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Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we find myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential (ΔΨm) permanently impairs mitochondria-endoplasmic reticulum (ER) contacts and abolish Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restores cytosolic Ca2+ homeostasis, remotivates myogenic spontaneous vasomotion, achieves optimal reperfusion, and ameliorates neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow. The no-reflow phenomenon after stroke is attributed to damaged spontaneous vasomotion of cerebral arterioles, which can be alleviated by maintaining mitochondria-ER contact-dependent Ca2+ oscillation. [ABSTRACT FROM AUTHOR]

This paper focuses mainly on developing single-step explicit integration algorithms considering the implicit treatment of velocity. A novel explicit algorithm (GSSI) is proposed and recommended as a self-starting dissipative alternative to the central difference methods in transient analysis. GSSI not only shares the same advantages as the central difference methods, such as second-order accuracy and computational cost, but also achieves flexible dissipation control and self-starting property. Remarkably, GSSI provides a significantly larger stability bound than the central difference methods in the damped case. GSSI imposes two algorithmic parameters ( ρ s and ρ b ) to flexibly adjust numerical dissipation at the bifurcation point. In general, the ρ b controls numerical dissipation at the bifurcation point, while the ρ s further adjusts the amount of dissipation in the low-frequency range. Spectral analysis and numerical examples are given solved to show the superiority of GSSI over the existing single-step explicit methods with respect to accuracy, stability, and dissipation control. [ABSTRACT FROM AUTHOR]

This paper proposes an implicit family of sub-step integration algorithms grounded in the explicit singly diagonally implicit Runge–Kutta (ESDIRK) method. The proposed methods achieve third-order consistency per sub-step, and thus, the trapezoidal rule is always employed in the first sub-step. This paper demonstrates for the first time that the proposed s-sub-step implicit method with s≤6\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ s\le 6 $$\end{document} can reach sth-order accuracy when achieving dissipation control and unconditional stability simultaneously. Hence, this paper develops, analyzes, and compares four cost-optimal high-order implicit algorithms within the present s-sub-step method using three, four, five, and six sub-steps. Each high-order implicit algorithm shares identical effective stiffness matrices to achieve optimal spectral properties. Unlike the published algorithms, the proposed high-order methods do not suffer from the order reduction for solving forced vibrations. Moreover, the novel methods overcome the defect that the authors’ previous algorithms require an additional solution to obtain accurate accelerations. Linear and nonlinear examples are solved to confirm the numerical performance and superiority of four novel high-order algorithms. [ABSTRACT FROM AUTHOR]

A novel family of composite sub-step algorithms with controllable numerical dissipations is proposed in this paper to obtain reliable numerical responses in structural dynamics. The new scheme is a self-starting, unconditionally stable and second-order-accurate two-sub-step algorithm with the same computational cost as the Bathe algorithm. The new algorithm can control continuously numerical dissipations in the high-frequency range in an intuitive way, and the ability of numerical dissipations can range from the non-dissipative trapezoidal rule to the asymptotic annihilating Bathe algorithm. Besides, the new algorithm only involves one free parameter and always achieves the identical effective stiffness matrices inside two sub-steps, which is not always achieved in three Bathe-type algorithms, to reduce the computational cost in the analysis of linear systems. Some numerical examples are given to show the superiority of the new algorithm over the Bathe algorithm and the CH- α algorithm. [ABSTRACT FROM AUTHOR]

Hypertension-related left ventricular hypertrophy is recognized as a good predictor of adverse cardiovascular events. However, the underlying mechanism of left ventricular hypertrophy is still not fully understood. This study employed liquid chromatography coupled with tandem mass spectrometry to investigate global changes in protein profile in myocardium of spontaneously hypertensive rat, a classical animal model of essential hypertension. There were 369 differentially expressed proteins in myocardium between spontaneously hypertensive rats and normotensive rats. Xenobiotic catabolic process, cholesterol binding and mitochondrial proton-transporting ATP synthase were found to be the most significantly enriched biological process, molecular function and cellular component terms of Gene Ontology, respectively. Drug metabolism-cytochrome P450 was revealed to be the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. FYN proto-oncogene, Src family tyrosine kinase was found to have the most interactions with other proteins. Differentially expressed proteins involved in xenobiotic catabolic process, lipid transport and metabolism, mitochondrial function might be targets for further study of hypertension-related left ventricular hypertrophy. [ABSTRACT FROM AUTHOR]

To explore the fractal dimension, particle shape, and particle breakage of calcareous sand (CS) under multi-level ending pressure, a series of one-dimensional compression experiments along with microscope image recognition tests were performed. Test results demonstrated that compression behavior of CS was similar to that of silt soil for the reason that considerable particle breakage occurred under high-stress level. In unloading process, rebound index of tested specimens was in the range of 0.0027–0.0052 which suggested that irrecoverable plastic deformation consists of the main part of compression. The shape index sphericity ( S C ), aspect ratio ( A R ), convexity ( C X ), and overall regularity ( O R ) increased as increasing axial stress or decreasing average grain size. Besides, there existed a turning point of axial stress of 3200 kPa; these shape indexes increased rapidly first and then approached to a stable value after that. At present study, the surface and mass fractal dimension of tested specimens were in the range of 1.12–1.93 and 2.14–2.92, respectively. Both fractal dimension and relative breakage ratio increased logarithmically as increasing axial stress from 0 to 6400 kPa. In addition, an increase in the average grain size led to an increase in the relative breakage ratio and a decrease in fractal dimension which indicated that larger particles are more easily broken for the reason that the stress concentration between granular grains. Furthermore, there existed approximate linear relations between surface or mass fractal dimension with relative breakage ratio which might be helpful to quantitate the particle breakage of granular materials. [ABSTRACT FROM AUTHOR]

The digital polymerase chain reaction (dPCR) is a new and developing nucleic acid detection technology with high sensitivity that can realize the absolute quantitative analysis of samples. In order to improve the accuracy of quantitative results, real-time digital PCR emphasizes the kinetic information during amplification to identify prominent abnormal data. However, it is challenging to use a unified standard to accurately classify the amplification curve of each well as negative and positive, due to the interference caused by various factors in the experiment. In this work, a normal distribution–based cycle threshold value self-correcting model (NCSM) was established, which focused on the feature of the cycle threshold values in amplification curves and conducted continuous detection and correction on the whole. The cycle threshold value distribution was closer to the ideal normal distribution to avoid the influence of interference. Thus, the model achieves a more accurate classification between positive and negative results. The corrective process was applied to plasmid samples and resulted in an accuracy improvement from 92 to 99%. The coefficient of variation was below 5% when considering the quantitation of a range between 100 and 10,000 copies. At the same time, by utilizing this model, the distribution of cycle threshold values at the endpoint can be predicted with fewer thermal cycles, which can reduce the cycling time by around 25% while maintaining a consistency of more than 98%. Therefore, using the NCSM can effectively enhance the quantitative accuracy and increase the detection efficiency based on the real-time dPCR platform. [ABSTRACT FROM AUTHOR]

The recently developed prime-editing (PE) technique is more precise than previously available techniques and permits base-to-base conversion, replacement, and insertions and deletions in the genome. However, previous reports show that the efficiency of prime editing is insufficient to produce genome-edited animals. In fact, prime-guide RNA (pegRNA) designs have posed a challenge in achieving favorable editing efficiency. Here, we designed prime binding sites (PBS) with a melting temperature (Tm) of 42 °C, leading to optimal performance in cells, and we found that the optimal Tm was affected by the culture temperature. In addition, the ePE3max system was developed by updating the PE architecture to PEmax and expressing engineered pegRNA (epegRNA) based on the original PE3 system. The updated ePE3max system can efficiently induce gene editing in mouse and rabbit embryos. Furthermore, we successfully generated a Hoxd13 (c. 671 G > T) mutation in mice and a Tyr (c. 572 del) mutation in rabbits by ePE3max. Overall, the editing efficiency of modified ePE3max systems is superior to that of the original PE3 system in producing genome-edited animals, which can serve as an effective and versatile genome-editing tool for precise genome modification in animal models. [ABSTRACT FROM AUTHOR]