AAAKB: A manually curated database for tracking and predicting genes of Abdominal aortic aneurysm (AAA).

Abdominal aortic aneurysm (AAA), an extremely dangerous vascular disease with high mortality, causes massive internal bleeding due to aneurysm rupture. To boost the research on AAA, efforts should be taken to organize and link the information about AAA-related genes and their functions. Currently, most researchers screen through genetic databases manually, which is cumbersome and time-consuming. Here, we developed "AAAKB" a manually curated knowledgebase containing genes, SNPs and pathways associated with AAA. In order to facilitate researchers to further explore the mechanism network of AAA, AAAKB provides predicted genes that are potentially associated with AAA. The prediction is based on the protein interaction information of genes collected in the database, and the random forest algorithm (RF) is used to build the prediction model. Some of these predicted genes are differentially expressed in patients with AAA, and some have been reported to play a role in other cardiovascular diseases, illustrating the utility of the knowledgebase in predicting novel genes. Also, AAAKB integrates a protein interaction visualization tool to quickly determine the shortest paths between target proteins. As the first knowledgebase to provide a comprehensive catalog of AAA-related genes, AAAKB will be an ideal research platform for AAA. Database URL: http://www.lqlgroup.cn:3838/AAAKB/.

Cathepsin B S-nitrosylation promotes ADAR1-mediated editing of its own mRNA transcript via an ADD1/MATR3 regulatory axis.

Genetic information is generally transferred from RNA to protein according to the classic "Central Dogma". Here, we made a striking discovery that post-translational modification of a protein specifically regulates the editing of its own mRNA. We show that S-nitrosylation of cathepsin B (CTSB) exclusively alters the adenosine-to-inosine (A-to-I) editing of its own mRNA. Mechanistically, CTSB S-nitrosylation promotes the dephosphorylation and nuclear translocation of ADD1, leading to the recruitment of MATR3 and ADAR1 to CTSB mRNA. ADAR1-mediated A-to-I RNA editing enables the binding of HuR to CTSB mRNA, resulting in increased CTSB mRNA stability and subsequently higher steady-state levels of CTSB protein. Together, we uncovered a unique feedforward mechanism of protein expression regulation mediated by the ADD1/MATR3/ADAR1 regulatory axis. Our study demonstrates a novel reverse flow of information from the post-translational modification of a protein back to the post-transcriptional regulation of its own mRNA precursor. We coined this process as "Protein-directed EDiting of its Own mRNA by ADAR1 (PEDORA)" and suggest that this constitutes an additional layer of protein expression control. "PEDORA" could represent a currently hidden mechanism in eukaryotic gene expression regulation.

Defogging Algorithm Based on Polarization Characteristics and Atmospheric Transmission Model.

We propose a polarized image defogging algorithm according to the sky segmentation results and transmission map optimization. Firstly, we propose a joint sky segmentation method based on scene polarization information, gradient information and light intensity information. This method can effectively segment the sky region and accurately estimate the global parameters such as atmospheric polarization degree and atmospheric light intensity at infinite distance. Then, the Gaussian filter is used to solve the light intensity map of the target, and the information of the polarization degree of the target is solved. Finally, based on the segmented sky region, a three-step transmission optimization method is proposed, which can effectively suppress the halo effect in the reconstructed image of large area sky region. Experimental results shows that defogging has a big improvement in the average gradient of the image and the grayscale standard deviation. Therefore, the proposed algorithm provides strong defogging and can improve the optical imaging quality in foggy scenes by restoring fog-free images.

Hsp90 S-nitrosylation at Cys521, as a conformational switch, modulates cycling of Hsp90-AHA1-CDC37 chaperone machine to aggravate atherosclerosis.

Endothelial dysfunction is the initial process of atherosclerosis. Heat shock protein 90 (Hsp90), as a molecular chaperone, plays a crucial role in various cardiovascular diseases. Hsp90 function is regulated by S-nitrosylation (SNO). However, the precise role of SNO-Hsp90 in endothelial dysfunction during atherosclerosis remains unclear. We here identified Hsp90 as a highly S-nitrosylated target in endothelial cells (ECs) by biotin switch assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The elevation of SNO-Hsp90 was observed in atherosclerotic human and rodent aortas as well as in oxidized LDL (oxLDL)-treated ECs. Inhibition of inducible nitric oxide synthase (iNOS) or transfection with Hsp90 cysteine 521 (Cys521) mutation plasmid decreased the level of SNO-Hsp90 in oxLDL-cultured ECs. Coimmunoprecipitation and proximity ligation assay demonstrated that SNO-Hsp90 at Cys521 suppressed the interaction between Hsp90 and activator of Hsp90 ATPase activity 1 (AHA1), but promoted the association of Hsp90 and cell division cycle 37 (CDC37). Hsp90 Cys521 mutation increased endothelial nitric oxide synthase (eNOS) activity and inhibited nuclear factor kappa-B (NF-κB) signaling, thereby increasing nitric oxide (NO) bioavailability and alleviating endothelial adhesion, inflammation and oxidative stress in oxLDL-treated ECs. Also, administration of endothelial-specific adeno-associated viruses of Cys521-mutated Hsp90 significantly mitigated vascular oxidative stress, macrophage infiltration and atherosclerosis lesion areas in high fat diet-fed ApoE-/- mice. In conclusion, SNO-Hsp90 at Cys521, that serves as a conformational switch, disrupts Hsp90/AHA1 interaction but promotes recruitment of CDC37 to exacerbate atherosclerosis.

S-nitrosylation of c-Jun N-terminal kinase mediates pressure overload-induced cardiac dysfunction and fibrosis.

Cardiac fibrosis (CF) is an irreversible pathological process that occurs in almost all kinds of cardiovascular diseases. Phosphorylation-dependent activation of c-Jun N-terminal kinase (JNK) induces cardiac fibrosis. However, whether S-nitrosylation of JNK mediates cardiac fibrosis remains an open question. A biotin-switch assay confirmed that S-nitrosylation of JNK (SNO-JNK) increased significantly in the heart tissues of hypertrophic patients, transverse aortic constriction (TAC) mice, spontaneously hypertensive rats (SHRs), and neonatal rat cardiac fibroblasts (NRCFs) stimulated with angiotensin II (Ang II). Site to site substitution of alanine for cysteine in JNK was applied to determine the S-nitrosylated site. S-Nitrosylation occurred at both Cys116 and Cys163 and substitution of alanine for cysteine 116 and cysteine 163 (C116/163A) inhibited Ang II-induced myofibroblast transformation. We further confirmed that the source of S-nitrosylation was inducible nitric oxide synthase (iNOS). 1400 W, an inhibitor of iNOS, abrogated the profibrotic effects of Ang II in NRCFs. Mechanistically, SNO-JNK facilitated the nuclear translocation of JNK, increased the phosphorylation of c-Jun, and induced the transcriptional activity of AP-1 as determined by chromatin immunoprecipitation and EMSA. Finally, WT and iNOS-/- mice were subjected to TAC and iNOS knockout reduced SNO-JNK and alleviated cardiac fibrosis. Our findings demonstrate an alternative mechanism by which iNOS-induced SNO-JNK increases JNK pathway activity and accelerates cardiac fibrosis. Targeting SNO-JNK might be a novel therapeutic strategy against cardiac fibrosis.

Melatonin Alleviates Cardiac Function in Sepsis-Caused Myocarditis via Maintenance of Mitochondrial Function.

Melatonin (N-acetyl-5-methoxytryptamine) has been shown to have a cardioprotective effect against myocarditis. However, the mechanisms underlying the protective role of melatonin (MLT) in sepsis-induced myocarditis are yet to be revealed. In this study, MLT was administrated to mice, 14 days before cecal ligation puncture surgery. Echocardiography results showed that MLT alleviated cardiac dysfunction in sepsis-induced myocarditis. Furthermore, MLT reduced cardiac inflammation by inhibiting the expression of Il-1α, Il-1ß, Il-6, and Mcp-1 messenger RNA (mRNA) levels. The RNA sequencing (RNA-seq) assays with heart tissues showed that MLT maintains the mitochondrial function in sepsis-caused myocarditis. Additionally, the production of reactive oxygen species (ROS) in heart tissues was suppressed by MLT. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced myocarditis, the results showed that MLT alleviated cardiac damage by regulating mitochondrial function and mitochondrial ROS.

Melatonin Alleviates Renal Injury in Mouse Model of Sepsis.

Melatonin (N-acetyl-5-methoxytryptamine; MLT) has been shown to have a renal-protective effect against kidney injury. However, the mechanisms underlying the protective role of MLT in sepsis-induced renal injury are yet to be revealed. In this study, MLT alleviated renal dysfunction with the increase of BUN (blood urea nitrogen) and SCR (serum creatinine) and reduction of fibrosis in the CLP (cecal ligation puncture) model. RNA-seq analysis showed that MLT repressed the oxidant stress in response to kidney injury. Our in vitro study showed that MLT suppresses LPS-induced accumulation of ROS (reactive oxygen species) production via SOD2 downregulation and Nox4 upregulation in HK-2 cells. Furthermore, we found that MLT alleviated the inflammatory response, with the mRNA-level reduction of Il-1α, Il-1ß, Mcp-1, and Tgf-ß1. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced acute kidney injury, the results showed that MLT alleviated renal damage by regulating the production of ROS.

Inhibition of HSP90 S-nitrosylation alleviates cardiac fibrosis via TGFß/SMAD3 signalling pathway.

BACKGROUND AND PURPOSE: Effective anti-fibrotic therapeutic solutions are unavailable so far. The heat shock protein 90 (HSP90) exerts deleterious effects in some fibrotic diseases. S-nitrosylation (SNO) of HSP90 affects its own function. However, little is known about its role in pathological stress. Here, we investigated the effect of SNO-HSP90 on cardiac fibrosis. EXPERIMENTAL APPROACH: SNO-HSP90 level was measured by biotin-switch. SNO sites were identified through mass spectrometry. S-nitrosylation site-mutated plasmids or adeno-associated virus, gene deletion, and pharmacological antagonists were used to identify the contribution of SNO-HSP90 to myocardial fibrosis. KEY RESULTS: SNO-HSP90 level was positively correlated with fibrosis marker expression in hearts from patients and significantly higher in fibrotic hearts from spontaneously hypertensive rats and mice subjected to transverse aortic constriction, as well as in angiotensin II- or isoprenaline-treated neonatal rat cardiac fibroblasts. S-nitrosylated site of HSP90 at cysteine 589 was identified. Inhibition of SNO-HSP90 by Cys589 mutation reduced fibrosis in angiotensin II- or isoprenaline-treated cardiac fibroblasts. Administration of recombinant adeno-associated virus of Cys589 mutation improved heart function and alleviated fibrosis in transverse aortic constriction mice. Mechanistically, SNO-HSP90 stimulated binding of TGFß receptor 2 to HSP90, in response to fibrotic stimuli, followed by increased phosphorylation and nuclear translocation of SMAD3. Additionally, inducible NO synthase (iNOS) deficiency or the iNOS inhibitor, 1400W, reduced SNO-HSP90 levels and activation of the TGFß/SMAD3 signalling pathway. CONCLUSIONS AND IMPLICATIONS: Genetic or pharmacological inhibition of SNO-HSP90 mitigates fibrosis through blocking the TGFß/SMAD3 signalling pathway, providing a potential therapy for cardiac remodelling.

HINT1 (Histidine Triad Nucleotide-Binding Protein 1) Attenuates Cardiac Hypertrophy Via Suppressing HOXA5 (Homeobox A5) Expression.

BACKGROUND: Cardiac hypertrophy is an important prepathology of, and will ultimately lead to, heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. This study aims to elucidate the effects and mechanisms of HINT1 (histidine triad nucleotide-binding protein 1) in cardiac hypertrophy and heart failure. METHODS: HINT1 was downregulated in human hypertrophic heart samples compared with nonhypertrophic samples by mass spectrometry analysis. Hint1 knockout mice were challenged with transverse aortic constriction surgery. Cardiac-specific overexpression of HINT1 mice by intravenous injection of adeno-associated virus 9 (AAV9)-encoding Hint1 under the cTnT (cardiac troponin T) promoter were subjected to transverse aortic construction. Unbiased transcriptional analyses were used to identify the downstream targets of HINT1. AAV9 bearing shRNA against Hoxa5 (homeobox A5) was administrated to investigate whether the effects of HINT1 on cardiac hypertrophy were HOXA5-dependent. RNA sequencing analysis was performed to recapitulate possible changes in transcriptome profile.Coimmunoprecipitation assays and cellular fractionation analyses were conducted to examine the mechanism by which HINT1 regulates the expression of HOXA5. RESULTS: The reduction of HINT1 expression was observed in the hearts of hypertrophic patients and pressure overloaded-induced hypertrophic mice, respectively. In Hint1-deficient mice, cardiac hypertrophy deteriorated after transverse aortic construction. Conversely, cardiac-specific overexpression of HINT1 alleviated cardiac hypertrophy and dysfunction. Unbiased profiler polymerase chain reaction array showed HOXA5 is 1 target for HINT1, and the cardioprotective role of HINT1 was abolished by HOXA5 knockdown in vivo. Hoxa5 was identified to affect hypertrophy through the TGF-ß (transforming growth factor ß) signal pathway. Mechanically, HINT1 inhibited PKCß1 (protein kinase C ß type 1) membrane translocation and phosphorylation via direct interaction, attenuating the MEK/ERK/YY1 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/yin yang 1) signal pathway, downregulating HOXA5 expression, and eventually attenuating cardiac hypertrophy. CONCLUSIONS: HINT1 protects against cardiac hypertrophy through suppressing HOXA5 expression. These findings indicate that HINT1 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.

Integration of Low-Cost GNSS and Monocular Cameras for Simultaneous Localization and Mapping.

Low-cost Global Navigation Satellite System (GNSS) receivers and monocular cameras are widely used in daily activities. The complementary nature of these two devices is ideal for outdoor navigation. In this paper, we investigate the integration of GNSS and monocular camera measurements in a simultaneous localization and mapping system. The proposed system first aligns the coordinates between two sensors. Subsequently, the measurements are fused by an optimization-based scheme. Our system can function in real-time and obtain the absolute position, scale, and attitude of the vehicle. It achieves a high accuracy without a preset map and also has the capability to work with a preset map. The system can easily be extended to create other forms of maps or for other types of cameras. Experimental results on a popular public dataset are presented to validate the performance of the proposed system.

Backplane aberration calibration of spatial light modulators using a phase-retrieval algorithm.

The calibration and correction of backplane aberration of a liquid-crystal spatial light modulator (LCSLM) are important for its proper functioning. To simplify the calibration procedurally, we study a random-illumination-phase-retrieval-based method. Our method improves the convergence of the phase-retrieval-based calibration and reduces the calibration complexity. However, the cross talk of the LCSLM deteriorates the calibration performance. We determined the relationship between the probability density function of the random phases and the light-intensity pattern and proposed an algorithm to compensate for the cross talk. We conducted a series of simulations to test the performance of the above-mentioned algorithms. The results show that our algorithms are effective and outperform other methods.

Oversaturated part-based visual tracking via spatio-temporal context learning.

Partial occlusion is one of the key challenging factors in a robust visual tracking method. To solve this issue, part-based trackers are widely explored; most of them are computationally expensive and therefore infeasible for real-time applications. Context information around the target has been used in tracking, which was recently renewed by a spatio-temporal context (STC) tracker. The fast Fourier transform adopted in STC equips it with high efficiency. However, the global context used in STC alleviates the performance when dealing with occlusion. In this paper, we propose an oversaturated part-based tracker based on spatio-temporal context learning, which tracks objects based on selected parts with spatio-temporal context learning. Furthermore, a structural layout constraint and a novel model update strategy are utilized to enhance the tracker's anti-occlusion ability and to deal with other appearance changes effectively. Extensive experimental results demonstrate our tracker's superior robustness against the original STC and other state-of-art methods.

L1 adaptive control of uncertain gear transmission servo systems with deadzone nonlinearity.

This paper deals with the adaptive control problem of Gear Transmission Servo (GTS) systems in the presence of unknown deadzone nonlinearity and viscous friction. A global differential homeomorphism based on a novel differentiable deadzone model is proposed first. Since there exist both matched and unmatched state-dependent unknown nonlinearities, a full-state feedback L1 adaptive controller is constructed to achieve uniformly bounded transient response in addition to steady-state performance. Finally, simulation results are included to show the elimination of limit cycles, in addition to demonstrating the main results in this paper.