Effects Of Unloading Research Articles

Acute effects of robot-assisted body weight unloading on biomechanical movement patterns during overground walking

Body weight unloading (BWU) is used in rehabilitation/training settings to reduce kinetic requirements, however different BWU methods may be unequally capable of preserving biomechanical movement patterns. Biomechanical analysis of both kinetic and kinematic movement trajectories rather than discrete variables has not previously been performed to describe the effect of BWU on gait patterns during horizontal walking. The aim of the present study was to investigate how robot-assisted BWU producing an dynamic unloading force on the body centre of mass, affects kinematic, kinetic, and spatiotemporal gait parameters in healthy young adults by use of time-continuous analysis. Twenty participants walked overground in a 3-D motion-capture lab at 0, 10, 20, 30, 40, and 50 % BWU at a self-selected speed. Vertical and anterior-posterior ground reaction forces (GRFs) and lower limb internal joint moments were obtained during the stance phase, while joint angles were obtained during entire strides. Time-continuous data were analysed using Statistical Parametric Mapping (SPM) and discrete data using conventional statistics to compare different BWU conditions by means of One-Way Repeated Measures Anova. With increasing BWU, corresponding reductions were observed for GRFs, internal joint moments, joint angles, walking speed, stride/step length and cadence. Observed effects were partially caused by decreased walking speed and increased BWU. While amplitude reductions were observed for kinetic and kinematic variables, trajectory shapes were largely preserved. In conclusion, dynamic robot-assisted BWU enables reduced kinetic requirements without distorting biomechanically normal gait patterns during overground walking in young healthy adults.

The effect of intra-aortic balloon pumping on hemodynamics and left ventricular load in Impella-supported condition: A simulation study

Abstract Introduction Intra-aortic balloon pumping (IABP) is a commonly used percutaneous mechanical circulatory support device. Although IABP combined with Impella, a percutaneous left ventricular assist device, has shown positive outcomes in a few case reports of acute heart failure, its hemodynamic and left ventricular (LV) unloading effects remain unclear. Purpose We conducted a simulation study to clarify the clinical benefits of adding IABP to Impella-supported conditions. Methods We used SimulinkⓇ for cardiovascular simulation. The systemic and pulmonary circulation were modelled by using a 5-element resistance-capacitance network with four ventricles represented by time-varying elastance and unidirectional valves (Figure 1A). We compared total systemic flow, coronary perfusion pressure (CPP), and pressure-volume relationships (PV loop) in severe LV dysfunction (LV end-systolic elastance: 0.2 mmHg/mL) under three scenarios: IABP with a 40 mL balloon volume added to baseline, IABP added to Impella CP support at P2 (partial support) and P8 (total support) (Figure 1B). Results As shown in Figure 2A, IABP increased total systemic flow and CPP, and shifted the PV loop to the left. In P2-Impella condition, the addition of IABP increased native cardiac output (0.3 to 0.7 L/min) and total systemic flow (2.7 to 2.9 L/min), while decreased Impella pump flow due to increased afterload of Impella during diastole. IABP further moved PV loop leftward and reduced LV pressure-volume area (PVA) by -3.8% from Impella only and -7.8% from baseline (Figure 2B). In P8-Impella condition, IABP did not change total systemic flow, CPP, or PV loop (Figure 2C). Conclusions The addition of IABP to Impella could increase CPP while increasing Impella pump afterload and decreasing Impella flow. Overall, IABP slightly increased total systemic flow and decreased LV workload in Impella partial support condition. In specific clinical situations, IABP has the potential to be used as adjuvant therapy alongside Impella partial support.Figure 1

Abstract 17687: Left Ventricular Unloading in Pulmonary Hypertension With Impella 5.5 as a Bridge to Heart Transplantation

A 59 year-old male with a history of triple-vessel coronary artery bypass graft surgery, ischemic cardiomyopathy with an implantable cardioverter defibrillator, pre- and post-capillary pulmonary hypertension, severe mitral regurgitation, paroxysmal atrial fibrillation, diabetes mellitus, hypertension was referred for transplant evaluation in the setting of cardiogenic shock despite inotropic support. His initial right heart catheterization showed RAP 21 mmHg, RVP 91/9 mmHg, PAP 88/31 mmHg with a mean of 50 mmHg, PCWP 22 mmHg, PVR 6.6 Wood units, SVR 857 dynes, and CO 4.85 l/min/CI 2.59 l/min/m 2 by thermodilution. His hospital course was complicated by acute renal failure requiring continuous renal replacement therapy. Inotropic support could not be weaned on multiple attempts, and pulmonary and wedge pressures remained significantly elevated despite a trial of inhaled nitric oxide. The patient underwent Impella 5.5 placement to assess the hemodynamic response of unloading the left ventricle. A repeat right heart catheterization showed a RAP 1 mmHg, RVP 42/1 mmHg, PAP 48/13 mmHg with a mean of 26 mmHg, PVR 2.3 Wood units, SVR 829 dynes, and CO 6.75 l/min/CI 3.74 l/min/m 2 by thermodilution. Measurements were obtained with Impella 5.5 at P-8 level, milrinone 0.2 mcg/kg/min, treprostinil 4 ng/kg/min, epoprostenol 1 mg every 6 hours, and sildenafil 10 mg in morning and afternoon and 15 mg in evening. The patient underwent successful heart and kidney transplantation. Post-transplantation right heart catheterization showed persistent pre-capillary pulmonary hypertension with normal filling pressures and CI. His pulmonary hypertension was managed with sildenafil 40 mg three times daily and ambrisentan 10 mg daily. This case demonstrates favorable hemodynamic effects of left ventricular unloading using Impella support with significant reduction in pulmonary vascular pressure to reach candidacy for heart transplantation.

Effects of Complex Triaxial Unloading Confining Stress Conditions on the Mechanical Behaviour and Fracture Mechanism of Sandstone

Effects of Complex Triaxial Unloading Confining Stress Conditions on the Mechanical Behaviour and Fracture Mechanism of Sandstone

Effects of exercise prehabilitation on muscle atrophy and contractile properties in hindlimb-unloaded rats.

Effective strategies for rapid recovery after surgery are needed. Therefore, we investigated the effects of exercise prehabilitation (EP) and hindlimb unloading (HU) on muscle loss and contractility. Twenty-two Sprague-Dawley rats (12 wk old) were divided into normal control (NCON, n = 5), hindlimb unloading control (HCON, n = 10), and exercise prehabilitation followed by hindlimb unloading (Ex-preH, n = 7) groups. Ex-PreH performed exercise training for 14 days before hindlimb unloading for 14 days. Body composition was evaluated, along with muscle strength and function. The soleus (SOL) and extensor digitorum longus (EDL) muscle contractile properties were analyzed at the whole-muscle level. The titin concentration and myosin heavy chain (MHC) type composition were analyzed. There were no effects of Ex-preH on total mass, lean mass, or muscle weight. Physical function was significantly higher in the Ex-preH group than in the HCON group (39.5° vs. 35.7°). The SOL twitch force (19.6 vs. 7.1 mN/m2 ) and specific force (107.3 vs. 61.2 mN/m2 ) were greater in Ex-preH group than in HCON group. EDL shortening velocity was higher in Ex-preH group than in HCON group (13.2 vs. 5.0 FL/s). The SOL full-length titin level was higher in Ex-preH group than in HCON group. Exercise prehabilitation did not prevent muscle mass loss followed by muscle wasting, although it minimized the reduction of physical function. Therefore, exercise prehabilitation should be considered for rapid functional recovery after disuse due to surgery and injuries.

Macroscopic and mesoscopic comparative study of frozen loess under loading and unloading

This paper utilizes computed tomography (CT) real–time observation technology to investigate the damage mechanism of frozen loess under loading and unloading. The intrinsic connections between macroscopic mechanical degradation and mesoscopic damage in frozen loess were established through a comparative analysis of macroscopic mechanical parameters (such as dissipation energy and elastic strain energy) and mesoscopic structural parameters (such as porosity increment and mesoscopic structural damage increment) of frozen loess under loading and unloading. Furthermore, the relationships between damage variables at different scales under the effects of loading and unloading were explored. The experimental results demonstrate that during the elastic strain stage, the dissipated energy, porosity increment, and microscopic damage increment of frozen soil exhibit a linear increase with strain. Following loading and unloading, the porosity is unable to be fully restored to its original state due to the development of new cracks. At this stage, the deformation is not entirely elastic and includes some plastic deformation. During the plastic deformation stage, the dissipated energy tends to stabilize, while the porosity increment and microscopic damage increment continue to increase substantially. The pore structure of a specimen undergoes significant alterations, with increased displacement and rearrangement of soil particles and ongoing expansion of cracks. The damage evolution trends at both the macroscale and mesoscale remain consistent during this stage. This study offers insights into the construction of a cross–scale macroscale/mesoscale ontological damage model, serving as a valuable reference for future research.

Enhancing microbial diversity as well as multi-organ health in hind-limb unloaded mice

During space travel, the gut microbiota is changed which can lead to health-related issues. Previously, we utilized the hind-limb unloaded (HU) mouse, which is an established ground-based in-vivo model of microgravity and observed altered gut microbiota. In this study, we evaluated the beneficial effects of novel bacterial conditioned media in HU mice to understand if they can offset the effects of unloading in the HU mouse model. We aimed to explore the influence of bacterial conditioned media on diversity and quantity of intestinal microbes in HU mice, and investigated the microarchitecture of mice retinas and kidneys to evaluate the potential systemic effects of bacterial conditioned media in HU mice. Four-month-old, male C57/Bl6 mice were separated into groups: including the ground-based control group, the HU group mice fed with vehicle as placebo (HU-placebo mice), and the HU group fed with bacterial conditioned media (HU-CP mice) and kept under controlled environmental conditions for three weeks. Next, mice were sacrificed; gut dissections were conducted, and metagenomic analysis of bacterial species was performed via DNA extraction and 16S rRNA analysis. The results revealed an HU-induced reduction in intestinal microbial diversity, and an increase in pathogenic bacteria dominated by Firmicutes (45%). In contrast, supplementation with bacterial conditioned media for three weeks led to a significant increase in gut microbial diversity with noticeable changes in the OTUs abundance in the HU mice. Additionally, HU-induced muscle weakness and structural abnormalities in the retina and kidney were partially prevented with bacterial conditioned media. Moreover, a greater diversity of several bacteria in the HU-CP was observed including, Bacteriodota, Firmicutes, Proteobacteria, Actionobacteriota, Verrucomicorbiota, Cyanobacteria, Gemmatimonadota, Acidobacteriota, Chloroflexi, Myxococcota, and others. Prospective research involving molecular mechanistic studies are needed to comprehend the systemic effects of bacterial metabolites conditioned media on experimental animal models under chronic stress.

Experimental Study on the Dilatancy and Energy Evolution Behaviors of Red-Bed Rocks under Unloading Conditions.

Surrounding rock deformation and consequent support failure are the most prominent issues in red-bed rock tunnel engineering and are mainly caused by the effects of unloading, rheology, and swelling. This study investigated the mechanical responses of two kinds of red-bed mudstone and sandstone under unloading conditions via laboratory observation. Volume dilation was observed on the rocks during unloading, and the dilatancy stress was linear with the initial confining pressure. However, the ratios of dilatancy stress to peak stress of the two rocks kept at a range from 0.8 to 0.9, regardless of confining pressures. Both the elastic strain energy and the dissipated energy evolved synchronously with the stress-strain curve and exhibited conspicuous confining pressure dependence. Special attention was paid to the evolution behavior of the dilatancy angle. The dilatancy angle changed linearly during unloading. When the confining pressure was 10 MPa, the dilatancy angle of mudstone decreased from 26.8° to 12.5° whereas the dilatancy angle of sandstone increased from 34.6° to 51.1°; when the confining pressure rose to 25 MPa, the dilatancy angle of mudstone and sandstone decreased from 45.8° to 17.4° and increased from 21.7° to 39.5°, respectively. To further understand the evolution of the dilatancy angle, we discussed the links between the variable dilatancy angle and the processes of rock deformation and energy dissipation.

НЕКОТОРЫЕ ЭПИЗОДЫ ЖИЗНИ АКАДЕМИКА Л. И. ЛОБКОВСКОГО (К 75-ЛЕТИЮ ЮБИЛЯРА)

This essay is dedicated to the 75th anniversary of the outstanding Russian scientist Leopold Isaevich Lobkovsky. The article describes the path of formation and professional transformation of a graduate of the Faculty of Mechanics and Mathematics of Lomonosov Moscow State University, who in the course of his work made a significant contribution to World science in the field of geodynamics. In particular, he created the prerequisites for a significant revision of the physical foundations of the theory of lithospheric plate tectonics and its transformation into the theory of tectonics of deformable lithospheric plates. The second important achievement of L. I. Lobkovsky is the creation of a keyboard model of island-arc systems and the trigger effect of energy unloading in subduction zones. The most important geopolitical achievement of the hero of the day is the creation of a model for the development of the Canadian Basin and the Arctic Ocean in the Mesozoic and Cenozoic. This made it possible to substantiate the continental nature of the vast areas of the Arctic for the declaration of Russian priority over them in the relevant UN commission.

Short-term hindlimb unloading negatively affects dopaminergic transmission in the nigrostriatal system of mice.

The nigrostriatal system composed of the dorsal striatum and the substantia nigra (SN) is highly involved in the control of motor behavior. Various extremal and pathological conditions as well as social isolation (SI) may cause an impairment of locomotor function; however, corresponding alterations in the nigrostriatal dopaminergic pathway are far from full understanding. Here, we analyzed the effect of 3-day hindlimb unloading (HU) and SI on the key players of dopamine transmission in the nigrostriatal system of CD1 mice. Three groups of mice were analyzed: group-housed (GH), SI, and HU animals. Our data showed a significant decrease in the expression and phosphorylation of tyrosine hydroxylase (TH) in the SN and dorsal striatum of HU mice that suggested attenuation of dopamine synthesis in response to HU. In the dorsal striatum of HU mice, the downregulation of TH expression was also observed indicating the effect of unloading; however, TH phosphorylation at Ser40 was mainly affected by SI pointing on an impact of isolation too. Expression of dopamine receptors D1 in the dorsal striatum of HU mice was increased suggesting a compensatory response, but the activity of downstream signaling pathways involving protein kinase A and cAMP response element-binding protein was inhibited. At the same time, SI alone did not affect expression of DA receptors and activity of downstream signaling in the dorsal striatum. Obtained data let us to conclude that HU was the main factor which impaired dopamine transmission in the nigrostriatal system but SI made some contribution to its negative effects.

One-Dimensional Reverse Consolidation Model for Basal Soil from Deep Excavation Based on the Continuous Drainage Boundary

Excavation-induced unloading effects and dewatering-induced groundwater seepage inevitably result in basal soil reverse consolidation in deep excavation. However, this reverse consolidation process is rarely considered because most previous analytical methods were developed based on total stress analyses. This study proposes a one-dimensional reverse consolidation model for basal soil of deep excavation. Based on the consolidation theory proposed by Terzaghi, governing equations of soil reverse consolidation caused by excavation and dewatering were separately established. The continuous drainage boundary was introduced to describe the construction processes. The reverse consolidation responses of basal soil were obtained by superimposing analytical solutions of the excess pore-water pressures that resulted from excavation and dewatering. The proposed model was verified by existing solutions and a well-documented excavation case history. Moreover, the reverse consolidation characteristics of basal soil were investigated by parametric analyses. Results indicate that the excavation-induced variations in pore-water pressure decreased with increasing excavation depth. The final pore-water pressure and effective stress were predominantly affected by excavation duration rather than interval distribution. In addition, a smaller coefficient of consolidation led to lower pore-water pressure and greater effective stress at a given excavation depth.

An electrical stimulation intervention protocol to prevent disuse atrophy and muscle strength decline: an experimental study in rat

BackgroundSkeletal muscle is negatively impacted by conditions such as spaceflight or prolonged bed rest, resulting in a dramatic decline in muscle mass, maximum contractile force, and muscular endurance. Electrical stimulation (ES) is an essential tool in neurophysiotherapy and an effective means of preventing skeletal muscle atrophy and dysfunction. Historically, ES treatment protocols have used either low or high frequency electrical stimulation (LFES/HFES). However, our study tests the use of a combination of different frequencies in a single electrical stimulation intervention in order to determine a more effective protocol for improving both skeletal muscle strength and endurance.MethodsAn adult male SD rat model of muscle atrophy was established through 4 weeks of tail suspension (TS). To investigate the effects of different frequency combinations, the experimental animals were treated with low (20 Hz) or high (100 Hz) frequency before TS for 6 weeks, and during TS for 4weeks. The maximum contraction force and fatigue resistance of skeletal muscle were then assessed before the animals were sacrificed. The muscle mass, fiber cross-sectional area (CSA), fiber type and related protein expression were examined and analyzed to gain insights into the mechanisms by which the ES intervention protocol used in this study regulates muscle strength and endurance.ResultsAfter 4 weeks of unloading, the soleus muscle mass and fiber CSA decreased by 39% and 58% respectively, while the number of glycolytic muscle fibers increased by 21%. The gastrocnemius muscle fibers showed a 51% decrease in CSA, with a 44% decrease in single contractility and a 39% decrease in fatigue resistance. The number of glycolytic muscle fibers in the gastrocnemius also increased by 29%. However, the application of HFES either prior to or during unloading showed an improvement in muscle mass, fiber CSA, and oxidative muscle fibers. In the pre-unloading group, the soleus muscle mass increased by 62%, while the number of oxidative muscle fibers increased by 18%. In the during unloading group, the soleus muscle mass increased by 29% and the number of oxidative muscle fibers increased by 15%. In the gastrocnemius, the pre-unloading group showed a 38% increase in single contractile force and a 19% increase in fatigue resistance, while in the during unloading group, a 21% increase in single contractile force and a 29% increase in fatigue resistance was observed, along with a 37% and 26% increase in the number of oxidative muscle fibers, respectively. The combination of HFES before unloading and LFES during unloading resulted in a significant elevation of the soleus mass by 49% and CSA by 90%, with a 40% increase in the number of oxidative muscle fibers in the gastrocnemius. This combination also resulted in a 66% increase in single contractility and a 38% increase in fatigue resistance.ConclusionOur results indicated that using HFES before unloading can reduce the harmful effects of muscle unloading on the soleus and gastrocnemius muscles. Furthermore, we found that combining HFES before unloading with LFES during unloading was more effective in preventing muscle atrophy in the soleus and preserving the contractile function of the gastrocnemius muscle.

Accumulated plastic deformation behavior of granite residual soil under cyclic loading considering the influence of initial unloading

In engineering practice, excavation near existing transport infrastructures is inevitable due to space limitations. The effect of excavation-induced unloading on soil response to subsequent traffic loads is well worth studying, yet previous studies mainly focused on the effect of initial loading (rather than unloading). Undrained cyclic triaxial tests on undisturbed granite residual soil were conducted to study the effect of initial unloading on accumulated plastic deformation behavior. The unloading effect was achieved by reducing cell pressure before cyclic loading. The influences of amplitude of cyclic stress (σd) and degree of initial unloading (Di) on accumulated plastic deformation behavior were investigated. The results indicate that accumulating mode of axial plastic strain changes gradually from “stabilization” to “failure” as σd increases. Initial unloading has a significant promoting effect on the development of accumulated axial strain, and the promoting effect heightens with the increase in Di. Besides, a comparative study was conducted by employing another two stress paths, and it is found that initial shearing stress path makes a considerable difference to accumulated plastic deformation behavior. Under the same Di and σd, soil specimen experiencing initial unloading shows a poorer capacity for resisting cyclic deformation, compared to the other initial shearing stress paths. An empirical model was developed for predicting accumulated axial strain under the condition that initial unloading occurs prior to cyclic loading, considering the effects of amplitude of cyclic stress and degree of initial unloading.

Negative Impact of Acute Reloading after Mechanical Left Ventricular Unloading.

Mechanical LV unloading for acute myocardial infarction (MI) is a promising supportive therapy to reperfusion. However, no data is available on exit strategy. We evaluated hemodynamic and cellular effects of reloading after Impella-mediated LV unloading in Yorkshire pigs. First, we conducted an acute study in normal heart to observe effects of unloading and reloading independent of MI-induced ischemic effects. We then completed an MI study to investigate optimal exit strategy on one-week infarct size, no-reflow area, and LV function with different reloading speeds. Initial studies showed that acute reloading causes an immediate rise in end-diastolic wall stress followed by a significant increase in cardiomyocyte apoptosis. The MI study did not result in any statistically significant findings; however, numerically smaller average infarct size and no-reflow area in the gradual reloading group prompt further examination of reloading approach as an important clinically relevant consideration.

Failure Mechanism of the Yizhuxiang Collapse under the Joint Effect of Freeze–Thaw and Mining

At 10:05 a.m. on 4 February 2022, the perilous rock mass Yizhuxiang in Leizu Town, Yuan’an County, Hubei Province, China collapsed on a large scale. The Yizhuxiang collapse was about 35 m in length, 52 m in height, and 29 m in maximum thickness. The volume of the collapse was 5.32 × 104 m3. It threatened the transport of the national trunk road, destroyed the branch road and some cement mixing station workshops, and caused serious economic losses. The rock mass exposed in the collapse was dolomite with developed joint fractures. Under the effects of mining and unloading, fractures occurred in the rock mass; the top of the rock mass was bent and deformed towards the free face; and tension cracks were formed on the rear edge. The safety ore pillar directly below the collapsed body was compressed and deformed under the action of gravity, thus accelerating the internal deformation of the rock mass and leading to the formation of multiple dominant joints inside the rock mass. In the winter of 2021, the weather was extreme, with heavy snowfall and low temperatures. Under the effects of freeze–thaw, the strength of the rock mass declined and the tension cracks further expanded so that the rock mass experienced an accelerated deformation and finally collapsed. Causes of the collapse include mining activity beneath the collapsed mass and heightened extreme weather. The cause of the landslide disaster in this area is, however, freeze–thaw, which deserves the attention of scholars and the vigilance of the local government.

Extracellular vesicle distribution and localization in skeletal muscle at rest and following disuse atrophy

BackgroundSkeletal muscle (SkM) is a large, secretory organ that produces and releases myokines that can have autocrine, paracrine, and endocrine effects. Whether extracellular vesicles (EVs) also play a role in the SkM adaptive response and ability to communicate with other tissues is not well understood. The purpose of this study was to investigate EV biogenesis factors, marker expression, and localization across cell types in the skeletal muscle. We also aimed to investigate whether EV concentrations are altered by disuse atrophy.MethodsTo identify the potential markers of SkM-derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, followed by fluorescence correlation spectroscopy measurements or qPCR. Single-cell RNA sequencing (scRNA-seq) data from rat SkM were analyzed to assess the EV biogenesis factor expression, and cellular localization of tetraspanins was investigated by immunohistochemistry. Finally, to assess the effects of mechanical unloading on EV expression in vivo, EV concentrations were measured in the serum by nanoparticle tracking analysis in both a rat and human model of disuse.ResultsIn this study, we show that the widely used markers of SkM-derived EVs, α-sarcoglycan and miR-1, are undetectable in serum EVs. We also found that EV biogenesis factors, including the tetraspanins CD63, CD9, and CD81, are expressed by a variety of cell types in SkM. SkM sections showed very low detection of CD63, CD9, and CD81 in myofibers and instead accumulation within the interstitial space. Furthermore, although there were no differences in serum EV concentrations following hindlimb suspension in rats, serum EV concentrations were elevated in human subjects after bed rest.ConclusionsOur findings provide insight into the distribution and localization of EVs in SkM and demonstrate the importance of methodological guidelines in SkM EV research.

Study on the Creep Characteristics and Fractional Order Model of Granite Tunnel Excavation Unloading in a High Seepage Pressure Environment

The creep associated with unloading surrounding rock during the excavation of deep tunnels seriously affects the stability of the tunnel, and a high seepage pressure will aggravate the strength attenuation and structural deterioration of the surrounding rock. Based on the background of the excavation-induced unloading of the surrounding rock of a deeply buried granite tunnel with high seepage pressure, in this paper we carry out a triaxial unloading seepage creep test that considers the effects of both excavation disturbance and seepage pressure. We also analyze the mechanism of unloading and seepage pressure leading to sample failure and construct a fractional creep damage constitutive model that considers the unloading effect. The results include the following findings, firstly, seepage pressure will affect the creep deformation of rock for a long time, and the circumferential expansion of the granite creep process is more obvious than the axial expansion. Secondly, a high seepage pressure will reduce the rock bearing capacity. Under 0, 2 and 4 MPa seepage pressures, the long-term strength of the samples are 193.7 MPa, 177.5 MPa and 162.1 MPa, respectively. Thirdly, the rock damage factor increases with increasing seepage pressure, time and deviatoric stress. Finally, the rationality of a fractional-order model that considers the effect of unloading and seepage is verified by the test data. These research results may provide some reference for the stability analysis of surrounding rock during excavation in environments under high-stress and high-seepage-pressure.

Experimental Study on the Difference Mechanism of Shaft Resistance between Uplift Piles and Compressive Piles

To study the formation mechanism of the lower shaft resistance of uplift piles compared to compression piles, the additional stress caused by uplift and compressive piles in the soil is obtained through indoor model tests with embedded micro earth pressure cells. The study shows that the uplift pile has an unloading effect in pile side soil, and the compressive pile has a loading effect in pile side soil. Closer to the loading point, the unloading effect of the uplift pile and the loading effect of the compressive pile becomes more obvious. The unloading effect decreases the shaft resistance of the uplift pile, and the loading effect increases the shaft resistance of the compressive pile. The tests also reveal that the distribution range of additional stress caused by a single pile is within 6 d from the axis of the pile. After considering the effects of loading and unloading of a single pile, the calculated uplift pile bearing capacity is close to the values of formulas such as Meyerhof and Deshmukh and the measured value.

Effect of mechanical unloading on genome-wide DNA methylation profile of the failing human heart.

Heart failure (HF) is characterized by global alterations in myocardial DNA methylation, yet little is known about the epigenetic regulation of the noncoding genome and potential reversibility of DNA methylation with left ventricular assist device (LVAD) therapy. Genome-wide mapping of myocardial DNA methylation in 36 patients with HF at LVAD implantation, 8 patients at LVAD explantation, and 7 nonfailing (NF) donors using a high-density bead array platform identified 2,079 differentially methylated positions (DMPs) in ischemic cardiomyopathy (ICM) and 261 DMPs in nonischemic cardiomyopathy (NICM). LVAD support resulted in normalization of 3.2% of HF-associated DMPs. Methylation-expression correlation analysis yielded several protein-coding genes that are hypomethylated and upregulated (HTRA1, FBXO16, EFCAB13, and AKAP13) or hypermethylated and downregulated (TBX3) in HF. A potentially novel cardiac-specific super-enhancer long noncoding RNA (lncRNA) (LINC00881) is hypermethylated and downregulated in human HF. LINC00881 is an upstream regulator of sarcomere and calcium channel gene expression including MYH6, CACNA1C, and RYR2. LINC00881 knockdown reduces peak calcium amplitude in the beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These data suggest that HF-associated changes in myocardial DNA methylation within coding and noncoding genomes are minimally reversible with mechanical unloading. Epigenetic reprogramming strategies may be necessary to achieve sustained clinical recovery from heart failure.

Comparative experimental investigation on true triaxial double-sided fast unloading rockburst and biaxial compression under high stress

To explore the effect of rapid excavation unloading under high pressure on delayed rockburst, a true triaxial double-sided rapid unloading rockburst experiment and a biaxial compression failure experiment without unloading were carried out. The results show that the rapid unloading of excavation before the occurrence of rockburst will cause unloading damage, and the axial strain, acoustic emission (AE) count, and AE energy will suddenly increase at the unloading point. The AE source shows that the rapid unloading produces many tensile cracks, mainly distributed near the free surface. The axial peak stress of the rockburst and the stored strain energy before failure are higher than those of biaxial compression, so the ejection velocity of free surface fragments is also higher at failure.