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Spinal Cord ischemia-reperfusion injury (SCII) is one of the most destructive complications in thoracic-abdominal aortic surgery, which can cause physical abnormalities, paralysis and even brain death. Evidence has shown that perillaldehyde (PAH) can ameliorate rat's cerebra ischemia-reperfusion injury. However, the effect of PAH on SCII remains unknown. The current study established SCII rat models and oxygen and glucose deprivation/reoxygenation-induced BV2 microglia models to explore whether PAH could alleviate SCII symptoms and to investigate underlying mechanism. SCII rats underwent severe neurologic motor dysfunction and histopathologic injury compared with the normal rats, which are exhibited by loss of motor neurons and decrease of nissl bodies. Treatment with PAH significantly ameliorated motor dysfunction and neuron damage. PAH downregulated the expression of NLR family pyrin domain containing 3, cleaved/pro caspase-1, interleukin-1β and interleukin-18 in spinal cord tissues of SCII rats. Besides, the contents of oxidative stress-related factors superoxide dismutase, manganese-dependent superoxide dismutase, catalase and glutathione peroxidase were significantly increased and malondialdehyde content was decreased after PAH treatment. PAH treatment upregulated the expression of nuclear factor-E2-related factor 2 and heme oxygenase-1 in spinal cord tissues of SCII rats. Our in vitro study confirmed that PAH inhibited microglial activation by activating the nuclear factor-E2-related factor 2/heme oxygenase-1 pathway, exhibited by alleviated inflammation and oxidative stress. This study elucidates that PAH has the potential value for treating SCII, which provides an experimental basis for clinical trials in the future. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play a significant role in regulating diverse physiological processes, and are regarded as novel diagnostic biomarkers. However, the sensitive and reliable miRNA detection remains a huge challenge. Herein, we propose a proximity ligated initiated magnesium ion (Mg2+)-dependent DNAzyme-powered signal cascade for sensitive, accurate and reliable detection of miRNAs. Three signal amplification processes are involved in this approach, including the target miRNA recycle, DNAzyme powered substrate cleavage, and catalytic hairpin reaction (CHA). Based on this, the approach shows a low limit of detection of 523 aM and a wide detection range of 7 orders of magnitudes, which is comparable or superior to most of the former miRNA detection methods. In addition, the approach also possesses a high selectivity to target miRNA, suggesting a potential promising future of the approach for rapid detection of miRNAs in the application of developing novel tools for skin cancer diagnosis, and recovery evaluation. [Display omitted] • Sensitive and reliable detection of miRNAs is highly-desired. • We propose a proximity ligated initiated magnesium ion (Mg2+)-dependent DNAzyme-powered signal cascade strategy for miRNA detection. • Target mediated proximity ligation endows the method a high specificity. • The approach shows a low limit of detection of 523 aM and a wide detection range of 7 orders of magnitudes. [ABSTRACT FROM AUTHOR]

In order to systematically analyze functionally relevant dynamical correlations within macromolecular complexes, we have developed computational methods based on the normal mode analysis of an elastic network model. First, we define two types of dynamical correlations (fluctuation-based and density-based), which are computed by summing up contributions from all low-frequency normal modes up to a given cutoff. Then we use them to select dynamically important “hinge residues” whose elastic distortion affects the fluctuations of a large number of residues. Second, in order to clarify long-range dynamical correlations, we decompose the dynamical correlations to individual normal modes to identify the most relevant modes. We have applied these methods to the analysis of the motor domain of Dictyostelium myosin and have obtained the following three interesting results that shed light on its mechanism of force generation: first, we find the hinge residues are distributed over several key inter-subdomain joints (including the nucleotide-binding pocket, the relay helix, the SH1 helix, the strut between the upper 50kDa and the lower 50kDa subdomains), which is consistent with their hypothesized roles in modulating functionally relevant inter-subdomain conformational changes; second, a single mode 7 (for structure 1VOM) is found to dominate the fluctuation-based correlations between the converter/strut and the nucleotide-binding pocket, revealing a surprising simplicity for their intriguing roles in the force generation mechanism; finally, we find a negative density-based correlation between the strut and the nucleotide-binding pocket, which is consistent with the hypothesized signaling pathway that links the actin-binding site''s opening/closing with the nucleotide-binding pocket''s closing/opening. [Copyright &y& Elsevier]

Here we perform a systematic exploration of the use of distance constraints derived from small angle X-ray scattering (SAXS) measurements to filter candidate protein structures for the purpose of protein structure prediction. This is an intrinsically more complex task than that of applying distance constraints derived from NMR data where the identity of the pair of amino acid residues subject to a given distance constraint is known. SAXS, on the other hand, yields a histogram of pair distances (pair distribution function), but the identities of the pairs contributing to a given bin of the histogram are not known. Our study is based on an extension of the Levitt-Hinds coarse grained approach to ab initio protein structure prediction to generate a candidate set of Cα backbones. In spite of the lack of specific residue information inherent in the SAXS data, our study shows that the implementation of a SAXS filter is capable of effectively purifying the set of native structure candidates and thus provides a substantial improvement in the reliability of protein structure prediction. We test the quality of our predicted Cα backbones by doing structural homology searches against the Dali domain library, and find that the results are very encouraging. In spite of the lack of local structural details and limited modeling accuracy at the Cα backbone level, we find that useful information about fold classification can be extracted from this procedure. This approach thus provides a way to use a SAXS data based structure prediction algorithm to generate potential structural homologies in cases where lack of sequence homology prevents identification of candidate folds for a given protein. Thus our approach has the potential to help in determination of the biological function of a protein based on structural homology instead of sequence homology. [Copyright &y& Elsevier]

Malignant melanoma (MM) causes 80% of skin cancer-related deaths and becomes the most lethal type of skin cancer. The molecular mechanism of MM is still not clear. This study aimed to reveal the relationship between MM and EIF3H. Clinical specimens were collected to preliminarily explore the role of EIF3H in MM. MM cell lines with EIF3H knockdown were constructed for investigating the effects of EIF3H on cell proliferation, apoptosis, cell cycle and cell motility. Mice xenograft model was constructed for verification in vivo. We found that EIF3H was obviously upregulated in MM tissues compared with normal skin tissues, which was correlated with tumor stage and risk of lymphatic metastasis. The in vitro results indicated that silencing EIF3H in MM cells could significantly suppress cell proliferation, promote cell apoptosis and induce cell cycle arrest. Moreover, EIF3H knockdown significantly restrained cell motility through regulating EMT-related proteins. The effects of EIF3H knockdown were also verified in mice xenograft model, which were represented by slower growth rate, smaller volume and lighter weight of tumors. Therefore, EIF3H was identified as a critical factor in the development and progression of MM which may be used as a novel therapeutic target in the treatment of MM. • EIF3H is highly expressed in malignant melanoma and correlated with tumor stage and risk of lymphatic metastasis. • Knockdown of EIF3H inhibits cell proliferation, cell migration and promotes cell apoptosis of melanoma in vitro. • Knockdown of EIF3H suppresses tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Monoclinic Li 2 TiO 3 (β -Li 2 TiO 3) is a kind of potential candidate for anodic material of high-safety lithium-ion batteries (LIBs) for its stable zero-strain layered structure; however, β -Li 2 TiO 3 has intermediate Li+ ​ion conductivity and low electronic conductivity, affecting its practical application. Herein, [002]-oriented β -Li 2 TiO 3 @C nanowires have been synthesized via a convenient low-temperature solid state method. The diffusion of Li+ ​along the ab plane of β -Li 2 TiO 3 has relatively low energy barrier, and the obtained [002]-oriented nanowires (with diameter of 50–70 ​nm) provide short and accessible Li+ ​diffusion pathways along the ab plane. In addition, the modification of carbon layers with optimal thickness (∼8 ​nm) can promote the Li+ transfer kinetics and improve the electronic conductivity. As a result, [002]-oriented β -Li 2 TiO 3 @C nanowires exhibit excellent electrochemical performance, involving high specific capacity (243.1 mAh g−1 at 50 ​mA ​g−1), high rate capability (173.6 and 155.3 mAh g−1 at current rates of 50 and 200 ​mA ​g−1), and good cyclic stability (160.9 mAh g−1 at 50 ​mA ​g−1 after 100 cycles). Therefore, [002]-oriented β -Li 2 TiO 3 @C nanowires have the potential to be used as anodic material for high-performance LIBs. This work could provide inspiration to improve the Li-ion storage property of anodic materials by purposely tailoring the structure and crystal orientation. The modification of carbon layer with optimal thickness (∼8 ​nm) can promote the Li+ ions transfer and improve the electronic conductivity; moreover, the diffusion of Li ​+ ​ions along the ab plane of β -Li 2 TiO 3 has low energy barrier. Thus, [002]-oriented β -Li 2 TiO 3 @C nanowires with small diameter possess excellent Li-ion storage property. [Display omitted] • [002]-oriented β -Li 2 TiO 3 @C nanowires are prepared by a low-temperature solid state method. • β -Li 2 TiO 3 @C nanowires with carbon thickness of 8 ​nm exhibit the best electrochemical properties. • β -Li 2 TiO 3 @C nanowires have good Li-ion storage property owing to carbon layer, c -axis-oriented growth, and small diameter. • This work supplies a simple, low-cost, and effective route to prepare other 1D Li x Ti y O z nanomaterials on a large scale. [ABSTRACT FROM AUTHOR]

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition that is characterized by an abnormal heart rhythm in response to physical or emotional stress. The majority CPVT patients carry mutations in the RYR2 gene that encodes the calcium release channel/ryanodine receptor (RyR2) in cardiomyocytes. The pathogenic mechanisms that account for the clinical phenotypes of CPVT are still elusive. We have identified a de novo mutation, A165D, from a CPVT patient. We found that CPVT phenotypes are recapitulated in A165D knock-in mice. The mutant RyR2 channels enhanced sarcoplasmic reticulum Ca 2+ release, triggered delayed afterdepolarization in cardiomyocytes. Structural analysis revealed that the A165D mutation is located in a loop that is involved in inter-subunit interactions in the RyR2 tetrameric structure, it disrupted conformational stability of the RyR2, which favored a closed-to-open state transition, resulting in a leaky channel. The loop also harbors several other CPVT mutations, which suggests a common pathogenic molecular mechanism of CPVT-causing mutations. Our data illustrated disease-relevant functional defects and provide a deeper mechanistic understanding of a life-threatening cardiac arrhythmia. [ABSTRACT FROM AUTHOR]

Abstract: In this study, rutile films consisting of rectangular nanorods were facilely deposited on glass substrates from strongly acid solution of TiCl4. The highly ordered array of nanorods was realized in presence of ionic liquid (IL) of [Bmim]Br by following a hydrothermal process. In this process, Degussa P25 nanoparticles served as seeds that were pre-deposited on the substrates to facilitate the array of rutile nanorods. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectrum were used to characterize the obtained nanorod films. The measurements showed that the nanorods were rectangular with width of 100–200nm and length of more than 1μm, and grew up typically along c-axis to form the arrays against the substrate. The presence of IL was found vital for the formation of rutile nanorods, and the suitable molar ratio of [Bmim]Br to TiCl4 ranged from 500:1 to 1500:1. The excessive [Bmim]Br may hinder the precipitation of rutile particles. [Copyright &y& Elsevier]