Co-methylation analyses identify CpGs associated with lipid traits in Chinese discordant monozygotic twins.

To control genetic background and early life milieu in genome-wide DNA methylation analysis for blood lipids, we recruited Chinese discordant monozygotic twins to explore the relationships between DNA methylations and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). 132 monozygotic (MZ) twins were included with discordant lipid levels and completed data. A linear mixed model was conducted in Epigenome-wide association study (EWAS). Generalized estimating equation model was for gene expression analysis. We conducted Weighted correlation network analysis (WGCNA) to build co-methylated interconnected network. Additional Qingdao citizens were recruited for validation. Inference about Causation through Examination of Familial Confounding (ICE FALCON) was used to infer the possible direction of these relationships. A total of 476 top CpGs reached suggestively significant level (P < 10-4), of which, 192 CpGs were significantly associated with TG (FDR < 0.05). They were used to build interconnected network and highlight crucial genes from WGCNA. Finally, four CpGs in GATA4 were validated as risk factors for TC; six CpGs at ITFG2-AS1 were negatively associated with TG; two CpGs in PLXND1 played protective roles in HDL-C. ICE FALCON indicated abnormal TC was regarded as the consequence of DNA methylation in CpGs at GATA4, rather than vice versa. Four CpGs in ITFG2-AS1 were both causes and consequences of modified TG levels. Our results indicated that DNA methylation levels of 12 CpGs in GATA4, ITFG2-AS1, and PLXND1 were relevant to TC, TG, and HDL-C, respectively, which might provide new epigenetic insights into potential clinical treatment of dyslipidemia.

Advancements in investigating the role of cerebral small vein loss in Alzheimer's disease-related pathological changes.

Alzheimer's disease (AD) is the prevailing type of dementia in the elderly, yet a comprehensive comprehension of its precise underlying mechanisms remains elusive. The investigation of the involvement of cerebral small veins in the advancement of AD has yet to be sufficiently explored in previous studies, primarily due to constraints associated with pathological staining techniques. However, recent research has provided valuable insights into multiple pathophysiological occurrences concerning cerebral small veins in AD, which may manifest sequentially, concurrently, or in a self-perpetuating manner. These events are presumed to be among the initial processes in the disease's progression. The impact of cerebral small vein loss on amyloid beta (Aß) clearance through the glial lymphatic system is noteworthy. There exists a potential interdependence between collagen deposition and Aß deposition in cerebral small veins. The compromised functionality of cerebral small veins can result in decreased cerebral perfusion pressure, potentially leading to cerebral tissue ischemia and edema. Additionally, the reduction of cerebral small veins may facilitate the infiltration of inflammatory factors into the brain parenchyma, thereby eliciting neuroinflammatory responses. Susceptibility-weighted imaging (SWI) is a valuable modality for the efficient assessment of cerebral small veins, precisely the deep medullary vein (DMV), and holds promise for the identification of precise and reliable imaging biomarkers for AD. This review presents a comprehensive overview of the current advancements and obstacles to the impairment of cerebral small veins in AD. Additionally, we emphasize future research avenues and the importance of conducting further investigations in this domain.

A landscape of Long non-coding RNAs reveals the leading transcriptome alterations in murine aorta during aging.

Considerable studies have given convincing evidence of a forefront position for vascular aging in preventing cardiovascular disease. Various functions of Long non-coding RNAs (lncRNAs) are becoming increasingly distinct in aging-related diseases. This study aims at a better insight into the expression profile and mechanisms of lncRNAs in vascular senescence. High-throughput sequencing was used to detect the differential expression (DE) of lncRNAs and mRNAs in the aorta of 96 W and 8 W-old mice, while 1423 lncRNAs and 80 mRNAs were differentially expressed. By performing GO and KEGG enrichment analysis, we found that DE lncRNAs were mainly involved in purine metabolism and cGMP-PKG signaling pathways. In addition, a co-expression functional network of DE lncRNAs and DE mRNAs was constructed, and ENSMUST00000218874 could interact with 41 DE mRNAs, suggesting that it may play an essential role in vascular senescence. This study reveals DE lncRNAs in naturally aging vascular, which may provide new ideas and targets for aging-related cardiovascular diseases.

Characteristics of health care interventions in affordable senior housing: A scoping review.

AIMS: Older adults in affordable senior housing often experience chronic illness and unmet health care needs. This review describes studies reporting the characteristics and primary outcomes of health care interventions for older adults living in affordable senior housing. DESIGN: A scoping review METHODS: After a systematic search in three databases, a team of investigators screened 1,284 titles and abstracts and selected 31 records with reports on 28 studies for review. Narrative synthesis was used to describe studies of interventions in senior housing and primary outcomes. RESULTS: Studies typically used observational designs and added clinical staff, such as nurses and social workers, to provide health care interventions in groups (n = 15) or with individuals (n = 13). Outcomes were classified in four groups: wellness, symptom management, health care use, and physical function. A subset of 23 studies (82.1%) reported effective interventions. IMPACT: Findings identify innovative interventions to promote health in affordable senior housing.

Study on the pathogenesis of Holmes tremor by multimodal 3D medical imaging: case reports of three patients.

BACKGROUND: We examined for the first time the imaging characteristics of Holmes tremor (HT) through multimodal 3D medical imaging. CASE PRESENTATION: Three patients with Holmes tremor who visited the Affiliated Hospital of Chengdu University of TCM from August 2018 to April 2021 were retrospectively investigated to summarize their clinical and imaging data. RESULTS: Holmes tremor in two of the three patients was caused by hypertensive cerebral hemorrhage and in the third patient induced by hemorrhage due to ruptured brain arteriovenous malformations. HT occurred 1 to 24 months after the primary disease onset and manifested as a tremor in the contralateral limb, mostly in the upper portion. Cranial MRI showed that the lesions involved the thalamus in all three patients. The damaged thalamic nuclei included the ventral anterior nucleus, ventral lateral nucleus and ventromedial lateral nucleus, and the damaged nerve fibers included left thalamocortical tracts in one patient. In the other two patients, the damaged thalamic nuclei included the centromedian and dorsomedial nucleus, and the damaged nerve fibers included left cerebellothalamic and thalamocortical tracts. One patient showed significant improvement after treatment with pramipexole while the other two patients exhibited a poor response, one of whom had no response to the treatment with pramipexole and was only significantly relieved by clonazepam. CONCLUSION: We used multimodal 3D medical imaging for the first time to analyze the pathogenesis of HT and found that multiple thalamic nuclei were damaged. The damaged nuclei and nerve fiber tracts of two patients were different from those of the third patient, with different clinical manifestations and therapeutic effects. Therefore, it is speculated that there may be multiple pathogeneses for HT.

Intakes of Specific Categories of Vegetables and Fruits Are Inversely Associated With Depressive Symptoms Among Adults.

BACKGROUND: Epidemiological evidence on the relationships between intakes of different categories of vegetables and fruits and depressive symptoms is very limited and inconsistent, especially with no evidence from the general population. This study aimed to estimate their relationships among a large general population. METHODS: The cross-sectional design was based on the National Health and Nutrition Examination Survey (2007-2014) and included 16,925 adults. Dietary information was attained from two nonconsecutive 24-hr dietary recalls. Patient Health Questionnaire was applied for measuring depressive symptoms. The associations between vegetables and fruits intakes and depressive symptoms were appraised utilizing logistic regression and restricted cubic spline. RESULTS: Compared with the lowest category of intake, the most-adjusted odds ratios of depressive symptoms for the highest intake category of tomatoes and tomato mixtures were 0.81 (95% confidence interval [CI], 0.66-0.99), and 0.64 (95% CI, 0.48-0.85) for dark-green vegetables, 0.67 (95% CI, 0.53-0.84) for other vegetables, 0.48 (95% CI, 0.29-0.79) for berries, 0.67 (95% CI, 0.55-0.82) for total vegetables, and 0.70 (95% CI, 0.57-0.86) for total fruits, and for the medium categories of bananas and dried fruits were 0.62 (95% CI, 0.41-0.95) and 0.39 (95% CI, 0.19-0.81), respectively. After sensitivity analysis further excluding subjects with co-morbid health conditions, these findings remained significant, except for bananas. An L-shaped relationship was observed between depressive symptoms and intake of total vegetables, while the association was linear with total fruits intake. CONCLUSIONS: Intakes of tomatoes and tomato mixtures, dark-green vegetables, other vegetables, berries, dried fruits, total vegetables, and total fruits were inversely related to depressive symptoms among adults.

MicroRNA 182 promotes T helper 1 cell by repressing hypoxia induced factor 1 alpha in experimental autoimmune encephalomyelitis.

MicroRNA 182 is important for the clonal expansion of CD4+ T cells (Th) following IL-2 stimulation and is a potential therapeutic target for autoimmune diseases. In the present study, we investigated the role of microRNA 182 in the differentiation of pro-inflammatory CD4+ T helper cell by overexpressing or silencing microRNA 182 expression both in in vivo and in vitro settings. We report that in the studied Chinese cohort, microRNA 182 is upregulated in patients with relapse and remitting multiple sclerosis (RRMS) and this upregulation is associated with increased IFN-γ producing CD4+ Th1 cells in the circulation. In the murine experimental autoimmune encephalomyelitis (EAE) model, global microRNA 182 overexpression exacerbates clinical symptoms and results in augmented CD4+ IFN-γ+ Th1 and CD4+ IL-17+ Th17 differentiation in vivo. Addition of microRNA 182 mimics in vitro represses both the protein expression and transcriptional activity of hypoxia induced factor 1α (HIF-1α) but increases the level of IFN-γ transcripts in sorted murine CD4+ T cells. Together, our results provide evidence that microRNA 182 may be one of the transitional hubs contribution to regulate Th cells expansion in response to self-antigens and differentiation of antigen specific Th cells during the progression of autoimmune inflammations.

Comparative study on pyrolysis of bamboo in microwave pyrolysis-reforming reaction by binary compound impregnation and chemical liquid deposition modified HZSM-5.

The deactivation of catalyst is a significant reason for its limited application during the catalytic fast pyrolysis (CFP) process. To reduce the coke formation, binary compound impregnation (BCI) and chemical liquid deposition (CLD) were used to modify HZSM-5 catalysts. At the same time, the self-designed microwave reactor separated the pyrolysis of bamboo and catalytic upgrading of primary vapor, which made the catalytic effect more thorough. Experimental results indicated that CLD used TiO2 deposition to cover external acid sites, while BCI by phosphorus-nickel could cover and partly destroy superficial acid sites through two different ways. Within the scope of the loaded amount studied, the yield of aromatic hydrocarbons in the oil phase increased at first and then decreased, while the coke formation reduced continuously. BTX (benzene, toluene and xylene), the most valuable product in bio-oil, drastically increased by 39.1% and 22.6% respectively over the CLD and BCI modified catalysts. Considering the catalytic performance as well as cost, CLD over HZSM-5 has more advantages in the CFP process to upgrade bio-oil.

Metabolic reprogramming orchestrates CD4+ T-cell immunological status and restores cardiac dysfunction in autoimmune induced-dilated cardiomyopathy mice.

Cellular autoimmune responses, especially those mediated by T-cells, play vital roles in the immunopathogenesis of dilated cardiomyopathy (DCM). Metabolic reprogramming directly controls T-cell function, imprinting distinct functional fates. However, its contribution to T-cell dysfunction and the immunopathogenesis of DCM is unknown. Here, we found that in DCM patients, CD4+ T-cells exhibited immune dysfunction and glycolytic metabolic reprogramming based on extracellular acidification and oxygen consumption rates. Similar results were observed in splenic and cardiac CD4+ T-cells from autoimmune-induced DCM mice. In vitro, the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) reversed T-cell dysfunction; thus, heightened metabolic activity directly controls CD4+ T-cell immunological status. Adoptive transfer of CD4+ T-cells from DCM mice to normal recipients induced cardiac remodeling and cardiac T-cell dysfunction. Strikingly, these effects were abolished by preconditioning cells with 2-DG, indicating that CD4+ T-cell dysfunction partially induced by metabolic reprogramming contributes to cardiac remodeling. Moreover, the microRNA let-7i modulated the metabolism and function of T-cells from DCM mice by directly targeting Myc. Collectively, our results show that metabolic reprogramming occurs in T-cells of autoimmune-induced DCM mice and patients. Further, our findings highlight that glycolytic metabolism is a critical contributor to T-cell dysfunction and DCM immunopathogenesis. Our data position the modulation of the metabolism as a central integrator for T-cell function, representing a promising strategy against autoimmune-mediated DCM progression.

Functional network analysis reveals biological roles of lncRNAs and mRNAs in MOG35-55 specific CD4+T helper cells.

Long non-coding RNAs have the potential to regulate immune responses. Their impact on multiple sclerosis has remained elusive. For illustrating their roles in experimental autoimmune encephalomyelitis (EAE) pathogenesis, we investigated the differential expression of lncRNAs and mRNAs in CD4+Th cells obtained from myelin oligodendrocytic glycoprotein35-55(MOG35-55)-induced EAE and complete Freund's adjuvant (CFA) controls. We observed differential expression of 1112 lncRNAs and 519 mRNAs in CD4+Th cells. The functional network showed lncRNAs had the capacity to modulate EAE pathogenesis via regulating many known EAE regulators such as Ptpn6. Predicting the function of lncRNAs demonstrated that dysregulated lncRNAs were closely associated with the development of EAE. These dysregulated lncRNAs may have function in EAE and they could be novel biomarkers and therapeutic targets of EAE. However, the precise mechanisms and biological functions of these specific lncRNAs in EAE pathogenesis require further study.

MicroRNA 182 inhibits CD4+CD25+Foxp3+ Treg differentiation in experimental autoimmune encephalomyelitis.

MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3+ T cells in the peripheral lymph nodes and spleen. In vivo study verified a positive correlation between microRNA 182 levels and symptom severity of EAE, and a negative correlation between microRNA 182 and the transcriptional factor Foxp3. In vitro polarization study also confirmed the contribution of Foxo1 in microRNA 182 mediated down-regulation of Foxp3+ T cells. Together, our results provide evidence that during the development of EAE, microRNA 182 repressed Treg cells differentiation through the Foxo1 dependent pathway.

Ferroptosis: Mechanisms and role in diabetes mellitus and its complications.

Diabetes mellitus (DM) and its complications are major diseases that affect human health and pose a serious threat to global public health. Although the prevention and treatment of DM and its complications are constantly being revised, optimal treatment strategies remain unavailable. Further exploration of new anti-diabetic strategies is an arduous task. Revealing the pathological changes and molecular mechanisms of DM and its complications is the cornerstone for exploring new therapeutic strategies. Ferroptosis is a type of newly discovered iron-dependent regulated cell death. Notably, the role of ferroptosis in the occurrence, development, and pathogenesis of DM and its complications has gradually been revealed. Numerous studies have shown that ferroptosis plays an important role in the pathophysiology and pathogenesis of DM and its associated complications. The aim of this review is to discuss the known underlying mechanisms of ferroptosis, the relationship between ferroptosis and DM, and the relationship between ferroptosis as a mode of cell death and diabetic kidney disease, diabetic retinopathy, diabetic cardiomyopathy, diabetic osteoporosis, diabetes-associated cognitive dysfunction, DM-induced erectile dysfunction, and diabetic atherosclerosis.

Research on process parameter optimization of irregular coal face.

Based on the engineering background of 1353 working face in Daizhuang Coalmine, the paper identifies three primary issues with the working face mining process: conventional pressure relief means are limited, risk of impact and the length of working face changes, It also proposes comprehensive control measures to improve the blasting roof cutting scheme, optimize mining speed and the location of the stopping line. The three improvement measures mentioned above are simulated numerically, and the effects of the drilling and blasting plan, mining speed, and stopping line location on stress distribution are determined. The results show that by implementing the three improvement measures, the stress variation interval can be efficiently controlled and the working face's production safety can be increased. Finally, it is determined that the 1353 working face of Daizhuang Coalmine adopts the pressure relief method of drilling on one side and cutting the roof 20 m deep on the other side, and the mining speed of the working face is 3 m/day and the length of the stopping line is 85 m. Based on the on-site monitoring results, the implementation of comprehensive treatment measures can effectively improve the surrounding rock state of 1353 working face, which has certain guiding significance for the mining of irregular working face.

Cortical Sulcal Abnormalities Revealed by Sulcal Morphometry in Patients with Chronic and Episodic Migraine.

Purpose: Previous studies have reported mixed results regarding the importance of cortical abnormalities in patients with migraines. However, cortical sulci, as a component of the cerebral cortex, have not been specifically investigated in migraine patients. Therefore, we aim to evaluate alterations in cortical sulcal morphology among patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs). Patients and Methods: In this cross-sectional study, structural magnetic resonance images were acquired from 35 patients with CM, 35 with EM, and 35 HCs. Cortical sulci were identified and reconstructed using the BrainVisa 5.0.4 software. We focused on regions involved in pain processing in which abnormal cortical structure were identified in previous neuroimaging studies. Morphometric analysis was performed to calculate sulcal parameters including mean depth, cortical thickness, and opening width. Partial correlation analyses of clinical characteristics and sulcal parameters were performed for CM, EM and the combined migraine (CM + EM) groups. Results: In comparison with HCs, both CM and EM groups showed increased opening width in bilateral insula. In comparison with HC and EM groups, CM patients showed increased cortical thickness in bilateral superior postcentral sulcus, bilateral median frontal sulcus and left superior parietal sulcus, as well as increased mean depth in the left anterior callosomarginal fissure and decreased mean depth in bilateral superior frontal sulcus and left median frontal sulcus. Migraine frequency and disease duration were both correlated with cortical thickness in bilateral superior postcentral sulcus. Conclusion: Abnormal sulcal morphometry primarily affected areas associated with pain processing in patients with migraine, with CM exhibiting more extensive abnormalities in areas related to sensory and affective processing. These changes may contribute to understanding the pathology of EM and CM.

Effective stabilization of heavy metals in solid waste and sludge pyrolysis using intercalated-exfoliated modified vermiculite: Experiment and simulation study.

Pyrolysis is effective in reducing the volume of solid waste and sludge, and produces less pollutants than incineration and landfill, but the process still suffers from heavy metal pollution. Four types of intercalated-exfoliated modified vermiculite (UIV, DIV, TIV and 3IV) were prepared using urea, dimethylsulfoxide, tributyl phosphate and 3-aminopropyltriethoxysilane as intercalators for the control of Cd, Cr, Cu, Pb and Zn in municipal sewage sludge (MSL), paper mill sludge (PML), municipal domestic waste (MWA) and aged refuse (AFE). The larger the interlayer spacing of the vermiculite, the more favorable the retention of heavy metals. 3IV was the most effective additive, with an average retention of more than 75 % of all heavy metals at 450 ℃ for the four raw materials. Cr, Cu, Pb and Zn were all at low potential ecological risk (Pr), while Cd was moderate or considerable Pr, and the addition of 3IV reduced the Pr. Distribution of intercalators between vermiculite interlayers was haphazard, and interlayer spacing results were close to those of the experiment (except for tributyl phosphate). The reactive electrons mainly flowed from the Highest Occupied Molecular Orbital (HOMO) of vermiculite flakes to the Lower Unoccupied Molecular Orbital (LUMO) of heavy metal chlorides. In contrast, the reactive electrons mostly flowed from the HOMO of heavy metal oxides to the LUMO of vermiculite flakes. Heavy metal oxides were more readily adsorbed on vermiculite flakes than heavy metal chlorides, and the adsorption capacity of Cr and Zn was stronger than that of Cd, Pb and Cu.

Arsenic trioxide alleviates atherosclerosis by inhibiting CD36-induced endocytosis and TLR4/NF-κB-induced inflammation in macrophage and ApoE-/- mice.

BACKGROUND: Inflammation and lipid accumulation are key events in atherosclerosis progression. Despite arsenic trioxide's (ATO) toxicity, at appropriate doses, it is a useful treatment for various diseases treatment. ATO prevents vascular restenosis; however, its effects on atherosclerotic plaque development and instability remain unclear. METHODS: ApoE-/- mice were fed high-fat diet for 4 months, and starting at the third month, ATO was intravenously administered every other day. Atherosclerotic lesion size, histological characteristics, and related protein and lipid profiles were assessed using samples from the aorta, carotid artery, and serum. The anti-inflammatory and anti-pyroptosis effects of ATO were investigated by stimulating RAW264.7 and THP-1 cell lines with oxidized low-density lipoprotein (ox-LDL) or lipopolysaccharide (LPS). RESULTS: ATO reduced atherosclerotic lesion formation and plasma lipid levels in ApoE-/- mice. In the serum and aortic plaques, ATO reduced the levels of pro-inflammatory factors, including interleukin (IL) 6 and tumor necrosis factor α, but increased IL-10 levels. Mechanistically, ATO promoted the CD36-mediated internalization of ox-LDL in a peroxisome proliferator-activated receptor γ-dependent manner. Furthermore, ATO downregulated Toll-like receptor 4 (TLR4) expression in plaques and macrophages and inhibited p65 nuclear translocation and IκBα degradation. ATO reduced macrophage pyroptosis by downregulating NLR family pyrin domain-containing 3 (NLRP3) expression and caspase 1 activation. CONCLUSION: ATO has potential atheroprotective effects, especially in macrophages. The mechanisms were inhibition of CD36-mediated foam cell formation and suppression of inflammatory responses and pyroptosis mediated by TLR4/nuclear factor κB and NLRP3 activation. Our findings provide evidence supporting the potential atheroprotective value of ATO.

Pseudo-targeted metabolic profile differences between emergency patients with type 1 and type 2 myocardial infarction diagnosed by optical coherence tomography.

BACKGROUND: It is difficult to distinguish type 2 myocardial infarction (T2MI) from type 1 myocardial infarction (T1MI), although their management varies. OBJECTIVES: Using optical coherence tomography (OCT) and pseudo-targeted metabolomics to identify biomarkers, investigate metabolic differences, and establish a T2MI subclassification. METHODS: Among 1519 patients with MI, 97 T2MI patients are identified who are 1:1 matched with 97 T1MI patients after considering age, gender, ST-segment elevation, time from onset to coronary angiography, and hs-cTnI on admission by propensity score matching. Plasma pseudo-targeted metabolomics at baseline was determined. RESULTS: The clinical characteristics of the two groups were comparable, while the T1MI showed more severe coronary lesions than T2MI according to OCT imaging. 90 differential metabolites were identified between the two groups, among 1027 endogenous metabolites in 20 classes. N-Acetyl-L-Leucine, free fatty acid (15:1), Thymidine-5'-triphosphate, Mevalonic acid 5-pyrophosphate, and five oligopeptides were candidate biomarkers (AUC ≥ 0.85) distinguishing T2MI from T1MI. 12 KEGG pathways showed significant differences, mainly involving amino acid, nucleotide, and their derivatives metabolism, and signaling pathways such as mTOR, cGMP-PKG, and cAMP. Other differences were observed in TCA cycle (P = 0.08) and ROS (P = 0.05). Proteolysis and coronary heart disease risk lipid level were lower in T2MI. T2MI had a decrease of differential abundance score in almost all the KEGG enrichment pathways. Furthermore, T2MI can be subdivided into three subtypes by hierarchical cluster analysis of AUCs with causes/triggers of T2MI. CONCLUSIONS: There are significant metabolic profile differences between T1MI and T2MI. Several candidate metabolic biomarkers can effectively distinguish the two groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov NCT03297164.

A Digital Intervention to Promote Self-Management Self-Efficacy Among Community-Dwelling Individuals With Stroke: Pilot Randomized Controlled Trial.

BACKGROUND: Digital interventions provided through smartphones or the internet that are guided by a coach have been proposed as promising solutions to support the self-management of chronic conditions. However, digital intervention for poststroke self-management is limited; we developed the interactive Self-Management Augmented by Rehabilitation Technologies (iSMART) intervention to address this gap. OBJECTIVE: This study aimed to examine the feasibility and initial effects of the iSMART intervention to improve self-management self-efficacy in people with stroke. METHODS: A parallel, 2-arm, nonblinded, randomized controlled trial of 12-week duration was conducted. A total of 24 participants with mild-to-moderate chronic stroke were randomized to receive either the iSMART intervention or a manual of stroke rehabilitation (attention control). iSMART was a coach-guided, technology-supported self-management intervention designed to support people managing chronic conditions and maintaining active participation in daily life after stroke. Feasibility measures included retention and engagement rates in the iSMART group. For both the iSMART intervention and active control groups, we used the Feasibility of Intervention Measure, Acceptability of Intervention Measure, and Intervention Appropriateness Measure to assess the feasibility, acceptability, and appropriateness, respectively. Health measures included the Participation Strategies Self-Efficacy Scale and the Patient-Reported Outcomes Measurement Information System's Self-Efficacy for Managing Chronic Conditions. RESULTS: The retention rate was 82% (9/11), and the engagement (SMS text message response) rate was 78% for the iSMART group. Mean scores of the Feasibility of Intervention Measure, Acceptability of Intervention Measure, and Intervention Appropriateness Measure were 4.11 (SD 0.61), 4.44 (SD 0.73), and 4.36 (SD 0.70), respectively, which exceeded our benchmark (4 out of 5), suggesting high feasibility, acceptability, and appropriateness of iSMART. The iSMART group showed moderate-to-large effects in improving self-efficacy in managing emotions (r=0.494), symptoms (r=0.514), daily activities (r=0.593), and treatments and medications (r=0.870), but the control group showed negligible-to-small effects in decreasing self-efficacy in managing emotions (r=0.252), symptoms (r=0.262), daily activities (r=0.136), and treatments and medications (r=0.049). In addition, the iSMART group showed moderate-to-large effects of increasing the use of participation strategies for management in the home (r=0.554), work (r=0.633), community (r=0.673), and communication activities (r=0.476). In contrast, the control group showed small-to-large effects of decreasing the use of participation strategies for management in the home (r=0.567), work (r=0.342, community (r=0.215), and communication activities (r=0.379). CONCLUSIONS: Our findings support the idea that iSMART was feasible to improve poststroke self-management self-efficacy. Our results also support using a low-cost solution, such as SMS text messaging, to supplement traditional therapeutic patient education interventions. Further evaluation with a larger sample of participants is still needed. TRIAL REGISTRATION: ClinicalTrials.gov 202004137; https://clinicaltrials.gov/study/NCT04743037?id=202004137&rank=1.

A potential early-atheroprotective target: Irgm1 mediates lymphangiogenesis through LEC autophagy by Tfeb translocation.

Lymphatic dysfunction is a pivotal pathological mechanism underlying the development of early atherosclerotic plaques. Potential targets of lymphatic function must be identified to realize the early prevention and treatment of atherosclerosis (AS). The immunity-related GTPase Irgm1 is involved in orchestrating cellular autophagy and apoptosis. However, the effect of Irgm1 on early AS progression, particularly through alterations in lymphatic function, remains unclear. In this study, we confirmed the protective effect of lymphangiogenesis on early-AS in vivo. Subsequently, an in vivo model of early AS mice with Irgm1 knockdown shows that Irgm1 reduces early atherosclerotic plaque burden by promoting lymphangiogenesis. Given that lymphatic endothelial cell (LEC) autophagy significantly contributes to lymphangiogenesis, Irgm1 may enhance lymphatic circulation by promoting LEC autophagy. Moreover, Irgm1 orchestrates autophagy in LECs by inhibiting mTOR and facilitating nuclear translocation of Tfeb. Collectively, these processes lead to lymphangiogenesis. Thus, this study establishes a link between Irgm1 and early AS, thus revealing a novel mechanism by which Irgm1 exerts an early protective influence on AS within the context of lymphatic circulation. The insights gained from this study have the potential to revolutionize the approach and management of AS onset.

An analysis of clinical characteristics of rare bilateral medial medullary infarction: An observational study.

This study aimed to characterize the risk factors, etiology, clinical manifestations, anatomical characteristics, stroke mechanisms, imaging features, and prognosis of bilateral medial medullary infarction (BMMI). A retrospective analysis was conducted on 11 patients with BMMI who met the inclusion criteria at the Affiliated Hospital of Xuzhou Medical University from January 2013 to January 2023. The patients' imaging and clinical features were analyzed and summarized. Eleven patients (7 male, 4 female), aged 46 to 62 years, met the inclusion criteria. Common clinical presentations included dysarthria (90.9%), dysphagia (90.9%), quadriplegia (81.8%), and so on. Within 72 hours of onset, 8 cases presented with quadriplegia, 2 cases with hemiplegia, and 1 case without limb paralysis. The main risk factor for BMMI was hypertension, followed by diabetes. "Heart appearance" infarcts occurred in 4 cases (36.4%), while "Y appearance" infarcts occurred in 7 cases (63.6%). Among the patients, 3 had unilateral vertebral artery stenosis or occlusion, 5 had bilateral vertebral artery stenosis or occlusion, 2 had normal vertebral basilar artery, and 1 did not undergo cerebrovascular examination. All patients received standardized treatment for cerebral infarction. The prognosis was poor, with 81.8% of patients having an unfavorable outcome, including 1 death, 9 cases of disability, and only 1 patient achieving self-care ability after recovery. BMMI is more prevalent in males aged 45 to 60 years. The main risk factors are hypertension and diabetes. Atherosclerosis is the primary etiological subtype. The main clinical manifestations are dyskinesia, dizziness, quadriplegia, and dysarthria. The prognosis of BMMI is poor. The specific imaging features of "heart appearance" or "Y appearance" infarcts aid in the diagnosis of BMMI.