The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests suc...The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.展开更多
BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neu...BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.展开更多
Background As the population in China rapidly ages,the prevalence of mild cognitive impairment(MCI)is increasing considerably.However,the causes of MCI vary.The continued lack of understanding of the various subtypes ...Background As the population in China rapidly ages,the prevalence of mild cognitive impairment(MCI)is increasing considerably.However,the causes of MCI vary.The continued lack of understanding of the various subtypes of MCI impedes the implementation of effective measures to reduce the risk of advancing to more severe cognitive diseases.Aims To estimate the prevalence and incidence rates of two MCI subtypes—amnestic MCI(aMCI)and vascular cognitive impairment without dementia(VCIND)—and to determine modifiable factors for them among older individuals in a multiregional Chinese cohort.Method This 1-year longitudinal study surveyed a random sample of participants aged≥60 years from a large,community-dwelling cohort in China.Baseline lifestyle data were self-reported,while vascular and comorbid conditions were obtained from medical records and physical examinations.In total,3514 and 2051 individuals completed the baseline and 1-year follow-up assessments,respectively.Logistic and linear regression analyses were used to identify the modifiable factors for MCI subtypes and predictors of cognitive decline,respectively.Results Among our participants,aMCI and VCIND demonstrated prevalence of 14.83%and 2.71%,respectively,and annual incidence(per 1000 person-years)of 69.6 and 10.6,respectively.The risk factor for aMCI was age,whereas its protective factors were high education level,tea consumption and physical activity.Moreover,VCIND risk factors were age,hypertension and depression.The presence of endocrine disease,cerebral trauma or hypertension was associated with a faster decline in cognition over 1 year.Conclusions MCI is a serious health problem in China that will only worsen as the population ages if no widespread interventions are implemented.Preventive strategies that promote brain activity and support healthy lifestyle choices are required.We identified modifiable factors for MCI in older individuals.The easy-to-adopt solutions such as tea consumption and physical activity can aid in preventing MCI.展开更多
The paper investigates the foaming and mildness properties of trehalolipids surfactant in rinse-off formulations,comparing it with the traditional nonionic surfactant alkyl-polyglycolide(APG).Both single surfactant an...The paper investigates the foaming and mildness properties of trehalolipids surfactant in rinse-off formulations,comparing it with the traditional nonionic surfactant alkyl-polyglycolide(APG).Both single surfactant and their surfactant complexes are evaluated.And the results show that trehalolipids have significant advantages in reducing surface tension,improving foam performance,and enhancing mildness.For mildness evaluation,multiple methods are employed in the study,including in vitro cell toxicity,inflammatory markers,colorimetric index of mildness CIM,and in vivo method of human skin patch test.The results show that the addition of trehalolipids increases IC50 and reduces the release of inflammatory markers of the binary surfactant system.However,the incorporation of trehalolipids has some negative effects on the skin’s lipid barrier function.Skin patch test results indicate that the addition of trehalolipids improves the mildness of surfactant system,particularly in sulfate-free system.Overall,trehalolipids,as nonionic surfactants,presents great potential to replace traditional surfactants in rinse off formulations with enhanced mildness and foam performance.展开更多
BACKGROUND Mild behavioral impairment(MBI)refers to the neurobehavioral symptoms observed in older adults that may be potential risk factors for neurodegenerative diseases.While a significant number studies have explo...BACKGROUND Mild behavioral impairment(MBI)refers to the neurobehavioral symptoms observed in older adults that may be potential risk factors for neurodegenerative diseases.While a significant number studies have explored the association between cerebrospinal fluid and MBI,only a few have examined the connection between plasma biomarkers and MBI.AIM To examine the prevalence of MBI in healthy older adults(HOAs)and individuals with mild cognitive impairment(MCI),as well as the association between MBI and plasma biomarkers of Alzheimer’s disease(AD).METHODS We enrolled a total of 241 subjects,which included 136 HOAs and 105 MCIs,from the Yuhua District of Shijiazhuang City,Hebei Province,China.The MBI symp-tom checklist(MBI-C)was utilized for the assessment and diagnosis of MBI,and a score of MBI-C≥6.5 was considered indicative of the condition.Fasting venous blood samples were collected from 70 patients,32 HOAs and 38 MCIs,and levels of amyloidβ-protein(Aβ)40,Aβ42,and hyperphosphorylated tau(p-Tau217)in these samples were measured using an enzyme-linked immunosorbent assay.RESULTS The prevalence of MBI in the HOAs and MCI groups was 4.4%and 15.3%,respectively(χ^(2)=7.262,P=0.007),with particularly notable decreases in motivation and increases in impulse dyscontrol(the highest detection rate)and social inappropriateness(P<0.05).The total MBI score correlated with Aβ42 and p-Tau217(r=-0.385,P=0.019;r=-0.330,P=0.041),but not with Aβ40 or the Aβ42/40 ratio.Among the subdomains,impulse dyscontrol was correlated with Aβ42(r=-0.401,P=0.025).CONCLUSION Both MCI and HOAs have exhibited a higher prevalence of MBI,with changes in impulse control behavior being the most common.MBI not only presents as an independent risk factor for cognitive decline but is also linked with AD-related peripheral biomarkers.展开更多
In the context of global aging,mild behavioral impairment(MBI)is present in 48.9%of patients with mild cognitive impairment(MCI).MBI,a neurobehavioral syndrome in the elderly,is an independent risk factor for cognitiv...In the context of global aging,mild behavioral impairment(MBI)is present in 48.9%of patients with mild cognitive impairment(MCI).MBI,a neurobehavioral syndrome in the elderly,is an independent risk factor for cognitive decline and is closely related to peripheral blood biomarkers associated with Alzheimer's disease,offering new diagnostic and interventional avenues for early MCI.To summarize evidence on peripheral blood biomarkers related to MBI and their underlying mechanisms involving neuroinflammation,tau pathology,and oxidative stress,a systematic review of studies published between 2015 and 2024 was conducted.MBI is closely associated with peripheral blood biomarker changes.Neuroinflammatory markers like glial fibrillary acidic protein and neurofilament light indicate astrocyte activation and neural circuit disruption,with glial fibrillary acidic protein levels correlating with impulse dyscontrol scores.Chitinase-3-like protein 1,a marker of blood-brain barrier integrity,exacerbates neuroinflammation and is linked to depressive symptoms and hippocampal atrophy.Elevated phosphorylated tau proteins in blood correlate with brain tau deposition,increasing the risk of MBI and impairing cognition.Oxidative stress markers damage neurons and disrupt neurotransmission,and concurrent alterations in malondialdehyde and superoxide dismutase levels significantly elevate the risk of MBI.The correlation between MBI and biomarkers offers new diagnostic and interventional directions for early MCI.Future research should standardize MBI assessment,conduct longitudinal studies,explore biomarker-MBI relationships,investigate psychosocial impacts,and develop advanced detection methods.展开更多
氨气(NH_(3))作为一种兼具储能的无碳燃料,在能源领域具有极大的应用前景。然而,NH_(3)的燃烧特性与常规碳氢燃料有着明显差异。该文通过数值模拟方法,研究了CH_(4)/NH_(3)的混合燃料低氧稀释(moderate or intense low-oxygen dilution,...氨气(NH_(3))作为一种兼具储能的无碳燃料,在能源领域具有极大的应用前景。然而,NH_(3)的燃烧特性与常规碳氢燃料有着明显差异。该文通过数值模拟方法,研究了CH_(4)/NH_(3)的混合燃料低氧稀释(moderate or intense low-oxygen dilution,MILD)燃烧特性。结果表明,在甲烷MILD燃烧中添加NH_(3)使出口NO排放亟剧增加。过量空气系数大于1时,减小过量空气系数使NO和CO的排放降低。NH_(3)中的N元素转化成NO的转化率随燃料中NH_(3)的增加和过量空气系数的降低而减小。展开更多
中强度低氧稀释(Moderate or Intense Low-oxygen Dilution,MILD)燃烧是一种新型低氧稀释燃烧技术,能够同时实现低NO_(x)和碳烟排放。基于化学动力学分析软件CHEMKIN-PRO中的对冲火焰模型,通过数值模拟研究了丙烷MILD燃烧方式下碳烟的...中强度低氧稀释(Moderate or Intense Low-oxygen Dilution,MILD)燃烧是一种新型低氧稀释燃烧技术,能够同时实现低NO_(x)和碳烟排放。基于化学动力学分析软件CHEMKIN-PRO中的对冲火焰模型,通过数值模拟研究了丙烷MILD燃烧方式下碳烟的生成路径及其与常规燃烧之间的差异,并深入探讨了拉伸率(50~80 s^(-1))和CO_(2)稀释(体积分数0~60%)对丙烷MILD方式下碳烟生成路径的影响。结果表明:MILD燃烧方式下碳烟生成的主要路径是2C_(3)H_(3)→A1、A1^(−)+H(+M)⇌A1(+M)、A1^(−)+CH_(4)⇌A1+CH_(3)、A1^(−)+C_(2)H_(4)⇌A1+C_(2)H_(3)、C_(6)H_(5)CH_(3)+H=A1+CH_(3)和C_(4)H_(5)^(-2)+C_(2)H_(2)=A1+H;与常规燃烧相比,MILD燃烧方式下2C_(3)H_(3)→A1和A1^(−)+H(+M)⇌A1(+M)反应速率降低,减少了A1生成进而抑制了碳烟成核,最终导致碳烟表面质量生长速率降低78.6%,最终碳烟峰值体积分数降低了83.7%;相比之下,MILD燃烧方式下2C_(3)H_(3)→A1路径对碳烟生成的贡献率降低了7.7%,而C_(6)H_(5)CH_(3)+H=A1+CH_(3)和C_(4)H_(5)^(-2)+C_(2)H_(2)=A1+H路径的贡献率重要性明显上升,分别提升5.36%和7.59%;此外,MILD燃烧方式下碳烟峰值体积分数随拉伸率的变化呈非线性特征,碳烟峰值体积分数随拉伸率的增加呈现先升高后降低的趋势,其机理源于成核速率的非单调变化与表面生长速率的持续上升之间的竞争效应。CO_(2)的物理和化学效应随着稀释比例的上升呈增加趋势,在稀释范围为0~40%时,CO_(2)的物理效应对碳烟峰值影响不大,CO_(2)通过CO+OH⇌CO_(2)+H反应促进H消耗从而削弱PAH生长所需的HACA机制,导致A1和A4物质的量分数显著降低,在CO_(2)稀释比例为60%时碳烟峰值体积分数进一步降低至6.4×10^(−9),从而进一步减少MILD燃烧方式下碳烟的生成。展开更多
Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as...Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as massive by-product,contribute to greenhouse effects and pose environmental challenges.Thus,the pursuit of nitrogen fixation through carbon–neutral pathways under benign conditions is a frontier of scientific topics,with the harnessing of solar energy emerging as an enticing and viable option.This review delves into the refinement strategies for scale-up mild photocatalytic nitrogen fixation,fields ripe with potential for innovation.The narrative is centered on enhancing the intrinsic capabilities of catalysts to surmount current efficiency barriers.Key focus areas include the in-depth exploration of fundamental mechanisms underpinning photocatalytic procedures,rational element selection,and functional planning,state-of-the-art experimental protocols for understanding photo-fixation processes,valid photocatalytic activity evaluation,and the rational design of catalysts.Furthermore,the review offers a suite of forward-looking recommendations aimed at propelling the advancement of mild nitrogen photo-fixation.It scrutinizes the existing challenges and prospects within this burgeoning domain,aspiring to equip researchers with insightful perspectives that can catalyze the evolution of cutting-edge nitrogen fixation methodologies and steer the development of next-generation photocatalytic systems.展开更多
OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran s...OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran sulfate sodium.After 7 d,mild moxibustion,α7 nicotinic acetylcholine receptors(α7nAchRs) antagonist(α-bungarotoxin,α-BGT),vesicular acetylcholine transport inhibitor(vesamicol hydrochloride,VH) and organic cation transporters inhibitor(quinine,Qu) treatments were performed once daily for 7 d.Haematoxylin and eosin staining was used for morphological evaluation of colon tissues.Enzymelinked immunosorbent assay(ELISA) was used to measure the protein expressions of interleukin-1β(IL-1β) and choline acetyltransferase(ChAT) in colon tissue.Reverse transcription quantitative real-time polymerase chain reaction(RT-q PCR) was used to detect the mRNA expressions of IL-1β,carnosine acetyltransferase(CarAT),ChAT,and nuclear factor kappa-B p65 subunit(NF-κB p65) in colon tissue.Western blot was used to detect NF-κB p65 protein expression in colon tissue.Immunofluorescence was used to detect the expressions of neuronal acetylcholine(nAch) and non-neuronal acetylcholine(nnAch,released by NNCS) in colon tissue.RESULTS:Mild moxibustion inhibited colon inflammation and repaired mucosal damage to the colon in UC rats.Meanwhile,mild moxibustion could downregulate the expressions of IL-1β,NF-κB p65 protein and mRNA(P < 0.01),and upregulate the expressions of ChAT protein and CarAT mRNA(P < 0.05,P < 0.01).The α7nAChR antagonist α-BGT can reverse the protective effect of mild moxibustion on the UC and the inhibitory effect on the inflammatory factors.VH cannot affect the effect of mild moxibustion on the expressions of IL-1β and nnAch,while Qu can reverse the effect of mild moxibustion on the expression of IL-1β and nnAch.CONCLUSIONS:Mild moxibustion can inhibite colon inflammation in UC rats,which is closely related to the release of acetylcholine by NNCS and its mediated mechanism of cholinergic anti-inflammation pathway.展开更多
BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patie...BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.展开更多
BACKGROUND Older adults with mild cognitive impairment(MCI)often show motor dysfunction,including slower gait and impaired handwriting.While gait and handwriting parameters are promising for MCI screening,their combin...BACKGROUND Older adults with mild cognitive impairment(MCI)often show motor dysfunction,including slower gait and impaired handwriting.While gait and handwriting parameters are promising for MCI screening,their combined potential to distinguish MCI from cognitively normal adults is unclear.AIM To assess gait and handwriting differences and their potential for screening MCI in older adults.METHODS Ninety-five participants,including 34 with MCI and 61 cognitively normal controls,were assessed for gait using the GAITRite^(R)system and handwriting with a dot-matrix pen.Five machine learning models were developed to assess the discriminative power of gait and handwriting data for MCI screening.RESULTS Compared to the cognitively normal group,the MCI group had slower gait velocity(Z=-2.911,P=0.004),shorter stride and step lengths(t=-3.005,P=0.003;t=2.863,P=0.005),and longer cycle,standing,and double support times(t=-2.274,P=0.025;t=-2.376,P=0.018;t=-2.717,P=0.007).They also had reduced cadence(t=2.060,P=0.042)and increased double support time variability(Z=-2.614,P=0.009).In handwriting,the MCI group showed lower average pressure(all tasks:Z=-2.135,P=0.033)and decreased accuracy(graphic task:Z=-2.447,P=0.014;Chinese character task:Z=-3.078,P=0.002).In the graphic task,they demonstrated longer time in air(Z=-2.865,P=0.004),reduced X-axis maximum velocities(Z=-3.237,P=0.001),and lower accelerations(X-axis:Z=-2.880,P=0.004;Y-axis:Z=-1.987,P=0.047)and maximum accelerations(X-axis:Z=-3.998,P<0.001;Y-axis:Z=-2.050,P=0.040).The multimodal analysis achieved the highest accuracy(74.4%)with the Gradient Boosting Classifier.CONCLUSION Integrating gait and handwriting kinematics parameters provides a viable method for distinguishing MCI,potentially supporting large-scale screening,especially in resource-limited settings.展开更多
New stared compounds including norfloxacin fragments were prepared via a multi-step route,which were employed as the target corrosion inhibitors(TCIs)for mild steel in 1 mol/L HCl solution.For comparisons,the linear c...New stared compounds including norfloxacin fragments were prepared via a multi-step route,which were employed as the target corrosion inhibitors(TCIs)for mild steel in 1 mol/L HCl solution.For comparisons,the linear compounds including a single norfloxacin part employed as the reference corrosion inhibitors(RCIs)were synthesized.The molecular structures of the stared compounds were confirmed.The material simulation calculations suggest the presence of large binding energies of the stared compounds on mild steel surface.The enhanced chemisorption of the stared compounds on mild steel surface was demonstrated,which could be resulted by the chemical complexion of the target stared molecules with iron atoms.The reinforced adsorption of the target compounds on mild steel surface was investigated by atomic force microscopy(AFM)and scanning electron microscopy(SEM).The electrochemical analyses reveal the super protection of the TCIs for mild steel in HCl solution,and the anticorrosion efficiency reaches 96.45%(TCI1,0.050 mM)and 96.61%(TCI2,0.010 mM)at 298 K.展开更多
Objective To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation(TET)protein 2 gene knockout(TET2^(-/-))mice with ulcerative colitis(UC)by regulating DNA methyltransfer...Objective To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation(TET)protein 2 gene knockout(TET2^(-/-))mice with ulcerative colitis(UC)by regulating DNA methyltransferase(DNMT)and DNA hydroxymethylase.Methods Male specific pathogen-free(SPF)grade C57BL/6J wild-type(WT)mice(n=8)and TET2^(-/-)mice(n=20)were used to establish UC models by freely drinking 3%dextran sulfate sodium solution for 7 d.After UC model validation through histopathological examination in two mice from each type,the remaining mice were divided into four groups(n=6 in each group):WT model(WT+UC),TET2^(-/-)model(TET2^(-/-)+UC),TET2^(-/-)mild moxibustion(TET2^(-/-)+MM),and TET2^(-/-)electroacupuncture(TET2^(-/-)+EA)groups.TET2^(-/-)+MM group received mild moxibustion on Tianshu(ST25)and Qihai(CV6)for 10 min daily for 7 d.The TET2^(-/-)+EA group also applied electroacupuncture(1 mA,2/100 Hz)at the same acupoints for 10 min daily for 7 d.The disease activity index(DAI)scores of each group of mice were accessed daily.The colon lengths of mice in groups were measured following intervention.The pathological changes in the colon tissues were observed with hematoxylin and eosin(HE)staining.The concentrations of interleukin(IL)-6,C-C motif chemokine 17(CCL17),and C-X-C motif chemokine ligand 10(CXCL10)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The expression of DNMT proteins(DNMT1,DNMT3A,and DNMT3B)in the colon tissues was detected by immunohistochemistry.The expression of 5-methylcytosine(5-mC),5-hydroxymethylcytosine(5-hmC),histone deacetylase 2(HDAC2),and DNA hydroxymethylase family proteins(TET 1 and TET3)was detected using immunofluorescence,which also determined the co-localization of TET1 and IL-6 protein.Results Compared with WT+UC group,TET2^(-/-)+UC group exhibited significantly higher DAI scores and shorter colon lengths(P<0.01).Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2^(-/-)mice(P<0.001).Histopathological scores of TET2^(-/-)+UC mice were significantly higher than those of WT+UC group(P<0.001)and were significantly reduced after both mild moxibustion and electroacupuncture interventions(P<0.001).Serum levels of IL-6,CCL17,and CXCL10 were significantly elevated in TET2^(-/-)+UC group compared with WT+UC group(P<0.001).Mild moxibustion significantly reduced IL-6,CCL17,and CXCL10 levels(P<0.001,P<0.001,and P<0.01,respectively),while electroacupuncture also significantly reduced IL-6,CCL17,and CXCL10 levels(P<0.05,P<0.01,and P<0.01,respectively).TET2^(-/-)+UC mice showed increased expression levels of DNMT1,DNMT3A,DNMT3B,and 5-mC(P<0.05,P<0.01 and P<0.001,respectively),with decreased expression levels of TET1,TET3,5-hmC,and HDAC2(P<0.001).Mild moxibustion significantly reduced DNMT1,DNMT3B,and 5-mC levels(P<0.05,P<0.01,and P<0.001,respectively),while increasing expression levels of TET1,TET3,5-hmC,and HDAC2(P<0.001,P<0.001,P<0.05,and P<0.001,respectively).Electroacupuncture significantly decreased 5-mC and DNMT3B levels(P<0.001 and P<0.01,respectively)and increased 5-hmC and HDAC2 levels(P<0.05 and P<0.001,respectively),but did not significantly affect TET1 and TET3 expression(P>0.05).Compared with TET2^(-/-)+MM group,TET2^(-/-)+EA group showed significantly higher 5-mC expression(P<0.001).TET2^(-/-)+UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium,whereas minimal IL-6 expression was observed in the other groups.Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation.Distinct mechanisms exist between the two interventions:mild moxibustion regulates both DNMT and hydroxymethylase,whereas electroacupuncture primarily affects DNMT.展开更多
Brain imaging is important in detecting Mild Cognitive Impairment(MCI)and related dementias.Magnetic Resonance Imaging(MRI)provides structural insights,while Positron Emission Tomography(PET)evaluates metabolic activi...Brain imaging is important in detecting Mild Cognitive Impairment(MCI)and related dementias.Magnetic Resonance Imaging(MRI)provides structural insights,while Positron Emission Tomography(PET)evaluates metabolic activity,aiding in the identification of dementia-related pathologies.This study integrates multiple data modalities—T1-weighted MRI,Pittsburgh Compound B(PiB)PET scans,cognitive assessments such as Mini-Mental State Examination(MMSE),Clinical Dementia Rating(CDR)and Functional Activities Questionnaire(FAQ),blood pressure parameters,and demographic data—to improve MCI detection.The proposed improved Convolutional Mixer architecture,incorporating B-cos modules,multi-head self-attention,and a custom classifier,achieves a classification accuracy of 96.3%on the Mayo Clinic Study of Aging(MCSA)dataset(sagittal plane),outperforming state-of-the-art models by 5%–20%.On the full dataset,the model maintains a high accuracy of 94.9%,with sensitivity and specificity reaching 89.1%and 98.3%,respectively.Extensive evaluations across different imaging planes confirm that the sagittal plane offers the highest diagnostic performance,followed by axial and coronal planes.Feature visualization highlights contributions from central brain structures and lateral ventricles in differentiating MCI from cognitively normal subjects.These results demonstrate that the proposed multimodal deep learning approach improves accuracy and interpretability in MCI detection.展开更多
文摘The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.
基金Supported by the Central Guided Local Science and Technology Development Fund Project for Science and Technology Innovation Base Construction,No.Guike ZY24212046National Natural Science Foundation of China,No.U22A2092+3 种基金Guangxi Education Science“the 14th Five-Year Plan”2024 Special Project“Research on Steam Education Practice in Rehabilitation Engineering”,No.2024ZJY304the Research Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi,No.2025KY2255the Innovation Project of GUET Graduate Education,No.2025YCXB010Natural Science Research Project of Guilin Life and Health Career Technical College,No.2025GKKY04.
文摘BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.
基金supported by the Major Project of Wuxi Municipal Health Commission[grant number:Z202406]the Jiangsu Commission of Health Program[grant number:M2024010]+3 种基金the National Key Research and Development Program[grant number:2022YFC3600600]the China Ministry of Science and Technology grants[grant number:2009BAI77B03]the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support[grant number:20172029]the Innovative Research Team of High-level Local Universities in Shanghai[grant number:ZDCX20211201].
文摘Background As the population in China rapidly ages,the prevalence of mild cognitive impairment(MCI)is increasing considerably.However,the causes of MCI vary.The continued lack of understanding of the various subtypes of MCI impedes the implementation of effective measures to reduce the risk of advancing to more severe cognitive diseases.Aims To estimate the prevalence and incidence rates of two MCI subtypes—amnestic MCI(aMCI)and vascular cognitive impairment without dementia(VCIND)—and to determine modifiable factors for them among older individuals in a multiregional Chinese cohort.Method This 1-year longitudinal study surveyed a random sample of participants aged≥60 years from a large,community-dwelling cohort in China.Baseline lifestyle data were self-reported,while vascular and comorbid conditions were obtained from medical records and physical examinations.In total,3514 and 2051 individuals completed the baseline and 1-year follow-up assessments,respectively.Logistic and linear regression analyses were used to identify the modifiable factors for MCI subtypes and predictors of cognitive decline,respectively.Results Among our participants,aMCI and VCIND demonstrated prevalence of 14.83%and 2.71%,respectively,and annual incidence(per 1000 person-years)of 69.6 and 10.6,respectively.The risk factor for aMCI was age,whereas its protective factors were high education level,tea consumption and physical activity.Moreover,VCIND risk factors were age,hypertension and depression.The presence of endocrine disease,cerebral trauma or hypertension was associated with a faster decline in cognition over 1 year.Conclusions MCI is a serious health problem in China that will only worsen as the population ages if no widespread interventions are implemented.Preventive strategies that promote brain activity and support healthy lifestyle choices are required.We identified modifiable factors for MCI in older individuals.The easy-to-adopt solutions such as tea consumption and physical activity can aid in preventing MCI.
文摘The paper investigates the foaming and mildness properties of trehalolipids surfactant in rinse-off formulations,comparing it with the traditional nonionic surfactant alkyl-polyglycolide(APG).Both single surfactant and their surfactant complexes are evaluated.And the results show that trehalolipids have significant advantages in reducing surface tension,improving foam performance,and enhancing mildness.For mildness evaluation,multiple methods are employed in the study,including in vitro cell toxicity,inflammatory markers,colorimetric index of mildness CIM,and in vivo method of human skin patch test.The results show that the addition of trehalolipids increases IC50 and reduces the release of inflammatory markers of the binary surfactant system.However,the incorporation of trehalolipids has some negative effects on the skin’s lipid barrier function.Skin patch test results indicate that the addition of trehalolipids improves the mildness of surfactant system,particularly in sulfate-free system.Overall,trehalolipids,as nonionic surfactants,presents great potential to replace traditional surfactants in rinse off formulations with enhanced mildness and foam performance.
基金Supported by the Government Funded Clinical Medicine Excellent Talents Training Project of Hebei Province,No.ZF2024136National Science Foundation of Hebei Province,No.H2022206544Science and Technology Program of Hebei Province,No.SG2021189。
文摘BACKGROUND Mild behavioral impairment(MBI)refers to the neurobehavioral symptoms observed in older adults that may be potential risk factors for neurodegenerative diseases.While a significant number studies have explored the association between cerebrospinal fluid and MBI,only a few have examined the connection between plasma biomarkers and MBI.AIM To examine the prevalence of MBI in healthy older adults(HOAs)and individuals with mild cognitive impairment(MCI),as well as the association between MBI and plasma biomarkers of Alzheimer’s disease(AD).METHODS We enrolled a total of 241 subjects,which included 136 HOAs and 105 MCIs,from the Yuhua District of Shijiazhuang City,Hebei Province,China.The MBI symp-tom checklist(MBI-C)was utilized for the assessment and diagnosis of MBI,and a score of MBI-C≥6.5 was considered indicative of the condition.Fasting venous blood samples were collected from 70 patients,32 HOAs and 38 MCIs,and levels of amyloidβ-protein(Aβ)40,Aβ42,and hyperphosphorylated tau(p-Tau217)in these samples were measured using an enzyme-linked immunosorbent assay.RESULTS The prevalence of MBI in the HOAs and MCI groups was 4.4%and 15.3%,respectively(χ^(2)=7.262,P=0.007),with particularly notable decreases in motivation and increases in impulse dyscontrol(the highest detection rate)and social inappropriateness(P<0.05).The total MBI score correlated with Aβ42 and p-Tau217(r=-0.385,P=0.019;r=-0.330,P=0.041),but not with Aβ40 or the Aβ42/40 ratio.Among the subdomains,impulse dyscontrol was correlated with Aβ42(r=-0.401,P=0.025).CONCLUSION Both MCI and HOAs have exhibited a higher prevalence of MBI,with changes in impulse control behavior being the most common.MBI not only presents as an independent risk factor for cognitive decline but is also linked with AD-related peripheral biomarkers.
文摘In the context of global aging,mild behavioral impairment(MBI)is present in 48.9%of patients with mild cognitive impairment(MCI).MBI,a neurobehavioral syndrome in the elderly,is an independent risk factor for cognitive decline and is closely related to peripheral blood biomarkers associated with Alzheimer's disease,offering new diagnostic and interventional avenues for early MCI.To summarize evidence on peripheral blood biomarkers related to MBI and their underlying mechanisms involving neuroinflammation,tau pathology,and oxidative stress,a systematic review of studies published between 2015 and 2024 was conducted.MBI is closely associated with peripheral blood biomarker changes.Neuroinflammatory markers like glial fibrillary acidic protein and neurofilament light indicate astrocyte activation and neural circuit disruption,with glial fibrillary acidic protein levels correlating with impulse dyscontrol scores.Chitinase-3-like protein 1,a marker of blood-brain barrier integrity,exacerbates neuroinflammation and is linked to depressive symptoms and hippocampal atrophy.Elevated phosphorylated tau proteins in blood correlate with brain tau deposition,increasing the risk of MBI and impairing cognition.Oxidative stress markers damage neurons and disrupt neurotransmission,and concurrent alterations in malondialdehyde and superoxide dismutase levels significantly elevate the risk of MBI.The correlation between MBI and biomarkers offers new diagnostic and interventional directions for early MCI.Future research should standardize MBI assessment,conduct longitudinal studies,explore biomarker-MBI relationships,investigate psychosocial impacts,and develop advanced detection methods.
文摘氨气(NH_(3))作为一种兼具储能的无碳燃料,在能源领域具有极大的应用前景。然而,NH_(3)的燃烧特性与常规碳氢燃料有着明显差异。该文通过数值模拟方法,研究了CH_(4)/NH_(3)的混合燃料低氧稀释(moderate or intense low-oxygen dilution,MILD)燃烧特性。结果表明,在甲烷MILD燃烧中添加NH_(3)使出口NO排放亟剧增加。过量空气系数大于1时,减小过量空气系数使NO和CO的排放降低。NH_(3)中的N元素转化成NO的转化率随燃料中NH_(3)的增加和过量空气系数的降低而减小。
基金financially supported by the National Natural Science Foundation of China(No.21675131)the Volkswagen Foundation(Freigeist Fellowship No.89592)+1 种基金the Natural Science Foundation of Chongqing(No.2020jcyj-zdxmX0003,CSTB2023NSCQ-MSX0924)the National Research Foundation,Singapore,and A*STAR(Agency for Science Technology and Research)under its LCER Phase 2 Programme Hydrogen&Emerging Technologies FI,Directed Hydrogen Programme(Award No.U2305D4003).
文摘Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as massive by-product,contribute to greenhouse effects and pose environmental challenges.Thus,the pursuit of nitrogen fixation through carbon–neutral pathways under benign conditions is a frontier of scientific topics,with the harnessing of solar energy emerging as an enticing and viable option.This review delves into the refinement strategies for scale-up mild photocatalytic nitrogen fixation,fields ripe with potential for innovation.The narrative is centered on enhancing the intrinsic capabilities of catalysts to surmount current efficiency barriers.Key focus areas include the in-depth exploration of fundamental mechanisms underpinning photocatalytic procedures,rational element selection,and functional planning,state-of-the-art experimental protocols for understanding photo-fixation processes,valid photocatalytic activity evaluation,and the rational design of catalysts.Furthermore,the review offers a suite of forward-looking recommendations aimed at propelling the advancement of mild nitrogen photo-fixation.It scrutinizes the existing challenges and prospects within this burgeoning domain,aspiring to equip researchers with insightful perspectives that can catalyze the evolution of cutting-edge nitrogen fixation methodologies and steer the development of next-generation photocatalytic systems.
基金National Natural Science Foundation of China:Study for the Mechanism of Moxibustion in Ulcerative Colitis based on the α7 Nicotinic Acetylcholine Receptor Mediated Cholinergic Antiinflammatory Pathway (No.82205293)National Natural Science Foundation of China:Study of the Central Nervous System Regulatory Mechanism of Moxibustion Repair of Ulcerative Colitis Gut Vascular Barrier Based on Ubiquitin Specific Peptidase 14 Deubiquitination (No.82274641)+3 种基金National Natural Science Foundation of China:Moxibustion Regulates P300-mediated Histone H3K27 Acetylation Modification in the Treatment of Crohn's Disease (No.82205262)National Natural Science Foundation of China:Study on the Protective Mechanism of Moxibustion on Intestinal Mucosal Barrier in Ulcerative Colitis based on GABAergic System (No.82105012)Shanghai Sailing Program:to Study the Protective Effect of Moxibustion on Intestinal Mucosal Barrier in Crohn's Disease Based on Histone H3 Acetylation Modification (No.22YF1444100)State Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project (No.zyyzdxk-2023068)。
文摘OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran sulfate sodium.After 7 d,mild moxibustion,α7 nicotinic acetylcholine receptors(α7nAchRs) antagonist(α-bungarotoxin,α-BGT),vesicular acetylcholine transport inhibitor(vesamicol hydrochloride,VH) and organic cation transporters inhibitor(quinine,Qu) treatments were performed once daily for 7 d.Haematoxylin and eosin staining was used for morphological evaluation of colon tissues.Enzymelinked immunosorbent assay(ELISA) was used to measure the protein expressions of interleukin-1β(IL-1β) and choline acetyltransferase(ChAT) in colon tissue.Reverse transcription quantitative real-time polymerase chain reaction(RT-q PCR) was used to detect the mRNA expressions of IL-1β,carnosine acetyltransferase(CarAT),ChAT,and nuclear factor kappa-B p65 subunit(NF-κB p65) in colon tissue.Western blot was used to detect NF-κB p65 protein expression in colon tissue.Immunofluorescence was used to detect the expressions of neuronal acetylcholine(nAch) and non-neuronal acetylcholine(nnAch,released by NNCS) in colon tissue.RESULTS:Mild moxibustion inhibited colon inflammation and repaired mucosal damage to the colon in UC rats.Meanwhile,mild moxibustion could downregulate the expressions of IL-1β,NF-κB p65 protein and mRNA(P < 0.01),and upregulate the expressions of ChAT protein and CarAT mRNA(P < 0.05,P < 0.01).The α7nAChR antagonist α-BGT can reverse the protective effect of mild moxibustion on the UC and the inhibitory effect on the inflammatory factors.VH cannot affect the effect of mild moxibustion on the expressions of IL-1β and nnAch,while Qu can reverse the effect of mild moxibustion on the expression of IL-1β and nnAch.CONCLUSIONS:Mild moxibustion can inhibite colon inflammation in UC rats,which is closely related to the release of acetylcholine by NNCS and its mediated mechanism of cholinergic anti-inflammation pathway.
文摘BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.
基金Supported by National Natural Science Foundation of China,No.72174061 and No.71704053Key Research and Development Program of Zhejiang Province,No.2025C02106+1 种基金China Scholarship Council Foundation,No.202308330251Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2022KY370。
文摘BACKGROUND Older adults with mild cognitive impairment(MCI)often show motor dysfunction,including slower gait and impaired handwriting.While gait and handwriting parameters are promising for MCI screening,their combined potential to distinguish MCI from cognitively normal adults is unclear.AIM To assess gait and handwriting differences and their potential for screening MCI in older adults.METHODS Ninety-five participants,including 34 with MCI and 61 cognitively normal controls,were assessed for gait using the GAITRite^(R)system and handwriting with a dot-matrix pen.Five machine learning models were developed to assess the discriminative power of gait and handwriting data for MCI screening.RESULTS Compared to the cognitively normal group,the MCI group had slower gait velocity(Z=-2.911,P=0.004),shorter stride and step lengths(t=-3.005,P=0.003;t=2.863,P=0.005),and longer cycle,standing,and double support times(t=-2.274,P=0.025;t=-2.376,P=0.018;t=-2.717,P=0.007).They also had reduced cadence(t=2.060,P=0.042)and increased double support time variability(Z=-2.614,P=0.009).In handwriting,the MCI group showed lower average pressure(all tasks:Z=-2.135,P=0.033)and decreased accuracy(graphic task:Z=-2.447,P=0.014;Chinese character task:Z=-3.078,P=0.002).In the graphic task,they demonstrated longer time in air(Z=-2.865,P=0.004),reduced X-axis maximum velocities(Z=-3.237,P=0.001),and lower accelerations(X-axis:Z=-2.880,P=0.004;Y-axis:Z=-1.987,P=0.047)and maximum accelerations(X-axis:Z=-3.998,P<0.001;Y-axis:Z=-2.050,P=0.040).The multimodal analysis achieved the highest accuracy(74.4%)with the Gradient Boosting Classifier.CONCLUSION Integrating gait and handwriting kinematics parameters provides a viable method for distinguishing MCI,potentially supporting large-scale screening,especially in resource-limited settings.
基金Funded by the National Natural Science Foundation of China(NSFC)of China(No.21878029)the Chongqing Science and Technology Commission(Nos.2022NSCQ-MSX1298 and CSTB2023NSCQ-MSX0345)。
文摘New stared compounds including norfloxacin fragments were prepared via a multi-step route,which were employed as the target corrosion inhibitors(TCIs)for mild steel in 1 mol/L HCl solution.For comparisons,the linear compounds including a single norfloxacin part employed as the reference corrosion inhibitors(RCIs)were synthesized.The molecular structures of the stared compounds were confirmed.The material simulation calculations suggest the presence of large binding energies of the stared compounds on mild steel surface.The enhanced chemisorption of the stared compounds on mild steel surface was demonstrated,which could be resulted by the chemical complexion of the target stared molecules with iron atoms.The reinforced adsorption of the target compounds on mild steel surface was investigated by atomic force microscopy(AFM)and scanning electron microscopy(SEM).The electrochemical analyses reveal the super protection of the TCIs for mild steel in HCl solution,and the anticorrosion efficiency reaches 96.45%(TCI1,0.050 mM)and 96.61%(TCI2,0.010 mM)at 298 K.
基金National Natural Science Foundation of China(82274641,81873372,and 82105012).
文摘Objective To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation(TET)protein 2 gene knockout(TET2^(-/-))mice with ulcerative colitis(UC)by regulating DNA methyltransferase(DNMT)and DNA hydroxymethylase.Methods Male specific pathogen-free(SPF)grade C57BL/6J wild-type(WT)mice(n=8)and TET2^(-/-)mice(n=20)were used to establish UC models by freely drinking 3%dextran sulfate sodium solution for 7 d.After UC model validation through histopathological examination in two mice from each type,the remaining mice were divided into four groups(n=6 in each group):WT model(WT+UC),TET2^(-/-)model(TET2^(-/-)+UC),TET2^(-/-)mild moxibustion(TET2^(-/-)+MM),and TET2^(-/-)electroacupuncture(TET2^(-/-)+EA)groups.TET2^(-/-)+MM group received mild moxibustion on Tianshu(ST25)and Qihai(CV6)for 10 min daily for 7 d.The TET2^(-/-)+EA group also applied electroacupuncture(1 mA,2/100 Hz)at the same acupoints for 10 min daily for 7 d.The disease activity index(DAI)scores of each group of mice were accessed daily.The colon lengths of mice in groups were measured following intervention.The pathological changes in the colon tissues were observed with hematoxylin and eosin(HE)staining.The concentrations of interleukin(IL)-6,C-C motif chemokine 17(CCL17),and C-X-C motif chemokine ligand 10(CXCL10)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The expression of DNMT proteins(DNMT1,DNMT3A,and DNMT3B)in the colon tissues was detected by immunohistochemistry.The expression of 5-methylcytosine(5-mC),5-hydroxymethylcytosine(5-hmC),histone deacetylase 2(HDAC2),and DNA hydroxymethylase family proteins(TET 1 and TET3)was detected using immunofluorescence,which also determined the co-localization of TET1 and IL-6 protein.Results Compared with WT+UC group,TET2^(-/-)+UC group exhibited significantly higher DAI scores and shorter colon lengths(P<0.01).Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2^(-/-)mice(P<0.001).Histopathological scores of TET2^(-/-)+UC mice were significantly higher than those of WT+UC group(P<0.001)and were significantly reduced after both mild moxibustion and electroacupuncture interventions(P<0.001).Serum levels of IL-6,CCL17,and CXCL10 were significantly elevated in TET2^(-/-)+UC group compared with WT+UC group(P<0.001).Mild moxibustion significantly reduced IL-6,CCL17,and CXCL10 levels(P<0.001,P<0.001,and P<0.01,respectively),while electroacupuncture also significantly reduced IL-6,CCL17,and CXCL10 levels(P<0.05,P<0.01,and P<0.01,respectively).TET2^(-/-)+UC mice showed increased expression levels of DNMT1,DNMT3A,DNMT3B,and 5-mC(P<0.05,P<0.01 and P<0.001,respectively),with decreased expression levels of TET1,TET3,5-hmC,and HDAC2(P<0.001).Mild moxibustion significantly reduced DNMT1,DNMT3B,and 5-mC levels(P<0.05,P<0.01,and P<0.001,respectively),while increasing expression levels of TET1,TET3,5-hmC,and HDAC2(P<0.001,P<0.001,P<0.05,and P<0.001,respectively).Electroacupuncture significantly decreased 5-mC and DNMT3B levels(P<0.001 and P<0.01,respectively)and increased 5-hmC and HDAC2 levels(P<0.05 and P<0.001,respectively),but did not significantly affect TET1 and TET3 expression(P>0.05).Compared with TET2^(-/-)+MM group,TET2^(-/-)+EA group showed significantly higher 5-mC expression(P<0.001).TET2^(-/-)+UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium,whereas minimal IL-6 expression was observed in the other groups.Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation.Distinct mechanisms exist between the two interventions:mild moxibustion regulates both DNMT and hydroxymethylase,whereas electroacupuncture primarily affects DNMT.
文摘Brain imaging is important in detecting Mild Cognitive Impairment(MCI)and related dementias.Magnetic Resonance Imaging(MRI)provides structural insights,while Positron Emission Tomography(PET)evaluates metabolic activity,aiding in the identification of dementia-related pathologies.This study integrates multiple data modalities—T1-weighted MRI,Pittsburgh Compound B(PiB)PET scans,cognitive assessments such as Mini-Mental State Examination(MMSE),Clinical Dementia Rating(CDR)and Functional Activities Questionnaire(FAQ),blood pressure parameters,and demographic data—to improve MCI detection.The proposed improved Convolutional Mixer architecture,incorporating B-cos modules,multi-head self-attention,and a custom classifier,achieves a classification accuracy of 96.3%on the Mayo Clinic Study of Aging(MCSA)dataset(sagittal plane),outperforming state-of-the-art models by 5%–20%.On the full dataset,the model maintains a high accuracy of 94.9%,with sensitivity and specificity reaching 89.1%and 98.3%,respectively.Extensive evaluations across different imaging planes confirm that the sagittal plane offers the highest diagnostic performance,followed by axial and coronal planes.Feature visualization highlights contributions from central brain structures and lateral ventricles in differentiating MCI from cognitively normal subjects.These results demonstrate that the proposed multimodal deep learning approach improves accuracy and interpretability in MCI detection.
