Highly Sensitive Biomimetic Crack Pressure Sensor with Selective Frequency Response.

High-sensitivity sensors in practical applications face the issue of environmental noise interference, requiring additional noise reduction circuits or filtering algorithms to improve the signal-to-noise ratio (SNR). To address this issue, this study proposes a biomimetic crack pressure sensor with selective frequency response based on hydrogel dampers. The core of this research is to construct a biomimetic crack pressure sensor with selective frequency response using the high-pass filtering characteristics of gelatin-chitosan hydrogels. This design, inspired by the slit sensilla and stratum corneum structure of spider legs, delves into the material properties and principles of hydrogel dampers, exploring their application in biomimetic crack pressure sensors, including parameter selection, structural design, and performance optimization. By delving into the nuanced characteristics and working principles of hydrogel dampers, their integration in biomimetic crack pressure sensors is examined, focusing on aspects like parameter selection, structural engineering, and performance enhancement to selectively sieve out low-frequency noise and transmit target vibrational signals. Experimental results demonstrate that this innovative sensor, while suppressing low-frequency vibration signals, can selectively detect high-frequency signals with high sensitivity. At different vibration frequencies, the relative change in resistance exceeds 200%, and the sensor sensitivity is 7 × 104 kPa-1. Furthermore, this sensor was applied to human voice detection, and the corresponding results verified its frequency-selective performance evidently. This study not only proposes a new design for pressure sensors but also offers fresh insights into the application of biomimetic crack pressure sensors in intricate environments.

Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Effect of doramectin on programmed cell death pathway in glioma cells

Purpose Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. Methods In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. Results We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. Conclusion Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy (AU)

Macrophage polarization states in atherosclerosis.

Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.

Effect of doramectin on programmed cell death pathway in glioma cells.

PURPOSE: Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. METHODS: In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. RESULTS: We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. CONCLUSION: Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy.

Protective Effects of MicroRNA-200b-3p Encapsulated by Mesenchymal Stem Cells-Secreted Extracellular Vesicles in Myocardial Infarction Via Regulating BCL2L11.

Background Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)-secreted EVs-derived miR-200b-3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl-2-like protein 11) . Methods and Results EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR-200b-3p for overexpression were injected into MI mice. The effect of miR-200b-3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR-200b-3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR-200b-3p on MI mice. EVs from MSCs were successfully extracted. MSCs-EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR-200b-3p further enhanced the effects of MSCs-EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR-200b-3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR-200b-3p-modified MSCs-EVs in MI mice. Conclusions A summary was obtained that miR-200b-3p-encapsulated MSCs-EVs protect against MI-induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.

Doramectin inhibits glioblastoma cell survival via regulation of autophagy in vitro and in vivo.

Glioblastoma (GBM) is one of the most widespread and lethal types of cancer. However, there are currently no drugs or therapeutic strategies that can completely cure GBM. Doramectin (DRM) has a broad range of activities against endoparasites and ectoparasites, and is extensively used in livestock. In the present study, the effect of DRM on the induction of autophagy in U87 and C6 GBM and glioma cell lines, as well as the mechanism of autophagy, were examined. First, transmission electron microscopy, plasmid transfection and western blot analysis demonstrated that DRM could induce autophagy in U87 and C6 cells in vitro. Next, MTT and colony formation assays revealed that DRM­induced autophagy prevented U87 and C6 cell viability and colony formation ratio. In addition, DRM­induced autophagy promoted U87 and C6 cell apoptosis, as indicated by DAPI analysis and flow cytometry. Furthermore, transcriptome analysis demonstrated that DRM modulated a number of genes and pathways involved in autophagy. In a nude mouse xenograft model, immunohistochemical staining and the TUNEL assay demonstrated that the effect of DRM on the tumor was consistent with that in vivo. These data indicated that DRM induced autophagy mainly by blocking the PI3K/AKT/mTOR signaling pathway in GBM cells. DRM­induced autophagy promoted the inhibition of GBM cell proliferation and apoptosis in vitro and in vivo. The present study suggested that DRM may be an effective drug for the treatment of GBM.

Lymphotoxin beta receptor is associated with regulation of microRNAs expression and nuclear factor-kappa B activation in lipopolysaccharides (LPS)-stimulated vascular smooth muscle cells.

BACKGROUND: The aim of present study is to investigate the role of lymphotoxin beta receptor (Ltßr) in lipopolysaccharides (LPS)-induced inflammation in vascular smooth muscle cells (VSMCs) and whether its effects are mediated by modulating microRNAs (miRNAs) and nuclear factor-kappa B (NF-κB). METHODS: Mouse aortic smooth muscle cell (SMC) line (MOVAS cells) were transduced with short hairpin Ltßr (shLtßr) and mRNA and protein expression level of Ltßr were measured by qPCR and Western blot in shLtßr-transduced cells. Lentiviral vector-transduced (control) and lentiviral vector/shLtßr-transduced MOVAS cells were stimulated with LPS (1 µg/mL) for 0, 16, or 24 h. Then the mRNA and protein levels of Ltßr, interleukin-18 (IL-18), p-p65, p65 and vascular cell adhesion molecule 1 (VCAM-1) were measured by real-time quantitative polymerase chain reaction (qPCR), Western blot and enzyme-linked immunosorbent assay (ELISA). Different miRNAs expression in LPS-stimulated normal and shLtßr-transduced cells were detected by small RNA sequencing (smRNA-seq). RESULTS: The mRNA and protein expression of Ltßr was significantly downregulated in shLtßr-transduced cells. LPS-increased the mRNA and protein levels of Ltßr, IL-18, p-p65 and VCAM-1 in were attenuated by shLtßr transducing compared with LPS-stimulated control group. Moreover, LPS treatment induced 10 upregulated and 64 downregulated miRNAs in shLtßr-transduced cells compared with control cells. Moreover, miR-146b-5p and miR-27a-5p levels were significantly decreased in shLtßr-transduced cells. CONCLUSIONS: Our results show for the first time that the role of Ltßr in regulating inflammatory response in LPS-stimulated VSMCs via modulating miRNAs and NF-κB pathway. Our findings might provide valuable information with respect to better understanding in the treatment of cardiovascular diseases, such as atherosclerosis.

Kidney-secreted erythropoietin lowers lipidemia via activating JAK2-STAT5 signaling in adipose tissue.

BACKGROUND: Dyslipidemia is commonly observed in various kidney diseases, renal specific secreted erythropoietin (EPO) may participate in this process. However, how this process is regulated remains elusive. METHOD: Dyslipidemia was evaluated in chronic kidney disease and ischemia kidney injury animal model. Primary cultured adipocytes were harvested to investigate the lipid metabolic effect of EPO. Lipidemia was evaluated in EPO treated animals. Blood samples from cardiac surgery-induced kidney injury patient were collected to assess correlationship between EPO and lipidemia. FINDINGS: We found a decrease in secreted EPO and hypertriglyceridemia in chronic kidney disease (CKD) mice. In contrast, in renal ischemia animal model, increased EPO triggered by hypoxia signaling activation, was accompanied by decreased triglyceride (TG) in serum. Mechanistically, circulating EPO modulated JAK2-STAT5 signaling, which in turn enhanced lipid catabolism in peripheral adipose tissue and contributed to dysregulated lipidemia. Delivering of recombinant EPO into both wild type and CKD mice suppressed TG in serum by accelerating lipid catabolism in adipose tissue. In a cohort of patients diagnosed with acute kidney injury after cardiopulmonary bypass surgery, the decreased TG and cholesterol negatively correlated with increased EPO in serum. INTERPRETATION: This study depicted a new mechanism by which renal secreted EPO controlled lipidemia in kidney diseases including chronic kidney disease. Circulating EPO stimulated lipid catabolism by targeting JAK2-STATA5 signaling in peripheral adipose tissue, providing new therapeutic target for dyslipidemia treatment. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81700640 and 81970608).

Serum alpha 1-antitrypsin predicts severe acute kidney injury after cardiac surgery.

BACKGROUND: Human alpha 1-antitrypsin (A1AT) is involved in the pathophysiological process underlying ischemic acute kidney injury (AKI). To test the hypothesis that serum A1AT (sA1AT) is a predictor for severe AKI after cardiopulmonary bypass (CPB), we conducted a prospective cohort study in 201 patients undergoing cardiac surgery. METHODS: We collected blood and urine samples, and analyzed the sA1AT and other injury biomarkers during the perioperative period. Severe AKI is defined as Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3, and overall AKI is defined as KDIGO stage 1, 2, or 3. RESULTS: Ninety-one (45.3%) patients developed overall AKI, and 22 (10.9%) among them developed severe AKI after operation. sA1AT level spiked 2 hours after surgery in patients who subsequently developed severe AKI, while serum creatinine peaked 12 hours after operation. Higher postoperative sA1AT independently correlated to the development of severe AKI [OR, 1.54 (1.17-2.03); P=0.002]. The highest quartile of postoperative sA1AT level was associated with 6-fold higher hazards of severe AKI compared to the lowest quartile. Higher sA1AT levels were correlated with longer stays in the intensive care unit and the hospital. For predicting severe AKI, the AUC of sA1AT 2 hours after CPB reached 0.814. After combining with urine T cell immunoglobulin mucin-1 and clinical model, the AUC improved to 0.923. CONCLUSIONS: In summary, sA1AT is a valuable predictor of severe AKI development and prolonged ICU and hospital stays in patients after cardiac surgery.

The role of deep hypothermic circulatory arrest in surgery for renal or adrenal tumor with vena cava thrombus: a single-institution experience.

BACKGROUND: The aim of this study was to review our experience in managing renal or adrenal tumors with level III or IV inferior vena cava thrombus by using deep hypothermic circulatory arrest (DHCA), and to evaluate survival outcomes. METHODS: Between September 2004 and March 2016, we treated 33 patients with renal or adrenal malignancy tumor and thrombus extending into the inferior vena cava. Patients were identified according to radiographic records and operative findings. Clinicopathological and operative characteristics were recorded, and comparisons of clinical and operative characteristics through DHCA were performed. A Cox regression model was used to determine predictors of perioperative mortality. RESULTS: Twenty-one out of 33 patients with level III (n = 15), level IV (n = 5), or level II (n = 1) renal or adrenal tumors were treated surgically through cardiopulmonary bypass (CPB) with DHCA, and 12 patients with level II or III tumors were treated surgically through normothermic CPB. Three complications were observed, and one death occurred perioperatively, owing to multiple organ failure. The overall perioperative mortality was 4.7%. There were significant differences in the clinicopathological characteristics, operative duration, estimated blood loss, transfusions and hospital stay depending on use of DHCA. Multivariate analysis indicated that the operative duration (OR, 3.78; P < 0.001), estimated blood loss (OR, 1.08; P = 0.02), and transfusion (OR, 2.13; P = 0.038) during/after surgery were positively associated with higher mortality and morbidity. DHCA failed to reach statistical significance (P = 0.378). CONCLUSIONS: Use of CPB and DHCA to treat renal or adrenal tumors allows for complete tumor resection, especially at the T4 stage. Although it can cause physical damage, this technique does not increase operative risk and is a relatively safe approach.

A Frequency-Domain Multipath Parameter Estimation and Mitigation Method for BOC-Modulated GNSS Signals.

As multipath is one of the dominating error sources for high accuracy Global Navigation Satellite System (GNSS) applications, multipath mitigation approaches are employed to minimize this hazardous error in receivers. Binary offset carrier modulation (BOC), as a modernized signal structure, is adopted to achieve significant enhancement. However, because of its multi-peak autocorrelation function, conventional multipath mitigation techniques for binary phase shift keying (BPSK) signal would not be optimal. Currently, non-parametric and parametric approaches have been studied specifically aiming at multipath mitigation for BOC signals. Non-parametric techniques, such as Code Correlation Reference Waveforms (CCRW), usually have good feasibility with simple structures, but suffer from low universal applicability for different BOC signals. Parametric approaches can thoroughly eliminate multipath error by estimating multipath parameters. The problems with this category are at the high computation complexity and vulnerability to the noise. To tackle the problem, we present a practical parametric multipath estimation method in the frequency domain for BOC signals. The received signal is transferred to the frequency domain to separate out the multipath channel transfer function for multipath parameter estimation. During this process, we take the operations of segmentation and averaging to reduce both noise effect and computational load. The performance of the proposed method is evaluated and compared with the previous work in three scenarios. Results indicate that the proposed averaging-Fast Fourier Transform (averaging-FFT) method achieves good robustness in severe multipath environments with lower computational load for both low-order and high-order BOC signals.

[Brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique for Stanford type A aortic dissection: analysis of 23 cases].

OBJECTIVE: To assess the clinical outcomes of brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique for treatment of Stanford type A aortic dissection. METHODS: Twenty-three patients with Stanford type A aortic dissection requiring arch replacement underwent brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique. The operations were performed within 72 h (20 cases) or 3-14 days (3 cases) after the onset of aortic dissection. RESULTS: There was no perioperative death in these cases. The mean extracorporeal circulation time was 209∓52 min, the aortic cross clamp time was 85∓21 min, and the mean chest tube output within the first 24 h after the operation was 570∓263 mL; none of the patients required chest reopening for management of bleeding. Postoperative acute renal failure requiring hemodialysis occurred in 3 cases, transient neurologic dysfunction in 2 cases, paraplegia in case and hematosepsis in 1 case. No such complications as permanent neurologic deficit or postoperative visceral malperfusion occurred in these cases. All the patients survived and were discharged from hospital without experiencing severe complications in the follow-up for 6-18 months. CONCLUSION: Brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique is a safe and simple procedure with controllable bleeding and can serve as an optional procedure for aortic arch replacement.

Plasma level of advanced oxidation protein products as a novel biomarker of acute lung injury following cardiac surgery.

This study was designed to test the hypothesis that whether the plasma level of advanced oxidant protein products (AOPPs) would be useful for the clinical diagnosis of acute lung injury (ALI) following cardiac surgery with the technique of cardiopulmonary bypass (CPB). In this prospective study, seventy consecutive adults undergoing open heart surgery with CPB were included and assigned into the ALI (n = 18) and non-ALI (n = 52) groups according to the American-European Consensus Criteria. Plasma concentrations of AOPPs were measured at baseline, postoperative 1 h, 12 h, 24 h, and 48 h. Eighteen patients (25.7 %) developed ALI after surgery. The plasma levels of AOPPs in the ALI group were significantly increased and remained considerably higher at all time points after operation (all P < 0.05). Multivariate logistic regression analysis revealed that the plasma level of AOPPs at 1 h after operation was an independent predictor for the diagnosis of ALI (OR 1.164; 95 % CI 1.068-1.269; P = 0.001). Plasma level of AOPPs could serve as an early biomarker of the incidence of ALI in adult patients who underwent open cardiac surgery with the technique of CPB.

Advanced oxidation protein products in predicting acute kidney injury following cardiac surgery.

To test the hypothesis whether serum advanced oxidation protein products (AOPP) are associated with increased acute kidney injury (AKI) after cardiopulmonary bypass (CPB) and could serve as a biomarker in this aspect, we performed a prospective cohort study. Thirty-five (22.3%) patients developed AKI, and 32 age- and gender-matched patients without AKI were selected as control. Serum AOPP 1 h after CPB were significantly higher among AKI patients compared with non-AKI patients (81.8 ± 18.6 versus 67.4 ± 12.5 µmol/L, p < 0.001), with an area under the receiver-operating characteristic (ROC) curve of 0.714. An optimal serum AOPP 1 h after CPB cutoff of 69.9 µmol/L had a sensitivity of 74%, specificity of 63% and a positive predictive value of 68% for predicting AKI. These results demonstrated that serum AOPP might be an early biomarker for AKI after CPB.

Is off-pump coronary artery bypass grafting superior to drug-eluting stents for the treatment of coronary artery disease? A meta-analysis of randomized and nonrandomized studies.

BACKGROUND: As drug-eluting stent (DES) has almost overcome the disadvantage of frequent restenosis, off-pump coronary artery bypass grafting (OPCAB) has been introduced to avoid complications of cardiopulmonary bypass. However, which approach may promise better outcomes for patients with coronary artery disease remains controversial. METHODS: Three databases were searched. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE), all-cause death, target vessel revascularization (TVR), repeat revascularization (RRV), myocardial infarction (MI), and cerebrovascular events (CVE). The relative risk (RR) was calculated as the summary statistic. RESULTS: 11,452 patients from 22 studies were included, of which 4949 patients underwent OPCAB and 6503 patients received DES. The cumulative rates of MACCE (RR [95% CI]=0.43 [0.34, 0.54], P<0.00001), all-cause death (RR [95% CI]=0.56 [0.33, 0.96], P=0.03), TVR (RR [95% CI]=0.33 [0.21, 0.53], P<0.00001), RRV (RR [95% CI]=0.22 [0.11, 0.42], P<0.00001) and MI (RR [95% CI]=0.13 [0.05, 0.29], P<0.00001) at 3 years were all lower in OPCAB group. The incidences of in-hospital death (RR [95% CI]=1.31 [0.81, 2.13], P=0.27) and MI (RR [95% CI]=1.03 [0.60, 1.78], P=0.92) were not different between groups, but the rate of in-hospital CVE was lower (RR [95% CI]=2.6355 [1.0033, 6.9228], P=0.05) in DES group. CONCLUSIONS: OPCAB presents better long-term outcomes of MACCE, all-cause mortality, TVR, RRV and MI but uncertain outcome of postoperative CVE without influencing the incidences of in-hospital death and MI.

Serum salusin-α levels are inversely correlated with the presence and severity of coronary artery disease.

We sought to measure serum salusin-α levels in patients with coronary artery disease (CAD) and to assess their correlation with the severity of the disease. We enrolled 172 patients with CAD and 91 controls. We assessed the angiographic severity of CAD by coronary atherosclerosis index (CAI) and detected serum salusin-α levels by enzyme-linked immunosorbent assay (ELISA). We demonstrated that CAD patients had significantly lower serum salusin-α levels compared to controls. Moreover, serum salusin-α levels were independently and negatively correlated with the presence and severity of CAD. These findings indicated that salusin-α might serve as a potential biomarker for predicting the development and progression of CAD.