Aerodynamic characteristics, the noise characteristics in the course of intermittence exhaust are investigated and the expressions for sound pressure level of the noise generated by single-pole source and quadrupole s...Aerodynamic characteristics, the noise characteristics in the course of intermittence exhaust are investigated and the expressions for sound pressure level of the noise generated by single-pole source and quadrupole source in the intermittence exhaust noise are established. The effects of all parameters in pneumatic system on the noise are also comprehensively studied.展开更多
The multi-pass intermittent local loading process,which features a more flexible processing path,can further enhance the second material distribution during local loading,improve the formability of components,and redu...The multi-pass intermittent local loading process,which features a more flexible processing path,can further enhance the second material distribution during local loading,improve the formability of components,and reduce forming loads.However,the absence of compatible forming equipment makes it difficult to control the constraint in the unloaded zones during the forming process.This difficulty complicates coordination and control of deformation,particularly for asymmetric rib-web components.Additionally,the current implementation involves multi-fire heating,a long process flow,and high energy consumption,which limits the popularization and application of the local loading process.In this study,a new multi-pass local loading hydraulic forming apparatus that can quickly and reliably switch between heavy-load deformation and low-load constraint for different local loading sub-dies was developed.A 10-tonne laboratory prototype was developed,and the forming characteristics during the forming process as well as the response characteristics of the hydraulic system during the multi-pass intermittent local loading of rib-web component were investigated using numerical simulations and physical experiments.Results indicated that,compared to a whole loading process with the same initial geometry of billet,the total forming load(i.e.,the sum of loaded and restrained loads)is reduced by more than 40%with the local loading process,and by nearly 50%with multi-pass local loading.The multi-pass local loading process allows for more effective control of material flow compared to single-pass local loading,leading to improved cavity filling and reduced flow line disturbance.For a large-scale,complex titanium alloy bulkhead,the cavity filling problem was addressed by optimizing the multi-pass local loading path with an unequal thickness billet.The dynamic performance of the multi-pass local loading hydraulic system was found to be robust,with stable pressure transitions during motion and load switching for the sub-die(s).The dynamic characteristic of the hydraulic cylinder when switching from non-moving/unloaded state to a moving/loading state are consistent whether a load is present or not.However,the dynamic characteristics differ when switching from a moving/loading state to non-moving/unloaded state,showing opposite behavior.The developed hydraulic drive mechanism provides a way for implementation of multi-pass local loading without auxiliary operation and extra heating.The results of the study provide a foundation for the industrial production of large-scale,complex components with reduced force requirement and low-energy consumption.展开更多
AIM:To summarize publication trends in the field of strabismus over the past 30y and predict future research hotspots.METHODS:A total of 2915 English-language articles and reviews on strabismus,published between 1993 ...AIM:To summarize publication trends in the field of strabismus over the past 30y and predict future research hotspots.METHODS:A total of 2915 English-language articles and reviews on strabismus,published between 1993 and 2022,were retrieved from the Web of Science Core Collection.Bibliometric analyses were performed using VOSviewer and CiteSpace software to explore publication trends,as well as the contributions and collaborative networks of countries/regions,authors,institutions,and journals.RESULTS:The annual number of publications on strabismus showed a consistent upward trend.The United States(USA)maintained a leading position in this research field while Republic of Korea and China emerged as rapidly advancing contributors over the last decade.The University of California,Los Angeles ranked as the most productive institution,and Jonathan M.Holmes from USA was the most productive author.Journal of AAPOS was the leading journal with the most strabismus publications,whereas the two most highly cited articles were both published in Ophthalmology.Co-occurrence analysis identified pivotal keywords and burst terms,including intermittent exotropia(IXT),acute acquired comitant esotropia(AACE),functional magnetic resonance imaging(fMRI),and surgical treatment,which were confirmed as predominant and frontier topics.CONCLUSION:This study provides a comprehensive bibliometric analysis of strabismus research,revealing the evolution of research hotspots over the past 30y and outlining several cutting-edge directions for future investigation.展开更多
Objective Cerebral venous outflow disorders(CVOD)can impair cerebral perfusion and produce diverse,often debilitating symptoms,substantially reducing quality of life.Intermittent hypoxiahyperoxia training(IHHT)has dem...Objective Cerebral venous outflow disorders(CVOD)can impair cerebral perfusion and produce diverse,often debilitating symptoms,substantially reducing quality of life.Intermittent hypoxiahyperoxia training(IHHT)has demonstrated therapeutic potential across various pathologies and may represent a promising non-pharmacological approach for CVOD management.Methods Patients with imaging-confirmed CVOD underwent 14 IHHT sessions,each comprising four cycles of 10-minute hypoxia(11%O_(2))stimulation and 20-minute hyperoxia(38%O_(2)).Physiological parameters and adverse events were monitored throughout the intervention.Clinical scales,24-hour ambulatory blood pressure,blood tests,jugular ultrasound,and perfusion imaging were assessed preand post-intervention.Results No participants experienced intolerable discomfort or severe adverse events;vital signs remained within normal ranges.No significant changes were observed in 24-hour blood pressure,blood cell counts,lipid profiles,or other blood markers.Notably,60%of patients(n=12)reported overall symptom improvement on the Patient Global Impression of Change scale.Headache severity,as measured by the visual analogue scale,significantly decreased(6.33±1.22 vs.4.89±2.03,P=0.016).In patients with internal jugular vein(IJV)stenosis,significant improvements were observed in regional cerebral blood flow(including the insula,occipital lobe,internal capsule,and lenticula)and left J3-segment IJV flow volume(107.27[47.50,160.00]vs.140.83[55.00,210.00]mL/min,P=0.011).Conclusion The current IHHT protocol is safe and well-tolerated in patients with CVOD.IHHT may alleviate CVOD-related symptoms by improving oxygen saturation,cerebral perfusion,and venous outflow pattern,supporting its potential as a non-invasive therapeutic strategy.展开更多
With the in-depth implementation of sustainable development strategies,hydrogen energy as a clean energy source is receiving increasing attention[1,2].Among the various methods of hydrogen production,the electrocataly...With the in-depth implementation of sustainable development strategies,hydrogen energy as a clean energy source is receiving increasing attention[1,2].Among the various methods of hydrogen production,the electrocatalytic decomposition of abundant seawater into hydrogen utilizing renewable energy has emerged as a green and promising approach.However,natural seawater contains complex components,such as halide ions,which lead to the corrosion of catalysts or the occurrence of competitive side reactions during the electrolysis process[3].展开更多
Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
Using the incompressible isotropic turbulent fields obtained from direct numerical simulation and large-eddy simulation,we studied the statistics of oscillation structures based on local zero-crossings and their relat...Using the incompressible isotropic turbulent fields obtained from direct numerical simulation and large-eddy simulation,we studied the statistics of oscillation structures based on local zero-crossings and their relation with inertial-range intermittency for transverse velocity and passive scalar.Our results show that for both the velocity and passive scalar,the local oscillation structures are statistically scaleinvariant at high Reynolds number,and the inertial-range intermittency of the overall flow region is determined by the most intermittent structures characterized by one local zero-crossing.Local flow patterns conditioned on the oscillation structures are characterized by the joint probability density function of the invariants of the filtered velocity gradient tensor at inertial range.We demonstrate that the most intermittent regions for longitudinal velocity tend to lay at the saddle area,while those for the transverse velocity tend to locate at the vortex-dominated area.The connection between the ramp-cliff structures in passive scalar field and the corresponding saddle regions in the velocity field is also verified by the approach of oscillation structure classification.展开更多
A conceptual model of intermittent joints is introduced to the cyclic shear test in the laboratory to explore the effects of loading parameters on its shear behavior under cyclic shear loading.The results show that th...A conceptual model of intermittent joints is introduced to the cyclic shear test in the laboratory to explore the effects of loading parameters on its shear behavior under cyclic shear loading.The results show that the loading parameters(initial normal stress,normal stiffness,and shear velocity)determine propagation paths of the wing and secondary cracks in rock bridges during the initial shear cycle,creating different morphologies of macroscopic step-path rupture surfaces and asperities on them.The differences in stress state and rupture surface induce different cyclic shear responses.It shows that high initial normal stress accelerates asperity degradation,raises shear resistance,and promotes compression of intermittent joints.In addition,high normal stiffness provides higher normal stress and shear resistance during the initial cycles and inhibits the dilation and compression of intermittent joints.High shear velocity results in a higher shear resistance,greater dilation,and greater compression.Finally,shear strength is most sensitive to initial normal stress,followed by shear velocity and normal stiffness.Moreover,average dilation angle is most sensitive to initial normal stress,followed by normal stiffness and shear velocity.During the shear cycles,frictional coefficient is affected by asperity degradation,backfilling of rock debris,and frictional area,exhibiting a non-monotonic behavior.展开更多
Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modula...Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified.This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper(SMAp)in modulating MSL across different complexity levels and for both hands,as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation.Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL,which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions,particularly in interhemispheric connections.These findings may have important clinical implications,particularly for motor rehabilitation in populations such as post-stroke patients.展开更多
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
The circadian clock is crucial for the progression of cardiovascular diseases.Our previous studies showed that acrolein,an environmental pollutant,exacerbated atherosclerosis by reducing CLOCK/BMAL1 levels and disrupt...The circadian clock is crucial for the progression of cardiovascular diseases.Our previous studies showed that acrolein,an environmental pollutant,exacerbated atherosclerosis by reducing CLOCK/BMAL1 levels and disrupting circadian rhythm;in contrast,intermittent fasting(IF),a dietary regimen,ameliorated acrolein-induced atherosclerosis.In the current study,mice were administered acrolein at a dose of 3 mg/(kg·day)via drinking water and subjected to IF for 18 h(from 0:00 to 18:00).We observed that IF reduced the formation of aortic lesions accelerated by acrolein in Apo E-/-mice.Upon exposure to acrolein,the expression of Rel A,Il1b,and Tnf increased in the liver and heart tissues,but these changes were reversed by IF treatment.Notably,IF treatment upregulated the expression of adenosine monophosphate(AMP)-activated protein kinase catalytic subunit alpha-1(AMPKα1),p-AMPKα1,and sirtuin 1(SIRT1),while inhibiting acrolein-induced mitogen-activated protein kinase(MAPK)activation.Additionally,the expression of circadian genes Clock/Bmal1 was suppressed and disrupted by acrolein,whereas IF restored their expression.Moreover,consistent with the in vivo findings,shortterm starvation in vitro,as a fasting cell model,alleviated the dysregulation of CLOCK/BMAL1 and upregulated SIRT1 expression by modulating the AMPK and reactive oxygen species(ROS)-MAPK pathways activated by acrolein.In summary,we demonstrated that IF suppressed the ROS-MAPK pathway but activated the AMPK pathway to enhance the expression of circadian clock genes,thereby ameliorating acrolein-induced atherogenesis,which may shed light on strategies for preventing cardiovascular diseases.展开更多
Objective Previous studies have yielded contradictory conclusions on the relationship between intermittent exotropia(IXT)and the magnitude of myopia,especially in children.The aim of this study was to determine the cl...Objective Previous studies have yielded contradictory conclusions on the relationship between intermittent exotropia(IXT)and the magnitude of myopia,especially in children.The aim of this study was to determine the clinical characteristics of IXT in children with myopia and myopic anisometropia.Methods We retrospectively evaluated the clinical data of patients(4–15 years of age)with convergence insufficiency(CI)-IXT and basic IXT who underwent surgery between 2022 and 2023.All patients underwent cycloplegia before the examinations and surgery.The degree of strabismus was measured when the patient viewed from the center of the glasses.Ocular dominance was routinely tested in children with IXT via the“hole-in-card test”after best-corrected visual acuity was obtained.Children were subsequently grouped into 2 groups(anisometropia and nonanisometropia)according to the difference in binocular spherical equivalent(SE)values(≥1.0 diopters[D]).Results A total of 197 patients were included in the study.The preoperative deviation at near was significantly lower in the basic IXT group than in the CI-IXT group,whereas the distance exodeviation was significantly greater in the basic IXT group than in the CI-IXT group(P<0.05).Patients with anisometropia were older than those without anisometropia(P<0.001).The dominant eyes had significantly less myopia than the nondominant eyes did in the CI-IXT and anisometropia groups(P=0.049 and P=0.003,respectively).High myopia was more prevalent in middle school students with IXT(16.67%)than in preschool students(4.55%)and primary schoolchildren(3.18%).The percentage of individuals with anisometropia(≥3.0 D)varied in the low(1.68%),moderate(8.7%),and high myopia groups(22.22%).Binomial logistic regression analysis revealed that age and SE of the dominant eye were independent factors related to anisometropia in children with IXT(P<0.001 and P<0.001,respectively).Conclusion Patients with IXT,especially those with anisometropia and CI-IXT,were shown to have less myopia in the dominant eye.Age and SE of the dominant eye were found to be independent factors related to anisometropia in children with IXT.展开更多
In this work, we address the codiagnosability analysis problem of a networked discrete event system under malicious attacks. The considered system is modeled by a labeled Petri net and is monitored by a series of site...In this work, we address the codiagnosability analysis problem of a networked discrete event system under malicious attacks. The considered system is modeled by a labeled Petri net and is monitored by a series of sites, in which each site possesses its own set of sensors, without requiring communication among sites or to any coordinators. A net is said to be codiagnosable with respect to a fault if at least one site could deduce the occurrence of this fault within finite steps. In this context, we focus on a type of malicious attack that is called stealthy intermittent replacement attack. The stealthiness demands that the corrupted observations should be consistent with the system's normal behavior, while the intermittent replacement setting entails that the replaced transition labels must be recovered within a bounded of consecutive corrupted observations(called as K-corruption intermittent attack). Particularly, there exists a coordination between attackers that are separately effected on different sites, which holds the same corrupted observation for each common transition under attacks. From an attacker viewpoint, this work aims to design Kcorruption intermittent attacks for violating the codiagnosability of systems. For this purpose, we propose an attack automaton to analyze K-corruption intermittent attack for each site, and build a new structure called complete attack graph that is used to analyze all the potential attacked paths. Finally, an algorithm is inferred to obtain the K-corruption intermittent attacks, and examples are given to show the proposed attack strategy.展开更多
In dynamic scenes,the pose estimation and map consistency of visual simultaneous localisation and mapping(visual SLAM)are affected by intermittent changes in object motion states.An adaptive motion-state estimation an...In dynamic scenes,the pose estimation and map consistency of visual simultaneous localisation and mapping(visual SLAM)are affected by intermittent changes in object motion states.An adaptive motion-state estimation and feature-reuse mechanism is proposed which restores features once objects become stationary.Camera ego-motion is com-pensated via projection-based point-to-point red-green-blue-depth(RGB-D)Iterative Closest Point;the alignment residual yields a short-term jitter score.An Extended Kalman Filter fuses the centre-pixel trajectory and depth of the object,using depth innovation as strong evidence to suppress false triggers.Applied adaptive decision thresholds involve resolution,ego-motion intensity,jitter,and reference depth,and are combined with dual/single triggering and hysteresis to achieve robust switching.When an object is considered static,its feature points are reused.On the Bonn RGB-D Dynamic Dataset(BONN)and TUM RGB-D SLAM Dataset and Benchmark(TUM),the proposed method matches or exceeds baselines:In intermittent-motion-dominated BONN sequences Placing_non_box,it re-duces the root-mean-square of the absolute trajectory error(ATE-RMSE)by 27%relative to the baseline,remains comparable to Ellipsoid-SLAM on TUM,and consistently outperforms ORB-SLAM3 in dynamic scenes.The hysteresis counter reading on Placing_non_box2 shows that the proposed method can reduce the motion-state misclassification rate by nearly 40%.From the ablation experiment results,we confirm that adaptive thresholds yield the most significant optimisation effect.The approach improves robustness and map completeness in dynamic environments without degrading performance in low-dynamic settings.展开更多
BACKGROUND 5-aminosalicylates(5-ASA)are the primary treatment for mild to moderate ulcerative colitis(UC).Maintenance therapy with 5-ASA has been shown to reduce both the risk of relapse and colorectal cancer.AIM To e...BACKGROUND 5-aminosalicylates(5-ASA)are the primary treatment for mild to moderate ulcerative colitis(UC).Maintenance therapy with 5-ASA has been shown to reduce both the risk of relapse and colorectal cancer.AIM To evaluate the outcomes of 5-ASA withdrawal due to non-adherence in UC patients while in remission on monotherapy.METHODS Adult patients with UC who were followed up between July 2019 and April 2025 were screened.Patients in remission receiving 5-ASA monotherapy who experienced treatment withdrawal due to non-adherence were included in this study.RESULTS Among 880 patients with UC,30(3.4%)had 5-ASA withdrawal due to nonadherence while in remission on monotherapy.Twelve patients(40%)had disease relapse after a median of 20 months.The rate of patients in remission was 89%in the first year,decreasing to 73%in the second year,and to 64%in the third year.There were no significant differences between patients with and without relapse in terms of demographics,disease extent,remission duration before 5-ASA withdrawal,previous medications,steroid dependence,5-ASA formulation,baseline inflammatory markers,or partial and endoscopic Mayo scores.Most patients(75%)who experienced relapse were successfully treated with 5-ASA monotherapy,while one-fourth of them required corticosteroids.No patients required biologic agents,hospitalization,or surgical intervention.CONCLUSION Intermittent therapy may be safe and feasible for UC patients,especially those in long-term remission,with treatment interruption up to one year considered acceptable.展开更多
BACKGROUND Intermittent fasting(IF),particularly time-restricted feeding(TRF),is increasingly popular has gained popularity for weight loss,yet management,but its effects impact on gut health remain unclear.Remains in...BACKGROUND Intermittent fasting(IF),particularly time-restricted feeding(TRF),is increasingly popular has gained popularity for weight loss,yet management,but its effects impact on gut health remain unclear.Remains inadequately understood.This study explores how investigated the effects of TRF effects on intestinal health and explored the underlying mechanisms.AIM To assess the effects of IF on intestinal health,elucidate the mechanisms involved.METHODS Mice were divided into two groups:Normal control(NC)and IF.The IF group underwent TRF,while the NC group had unrestricted access to food.Body weight,fecal characteristics,and intestinal morphology were analyzed.Colon tissue,serum,and fecal samples were collected for histological analysis,enzymelinked immunosorbent assay,flow cytometry,16S rRNA sequencing,and metabolomic profiling.RESULTS IF significantly affected body weight and intestinal morphology,compromised the intestinal barrier,increased pro-inflammatory cytokines,and heightened gut immune activation(P<0.05).It also disrupted the gut microbiota,promoting proinflammatory bacteria,reducing anti-inflammatory metabolites,and elevating pro-inflammatory metabolites(P<0.05).Indoleacrylic acid(IAA)supplementation notably alleviated intestinal inflammation and reversed immune dysfunction induced by IF(P<0.05).CONCLUSION Prolonged IF exacerbates intestinal inflammation by impairing gut barrier integrity and disrupting microbial homeostasis.However,IAA supplementation effectively mitigates fasting-induced intestinal inflammation and immune imbalance,suggesting its potential as a therapeutic agent.展开更多
Intermittent heating is an energy-saving heating mode,which can save energy in terms of time,and thus is worth promoting,particularly in residential heating scenarios.Conventional radiant heating terminals,that is flo...Intermittent heating is an energy-saving heating mode,which can save energy in terms of time,and thus is worth promoting,particularly in residential heating scenarios.Conventional radiant heating terminals,that is floor heating,and convective heating terminals,that is fan coils,cannot achieve both intermittent and thermal comfort during intermittent heating.Therefore,this study proposes a switchable convective-radiant heating regulation method for floor heating and fan coils to achieve a comfortable indoor environment with high thermal response speed.Furthermore,a novel combined radiant-convective heating terminal was proposed for a reliable and effective solution.Results showed that the proposed switchable method could increase both intermittence and thermal comfort.In addition,the heating terminal showed better heating performance than the combination of two conventional terminals at the key points of heating capacity,flexibility,and thermal response.It could initially heat up a typical residential space within 20-40 min and then stabilize the room temperature in a comfortable range of 18-22℃,showing great potential for intermittent heating in room-scale heating conditions.This study provides a reference technique for intermittent heating with reduced system complexity and precise environmental control.展开更多
Cardiolipins(CLs),the mitochondria-specific class of phospholipids,are crucial to energy metabolism,cristae structure,and cell apoptosis.CLs present significant challenges in lipidomics analysis due to their structura...Cardiolipins(CLs),the mitochondria-specific class of phospholipids,are crucial to energy metabolism,cristae structure,and cell apoptosis.CLs present significant challenges in lipidomics analysis due to their structural diversity with up to four fatty acyl side chains.In this study,we developed CLAN(Cardio Lipin ANalysis),a comprehensive computational pipeline designed to improve the accuracy and coverage of cardiolipin identification.CLAN integrates three innovative modules:A cardiolipin identification module that utilizes specific fragmentation rules for precise characterization of CLs and their acyl side chains;a false positives detection module that employs retention time(RT)criteria to reduce false positives;and a prediction module that constructs regression models to identify CLs lacking authentic MS/MS spectra.CLAN achieved better identification accuracy and the highest recall rate for potential CL identification compared to the existing lipid identification tools.Furthermore,we applied CLAN program to an intermittent fasting mouse model,delineating tissue-specific CL alterations across 10 tissues.Every-other-day fasting(EODF)can partially counteract the disruption of the CL atlas across multiple tissues caused by high-fat-high-sugar diet feeding,providing novel insights into mitochondrial lipid metabolism under dietary interventions.Taken together,this work not only advances CL identification methodology but also underscores CLAN's potential in comprehensive analysis of CL atlas in the EODF animal model.CLAN is freely accessible on Git Hub.展开更多
Objective:A complex relationship exists between obstructive sleep apnea syndrome and diabetes mellitus(DM).Chronic intermittent hypoxia(CIH),which is a core pathological feature of obstructive sleep apnea syndrome,may...Objective:A complex relationship exists between obstructive sleep apnea syndrome and diabetes mellitus(DM).Chronic intermittent hypoxia(CIH),which is a core pathological feature of obstructive sleep apnea syndrome,may play an important role in the onset and development of DM-related atherosclerosis(DM-AS).This study aimed to investigate the mechanism of action of tetramethylpyrazine(TMP)in CIH-associated DM-AS.Methods:In vivo,a DM-AS mouse model was established by intraperitoneal injection of streptozotocin combined with a high-fat diet.They were exposed to CIH or normoxic conditions for 8 weeks and received different doses of TMP,rosuvastatin,toyocamycin,and purified water.Glycolipid metabolism,inflammation levels,degree of aortic AS,and expression levels of endoplasmic reticulum stress(ERS)and autophagy proteins were examined in mice.In vitro,human umbilical vein endothelial cells(HUVECs)were treated with high glucose and fat in combination with insulin to establish an insulin-resistant cell model(HUVEC-IR).After pretreatment with 4μ8C(IRE1 inhibitor)and different doses of TMP,intermittent hypoxic intervention was performed.Changes in cell morphology,proliferative activity,glucose consumption,and ability to migrate were observed,and the expression levels of ERS and autophagy proteins were detected.Results:In vivo experiments showed that CIH significantly increased blood glucose levels and Homeostasis Model Assessment of Insulin Resistance(HOMA-IR)(P<0.001 or P<0.05),low-density lipoprotein cholesterol(LDL-C)content(P<0.001),and the levels of three inflammatory factors[interleukin-1 beta(IL-1β),IL-6,and tumor necrosis factor-alpha(TNF-α)]in the mice(P<0.001)compared with those of the mice with DM alone;moreover,the aortic atherosclerotic(AS)plaque area in CIH mice was significantly enlarged(P<0.001).Western blotting results showed that the expressions of aortic IRE1α,XBP1s,Beclin1,and LC3A proteins were significantly increased in CIH mice compared with DM mice(P<0.05).After treatment with different doses of TMP,rosuvastatin calcium,and toyocamycin,serum inflammation and lipid levels and plaque area were significantly reduced in mice(P<0.001 and P<0.001,respectively).The expression levels of aortic XBP1s,Beclin1,and LC3A were reduced in TMP-and toyocamycin-treated mice(P<0.05).In the in vitro experiments,compared with normoxic cells,the cells treated with intermittent hypoxia(IH)showed a significant decrease in cell migration distance(P<0.05),a significant increase in apoptosis rate(P<0.001),a substantial increase in proliferation inhibition rate(P<0.001),a significant increase in the levels of XBP1s and LC3A proteins(P<0.05),and an increase in the number of autophagic vesicles/lysosomes,as observed under transmission electron microscopy.After treatment with different doses of TMP and 4μ8C,cell morphology was significantly restored,apoptosis rate significantly reduced(P<0.001),and XBP1s,Beclin1,and LC3A expressions significantly inhibited(P<0.05).Conclusion:CIH promoted the onset of DM-AS,whereas TMP attenuated ERS and excessive autophagy by modulating the IRE1α-XBP1 signaling pathway and inhibiting XBP1 splicing,thereby ameliorating DM-AS exacerbated by CIH.展开更多
基金Special Fund for the Whole Nation Excellent Doctorate Thesis of the Colleges and University of China.
文摘Aerodynamic characteristics, the noise characteristics in the course of intermittence exhaust are investigated and the expressions for sound pressure level of the noise generated by single-pole source and quadrupole source in the intermittence exhaust noise are established. The effects of all parameters in pneumatic system on the noise are also comprehensively studied.
基金the supports of the National Natural Science Foundation of China(Grant No.52375378)。
文摘The multi-pass intermittent local loading process,which features a more flexible processing path,can further enhance the second material distribution during local loading,improve the formability of components,and reduce forming loads.However,the absence of compatible forming equipment makes it difficult to control the constraint in the unloaded zones during the forming process.This difficulty complicates coordination and control of deformation,particularly for asymmetric rib-web components.Additionally,the current implementation involves multi-fire heating,a long process flow,and high energy consumption,which limits the popularization and application of the local loading process.In this study,a new multi-pass local loading hydraulic forming apparatus that can quickly and reliably switch between heavy-load deformation and low-load constraint for different local loading sub-dies was developed.A 10-tonne laboratory prototype was developed,and the forming characteristics during the forming process as well as the response characteristics of the hydraulic system during the multi-pass intermittent local loading of rib-web component were investigated using numerical simulations and physical experiments.Results indicated that,compared to a whole loading process with the same initial geometry of billet,the total forming load(i.e.,the sum of loaded and restrained loads)is reduced by more than 40%with the local loading process,and by nearly 50%with multi-pass local loading.The multi-pass local loading process allows for more effective control of material flow compared to single-pass local loading,leading to improved cavity filling and reduced flow line disturbance.For a large-scale,complex titanium alloy bulkhead,the cavity filling problem was addressed by optimizing the multi-pass local loading path with an unequal thickness billet.The dynamic performance of the multi-pass local loading hydraulic system was found to be robust,with stable pressure transitions during motion and load switching for the sub-die(s).The dynamic characteristic of the hydraulic cylinder when switching from non-moving/unloaded state to a moving/loading state are consistent whether a load is present or not.However,the dynamic characteristics differ when switching from a moving/loading state to non-moving/unloaded state,showing opposite behavior.The developed hydraulic drive mechanism provides a way for implementation of multi-pass local loading without auxiliary operation and extra heating.The results of the study provide a foundation for the industrial production of large-scale,complex components with reduced force requirement and low-energy consumption.
基金Supported by National Natural Science Foundation of China(No.82020108006,No.81730025).
文摘AIM:To summarize publication trends in the field of strabismus over the past 30y and predict future research hotspots.METHODS:A total of 2915 English-language articles and reviews on strabismus,published between 1993 and 2022,were retrieved from the Web of Science Core Collection.Bibliometric analyses were performed using VOSviewer and CiteSpace software to explore publication trends,as well as the contributions and collaborative networks of countries/regions,authors,institutions,and journals.RESULTS:The annual number of publications on strabismus showed a consistent upward trend.The United States(USA)maintained a leading position in this research field while Republic of Korea and China emerged as rapidly advancing contributors over the last decade.The University of California,Los Angeles ranked as the most productive institution,and Jonathan M.Holmes from USA was the most productive author.Journal of AAPOS was the leading journal with the most strabismus publications,whereas the two most highly cited articles were both published in Ophthalmology.Co-occurrence analysis identified pivotal keywords and burst terms,including intermittent exotropia(IXT),acute acquired comitant esotropia(AACE),functional magnetic resonance imaging(fMRI),and surgical treatment,which were confirmed as predominant and frontier topics.CONCLUSION:This study provides a comprehensive bibliometric analysis of strabismus research,revealing the evolution of research hotspots over the past 30y and outlining several cutting-edge directions for future investigation.
基金sponsored by the National Natural Science Foundation of China(Nos.82027802,82101389,82274401,and 81971114)Beijing Nova Program(No.20230484286)+1 种基金Beijing Natural Science Foundation(7254366)the General Project of Science and Technology of Beijing Municipal Education Commission(No.KM202110025018).
文摘Objective Cerebral venous outflow disorders(CVOD)can impair cerebral perfusion and produce diverse,often debilitating symptoms,substantially reducing quality of life.Intermittent hypoxiahyperoxia training(IHHT)has demonstrated therapeutic potential across various pathologies and may represent a promising non-pharmacological approach for CVOD management.Methods Patients with imaging-confirmed CVOD underwent 14 IHHT sessions,each comprising four cycles of 10-minute hypoxia(11%O_(2))stimulation and 20-minute hyperoxia(38%O_(2)).Physiological parameters and adverse events were monitored throughout the intervention.Clinical scales,24-hour ambulatory blood pressure,blood tests,jugular ultrasound,and perfusion imaging were assessed preand post-intervention.Results No participants experienced intolerable discomfort or severe adverse events;vital signs remained within normal ranges.No significant changes were observed in 24-hour blood pressure,blood cell counts,lipid profiles,or other blood markers.Notably,60%of patients(n=12)reported overall symptom improvement on the Patient Global Impression of Change scale.Headache severity,as measured by the visual analogue scale,significantly decreased(6.33±1.22 vs.4.89±2.03,P=0.016).In patients with internal jugular vein(IJV)stenosis,significant improvements were observed in regional cerebral blood flow(including the insula,occipital lobe,internal capsule,and lenticula)and left J3-segment IJV flow volume(107.27[47.50,160.00]vs.140.83[55.00,210.00]mL/min,P=0.011).Conclusion The current IHHT protocol is safe and well-tolerated in patients with CVOD.IHHT may alleviate CVOD-related symptoms by improving oxygen saturation,cerebral perfusion,and venous outflow pattern,supporting its potential as a non-invasive therapeutic strategy.
基金financially supported by the Natural Science Research Start-up Foundation of Recruiting Talents of Nanjing University of Posts and Telecommunications(No.NY223016)Qinglan Project of Jiangsu Province of China2024 Nanjing Science and Technology Innovation Program(No.NJKCZYZZ2024-06)。
文摘With the in-depth implementation of sustainable development strategies,hydrogen energy as a clean energy source is receiving increasing attention[1,2].Among the various methods of hydrogen production,the electrocatalytic decomposition of abundant seawater into hydrogen utilizing renewable energy has emerged as a green and promising approach.However,natural seawater contains complex components,such as halide ions,which lead to the corrosion of catalysts or the occurrence of competitive side reactions during the electrolysis process[3].
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
文摘Using the incompressible isotropic turbulent fields obtained from direct numerical simulation and large-eddy simulation,we studied the statistics of oscillation structures based on local zero-crossings and their relation with inertial-range intermittency for transverse velocity and passive scalar.Our results show that for both the velocity and passive scalar,the local oscillation structures are statistically scaleinvariant at high Reynolds number,and the inertial-range intermittency of the overall flow region is determined by the most intermittent structures characterized by one local zero-crossing.Local flow patterns conditioned on the oscillation structures are characterized by the joint probability density function of the invariants of the filtered velocity gradient tensor at inertial range.We demonstrate that the most intermittent regions for longitudinal velocity tend to lay at the saddle area,while those for the transverse velocity tend to locate at the vortex-dominated area.The connection between the ramp-cliff structures in passive scalar field and the corresponding saddle regions in the velocity field is also verified by the approach of oscillation structure classification.
基金financially supported by the National Natural Science Foundation of China(Grant No.42172292)Taishan Scholars Project Special Funding,and Shandong Energy Group(Grant No.SNKJ 2022A01-R26).
文摘A conceptual model of intermittent joints is introduced to the cyclic shear test in the laboratory to explore the effects of loading parameters on its shear behavior under cyclic shear loading.The results show that the loading parameters(initial normal stress,normal stiffness,and shear velocity)determine propagation paths of the wing and secondary cracks in rock bridges during the initial shear cycle,creating different morphologies of macroscopic step-path rupture surfaces and asperities on them.The differences in stress state and rupture surface induce different cyclic shear responses.It shows that high initial normal stress accelerates asperity degradation,raises shear resistance,and promotes compression of intermittent joints.In addition,high normal stiffness provides higher normal stress and shear resistance during the initial cycles and inhibits the dilation and compression of intermittent joints.High shear velocity results in a higher shear resistance,greater dilation,and greater compression.Finally,shear strength is most sensitive to initial normal stress,followed by shear velocity and normal stiffness.Moreover,average dilation angle is most sensitive to initial normal stress,followed by normal stiffness and shear velocity.During the shear cycles,frictional coefficient is affected by asperity degradation,backfilling of rock debris,and frictional area,exhibiting a non-monotonic behavior.
基金supported by grants from the Zhejiang Provincial Natural Science Foundation(LGJ22H180001)Zhejiang Medical and Health Science and Technology Project(2021KY249)the National Key R&D Program of China(2017YFC1310000).
文摘Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified.This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper(SMAp)in modulating MSL across different complexity levels and for both hands,as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation.Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL,which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions,particularly in interhemispheric connections.These findings may have important clinical implications,particularly for motor rehabilitation in populations such as post-stroke patients.
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Key Project of Jiangsu Commission of Health(Grant No.ZD2022012)。
文摘The circadian clock is crucial for the progression of cardiovascular diseases.Our previous studies showed that acrolein,an environmental pollutant,exacerbated atherosclerosis by reducing CLOCK/BMAL1 levels and disrupting circadian rhythm;in contrast,intermittent fasting(IF),a dietary regimen,ameliorated acrolein-induced atherosclerosis.In the current study,mice were administered acrolein at a dose of 3 mg/(kg·day)via drinking water and subjected to IF for 18 h(from 0:00 to 18:00).We observed that IF reduced the formation of aortic lesions accelerated by acrolein in Apo E-/-mice.Upon exposure to acrolein,the expression of Rel A,Il1b,and Tnf increased in the liver and heart tissues,but these changes were reversed by IF treatment.Notably,IF treatment upregulated the expression of adenosine monophosphate(AMP)-activated protein kinase catalytic subunit alpha-1(AMPKα1),p-AMPKα1,and sirtuin 1(SIRT1),while inhibiting acrolein-induced mitogen-activated protein kinase(MAPK)activation.Additionally,the expression of circadian genes Clock/Bmal1 was suppressed and disrupted by acrolein,whereas IF restored their expression.Moreover,consistent with the in vivo findings,shortterm starvation in vitro,as a fasting cell model,alleviated the dysregulation of CLOCK/BMAL1 and upregulated SIRT1 expression by modulating the AMPK and reactive oxygen species(ROS)-MAPK pathways activated by acrolein.In summary,we demonstrated that IF suppressed the ROS-MAPK pathway but activated the AMPK pathway to enhance the expression of circadian clock genes,thereby ameliorating acrolein-induced atherogenesis,which may shed light on strategies for preventing cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(No.82371093 and No.81970844).
文摘Objective Previous studies have yielded contradictory conclusions on the relationship between intermittent exotropia(IXT)and the magnitude of myopia,especially in children.The aim of this study was to determine the clinical characteristics of IXT in children with myopia and myopic anisometropia.Methods We retrospectively evaluated the clinical data of patients(4–15 years of age)with convergence insufficiency(CI)-IXT and basic IXT who underwent surgery between 2022 and 2023.All patients underwent cycloplegia before the examinations and surgery.The degree of strabismus was measured when the patient viewed from the center of the glasses.Ocular dominance was routinely tested in children with IXT via the“hole-in-card test”after best-corrected visual acuity was obtained.Children were subsequently grouped into 2 groups(anisometropia and nonanisometropia)according to the difference in binocular spherical equivalent(SE)values(≥1.0 diopters[D]).Results A total of 197 patients were included in the study.The preoperative deviation at near was significantly lower in the basic IXT group than in the CI-IXT group,whereas the distance exodeviation was significantly greater in the basic IXT group than in the CI-IXT group(P<0.05).Patients with anisometropia were older than those without anisometropia(P<0.001).The dominant eyes had significantly less myopia than the nondominant eyes did in the CI-IXT and anisometropia groups(P=0.049 and P=0.003,respectively).High myopia was more prevalent in middle school students with IXT(16.67%)than in preschool students(4.55%)and primary schoolchildren(3.18%).The percentage of individuals with anisometropia(≥3.0 D)varied in the low(1.68%),moderate(8.7%),and high myopia groups(22.22%).Binomial logistic regression analysis revealed that age and SE of the dominant eye were independent factors related to anisometropia in children with IXT(P<0.001 and P<0.001,respectively).Conclusion Patients with IXT,especially those with anisometropia and CI-IXT,were shown to have less myopia in the dominant eye.Age and SE of the dominant eye were found to be independent factors related to anisometropia in children with IXT.
基金supported in part by the IN2CCAM project that has received funding from the European Union's Horizon Europe research and innovation programme(101076791)the National Natural Science Foundation of China(62403378)the Natural Science Basic Research Program of Shaanxi Province(2024JC-YBQN-0669)
文摘In this work, we address the codiagnosability analysis problem of a networked discrete event system under malicious attacks. The considered system is modeled by a labeled Petri net and is monitored by a series of sites, in which each site possesses its own set of sensors, without requiring communication among sites or to any coordinators. A net is said to be codiagnosable with respect to a fault if at least one site could deduce the occurrence of this fault within finite steps. In this context, we focus on a type of malicious attack that is called stealthy intermittent replacement attack. The stealthiness demands that the corrupted observations should be consistent with the system's normal behavior, while the intermittent replacement setting entails that the replaced transition labels must be recovered within a bounded of consecutive corrupted observations(called as K-corruption intermittent attack). Particularly, there exists a coordination between attackers that are separately effected on different sites, which holds the same corrupted observation for each common transition under attacks. From an attacker viewpoint, this work aims to design Kcorruption intermittent attacks for violating the codiagnosability of systems. For this purpose, we propose an attack automaton to analyze K-corruption intermittent attack for each site, and build a new structure called complete attack graph that is used to analyze all the potential attacked paths. Finally, an algorithm is inferred to obtain the K-corruption intermittent attacks, and examples are given to show the proposed attack strategy.
文摘In dynamic scenes,the pose estimation and map consistency of visual simultaneous localisation and mapping(visual SLAM)are affected by intermittent changes in object motion states.An adaptive motion-state estimation and feature-reuse mechanism is proposed which restores features once objects become stationary.Camera ego-motion is com-pensated via projection-based point-to-point red-green-blue-depth(RGB-D)Iterative Closest Point;the alignment residual yields a short-term jitter score.An Extended Kalman Filter fuses the centre-pixel trajectory and depth of the object,using depth innovation as strong evidence to suppress false triggers.Applied adaptive decision thresholds involve resolution,ego-motion intensity,jitter,and reference depth,and are combined with dual/single triggering and hysteresis to achieve robust switching.When an object is considered static,its feature points are reused.On the Bonn RGB-D Dynamic Dataset(BONN)and TUM RGB-D SLAM Dataset and Benchmark(TUM),the proposed method matches or exceeds baselines:In intermittent-motion-dominated BONN sequences Placing_non_box,it re-duces the root-mean-square of the absolute trajectory error(ATE-RMSE)by 27%relative to the baseline,remains comparable to Ellipsoid-SLAM on TUM,and consistently outperforms ORB-SLAM3 in dynamic scenes.The hysteresis counter reading on Placing_non_box2 shows that the proposed method can reduce the motion-state misclassification rate by nearly 40%.From the ablation experiment results,we confirm that adaptive thresholds yield the most significant optimisation effect.The approach improves robustness and map completeness in dynamic environments without degrading performance in low-dynamic settings.
文摘BACKGROUND 5-aminosalicylates(5-ASA)are the primary treatment for mild to moderate ulcerative colitis(UC).Maintenance therapy with 5-ASA has been shown to reduce both the risk of relapse and colorectal cancer.AIM To evaluate the outcomes of 5-ASA withdrawal due to non-adherence in UC patients while in remission on monotherapy.METHODS Adult patients with UC who were followed up between July 2019 and April 2025 were screened.Patients in remission receiving 5-ASA monotherapy who experienced treatment withdrawal due to non-adherence were included in this study.RESULTS Among 880 patients with UC,30(3.4%)had 5-ASA withdrawal due to nonadherence while in remission on monotherapy.Twelve patients(40%)had disease relapse after a median of 20 months.The rate of patients in remission was 89%in the first year,decreasing to 73%in the second year,and to 64%in the third year.There were no significant differences between patients with and without relapse in terms of demographics,disease extent,remission duration before 5-ASA withdrawal,previous medications,steroid dependence,5-ASA formulation,baseline inflammatory markers,or partial and endoscopic Mayo scores.Most patients(75%)who experienced relapse were successfully treated with 5-ASA monotherapy,while one-fourth of them required corticosteroids.No patients required biologic agents,hospitalization,or surgical intervention.CONCLUSION Intermittent therapy may be safe and feasible for UC patients,especially those in long-term remission,with treatment interruption up to one year considered acceptable.
基金Supported by the Anhui University Research Project,No.2022AH051171Natural Science Foundation Project of Anhui Province,No.2408085QH271+6 种基金Anhui Medical University Scientific Research Level Improvement Plan,No.2022xkjT028Health Research Project of Anhui Province,No.AHWJ2023A30047the Anhui Provincial Natural Science Foundation,No.2208085MH240the Scientific Research Project of Anhui Provincial Department of Education,No.2022AH051167the Anhui Quality Engineering Project,No.2023sx200,No.2023jyjxggyjY087 and No.2023zyxwjxalk046the Anhui Provincial Postgraduate Education Quality Project,No.2024cxcysj062and Anhui Medical University Graduate Research and Practice Innovation Project,No.YJS20240095.
文摘BACKGROUND Intermittent fasting(IF),particularly time-restricted feeding(TRF),is increasingly popular has gained popularity for weight loss,yet management,but its effects impact on gut health remain unclear.Remains inadequately understood.This study explores how investigated the effects of TRF effects on intestinal health and explored the underlying mechanisms.AIM To assess the effects of IF on intestinal health,elucidate the mechanisms involved.METHODS Mice were divided into two groups:Normal control(NC)and IF.The IF group underwent TRF,while the NC group had unrestricted access to food.Body weight,fecal characteristics,and intestinal morphology were analyzed.Colon tissue,serum,and fecal samples were collected for histological analysis,enzymelinked immunosorbent assay,flow cytometry,16S rRNA sequencing,and metabolomic profiling.RESULTS IF significantly affected body weight and intestinal morphology,compromised the intestinal barrier,increased pro-inflammatory cytokines,and heightened gut immune activation(P<0.05).It also disrupted the gut microbiota,promoting proinflammatory bacteria,reducing anti-inflammatory metabolites,and elevating pro-inflammatory metabolites(P<0.05).Indoleacrylic acid(IAA)supplementation notably alleviated intestinal inflammation and reversed immune dysfunction induced by IF(P<0.05).CONCLUSION Prolonged IF exacerbates intestinal inflammation by impairing gut barrier integrity and disrupting microbial homeostasis.However,IAA supplementation effectively mitigates fasting-induced intestinal inflammation and immune imbalance,suggesting its potential as a therapeutic agent.
基金supported by the China National Key Research and Development Program"Integrated convection/radiation coupling terminals for local environment"(2022YFC3801502)the National Natural Science Foundation of China(52108082,52130803,and 52394223)+2 种基金the China Postdoctoral Science Foundation(2023M732479)the Natural Science Foundation of Sichuan Province of China(2024NSFSC0916)the New Cornerstone Science Foundation through the XPLORER PRIZE。
文摘Intermittent heating is an energy-saving heating mode,which can save energy in terms of time,and thus is worth promoting,particularly in residential heating scenarios.Conventional radiant heating terminals,that is floor heating,and convective heating terminals,that is fan coils,cannot achieve both intermittent and thermal comfort during intermittent heating.Therefore,this study proposes a switchable convective-radiant heating regulation method for floor heating and fan coils to achieve a comfortable indoor environment with high thermal response speed.Furthermore,a novel combined radiant-convective heating terminal was proposed for a reliable and effective solution.Results showed that the proposed switchable method could increase both intermittence and thermal comfort.In addition,the heating terminal showed better heating performance than the combination of two conventional terminals at the key points of heating capacity,flexibility,and thermal response.It could initially heat up a typical residential space within 20-40 min and then stabilize the room temperature in a comfortable range of 18-22℃,showing great potential for intermittent heating in room-scale heating conditions.This study provides a reference technique for intermittent heating with reduced system complexity and precise environmental control.
基金supported by grants from the National Key Research and Development Program of China(No.2022YFE0205800)the National Natural Science Foundation of China(No.21974114)+5 种基金Major Science and Technology Special Project of Fujian Province(No.2022YZ036012)the Fundamental Research Funds for the Central Universities(No.20720220003)Project“111”sponsored by the State Bureau of Foreign Experts and Ministry of Education of China(No.BP0618017)to S.-H.LinNatural Science Foundation of Fujian Province of China(No.2022J01330)Natural Science Foundation of Xiamen City of China(No.3502Z20227208)the China Scholarship Council(No.202308350047)to J.Zeng。
文摘Cardiolipins(CLs),the mitochondria-specific class of phospholipids,are crucial to energy metabolism,cristae structure,and cell apoptosis.CLs present significant challenges in lipidomics analysis due to their structural diversity with up to four fatty acyl side chains.In this study,we developed CLAN(Cardio Lipin ANalysis),a comprehensive computational pipeline designed to improve the accuracy and coverage of cardiolipin identification.CLAN integrates three innovative modules:A cardiolipin identification module that utilizes specific fragmentation rules for precise characterization of CLs and their acyl side chains;a false positives detection module that employs retention time(RT)criteria to reduce false positives;and a prediction module that constructs regression models to identify CLs lacking authentic MS/MS spectra.CLAN achieved better identification accuracy and the highest recall rate for potential CL identification compared to the existing lipid identification tools.Furthermore,we applied CLAN program to an intermittent fasting mouse model,delineating tissue-specific CL alterations across 10 tissues.Every-other-day fasting(EODF)can partially counteract the disruption of the CL atlas across multiple tissues caused by high-fat-high-sugar diet feeding,providing novel insights into mitochondrial lipid metabolism under dietary interventions.Taken together,this work not only advances CL identification methodology but also underscores CLAN's potential in comprehensive analysis of CL atlas in the EODF animal model.CLAN is freely accessible on Git Hub.
基金the National Natural Science Foundation of China(82074264)。
文摘Objective:A complex relationship exists between obstructive sleep apnea syndrome and diabetes mellitus(DM).Chronic intermittent hypoxia(CIH),which is a core pathological feature of obstructive sleep apnea syndrome,may play an important role in the onset and development of DM-related atherosclerosis(DM-AS).This study aimed to investigate the mechanism of action of tetramethylpyrazine(TMP)in CIH-associated DM-AS.Methods:In vivo,a DM-AS mouse model was established by intraperitoneal injection of streptozotocin combined with a high-fat diet.They were exposed to CIH or normoxic conditions for 8 weeks and received different doses of TMP,rosuvastatin,toyocamycin,and purified water.Glycolipid metabolism,inflammation levels,degree of aortic AS,and expression levels of endoplasmic reticulum stress(ERS)and autophagy proteins were examined in mice.In vitro,human umbilical vein endothelial cells(HUVECs)were treated with high glucose and fat in combination with insulin to establish an insulin-resistant cell model(HUVEC-IR).After pretreatment with 4μ8C(IRE1 inhibitor)and different doses of TMP,intermittent hypoxic intervention was performed.Changes in cell morphology,proliferative activity,glucose consumption,and ability to migrate were observed,and the expression levels of ERS and autophagy proteins were detected.Results:In vivo experiments showed that CIH significantly increased blood glucose levels and Homeostasis Model Assessment of Insulin Resistance(HOMA-IR)(P<0.001 or P<0.05),low-density lipoprotein cholesterol(LDL-C)content(P<0.001),and the levels of three inflammatory factors[interleukin-1 beta(IL-1β),IL-6,and tumor necrosis factor-alpha(TNF-α)]in the mice(P<0.001)compared with those of the mice with DM alone;moreover,the aortic atherosclerotic(AS)plaque area in CIH mice was significantly enlarged(P<0.001).Western blotting results showed that the expressions of aortic IRE1α,XBP1s,Beclin1,and LC3A proteins were significantly increased in CIH mice compared with DM mice(P<0.05).After treatment with different doses of TMP,rosuvastatin calcium,and toyocamycin,serum inflammation and lipid levels and plaque area were significantly reduced in mice(P<0.001 and P<0.001,respectively).The expression levels of aortic XBP1s,Beclin1,and LC3A were reduced in TMP-and toyocamycin-treated mice(P<0.05).In the in vitro experiments,compared with normoxic cells,the cells treated with intermittent hypoxia(IH)showed a significant decrease in cell migration distance(P<0.05),a significant increase in apoptosis rate(P<0.001),a substantial increase in proliferation inhibition rate(P<0.001),a significant increase in the levels of XBP1s and LC3A proteins(P<0.05),and an increase in the number of autophagic vesicles/lysosomes,as observed under transmission electron microscopy.After treatment with different doses of TMP and 4μ8C,cell morphology was significantly restored,apoptosis rate significantly reduced(P<0.001),and XBP1s,Beclin1,and LC3A expressions significantly inhibited(P<0.05).Conclusion:CIH promoted the onset of DM-AS,whereas TMP attenuated ERS and excessive autophagy by modulating the IRE1α-XBP1 signaling pathway and inhibiting XBP1 splicing,thereby ameliorating DM-AS exacerbated by CIH.
