Sex-based outcomes after thoracic endovascular aortic repair: a systematic review and meta-analysis.

OBJECTIVE: As it remains unclear whether there are sex-based differences in clinical outcomes after thoracic endovascular aortic repair (TEVAR), this meta-analysis aimed to evaluate differences in early outcomes and overall survival between female and male patients who underwent TEVAR. METHODS: PubMed, Embase, Web of Science, and Cochrane Central databases were searched for eligible studies published through June 10, 2023, that reported sex-based differences in clinical outcomes after TEVAR. The primary outcome was operative mortality; second outcomes included stroke, spinal cord ischemia (SCI), acute kidney injury (AKI), hospital length of stay (LOS), and overall survival. Patient characteristics, operative data, and early outcomes were aggregated using the random-effects model, presenting pooled risk ratio (RR) or standardized mean difference (SMD) along with their corresponding 95% confidence intervals (CIs). Overall survival was assessed by reconstructing individual patient data to generate sex-specific pooled Kaplan-Meier curves. This study was registered in PROSPERO (CRD42023426069). RESULTS: Out of the 1785 studies retrieved, 14 studies met all eligibility criteria, encompassing a total of 17374 patients, comprising 5026 females and 12348 males. Female patients were older, had a smaller maximum aortic diameter, had lower rates of smoking and coronary artery disease, and had higher rates of anemia. Intraoperatively, females were more likely to use iliac conduits and require blood transfusions. There were no sex-based differences in operative mortality (RR: 1.12, 95% CI: 0.90-1.40; p=0.309), stroke (RR: 1.14, 95% CI: 0.95-1.38; p=0.165), SCI (RR: 1.33, 95% CI: 0.83-2.14; p=0.234), AKI (RR: 0.78, 95% CI: 0.52-1.17; p=0.228), and hospital LOS (SMD: 0.09, 95% CI: -0.03 to 0.20; p=0.141). Pooled Kaplan-Meier estimates showed a worse overall survival in female patients compared with male patients (87.2% vs. 89.8% at 2-year, log-rank p=0.001). CONCLUSIONS: Among patients treated by TEVAR, female sex was not associated with increased risk of operative mortality or major morbidity. However, females exhibited a lower overall survival after TEVAR compared with males.

Optimizing health resource allocation for improving timely HIV diagnosis in China.

INTRODUCTION: The Joint United Nations Programme on HIV/AIDS (UNAIDS) updated the 95-95-95 targets for the HIV endgame in 2030. To achieve the first target in a timely manner, we investigate the optimized strategy of resource allocation to maximize timely HIV diagnosis in 14 populations in China. METHODS: We developed a mathematical model by integrating epidemiological, demographical and behavioural data from 12 high-risk and two general populations to evaluate the impact of various resource allocation strategies of HIV testing on HIV incidence in China. We identified the optimized allocation strategy that maximizes the number of HIV diagnoses at an estimated total spending on HIV tests in China and calculated the per-capita cost of new HIV case detection. RESULTS: We estimated that 144,795 new HIV cases may occur annually in 14 populations in China, with a total annual spending of US$2.8 billion on HIV testing. The largest proportion of spending was allocated to general males (44.0%), followed by general females (42.6%) and pregnant women (5.1%). Despite this allocation strategy, only 45.5% (65,867/144,795, timely diagnosis rate) of annual new infections were diagnosed within a year of acquisition, with a cost of $42,852 required for each new HIV case detection. By optimizing the allocation of HIV testing resources within the same spending amount, we found that general females received the highest proportion of spending allocation (45.1%), followed by low-risk men who have sex with men (13.9%) and pregnant women (8.4%). In contrast, the proportion of spending allocation for the general males decreased to 0.2%. With this optimized strategy, we estimated that 120,755 (83.4%) of annual new infections would be diagnosed within a year of acquisition, with the cost required for one HIV case detection reduced to $23,364/case. Further spending increases could allow for significant increases in HIV testing among lower-risk populations. CONCLUSIONS: Optimizing resource allocation for HIV testing in high-risk populations would improve HIV timely diagnosis rate of new infections and reduce cost per HIV case detection.

The propagation of disturbances in ecological networks.

Despite the development of network science, we lack clear heuristics for how far different disturbance types propagate within and across species interaction networks. We discuss the mechanisms of disturbance propagation in ecological networks, and propose that disturbances can be categorized into structural, functional, and transmission types according to their spread and effect on network structure and functioning. We describe the properties of species and their interaction networks and metanetworks that determine the indirect, spatial, and temporal extent of propagation. We argue that the sampling scale of ecological studies may have impeded predictions regarding the rate and extent that a disturbance spreads, and discuss directions to help ecologists to move towards a predictive understanding of the propagation of impacts across interacting communities and ecosystems.

Integrated 4D label-free proteomics and data mining to elucidate the effects of thermal processing on crisp grass carp protein profiles.

The crisp grass carp (CGC; Ctenopharyngodon idellus C. et V.), known for its unique texture and flavour, is a culinary delicacy whose quality is significantly influenced by thermal processing. This study employed 4D label-free proteomics and data mining techniques to investigate the proteomic changes in CGC muscle tissue induced by various heating temperatures. CGC samples were subjected to a series of heat treatments at increasing temperatures from 20 °C to 90 °C. Proteins were extracted, digested, and analysed using high-resolution mass spectrometry. The proteomic data were then subjected to extensive bioinformatics analysis, including GO and KEGG pathway enrichment. We identified a total of 1085 proteins, 516 of which were shared across all the temperature treatments, indicating a core proteome responsible for CGC textural properties. Differential expression analysis revealed temperature-dependent changes, with significant alterations observed at 90 °C, suggesting denaturation or aggregation of proteins at higher temperatures. Functional enrichment analysis indicated that proteins involved in amino acid metabolism, glutathione metabolism, and nucleotide metabolism were particularly affected by heat. Textural analysis correlated these proteomic changes with alterations in CGC quality attributes, pinpointing 70 °C as the optimum temperature for maintaining the desired texture. A strong positive correlation between specific upregulated proteins was identified, such as the tubulin alpha chain and collagen alpha-1(IV) chain, and the improved textural properties of CGC during thermal processing, suggesting their potential as the potential biomarkers. This study offers a comprehensive proteomic view of the thermal stability and functionality of CGC proteins, delivering invaluable insights for both the culinary processing and scientific management of CGC. Our findings not only deepen the understanding of the molecular mechanisms underpinning the textural alterations in CGC during thermal processing but also furnish practical insights for the aquaculture industry. These insights could be leveraged to optimize cooking techniques, thereby enhancing the quality and consumer appeal of CGC products.

Multi-omics and single-cell sequencing analyses reveal the potential significance of circadian pathways in cancer therapy.

BACKGROUND: Circadian rhythm disturbance is an independent risk factor for cancer. However, few studies have been reported on circadian rhythm related genes (CRGs) in cancer, so it is important to further explore the impact of CRGs in pan-cancer. RESEARCH DESIGN AND METHODS: The Cancer Genome Atlas database was used to collect cancer-related data such as copy number variation, single nucleotide variants, methylation, and survival differences. Immunohistochemistry (IHC) was used to verify the expression of circadian rhythm hub genes. The circadian pathway scores (CRS) were calculated using single-sample gene enrichment analysis. TIMER and GEPIA databases were used for immune-cell integration and assessment. Single-cell sequencing data was used to evaluate the abundance of CRS in tumor microenvironment cells. RESULTS: In this study, we found that the expression of circadian pathway varies between tumors. CSNK1E was significantly up-regulated in most tumors and CRY2 was significantly down-regulated in most tumors. The protein interaction network suggested CRY2 as the core gene and IHC verified its significant low expression in KIRC. In addition, CRGs were found to be protective factors in most tumors and have the potential to act as specific immune markers in different tumors. CRS was significantly lower in abundance in most tumors. CRS was significantly associated with overall survival in tumor patients and associated with the expression of many immune cells in the tumor immune microenvironment. CRS is significantly associated with tumor mutational burden and microsatellite instability scores in most tumors and may serve as a potential immunotherapeutic marker. CONCLUSIONS: The circadian rhythm pathway may be a breakthrough point in regulating the tumor microenvironment meanwhile a suitable immunotherapy method in the future.

Differential Gut Microbiota, Dietary Intakes in Constipation Patients with or without Hypertension.

SCOPE: Diet and gut microbiota are involved in blood pressure regulations, but few studies have focused on the constipation patients. The study seeks to identify differences in gut microbiota between hypertensive and normotensive subjects in constipation patients, analyzes the relationship between dietary patterns and blood pressure, and explores mediation effects of gut microbiota. METHODS AND RESULTS: Gut microbial genera and dietary information of 186 functional constipation participants are characterized by 16S rRNA sequencing and a food frequency questionnaire. The hypertensive subjects shows lower α-diversity and ß-diversity of gut microbiota than normotensive (p < 0.05) and 17 differential microbial genera. The dried-beans intake frequency inversely correlated with systolic and diastolic blood pressure after multivariate adjustment (r = -0.273, p-FDR < 0.01; r = -0.251, p-FDR = 0.026, respectively). Logistic regression indicates that the individuals often consumed dried-beans have a lower hypertension risk than those never consumed [OR = 0.137, 95% CI: (0.022, 0.689), p = 0.022]. A marginal mediating effect of the genus Monoglobus is observed for the association between high-fiber dietary pattern and hypertension. CONCLUSION: In patients with functional constipation, hypertension-related gut microbial differences are identified. Dried-beans intake is inversely associated with blood pressure, and a genus may potentially mediate the association between high-fiber dietary pattern and hypertension.

Effect of glucocorticoid for patients with type A aortic dissection undergoing surgical repair with deep hypothermic circulatory arrest: A single-center, retrospective study.

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

LINC02015 modulates the cell proliferation and apoptosis of aortic vascular smooth muscle cells by transcriptional regulation and protein interaction network.

Long intergenic nonprotein coding RNA 2015 (LINC02015) is a long non-coding RNA that has been found elevated in various cell proliferation-related diseases. However, the functions and interactive mechanism of LINC02015 remain unknown. This study aimed to explore the role of LINC02015 in the cell proliferation and apoptosis of vascular smooth muscle cells (VSMCs) to explain the pathogenesis of aortic diseases. Ascending aorta samples and angiotensin-II (AT-II) treated primary human aortic VSMCs (HAVSMCs) were used to evaluate the LINC02015 expression. RNA sequencing, chromatin isolation by RNA purification sequencing, RNA pull-down, and mass spectrometry (MS) were applied to explore the potential interacting mechanisms. LINC02015 expression was found elevated in aortic dissection and AT-II-treated HAVSMCs. Cell proliferation and cell cycle were activated in HAVSMCs with LINC02015 knockdown. The cyclins family and caspase family were found to participate in regulating the cell cycle and apoptosis via the NF-κB signaling pathway. RXRA was discovered as a possible hub gene for LINC02015 transcriptional regulating networks. Besides, the protein interaction network of LINC02015 was revealed with candidate regulating molecules. It was concluded that the knockdown of LINC02015 could promote cell proliferation and inhibit the apoptosis of HAVSMCs through an RXRA-related transcriptional regulation network, which could provide a potential therapeutic target for aortic diseases.

No Sex-Based Differences Exist in Clinical Outcomes of Extended Aortic Arch Repair for Acute Type A Aortic Dissection.

BACKGROUND: Reports regarding the association between sex and clinical outcomes after surgical repair of acute type A aortic dissection (ATAAD) are not exhaustive and in part even conflicting. METHODS: A total of 786 eligible adult patients with ATAAD undergoing extended arch repair from January 2015 to December 2021 were included. They were divided into a female group (n = 161) and a male group (n = 625). In-hospital outcomes (surgical mortality and major postoperative morbidity) and midterm outcomes (survival and aortic reintervention) between the 2 groups were compared before and after propensity score matching (1:1). RESULTS: Compared with male patients, female patients were more likely to be older (median [interquartile range]: 57 [46-67] vs 50 [42-59] years; P < 0.001) and to have a lower body mass index, but were less likely to be current smokers. Operative death occurred in 66 patients (6.8% female vs 8.8% male), without significant differences between groups before and after matching (P = 0.422 and P > 0.999, respectively). Major postoperative morbidity was observed in 313 patients (39.8%), including 57 (35.4%) female and 256 (41.0%) male patients (P = 0.199). Sex-based grouping was not significantly associated with operative mortality or major postoperative morbidity. The 5-year cumulative survival and incidence of aortic reintervention among female patients were 90.6% and 6.0%, respectively, which were not statistically different from those observed in male patients before and after matching. CONCLUSIONS: No sex-based differences were found in terms of in-hospital and midterm outcomes of extended arch repair for ATAAD.

Three-Dimensional Cardiomyocyte-Nanobiosensing System for Specific Recognition of Drug Subgroups.

Abnormal cardiac electrophysiological activities significantly contribute to the incidence of cardiovascular diseases. Therefore, it is crucial to recognize effective drugs, which require an accurate, stable, and sensitive platform. Although conventional extracellular recordings offer a non-invasive and label-free manner to monitor the electrophysiological state of cardiomyocytes, the misrepresented and low-quality extracellular action potentials are difficult to provide accurate and high-content information for drug screening. This study presents the development of a three-dimensional cardiomyocyte-nanobiosensing system that can specifically recognize drug subgroups. The nanopillar-based electrode is manufactured by template synthesis and standard microfabrication technology on a porous polyethylene terephthalate membrane. Based on the cardiomyocyte-nanopillar interface, high-quality intracellular action potentials can be recorded by the minimally invasive electroporation. We validate the performance of a cardiomyocyte-nanopillar-based intracellular electrophysiological biosensing platform by two subclasses of sodium channel blockers, quinidine and lidocaine. The recorded intracellular action potentials accurately reveal the subtle differences between these drugs. Our study indicates that high-content intracellular recordings utilizing nanopillar-based biosensing can provide a promising platform for the electrophysiological and pharmacological investigation of cardiovascular diseases.

Modelling the impact of treatment adherence on the transmission of HIV drug resistance.

INTRODUCTION: A lower adherence rate (percentage of individuals taking drugs as prescribed) to ART may increase the risk of emergence and transmission of HIV drug resistance, decrease treatment efficacy, and increase mortality rate. Exploring the impact of ART adherence on the transmission of drug resistance could provide insights in controlling the HIV epidemic. METHODS: We proposed a dynamic transmission model incorporating the CD4 cell count-dependent rates of diagnosis, treatment and adherence with transmitted drug resistance (TDR) and acquired drug resistance. This model was calibrated and validated by 2008-2018 HIV/AIDS surveillance data and prevalence of TDR among newly diagnosed treatment-naive individuals from Guangxi, China, respectively. We aimed to identify the impact of adherence on drug resistance and deaths during expanding ART. RESULTS: In the base case (ART at 90% adherence and 79% coverage), we projected the cumulative total new infections, new drug-resistant infections, and HIV-related deaths between 2022 and 2050 would be 420 539, 34 751 and 321 671. Increasing coverage to 95% would reduce the above total new infections (deaths) by 18.85% (15.75%). Reducing adherence to below 57.08% (40.84%) would offset these benefits of increasing coverage to 95% in reducing infections (deaths). Every 10% decrease in adherence would need 5.07% (3.62%) increase in coverage to avoid an increase in infections (deaths). Increasing coverage to 95% with 90% (80%) adherence would increase the above drug-resistant infections by 11.66% (32.98%). CONCLUSIONS: A decrease in adherence might offset the benefits of ART expansion and exacerbate the transmission of drug resistance. Ensuring treated patients' adherence might be as important as expanding ART to untreated individuals.

A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart.

Tamoxifen, a selective estrogen receptor modulator, was initially used to treat cancer in women and more recently to induce conditional gene editing in rodent hearts. However, little is known about the baseline biological effects of tamoxifen on the myocardium. In order to clarify the short-term effects of tamoxifen on cardiac electrophysiology of myocardium, we applied a single-chest-lead quantitative method and analyzed the short-term electrocardiographic phenotypes induced by tamoxifen in the heart of adult female mice. We found that tamoxifen prolonged the PP interval and caused a decreased heartbeat, and further induced atrioventricular block by gradually prolonging the PR interval. Further correlation analysis suggested that tamoxifen had a synergistic and dose-independent inhibition on the time course of the PP interval and PR interval. This prolongation of the critical time course may represent a tamoxifen-specific ECG excitatory-inhibitory mechanism, leading to a reduction in the number of supraventricular action potentials and thus bradycardia. Segmental reconstructions showed that tamoxifen induced a decrease in the conduction velocity of action potentials throughout the atria and parts of the ventricles, resulting in a flattening of the P wave and R wave. In addition, we detected the previously reported prolongation of the QT interval, which may be due to a prolonged duration of the ventricular repolarizing T wave rather than the depolarizing QRS complex. Our study highlights that tamoxifen can produce patterning alternations in the cardiac conduction system, including the formation of inhibitory electrical signals with reduced conduction velocity, implying its involvement in the regulation of myocardial ion transport and the mediation of arrhythmias. A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart（Figure 9）. A working model of tamoxifen producing acute electrical disturbances in the myocardium. SN, sinus node; AVN, atrioventricular node; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.

Septuagenarians with acute type A aortic dissection undergoing extended aortic arch repair: a retrospective cohort study.

BACKGROUND: Extended arch repair in elderly patients with acute type A aortic dissection (ATAAD) remains challenging for cardiac surgeons. Data on extended arch repair for ATAAD in septuagenarians are scarce. MATERIALS AND METHODS: Consecutive adult patients with ATAAD undergoing extended arch repair from January 2015 to December 2021 were identified. According to age at presentation, 714 eligible patients were entered into either an elderly group (septuagenarians, n =65) or a control group (patients aged less than 70, n =649). Using propensity score matching, 60 pairs of patients were successfully established at a 1:1 ratio. In-hospital outcomes (operative death and major postoperative morbidity) and midterm outcomes (survival and aortic reintervention) were compared before and after matching. RESULTS: Operative death occurred in 64 patients (9.0%), including seven septuagenarians (10.8%) and 57 (8.8%) from the control group, without significant differences between groups before and after matching ( P =0.593 and 0.774, respectively). Major postoperative morbidity was observed in 298 patients (41.7%), including 29 (44.6%) in the elderly group and 269 (41.4%) in the control group ( P =0.622). Age-based grouping was not significantly associated with operative mortality or major postoperative morbidity in the crude, multivariable, and propensity score analyses. The 5-year cumulative survival and cumulative aortic reintervention rates in the elderly group were 83.5 and 4.6%, respectively, which were not statistically different from those in the control group before and after matching. CONCLUSIONS: Extended arch repair may be safely and effectively performed in septuagenarians with ATAAD, with in-hospital and midterm outcomes comparable to those obtained in patients aged less than 70 years.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber ­ gut microbiota (Anaerostipes)­constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.

Instant Coffee Is Negatively Associated with Telomere Length: Finding from Observational and Mendelian Randomization Analyses of UK Biobank.

Telomere length, as a biomarker of accelerated aging, is closely related to many chronic diseases. We aimed to explore the association between coffee consumption and telomere length. Our study included 468,924 participants from the UK Biobank. Multivariate linear models (observational analyses) were conducted to evaluate the associations of coffee intake, instant coffee intake, and filtered coffee intake with telomere length. In addition, we evaluated the causality of these associations in Mendelian randomization (MR) analyses by four methods (inverse-variance weighted (IVW), MR pleiotropy residual sum and outlier (MR-PRESSO), MR-Egger, and weighted median). Observational analyses indicated that coffee intake and instant coffee intake were negatively correlated with telomere length, which was equal to 0.12 year of age-related decrease in telomere length for each additional cup of coffee intake (p < 0.001), and 0.38 year of age-related decrease in telomere length for each additional cup of instant coffee intake (p < 0.001), respectively. There was no significant correlation between filtered coffee and telomere length (p = 0.862). Mendelian randomization analyses supported the results of observational analyses. Coffee intake was found to have a causal effect on telomere length through weighted median analysis (p = 0.022), and instant coffee intake had a causal effect on telomere length through IVW analysis (p = 0.019) and MR-PRESSO analysis (p = 0.028). No causal relationship was found between filtered coffee intake and telomere length (p > 0.05). Coffee intake, particularly instant coffee, was found to have an important role in shortening telomere length.

A hiPSC-derived lineage-specific vascular smooth muscle cell-on-a-chip identifies aortic heterogeneity across segments.

Aortic aneurysm (AA), a potentially lethal condition with the characteristic of aortic dilatation, can only be treated by surgical or endovascular procedures. The underlying mechanisms of AA are unclear and early preventive treatment is still insufficient due to segmental aortic heterogeneity and the limitations of current disease models. Here, we firstly established a comprehensive lineage-specific vascular smooth muscle cell (SMC)-on-a-chip model using human induced pluripotent stem cells to yield cell lineages representing different segments of the aorta and tested the constructed organ-on-a-chip model under various tensile stress conditions. Bulk RNA sequencing, RT-qPCR, immunofluorescence, western blot and FACS analyses were performed to discover the segmental aortic heterogeneity of response for tensile stress and drug testing. The appropriate stretching frequency for all lineages of SMCs was 1.0 Hz, paraxial mesoderm (PM) SMCs were more sensitive to tensile stress than lateral mesoderm (LM) SMCs and neural crest (NC) SMCs. These differences may be related to the different transcriptional profiles of the tension-stressed distinct lineage-specific vascular SMCs, specifically in relation to the PI3K-Akt signaling pathway. Also, the organ-on-a-chip displayed contractile physiology, perfect fluid coordination, and was conducive to drug testing, displaying heterogeneous segmental aortic responses. Compared with LM-SMCs and NC-SMCs, PM-SMCs were more sensitive to ciprofloxacin. The model is evaluated as a novel and suitable supplement to AA animal models for determining differential physiology and drug response in different parts of the aorta. Furthermore, this system could pave the way for disease modeling, drug testing, and the personalized treatment of patients with AA in the future.

Nicotinamide Mononucleotide Alleviates Angiotensin II-Induced Human Aortic Smooth Muscle Cell Senescence in a Microphysiological Model.

ABSTRACT: The occurrence and development of aortic aneurysms are accompanied by senescence of human aortic smooth muscle cells (HASMCs). Because the mechanism of HASMC senescence has not been fully elucidated, the efficacy of various antisenescence treatments varies. Decreased nicotinamide adenine dinucleotide (NAD + ) levels are one of the mechanisms of cell senescence, and there is a lack of evidence on whether increasing NAD + levels could alleviate HASMC senescence and further retard the progression of aortic aneurysms.We constructed an HASMC-based organ-on-a-chip microphysiological model. RNA sequencing was performed on cell samples from the vehicle control and angiotensin II groups to explore biological differences. We detected cellular senescence markers and NAD + levels in HASMC-based organ-on-a-chip. Subsequently, we pretreated HASMC using the synthetic precursor of NAD + , nicotinamide mononucleotide, and angiotensin II treatment, and used rhythmic stretching to investigate whether nicotinamide mononucleotide could delay HASMC senescence.The HASMC-based organ-on-a-chip model can simulate the biomechanical microenvironment of HASMCs in vivo, and the use of angiotensin II in the model replicated senescence in HASMCs. The senescence of HASMCs was accompanied by downregulation of the expression level of nicotinamide phosphoribosyltransferase and NAD + . Pretreatment with nicotinamide mononucleotide significantly increased the NAD + level and alleviated the senescence of HASMCs, but did not change the expression level of nicotinamide phosphoribosyltransferase.Our study provides a complementary research platform between traditional cell culture and animal experiments to explore HASMC senescence in aortic aneurysms. Furthermore, it provides evidence for NAD + boosting therapy in the clinical treatment of aortic aneurysms.

Automatic segmentation of thrombosed aortic dissection in post-operative CT-angiography images.

PURPOSE: The thrombus in the false lumen (FL) of aortic dissection (AD) patients is a meaningful indicator to determine aortic remodeling but difficult to measure in clinic. In this study, a novel segmentation strategy based on deep learning was proposed to automatically extract the thrombus in the FL in post-operative computed tomography angiography (CTA) images of AD patients, which provided an efficient and convenient segmentation method with high accuracy. METHODS: A two-step segmentation strategy was proposed. Each step contained a convolutional neural network (CNN) to segment the aorta and the thrombus, respectively. In the first step, a CNN was used to obtain the binary segmentation mask of the whole aorta. In the second step, another CNN was introduced to segment the thrombus. The results of the first step were used as additional input to the second step to highlight the aorta in the complex background. Moreover, skip connection attention refinement (SAR) modules were designed and added in the second step to improve the segmentation accuracy of the thrombus details by efficiently using the low-level features. RESULTS: The proposed method provided accurate thrombus segmentation results (0.903 ± 0.062 in dice score, 0.828 ± 0.092 in Jaccard index, and 2.209 ± 2.945 in 95% Hausdorff distance), which showed improvement compared to the methods without prior information (0.846 ± 0.085 in dice score) and the method without SAR (0.899 ± 0.060 in dice score). Moreover, the proposed method achieved 0.967 ± 0.029 and 0.948 ± 0.041 in dice score of true lumen (TL) and patent FL (PFL) segmentation, respectively, indicating the excellence of the proposed method in the segmentation task of the overall aorta. CONCLUSIONS: A novel CNN-based segmentation framework was proposed to automatically obtain thrombus segmentation for thrombosed AD in post-operative CTA images, which provided a useful tool for further application of thrombus-related indicators in clinical and research application.

Adverse effects of ambient fine particulate matter (PM2.5 ) on vascular smooth muscle cells.

Cardiovascular diseases are the leading cause of death worldwide. Meanwhile, environment air pollution has become a serious health risk factor, contributing to the mortality of respiratory and cardiovascular diseases. A substantial body of evidence has shown that many types of vascular diseases are related to air pollution. The physiology and pathophysiology of the three layers of vascular vessels, especially the inner and medial layer, contribute to the process of vascular diseases. Vascular smooth muscle cells (VSMCs) are the predominant cells in the medial layer, and several studies have indicated that air pollution has an adverse effect on VSMCs. There are numerous sources of air pollution across the world, and the components of air pollutants are a complex mixture of gaseous pollutants and particulate matter. Among these air pollutants, particulate matter (PM)2.5 presents the highest risk factor leading to global mortality from cardiovascular disease and disability. In this review, we primarily focus on the impacts of PM2.5 exposure on VSMCs. We further discuss the correlation between exposure to PM2.5 and other vascular diseases and present potential protective and treatment strategies to decrease vascular mortality related to air pollution.