Role of hypoxia in cellular senescence.

Senescent cells persist and continuously secrete proinflammatory and tissue-remodeling molecules that poison surrounding cells, leading to various age-related diseases, including diabetes, atherosclerosis, and Alzheimer's disease. The underlying mechanism of cellular senescence has not yet been fully explored. Emerging evidence indicates that hypoxia is involved in the regulation of cellular senescence. Hypoxia-inducible factor (HIF)- 1α accumulates under hypoxic conditions and regulates cellular senescence by modulating the levels of the senescence markers p16, p53, lamin B1, and cyclin D1. Hypoxia is a critical condition for maintaining tumor immune evasion, which is promoted by driving the expression of genetic factors (such as p53 and CD47) while triggering immunosenescence. Under hypoxic conditions, autophagy is activated by targeting BCL-2/adenovirus E1B 19-kDa interacting protein 3, which subsequently induces p21WAF1/CIP1 as well as p16Ink4a and increases ß-galactosidase (ß-gal) activity, thereby inducing cellular senescence. Deletion of the p21 gene increases the activity of the hypoxia response regulator poly (ADP-ribose) polymerase-1 (PARP-1) and the level of nonhomologous end joining (NHEJ) proteins, repairs DNA double-strand breaks, and alleviates cellular senescence. Moreover, cellular senescence is associated with intestinal dysbiosis and an accumulation of D-galactose derived from the gut microbiota. Chronic hypoxia leads to a striking reduction in the amount of Lactobacillus and D-galactose-degrading enzymes in the gut, producing excess reactive oxygen species (ROS) and inducing senescence in bone marrow mesenchymal stem cells. Exosomal microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play important roles in cellular senescence. miR-424-5p levels are decreased under hypoxia, whereas lncRNA-MALAT1 levels are increased, both of which induce cellular senescence. The present review focuses on recent advances in understanding the role of hypoxia in cellular senescence. The effects of HIFs, immune evasion, PARP-1, gut microbiota, and exosomal mRNA in hypoxia-mediated cell senescence are specifically discussed. This review increases our understanding of the mechanism of hypoxia-mediated cellular senescence and provides new clues for anti-aging processes and the treatment of aging-related diseases.

Recombinant ferritins for multimodal nanomedicine.

In all living organisms, ferritins are a group of proteins important for maintaining iron homeostasis. Increasing amount of studies has shown that recombinant ferritins can be widely used in multimodal nanomedicine, especially for anticancer treatment and vaccination. Recombinant particles prepared by fusing viral proteins and ferritin subunits produce a better immune response and higher antibody titres. Moreover, actively-targeted ferritin nanoparticles can recognise receptors and deliver natural or chemical drugs specifically to the tumour tissue. In addition, ferritin-linked or loaded with contrast agents or fluorescent dyes can be used as multimodal particles useful cancer theranostics. In this review, we fully summarised the unitisation of recombinant ferritins in multimodal nanomedicine. The research progress of using recombinant ferritins as nanovaccines, nanozymes, and bioengineered nanocarriers for targeted therapy and bioimaging is emphasised.

The effects of short-term exposure to air pollution on mortality in Baotou, China, during 2015-2019.

Air pollution was considered one of the main causes linked to increased morbidity and mortality around the world. This study aimed to estimate the effect of air pollutants on daily death in Baotou city of Inner Mongolia. Daily deaths data were provided by Baotou Centers for Disease Control and Prevention for the years 2015-2019 (Baotou CDC). The air pollutants, PM2.5, PM10, NO2, SO2, CO and maximum 8-h average concentrations of O3, came from the eight environmental monitoring stations in Baotou city. Time-series plots were used to exploit the trend of air pollutants at calendar time. Generalized additive model was used to estimate the effect of air pollutants on daily death. Restricted cubic spline was employed to investigate non-line relationships between air pollutants and daily death. After adjusting the meteorological factors, non-accidental daily deaths were related to PM2.5 (ER = 0.074%) and PM10 (ER = 0.023%), respectively. In stratified analysis, population aged over 65 years and females were more sensitive to air pollutants exposure and warm season might make people more susceptible to air pollutants compared with cold season. PM2.5 and PM10 increase the risk of non-accidental and cardiovascular daily death, but not respiratory daily death.

The Relationship between the Incidence of Postoperative Cognitive Dysfunction and Intraoperative Regional Cerebral Oxygen Saturation after Cardiovascular Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: To assess whether intraoperative monitoring and intervention of regional cerebral oxygen saturation levels can reduce the incidence of postoperative cognitive dysfunction in patients undergoing cardiovascular surgery and contribute to patient prognosis. Methods: The Cochrane Library, PubMed, and the Web of Science were systematically searched for relevant randomized controlled trials involving the effects of cerebral oxygen saturation on the cognitive function of patients after cardiovascular surgery from January 1, 2000 to May 1, 2022. The primary outcome was the incidence of postoperative cognitive dysfunction. The secondary outcomes were length of hospital stay, length of intensive care unit (ICU) stay, length of mechanical ventilation, length of cardiopulmonary bypass, and other major postoperative outcomes such as renal failure, infection, arrhythmia, hospital mortality, and stroke. Data were pooled using the risk ratio or standardized mean difference with 95% confidence interval (CI). The original study protocol was registered prospectively with PROSPERO (CRD42020178068). Results: A total of 13 randomized controlled trials involving 1669 cardiovascular surgery patients were included. Compared with the control group, the risk of postoperative cognitive dysfunction was significantly lower in the intervention group (RR = 0.50; 95% CI: 0.30 to 0.85; p = 0.01; I 2 = 71%). The Duration of stay in intensive care units in the intervention group was also significantly shorter than that in the control group (standard mean difference (SMD) = -0.14; 95% CI: -0.26 to -0.01; p = 0.03; I 2 = 26%). Univariate meta-regression analyses showed that age is a major source of heterogeneity. Conclusions: Our current study suggests that intraoperative cerebral oxygen saturation monitoring and intervention can significantly reduce the incidence of postoperative cognitive dysfunction, and the length of intensive care unit stay after intervention is considerably reduced. Given that some limits in this review, more high-quality, and long-term trials are still needed to certify our findings.

Association of household solid fuel use and long-term exposure to PM2.5 with arthritis in middle-aged and older population in China: A cohort study.

Air pollutants are common modifiable risk factors for arthritis. To explore the longitudinal effects of air pollution on arthritis based on a cohort study in middle-aged and elder people of China. Data was obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 7449 participants aged 45 years and older were involved in our study. The generalized linear mixed models were conducted to examine the separate and joint effects of household air pollution and outdoor air pollution on arthritis, respectively. We found a strong significant association between air pollution and arthritis incidence. Individuals cooking primarily with solid fuel were more likely in higher risk of arthritis compared with cleaner fuel (OR= 1.15; 95% CI: 1.08-1.23). The group-based trajectory model identified four trajectory groups, compared with group "High-Decreasing rapidly", adjusted ORs of incident arthritis for group "Middle-Decreasing moderately", "Low-Decreasing slowly" and "Low-Stably" were 1.36 (95% CI, 1.03-1.79), 1.36 (95% CI, 1.01-1.83) and 1.81 (95% CI, 1.30-2.52), respectively. These associations were generally higher in participants younger than 65 years. In addition, solid fuel use and PM2.5 exposure had additive and multiplicative effects on arthritis. The results suggested that solid fuel use and long-term PM2.5 exposure were associated with a higher incidence of arthritis. Therefore, it is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to reduce PM2.5 concentration.

T-2 Toxin Induces Immunosenescence in RAW264.7 Macrophages by Activating the HIF-1α/cGAS-STING Pathway.

T-2 toxin induces cell immunotoxicity by triggering an intracellular hypoxic microenvironment and activates hypoxia-inducible factor-1α (HIF-1α), which exerts cellular protective effects. Mycotoxins can also induce senescence. The aging of immune function, termed "immunosenescence," is an important factor in the decline of biological immunity and accelerates senescence. However, the mechanism underlying T-2 toxin-induced immunosenescence remains unclear. This study aimed to elucidate the roles of HIF-1α and cGAS-STING signaling in this process and uncover the mechanisms through which T-2 toxin impacts cytoskeletal integrity and cellular senescence using a RAW264.7 macrophage model. The cells were treated with T-2 toxin (14 nM) for 1-24 h. We revealed that T-2 toxin-induced immunosenescence in RAW264.7 cells by activating the HIF-1α/cGAS-STING axis. The cGAS-STING pathway promotes cell senescence and apoptosis; however, we revealed that HIF-1α negatively regulated this pathway, thereby inhibiting cellular senescence and apoptosis. However, PARP 1 cleavage by caspase 3/9 inhibited DNA repair and accelerated the transition from senescence to apoptosis. At the late stages of T-2 toxin exposure (12 h), HIF-1α accelerated cellular senescence by disrupting the dynamic balance of cytoskeletal α-tubulin and F-actin and destabilizing the cytoskeletal structure. Our research demonstrates that T-2 toxin induces immunosenescence in RAW264.7 cells by activating the cGAS-STING pathway, with HIF-1α signaling serving as a negative regulator. This study provides a deeper understanding of T-2 toxin-induced immunosenescence.

A Mendelian analysis of the relationships between immune cells and breast cancer.

Background: Emerging evidence showed immune cells were associated with the development of breast cancer. Nonetheless, the causal link between them remains uncertain. Consequently, the objective of this study was to investigate the causal connection between immune traits and the likelihood of developing breast cancer. Methods: A two-sample Mendelian randomization (MR) analysis was conducted to establish the causal relationship between immune cells and breast cancer in this study. Utilizing publicly accessible genetic data, we investigated causal connections between 731 immune cells and the occurrence of breast cancer. The primary approach for exploring this relationship was the application of the inverse-variance-weighted (IVW) method. Furthermore, sensitivity analyses, encompassing the leave-one-out analysis, Cochran Q test, and Egger intercept test were performed to validate the reliability of the Mendelian randomization results. Finally, we used Bayesian Weighted Mendelian Randomization (BWMR) approach to test the results of MR study. Results: According to the Bonferroni correction, no immune trait was identified with a decreased or increased risk of overall breast cancer risk. As for the ER+ breast cancer, 6 immune trait was identified after the Bonferroni method. the IVW method results showed that CD45RA- CD4+ %CD4+ (p-value:1.37×10-6), CD8dim %T cell (p-value:4.62×10-43), BAFF-R on IgD+ CD38- unsw mem (p-value:6.93×10-5), CD27 on PB/PC (p-value:2.72×10-18) lowered the risk of breast cancer. However, CD19 on IgD- CD38br (p-value:1.64×10-6), CD25 on IgD+ CD38dim (p-value: - ∞) were associated with a higher risk of developing breast cancer. As for the CX3CR1 on CD14+ CD16- monocyte (p-value: 1.15×10-166), the IVW method clearly demonstrated a protective effect against ER- breast cancer. For the above positive results, BAFF-R on IgD+ CD38- unsw mem was the sole association linked to reduced breast cancer risk using the BWMR method. The intercept terms' p-values in MR-Egger regression all exceeded 0.05, indicating the absence of potential horizontal pleiotropy. Conclusion: Through genetic approaches, our study has illustrated the distinct correlation between immune cells and breast cancer, potentially paving the way for earlier diagnosis and more efficient treatment alternatives.

Aortic diameter remodeling after frozen elephant trunk as a predictor of early outcomes in thoracoabdominal aortic repair.

OBJECTIVE: Patients who underwent previous frozen elephant trunk implantation for Stanford type A aortic dissection remain at risk for secondary intervention due to unsuccessful distal aortic remodeling. We aimed to investigate the impact of distal aortic remodeling on early outcomes in patients who underwent 2-stage thoracoabdominal aortic repair. METHODS: A total of 106 patients who previously underwent frozen elephant trunk implantation and thoracoabdominal aortic repair between October 2014 and December 2022 were enrolled in this study. The extent of distal aortic remodeling was evaluated, including aortic diameter, area ratio of the false lumen/aortic lumen, and patency of the false lumen at 3 levels of the aorta. Logistic regression analyses were performed to investigate the risk factors for early outcomes. RESULTS: The aortic diameter at the distal frozen elephant trunk was significantly larger in patients who died early than in surviving patients (79.19 ± 22.89 mm vs 46.84 ± 19.17 mm, respectively, adjusted P = .001). The optimal cutoff value for the aortic diameter at the distal frozen elephant trunk was 60 mm. Patients with an aortic diameter 60 mm or more at the distal frozen elephant trunk had worse early outcomes (P < .05), including prolonged intubation, early death, and postoperative complications. The aortic diameter at the distal frozen elephant trunk was identified as a significant risk factor for early death in patients undergoing thoracoabdominal aortic repair. CONCLUSIONS: Patients undergoing thoracoabdominal aortic repair with an aortic diameter 60 mm or more at the distal frozen elephant trunk have worse early outcomes. Moreover, an aortic diameter at the distal frozen elephant trunk is a significant risk factor for early death in patients undergoing thoracoabdominal aortic repair.

Deciphering the circulating immunological landscape of thoracic aortic aneurysm: Insights from a two-sample Mendelian randomization study.

Background: Thoracic Aortic Aneurysm (TAA) poses significant health risks due to aortic dilation. Recent evidence suggests a pivotal role for the immune-inflammatory response in the mechanism of aortic aneurysm formation. In this study, we aim to investigate the causal relationship between circulating immune cells and TAA. Methods: This study employs a two-sample Mendelian Randomization (MR) approach, utilizing genome-wide association study (GWAS) summary statistics for 731 immune cell types and two TAA data from large-scale studies. Causal effects of both peripheral immune cells on TAA and TAA on peripheral immune cells are explored. To ensure more accurate results, we intersected the findings from two TAA data from large-scale studies, excluding results where the direction of the odds ratio (OR) was inconsistent. Findings: The study identifies specific immune cells associated with TAA. Notably, CD45+ NKT cell (OR: 0.95, 95CI%: 0.90-0.99 in FinnGen study; OR: 0.91, 95CI%: 0.84-0.99 in CHIP + MGI study) and CD45+ HLA-DR + CD8+ T cells (OR: 0.95, 95CI%: 0.90-0.99 in FinnGen study; OR: 0.90, 95CI%: 0.82-0.99 in CHIP + MGI study) demonstrate a protective role against TAA. In addition, CD28+ CD45RA- CD8+ T cells (relative cell counts and absolute cell counts) and HVEM + CM + CD8+ T cells are adversely affected by TAA. Interpretation: The findings indicate that the potential protective influence exerted by specific subsets of peripheral NKT cells and CD8+ T cells in mitigating the development of TAA, while simultaneously highlighting the reciprocal effects of TAA on peripheral Treg cells subsets and T cell subsets. The complex interaction between immune cells and TAA could provide valuable clues for earlier detection and more efficacious treatment strategies for TAA.

Age-associated changes in innate and adaptive immunity: role of the gut microbiota.

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors.

Long-term outcomes of extensive thoracoabdominal aortic aneurysm repair utilizing normothermic iliac perfusion: A retrospective cohort study with 10-year single-center experience.

BACKGROUND: Normothermic iliac perfusion has been increasingly utilized for TAAA repair; however, the long-term outcomes in large samples are lacking. This study was designed to assesses the perioperative and long-term results of thoracoabdominal aortic repair using normothermic iliac perfusion. METHODS: We retrospectively analyzed 156 patients having Crawford extent II or III thoracoabdominal aortic aneurysm replacement with normothermic iliac perfusion from 2012 to 2022. Primary endpoints were composite adverse events and long-term survival, which encompassed 30-day mortality, persistent stroke, persistent paraplegia, and acute renal failure needing continuous dialysis. The cohort was divided into two subgroups based on the use of selective visceral and cold renal perfusion techniques. RESULTS: The combined adverse event rate was 14.1%. Specific rates were: 30-day mortality (4.5%), persistent stroke (1.9%), persistent paraplegia (4.5%), and renal failure requiring persistent dialysis (3.2%). The median follow-up time was 67 months. Overall survival rates at 1, 3, 5, 7, and 10 years were 91.6%, 90.0%, 85.4%, 77.6%, and 69.7%, respectively. Subgroup analysis showed the visceral and renal perfusion group had a significantly reduced adverse event incidence compared to the nonperfusion group (6.5% vs. 19.1%, P=0.026). Multivariable logistic regression analysis confirmed selective visceral and cold renal perfusion techniques as protective factors against postoperative adverse events (OR 0.30, 95%CI 0.09-0.94; P=0.038). Multivariable Cox regression analysis identified age ≥50 years (HR 2.63, 95%CI 1.10-6.27; P=0.029) and NYHA grade ≥III (HR: 3.20, 95% CI: 1.04-9.87; P=0.043) as independent risk factors predicting overall survival. CONCLUSIONS: Normothermic iliac perfusion is a feasible option for thoracoabdominal aortic repair with cost benefits and simpler management, and selective visceral and cold renal perfusion techniques may further improve its safety and effectiveness. However, enhanced vigilance and meticulous care are essential, particularly for elderly patients and those with cardiac insufficiency.

Stimuli-responsive AIEgens with an ultra acidochromic scope for self-reporting soft actuators.

This study develops a series of NBI-based acidochromic AIEgens engineered for ultra-wide acidochromic scope in self-reporting soft actuators, establishing the relationship between the photophysical properties and structural configurations of the AIEgens, further investigating their acidochromic behavior and fabricating acidity monitoring chips. The acidochromic behaviors were thoroughly investigated, and high-precision acidity monitoring chips were fabricated. We confirmed the protonation order of nitrogen atoms within the molecules and elucidated the acidochromic mechanisms through DFT and 1H NMR analyses. Utilizing these findings, we designed acid-driven hydrogel-based biomimetic actuators that can self-report and control the release of heavy loads under acidic conditions. These actuators hold significant potential for applications in targeted drug delivery within acidic biological environments, controlled release systems, and specialized transportation of heavy loads under acidic conditions.

Comparison of Safety and Effectiveness of Local or General Anesthesia after Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis.

It remains controversial to choose anesthesia for transcatheter aortic valve implantation (TAVI). A meta-analysis of cohort studies was conducted to assess the efficacy and safety of local anesthesia (LA) compared to general anesthesia (GA) in TAVI. All relevant studies published from 1 January 2002, to 31 June 2022, were searched in Ovid, PubMed, Embase, Web of Science, and Cochrane Library. A total of 34 studies involving 23,480 patients were included in the meta-analysis. TAVI with LA was associated with a significant reduction in hospital stay [WMD = −2.48, 95% CI (−2.80, −2.16), p < 0.00001], operative [WMD = −12.25, 95% CI (−13.73, −10.78), p < 0.00001] and fluoroscopy time [WMD = −3.30, 95% CI (−5.40, −1.19), p = 0.002], and an increased risk of acute kidney injury [OR = 1.31, 95% CI (1.01, 1.69), p = 0.04] and a reduced incidence of major bleeding [OR = 0.59, 95% CI (0.46, 0.75), p < 0.0001] and the use of cardiovascular drugs [OR = 0.17, 95% CI (0.05, 0.57), p = 0.004]. No differences were found between LA and GA for 30-day mortality, procedural success rate, myocardial infarction, permanent pacemaker implantation, paravalvular leak, shock, and cerebrovascular events. Overall, 4.4% of LA converted to GA. Based on current evidence, our results suggested that LA strategies reduced hospital stay, operative time, fluoroscopy time, cardiovascular drug consumption, and major bleeding rates in patients undergoing TAVI but led to increased acute kidney injury rates. Further studies and randomized trials are required to verify the presented findings and to identify patients who might benefit from LA.

The impact of antiplatelet therapy on the descending thoracic aorta fate and long-term prognosis of extensive repaired type A aortic dissection.

OBJECTIVES: To evaluate the impact of antiplatelet therapy on the long-term descending thoracic aorta (DTA) fate and prognosis of extensive repaired type A aortic dissection (TAAD). METHODS: 1147 eligible TAAD patients from January 2010 to December 2019 were stratified into non-antiplatelet (n = 754) and antiplatelet groups (n = 393). The primary end points were overall survival, and DTA remodelling, including false lumen (FL) thrombosis and aortic redilation. The secondary end points were DTA reintervention or rupture and major bleeding events (MBEs). RESULTS: The 5-year overall survival rates were 95.6% and 94.3% in the non-antiplatelet and antiplatelet groups (P = 0.53), respectively. In the stent covering segment, the 1-year FL complete thrombosis rates were 92.1% and 92.4% in the non-antiplatelet and antiplatelet groups (P = 0.27), respectively, while in the stent uncovering segment, the 5-year FL complete thrombosis rates were 47.1% and 56.5% in the non-antiplatelet and antiplatelet groups (P = 0.12), respectively. Antiplatelet therapy was not an independent predictor of aortic redilation at the pulmonary artery bifurcation (ß±SE = -0.128 ± 0.203, P = 0.53), diaphragm (ß±SE = 0.143 ± 0.152, P = 0.35) or coeliac artery (ß±SE = 0.049 ± 0.136, P = 0.72) levels. With death as a competing risk, the cumulative incidences of DTA reintervention or rupture at 5 years were 4.6% and 4.0% in the non-antiplatelet and antiplatelet groups (sHR = 0.85, 95% CI, 0.49∼1.19; P = 0.58), respectively, and the 5-year cumulative incidences of MBEs were 2.1% and 2.3% in the non-antiplatelet and antiplatelet groups (sHR = 0.82, 95% CI, 0.56∼2.67; P = 0.62), respectively. CONCLUSIONS: Antiplatelet therapy did not impact long-term DTA FL thrombosis, redilation, reintervention or rupture, MBEs or overall survival on extensive repaired TAAD. Thus, antiplatelet therapy can be administered as indicated on extensive repaired TAAD.

Nano-silica anti-icing coatings for protecting wind-power turbine fan blades.

Wind power is a promising electricity source. Nevertheless, wind turbine blade icing can cause severe problems in turbine operation. In this study, SiO2 spherical nanoparticles (∼90 nm), produced by RF (radio frequency) plasma spheroidization, were mixed with E51, PDMS, and ethyl acetate, and sprayed on the surface of aluminum plates and regular power windmill fan blades which were already coated with polyurethane primer. XPS and IR spectroscopies revealed the development of SiC and SiPh (Ph = phenolic ring) bonds, whose formation should be favored by the ultrasound and curing processes at 50 °C. The integrity of the coating/substrate interface, whose strength is ascribed to hydrogen bonds, was maintained after 100 icing-melting cycles. The coatings display superhydrophobic behavior and excellent anti-icing performance, along with stability in abrasion, sunlight and self-cleaning ability towards solid pollutants.

Pandemic effect on corporate financial asset holdings: Precautionary or return-chasing?

This study empirically investigates whether and how the COVID-19 pandemic affects corporate financial asset holdings. We find that firms with higher pandemic exposure are less likely to hold financial assets. Mechanism analyses suggest that the return-chasing rationale dominates the precautionary motive concerning the pandemic effect on corporate financial asset holdings. Furthermore, firms prefer to liquidate highly liquid financial assets to fill the pandemic-induced liquidity shortage. This study contributes to the economic consequences of the COVID-19 pandemic regarding corporate portfolio choice, and sheds light on corporate resilience to crises.

ISC-MTI: An IPFS and smart contract-based framework for machine learning model training and invocation.

Due to centralized storage, centralization problems are common in machine learning model training and invocation, which makes train data and trained models extremely vulnerable to tampering and stealing. A safe framework for training and invoking models called ISC-MTI (IPFS (InterPlanetary File System) and Smart Contract-Based Method for Storage and Invocation of Machine Learning Mobel) is proposed in this paper. The framework uses IPFS as the storage solution, EOS (Enterprise Operation System) blockchain as the smart contract platform, RSA and AES as the implementation of encrypted communication. The Action responsible for invoking the training data and trained models in the smart contract and the model training, uploading, and invoking methods are designed. The experimental results demonstrate that ISC-MTI can improve the safety of model training and invocation with losing a little efficiency. Simultaneously, ISC-MTI can provide anti-theft model capabilities, traceability, tamper resistance, reliability, and privacy for the process.

Impact of frozen elephant trunk on the outcomes of thoracoabdominal aortic repair with normothermic iliac perfusion.

Background: Frozen elephant trunk technique (FET) has been proven to provide an excellent landing zone for second-stage thoracoabdominal (TA) aortic repair. The aim of this study was to evaluate the impact of FET in TA aortic repair with normothermic iliac perfusion. Methods: From January 2008 to December 2019, 144 patients undergoing TA repair with normothermic iliac perfusion were enrolled in this study. Early and mid-term outcomes of patients with previous FET implantation (group A, n = 62) were compared with patients without previous FET implantation (group B, n = 82). The logistic regression analysis was performed to investigate the risk factors for adverse events, which were defined as early death, permanent stroke, permanent paraplegia, or permanent renal failure necessitating dialysis. Results: The proximal aortic clamp time and operating time was 14.26 ± 5.57 min and 357.40 ± 94.51 respectively in group A, which were both significantly shorter than that in group B (18.67 ± 5.24 min and 18.67 ± 5.24 min). The incidence of adverse event was significantly lower in group A than that in group B (9.7% vs. 25.6%, P = 0.027). There was no significant difference between two groups with regard to other complications or late outcomes. In addition, age >50 years, a Ccr < 90 ml/min/1.73 m2 and the operating time were identified as significant risk factors through logistic regression analysis for adverse events of TA repair. Conclusions: The FET technique simplifies the operative technique of proximal anastomosis, decreases the operating time and improves the early outcomes in TA repair, whereas does not provide a significant benefit with regard to late outcomes. Long-term follow-up and studies with larger sample sizes are necessary for further confirmation.

Interleukin 2 receptor subunit beta as a novel hub gene plays a potential role in the immune microenvironment of abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is potentially life threatening and characterized by immune-inflammatory cell infiltration and extracellular matrix degradation. Currently, pharmacotherapy mainly aims to control risk factors without reversion of the dilated aorta. This study analyzed the immune-inflammatory response and identified the immune-related hub genes of AAA. METHOD: Gene Expression Omnibus datasets (GSE57691, GSE47472 and GSE7084) were downloaded. After identification of GSE57691 differentially expressed genes (DEGs), weighted gene co-expression network analysis of the DEGs was performed. Through enrichment analysis of each module and screening in Immunology Database and Analysis Portal, immune-related hub genes were identified via protein-protein interaction (PPI) network construction and lasso regression. CIBERSORT was utilized to analyze AAA immune infiltration. The correlations between the immune-related hub genes and infiltrating immune cells were investigated. Receiver operating characteristic (ROC) curve analysis was performed to determine immune-related hub gene cutoff values, which were validated in GSE47472 and GSE7084. RESULT: In GSE57691, 1,018 DEGs were identified. Five modules were identified in the co-expression network. The blue and green modules were found to be related to immune-inflammatory responses, and 61 immune-related genes were identified. PPI and lasso regression analyses identified FOS, IL-6 and IL2RB as AAA immune-related hub genes. CIBERSORT analysis indicated significantly increased infiltration of naive B cells, memory activated CD4 T cells, follicular helper T cells, monocytes and M1 macrophages and significantly decreased infiltration of M2 macrophages in AAA compared with normal samples. IL2RB was more strongly associated with immune infiltration in AAA than were FOS and IL6. The IL2RB area under the ROC curve (AUC) value was > 0.9 in both the training and validation set, demonstrating its strong, stable diagnostic value in AAA. CONCLUSION: AAA and normal samples had different immune infiltration statuses. IL2RB was identified as an immune-related hub gene and a potential hub gene with significant diagnostic value in AAA.

lncRNA DARS-AS1 Modulates TSPAN1-Mediated ITGA2 Hypomethylation by Interaction with miR-194-5p Thus Promoting Ovarian Cancer Progression.

Objective: Ovarian cancer (OC) is usually called the "silent killer" due to its asymptomatic characteristics until advanced stages, thus being a significant threat to female health worldwide. In this work, we characterized an oncogenic DARS-AS1 role in OC. Methods: The aggressiveness behaviors of the OC cell model were examined by CCK-8 assay, transwell invasion assay, flow cytometry, and immunoblotting analysis of apoptosis-related proteins. Interactions of miR-194-5p with lncRNA DARS-AS1 or TSPAN1 and of TSPAN1 with ITGA2 were validated by using a luciferase activity assay and chromatin immunoprecipitation (ChIP) assay. Results: The OC cell model exhibited overexpressed lncRNA DARS-AS1 compared to normal cells. lncRNA DARS-AS1 knockdown led to reduced OC cell growth and metastasis while inducing the apoptosis in the OC cell model. lncRNA DARS-AS1 positively regulated TSPAN1 expression by binding with miR-194-5p and TSPAN1-mediated ITGA2 hypomethylation in OC cells. Further rescue function studies demonstrated that lncRNA DARS-AS1 affected OC cell viability, migration, invasion, and apoptosis ability by modulating miR-194-5p and TSPAN1 expressions. Conclusion: Our work demonstrates that lncRNA DARS-AS1 promotes OC progression by modulating TSPAN1 and ITGA2 hypomethylation by binding with miR-194-5p.