The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

WavNet — Visual saliency detection using Discrete Wavelet Convolutional Neural Network

In the recent advancements in image and video analysis, the detection of salient regions in the image becomes the initial step. This plays a crucial role in deciding the performance of such algorithms. In this work, a Multi-Resolution Feature Extraction (MRFE) technique that makes use of Discrete Wavelet Convolutional Neural Network (DWCNN) for generating features is employed. An Enhanced Feature Extraction (EFE) module extracts additional features from the high level features of the DWCNN, which are used to frame both channel as well as spatial attention models for yielding contextual attention maps. A new hybrid loss function is also proposed, which is a combination of Balanced Cross Entropy (BCE) loss and Edge based Structural Similarity (ESSIM) loss that effectively identifies and segments the salient regions with clear boundaries. The method is tested exhaustively with five different benchmark datasets and is proved superior to the existing state-of-the-art methods with a minimum Mean Absolute error (MAE) of 0.03 and F-measure of 0.956.     

Structural Aspects and Prediction of Calmodulin-Binding Proteins

Calmodulin (CaM) is an important intracellular protein that binds Ca²⁺ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca²⁺ concentration through interactions with CaM.     

Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Optimized microwave absorption properties by tailoring the morphology of carbon coated TiC nanoparticles by N2 pressure

Increasing the dielectric loss capacity plays an important role in enhancing the electromagnetic absorption performance of materials. It remains a challenge to simultaneously introduce multiple types of dielectric losses in the material. In this work, we show that the atomic and interfacial dipole polarizations can be simultaneously enhanced by substituting N species into both carbon coating layers and bulk TiC lattices of a core-shell TiC@C material. Additionally, substitution of N species results more exposed TiC(111) facets and refines the TiC grain sizes in the bulk material, which is beneficial for enhancing the scattering of the external electromagnetic waves. The maximum reflection loss of the N substituted TiC@C material is measured as ?47.1 dB with an effective absorbing bandwidth of 4.83 GHz at 1.9 mm, which illustrates a valuable way to further tuning the electromagnetic absorption performance of this type of materials.     

In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value.     

川中地区侏罗系沙溪庙组致密气处理和解释关键技术与应用

四川盆地蕴含丰富的致密砂岩气资源，近期利用高精度三维资料开展侏罗系沙溪庙组河道砂体勘探取得突出成效。沙溪庙组河道砂体具有横向变化快、储层非均质性强的特点，因此提高河道砂体的边界识别及其含气性预测精度是致密气地震勘探的关键。通过开展AVO特征低频保护的“六分法”（分类、分频、分时、分域、分步和分区）高保真叠前去噪、近地表Q补偿和OVT域叠前时间偏移等技术攻关，形成了一套针对川中地区侏罗系沙溪庙组致密气藏的“双高”（高保真、高分辨率）地震处理技术，并创新应用“双亮点”属性及多波、多分量砂体含气性地震预测等解释技术，提高了含气砂体预测精度。该技术系列在川中沙溪庙组致密气预测应用成果显著，地震数据频带得到了拓宽，低频信息更加丰富，资料信噪比明显提升，河道边界及其含气性预测的精度大幅提高，钻井成功率超过83%，应用成果有力地支撑了该地区沙溪庙组致密气的增储上产。     

纳米级超声造影剂的理论研究进展

为了克服超声造影剂中微米级气泡尺寸较大的局限性,大量研究人员对超声应用的替代造影剂(纳米级造影剂)进行了研究。随着生物纳米技术的飞速发展,纳米级超声造影剂在诊断与治疗领域有着广阔的发展前景。与超声造影剂中的微米级气泡相比,纳米级造影剂粒径较小,渗透能力极强,可以通过血管内皮间隙,进而可以实现血管外病变部位的显影。文中详细论述了超声造影剂在超声作用下的行为以及2种主要的纳米级造影剂:纳米气泡和纳米液滴造影剂,对其理论研究进展进行了总结,并提出了目前仍存在的一些问题及其未来的研究方向。