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Cathepsin B (CTSB) is a powerful lysosomal protease. This review evaluated CTSB gene knockout (KO) outcomes for amelioration of brain dysfunctions in neurologic diseases and aging animal models. Deletion of the CTSB gene resulted in significant improvements in behavioral deficits, neuropathology, and/or biomarkers in traumatic brain injury, ischemia, inflammatory pain, opiate tolerance, epilepsy, aging, transgenic Alzheimer's disease (AD), and periodontitis AD models as shown in 12 studies. One study found beneficial effects for double CTSB and cathepsin S KO mice in a multiple sclerosis model. Transgenic AD models using amyloid precursor protein (APP) mimicking common sporadic AD in three studies showed that CTSB KO improved memory, neuropathology, and biomarkers; two studies used APP representing rare familial AD and found no CTSB KO effect, and two studies used highly engineered APP constructs and reported slight increases in a biomarker. In clinical studies, all reports found that CTSB enzyme was upregulated in diverse neurologic disorders, including AD in which elevated CTSB was positively correlated with cognitive dysfunction. In a wide range of neurologic animal models, CTSB was also upregulated and not downregulated. Further, human genetic mutation data provided precedence for CTSB upregulation causing disease. Thus, the consilience of data is that CTSB gene KO results in improved brain dysfunction and reduced pathology through blockade of CTSB enzyme upregulation that causes human neurologic disease phenotypes. The overall findings provide strong support for CTSB as a rational drug target and for CTSB inhibitors as therapeutic candidates for a wide range of neurologic disorders. SIGNIFICANCE STATEMENT: This review provides a comprehensive compilation of the extensive data on the effects of deleting the cathepsin B (CTSB) gene in neurological and aging mouse models of brain disorders. Mice lacking the CTSB gene display improved neurobehavioral deficits, reduced neuropathology, and amelioration of neuronal cell death and inflammatory biomarkers. The significance of the compelling CTSB evidence is that the data consilience validates CTSB as a drug target for discovery of CTSB inhibitors as potential therapeutics for treating numerous neurological diseases.

For the expansion soil slope in the JiangHuai area before the disposal of the neglect of expansion of the weak defects and slope disposal after the poor long-term stability of the current situation. This study investigates the ability of ecological slope protection technology to cope with the destabilizing geohazard of expansive soil slopes. Analyzing the collapse reasons of weak expansive soil slopes in the JiangHuai region based on the reinforcement project of expansive soil slopes along highways in the JiangHuai region, combined with actual engineering research, a "storage-resistance" water regulation ecological prevention and control technology is proposed. The feasibility and sustainability of the ecological slope protection technology is discussed in terms of its principles and influencing factors, and the protection effect is verified by combining numerical simulation and field test methods. Research findings suggest that the "storage-resistance" technology effectively prevents rainwater infiltration, particularly under light rain conditions, with continuous blocking capability. Under rainstorm conditions, it can prevent infiltration for about 4 h, significantly enhancing slope stability. Slope rate variations show no significant impact on reinforced slope stability, with maximum deformation occurring at the slope's foot after rainfall. Reinforcement plans should prioritize strengthening support at the slope's base. Proper selection and optimization of technical parameters can lead to more economical and sustainable solutions while extending protection time. Field trials confirm the suitability of the "storage and blocking" water regulation ecological control technology for the JiangHuai region, particularly where light rain prevails. These findings suggest that ecological control techniques for expansive soil slopes can effectively regulate slope moisture changes and reduce the geohazard risk of expansive soil slope instability. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short‐term memory loss and reduced amyloid‐beta (Aβ) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aβ plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy‐lysosome pathway in astrocytes, thereby mediating Aβ clearance and alleviating AD pathology. ECM remodeling also promoted Aβ plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy‐lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease. [ABSTRACT FROM AUTHOR]

The clogging induced by particle transport is often mentioned in the practice of vacuum preloading, but the percolation behavior of soft clay under negative pressure is still not clear. To understand this, the percolation behavior was investigated using an artificial paste of silica sand and kaolinite under different hydraulic pressures. The hydraulic conductivity under positive pressure (90 kPa) was about twice as high as that of negative pressure (−90 kPa). However, the transport capacity and leached particle size under negative pressure were more significant than those under positive pressure, despite the same tendency of the porosity under the positive or negative pressure. This is an interesting and paradoxical finding, suggesting complexity accompanying the erosion and clogging under the nominal hydraulic gradient, where a higher concentration of the hydraulic gradient occurs under negative pressure. The percolation under negative pressure––a self-adaptive process––included three elements: (1) the colloidal transport of clay minerals; (2) colloid accumulation and clogging in the seepage channel close to the outlet; and (3) a gradient concentration close to the outlet. [ABSTRACT FROM AUTHOR]

This study proposes a closed‐form solution for axisymmetric electro‐osmotic consolidation of unsaturated soil under semi‐permeable boundary conditions. The governing equations are formulated to allow for vertical and radial flows of liquid and air phases. The techniques of eigenfunction expansion and Laplace transformation are employed to develop the exact solution for excess pore‐air (EPAP) and pore‐water pressures (EPWP). The proposed solution is first validated by comparing it to an existing solution, followed by verification through finite element simulations. Both methods of validation confirm the accuracy of the analytical solution. Then, based on the obtained solution, the effects of vertical flow, semi‐permeable boundary conditions, electrical voltage, electro‐osmosis conductivity and spacing ratio re/rw on the consolidation profile have been further investigated. Parametric studies show that the EPWP at the steady state depends on the electro‐osmosis conductivity and applied electricity gradient. In addition, the dissipation rates of EPWP and EPAP in the axisymmetric electro‐osmotic consolidation would be underestimated if the vertical flows are neglected. The semi‐permeable boundary conditions have great influences on the dissipation rate and the steady‐state solution. The proposed solution could serve as a theoretical basis for axisymmetric electro‐osmotic consolidation of unsaturated soil. [ABSTRACT FROM AUTHOR]