BACKGROUND:Atherosclerosis is driven by metabolic-immune crosstalk, in which trained immunity sustains vascular inflammation. MAP17 (membrane-associated protein 17), a redox- and metabolism-regulating adaptor protein, functions as a potential upstream driver of SGLT2 (sodium-glucose cotransporter 2). We aimed to determine whether MAP17 links hyperglycemia to glycolytic activation, inflammatory polarization, and plaque progression in atherosclerosis. METHODS:MAP17 expression and its correlations with clinical risk factors were analyzed in serum from 30 patients with atherosclerosis. A trained immunity model was established in bone marrow-derived macrophages via sustained high glucose and IFN-γ (interferon-γ)/lipopolysaccharide stimulation. Functional assays were performed after MAP17 overexpression/knockdown, SGLT2 silencing, or glycolysis inhibition. RESULTS:MAP17 was significantly coupregulated in patients with atherosclerosis, with the highest levels observed in those with concomitant diabetes or metabolic syndrome, and closely associated with elevated proinflammatory M1-like cytokines. Immunohistochemistry of carotid plaques confirmed its colocalization with SGLT2 within CD68+ macrophage-rich, lipid-laden, and inflamed regions. In bone marrow-derived macrophages, high glucose robustly induced MAP17 expression, which unidirectionally upregulated SGLT2, enhanced glycolytic flux, increased lactate production, and promoted M1-like polarization and foam cell formation. MAP17 knockdown markedly suppressed SGLT2 expression, glycolysis, and TNF-α (tumor necrosis factor-α)/IL (interleukin)-1β secretion, whereas MAP17 overexpression restored glycolytic activity, proinflammatory phenotype, and foam cell generation even in SGLT2-deficient cells. In diabetic chimeric Apoe-/- mice, MAP17 activation correlated with increased glycolytic marker expression, higher proinflammatory M1-like macrophage ratios, aggravated vascular inflammation, and greater plaque burden; these effects were mitigated by MAP17 or SGLT2 silencing, or by glycolysis inhibition. CONCLUSIONS:MAP17 is a key upstream controller of the SGLT2-glycolysis axis that promotes trained immunity and accelerates atherosclerosis. Targeting MAP17 may disrupt the metabolic-inflammatory feedback loop and represents a promising therapeutic strategy for diabetic atherosclerosis.

Disturbed blood flow induces early endothelial inflammation in atherosclerosis, yet the precise mechanisms of endothelial sensing of disturbed flow remain incompletely understood. In this study, we integrated proteomic profiling of human endothelial cells (ECs) subjected to disturbed flow with coronary artery disease risk related genes from large-scale genome-wide association studies (GWAS). We identified mortality factor 4-like protein 1 (MORF4L1, also called MRG15) as a critical modulator in the pathogenesis of atherosclerosis induced by disturbed flow. We show that the expression of MRG15 is markedly reduced in ECs of human aortic atherosclerotic plaques, as well as in ECs exposed to disturbed flow in mouse carotid artery and in cultured human umbilical vein endothelial cells (HUVECs). Endothelial-specific deletion of Mrg15 significantly worsened, while its overexpression attenuated endothelial inflammation and atherosclerotic lesions in turbulent blood flow- or Western diet-induced mouse atherosclerosis model. Single-cell transcriptomics showed that Mrg15 deficiency increased endothelial inflammation and intercellular adhesion molecule 1 (Icam1) expression, and enhanced integrin-mediated adhesion pathways. Mechanistically, MRG15 facilitated the recruitment of enhancer of zeste homolog 2 (EZH2) to maintain repressive histone H3 lysine 27 trimethylation (H3K27me3) marks on the promoters of ICAM1 and integrin subunit alpha 5 (ITGA5). Disturbed blood flow rapidly led to an elevation of protein neddylation, which subsequently induced neddylation-dependent degradation of MRG15 within endothelial cells. This degradation of MRG15 alleviated the transcriptional repression of ICAM1 and ITGA5, thereby enhancing monocyte adhesion to ECs. These findings highlight endothelial MRG15 as a mechanosensitive suppressor of atherosclerosis induced by disturbed flow. Consequently, MRG15 emerges as a promising novel therapeutic target for atherosclerosis. ### Competing Interest Statement The authors have declared no competing interest.

BackgroundBone cement leakage is a complication of percutaneous vertebroplasty. However, the cement can extremely rarely extravasate into the heart and pulmonary arteries and form cord-like foreign bodies, inducing acute massive pulmonary thromboembolism.Case presentationWe present a case of a patient who developed acute massive pulmonary thromboembolism within 2 weeks after PVP, resulting from bone cement leakage into the heart and pulmonary arteries with subsequent thrombosis. Lower extremity vascular ultrasonography ruled out the possibility of thrombus detachment secondary to deep venous thrombosis. Computed tomography pulmonary angiography revealed strip-shaped hypodense filling defects in the main trunks and some branch arteries of the bilateral pulmonary arteries and a cord-like hyperdense shadow. Combined computed tomography pulmonary angiography and three-dimensional reconstruction of the thoracic spine showed that the cord-like foreign body originated from the 8th thoracic vertebra, entered the azygos vein through the vertebral venous system, then continuously traversed the superior vena cava and right cardiac system, and finally extended to the main trunk of the right pulmonary artery, as well as the branches of both pulmonary arteries. Following aggressive surgical thrombolysis and postoperative anticoagulant therapy, the patient’s symptoms immediately improved. Nevertheless, computed tomography pulmonary angiography still showed the cord-like foreign body after 3 months.ConclusionMoreover, this report retrospectively analyzes the diagnostic and therapeutic strategies for pulmonary thromboembolism secondary to bone cement leakage after percutaneous vertebroplasty through a literature review.

PURPOSE:To evaluate the clinical efficacy of the PVCA (The degree of cervical vascular injury is defined mainly based on 4 dimensions: Penetration site, injured Vessel, Clinical manifestations, and Associated injuries.) classification in guiding management of cervical vascular trauma. METHODS:The PVCA classification system was further developed based on various clinical classifications of carotid artery trauma, incorporating prior clinical experience in managing massive cervical hemorrhage. We retrospectively analyzed 43 patients with cervical vascular trauma treated at 4 tertiary centers between January 2022 and December 2024. Patients with confirmed cervical vascular trauma were included, while patients with incomplete clinical data, loss to follow-up, or concurrent life-threatening injuries that precluded definitive vascular management were excluded. PVCA classification was applied to guide management. Outcomes, including choice of surgical approach, hemostasis success, vascular repair integrity, neurological recovery, and complications, were assessed. Descriptive statistics were used to summarize baseline characteristics and outcome measures. Continuous variables were presented as mean ± standard deviation, and categorical variables as frequencies and percentages. Group comparisons were performed using the χ2 test or Fisher's exact test, based on expected frequencies. RESULTS:A total of 43 patients (mean age (42.58 ± 10.77) years; 62.8% male) were classified by PVCA (P1: 14.0%, P2: 69.8%, P3: 16.3%; V1: 62.8%, V2: 23.3%, V3: 7.0%, V4: 7.0%; C0: 20.9%, C1: 69.8%, C2: 9.3%; A0: 95.3%, A1: 4.7%). All patients underwent successful intervention (open surgery: 53.5%, endovascular: 32.6%, hybrid: 14.0%), with 100% hemostasis and improved cerebral perfusion. PVCA dimensions demonstrated differential guiding value for surgical approach. Penetration site (P) was the strongest determinant (p < 0.001): 76.7% of P2 patients received open surgery, while 66.7% of P1 and 85.7% of P3 underwent endovascular repair, with hybrid procedures reserved for cases complicated by hematoma or retained foreign bodies. Injured vessel type (V) also significantly influenced strategy (p = 0.026): all V3 lesions were managed by open ligation, and 66.7% of V4 injuries required hybrid surgery. Clinical manifestations (C) and associated injuries (A) had no independent effect on surgical choice (p = 0.390 and p = 0.386). Perioperative complications occurred in 4 patients: 3 cranial nerve injuries (all in the P2 zone, 10.0% vs. 0% in other zones; p = 0.046) and 1 hyperperfusion syndrome. Nerve injuries were confined to the P2 subtype, with a significantly higher rate in A1 patients (100.0%, 2/2) than in A0 patients (2.4%, 1/41) (p = 0.048). Hyperperfusion syndrome occurred exclusively in the C2 subtype (25.0%, 1/4 vs. 0/39 in C0/C1). Overall complication rates were significantly elevated in A1 (100.0%) and C2 (25.0%) subtypes (p = 0.048 and p = 0.042, respectively). At a mean follow-up of (15.53 ± 3.90) months, asymptomatic >50% in-stent restenosis was detected in 2 patients (4.7%); no other stent or vessel complications were observed. CONCLUSION:The PVCA classification system effectively guides surgical decision-making in cervical vascular trauma, with penetration site (P) as the strongest determinant of surgical approach and injured vessel type (V) further refining strategy. By also identifying high-risk subtypes for complications-P2 for cranial nerve injury, and A1/C2 for overall adverse events-the system enables tailored intervention and targeted complication prevention, ultimately optimizing individualized management and improving clinical outcomes.

BACKGROUND:Endothelial dysfunction is critical for the pathogenesis of atherosclerosis, particularly in arterial regions exposed to disturbed flow (DF). ADCY4 (adenylate cyclase 4) catalyzes the production of cAMP (cyclic adenosine monophosphate), a ubiquitous second messenger that regulates cellular and physiological processes. This study investigated ADCY4 as a shear-stress-responsive gene in endothelial cells (ECs) for the regulation of vascular endothelial inflammation during atherogenesis. METHODS:Integrated analysis of RNA sequencing data sets from human vascular ECs exposed to unidirectional flow or DF, and single-cell RNA-seq data from mouse partial ligation carotid arteries, was performed. ADCY4 expression was quantified in cultured ECs under various flow conditions. Nanoparticles carrying Cdh5 promoter-driven CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) and Adcy4-specific guide RNA plasmids were used to achieve EC-specific Adcy4 knockout in ApoE-/- mice for atherogenesis studies. RESULTS:ADCY4 was upregulated in ECs under unidirectional flow but downregulated under DF. We identified that KLF2 (Krüppel-like factor 2) directly bound to the ADCY4 promoter and transcriptionally enhanced its expression in human aortic ECs. ADCY4 knockdown in ECs under unidirectional flow increased proinflammatory gene expression and monocyte adhesion, whereas ADCY4 overexpression under DF produced opposite changes. Further studies showed ADCY4 attenuated endothelial inflammation by inhibiting NF-κB (nuclear factor κB) signaling. We performed partial carotid ligation in the high-fat diet-fed ApoE-/- mouse atherosclerosis model, demonstrating that EC-specific Adcy4 knockout increased vascular endothelial inflammation and monocyte infiltration, thus promoting atherosclerotic plaque formation. Aggravated atherogenesis was also observed in EC-Adcy4 knockout high-fat diet-fed ApoE-/- mice, with increased atherosclerotic lesions in en face aortas and aortic arches. Finally, semaglutide increased ADCY4 expression in human aortic ECs under DF and reduced vascular endothelial inflammation, monocyte accumulation, and atherosclerotic plaque formation. These beneficial effects were substantially impaired when EC ADCY4 was absent. CONCLUSIONS:ADCY4 regulation of the cAMP/PKA (protein kinase A)-NF-κB pathway in the endothelium advances our understanding of vascular inflammation in atherogenesis and provides opportunities for therapeutic intervention of atherosclerotic cardiovascular disease.

BACKGROUND:Vascular remodeling is a central characteristic of pulmonary hypertension (PH), yet the precise mechanisms underlying this process remain poorly understood. METHODS:The coimmunoprecipitation assay was used to explore prolyl hydroxylase that modifies BACH1 (BTB and CNC homology 1). Cultured pulmonary artery smooth muscle cells, rodent models with PH, specimens from patients with idiopathic pulmonary arterial hypertension, and single-nucleus RNA sequencing were used to study the role of BACH1 in the regulation of PH and the underlying mechanisms. RESULTS:In this study, we found that the transcription factor BACH1 was upregulated in lung tissues and pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension and animals with experimental PH. Under normoxia, the prolyl hydroxylation of BACH1, mediated by PHD (prolyl hydroxylase) 2, facilitated BACH1 degradation by VHL (von Hippel-Lindau) protein. Hypoxic exposure decreased this prolyl hydroxylation with subsequent increased BACH1 protein stability. The deficiency or overexpression of BACH1 in smooth muscle cells in mice alleviated or exacerbated pulmonary vascular remodeling and hypoxia-induced PH. Hypoxia triggered the accumulation of BACH1 and its recruitment to the promoter region of TGFBR2 (transforming growth factor β receptor type II) in smooth muscle cells. This recruitment activated TGFBR2 transcription, thereby promoting vascular remodeling by upregulating SMAD (suppressor of mothers against decapentaplegic) signaling and extracellular matrix deposition. Decreased TGFBR2 expression or inhibited kinase activity significantly attenuated the BACH1-induced extracellular matrix genes. Furthermore, the BACH1-enhanced PH development was blunted by a TGFBR2 kinase inhibitor. CONCLUSIONS:Our study illustrates that BACH1 is prolyl-hydroxylated in an oxygen/PHD-dependent manner, affecting its stability through VHL. BACH1 is crucial for hypoxia-induced PH by activating TGFBR2/SMAD in smooth muscle cells. Thus, BACH1 inhibition may be a potential therapeutic strategy for PH.

Aims Plaque regions in atherosclerosis (AS) exhibit sustained moderate hypoxia, which may impair endothelial function and influence vascular smooth muscle cell (VSMC) behavior. This study aims to investigate hypoxia-responsive endothelial-derived long noncoding RNAs (lncRNAs), and their role in enhancing oxidized low-density lipoprotein(ox-LDL)-induced phenotypic switching of VSMCs. Materials and methods Differentially expressed lncRNAs in endothelial cells (ECs) under hypoxia were selected for analysis and validated by qRT-PCR. Luciferase and ChIP-PCR assays were performed to assess HIF-2α-mediated transcriptional regulation of MSTRG.12883.2. Bioinformatic analysis, luciferase and RIP assays were conducted to examine the interaction between MSTRG.12883.2 and the miR-632/KLF4 axis. Exosomes were isolated and characterized, and exosome-dependent transfer of MSTRG.12883.2 from ECs to VSMCs was demonstrated. Phenotypic switching of VSMCs was evaluated using functional assays (CCK-8 and migration assays) and molecular analyses (ELISA and Western blotting). Key findings MSTRG.12883.2 was identified as a hypoxia-induced, endothelial-enriched lncRNA transcriptionally regulated by HIF-2α. Preferentially enriched in exosomes, it is transferred from ECs to VSMCs. Mechanistically, MSTRG.12883.2 acts as a competing endogenous RNA that sponges miR-632, thereby relieving KLF4 repression and facilitating the ox-LDL-induced transition of VSMCs from a contractile to a synthetic phenotype. Significance We reveal that the unique plaque microenvironment triggers the expression of endothelial-derived MSTRG.12883.2, leading to its exosomal transfer to VSMCs. This hypoxia-responsive axis serves as a key driver of plaque destabilization and vascular remodeling. Together, these findings highlight a critical layer of endothelial-VSMC communication in AS and position MSTRG.12883.2 as a potent diagnostic and therapeutic target.

Hemorrhage control remains a critical challenge in clinical and emergency medicine. In this work, we developed a multifunctional hemostatic sponge (GPZ sponge) composed of a gelatin-polyvinyl alcohol matrix reinforced with zein nanoparticles (ZNPs). The incorporation of ZNPs endowed the sponge with stable fixation on moist tissue surfaces while allowing ethanol-triggered facile removal. Upon hydration, the sponge transformed into a dense hydrogel capable of withstanding burst pressures exceeding 140 mmHg and achieving rapid, thrombin-independent hemostasis through enhanced platelet aggregation. Moreover, the intrinsic antioxidant activity of ZNPs conferred efficient reactive oxygen species scavenging. In rat liver bleeding models, the GPZ sponge resulted in minimal blood loss (similar to 0.11 g), which was dramatically lower than that observed with the commercial gelatin sponge (similar to 1.19 g), highlighting its outstanding hemostatic efficacy. Furthermore, it achieved effective hemostasis in rat cardiac puncture, rabbit femoral artery, and heparinized porcine carotid artery injury models, demonstrating robust performance under severe and high-pressure bleeding conditions. In full-thickness skin wounds treated with GPZ sponge, the closure ratio reached 97.2% at day 14, significantly higher than 80.9% in the commercial gelatin sponge group. Collectively, these findings demonstrate that the GPZ sponge is an easily fabricated and highly efficient hemostatic material with strong translational potential for next-generation clinical and emergency wound care.

CHI3L1 is strongly associated with atherosclerosis, but its role in macrophages remains unknown. In this study, we observed a significant up-regulation of CHI3L1 in both carotid plaques and serum of symptomatic patients, and demonstrated that CHI3L1 impairs the efferocytosis of macrophages by down-regulating crucial efferocytic mediator MFGE8 through inhibiting ATF2, which binds directly to the enhancer of MFGE8. In human plaques, we observed a negative correlation between CHI3L1 expression and both ATF2 and MFGE8 levels, further proved their involvement in plaque destabilization. Using Ldlr–/– mice with tandem carotid stenosis surgery, we demonstrated that administration of CHI3L1 protein resulted in enlarged atherosclerotic necrotic cores and decreased MFGE8 and ATF2 levels. Conversely, treatment with a CHI3L1 blocking antibody exhibited the opposite trend. In conclusion, CHI3L1 destabilizes atherosclerotic plaque by impairing macrophagic efferocytosis through the down-regulation of ATF2-induced MFGE8 expression. Targeting CHI3L1 may offer a promising therapeutic strategy for the treatment of atherosclerosis.

Nicotinamide mononucleotide (NMN), a precursory metabolite of NAD, has been demonstrated to boost cellular NAD level that is coupled with various age-related beneficial effects in animal models. NAD-capped RNA (NAD-RNA) represents a critical but poorly studied modification at the epitranscriptomic level. Here we examine the impact of NMN supplementation on NAD-RNA in human peripheral blood mononuclear cells (PBMCs). We demonstrated that NMN supplementation increases NAD turnover coupled with a reduction in NAD-capped RNAs in both human and dog, revealing blood-derived NAD-RNAs as potential biomarkers sensitized to NMN exposure.

Background:Treatment for varicose veins has transitioned from invasive surgical interventions to minimally invasive, targeted, and personalized procedures. Limited data exist on the longterm outcomes of glue ablation (GA) as a new minimally invasive treatment. This study was conducted to evaluate the long-term safety and efficacy of GA for varicose veins. Methods:Data were collected in a multicenter, prospective registry. Patients were randomly allocated to the experimental group (GA) or the control group (radiofrequency ablation [RFA]). The follow-up assessments were conducted at 7 days, 30 days, 3 months, 6 months, and 12 months after surgery. The non-inferiority of GA to RFA was assessed based on the primary outcome of the rate of complete great saphenous vein (GSV) closure at 3 months. Additional outcomes included the rate of complete GSV closure at 12 months, procedural duration, pain score, ecchymosis, and preoperative and postoperative Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire Score. Results:Overall, 177 patients were treated (experimental group, n = 89; control group, n = 88). The mean age was 56.25 ± 12.23 years, and 61.58% were female. The mean target vessel diameter was 7.94 ± 2.09 mm, with a maximum diameter of 12 mm. The GA group did not experience any device-related adverse complications. Tumescent fluid was utilized in the RFA group but not in the GA group. GA was statistically non-inferior to RFA (lower boundary of the 95% confidence interval [CI] for the absolute difference in the mean rate of 3-month complete GSV closure did not reach the non-inferiority margin of -10%) (absolute difference -0.03%; one-sided 95% CI -3.19%; P < 0.001). The GSV closure rate at 12 months was higher in the GA group than in the RFA group (absolute difference 7.04%; one-sided 95% CI 1.09%). The GA group exhibited a significantly longer surgical duration than the RFA group (P = 0.031). The comparisons of other secondary endpoints between the groups did not yield any significant findings. Conclusion:The 3-month rate of complete GSV closure with GA was non-inferior to that with RFA in the treatment of varicosity, but the surgical duration was longer. The efficacy of GA therapy still requires validation through large-scale clinical trials with long-term follow-up periods.

Estimation of chronological age is particularly informative in forensic contexts. Assessment of DNA methylation status allows for the prediction of age, though the accuracy may vary across models. In this study, we started with a carefully designed discovery cohort with more elderly subjects than other age categories, to diminish the effect of epigenetic drifting. We applied multiplexing and massive parallel sequencing of targeted DNA methylation, which let us to construct a model comprising 25 CpG sites with substantially improved accuracy (MAE = 2.279, R = 0.920). This model is further validated by an independent cohort (MAE = 2.204, 82.7% success (±5 years)). Remarkably, in a multi-center test using trace blood samples from forensic caseworks, the correct predictions (±5 years) are 91.7%. The nature of our analytical pipeline can easily be scaled up with low cost. Taken together, we propose a new age-prediction model featuring accuracy, sensitivity, high-throughput, and low cost. This model can be readily applied in both classic and newly emergent forensic contexts that require age estimation.

Objective: This study explores the role of methoxy polyethylene glycol@Elabela-11 (mPEG@ELA-11), a pH-responsive ELA-11 conjugate, in modulating macrophage function and attenuating atherosclerosis, focusing on the protein kinase B (AKT)-mediated endoplasmic reticulum (ER) stress pathway as a molecular target. Impact Statement: We reveal that ELA-11 alleviates atherosclerosis by suppressing macrophage foam cell formation, M1 polarization, and apoptosis via the AKT-ER stress pathway. We also develop mPEG@ELA-11, a novel pH-responsive nanocarrier, to enhance targeted drug delivery and therapeutic efficacy, offering a breakthrough for peptide-based cardiovascular nanomedicine. Introduction: Atherosclerosis, driven by macrophage dysfunction and lipid accumulation, is a major global killer. ELA-11, a fragment of Elabela peptide, shows cardiovascular protective effects, but its role in atherosclerosis and optimal delivery remain unstudied. Methods: Elabela mRNA (APELA) expression was analyzed in human carotid atherosclerotic plaques using real-time quantitative PCR analysis, and serum ELA levels were quantified via enzyme-linked immunosorbent assay in patients with carotid stenosis. In vitro studies on RAW264.7 macrophages evaluated mPEG@ELA-11 effects on oxidized low-density lipoprotein-induced foam cell formation, polarization, and apoptosis. In vivo efficacy was tested in ApoE-/- mice, comparing mPEG@ELA-11 with free ELA-11, and its pH-responsive release mechanism was characterized. Results: APELA was down-regulated in human atherosclerotic plaques, especially unstable lesions. mPEG@ELA-11 suppressed foam cell formation, M1 polarization, and apoptosis by inhibiting the AKT-ER stress pathway in vitro. In mice, it reduced plaque area more effectively than free ELA-11 attributed to pH-triggered release. Conclusion: The pH-responsive mPEG@ELA-11 alleviates atherosclerosis by modulating macrophages via the AKT-ER stress pathway, with favorable targeting and safety, representing a promising targeted peptide nanomedicine for atherosclerosis.

Inspired by the critical role of platelets in hemostasis, hemostatic agents aim to enable rapid blood clotting, essential for saving lives in severe hemorrhages. Traditional hemostatic methods often rely on the slow binding of limited cellular components and proteins rendering them inadequate for critical scenarios. In this study, macroscopic supramolecular hemostatic materials capable of moisture-triggered release of nanosized glycan-based platelet substitutes (PS) are developed to facilitate expedited hemostasis. The inherent supramolecular chemistry of these glycan-based PS modified with catechol and alkyl enables instant amalgamation with red blood cells and albumin, forming a durable blood gel that exhibits self-healing and anti-adhesion properties, effectively minimizing rebleeding and postoperative complications. Meanwhile, the PS Pad instantly adheres to various organs and resists arterial blood pressure by constructing a microstructure-adapting PS layer on the tissue surface. In rodent and porcine trauma models of liver and femoral arteries with coagulation disorders, the PS-releasing hemostat stops bleeding within 45 s and is easily detached without rebleeding after use. The integration of fast-acting supramolecular interactions, biocompatibility, and self-healing characteristics positions these materials as promising candidates for rapid hemostatic solutions and potential translational applications in managing severe traumatic bleeding.

Nucleotide-containing metabolites, e.g., NAD, can serve as noncanonical initiating nucleotides (NCIN) during transcription, yielding NCIN-capped RNAs (NCIN-RNAs). Current profiling strategies are limited to detecting specific metabolite caps and lack an epitranscriptome-wide approach for quantifying the ratio between NCIN- and m7G-capped forms. Here, we develop the CompasSeq analytical platform, which integrates experimental and computational frameworks, enabling comprehensive and quantitative assessment of NCIN-RNAs at the transcript resolution. CompasSeq utilizes carefully devised enzymatic reactions to selectively capture NCIN-RNAs. By introducing proper spike-ins, CompasSeq can analyze the stoichiometry of NCIN caps. We further design an orthogonal method, the quantitative exoribonuclease reduction assay, to validate newly identified NCIN-RNAs and their capping ratios. Using CompasSeq, we quantify previously unexplored NCIN capping percentages from mouse liver and illustrate their age-associated dynamics. Moreover, we uncover a dichotomy between RNA expression and NCIN capping in genes impinging on age-related pathways. Our study presents both experimental and computational solutions for in-depth analysis of NCIN-RNAs, paving the road for functional investigations into NCIN-RNAs.

Carotid artery plaques pose a significant threat to human life and health, with the hemodynamics playing a crucial role in their formation and progression. In this study, we reconstructed geometric models of pre-pathological carotid arteries from the computed tomography angiography images. Using computational methods of fluid–structure interaction, key hemodynamic parameters that influence the plaques formation are investigated in the carotid arteries, such as time-averaged wall shear stress and oscillatory shear index (OSI). Additionally, a correlation between the shape index of endothelial cells and the hemodynamic parameters is established. Then, combining the pathology of atherosclerosis, a set of mathematical models is constructed to describe the transendothelial transport and evolution of key substances involved in plaque formation within the carotid arterial wall, thereby predicting high-risk areas for plaque formation. The results indicate a higher risk area around the carotid bifurcation, consistent with recirculation zones of blood flow and characterized by low WSS and high OSI. The risk areas predicted by our mathematical models are well validated by clinical images, suggesting the accuracy of models established in the study. This method predicts high-risk areas of plaque formation and provides valuable guidance for the clinical diagnosis and treatment.

OBJECTIVES:This study aimed to assess the midterm outcomes of a novel embedded modular single-branched stent-graft (EMSBSG) designed to preserve the left subclavian artery (LSA) of type B aortic dissection (TBAD). METHODS:From December 2020 to November 2021, a total of 120 patients with TBAD treated with an EMSBSG were enrolled in a multicenter prospective clinical trial at 18 Chinese tertiary hospitals. Follow-up computed tomography angiography scanning was conducted at 1, 6, and 12 months postprocedure. RESULTS:The technical success rate was 99.17% (n = 119/120), with only 1 technical failure attributed to aortic intimo-intimal intussusception. The 30-day mortality rate was 0.83% (n = 1). Thirty-day major complications included 2 cases (1.67%) of retrograde type A aortic dissection (RTAD), 3 cases (2.50%) of stroke, and 6 cases (5.22%) of Type Ia endoleaks. The median follow-up time was 12.84 (range, 11-16) months. The 1-year mortality rate was 4.17% (n = 5/120), and the follow-up patency rate of the branch section was 99.09% (n = 109/110). The overall 12-month reintervention rate was 4.17% (n = 5), including 3 RTAD cases, 2 Type I endoleaks, and 1 stent-induced new entry. CONCLUSION:For patients with TBAD involving the LSA, the midterm outcomes are encouraging for EMSBSG as a relatively safe, effective, and noncustomized endovascular option. However, long-term outcomes warrant attention and further investigation.Clinical ImpactThe midterm outcomes indicate that EMSBSG offers a safe, and effective endovascular option for preserving the LSA in patients with TBAD. The EMSBSG achieves LSA preservation through a non-customized endovascular solution, making it particularly suitable for emergency procedures. The core innovation of EMSBSG lies in its flexible, modular Embedded design, which adapts to the anatomical characteristics of TBAD in patients.

In this study, the growth and rupture of plaque were investigated to predict the development of carotid atherosclerosis and plaque. Realistic 3D models of multi-component plaque and carotid artery were established in healthy, mild, moderate, and severe stenosis. Fluid–structure interaction (FSI) simulations were performed on these models, and the wall shear stress (WSS), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and wall tensile stress (WTS) in a natural cardiac cycle were analyzed to assess the epidermal rupture, growth tendency, and internal rupture of plaques in a natural state. Results show that in severe stenosis, the WSS at the stenosis sites exceeds the threshold of rupture during almost the entire cardiac cycle, thus causing an epidermal injury, bringing about plaque detachment and thrombosis. TAWSS decreased and OSI and RRT increased in the bifurcation region and the downstream region of the plaque. The deposition is more likely to occur in these regions. A higher degree of stenosis will increase the OSI and RRT in the downstream region of the plaque, leading to continuous deterioration of the plaque, while the degree of stenosis has little effect on the upstream region of the plaque. The fibrous cap is the starting point for rupture within the plaque, and calcification increases the stress on the fibrous cap, thereby increasing the risk of rupture.