Investigating the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles in atherosclerosis treatment.

BACKGROUND: Carthamus tinctorius L., a traditional herbal medicine used for atherosclerosis (AS), lacks a clear understanding of its therapeutic mechanisms. This study aimed to investigate the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles (CDNVs) in AS treatment. METHODS: CDNVs were isolated and characterized using improved isolation methods. Transmission electron microscopy, nanoparticle tracking analysis, and protein analysis confirmed their morphology, size, and protein composition. Small RNA sequencing was performed to identify the miRNA profile of CDNVs, and bioinformatics analysis was used to determine their potential biological roles. In vivo biodistribution and toxicity studies were conducted in mice to assess the stability and safety of orally administered CDNVs. The anti-atherosclerotic effects of CDNVs were evaluated in ApoE-/- mice through plaque burden analysis. The protective effects of CDNVs on ox-LDL-treated endothelial cells were assessed through proliferation, apoptosis, reactive oxygen species activation, and monocyte adhesion assays. miRNA and mRNA sequencing of CDNV-treated endothelial cells were performed to explore their regulatory effects and potential target genes. RESULTS: CDNVs were successfully isolated and purified from Carthamus tinctorius L. tissue lysates. They exhibited a saucer-shaped or cup-shaped morphology, with an average particle size of 142.6 ± 0.7 nm, and expressed EV markers CD63 and TSG101. CDNVs contained proteins, small RNAs, and metabolites, including the therapeutic compound HSYA. Small RNA sequencing identified 95 miRNAs, with 10 common miRNAs accounting for 72.63% of the total miRNAs. These miRNAs targeted genes involved in cell adhesion, apoptosis, and cell proliferation, suggesting their relevance in cardiovascular disease. Orally administered CDNVs were stable in the gastrointestinal tract, absorbed into the bloodstream, and accumulated in the liver, lungs, heart, and aorta. They significantly reduced the burden of atherosclerotic plaques in ApoE-/- mice and exhibited superior effects compared to HSYA. In vitro studies demonstrated that CDNVs were taken up by HUVECs, promoted proliferation, attenuated ox-LDL-induced apoptosis and ROS activation, and reduced monocyte adhesion. CDNV treatment resulted in significant changes in miRNA and mRNA expression profiles of HUVECs, with enrichment in inflammation-related genes. CXCL12 was identified as a potential direct target of miR166a-3p. CONCLUSION: CDNVs isolated from Carthamus tinctorius L. tissue lysates represent a promising oral therapeutic option for cardiovascular diseases. The delivery of miRNAs by CDNVs regulates inflammation-related genes, including CXCL12, in HUVECs, suggesting their potential role in modulating endothelial inflammation. These findings provide valuable insights into the therapeutic potential of CDNVs and their miRNAs in cardiovascular disease.

Toll-like receptor activation regulates the paracrine effect of adipose-derived mesenchymal stem cells on reversing osteoarthritic phenotype of chondrocytes.

BACKGROUND: The therapeutic efficacy of intra-articular mesenchymal stem cells (MSCs) injection for patients with osteoarthritis (OA) currently exhibits inconsistency, and the underlying mechanism remains elusive. It has been postulated that the immunomodulatory properties and paracrine activity of MSCs might be influenced by the inflammatory micro-environment within osteoarthritic joints, potentially contributing to this observed inconsistency. METHODS: Adipose-derived MSCs (ADSCs) were isolated from SD rats and pre-treated with Toll-like receptor 3 (TLR3) agonist Poly I:C or Toll-like receptor 4 (TLR4) agonist LPS. The pre-treated ADSCs were then co-cultured with IL-1ß-induced osteoarthritic chondrocytes using a Transwell system to analyze the paracrine effect of ADSCs on reversing the osteoarthritic phenotype of chondrocytes. RESULTS: RT-PCR and Western blot analysis revealed that Poly I:C and LPS pre-treatments up-regulated the expression of IL-10 and IL-6 in ADSCs, respectively. Furthermore, only Poly I:C-preconditioned ADSCs significantly promoted proliferation while inhibiting apoptosis in IL-1ß-treated chondrocytes. Additionally, Poly I:C-preconditioned ADSCs downregulated MMP13 expression while upregulating aggrecan and collagen II expression levels in IL-1ß-treated chondrocytes. CONCLUSIONS: TLR3 activation polarizes ADSCs into an immunomodulatory phenotype distinct from TLR4 activation, exerting differential effects on reversing the osteoarthritic phenotype of chondrocytes; thus indicating that MSCs' paracrine effect regulated by TLRs signaling impacts the efficacy of intra-articular MSCs injection.

Physiological and Biochemical Properties of Cotton Seedlings in Response to Cu2+ Stress.

Copper(II) (Cu2+) is essential for plant growth and development. However, high concentrations are extremely toxic to plants. We investigated the tolerance mechanism of cotton under Cu2+ stress in a hybrid cotton variety (Zhongmian 63) and two parent lines with different Cu2+ concentrations (0, 0.2, 50, and 100 µM). The stem height, root length, and leaf area of cotton seedlings had decreased growth rates in response to increasing Cu2+ concentrations. Increasing Cu2+ concentration promoted Cu2+ accumulation in all three cotton genotypes' roots, stems, and leaves. However, compared with the parent lines, the roots of Zhongmian 63 were richer in Cu2+ and had the least amount of Cu2+ transported to the shoots. Moreover, excess Cu2+ also induced changes in cellular redox homeostasis, causing accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Conversely, antioxidant enzyme activity increased, while photosynthetic pigment content decreased. Our findings indicated that the hybrid cotton variety fared well under Cu2+ stress. This creates a theoretical foundation for the further analysis of the molecular mechanism of cotton resistance to copper and suggests the potential of the large-scale planting of Zhongmian 63 in copper-contaminated soils.

N6-Methyladenosine Demethylase FTO (Fat Mass and Obesity-Associated Protein) as a Novel Mediator of Statin Effects in Human Endothelial Cells.

BACKGROUND: N6-methyladenosine (m6A) plays a critical role in various biological processes. However, no study has addressed the role of m6A modification in the statin-induced protection of endothelial cells (ECs). METHODS: Quantitative real-time polymerase chain reaction and Western blotting analyses were used to study the expression of m6A regulatory genes in atorvastatin-treated ECs. Gain- and loss-of-function assays, methylated RNA immunoprecipitation analysis, and dual-luciferase reporter assays were performed to clarify the function of FTO (fat mass and obesity-associated protein) in ECs. RESULTS: Atorvastatin decreased FTO protein expression in ECs. The knockdown of FTO enhanced the mRNA and protein expression of KLF2 (Kruppel-like factor 2) and eNOS (endothelial NO synthase) but attenuated TNFα (tumor necrosis factor alpha)-induced VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) expression, as well as the adhesion of monocytes to ECs. Conversely, FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. Subsequent investigations demonstrated that KLF2 and eNOS are functionally critical targets of FTO. Mechanistically, FTO interacted with KLF2 and eNOS transcripts and regulated their expression in an m6A-dependent manner. After FTO silencing, KLF2 and eNOS transcripts with higher levels of m6A modification in their 3' untranslated regions were captured by YTHDF3 (YT521-B homology m6A RNA-binding protein 3), resulting in mRNA stabilization and the induction of KLF2 and eNOS protein expression. CONCLUSIONS: FTO might serve as a novel molecular target to modulate endothelial function in vascular diseases.

Identification of a long noncoding RNA Gm17501 as a novel negative regulator of cardiac hypertrophy.

Pathological cardiac hypertrophy is an independent risk factor for the development of heart failure. Long noncoding RNAs (lncRNAs), an emerging class of non-protein-coding transcripts, are involved in regulation of multiple cardiac diseases through diverse molecular mechanism, whereas the role of cytoplasmic lncRNAs in regulating cardiac hypertrophy remains unclear. In this study, we identified a novel and functional long noncoding RNA Gm17501, which was predominantly expressed in the cytoplasm of cardiomyocytes. The expression level of lncRNA Gm17501 was altered in cardiac hypertrophy induced by pressure overload and phenylephrine treatment. Moreover, lncRNA Gm17501 expression was decreased in the heart tissue of patients with heart failure. Silencing lncRNA Gm17501 aggravated cardiac hypertrophy under pathological stress. Inhibition of lncRNA Gm17501 did not alter the expression of nearby genes but decreased mRNA level of calcium handling proteins which were involved in cardiac contraction. Therefore, the cytoplasmic lncRNA Gm17501 might protect cardiomyocytes against hypertrophy, possibly by maintaining calcium signaling pathway.

Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

General Model for Defect Dynamics in Ionizing-Irradiated SiO2 -Si Structures.

Irradiation damage is a key issue for the reliability of semiconductor devices under extreme environments. For decades, the ionizing-irradiation-induced damage in transistors with silica-silicon (SiO2 -Si) structures at room temperature has been modeled by a uniform generation of E'γ centers in the bulk silica region through the capture of irradiation-induced holes, and an irreversible conversion from E'γ to Pb centers at the SiO2 /Si interface through reactions with hydrogen molecules (H2 ). However, the traditional model fails to explain experimentally-observed dose dependence of the defect concentrations, especially at low dose rate. Here, it is proposed that the generation of E'γ centers is decelerated because the holes migrate dispersively in disordered silica and the diffusion coefficient decays as the irradiation goes on. It is also proposed that the conversion between E'γ and Pb centers is reversible because the huge activation energy of the reverse reaction can be reduced by a "phonon-kick" effect of the vibrational energy of H2 and Pb centers transferred from nearby nonradiative recombination centers. Experimental studies are carried out to demonstrate that the derived analytic model based on these two new concepts can consistently explain the fundamental but puzzling dose dependence of the defect concentrations for an extremely wide dose rate range.

Primary colonic melanoma: a rare entity.

Gastrointestinal melanoma is usually metastatic in origin, and primary melanoma within the gastrointestinal tract is rarely reported. Colon is considered to be an extremely uncommon site for primary melanomas. Herein, we report the first case of a large primary melanoma within the transverse colon with gastric involvement. CT scan found a mass within the colon, which seemed to connect to the gastric antrum. Esophagogastroscopy showed an ulcerated lesion in the greater curvature of the stomach. Subsequent colonoscopy identified a large ulcerated lesion rendering significant stenosis of the transverse colon. Biopsy following colonoscopy indicated a diagnosis of colonic melanoma based on pathological findings, which identified submucosal malignant melanoma cells with epithelioid and spindle features. Immunohistochemical stains were positive for S-100, HMB-45, Vimentin, and Melan-A. A series of clinical and imaging examinations revealed no suspicious primary cutaneous or ocular lesions. The diagnosis of primary colonic melanoma was considered. A radical transverse colectomy with subtotal gastrectomy were conducted subsequently. Definite diagnosis of primary colonic melanoma can be established after ruling out the possibility of being a metastasis from other more common primary sites. Primary colonic melanomas are a challenge to diagnose and often need a multidisciplinary treatment approach, including surgery, BRAF-targeted therapy, and immunotherapy.

Cardiac Nestin+ Mesenchymal Stromal Cells Enhance Healing of Ischemic Heart through Periostin-Mediated M2 Macrophage Polarization.

Mesenchymal stromal cells (MSCs) show potential for treating cardiovascular diseases, but their therapeutic efficacy exhibits significant heterogeneity depending on the tissue of origin. This study sought to identify an optimal source of MSCs for cardiovascular disease therapy. We demonstrated that Nestin was a suitable marker for cardiac MSCs (Nes+cMSCs), which were identified by their self-renewal ability, tri-lineage differentiation potential, and expression of MSC markers. Furthermore, compared with bone marrow-derived MSCs (Nes+bmMSCs) or saline-treated myocardial infarction (MI) controls, intramyocardial injection of Nes+cMSCs significantly improved cardiac function and decreased infarct size after acute MI (AMI) through paracrine actions, rather than transdifferentiation into cardiac cells in infarcted heart. We further revealed that Nes+cMSC treatment notably reduced pan-macrophage infiltration while inducing macrophages toward an anti-inflammatory M2 phenotype in ischemic myocardium. Interestingly, Periostin, which was highly expressed in Nes+cMSCs, could promote the polarization of M2-subtype macrophages, and knockdown or neutralization of Periostin remarkably reduced the therapeutic effects of Nes+cMSCs by decreasing M2 macrophages at lesion sites. Thus, the present work systemically shows that Nes+cMSCs have greater efficacy than do Nes+bmMSCs for cardiac healing after AMI, and that this occurs at least partly through Periostin-mediated M2 macrophage polarization.

Hydrogel composite of lanthanum and Halorubrum ejinoor sp. cell lysate as an adsorbing material.

OBJECTIVES: Although halophilic archaea are rich in natural environments, their biotechnological applications are not as prevalent as those of other extremophiles, such as thermophiles and alkaliphiles. This study presents an simple method to prepare a hydrogel composite using crude cell lysate of a halophilic archaea, Halorubrum ejinoor sp. (H.e.) which was isolated from a saline lake in Inner Mongolia, China. Furthermore, formation mechanism and potential applications of the hydrogel as an adsorbing material are discussed. RESULTS: Halorubrum ejinoor sp. (H.e.) cell lysate was firstly prepared by adding pure water onto the H.e. cell pellet, followed by a short incubation at 60 °C. The cell lysate was injected into different metal ion (or H+) solutions to obtain the hydrogel composite. It was observed that H+, Fe3+, La3+, Cu2+, and Ca2+ induced gelation of the cell lysate, while Fe2+, Co2+, Ni2+, Mg2+, Na+, and K+ did not. DNA and extracellular polysaccharides (EPS) in the H.e. cell lysate were found to be responsible for the gelation reaction. These results suggest that DNA and EPS should be crosslinked by metal ions (or H+) and form a networked structure in which the metal ion (or H+) serves as an anchor point. Potential application of the hydrogel as an adsorbing material was explored using La3+-induced H.e. hydrogel composite. The hydrogel composite can adsorb the fluoride, phosphate and DNA-binding carcinogenic agents, such as acridine orange. CONCLUSIONS: The simplicity and cost effectiveness of the preparation method might make H.e. hydrogel a promising adsorbing material. This work is expected to expand the technical applications of haloarchaea.

End-to-end automatic differentiation of the coronavirus disease 2019 (COVID-19) from viral pneumonia based on chest CT.

PURPOSE: In the absence of a virus nucleic acid real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test and experienced radiologists, clinical diagnosis is challenging for viral pneumonia with clinical symptoms and CT signs similar to that of coronavirus disease 2019 (COVID-19). We developed an end-to-end automatic differentiation method based on CT images to identify COVID-19 pneumonia patients in real time. METHODS: From January 18 to February 23, 2020, we conducted a retrospective study and enrolled 201 patients from two hospitals in China who underwent chest CT and RT-PCR tests, of which 98 patients tested positive for COVID-19 (118 males and 83 females, with an average age of 42 years). Patient CT images from one hospital were divided among training, validation and test datasets with an 80%:10%:10% ratio. An end-to-end representation learning method using a large-scale bi-directional generative adversarial network (BigBiGAN) architecture was designed to extract semantic features from the CT images. The semantic feature matrix was input for linear classifier construction. Patients from the other hospital were used for external validation. Differentiation accuracy was evaluated using a receiver operating characteristic curve. RESULTS: Based on the 120-dimensional semantic features extracted by BigBiGAN from each image, the linear classifier results indicated that the area under the curve (AUC) in the training, validation and test datasets were 0.979, 0.968 and 0.972, respectively, with an average sensitivity of 92% and specificity of 91%. The AUC for external validation was 0.850, with a sensitivity of 80% and specificity of 75%. Publicly available architecture and computing resources were used throughout the study to ensure reproducibility. CONCLUSION: This study provides an efficient recognition method for coronavirus disease 2019 pneumonia, using an end-to-end design to implement targeted and effective isolation for the containment of this communicable disease.

Improved Performance of SRAM-Based True Random Number Generator by Leveraging Irradiation Exposure.

Encryption is an important step for secure data transmission, and a true random number generator (TRNG) is a key building block in many encryption algorithms. Static random-access memory (SRAM) chips can be easily available sources of true random numbers, benefiting from noisy SRAM cells whose start-up values flip between different power-on cycles. Embarking from this phenomenon, a novel performance (i.e., randomness and throughput) improvement method of SRAM-based TRNG is proposed, and its implementation can be divided into two phases: irradiation exposure and hardware postprocessing. As the randomness of original SRAM power-on values is fairly low, ionization irradiation is utilized to enhance its randomness, and the min-entropy can increase from about 0.03 to above 0.7 in the total ionizing irradiation (TID) experiments. Additionally, while the data remanence effect hampers obtaining random bitstreams with high speed, the ionization irradiation can also weaken this impact and improve the throughput of TRNG. In the hardware postprocessing stage, Secure Hash Algorithm 256 (SHA-256) is implemented on a Field Programmable Gate Array (FPGA) with clock frequency of 200 MHz. It can generate National Institute of Standards and Technology (NIST) SP 800-22 compatible true random bitstreams with throughput of 178 Mbps utilizing SRAM chip with 1 Mbit memory capacity. Furthermore, according to different application scenarios, the throughput can be widely scalable by adjusting clock frequency and SRAM memory capacity, which makes the novel TRNG design applicable for various Internet of Things (IOT) devices.

A Sprayed Graphene Pattern-Based Flexible Strain Sensor with High Sensitivity and Fast Response.

Flexible strain sensors have a wide range of applications in biomedical science, aerospace industry, portable devices, precise manufacturing, etc. However, the manufacturing processes of most flexible strain sensors previously reported have usually required high manufacturing costs and harsh experimental conditions. Besides, research interests are often focused on improving a single attribute parameter while ignoring others. This work aims to propose a simple method of manufacturing flexible graphene-based strain sensors with high sensitivity and fast response. Firstly, oxygen plasma treats the substrate to improve the interfacial interaction between graphene and the substrate, thereby improving device performance. The graphene solution is then sprayed using a soft PET mask to define a pattern for making the sensitive layer. This flexible strain sensor exhibits high sensitivity (gauge factor ~100 at 1% strain), fast response (response time: 400⁻700 µs), good stability (1000 cycles), and low overshoot (<5%) as well. Those processes used are compatible with a variety of complexly curved substrates and is expected to broaden the application of flexible strain sensors.

Vasodilator-stimulated phosphoprotein (VASP), a novel target of miR-4455, promotes gastric cancer cell proliferation, migration, and invasion, through activating the PI3K/AKT signaling pathway.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs which play important roles in the carcinogenesis of gastric cancer (GC). Expression profiling of miRNAs in paired gastric cancer and adjacent normal gastric tissues has demonstrated that miR-4455 is down-regulated in gastric cancer tissues, but its functional role in the carcinogenesis of GC had not previously been investigated. AIMS: The purpose of this study was to investigate the functional and biological mechanisms of miR-4455 in the progression of GC, in vitro. METHODS: Expression of miR-4455 was compared in human GC tissue samples and paired adjacent normal tissue samples. The in vitro effects of miR-4455 expression in MGC-803 cells on their proliferation, invasion, and migration were assessed by MTT assays and 5-bromo-2'-deoxyuridine staining, matrigel-invasion analysis and wound healing assays. Bioinformatics analysis (using PicTar, target scan and miRBase target) was used to identify potential targets for miR-4455, and the luciferase reporter assay, qRT-PCR and Western-blotting analyses were used to confirm VASP as the target of miR-4455. In addition, the effects of downregulation of VASP on the activation of PI3K/AKT signaling pathway were measured using Western-blot analysis. RESULTS: The expression of miR-4455 was markedly down-regulated in gastric cancer tissues vs. adjacent normal tissues, and miR-4455 expression inhibited the proliferation, invasion and migration of MGC-803 GC cells in vitro. Luciferase reporter assays revealed that miR-4455 inhibited VASP expression by targeting the 3'-UTR sequence of VASP. Furthermore, silencing of VASP markedly inhibited the activation of the PI3K/AKT signaling pathway. CONCLUSION: Our results suggest that miR-4455 functions as a tumor suppressor in gastric cancer, by targeting VASP leading to activation of the PI3K/AKT signaling pathway and the inhibition of VASP mediated proliferation, migration and invasion of gastric cancer cells.

High Dynamic Micro Vibrator with Integrated Optical Displacement Detector for In-Situ Self-Calibration of MEMS Inertial Sensors.

The scale factor drifts and other long-term instability drifts of Micro-Electro-Mechanical System (MEMS) inertial sensors are the main contributors of the position and orientation errors in high dynamic environments. In this paper, a novel high dynamic micro vibrator, which could provide high acceleration and high angular rate rotation with integrated optical displacement detector, is proposed. Commercial MEMS inertial sensors, including 3-axis accelerometer and 6-axis inertial measurement unit which is about 3 mm * 3 mm * 1 mm with 19 mg, could be bonded on the vibration platform of the micro vibrator to perform in-situ during the self-calibration procedure. The high dynamic micro vibrator is fabricated by a fully-integrated MEMS process, including lead zirconate titanate (PZT) film deposition, PZT and electrodes patterning, and structural ion etching. The optical displacement detector, using vertical-cavity surface-emitting laser (VCSEL) and photoelectric diodes (PD), is integrated on the top of the package to measure the 6-DOF vibrating displacement with the detecting resolution of 150 nm in the range of 500 μm. The maximum out-of-plane acceleration of the z-axis vibrating platform loaded with commercial 3-axis accelerometer (H3LIS331DL) achieves above 16 g and the maximum angular velocity achieves above 720°/s when the driving voltage is ±6 V.

High and Temperature-Insensitive Piezoelectric Strain in Alkali Niobate Lead-free Perovskite.

With growing concern over world environmental problems and increasing legislative restriction on using lead and lead-containing materials, a feasible replacement for lead-based piezoceramics is desperately needed. Herein, we report a large piezoelectric strain (d33*) of 470 pm/V and a high Curie temperature (Tc) of 243 °C in (Na0.5K0.5)NbO3-(Bi0.5Li0.5)TiO3-BaZrO3 lead-free ceramics by doping MnO2. Moreover, excellent temperature stability is also observed from room temperature to 170 °C (430 pm/V at 100 °C and 370 pm/V at 170 °C). Thermally stimulated depolarization currents (TSDC) analysis reveals the reduced defects and improved ferroelectricity in MnO2-doped piezoceramics from a macroscopic view. Local poling experiments and local switching spectroscopy piezoresponse force microscopy (SS-PFM) demonstrates the enhanced ferroelectricity and domain mobility from a microscopic view. Distinct grain growth and improvement in phase angle may also account for the enhancement of piezoelectric properties.

Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial inflammation.

Although many studies have described the roles of microRNAs (miRNAs) in the modulation of the endothelial response to shear stress, the mechanisms remain incompletely understood. Here, we demonstrate that miR-34a expression in endothelial cells was downregulated by atheroprotective physiological high shear stress (HSS), whereas it was upregulated by atheroprone oscillatory shear stress (OSS). Blockade of endogenous miR-34a dramatically decreased basal vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression levels. Conversely, miR-34a overexpression increased the protein levels of VCAM-1 and ICAM-1, consequently promoting monocyte adhesion to endothelial cells. Furthermore, miR-34a overexpression attenuated HSS-mediated suppression of VCAM-1 protein expression on endothelial cells, but promoted HSS-induced ICAM-1 expression. In addition, the OSS induction of endothelial cell VCAM-1 and ICAM-1 was suppressed by using an miR-34a inhibitor, which led to a reduction of monocyte adhesion to endothelial cells. Mechanistically, sirtuin 1 overexpression partially prevented miR-34a-induced VCAM-1 and ICAM-1 expression. Subsequent investigation demonstrated that miR-34a increased nuclear factor κB (NF-κB) p65 subunit (also known as RelA) acetylation (on residue Lys310), and silencing NF-κB signaling reduced miR-34a-induced VCAM-1 and ICAM-1 protein expression. These results demonstrate that miR-34a is involved in the flow-dependent regulation of endothelial inflammation.

A Nonlinearity Mitigation Method for a Broadband RF Front-End in a Sensor Based on Best Delay Searching.

The cognitive radio wireless sensor network (CR-WSN) is experiencing more and more attention for its capacity to automatically extract broadband instantaneous radio environment information. Obtaining sufficient linearity and spurious-free dynamic range (SFDR) is a significant premise of guaranteeing sensing performance which, however, usually suffers from the nonlinear distortion coming from the broadband radio frequency (RF) front-end in the sensor node. Moreover, unlike other existing methods, the joint effect of non-constant group delay distortion and nonlinear distortion is discussed, and its corresponding solution is provided in this paper. After that, the nonlinearity mitigation architecture based on best delay searching is proposed. Finally, verification experiments, both on simulation signals and signals from real-world measurement, are conducted and discussed. The achieved results demonstrate that with best delay searching, nonlinear distortion can be alleviated significantly and, in this way, spectrum sensing performance is more reliable and accurate.

AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress.

AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress.