Association between lipoprotein(a), fibrinogen and their combination with all-cause, cardiovascular disease and cancer-related mortality: findings from the NHANES.

BACKGROUND: There is evidence indicating that both lipoprotein(a) [Lp(a)] and fibrinogen (FIB) are associated with mortality, However, the impact of their combination on mortality has not been determined. Thus, the aim of this study was to examine the association between the combination of Lp(a) and FIB with all-cause and cause-specific mortality. METHODS: This prospective cohort study enrolled 4,730 participants from the third National Health and Nutrition Examination Survey. The exposure variables included Lp(a), FIB and their combination, while the outcome variables consisted of all-cause, cardiovascular disease (CVD) and cancer-related mortality. Multivariate COX regression, subgroup analysis, sensitivity analysis and restricted cubic spline (RCS) were used to investigate the association between Lp(a), FIB and their combination with all-cause, CVD and cancer-related mortality. RESULTS: Over a median follow-up period of 235 months, 2,668 individuals died, including 1,051 deaths attributed to CVD and 549 deaths due to cancer. Multivariate Cox regression analyses revealed independent associations between both Lp(a) and FIB with all-cause, CVD, and cancer-related mortality. Compared to participants in the 1st to 50th percentiles of both Lp(a) and FIB, those in the 90th to 100th percentiles exhibited multivariable adjusted HRs of 1.813 (95% CI: 1.419-2.317, P < 0.001), 2.147 (95% CI: 1.483-3.109, P < 0.001) and 2.355 (95% CI: 1.396, 3.973, P = 0.001) for all-cause, CVD and cancer-related mortality, respectively. Subgroup and sensitivity analyses did not substantially attenuate the association between the combination of high Lp(a) and high FIB with the risk of all-cause and CVD-related mortality. Additionally, the RCS analysis showed that the relationship between Lp(a) and the risk of all-cause and cancer-related mortality, as well as the relationship between FIB and the risk of cancer-related mortality, were linear (P for nonlinearity > 0.05). Conversely, the relationship between Lp(a) and the risk of CVD-related mortality, as well as the relationship between FIB and the risk of all-cause and CVD-related mortality, were nonlinear (P for nonlinearity < 0.05). CONCLUSIONS: High levels of Lp(a) and FIB together conferred a greater risk of mortality from all-cause, CVD and cancer.

Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.

Background: This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements. Methods: A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized. Results: In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (ß = 0.433, P < 0.001) and a longer disease duration (ß = 0.438, P < 0.001). Conclusions: WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.

There was a similar U-shaped nonlinear association between waist-to-height ratio and the risk of new-onset hypertension: findings from the CHNS.

Background: The association between waist-to-height ratio (WHtR) with hypertension has not been adequately explained, so in this study we sought to clarify the predictive role of WHtR on the incidence of hypertension as well as the potential nonlinear associations in the general population. Methods: In this large prospective cohort study, a total of 4,458 individuals from the China Health and Nutrition Survey (CHNS) were included in the analysis. Multivariate Cox regression analyses, subgroup analyses, receiver operator characteristic (ROC) and restricted cubic spline (RCS) analyses were used to examine the association of WHtR with the risk of new-onset hypertension. Results: Hypertension occurred in 32.8% of participants during the maximum six-year follow-up period. Compared with the group with lower WHtR, the group with higher WHtR had a higher incidence of hypertension (p < 0.001). Multivariate Cox regression analysis showed that the risk of hypertension was 1.45 times higher in the high WHtR group than in the low WHtR group, and that the risk of hypertension increased by 30.4% for every 0.1 unit increase in WHtR (p < 0.001). Subgroup analyses also validated the stratified associations between WHtR and the risk of new-onset hypertension in most subgroups (p < 0.05). ROC analyses also revealed that WHtR was superior to body mass index in predicting new-onset hypertension (AUC: 0.626 vs. 0.607, p = 0.009). Further RCS analysis detected a nonlinear association between WHtR and risk of new-onset hypertension (P for nonlinearity <0.001). Conclusion: WHtR was nonlinearly associated with the risk of new-onset hypertension in the general population.

Association of lipoprotein(a) with left ventricular hypertrophy assessed by electrocardiogram in adults: a large cross-sectional study.

Background and aims: Increasing evidence supports a causal relationship between lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular disease, yet its association with left ventricular hypertrophy (LVH) assessed by electrocardiogram (ECG) remains unknown. The aim of this study was to explore the relationship between Lp(a) and LVH assessed by ECG in general population. Methods and results: In this cross-sectional study, we screened 4,052 adults from the participants of the third National Health and Nutrition Examination Survey for analysis. Lp(a) was regarded as an exposure variable. LVH defined by the left ventricular mass index estimated from ECG was considered as an outcome variable. Multivariate logistic regression and restricted cubic spline (RCS) were used to assess the relationship between Lp(a) and LVH. Individuals with LVH had higher Lp(a) compared to individuals without LVH (P< 0.001). In the fully adjusted model, Lp(a) was strongly associated with LVH when as a continuous variable (per 1-unit increment, OR: 1.366, 95% CI: 1.043-1.789, P = 0.024), and higher Lp(a) remained independently associated with a higher risk of LVH when participants were divided into four groups according to quartiles of Lp(a) (Q4 vs Q1, OR: 1.508, 95% CI: 1.185-1.918, P = 0.001). And in subgroup analysis, this association remained significant among participants< 60 years, ≥ 60 years, male, with body mass index< 30 kg/m2, with hypertension and without diabetes (P< 0.05). In addition, we did not observe a nonlinear and threshold effect of Lp(a) with LVH in the RCS analysis (P for nonlinearity = 0.113). Conclusion: Lp(a) was closely associated with LVH assessed by ECG in general population.

Exploring a new mechanism between lactate and VSMC calcification: PARP1/POLG/UCP2 signaling pathway and imbalance of mitochondrial homeostasis.

Lactate leads to the imbalance of mitochondria homeostasis, which then promotes vascular calcification. PARP1 can upregulate osteogenic genes and accelerate vascular calcification. However, the relationship among lactate, PARP1, and mitochondrial homeostasis is unclear. The present study aimed to explore the new molecular mechanism of lactate to promote VSMC calcification by evaluating PARP1 as a breakthrough molecule. A coculture model of VECs and VSMCs was established, and the model revealed that the glycolysis ability and lactate production of VECs were significantly enhanced after incubation in DOM. Osteogenic marker expression, calcium deposition, and apoptosis in VSMCs were decreased after lactate dehydrogenase A knockdown in VECs. Mechanistically, exogenous lactate increased the overall level of PARP and PARylation in VSMCs. PARP1 knockdown inhibited Drp1-mediated mitochondrial fission and partially restored PINK1/Parkin-mediated mitophagy, thereby reducing mitochondrial oxidative stress. Moreover, lactate induced the translocation of PARP1 from the nucleus to the mitochondria, which then combined with POLG and inhibited POLG-mediated mitochondrial DNA synthesis. This process led to the downregulation of mitochondria-encoded genes, disturbance of mitochondrial respiration, and inhibition of oxidative phosphorylation. The knockdown of PARP1 could partially reverse the damage of mitochondrial gene expression and function caused by lactate. Furthermore, UCP2 was upregulated by the PARP1/POLG signal, and UCP2 knockdown inhibited Drp1-mediated mitochondrial fission and partially recovered PINK1/Parkin-mediated mitophagy. Finally, UCP2 knockdown in VSMCs alleviated DOM-caused VSMC calcification in the coculture model. The study results thus suggest that upregulated PARP1 is involved in the mechanism through which lactate accelerates VSMC calcification partly via POLG/UCP2-caused unbalanced mitochondrial homeostasis.

LINC00346 regulates NLRP1-mediated pyroptosis and autophagy via binding to microRNA-637 in vascular endothelium injury.

Endothelial injury and dysfunction contributes to atherosclerosis. LINC00346 plays a key role in vascular endothelial cell injury, however, the specific mechanism remains unclear. This study intends to further explore the relationship between LINC00346 and vascular endothelial injury. Circulating LINC00346 was significantly elevated in patients with coronary artery disease and had high diagnostic value for coronary artery disease. In cell experiments, we found that LINC00346 expression was significantly increased in the oxidized low-density lipoprotein (ox-LDL) intervention group, and LINC00346 knockdown delayed ox-LDL induced human umbilical vein endothelial cell (HUVEC) endothelial-to-mesenchymal transition. In addition, knockdown of LINC00346 mitigated ox-LDL-induced NOD-like receptor protein 1 (NLRP1)-mediated inflammasome formation and pyroptosis, but had no significant effect on NLRP3. By observing the number of autophagosome and detecting intracellular autophagic flux, we found that LINC00346 knockdown inhibited the ox-LDL-induced increase in intracellular autophagy level. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay were performed to confirm the inter-molecular interaction. LINC00346 acted as microRNA-637 sponge to up-regulate the expression of NLRP1. Up-regulation of microRNA-637 alleviated NLRP1-mediated pyroptosis in HUVEC and reduced intracellular autophagosome and autolysosome formation. Finally, we explored whether pyropotosis and autophagy interact with each other. We found that inhibition of intracellular autophagy could alleviate NLRP1-mediated pyroptosis. In conclusion, LINC00346 inhibited the activation of NLRP1-mediated pyroptosis and autophagy via binding to microRNA-637, therefore mitigating vascular endothelial injury.

A 3D culture system improves the yield of MSCs-derived extracellular vesicles and enhances their therapeutic efficacy for heart repair.

BACKGROUND: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs), due to their inner functional substances, have shown great value in treating acute myocardial infarction (AMI). However, their clinical application is limited by a low yield. In the present study, we cultured EVs using a hollow fiber bioreactor-based three-dimensional (3D) system, and assessed their therapeutic effectiveness on AMI. METHODS: The MSCs separated from fresh human umbilical cord were planted into the flasks of two systems: two-dimensional (2D) culture and hollow-fiber-bioreactor based 3D culture. EVs were extracted from the culture supernatants. Characteristics and yields of EVs from two culture systems, namely 2D-EVs and 3D-EVs, were compared. A rat model of AMI was built up to assess their therapeutic efficacy on AMI. RESULTS: The yield of 3D-EVs was higher, with biofunctions similar to those of 2D-EVs. 3D-EVs repressed the apoptosis of cardiomyocytes, facilitated angiogenesis, and regulated the transition of macrophage subpopulations after myocardial infarction, and eventually improved cardiac function in the AMI rats. CONCLUSIONS: The hollow fiber 3D culture system can increase the yield of MSCs-derived EVs to render a strong cardioprotective effect in AMI rats.

The eisosomes contribute to acid tolerance of yeast by maintaining cell membrane integrity.

Microbes have evolved multiple mechanisms to resist environmental stresses, which are regulated in complex and delicate ways. Though the role of cell membranes in acid resistance from the perspective of physicochemical properties and membrane proteins has been deeply studied, the function of eisosomes is still in its infancy. In this study, we firstly reported the dynamic changes of eisosomes under acid stress and the decreased acid tolerance of yeasts caused by eisosome disruption. Physiological indicators and non-targeted lipid profiling revealed that eisosome disruption caused changes in multiple lipids and imbalances in lipid homeostasis, which are responsible for membrane integrity damage. Thus the increased infiltration of carboxylic acids and the raised ROS levels were detected in strains with disrupted eisosome assembly, resulting in decreased cellular tolerance. The results here provide novel insights into the acid-resistant mechanism of yeasts from the perspective of the cell membrane subdomain, which has practical impacts on green biological manufacturing and food preservation.

Serum uric acid was non-linearly associated with the risk of all-cause and cardiovascular death in individuals with coronary heart disease: a large prospective cohort study.

Objective: To investigate the association of serum uric acid (SUA) with all-cause and cardiovascular death in individuals with coronary heart disease (CHD). Methods: In this prospective cohort study, 1556 individuals from the National Health and Nutrition Examination Survey (1999-2015) were included in the analysis. Multivariate COX regression analysis, restricted cubic spline plot (RCS) and threshold effect were used to investigate the association between SUA and all-cause and cardiovascular death in individuals with CHD. Results: In the fully adjusted model, when SUA was regarded as a continuous variable, it was closely associated with the risk of all-cause and cardiovascular death (P < 0.01). When all participants were divided into four groups according to the quartile of SUA, compared with Q1 group, only individuals in Q4 group had higher risk of all-cause and cardiovascular death (P = 0.002 and 0.034). The following subgroup analysis showed that the association between SUA and all-cause death risk was still statistically significant in individuals over 60 years old, male, with hypertension, without diabetes and with chronic kidney disease, while the association with cardiovascular death risk only persisted in individuals over 60 years old and male (P < 0.05). Further sensitivity analysis showed that SUA was still closely associated with all-cause and cardiovascular death, whether as a continuous variable or a classified variable (P = 0.007 and 0.044). RCS analysis revealed that SUA had a nonlinear association with all-cause and cardiovascular death risk (P for nonlinearity < 0.01). Threshold effect analysis showed that SUA below 345 umol/L was negatively associated with all-cause and cardiovascular death risk (P < 0.05), while SUA above 345 umol/L was positively associated with all-cause and cardiovascular death risk (P < 0.001), and the 2-piecewise regression model was better than the 1-line regression model (P for likelihood ratio test < 0.05). Conclusion: SUA had a nonlinear association with all-cause and cardiovascular death risk in individuals with CHD.

Machine learning-based gray-level co-occurrence matrix signature for predicting lymph node metastasis in undifferentiated-type early gastric cancer.

BACKGROUND: The most important consideration in determining treatment strategies for undifferentiated early gastric cancer (UEGC) is the risk of lymph node metastasis (LNM). Therefore, identifying a potential biomarker that predicts LNM is quite useful in determining treatment. AIM: To develop a machine learning (ML)-based integral procedure to construct the LNM gray-level co-occurrence matrix (GLCM) prediction model. METHODS: We retrospectively selected 526 cases of UEGC confirmed through pathological examination after radical gastrectomy without endoscopic treatment in four tertiary hospitals between January 2015 to December 2021. We extracted GLCM-based features from grayscale images and applied ML to the classification of candidate predictive variables. The robustness and clinical utility of each model were evaluated based on the following factors: Receiver operating characteristic curve (ROC), decision curve analysis, and clinical impact curve. RESULTS: GLCM-based feature extraction significantly correlated with LNM. The top 7 GLCM-based factors included inertia value 0° (IV_0), inertia value 45° (IV_45), inverse gap 0° (IG_0), inverse gap 45° (IG_45), inverse gap full angle (IG_all), Haralick 30° (Haralick_30), Haralick full angle (Haralick_all), and Entropy. The areas under the ROC curve (AUCs) of the random forest classifier (RFC) model, support vector machine, eXtreme gradient boosting, artificial neural network, and decision tree ranged from 0.805 [95% confidence interval (CI): 0.258-1.352] to 0.925 (95%CI: 0.378-1.472) in the training set and from 0.794 (95%CI: 0.237-1.351) to 0.912 (95%CI: 0.355-1.469) in the testing set, respectively. The RFC (training set: AUC: 0.925, 95%CI: 0.378-1.472; testing set: AUC: 0.912, 95%CI: 0.355-1.469) model that incorporates Entropy, Haralick_all, Haralick_30, IG_all, IG_45, IG_0, and IV_45 had the highest predictive accuracy. CONCLUSION: The evaluation results indicate that the method of selecting radiological and textural features becomes more effective in the LNM discrimination against UEGC patients. Additionally, the ML-based prediction model developed using the RFC can be used to derive treatment options and identify LNM, which can hence improve clinical outcomes.

High Throughput Preparation of Ag-Zn Alloy Thin Films for the Electrocatalytic Reduction of CO2 to CO.

Ag-Zn alloys are identified as highly active and selective electrocatalysts for CO2 reduction reaction (CO2RR), while how the phase composition of the alloy affects the catalytic performances has not been systematically studied yet. In this study, we fabricated a series of Ag-Zn alloy catalysts by magnetron co-sputtering and further explored their activity and selectivity towards CO2 electroreduction in an aqueous KHCO3 electrolyte. The different Ag-Zn alloys involve one or more phases of Ag, AgZn, Ag5Zn8, AgZn3, and Zn. For all the catalysts, CO is the main product, likely due to the weak CO binding energy on the catalyst surface. The Ag5Zn8 and AgZn3 catalysts show a higher CO selectivity than that of pure Zn due to the synergistic effect of Ag and Zn, while the pure Ag catalyst exhibits the highest CO selectivity. Zn alloying improves the catalytic activity and reaction kinetics of CO2RR, and the AgZn3 catalyst shows the highest apparent electrocatalytic activity. This work found that the activity and selectivity of CO2RR are highly dependent on the element concentrations and phase compositions, which is inspiring to explore Ag-Zn alloy catalysts with promising CO2RR properties.

Characteristics of White Matter Integrity During Different Phases of Abstinence in Heroin Use Disorders: A Diffusion Tensor Imaging Study.

OBJECTIVES: The recovery of heroin-induced white matter impairment during abstinence has been reported, determining the characteristics of this recovery can help to improve the therapeutic strategies. In this study, we explored white matter characteristics in heroin use disorders during different phases of abstinence by using a quantitative diffusion tensor imaging method. METHODS: Seventeen and 22 male patients with long- and short-term abstinence (LA and SA, respectively) from heroin use and 20 male healthy controls participated in this study. Voxel-wise diffusion tensor imaging method was used for the comparison of fractional anisotropy (FA). Radial diffusivity (RD) and axial diffusivity (AD) were induced to explore the pathological characteristics of FA. The correlation between diffusion tensor indices and duration of abstinence was further analyzed. RESULTS: Compared to the healthy controls, patients with SA had significantly reduced FA in extensive white matter regions, while those with LA had only 2 clusters that showed reduced FA, which were located mainly in the genu of the corpus callosum, forceps minor, uncinate fasciculus, left inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and posterior thalamic radiation. Significantly increased RD with unchanged axial diffusivity were detected. FA in the regions with the significant intergroup difference between SA and LA correlated positively with the duration of abstinence. The RD in these regions correlated negatively with the duration of abstinence. CONCLUSIONS: The findings suggested that the time-dependent recovery of white matter, especially the restoration of the myelin sheath, occurred in patients with LA. Longer-abstinent duration with strategies of enhancing myelination may improve treatment effectiveness.

Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: The effect of dapagliflozin (DAPA) on the prognosis of patients with acute myocardial infarction (AMI) is unclear. The present study was conducted to evaluate the association between DAPA administration and adverse events in patients with AMI undergoing percutaneous coronary intervention (PCI). METHODS: This single-center retrospective analysis study included a total of 786 patients with AMI from January 2019 to August 2021 who were or were not administered DAPA at discharge. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall deaths, heart failure, nonfatal MI, nonfatal stroke, and unplanned repeat revascularization (URR). Differences in the triglyceride glucose (TyG) index and the atherogenic index of plasma (AIP) both during hospitalization and 12 months after discharge (if achievable) were also compared. RESULTS: During a median follow-up of 23 months, 130 patients had MACE (118 in the DAPA-free group and 12 in the DAPA group). Kaplan-Meier survival analyses revealed that the cumulative incidence of MACE (log-rank test, p = 0.009), heart failure (p = 0.003), nonfatal MI (p = 0.005), and URR (p = 0.031) was higher in the DAPA-free group. In addition, the multivariate Cox analysis showed that DAPA was significantly associated with the reduced risk of MACE (hazard ratio = 0.170, 95% confidence interval = 0.078-0.373, p < 0.001). Considering each specific adverse event, the DAPA-free group was associated with heart failure, nonfatal MI, and URR in multivariate Cox regression analyses. Stratification analyses suggested that DAPA has a strong protective effect in patients with AMI of advanced age with concomitant diabetes or those who are not on angiotensin receptor enkephalinase inhibitors. Furthermore, the TyG index and AIP of the patients 12 months after DAPA administration at discharge were significantly lower than those during hospitalization. CONCLUSIONS: DAPA is an independent protective factor against MACE and may provide incremental prognostic information in patients with AMI undergoing PCI.

Sex Differences in Intracranial Atherosclerotic Plaques Among Patients With Ischemic Stroke.

Objective: High-risk intracranial arterial plaques are the most common cause of ischemic stroke and their characteristics vary between male and female patients. However, sex differences in intracranial plaques among symptomatic patients have rarely been discussed. This study aimed to evaluate sex differences in intracranial atherosclerotic plaques among Chinese patients with cerebral ischemia. Methods: One hundred and ten patients who experienced ischemic events underwent 3T cardiovascular magnetic resonance vessel wall scanning for the evaluation of intracranial atherosclerotic disease. Each plaque was classified according to its likelihood of causing a stroke (as culprit, uncertain, or non-culprit). The outer wall area (OWA) and lumen area of the lesion and reference sites were measured, and the wall and plaque areas, remodeling ratio, and plaque burden (characterized by a normalized wall index) were further calculated. The composition (T1 hyperintensity, enhancement) and morphology (surface irregularity) of each plaque were analyzed. Sex differences in intracranial plaque characteristics were compared between male and female patient groups. Results: Overall, 311 plaques were detected in 110 patients with ischemic stroke (81 and 29 male and female patients, respectively). The OWA (P < 0.001) and wall area (P < 0.001) of intracranial arterial lesions were significantly larger in male patients. Regarding culprit plaques, the plaque burden in male patients was similar to that in female patients (P = 0.178, odds ratio [OR]: 0.168, 95% confidence interval [CI]: -0.020 to 0.107). However, the prevalence of plaque T1 hyperintensity was significantly higher than that in female patients (P = 0.005, OR: 15.362, 95% CI: 2.280-103.49). In the overall ischemic stroke sample, intracranial T1 hyperintensity was associated with male sex (OR: 13.480, 95% CI: 2.444-74.354, P = 0.003), systolic blood pressure (OR: 1.019, 95% CI: 1.002-1.036, P = 0.031), and current smoker (OR: 3.245, 95% CI: 1.097-9.598, P = 0.033). Conclusion: For patients with ischemic stroke, the intracranial plaque burden in male patients was similar to that in female patients; however, the plaque characteristics in male patients are associated with higher risk, especially in culprit plaques.

Radiomics Nomogram for Predicting Stroke Recurrence in Symptomatic Intracranial Atherosclerotic Stenosis.

Objective: To develop and validate a radiomics nomogram for predicting stroke recurrence in symptomatic intracranial atherosclerotic stenosis (SICAS). Methods: The data of 156 patients with SICAS were obtained from the hospital database. Those with and without stroke recurrence were identified. The 156 patients were separated into a training cohort (n = 110) and a validation cohort (n = 46). Baseline clinical data were collected from our medical records, and plaque radiological features were extracted from vascular wall high-resolution imaging (VW-HRMRI). The imaging sequences included 3D-T1WI-VISTA, T2WI, and 3D-T1WI-VISTA-enhanced imaging. Least absolute shrinkage and selection operator (LASSO) analysis were used to select the radiomics features associated with stroke recurrence. Then, multiple logistic regression analysis of clinical risk factors, radiological features, and radiomics signatures were performed, and a predictive nomogram was constructed to predict the probability of stroke recurrence in SICAS. The performance of the nomogram was evaluated. Results: Diabetes mellitus, plaque burden, and enhancement ratio were independent risk factors for stroke recurrence [odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.04-3.79, p = 0.018; OR = 1.76, per 10% increase, 95% CI, 1.28-2.41, p < 0.001; and OR = 1.94, 95% CI: 1.27-3.09, p < 0.001]. Five features of 3D-T1WI-VISTA, six features of T2WI, and nine features of 3D-T1WI-VISTA-enhanced images were associated with stroke recurrence. The radiomics signature in 3D-T1WI-VISTA-enhanced images was superior to the radiomics signature of the other two sequences for predicting stroke recurrence in both the training cohort [area under the curve (AUC), 0.790, 95% CI: 0.669-0.894] and the validation cohort (AUC, 0.779, 95% CI: 0.620-0.853). The combination of clinical risk factors, radiological features, and radiomics signature had the best predictive value (AUC, 0.899, 95% CI: 0.844-0.936 in the training cohort; AUC, 0.803, 95% CI: 0.761-0.897 in the validation cohort). The C-index of the nomogram was 0.880 (95% CI: 0.805-0.934) and 0.817 (95% CI: 0.795-0.948), respectively, in the training and validation cohorts. The decision curve analysis further confirmed that the radiomics nomogram had good clinical applicability with a net benefit of 0.458. Conclusion: The radiomics features were helpful to predict stroke recurrence in patients with SICAS. The nomogram constructed by combining clinical high-risk factors, plaque radiological features, and radiomics features is a reliable tool for the individualized risk assessment of predicting the recurrence of SICAS stroke.

Super-sensitive bifunctional nanoprobe: Self-assembly of peptide-driven nanoparticles demonstrating tumor fluorescence imaging and therapy.

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment; however, biocompatibility and targeted penetration of these nanomaterials remain as limitations, which lead to serious side effects and significantly narrow the scope of their application. The self-assembly of intermediate filaments with arginine-glycine-aspartate (RGD) peptide (RGD-IFP) was triggered by the hydrophobic cationic molecule 7-amino actinomycin D (7-AAD) to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment. The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes, ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA. It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential, but also potent antitumor therapeutic effects in vivo. The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.

KLF2 mediates the suppressive effect of BDNF on diabetic intimal calcification by inhibiting HK1 induced endothelial-to-mesenchymal transition.

Diabetic vascular calcification in the arterial intima is closely associated with endothelial-to-mesenchymal transition (EndMT). Glucose metabolism reprogramming is involved in EndMT. Although brain-derived neurotrophic factor (BDNF) and Krüppel-like family of transcription factor 2 (KLF2) play protective roles in the physiological activity of the vascular endothelium, the underlying mechanisms are unclear. Human umbilical vein endothelial cells (HUVECs) were incubated with diabetic osteogenic medium (DOM) to induce EndMT and accelerate osteogenic differentiation. Glycolysis in HUVECs was assessed by monitoring glucose uptake, lactate production, extracellular acidification rate and expression of key glycolytic enzymes. DOM induced EndMT and accelerated osteo-induction in HUVECs, which was alleviated by BDNF/tropomyosin receptor kinase B (TrkB) pathway. Mechanistically, DOM caused hyperactivation of glycolysis in HUVECs and inhibition of the BDNF/TrkB pathway. BDNF preserved KLF2 and downregulated hexokinase 1 (HK1) in HUVECs after DOM treatment. Furthermore, KLF2 interacted with HK1. Increased KLF2 alleviated HK1-mediated glucose metabolism abnormality. HK1 knockdown or a targeted glycolysis inhibitor suppressed EndMT, apoptosis, inflammation and vascular calcification of HUVECs after DOM exposure. This study suggests that KLF2 mediates the suppressive effect of BDNF on diabetic intimal calcification by inhibiting HK1-induced glucose metabolism reprogramming and the EndMT process.

Plaque Characteristics in Young Adults With Symptomatic Intracranial Atherosclerotic Stenosis: A Preliminary Study.

PURPOSE: To determine how intracranial vascular wall and atherosclerosis plaque characteristics differ between young and old adults with sICAS. METHODS: Eighty-four consecutive patients with sICAS who underwent high-resolution magnetic resonance imaging (HRMRI) from December 2017 to July 2020 were retrospectively collected. These participants were divided into young adult group (18-50 years, n = 28) and old adult group (>50 years, n = 56). Reviewers were blinded to any clinical information and HRMRI scans were analyzed for qualitative and quantitative indicators of vascular walls and plaque at the maximal lumen narrowing site using the independent-sample t-test, Mann-Whitney U-test, chi-square test or Fisher exact test, and logistic regression analysis. RESULTS: Young patients with sICAS had significantly smaller maximum wall thickness (1.45 ± 0.38 vs.1.75 ± 0.51 mm2, P = 0.003), higher prevalence of positive remodeling (53.57 vs. 21.43%, P = 0.003), and lower prevalence of diabetes mellitus (14.29 vs. 35.71%, P = 0.04) than old patients. Plaque burden and other plaque features were comparable between young and old patients. CONCLUSION: Young patients with sICAS have smaller maximum wall thickness and greater ability to reconstruct, and are more likely to show positive remodeling, which may lead to some atherosclerotic lesions being missed. Young patients with evidence of vessel narrowing should be carefully examined for presence of high-risk atherosclerotic plaque.

High expression of CLEC10A in head and neck squamous cell carcinoma indicates favorable prognosis and high-level immune infiltration status.

Immunotherapy has emerged as a promising treatment modality for HNSCC. However, only a small proportion of HNSCC patients experience clinical benefits from immunotherapy and identifying molecular markers that can serve as effective prognostic signatures and predictive indicators for immunotherapy response in patients with HNSCC is critical. CLEC10A has attracted attention because of its important role in improving the antitumor activity of immune cells. However, to our knowledge, no study has evaluated the role of CLEC10A in HNSCC prognosis, progression, and immune microenvironment. In the present study, we comprehensively analyzed expression profiles of CLEC10A and its association with tumor progression, HPV status, and survival of patients. Moreover, we explored the association between CLEC10A expression relative to immune infiltration and the response to immunotherapy. We explored the association between the timing of the receipt of palliative care relative to cancer diagnosis and survival. Our results revealed that CLEC10A has decreased expression in HNSCC compared with normal tissues, and that low expression of CLEC10A was associated with an advanced clinical stage and poor prognosis. Furthermore, a higher level of CLEC10A expression correlated with immune infiltration presence and response to immunotherapy in HNSCC. Thus, we demonstrated that CLEC10A could be a potential prognostic marker in patients with HNSCC, and a potential target for immunotherapy.

Evaluating intracranial artery dissection by using three-dimensional simultaneous non-contrast angiography and intra-plaque hemorrhage high-resolution magnetic resonance imaging: a retrospective study.

BACKGROUND: There was no previous report on the three-dimensional simultaneous non-contrast angiography and intra-plaque hemorrhage (3D-SNAP) magnetic resonance imaging (MRI) sequence to diagnose intracranial artery dissection (IAD). PURPOSE: To improve the diagnostic accuracy and guide the clinical treatment for IAD by elucidating its pathological features using 3D-SNAP MRI. MATERIAL AND METHODS: From January 2015 to September 2018, 113 patients with suspected IAD were analyzed. They were divided into IAD and non-IAD groups according to the spontaneous coronary artery dissection (SCAD) criteria. All patients underwent 3D-SNAP, 3D-TOF, T2W imaging, 3D-PD, 3D-T1W-VISTA, and 3D-T1WCE) using 3.0-T MRI; clinical data were collected. The IAD imaging findings (intramural hematoma, double lumen, intimal flap, aneurysmal dilatation, stenosis, or occlusion) in every sequence were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficiency of each sequence. RESULTS: There was a significant difference in the probability of intramural hematoma, relative signal intensity of intramural hematoma, double lumen, stenosis, or occlusion signs on 3D-TOF, T2W, 3D-PD, 3D-T1W-VISTA, 3D-SNAP, and 3D-T1WCE sequences (P<0.05). The 3D-SNAP and 3D-T1WCE sequences were most sensitive for diagnosing intramural hematoma and displaying double-lumen signs, respectively. The diagnostic efficiency of the 3D-SNAP sequence combined with 3D-T1WCE was the highest (area under the curve [AUC] 0.966). The AUC value of the 3D-SNAP sequence (AUC 0.897) was slightly inferior to that of 3D-T1W enhancement (AUC 0.903). CONCLUSION: 3D-SNAP MRI is a non-invasive and effective method and had the greatest potential among those methods tested for improving the diagnostic accuracy for IAD.