NEDD4L is a promoter for angiogenesis and cell proliferation in human umbilical vein endothelial cells.

Dysregulated angiogenesis leads to neovascularization, which can promote or exacerbate various diseases. Previous studies have proved that NEDD4L plays an important role in hypertension and atherosclerosis. Hence, we hypothesized that NEDD4L may be a critical regulator of endothelial cell (EC) function. This study aimed to define the role of NEDD4L in regulating EC angiogenesis and elucidate their underlying mechanisms. Loss- and gain-of-function of NEDD4L detected the angiogenesis and mobility role in human umbilical vein endothelial cells (HUVECs) using Matrigel tube formation assay, cell proliferation and migration. Pharmacological pathway inhibitors and western blot were used to determine the underlying mechanism of NEDD4L-regulated endothelial functions. Knockdown of NEDD4L suppressed tube formation, cell proliferation and cell migration in HUVECs, whereas NEDD4L overexpression promoted these functions. Moreover, NEDD4L-regulated angiogenesis and cell progression are associated with the phosphorylation of Akt, Erk1/2 and eNOS and the expression of VEGFR2 and cyclin D1 and D3. Mechanically, further evidence was confirmed by using Akt blocker MK-2206, Erk1/2 blocker U0126 and eNOS blocker L-NAME. Overexpression NEDD4L-promoted angiogenesis, cell migration and cell proliferation were restrained by these inhibitors. In addition, overexpression NEDD4L-promoted cell cycle-related proteins cyclin D1 and D3 were also suppressed by Akt blocker MK-2206, Erk1/2 blocker U0126 and eNOS blocker L-NAME. Our results demonstrated a novel finding that NEDD4L promotes angiogenesis and cell progression by regulating the Akt/Erk/eNOS pathways.

Maximizing synchronizability of networks with community structure based on node similarity.

In reality, numerous networks have a community structure characterized by dense intra-community connections and sparse inter-community connections. In this article, strategies are proposed to enhance synchronizability of such networks by rewiring a certain number of inter-community links, where the research scope is complete synchronization on undirected and diffusively coupled dynamic networks. First, we explore the effect of adding links between unconnected nodes with different similarity levels on network synchronizability and find that preferentially adding links between nodes with lower similarity can improve network synchronizability more than that with higher similarity, where node similarity is measured by our improved Asymmetric Katz (AKatz) and Asymmetric Leicht-Holme-Newman (ALHNII) methods from the perspective of link prediction. Additional simulations demonstrate that the node similarity-based link-addition strategy is more effective in enhancing network synchronizability than the node centrality-based methods. Furthermore, we apply the node similarity-based link-addition or deletion strategy as the valid criteria to the rewiring process of inter-community links and then propose a Node Similarity-Based Rewiring Optimization (NSBRO) algorithm, where the optimization process is realized by a modified simulated annealing technique. Simulations show that our proposed method performs better in optimizing synchronization of such networks compared with other centrality-based heuristic methods. Finally, simulations on the Rössler system indicate that the network structure optimized by the NSBRO algorithm also leads to better synchronizability of coupled oscillators.

Long-range surface plasmon resonance sensor based on dielectric/silver coated hollow fiber with enhanced figure of merit.

A long-range surface plasmon resonance (LRSPR) sensor based on dielectric/silver-coated hollow fiber (HF) is proposed. It can detect the refractive index (RI) of sensed liquid filled in the hollow core of the sensor. A HF LRSPR sensor with 90-nm-thick silver layer and 260-nm-thick OC300 layer is fabricated. Experiments are taken to evaluate the performance of the sensor by measuring the transmission spectra. Theoretical analysis based on a ray model is also taken, and the results agree well with the experimental results. The proposed sensor has similar sensitivity but much smaller SPR dip width than the silver-coated HF SPR sensor. Thus figure of merit of the sensor is enhanced approximately five times. The stability of the sensor is also improved because the dielectric layer acts as a protection layer for the damageable silver layer.

The Impact of Vp-Porin, an Outer Membrane Protein, on the Biological Characteristics and Virulence of Vibrio Parahaemolyticus.

Porins are crucial proteins located in the outer membrane that directly influence antimicrobial resistance mechanisms and virulence in bacteria. In this study, a porin gene (Vp-porin) was cloned in V. parahaemolyticus, and the function of Vp-Porin in biological characteristics and virulence was investigated. The results of sequence analysis showed that Vp-Porin is highly conserved in Vibrio spp., and the predicted 3D structure showed it could form a 20-strand transmembrane ß-barrel domian. Membrane permeabilization provides evidence that the membrane integrity of ∆Vp-porin was damaged and the sensitivity to tetracycline, polymyxin B, rifampicin and cephalothin of ∆Vp-porin obviously increased. In addition, loss of Vp-porin damaged motility due to downregulated flagellar synthesis. In addition, ∆Vp-porin exhibited attenuated cytotoxicity to Tetrahymena. The relative survival rate of Tetrahymena infection with ∆Vp-porin was 86%, which is much higher than that with WT (49%). Taken together, the results of this study indicate that Vp-Porin in V. parahaemolyticus plays various roles in biological characteristics in membrane integrity, antimicrobial resistance and motility and contributes to virulence.

Neddylation pathway regulates the proliferation and survival of macrophages.

Neddylation is a new type of protein post-translational modification which adds the ubiquitin-like molecule Nedd8 to target proteins. The well-identified targets of neddylation are cullins, which serve as essential components of Cullin-RING E3 ligases (CRL). It is reported that inhibition of neddylation repressed NF-κB-mediated proinflammatory cytokine production in macrophages. However, the role of neddylation in the proliferation and survival of macrophages has not been well defined. Here we report that partial inactivation of the neddylation pathway by a specific Nedd8-activating enzyme E1 (NAE) inhibitor MLN4924 reduced LPS-induced production of the proinflammatory cytokines TNF-α and IL-6 without obvious impairment of cell viability. However, persistent and severe inactivation of neddylation by MLN4924 significantly inhibited cell proliferation by inducing G2 phase cell-cycle arrest and further triggered cell death by inducing apoptosis in RAW264.7 macrophages. Mechanistic analysis revealed that inactivation of neddylation blocked cullin neddylation, inhibited CRL E3 ligase activity, and thus led to the accumulation of CRL substrates, resulting in cell-cycle arrest, DNA damage response and apoptosis. The findings revealed that neddylation serves as an important signaling pathway regulating the proliferation and survival of macrophages.

Hollow fiber surface plasmon resonance sensor for the detection of liquid with high refractive index.

A new kind of surface plasmon resonance (SPR) sensor based on silver-coated hollow fiber (HF) structure for the detection of liquids with high refractive index (RI) is presented. Liquid sensed medium with high RI is filled in the hollow core of the HF and its RI can be detected by measuring the transmission spectra of the HF SPR sensor. The designed sensors with different silver thicknesses are fabricated and the transmission spectra for filled liquids with different RI are measured to investigate the performances of the sensors. Theoretical analysis is also carried out to evaluate the performance. The simulation results agree well with the experimental results. Factors that might affect sensitivity and detection accuracy of the sensor are discussed. The highest sensitivity achieved is 6,607 nm/RIU, which is comparable to the sensitivities of the other reported fiber SPR sensors.

Flexible silver-coated hollow fibers for remote Raman spectroscopic measurements.

A Raman remote spectroscopy system was established by using flexible hollow fibers (HFs) as laser excitation fiber and signal collection fiber. Experimental evaluations with various optical fiber combinations were carried out. Experiments were conducted by using silver-coated HFs as both remote transmission fiber and sample cells for liquid sample detection. Good linearity for concentration detection of liquid was obtained with clean background and signal enhancement. Theoretical analysis was carried out to optimize the length of the liquid cell. Measured data show good agreement with the simulation result. HF has shown potentiality in applications for remote and noninvasive Raman detection.

Corrigendum: The Regulation Mechanisms and Clinical Application of MicroRNAs in Myocardial Infarction: A Review of the Recent 5 Years.

[This corrects the article DOI: 10.3389/fcvm.2021.809580.].

The Regulation Mechanisms and Clinical Application of MicroRNAs in Myocardial Infarction: A Review of the Recent 5 Years.

Myocardial infarction (MI) is the most frequent end-point of cardiovascular pathology, leading to higher mortality worldwide. Due to the particularity of the heart tissue, patients who experience ischemic infarction of the heart, still suffered irreversible damage to the heart even if the vascular reflow by treatment, and severe ones can lead to heart failure or even death. In recent years, several studies have shown that microRNAs (miRNAs), playing a regulatory role in damaged hearts, bring light for patients to alleviate MI. In this review, we summarized the effect of miRNAs on MI with some mechanisms, such as apoptosis, autophagy, proliferation, inflammatory; the regulation of miRNAs on cardiac structural changes after MI, including angiogenesis, myocardial remodeling, fibrosis; the application of miRNAs in stem cell therapy and clinical diagnosis; other non-coding RNAs related to miRNAs in MI during the past 5 years.

Blockage of autophagy pathway enhances Salmonella tumor-targeting.

Previous studies have shown that strains of Salmonella typhimurium specifically target tumors in mouse models of cancer. In this study, we report that tumor-targeting Salmonella typhimurium A1-R (A1-R) or VNP20009 induced autophagy in human cancer cells, which serves as a defense response. Functionally, by knockdown of essential autophagy genes Atg5 or Beclin1 in bacteria-infected cancer cells, the autophagy pathway was blocked, which led to a significant increase of intracellular bacteria multiplication in cancer cells. Genetic inactivation of the autophagy pathway enhanced A1-R or VNP20009-mediated cancer cell killing by increasing apoptotic activity. We also demonstrate that the combination of pharmacological autophagy inhibitors chloroquine (CQ) or bafilomycin A1 (Baf A1) with tumor-targeting A1-R or VNP20009 significantly enhanced cancer-cell killing compared with Salmonella infection alone. These findings provide a proof-of-concept of combining autophagy inhibitors and tumor-targeting Salmonella to enhance cancer-cell killing.