The core mechanisms underlying aging involve genomic instability, cellular senescence, mitochondrial dysfunction, and chronic inflammation, necessitating multi-dimensional therapeutic interventions. Treg-derived extracellular vesicles (Treg-EVs) therapy, which circumvents the safety risks associated with live cell therapies, exhibits the potential to modulate metabolic and immune functions, offering promise for healthy aging. Here, we isolated Tregs from young male C57BL/6 mice and collected Treg-EVs. In vitro experiments demonstrated that Treg-EVs significantly attenuated cellular senescence, reduced reactive oxygen species (ROS) accumulation, and enhanced mitochondrial respiration in HL-1 and HT22 senescent cell models. In vivo experimental data revealed that young Treg-EVs promoted mitochondrial biogenesis, facilitated vascular repair and regeneration, as well as attenuated inflammatory responses, and ultimately prolonged the survival of aged male C57BL/6 mice. This study demonstrates the ability of Treg-EVs therapy to reverse multiple aging-related abnormal phenotypes, providing a promising strategy for treating aging and its associated diseases.

Glymphatic system function has been increasingly linked to cognition in cerebral small vessel disease (CSVD), although the underlying pathological mechanisms related to brain metabolism remain to be fully clarified. Iron overload within white matter hyperintensity (WMH), potentially reflecting metabolic abnormalities, may play a pivotal role in this process. This study investigated whether WMH iron burden mediates the association between glymphatic dysfunction and cognitive impairment in CSVD. A total of 102 patients with CSVD and 29 matched healthy controls (HCs) underwent brain MRI and cognitive assessments. WMH iron burden was quantified using a sub-voxel quantitative approach, while glymphatic function was assessed with the Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS) index. Correlation and mediation analyses were then conducted to evaluate relationships among WMH iron burden, DTI-ALPS index, and cognitive scores. Compared with HCs, CSVD patients exhibited significantly higher WMH iron burden, lower DTI-ALPS index, and poorer cognitive performances. Elevated WMH iron burden was associated with deficits in attention-executive (att-exe), memory, and visual-spatial domains, whereas reduced DTI-ALPS index correlated with impaired att-exe and memory function. Importantly, WMH iron burden fully mediated the link between DTI-ALPS index and both att-exe function (p < 0.001) and memory (p = 0.02) in the CSVD group. These findings noninvasively identify WMH iron overload, a probable representative of microglial activation, as a key mediator between glymphatic dysfunction and cognitive decline in CSVD, prompting a potential therapeutic target for disease management.

Background There is growing evidence that cigarette smoking is associated with abnormal white matter (WM) microstructure. However, traditional research using group-level mass-univariate statistical analysis, despite strict multiple comparison corrections, may still yield false positives or false negatives. In this study, a multivariate machine learning method was performed to enhance the identification of smoking-related WM regions. Methods The whole-brain skeletonized maps of diffusion metrics derived from diffusion tensor imaging of 60 tobacco use disorder (TUD) participants and 66 non-TUD subjects were utilized as classification features. A linear support vector machine (SVM) classifier was trained to differentiate between TUD and non-TUD individuals, and smoking-related WM regions were determined using discriminative score. Correlation analysis was conducted to evaluate the relationship between classification scores and smoking-related variables among TUD participants. Results The SVM classifier achieved an accuracy over 0.80 and an area under the curve exceeding 0.91, with maximal discriminative weights localized to the anterior corona radiata, posterior thalamic radiation, and genu of the corpus callosum (i.e., forceps minor). Moreover, classification scores were positively correlated with the onset age of cigarette use. Conclusions Our multivariate approach using whole-brain skeletonized maps of diffusion metrics outperformed those using regional features, demonstrating superior classification performance. The WM discriminative regions identified by our approach may offer a more effective way to distinguish individuals with nicotine addiction, potentially advancing our understanding of smoking-related brain alterations.

Immune disorders are intimately involved in the pathological progression of myocardial ischemia-reperfusion injury (MIRI) and exacerbate cardiac cell damage and mitochondria-related metabolic abnormalities. However, low-immunogenic therapeutic strategies targeting the compromised immune-metabolic microenvironment remain a major challenge. Here, we developed a syngenic reparative macrophage system for the selective delivery of nanoscale drugs by modifying liposomes loaded with nano-Pt/Se and c176 onto the surface of M2 macrophages (PS-c@M). In MIRI mice, transplanted PS-c@M was actively recruited to the myocardial ischemic region, maintained long-lasting residence, and responsively released surface-loaded nanomedicines, which in turn synergistically promoted cardiac cell survival and activated extracellular repair and angiogenesis, thus exerting long-term cardioprotective effects. Specifically, PS-c@M significantly inhibited STING-related signaling pathways, thereby remodeling the immune-inflammatory homeostasis, as evidenced by the increased proportions of M2 macrophages, reparative cardiac resident macrophages, and regulatory T cells and the decreased recruitment and infiltration of M1 macrophages and neutrophils. Moreover, PS-c@M facilitated mitochondrial oxidative phosphorylation and suppressed mitochondria-associated ferroptosis and oxidative damage. This study highlights a low-immunogenic targeted therapeutic strategy based on syngenic reparative macrophages as efficient nanomedicine carriers, with potential for development and application in a wide range of immune and inflammation-related diseases.

Neuroimaging studies revealed that smoking is associated with abnormal white matter (WM) microstructure. However, results are controversial, and the impact of smoking on the WM integrity in young smokers is still unclear. In this study, we used diffusion tensor imaging to investigate the smoking-related WM alterations in young adult smokers. One hundred and twenty-six subjects (60 current smokers and 66 nonsmokers) aged 18-29 years participated in the study. The tract-based spatial statistics with multiple diffusion indices was applied to explore diffusivity patterns associated with smoking. Correlation analysis was performed to evaluate relationships between fractional anisotropy (FA) and smoking-related variables in young adult smokers. Compared with nonsmokers, young adult smokers showed higher FA dominantly in the anterior cerebral WM regions, while lower FA mainly in the posterior cerebral WM areas. The dominant diffusivity pattern for regions with larger FA was characterized by lower radial and axial diffusion (Dr and Da), while in areas with smaller FA, higher Dr without significant difference in Da was the main diffusivity pattern. Moreover, diffusion indices in the genu and body of the corpus callosum were related with smoking-related variables. Our findings indicate that smoking may have differential effects on the WM integrity in the anterior and posterior parts of the brain, and may also accelerate brain aging in young adult smokers.

Introduction: Many studies have found sex differences in alterations of brain function in cigarette-smoking adults from the perspective of functional activity or connectivity. However, no studies have systematically found different alteration patterns in brain functional topology of cigarette-smoking men and women from three perspectives: nodal and network efficiency and modular connections. Aims and Methods: Fifty-six tobacco use disorder (TUD) participants (25 women) and 66 non-TUD participants (28 women) underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed, and a two-way analysis of covariance with false discovery rate correction (q < 0.05) was performed to investigate whether men and women TUD participants had different alterations in the topological features at global, modular, and nodal levels. Results: Compared to non-TUD participants, men but not women TUD participants showed significantly lower global efficiency (lower intermodular connections between the visual and executive control and between the visual and subcortical modules did not pass the correction) and significantly lower nodal global efficiency in the right superior occipital gyrus, bilateral fusiform gyrus, the right pallidum, right putamen, the bilateral paracentral lobule, the postcentral gyrus, and lower nodal local efficiency in the left paracentral lobule. Conclusions: Men and women TUD participants have different topological properties of brain functional network, which may contribute to our understanding of neural mechanisms underlying sex differences in TUD. Implications: Compared to non-TUD participants, we found men but not women TUD participants with significantly lower network metrics at global, modular, and nodal levels, which could improve our understanding of neural mechanisms underlying sex differences in TUD and lay a solid foundation for future sex-based TUD prevention and treatment.

Insufficient angiogenic stimulation and dysregulated glycolipid metabolism in senescent vascular endothelial cells (VECs) constitute crucial features of vascular aging. Concomitantly, the generation of excess senescence-associated secretory phenotype (SASP) and active immune-inflammatory responses propagates within injured vessels, tissues, and organs. Until now, targeted therapies that efficiently rectify phenotypic abnormalities in senescent VECs have still been lacking. Here, we constructed a Pd/hCeO(2)-BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors and modified with platelet membranes and investigated its therapeutic role in aged mice. PCBP showed significant maintenance in aged organs and demonstrated excellent biocompatibility. Through cyclic tail vein administration, PCBP extended the lifespan and steadily ameliorated abnormal phenotypes in aged mice, including SASP production, immune and inflammatory status, and age-related metabolic disorders. In senescent ECs, PCBP mediated the activation of vascular endothelial growth factor (VEGF) signaling and glycolysis and inhibition of FABP4 by inducing the synthesis of hypoxia-inducible factor-1 alpha, thereby reawakening neovascularization and restoring glycolipid metabolic homeostasis. In conclusion, the PCBP nanocapsule system provides a promising avenue for interventions against aging-induced dysfunction.

BackgroundMany reports have focused on cigarette smoking and internet gaming disorder (IGD), with widespread alterations of resting-state functional connectivity (rsFC) in the reward and memory circuits, respectively. Epidemiological studies have also shown high comorbidity of cigarette smoking and IGD. However, the underlying mechanisms are still unknown. Therefore, this study investigates the comorbidity and interaction effects between smoking and IGD from the rsFC perspective.MethodsResting-state functional magnetic imaging data were collected from 60 healthy controls (HC), 46 smokers, 38 IGD individuals, and 34 IGD comorbid with smoking (IGDsm) participants. Voxel-wise rsFC maps were calculated for all subjects with the ventral tegmental area, rostral hippocampus, and caudal hippocampus as regions of interest, respectively.ResultsSignificant interaction effects between smoking and IGD were mainly involved in the reward and memory circuits; that is, the rsFC between the ventral tegmental area and right nucleus accumbens, between the rostral hippocampus and bilateral nucleus accumbens, sensorimotor areas, and left middle temporal gyrus. Specifically, in these circuits, smokers showed decreased rsFC compared to the HC group, while IGDsm showed increased rsFC compared to smokers and IGD individuals. The IGDsm and HC groups showed no significant difference. The altered rsFC also correlated with clinical measures.ConclusionThese findings indicate that lower rsFC in smokers or IGD individuals increases under the effect of another type of addiction, such as smoking and IGD, but only increases to the normal state, which might explain the comorbidity and interaction between smoking and IGD from the perspective of functional circuits.

Purpose To identify cerebral radiomic features related to the diagnosis of Internet gaming disorder (IGD) and construct a radiomics-based machine-learning model for IGD diagnosis. Methods A total of 59 treatment-naïve subjects with IGD and 69 age- and sex-matched healthy controls (HCs) were recruited and underwent anatomic and diffusion-tensor magnetic resonance imaging (MRI). The features of the morphometric properties of gray matter and diffusion properties of white matter were extracted for each participant. After excluding the noise feature with single-factor analysis of variance, the remaining 179 features were included in an all-relevant feature selection procedure within cross-validation loops to identify features with significant discriminative power. Random forest classifiers were constructed and evaluated based on the identified features. Results No overall differences in the total brain volume (1,555,295.64 ± 152,316.31 mm3 vs. 154,491.19 ± 151,241.11 mm3), total gray (709,119.83 ± 59,534.46 mm3 vs. 751,018.21 ± 58,611.32 mm3) and white (465,054.49 ± 51,862.65 mm3 vs. 470,600.22 ± 47,006.67 mm3) matter volumes, and subcortical region volume (63,882.71 ± 5110.42 mm3 vs. 64,764.36 ± 4332.33 mm3) between the IGD and HC groups were observed. The mean classification accuracy was 73%. An altered cortical shape in the bilateral fusiform, left rostral middle frontal (rMFG), left cuneus, left parsopercularis (IFG), and regions around the right uncinate fasciculus (UF) and left internal capsule (IC) contributed significantly to group discrimination. Conclusions: Our study found the brain morphology alterations between IGD subjects and HCs through a radiomics-based machine-learning method, which may help revealing underlying IGD-related neurobiology mechanisms.

In order to eliminate or slow down the signal reflection of the electronic controller of the electric power steering（EPS）system, the phenomena of overshoot, undershoot, ringing and hookback of the signal caused by unstable transient impedance were analyzed and verified under the electronic control system.The causes of signal reflection were discussed, then the signal integrity of the electronic power steering system controller（ECU）was designed.Finally, the signal integrity was verified by driving the permanent magnet synchronous motor circuit with an example.It solves the problem of signal waveform distortion caused by interconnection, power supply, devices, etc.It meets the requirements of the system for signal quality and has a certain reference for the design of EPS system.

Internet gaming disorder (IGD) has a great negative impact on teenagers’ study and life. It has been included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders in 2013. However, the neural mechanism of its effect is yet to be unveiled. In this study, we used resting-state functional magnetic resonance imaging (resting-state fMRI) to explore the differences of rich club structures in the functional brain networks of 30 IGD subjects and 30 age/sex-matched healthy controls. The rich club was found in both IGD subjects and healthy controls, involving important brain regions in default mode, executive control, salience, sensorimotor, auditory and visual networks. IGD subjects had significantly higher rich club connection and higher degree in the right pars orbitalis of inferior frontal gyrus than healthy controls. These findings might suggest that IGD might be more correlated with damage to the rich club connection.

Many reports indicated that cigarette smoking was associated with internet gaming disorder (IGD). However, the underlying mechanism of comorbidity between smoking and IGD and whether they had interaction effects on topological organization of brain functional network are still unknown. Therefore, we investigated the interaction between smoking and IGD in resting-state brain functional networks for 60 healthy controls, 46 smokers, 38 IGD individuals and 34 IGD comorbid with smoking participants. The modular structures of functional networks were explored and participation coefficient (Pc) was used to characterize the importance of each brain region in the communication between modules. Significant main effect of IGD was found in the left superior frontal gyrus, bilateral medial part of superior frontal gyrus and bilateral posterior cingulate gyrus with lower Pc in IGD group than in non-IGD group. Significant interaction effects between smoking and IGD were found in the left posterior orbital gyrus, right lateral orbital gyrus, left supramarginal gyrus, left middle temporal gyrus and left inferior temporal gyrus. The interaction in these brain regions was characterized by no significant difference or significantly decreased Pc in smokers or IGD individuals while significantly increased Pc in IGD comorbid with smoking group under the influence of IGD or smoking. Our findings provide valuable information underlying the neurophysiological mechanisms of smoking and IGD, and also offer a potential target for future clinical treatment of smoking and IGD comorbidity.

Biological sex may play a large role in cigarette use and cessation outcomes and neuroimaging studies have demonstrated that cigarette smoking is associated with sex-related differences in brain structure and function. However, less is known about sex-specific alterations in spontaneous brain activity in cigarette smokers. In this study, we investigated the sex-related effects of cigarette smoking on local spontaneous brain activity using regional homogeneity (ReHo) based on resting-state fMRI. Fifty-six smokers (24 females) and sixty-three (25 females) healthy non-smoking controls were recruited. Whole-brain voxelwise 2-way analysis of covariance of ReHo was performed to detect brain regions with sex-dependent alterations on the spontaneous brain activity. Compared to non-smokers, smokers exhibited significant ReHo differences in several brain regions, including the right medial orbitofrontal cortex extended to the ventral striatum/amygdala/parahippocampus, left precuneus, and bilateral cerebellum crus. Smoking and sex interaction analysis revealed that male smokers showed significantly lower ReHo in the right ventral striatum, left cerebellum crus1, and left fusiform gyrus compared to male non-smokers, whereas there are no significant differences between female smokers and non-smokers. Furthermore, the ReHo within the left cerebellum crus1 was negatively correlated with craving scores in male smokers but not in female smokers. Such sex-dependent differences in spontaneous brain activity lays a foundation for further understanding the neural pathophysiology of sex-specific effects of nicotine addiction and promoting more effective health management of quitting smoking.

1Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Psychological Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 4Key Laboratory of Brain Functional Genomics (MOE&STCSM), Shanghai ChangningECNU Mental Health Center, School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China

基于EPS电流采样模块容差分析,利用了PSPICE软件对EPS采样电路误差进行了仿真和分析,讨论了元器件参数的温漂变化、精度以及环境温度对采样电路的影响,并对灵敏度以及最坏情况的结果进行了计算和探讨.结果表明:在EPS中,最坏情况分析法是目前应用范围最广泛、操作最简便的方法,该方法确保了所有零件组合的容差在最大范围或最小范围都有考虑,符合实际应用产品的严谨度和高可靠性,为EPS电流采样电路的可靠性设计提供了参考.

The high prevalence of somatic symptom disorder (SSD) led to cumulative burdens to the medical system. However, the pathogenesis of this disease still remains unclear. Graph theoretical analysis discovered altered network topology across various psychiatric disorders, yet alteration in the topological structure of brain functional network in SSD patients is still unexplored. Catastrophizing is a common cognitive distortion in SSD. We hypothesize that the network topological metrics of SSD should be altered, and should correlate with catastrophizing scales. 32 medication-naïve, first-episode SSD patients and 30 age, gender matched HCs were recruited. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA) and Cognitive Emotion Regulation Questionnaire (CERQ) were accessed. Functional MRI were scanned and brain functional networks were constructed based on 166 anatomically cerebrum regions from the automated anatomical labeling 3 (AAL3) template. Network topological metrics were calculated and compared between the two groups. Correlation between these metrics and clinical scales were also calculated. Network global efficiency of SSD was significantly lower than that of HC. Nodal global efficiency of the left subgenual anterior cingulate cortex (sgACC) of SSD was significantly lower than that of HC. FCs between the left sgACC and other 21 seed nodes were significantly declined in SSD in comparison with HC. In SSD group, HAMD total score was significantly negatively correlated with the connection between the left medial superior frontal gyrus and the left sgACC. CERQ catastrophizing score was significantly negatively correlated with nodal global efficiency of left sgACC and with the FCs between the left sgACC and other 13 seed nodes. Catastrophizing could reflect the specific sgACC-centered dysfunction of brain network global efficiency of SSD. The left sgACC may be a future treatment target of dealing with catastrophizing, which is a core cognitive distortion of SSD.

Objective Catastrophizing is commonly co-occurrence with anxiety in somatic symptom disorder (SSD). However, the quantitative relationship between catastrophizing and anxiety in SSD and its underlying neuropsychopathology remains unclear. Methods To address the issue, twenty-eight SSD patients and twenty-nine healthy controls (HCs) completed the Hamilton anxiety scale and the catastrophizing subscale of the cognitive emotion regulation questionnaire. Then they underwent structural magnetic resonance imaging and voxel-based morphometry analysis was performed to obtain gray matter density (GMD) of the dorsomedial prefrontal cortex (dmPFC). Results Independent samples t-tests showed no significance between SSD patients and HCs in the scores on the catastrophizing subscale and GMD of the dmPFC. However, correlation analysis found that catastrophizing was significantly positively associated with anxiety in SSD. Further, mediation analyses revealed that GMD of the dmPFC (bilateral medial Brodmann area 8) mediated the relationship between catastrophizing and anxiety in SSD. Conclusion These findings support Kirmayer’s disease model of SSD that catastrophic interpretations of somatic symptoms resulted in increased anxiety and demonstrate that the dmPFC may be a potential neural site linking catastrophizing and anxiety in SSD.

目的 探讨不同MR成像技术评价皮层下血管性认知功能障碍(SVCI)患者脑白质高信号(WMH)半暗带(WMH-P)的价值.方法 对29例SVCI患者行弥散加权成像(DTI)、三维动脉自旋标记(3D-ASL)和酰胺质子化学交换饱和转移(CEST APT)扫描及神经心理学评估.将WMH周围1 cm范围为定义WMH-P,分别测量WMH、WMH-P及WMH-P以外正常表观白质(NAWM)的各项成像参数值,并与认知评分进行相关性分析.结果 FA和MD值在WMH、WMH-P及WMH-P以外NAWM之间差异均有统计学意义(P均＜0.05),脑血流量(CBF)在WMH-P与WMH-P以外NAWM以及WMH与WMH-P以外NAWM之间均有统计学意义(P均＜0.05).WMH-P和WMH-P以外NAWM的FA值与MoCA评分呈显著正相关(P均＜0.05).结论 DTI技术与3D-ASL能反映SVCI患者脑白质病变范围及进展趋势;WMH-P的FA值能较好地评价SVCI患者认知功能水平.

Converging lines of evidence indicates that smoking and internet gaming disorder (IGD) affect spontaneous brain activity, respectively. However, little is known about whether these two factors work together on the human brain. In this study, we investigated the interaction between smoking and IGD on local spontaneous brain activity using amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI (rs-fMRI). Forty-six cigarette smokers, 38 IGD individuals, 34 participants with both IGD and cigarette smoking (IGD-Smoking), and 60 healthy individuals involved in the study. Voxel-wise analysis of covariance of ALFF revealed that there were significant interactions between IGD by smoking in the right medial pre-frontal cortex (MPFC)/ventral striatum, bilateral cerebellar, and visual-related regions as well as the left temporal gyrus. In the right MPFC/ventral striatum and left temporal gyrus, ALFF in smoking group was significantly higher than healthy group while there were no significant ALFF differences between IGD-Smoking group and IGD group. While in the bilateral cerebellar and visual-related regions, ALFF in the smoking group was significantly lower than healthy group while ALFF in IGD-Smoking group did not show significant difference with IGD group. In addition, in the smoking group, ALFF of the right MPFC/ventral striatum was associated positively with anxiety and depression scores while the ALFF value in the smoking group had a trend toward negative correlation with SDS scores in the bilateral cerebellar and visual-related regions. The ALFF value in the smoking group was associated positively with anxiety score in the left temporal gyrus. These findings indicate that smoking and IGD interacted with each other in the human brain. Our results, in terms of spontaneous brain activity, may imply the fact that IGD people are more tended to get smoking. Moreover, it is possible to predict that smokers may be more easily to get internet addiction than healthy people.

Recent studies have demonstrated sex-specific differences in etiology, course and brain dysfunction that are associated with cigarette smoking. However, little is known about sex-specific differences in subcortical structure and function. In this study, structural and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 cigarette smokers (25 females) and 67 nonsmokers (28 females). The structural MRI was applied to identify deficits in sex-specific subcortical volume. Using resting-state fMRI, sex-related alterations in resting-state functional connectivity (rsFC) were investigated in subcortical nuclei with volume deficits as seed regions. Compared to nonsmokers, male but not female smokers demonstrated a significantly smaller volume in the left caudate, while female but not male smokers showed a smaller volume in the right amygdala. Resting-state FC analysis revealed that male but not female smokers had increased rsFC between the left caudate and the left prefrontal cortex but decreased rsFC within the bilateral caudate and between the right amygdala and right orbitofrontal cortex (OFC). Furthermore, the right amygdala volume was negatively correlated with the impulsivity score in female but not male smokers. The rsFC of the right amygdala-OFC circuit was negatively associated with the craving score in male but not female smokers. These findings indicate that cigarette smoking may have differential effects on the caudate and amygdala volumes as well as rsFC between men and women, contributing to our knowledge of sex-specific effects of nicotine addiction. Such sex-specific differences in subcortical structure and function may provide a methodological framework for the development of sex-specific relapse prevention therapies.