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VAV2 is an activator of RHO GTPases that promotes and maintains regenerative proliferation-like states in normal keratinocytes and oral squamous cell carcinoma (OSCC) cells. Here, we demonstrate that VAV2 also regulates ribosome biogenesis in those cells, a program associated with poor prognosis of human papilloma virus-negative (HPV−) OSCC patients. Mechanistically, VAV2 regulates this process in a catalysis-dependent manner using a conserved pathway comprising the RAC1 and RHOA GTPases, the PAK and ROCK family kinases, and the c-MYC and YAP/TAZ transcription factors. This pathway directly promotes RNA polymerase I activity and synthesis of 47S pre-rRNA precursors. This process is further consolidated by the upregulation of ribosome biogenesis factors and the acquisition of the YAP/TAZ-dependent undifferentiated cell state. Finally, we show that RNA polymerase I is a therapeutic Achilles’ heel for both keratinocytes and OSCC patient-derived cells endowed with high VAV2 catalytic activity. Collectively, these findings highlight the therapeutic potential of modulating VAV2 and the ribosome biogenesis pathways in both preneoplastic and late progression stages of OSCC. [ABSTRACT FROM AUTHOR]

The rock characteristic and size-frequency distribution (SFD) on Mars are important for understanding the geologic and geomorphic history of the surface, for evaluating the trafficability of roving, and for planning the potential infrastructure construction. Tianwen-1, China's first autonomous Mars exploration mission, formed an excavated depression during touchdown, which has been the deepest depression on the Martian surface so far compared with others. According to the images captured using the Navigation and Terrain Cameras (NaTeCams) onboard the rover, Zhurong, the SFD of rocks is calculated and compared inside the excavated depression, within and out of the blast zone. For the first time, the rock size distribution inside the excavated depression is obtained, exposing the geological features of the shallow subsurface on Mars at a depth of tens of centimeters, which will surely be important for future drilling missions. It is found that the rock abundance in the depression is smaller than the original abundance on the surface, and the distribution of rocks in the blast zone on the surface is greatly influenced by the touchdown. In addition, based on the fractal dimension of rock sizes, the rocks (>10 mm) at the shallow subsurface of the Zhurong landing site may experience two different geological processes. [ABSTRACT FROM AUTHOR]

Background and aims: The way in which roots distribute throughout the critical zone influences soil and critical zone formation, as well as water, nutrient and energy fluxes. Root distributions, however, are also influenced by how the critical zone functions. Rapid vegetation changes offer a valuable setting to disentangle these reciprocal effects, and to observe the early changes that occur in the critical zone and how this affects its evolution. Methods: We took advantage of recent exotic Pinus elliottii stands established over native mountain grasslands, to compare how roots of contrasting plant life forms occupy the soil-saprolite-rock continuum. We combined root count and biomass measurements across 2-m-deep observation pits into the saprolite, coupled with topsoil removal plots describing the coarse root transport system introduced by pines. Results: Pine stands had four-fold more root biomass than grasslands (1.74 vs 0.41 kg of dry matter per square meter) and allocated a greater proportion of their fine roots into the saprolite. Pines also developed a coarse root transport system with profuse superficial lateral roots and irregularly distributed sinker roots occupying deep cracks for the first time. Conclusion: The establishment of exotic pines over grasslands reshaped and expanded the root zone in only four decades, highlighting the capacity of vegetation to rapidly change the occupancy and dynamics of the critical zone. [ABSTRACT FROM AUTHOR]

In the present work, important aspects of time-dependent nonlinear 3D finite element (FE) models for deep tunnel advance by the New Austrian Tunneling Method (NATM), characterized by repeated sequences of excavation, securing, and idle periods, are discussed on the example of a 3D finite element model of a stretch of the Brenner Base Tunnel, which is currently constructed between Austria and Italy. Nonlinear material models are utilized for representing the surrounding rock mass and the shotcrete shell. Based on the finite element model, strategies for the efficient implementation into a parallel distributed memory numerical code are proposed. They are essential to achieve reasonable computation times for numerical simulations of tunneling based on large 3D FE models. In particular, the implementation of the construction procedure, parallel computing and communication specific details, and efficient linear solvers for the global equation system within the incremental-iterative Newton-Raphson scheme are addressed. Furthermore, possible extensions of the material models for rock mass and shotcrete, used in the 3D FE model, are presented. They concern (i) a gradient-enhanced model for transversely isotropic rock and rock mass, taking into account hardening and softening behavior and (ii) the extension of the shotcrete model to nonlinear creep and damage due to creep. The possible benefits of the model extensions in numerical simulations of tunneling by the NATM are discussed. [ABSTRACT FROM AUTHOR]

Rock fragment size is a key variable in several mining stages such as underground mine design, equipment selection, and mineral processing. In Block Caving, rock fragment sizes are affected by fragmentation during gravity flow in the ore column while ore is being extracted from drawpoints. Additionally, smaller fragments can percolate between large fragments during gravity flow. These two phenomena — rock fragmentation and particle percolation — are not easy to simulate at a large scale in Block Caving. In this paper, a fragmentation model in a cellular automata gravity flow simulator is proposed to model rock fragmentation during flow at large scales. The fragmentation model uses the rock strength, vertical stresses, and travel distance as inputs to estimate the rock breakage and was calibrated with experimental and mine data. The mine scale results show an error of 9% and 7% of the fragmentation in the zones evaluated. This error rate is considered low due to the variability of the phenomena involved. Then, integrating a fragmentation model into a gravity flow simulator can more realistically represent ore fragmentation in caving-mine to generate flow simulations. [ABSTRACT FROM AUTHOR]

Currently, drilling of directional oil and gas wells under complex technical-technological and mining-geological conditions requires the use of drill pipes made of various materials. In turn, to choose rational modes of strengthening drill pipes and drill string layouts, information on the contact forces and friction forces of the drill string pipes on boreholes is necessary. Drill pipe curved sections friction with boreholes and drill bit resistance moment changes are the main causes of uneven rotation of a drill string during rotary or combined drilling methods and the occurrence of parametric oscillations. To reduce the cost of mechanical energy for well wiring, it is necessary to take into account the "drill string–borehole rocks" force interaction to estimate the magnitude of the frictional forces and their influence on the technological parameters of the drilling process. To solve this problem, mathematical models of "conventionally vertical and inclined drill string sections–borehole" were built. Based on the industrial data, an analysis of the force interaction of a deformed drill string composed of pipes made of different materials (aluminum, titanium, steel) was carried out. Analytical dependences were obtained for determining the contact forces and friction of the pipes on boreholes. A numerical study of the change of these power factors depending on the depth of the well under conditions of intensive vibration loading was carried out. The amplitude values of these forces, the frequency of their change for good sections, as well as the places for the most rational installation of drill pipes in the layout of the drill string were estimated. It was established that the intensity of contact and friction forces for steel drill pipes is greater than for titanium or aluminum ones. It is shown that the greater impact of a solid steel string on contact forces and frictional forces compared to a layout with sections of titanium or aluminum pipes in the range of vibration frequencies of 8–22 Hz corresponds to a bit rotation frequency of 70–80 rpm. The practical application of the obtained research results will contribute to the improvement of technical and economic indicators of the well drilling process. [ABSTRACT FROM AUTHOR]

Background: Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics. Results: Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation. Conclusions: Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications. [ABSTRACT FROM AUTHOR]

Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm's aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 μg/cm2 vs. 96.8 μg/cm2, respectively). The nanoparticle size (144.0 ± 15.6 nm to 835.9 ± 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen's Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (>94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs. [ABSTRACT FROM AUTHOR]

During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as “culture adaptation.” This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions. [ABSTRACT FROM AUTHOR]

We investigate and study on mathematical structures involving mathematical models and others associated with seismic waves in an earthquake. Our first aim is to give some novel formulas and certain finite sums including the Bernoulli numbers and the Hermite polynomials with the aid of generating functions, the Riemann integral, and the Volkenborn integral. The second aim is to examine the seismic wave propagation in different geological units with the help of special polynomials containing the Hermite polynomials and their graph fitting of functions. To evaluate the shape of the seismic waves propagating within the ground (rock and/or soil), we use comparing method with the graph of the Hermite polynomials and functions and the polynomial Rocking Bearings. Furthermore, we also define generating function for the polynomial type Rocking Bearings. We give open problems on this generating function and earthquake facts. By applying partial derivative operator to the generating function for the m-parametric Hermite type polynomials, we give a novel recurrence relation and derivative formulas for these polynomials. We also give a new general formula for monomials in terms of these polynomials. Moreover, for the purpose of visualizing curve fitting approach to the seismic waves, we draw many plots of the Hermite functions with Mathematica (Version 12.0.0) with their codes. Finally, with the aid of these graphs, we give useful evaluation on the shapes of the seismic waves propagated in the ground (rock and/or soil). [ABSTRACT FROM AUTHOR]

This study has carried out three-dimensional nonlinear elastoplastic analyses to understand the behaviour of tunnels constructed in rock having reinforced concrete lining when subjected to impact loading. The Lagrangian analysis tool has been used to create geometry and mesh the different parts of the present rock tunnel model through Abaqus/Explicit software. 3D lagrangian elements have been used to model the rock and concrete lining. The hoop and longitudinal bars of the reinforcement cage have been modelled using a beam element. The impact resistance behaviour of rock tunnel constructed in three different stages of weathered Quartzite has been simulated to understand the stability characteristics of the tunnel. The three-dimensional missile has been considered a rigid material to incorporate the maximum penetration in the rock when it hits the tunnel surface from 100 m. The four different missile weights i.e. 50 kg, 100 kg, 150 kg and 200 kg have been considered to contemplate the extent of deformation and damage In the tunnel. Moreover, the effect of overburden depth variation has been incorporated in terms of H/D ratio, which is defined as the ratio of overburden depth to diameter of the tunnel. The Ducker-Prager constitutive model with strain-rate dependence and dynamic increase factor is considered to simulate the behaviour of Quartzite rock. Johnson-Cook material model is used for steel bars of reinforcement cage and Ducker-Prager model with strain-rate and dynamic increase factor has been considered for reinforced concrete lining of the tunnel. The analyses results were studied for deformation, particle velocity, particle acceleration and damage in rockmass surrounding the tunnel and its reinforced concrete lining. It has been observed that reinforced concrete lining experiences a significant amount of compression and tension damage at the crown of the tunnel and this damage remains concentrated in the middle one-third section of tunnel length irrespective of change in weight of missile and H/D ratio. It has been concluded that a slightly weathered Quartzite rock tunnel has 18% more impact resistance than a medium weathered rock tunnel and 41% from a highly weathered rock tunnel. Moreover, the particle velocity is found to be inversely proportional to the strength of the surrounding rockmass. Further, particle acceleration generated due to impact loading changes proportionally with the rise in the degree of weathering in rocks. Also, it has been concluded that rock tunnels having a H/D ratio of 2.0 has 4-times higher impact resistance in terms of tension damage than the rock tunnels having a H/D ratio of 0.5. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Geológico y Minero is the property of Instituto Tecnologico Geominero De Espana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rho‐associated coiled‐coil kinases (ROCKs) are key downstream effectors of small GTPases. ROCK plays a central role in diverse cellular events with accumulating evidence supporting the concept that ROCK is important in tumor development and progression. Numerous ROCK inhibitors have been investigated for their therapeutic potential in the treatment of cancers. In this article, we review recent research progress on ROCK inhibitors, especially those with potential for the treatment of cancers, reported in the literature from 2015 to 2021. Most ROCK inhibitors show potent in vitro and in vivo antitumor activities and have potential in the treatment of cancers. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most predominant form of dementia. Rho-associated coiled coil kinase (ROCK) inhibitor, fasudil, is one of the candidate drugs against the AD progression. Objective: We aimed to investigate possible changes of AD associated markers in three-dimensional neuro-spheroids (3D neuro-spheroids) generated from induced pluripotent stem cells derived from AD patients or healthy control subjects (HC) and to determine the impact of pharmacological intervention with the ROCK inhibitor fasudil. Methods: We treated 3D neuro-spheroids with fasudil and tested the possible effect on AD markers by ELISA, transcriptomic and proteomic analyses. Results: Transcriptomic analysis revealed a reduction in the expression of AKT serine/threonine-protein kinase 1 (AKT1) in AD neuro-spheroids, compared to HC. This decrease was reverted in the presence of fasudil. Proteomic analysis showed up- and down-regulation of proteins related to AKT pathway in fasudil-treated neuro-spheroids. We found an evident increase of phosphorylated tau at four different residues (pTau181, 202, 231, and 396) in AD compared to HC-derived neuro-spheroids. This was accompanied by a decrease of secreted clusterin (clu) and an increase of intracellular clu levels in AD patient-derived neuro-spheroids. Increases of phosphorylated tau in AD patient-derived neuro-spheroids were suppressed in the presence of fasudil. Conclusions: Fasudil modulates clu protein levels and enhances AKT1 that results in the suppression of AD associated tau phosphorylation. [ABSTRACT FROM AUTHOR]

Copyright of World Nuclear Geoscience is the property of World Nuclear Geoscience Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Celem artykułu jest ukazanie muzyki rockowej jako narzędzia ewangelizacji. Sobór Watykański II zapoczątkował nową relację środowiska kościelnego ze światem kultury i sztuki. Wspólnota Kościoła, w odpowiedzi na wezwanie do dzieła „nowej ewangelizacji”, podjęła niespotykane dotąd formy apostolstwa, które niejednokrotnie budziły kontrowersje. Jedną z nich jest ewangelizacja poprzez muzykę rockową. Dla jednych taka forma muzyki, prezentująca estetykę daleką od zaleceń zebranych w dokumentach Kościoła Katolickiego, oraz jej ładunek kulturowo-światopoglądowy jednoznacznie dyskwalifikuje ją jako narzędzie ewangelizacji. Dla innych natomiast rock pełni ważną funkcję ewangelizacyjną, gdyż taka forma muzyki stanowi odpowiedź na oczekiwania kultury młodzieżowej. Rock z ewangelicznym przesłaniem staje się pomostem, przez który wspólnota Kościoła może dotrzeć z Dobrą Nowiną do młodego pokolenia, coraz częściej żyjącego poza jego strukturami. W konsekwencji, w ramach klasyfikacji takiej twórczości, używa się określenia „rock chrześcijański”, wskazując na odmienność prezentowanych wartości i przesłania. Fenomen „rocka chrześcijańskiego” ukazuje dwa ważne aspekty. Pierwszy ukazuje, jak radykalną przemianę form muzycznych przechodzi muzyka religijna, aby odpowiedzieć na potrzeby czasu. Z drugiej, że przesłanie Ewangelii realnie wkroczyło w świat muzyki rozrywkowej i zaczęło się nią posługiwać dla osiągnięcia własnych celów. Ujęcie historyczne problemu stanowi inspirację do podjęcia kolejnych badań, np. w wymiarze socjologicznym i kulturowym.

Biomineralization had apparently evolved independently in different phyla, using distinct minerals, organic scaffolds, and gene regulatory networks (GRNs). However, diverse eukaryotes from unicellular organisms, through echinoderms to vertebrates, use the actomyosin network during biomineralization. Specifically, the actomyosin remodeling protein, Rho-associated coiled-coil kinase (ROCK) regulates cell differentiation and gene expression in vertebrates’ biomineralizing cells, yet, little is known on ROCK’s role in invertebrates’ biomineralization. Here, we reveal that ROCK controls the formation, growth, and morphology of the calcite spicules in the sea urchin larva. ROCK expression is elevated in the sea urchin skeletogenic cells downstream of the Vascular Endothelial Growth Factor (VEGF) signaling. ROCK inhibition leads to skeletal loss and disrupts skeletogenic gene expression. ROCK inhibition after spicule formation reduces the spicule elongation rate and induces ectopic spicule branching. Similar skeletogenic phenotypes are observed when ROCK is inhibited in a skeletogenic cell culture, indicating that these phenotypes are due to ROCK activity specifically in the skeletogenic cells. Reduced skeletal growth and enhanced branching are also observed under direct perturbations of the actomyosin network. We propose that ROCK and the actomyosin machinery were employed independently, downstream of distinct GRNs, to regulate biomineral growth and morphology in Eukaryotes.

Our previous studies demonstrated that traumatic brain injury (TBI) and ventricular administration of thrombin caused hippocampal neuron loss and cognitive dysfunction via activation of Src family kinases (SFKs). Based on SFK localization in brain, we hypothesized SFK subtypes Fyn and c-Src, as well as SFK downstream molecule Rho-associated protein kinase (ROCK), contribute to cell death and cognitive dysfunction after TBI. We administered nanoparticle wrapped small interfering RNA (siRNA)-Fyn and siRNA-c-Src, or ROCK inhibitor Y-27632 to adult rats subjected to moderate lateral fluid percussion (LFP)-induced TBI. Spatial memory function was assessed from 12 to 16 days, and NeuN stained hippocampal neurons were assessed 16 days after TBI. The combination of siRNA-Fyn and siRNA-c-Src, but neither alone, prevented hippocampal neuron loss and spatial memory deficits after TBI. The ROCK inhibitor Y-27632 also prevented hippocampal neuronal loss and spatial memory deficits after TBI. The data suggest that the combined actions of three kinases (Fyn, c-Src, ROCK) mediate hippocampal neuronal cell death and spatial memory deficits produced by LFP-TBI, and that inhibiting this pathway prevents the TBI-induced cell death and memory deficits.

The use of geothermal energy, which comes from both deep geothermal systems and the shallow underground, has been developing rapidly in the last few decades. The purpose of the paper is to present the results of measurements of the thermal properties of all rock samples and sediments that were available from boreholes, two tunnels and numerous surface locations in Slovenia in the period from 1982 to the end of 2022. In relation to the shallow geothermal potential, a special effort is needed to characterize the thermal properties of the rocks and sediments and to implement thermal energy transfer technology. In this sense, knowledge of the thermal conductivity of rocks and sediments is required to assess the possibility of low-enthalpy heat exchange in a given local area. The largest number of measurements was taken to determine thermal conductivity. Determinations of thermal diffusivity were carried out on a much smaller number of rock and sediment samples, as well as determinations of radiogenic heat production in rocks. The results of thermal conductivity measurements on 430 samples from 119 wells, 20 samples from two tunnels and 156 samples from surface locations are shown. The highest thermal conductivities are shown by samples of dolomite, quartz conglomerate and conglomerate, phyllonite, quartz phyllite and gneiss, while the lowest are measured in sediments such as clay, lignite with clay, peat and dry sand. The determined radioactive heat generation is the lowest for milonitized dolomite and highest for dark grey sandstone with shale clasts. Our results are comparable to those already published worldwide, and they could be the basis for the possible future Slovenian standard for the thermal properties of measured rocks and sediments.

As one of the most important parameters to express radiation's harmful effects is excess lifetime cancer risk, which is presented in the literature with the empirical relationship, an alternative association was developed for excess lifetime cancer risk in this study. This relationship included radiological risk parameters and the average life expectancy and also does not require a coefficient recommended by organizations. The selected area is Çünür district of Isparta province in Türkiye, which is approximately 12.5 km2. The gamma-ray spectrometry studies were carried out at 270 different points. In this study, the radioactive elements (U, Th, and K) are directly measured on the geological materials (trachyandesite, flysch, limestone, and soil) using a gamma-ray spectrometer device. Maps were created to compare the outcomes of excess lifetime cancer risk determined with the new approach and calculated using the existing relationship in the literature. Also, the calculated radiological risk parameters were mapped to evaluate the study area in general. In addition to these, the relationships between each other radioactive elements and the relationships between the radioactive elements and the radiological risk parameters were investigated.

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS- or stearic acid (SA)-induced inflammatory responses in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK, which acts downstream of TPR, attenuated LPS- and/or SA-induced pro-inflammatory responses. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, the TPR agonist by itself elicits an inflammatory response, which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs, and this effect is mediated via TLR4 and/or ROCK signaling.

Fatigue damage can occur in surface rock engineering due to various factors, including earthquakes, blasting, and impacts. The underlying cause for the variations in physical and mechanical properties of the rock resulting from impact loading is the alteration in the internal pore structure. To investigate the evolution characteristics of the pore structure under impact fatigue damage, red sandstone subjected to cyclic impact compression by split Hopkinson pressure bar (SHPB) was analyzed using nuclear magnetic resonance (NMR) technology. The parameters describing the evolution of pore structure were obtained and quantified using fractal methods. The development of the pore structure in rocks subjected to cyclic impact was quantitatively analyzed, and two fractal evolution models based on pore size and pore connectivity were constructed. The results indicate that with an increasing number of impact loading cycles, the porosity of the red sandstone gradually increases, the T2 cutoff (T2c) value decreases, the most probable gray value of magnetic resonance imaging (MRI) increases, the pores’ connectivity is enhanced, and the fractal dimension decreases gradually. Moreover, the pore distribution space tends to transition from three-dimensional to two-dimensional, suggesting the expansion of dominant pores into clusters, forming microfractures or even macroscopic fissures. The findings provide valuable insights into the impact fatigue characteristics of rocks from a microscopic perspective and contribute to the evaluation of time-varying stability and the assessment of progressive damage in rock engineering.

Under compressive loading, rocks emit electromagnetic waves, and monitoring electromagnetic signals has become a key means of predicting dynamic rock disasters. To understand how dynamic potential is generated in rocks under compressive loading, the relationship between the compressive loading (P) and the stimulated potential (E) is seen as a circuit system (H(t)). A circuit analysis model has been established to study how rock particles restructure under compressive loading. Experimental tests were conducted to measure the input excitation (E) and output response (Uσ(t)) or (Iσ(t)) of the rock specimens, with four types of rocks being tested. The experiments revealed that voltage, current, frequency, and impedance changed during the particle reorganization process under compressive loading, showing that the electromagnetic radiation of the rock specimens mainly came from the current generated by the internal particle reorganization. The intensity of electromagnetic radiation was found to depend on the load size and dynamic impedance (Zσ), with the dynamic impedance (Zσ) consisting of the microelement total resistance (Rσ), capacitance (Cσ), and inductance (Lσ). The variation of dynamic impedance (Zσ) is related to the rock type. The research findings have contributed to elucidating the mechanism of electromagnetic radiation generated by rocks under load.

Lung epithelial development relies on the proper balance of cell proliferation and differentiation to maintain homeostasis. When this balance is disturbed, it can lead to diseases like cancer, where cells undergo hyperproliferation and then can undergo migration and metastasis. Lung cancer is one of the deadliest cancers, and even though there are a variety of therapeutic approaches, there are cases where treatment remains elusive. The rho-associated protein kinase (ROCK) has been thought to be an ideal molecular target due to its role in activating oncogenic signaling pathways. However, in a variety of cases, inhibition of ROCK has been shown to have the opposite outcome. Here, we show that ROCK inhibition with y-27632 causes abnormal epithelial tissue development in Xenopus laevis embryonic skin, which is an ideal model for studying lung cancer development. We found that treatment with y-27632 caused an increase in proliferation and the formation of ciliated epithelial outgrowths along the tail edge. Our results suggest that, in certain cases, ROCK inhibition can disturb tissue homeostasis. We anticipate that these findings could provide insight into possible mechanisms to overcome instances when ROCK inhibition results in heightened proliferation. Also, these findings are significant because y-27632 is a common pharmacological inhibitor used to study ROCK signaling, so it is important to know that in certain in vivo developmental models and conditions, this treatment can enhance proliferation rather than lead to cell cycle suppression.

Accurately identifying the high-temperature history experienced by rocks is essential for understanding their behaviour and predicting properties. However, current approaches are limited by the heterogeneity of rocks, test scale and costs. Here, we proposed an economical, efficient and accurate approach to identifying the rocks after high-temperature deterioration via deep learning. This deep learning-based method exhibited superior abilities in distinguishing the heat-treated rock. Using a scanning electron microscopy (SEM) image covering a size of 14.6 μm × 14.6 μm, the high-temperature deterioration history of rocks can be recognized with an accuracy of 80.2%. Features such as cracks, rock patterns, and cleavage steps in SEM images would further improve the recognition accuracy. For example, SEM images with higher fractal box dimensions show a higher recognization accuracy, especially for temperatures under 600 °C. Besides, using the deep Taylor decomposition algorithm, the high-temperature deterioration regions of the rocks in the microscale were successfully located, extracted, and characterized for the first time. This study highlights the vast potential of the deep learning-based approach in damage deterioration identification of rock after high temperature, which significantly extends the application of deep learning in underground projects.

While yes-associated protein (YAP) is now recognized as a potent mechanosensitive transcriptional regulator to affect cell growth and differentiation including the osteogenic transcription of mesenchymal stem cells (MSCs), most studies have reported the YAP mechanosensing of static mechanophysical cues such as substrate stiffness. We tested MSC response to dynamic loading, i.e., cyclic mechanical stretching, and assessed YAP mechanosensing and resultant MSC osteogenesis. We showed that cyclic stretching at 10% strain and 1 Hz frequency triggered YAP nuclear import in MSCs. YAP phosphorylation at S127 and S397, which is required for YAP cytoplasmic retention, was suppressed by cyclic stretch. We also observed that anti-YAP-regulatory Hippo pathway, LATS phosphorylation, was significantly decreased by stretch. We confirmed the stretch induction of MSC osteogenic transcription and differentiation, and this was impaired under YAP siRNA suggesting a key role of YAP dynamic mechanosensing in MSC osteogenesis. As an underlying mechanism, we showed that the YAP nuclear transport by cyclic stretch was abrogated by ROCK inhibitor, Y27632. ROCK inhibitor also impaired the stretch induction of F-actin formation and MSC osteogenesis, thus implicating the role of the ROCK-F-actin cascade in stretch-YAP dynamic mechanosensing-MSC osteogenesis. Our results provide insight into bone tissue engineering and skeletal regenerative capacity of MSCs especially as regards the role of dynamic mechanical loading control of YAP-mediated MSC osteogenic transcription.

To fulfill the requirement for deformation measurement within the failure area during rock failure, a newly developed digital image algorithm, known as the corner correlation method, was implemented. A corner correlation measurement system was established by utilizing a Split Hopkinson Pressure Bar (SHPB) and a high-speed camera. The study focused on monitoring the deformation and failure characteristics of sandstone samples under dynamic loading. The results show that the corner correlation method has its unique advantages in rock dynamic mechanics experiments, and can obtain the deformation of the failure region during the rock failure process. Specifically, the initiation, extension, and contraction processes of surface cracks on sandstone were examined. Parameters such as crack width, width propagation rate, and extension shrinkage rate were measured. The entire crack development process was analyzed, including crack width, crack initiation point, crack extension and contraction trajectory, elongation and contraction velocity, width expansion rate, and longitudinal crack penetration, which were obtained at any given time on the surface of the rock sample. Additionally, the attenuation law of stress, characterized by an exponential decay of the stress peak value, was obtained through numerical simulation using a similar model.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease without early diagnostic and specific therapeutic approaches. Podocyte apoptosis and loss play important roles in the pathological process of DKD. This study aimed to explore whether urinary exosomes from type 2 diabetes patients with DKD could induce podocyte apoptosis and the underlying pathological mechanisms. The exosomes were isolated from the urine samples of patients with DKD (DKD-Exo). Later, they were taken up and internalized by MPC5 cells. MPC5 cells were co-cultured with DKD-Exo (45 μg/ml) for 24 h in the presence or absence of microRNA-145-5p (miR-145-5p) inhibitor, fasudil and pcDNA-Srgap2 transfection. MiR-145-5p and Srgap2 expression was evaluated using real-time quantitative PCR. The protein levels of Srgap2, Bcl-2, Bax, and cleaved caspase-3, as well as ROCK activity were determined using Western blotting. Cell apoptosis was measured using flow cytometry and the TUNEL assay. miR-145-5p expression in MPC5 cells exposed to DKD-Exo was markedly upregulated. miR-145-5p negatively regulated Srgap2 levels. Exposure of MPC5 cells to DKD-Exo reduced Srgap2 expression and activated ROCK, which was partly reversed by the presence of the miR-145-5p inhibitor or Srgap2 overexpression. The apoptosis of MPC5 cells exposed to DKD-Exo increased significantly, which was counteracted by the addition of the miR-145-5p inhibitor and fasudil. The results showed that urinary exosomal miR-145-5p from patients with DKD induced podocyte apoptosis by inhibiting Srgap2 and activating the RhoA/ROCK pathway, suggesting that urinary exosomal miR-145-5p is involved in the pathological process of DKD and could become a noninvasive diagnostic biomarker for DKD.

Drilling and blasting is still the most widely used method for tunnel excavation in hard rocks. However, this method causes damage to adjacent buildings and structures mainly because of tunnel blast-induced vibrations. Currently, no specific guidelines are available for optimizing the design of damping holes during controlled blasting. Therefore, this study analyzes the vibration reduction mechanism of damping holes. Six key factors, namely, hole radius, hole spacing, coverage length, arrangement type, number of rows, and row spacing, that can affect the blasting vibration reduction were analyzed theoretically. Six groups of 30 numerical models were established using LS-DYNA. The influences of the six factors on the average and maximum velocities and stress vibration reduction were analyzed to quantitatively evaluate their damping effects. Then, optimization design suggestions for damping holes were proposed. The results revealed that it is necessary to increase the hole diameter and reduce the hole and row spacings as much as possible. The reasonable coverage length of damping holes is 1.5 times the coverage length of blasting holes. The blossom-type arrangement is recommended for practical engineering applications and the number of rows of damping holes should not exceed four. Guidelines for reducing vibration in adjacent tunnel blasting were formulated. Finally, the optimized damping hole design was applied to a typical tunnel project, which verified its reasonability and applicability.

GPR55 is involved in many physiological and pathological processes. In cancer, GPR55 has been described to show accelerating and decelerating effects in tumor progression resulting from distinct intracellular signaling pathways. GPR55 becomes activated by LPI and various plant-derived, endogenous, and synthetic cannabinoids. Cannabinoids such as THC exerted antitumor effects by inhibiting tumor cell proliferation or inducing apoptosis. Besides its effects through CB1 and CB2 receptors, THC modulates cellular responses among others via GPR55. Previously, we reported a reduction in Ki67-immunoreactive nuclei of human glioblastoma cells after GPR55 activation in general by THC and in particular by LPI. In the present study, we investigated intracellular mechanisms leading to an altered number of Ki67+ nuclei after stimulation of GPR55 by LPI and THC. Pharmacological analyses revealed a strongly involved PLC-IP3 signaling and cell-type-specific differences in Gα-, Gβγ-, RhoA-ROCK, and calcineurin signaling. Furthermore, immunochemical visualization of the calcineurin-dependent transcription factor NFAT revealed an unchanged subcellular localization after THC or LPI treatment. The data underline the cell-type-specific diversity of GPR55-associated signaling pathways in coupling to intracellular G proteins. Furthermore, this diversity might determine the outcome and the individual responsiveness of tumor cells to GPR55 stimulation by cannabin oids. [ABSTRACT FROM AUTHOR]

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Purpose. To develop new resource-saving method of underground construction and evaluate how effective it is, to set thresholds for safe seismic ground vibrations which accompany explosions during breaking in mine workings. Methodology. The work used method of analysing mining and geological conditions of workings, field surveys of rock conditions in face, experiments are conducted on rock samples taken from blasting sites, more detailed data are obtained on rock properties, type and direction of development of crack systems along the workings cross-section by funneling method and approved research methods in accordance with current State Standards. Findings. Research has been carried out to determine main features of physical and mechanical properties of rocks, fracture and tectonic structure of rock mass and development of fracture systems. According to the results of ejection funnel parameters, the anisotropy coefficient was calculated, and according to data on identification of crack systems and their density, fracture coefficient was calculated. The experimental data obtained were used to adjust rational distances between contour boreholes and along the entire cross-section of working face. Based on corrected drilling and blasting operations (DBO), experimental explosions were carried out in workings. It was established that the borehole utilisation rate (BUR) was 0.95–0.97, uniformity of rock mass crushing was achieved, and explosive material consumption was reduced by 10–15 %. Instrumental measurements of explosion impact in workings proved seismic ground vibrations at protected facilities amounted to 0.4 cm/s with a duration of 0.05 s, which did not exceed the State Standard. [ABSTRACT FROM AUTHOR]

Due to the differences in techniques between the shield method and the mining method, it is not appropriate to directly draw from the relevant research results and experience of the mining method to calculate the surrounding rock pressure on shield tunnels. And the whole-soil column theory and the Terzaghi theory are only applicable to soft soil strata. Therefore, based on the theory of elasticity and construction characteristics of the shield method, this study has explored the surrounding rock pressure on the shield segment structure in rock strata. Based on the NATM and the ADECO-RS, the impact of the synchronous grouting layer, and the thick-walled cylinder theory, we have established the relationship among the surrounding rock, the synchronous grouting layer, and the segment and obtained the formula to calculate the surrounding rock pressure acting on the shield segment structure in rock strata. Additionally, we took the shield tunnels with moderately weathered and lightly weathered mixed granite on a road tunnel as the research targets and adopted the analytical method to calculate the surrounding rock pressure, which is 0.276 γ H and 0.192 γ H , respectively. [ABSTRACT FROM AUTHOR]

The activities of quarrying in Ebonyi State have resulted in the loss of soil nutrients and an increase in soil pollution. This paper examines the environmental impact of quarrying on soil quality in the three zones of Ebonyi State, south-eastern Nigeria. To achieve the main aim of the study, three objectives were set: access the environmental impact of quarrying on the soil quality of the three zones of Ebonyi district; examine the physico-chemical properties of the soil; and evaluate the environmental impact of quarrying on the heavy metal content of the soil. The auger and core samples were collected at a depth of 20 cm to obtain physicochemical soil properties and heavy metal content. The generated data were subjected to factor analysis, which consists of a correlation matrix, KMO and Bartlett's test, communalities, total variance, scree plot, and component matrix. The major results showed that quarrying has significantly negatively impacted the soils of the three zones of Ebonyi State, as it has led to distortions in soil quality. The results also proved that soil quality within 0–50 m of quarry sites was found to be poorer than in the control area. Positive correlation matrix studies between the quarry locations revealed a common origin of pollution and the negative impact of quarry activities on soil. Based on the results, the study strongly recommends that such soils not be used for agricultural production unless remediation methods are in place, such as bioremediation, soil washing, and thermal desorption. [ABSTRACT FROM AUTHOR]

The mechanical properties of fractured rock have always been a focal point in the rock mechanics field. Based on previous research, this paper proposes improvements to the SPH method and applies it to the study of crack propagation in fractured rocks. By conducting uniaxial compression tests and simulating crack propagation on various specimens with different crack shapes, the characteristics of crack propagation were obtained. The comparison between the simulated results in this study and existing experimental and numerical simulation results confirms the validity of the SPH method employed in this paper. The present study utilizes the proposed methodology to analyze the influence of the crack angle, width, and orientation on crack propagation. The SPH method employed in this study effectively demonstrates the expansion process of fractured rock under uniaxial compression, providing valuable insights for the engineering applications of SPH. [ABSTRACT FROM AUTHOR]

The peak dilation angle is an important mechanical feature of rock discontinuities, which is significant in assessing the mechanical behaviour of rock masses. Previous studies have shown that the efficiency and accuracy of traditional experimental methods and analytical models in determining the shear dilation angle are not completely satisfactory. Machine learning methods are popular due to their efficient prediction of outcomes for multiple influencing factors. In this paper, a novel hybrid machine learning model is proposed for predicting the peak dilation angle. The model incorporates support vector regression (SVR) techniques as the primary prediction tools, augmented with the grid search optimization algorithm to enhance prediction performance and optimize hyperparameters. The proposed model was employed on eighty-nine datasets with six input variables encompassing morphology and mechanical property parameters. Comparative analysis is conducted between the proposed model, the original SVR model, and existing analytical models. The results show that the proposed model surpasses both the original SVR model and analytical models, with a coefficient of determination (R2) of 0.917 and a mean absolute percentage error (MAPE) of 4.5%. Additionally, the study also reveals that normal stress is the most influential mechanical property parameter affecting the peak dilation angle. Consequently, the proposed model was shown to be effective in predicting the peak dilation angle of rock discontinuities. [ABSTRACT FROM AUTHOR]

Grip and elbow flexor strength and endurance are crucial performance surrogates in competitive climbing. Thus, we examined the effects of blood flow restricted (BFR) climbing on grip and elbow flexor performance. Fifteen trained climbers (8 females; 20.8 ± 7.0 yrs; 1.72 ± 0.08 m; 63.0 ± 9.7 kg; 21.7 ± 2.7 IRCRCA grade) were either assigned to the intervention (BFR) or control (noBFR) group, using the minimization method (Strata: age, height, body mass, gender, and IRCRA grade). While BFR was used during low-intensity climbing training (2-times 10 min/session; 3-times/week), noBFR followed identical training protocols without BFR over 5 weeks. BFR of the upper limb was applied via customized pneumatic cuffs (occlusion pressure: 120 ± 23 mmHg, 75%; occlusion pressure). Endurance and strength performances were assessed via one-handed rung pulling (GripSTRENGTH), one-handed bent arm lock off at 90° (ArmSTRENGTH), static-intermitted finger hang (GripENDURANCE), and bent arm hang (ArmENDURANCE). Bayesian credible intervals revealed increased GripENDURANCE (+21 s (95% credible interval: −2 to 43 s)) and ArmENDURANCE +11 s (−5 to 27 s); adaptations via BFR. In contrast, GripSTRENGTH +4 N (−40 to 48 N) and ArmSTRENGTH +4 N (−68 to 75 N) were not affected by the BFR intervention. Fifteen cumulative sessions of BFR application with a cumulative total BFR load of 5 h over a 5 weeks macrocycle remarkably increased grip and elbow flexor endurance. Thus, BFR might serve as a promising means to improve relevant performance surrogates in trained climbers. Blood flow restricted (BFR) climbing induced superior grip and elbow flexor endurance adaptations compared to non-restricted climbing training over a 5-week lasting training period BFR and non-BFR climbing training induced similar grip and elbow flexor strength adaptations Therefore, BFR served as a feasible, promising and beneficial complementary training stimuli additionally to the sheduled climbing training program. [ABSTRACT FROM AUTHOR]

The purpose of the paper is to highlight the peculiarities of vocal improvisation in rock music. The historical and theoretical aspects of the research problem are characterised, the works of famous rock singers whose vocal improvisation has become an integral part of their musical activity are analysed. Research methodology. To achieve this goal, a set of methods was used, namely: general scientific methods - analysis, synthesis, generalisation, systematisation - were used to develop the problem; specific scientific methods: historical-genetic and retrospective analysis, which clarified the formation and development of rock music; comparative and contrastive analysis, which was used to outline vocal improvisation in rock music; biographical method, which was used to analyse vocal improvisation in the activities of famous rock singers. The scientific novelty lies in the fact that for the first time the features of vocal improvisation in rock music are presented. Conclusions. The article focuses on the concept of "vocal improvisation" (the process of creating music with the voice without pre-prepared musical or textual materials), reveals its essential aspects in rock music, which are hidden in a special tension, energy, emotional load, melody, smooth transitions between notes, the use of a rough voice, special effects such as echo, reverb, vocal filters. The features of vocal improvisation are analysed on the example of the works of Freddie Mercury (rock band "Queen"), Robert Plant (rock band "Led Zeppelin"), Steven Tyler (rock band "Aerosmith"). It has been found that a wide vocal range, the use of high notes, spontaneous vocal phrases and sounds are characteristic of Freddie Mercury ("Bohemian Rhapsody", "Galileo", "Someone to Love"). Whereas strong, expressive vocals and the ability to vary vocal riffs characterize Robert Plant ("Whole Lotta Love", "Dazed and Confused", "Black Dog") and Steven Tyler ("Dream", "Sweet Emotions", "Mama Kin"). The focus is on vocal improvisation in rock music of the early ХХІ century, which is characterized by eclectic styles, the use of technology, and variations in lyrics. [ABSTRACT FROM AUTHOR]

With the development of data collection and storage capabilities in recent decades, abundant data have been accumulated in geotechnical engineering fields, providing opportunities for the usage of machine learning approaches. Thus, a rising number of scholars are adopting machine learning techniques to settle geotechnical issues. In this paper, the application of three popular machine learning algorithms, support vector machine (SVM), artificial neural network (ANN), and decision tree (DT), as well as other representative algorithms in geotechnical engineering, is reviewed. Meanwhile, the applicability of diverse machine learning algorithms in settling specific geotechnical engineering issues is compared. The main findings are as follows: ANN, SVM, and DT have been widely adopted to solve a variety of geotechnical engineering issues, such as the classification of soil and rock types, predicting the properties of geotechnical materials, etc. Based on the collected relevant research, the performance of random forest (RF) in sorting soil types and assessing landslide susceptibility is satisfying; SVM has high precision in classifying rock types and forecasting rock deformation; and backpropagation ANNs and Hopfield ANNs are recommended to forecast rock compressive strength and soil settlement, respectively. [ABSTRACT FROM AUTHOR]

Understanding the response mechanism of multiparameter rock fractures can improve the accuracy of crack diagnosis. In this study, three types of rock samples with notches were subjected to three-point bending tests. The fracture morphology was observed using scanning electron microscopy, and real-time resistivity and acoustic emission (AE) data were used to describe the crack propagation. The spatial distribution of the electric potential was simulated based on practical crack morphologies and can explain the correlation between rock fracture and rock resistivity or AE. The results reveal that the initiation and propagation of cracks reconstructs the electrical potential distribution characteristics of the rock samples and changed their overall resistivity. The crack growth rate was proportional to the rate of increase in the resistivity rate, and the resistivity increased with nonuniform crack growth. Crack geometry complexity affected circuit connectivity, and a higher resistivity change rate was typically caused by cracks with more uniform propagation. The resistivity variation had the same trend as the fracture toughness, whereas the AE energy exhibited a similar trend to the fracture energy evolution. The cumulative AE count of the granite fracture was the largest, and the peak AE count of coal was larger than that of sandstone. In the main frequency band of 100 ± 25 kHz, a relatively large AE event occurred during crack initiation, and the AE amplitude of granite was the largest. The primary fracture propagation increased the peak AE count, amplitude, energy, and fracture energy release efficiency. During rock fracture, the opening of a microscopic bedding plane and a matrix fracture results in time-varying resistivity and AE characteristics. The complementary electrical and acoustic parameters help describe the details of crack propagation behaviour. Highlights: Cracks restructure the electrical potential distributions in rock samples and change the resistivity. The acoustic emission (AE) energy exhibits a similar trend to the fracture energy evolution. The relationship between the resistivity and AE is mutually verified and complementary. [ABSTRACT FROM AUTHOR]

Purpose: To assess the combined effects of omidenepag (OMD), a selective EP2 agonist, and ripasudil (Rip), an inhibitor of rho-associated coiled-coil containing protein kinases, on the human orbital adipose tissue, two-dimensional (2D) or three-dimensional (3D) cultures of human orbital fibroblasts (HOFs) were employed. Methods: Cellular metabolic functions (2D), physical (3D), lipid staining (3D), and quantitative polymerase chain reaction for adipogenesis-related genes, PPARγ and AP2, and extracellular matrix (ECM) molecules, including collagen (COL)1, 4, and 6, and fibronectin (FN) (3D) were evaluated in the presence of OMD (100 nM) and/or Rip (10 μM). Results: Real-time metabolic analyses revealed that the adipogenic differentiation (DIF+) with OMD significantly shifted an energetic state toward energetic, whereas DIF+ with Rip significantly shifted that toward quiescent. In the case of both drugs upon DIF+, the metabolic effect of OMD was predominant. DIF+ induced enlargement and stiffed 3D spheroid with increased lipid staining and mRNA expression of adipogenesis-related genes, COL4 and COL6, and decreased the expression of COL1. In the presence of OMD and/or Rip to DIF+, (1) the sizes were further increased by Rip and the stiffness was significantly decreased by OMD or Rip and (2) COL4 or AP2 expression was substantially increased by OMD or Rip, respectively. Conclusion: The results presented herein indicate that the metabolic effects of OMD and Rip exerted opposing effects and the effects of OMD toward Ap2 and ECM expressions were distinct from those of Rip, but the effects of OMD toward the physical aspects and adipogenesis of the 3D cultured HOFs were similar to the effects of Rip. [ABSTRACT FROM AUTHOR]