological Inflexibility Scale(MPIS),Affect Balance Scale(ABS),Ruminative Response Scale(RRS),Pittsburgh Sleep Quality Index(PSQI).We utilized moderated-mediation analysis to explore the mechanism of action among variables.Emotional balance mediated the relationship between psychological inflexibility and sleep quality,and rumination moderated the direct effect of psychological inflexibility on sleep quality and the mediating effect of emotional balance.Specifically,the direct effect of psychological inflexibility on sleep quality and the mediating effect of emotional balance increased with the increase in rumination level.High levels of rumination in individuals exacerbate the negative effects of psychological inflexibility on sleep quality.It also enhances the disruption of psychological inflexibility on the individual’s emotional balance ability,which leads to poorer sleep quality.The results contribute to the evidence of how psychological inflexibility explains the sleep quality of college students and how sleep quality can be improved by psychological inflexibility interventions,rumination interventions,and emotional balance interventions.Student development services should provide targeted students’sleep quality counseling for the promotion and maintenance of college students’physical and mental health.
基金supported by the Ministry of Education of Humanities and Social Science project(Grant No.22YJC890024).
文摘Background:The aging global population necessitates innovative strategies to enhance older adults’health and quality of life.Physical activity(PA)is crucial for healthy aging,yet many older adults struggle to exercise regularly.Artificial intelligence(AI)-powered social robots offer an interactive,engaging,and personalized solution to promote PA among this demographic.This systematic review investigated the role of AI-powered social robots in encouraging PA in older adults.Methods:We conducted a systematic literature search in databases including PubMed,IEEE Xplore,Scopus,Cochrane Library,and Web of Science,focusing on studies published until February 2024.We included peer-reviewed articles reporting empiricalfindings on designing,implementing,and evaluating AI-enabled social robots to promote PA among older adults.Studies were conducted in nursing homes,rehabilita-tion centers,community centers,and home environments.Results:A total of 19 studies were included in the review.Analysis reveals that AI-powered social robots effectively motivate older adults to engage in PAs,leading to increased exercise adherence,higher engagement levels,and extended training durations.Social robots have demon-strated effectiveness across various environments,including nursing homes,rehabilitation centers,community centers,home environments,and elder care facilities.In structured environments like nursing homes and rehabilitation centers,robots help maintain regular exercise routines,improving adherence and recovery outcomes.In community and elder care centers,robots promote PA and social engagement by facilitating group exercises and enhancing participation.In home environments,robots provide personalized support for daily activities,offering reminders and engagement,which fosters long-term activity engagement.User acceptance and satisfaction are high,with participantsfinding the robots engaging and enjoyable.Additionally,several studies indicate potential health benefits,such as improved medication adherence,better sleep patterns,and enhanced overall well-being.Nevertheless,additional research is imperative to address unresolved issues concerning the technolog-ical maintenance costs,design constraints,and adaptability of AI-powered social robots to specific user demographics.Conclusion:AI-powered social robots play a promising role in promoting PA among older adults,enhancing their health,well-being,and inde-pendence.This review provides insights for researchers,designers,and healthcare professionals developing AI-enabled social robotic systems for older adults.
文摘Background: Neighborhood built environment may profoundly influence children's physical activity(PA) and body weight. This study systematically reviewed scientific evidence regarding the impact of built environment on PA and obesity among children and adolescents in China.Methods: A keyword and reference search was conducted in Active Living Research, Cochrane Library, PubMed, and Web of Science. Studies that met all of the following criteria were included in the review:(1) study designs—experimental studies, observational studies, and qualitative studies;(2) study subjects—Chinese children and/or adolescents aged 17 years;(3) exposures—neighborhood built environment;(4)outcomes—PA and/or body weight status;(5) article type—peer-reviewed publications;(6) time window of search—from the inception of an electronic bibliographic database to May 31, 2018;(7) country—China; and(8) language—articles written in English.Results: A total of 20 studies, including 16 cross-sectional studies, 3 longitudinal studies, and 1 descriptive study, met the predetermined selection criteria and were included in the review. A total of 13 studies adopted subjective built environment measures reported by parents and/or children, 2 adopted objective measures(e.g., geographical information system, field observations), and 5 adopted both objective and subjective measures. PA behaviors included PA, physical inactivity, sedentary behavior, active/passive commuting from/to school, and park visits. Among the 16 studies that provided some quantitative estimates of the influence of built environment on PA and body weight status, all reported a statistically significant relationship in the expected direction. Availability and accessibility in proximity to greenspaces, parks, recreational facilities,and sidewalks were found to be associated with increased PA levels, reduced sedentary behaviors, and/or active commuting among Chinese children and adolescents. In contrast, the absence of bike lanes and living in higher density residential areas were associated with increased likelihood of childhood overweight and obesity.Conclusion: Neighborhood built environment plays an important role in Chinese children's PA engagement and weight outcomes. Building new exercise facilities and enhancing the accessibility of existing facilities hold the potential to enhance PA engagement among Chinese children and adolescents. In addition, urban designs that incorporate sidewalks, bike lanes, walking paths, less motorized traffic, and lower residential density are likely to promote PA and prevent childhood obesity in China.
基金This research was financially supported by the National Key Research and Development Program of China(award number:2017YFD0500500)the Science&Technological Project of Shaanxi Province,China(award number:2017 TSCXL-NY-04-01).
文摘Background:Starch is an important substance that supplies energy to ruminants.To provide sufficient energy for high-yielding dairy ruminants,they are typically fed starch-enriched diets.However,starch-enriched diets have been proven to increase the risk of milk fat depression(MFD)in dairy cows.The starch present in ruminant diets could be divided into rumen-degradable starch(RDS)and rumen escaped starch(RES)according to their different degradation sites(rumen or intestine).Goats and cows have different sensitivities to MFD.Data regarding the potential roles of RDS in milk fat synthesis in the mammary tissue of dairy goats and in regulating the occurrence of MFD are limited.Results:Eighteen Guanzhong dairy goats(day in milk=185±12 d)with similar parity,weight,and milk yield were selected and randomly assigned to one of three groups(n=6),which were fed an LRDS diet(Low RDS=20.52%),MRDS diet(Medium RDS=22.15%),or HRDS diet(High RDS=24.88%)for 5 weeks.Compared with that of the LRDS group,the milk fat contents in the MRDS and HRDS groups significantly decreased.The yields of short-,mediumand long-chain fatty acids decreased in the HRDS group.Furthermore,increased RDS significantly decreased ruminal B.fibrisolvens and Pseudobutyrivibrio abundances and increased the trans-10,cis-12 conjugated linoleic acid(CLA)and trans-10 C18:1 contents in the rumen fluid.A multiomics study revealed that the HRDS diet affected mammary lipid metabolism down-regulation of ACSS2,MVD,AGPS,SCD5,FADS2,CERCAM,SC5D,HSD17B7,HSD17B12,ATM,TP53RK,GDF1 and LOC102177400.Remarkably,the significant decrease of INSIG1,whose expression was depressed by trans-10,cis-12 CLA,could reduce the activity of SREBP and,consequently,downregulate the downstream gene expression of SREBF1.Conclusions:HRDS-induced goat MFD resulted from the downregulation of genes involved in lipogenesis,particularly,INSIG1.Specifically,even though the total starch content and the concentrate-to-fiber ratio were the same as those of the high-RDS diet,the low and medium RDS diets did not cause MFD in lactating goats.
基金funded by the National Natural Science Foundation of China(Grant No.81970188)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant No.2016-12M-1-001)。
文摘Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
基金supported by the grants from the Sichuan Science and Technology Program,China(Grant Nos.:2023NSFSC0614 and 2022YFS0624)Southwest Medical University Science and Technology Program,China(Grant No.:2021ZKZD017)+2 种基金the Luzhou Science and Technology Program,China(Grant Nos.:2022-YJY-127,2022YFS0624-B1,2022YFS0624-C1,and 2022YFS0624-B3)the Open Research Project Program funded by the Science and Technology Development Fund(Grant No.:SKL-QRCM(UM)-2020-2022)the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao,Macao,China)(Grant No.:SKL-QRCMOP21006).
文摘As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
基金Supported by National Institutes of Health grants,RO1ES005116(Santella RM)and P30ES009089(Santella RM)
文摘AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicated in additional prospective studies.
基金Supported by the National Natural Science Foundation of China, No. 30170827 and 30070671
文摘AIM： To explore the interaction models of the cytochrome P-450 （CYP） 1A1 Valvariant and glutathione S-transferase （GST） M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS： A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblingsin-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS： The frequency of the CYPIA1 Valvariant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 （95% confidence interval [95%CI]： 1.2-3.1, P〈0.01）. It showed a significant type 2 form of interaction model when both CYPIA1 Valvariant allele and former tobacco smoking existed （i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYPIA1 variant alone）. The interaction index y was 2.8, and OReg （95%CI） was 5.0 （1.9-13.4）. GSTM1 null genctype and former tobacco smoking were significant in a type 4 interaction model （i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects）. The interaction index y and OReg （95%CI） were 3.4 and 8.4 （3.4-20.9）, respectively.CONCLUSION： Different interaction models of CYPIA1 Valvariant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.
文摘Purpose This scoping review aimed to offer researchers and practitioners an understanding of artificial intelligence(AI)applications in physical activity(PA)interventions;introduce them to prevalent machine learning(ML),deep learning(DL),and reinforcement learning(RL)algorithms;and encourage the adoption of AI methodologies.Methods A scoping review was performed in PubMed,Web of Science,Cochrane Library,and EBSCO focusing on AI applications for promoting PA or predicting related behavioral or health outcomes.AI methodologies were summarized and categorized to identify synergies,patterns,and trends informing future research.Additionally,a concise primer on predominant AI methodologies within the realm of PA was provided to bolster understanding and broader application.Results The review included 24 studies that met the predetermined eligibility criteria.AI models were found effective in detecting significant patterns of PA behavior and associations between specific factors and intervention outcomes.Most studies comparing AI models to traditional statistical approaches reported higher prediction accuracy for AI models on test data.Comparisons of different AI models yielded mixed results,likely due to model performance being highly dependent on the dataset and task.An increasing trend of adopting state-of-the-art DL and RL models over standard ML was observed,addressing complex human–machine communication,behavior modification,and decision-making tasks.Six key areas for future AI adoption in PA interventions emerged:personalized PA interventions,real-time monitoring and adaptation,integration of multimodal data sources,evaluation of intervention effectiveness,expanding access to PA interventions,and predicting and preventing injuries.Conclusion The scoping review highlights the potential of AI methodologies for advancing PA interventions.As the field progresses,staying informed and exploring emerging AI-driven strategies is essential for achieving significant improvements in PA interventions and fostering overall well-being.
