Mechanical effects modulate drug resistance in MCF-7-derived organoids: Insights into the wnt/ß-catenin pathway.

Addressing drug resistance poses a significant challenge in cancer treatment, as cancer cells develop diverse mechanisms to evade chemotherapy drugs, leading to treatment failure and disease relapse. Three-dimensional (3D) cell culture has emerged as a valuable model for studying drug resistance, although the underlying mechanisms remain elusive. By obtaining a better understanding of drug resistance within the 3D culture environment, we can develop more effective strategies to overcome it and improve the success of cancer treatments. Notably, the physical structure undergoes notable changes in 3D culture, with mechanical effects believed to play a pivotal role in drug resistance. Hence, our study aimed to explore the influence of mechanical effects on drug resistance by analyzing data related to "drug resistance" and "mechanobiology". Through this analysis, we identified ß-catenin and JNK1 as potential factors, which were further examined in MCF-7 cells cultivated under both 2D and 3D culture conditions. Our findings demonstrate that ß-catenin is activated through canonical and non-canonical pathways and associated with the drug resistance, particularly in organoids obtained under 3D culture.

Elevating Surface-Enhanced Infrared Absorption with Quantum Mechanical Effects of Plasmonic Nanocavities.

Plasmonic nanocavities, with the ability to localize and concentrate light into nanometer-scale dimensions, have been widely used for ultrasensitive spectroscopy, biosensing, and photodetection. However, as the nanocavity gap approaches the subnanometer length scale, plasmonic enhancement, together with plasmonic enhanced optical processes, turns to quenching because of quantum mechanical effects. Here, instead of quenching, we show that quantum mechanical effects of plasmonic nanocavities can elevate surface-enhanced infrared absorption (SEIRA) of molecular moieties. The plasmonic nanocavities, nanojunctions of gold and cadmium oxide nanoparticles, support prominent mid-infrared plasmonic resonances and enable SEIRA of an alkanethiol monolayer (CH3(CH2)n-1SH, n = 3-16). With a subnanometer cavity gap (n < 6), plasmonic resonances turn to blue shift and the SEIRA signal starts a pronounced increase, benefiting from the quantum tunneling effect across the plasmonic nanocavities. Our findings demonstrate the new possibility of optimizing the field enhancement and SEIRA sensitivity of mid-infrared plasmonic nanocavities.

Strain-Stabilized Ceramic-Sulfide Electrolytes.

Ceramic-sulfide solid electrolytes are a promising material system for enabling solid-state batteries. However, one challenge that remains is the discrepancy in the reported electrochemical stability. Recent work has suggested that it may be due to the sensitivity of ceramic sulfides to mechanically induced stability. Small changes in ceramic-sulfide microstructure, for example, have been shown to cause substantial differences in the electrochemical stability. In this work, a rigorous theoretical framework is constructed to enable the simulation of such mechanically induced stability for a generalized constraint mechanism. It is shown that the susceptibility for voltage widening in ceramic sulfides can be significantly influenced by the choice of different decay morphology models. This results in a less intrusive microstructure requirement for improved stability, which stems from the tendency of sulfides to decay via inclusions rather than homogeneously. This predicted decay morphology is experimentally confirmed. Li10 GeP2 S12 is stabilized by a thin amorphous shell, which prior models predict is too thin for stabilization. The generality of this framework is discussed in light of stabilization methods beyond microstructure, such as on the battery cell level. The relation of our picture to the observed lithium metal formation in ceramic sulfides is also discussed.

Detection of Magnetomechanical Effect in Structural Steel Using GMR 2nd Order Gradiometer Based Sensors.

The magneto-mechanical behaviour of structural steel specimens stressed up to the plastic deformation stage was investigated using a 2nd order gradiometer based on Giant Magneto Resistive (GMR) sensors. The correlation between the gradient of the magnetization and the dislocation density before the crack initiation inside the test material was reported. The capability of the GMR scanning sensor to detect the residual magnetization due to the tensile stress with a non-invasive technique was demonstrated.

Acoustic Emission from Organic Martensites.

In salient effects, still crystals of solids that switch between phases acquire a momentum and are autonomously propelled because of rapid release of elastic energy accrued during a latent structural transition induced by heat, light, or mechanical stimulation. When mechanical reconfiguration is induced by change of temperature in thermosalient crystals, bursts of detectable acoustic waves are generated prior to self-actuation. These observations provide compelling evidence that the thermosalient transitions in organic and organic-containing crystals are molecular analogues of the martensitic transitions in some metals, and metal alloys such as steel and shape-memory alloys. Within a broader context, these results reveal that, akin to metallic bonding, the intermolecular interactions in molecular solids are capable of gradual accrual and sudden release of a substantial amount of strain during anisotropic thermal expansion, followed by a rapid transformation of the crystal packing in a diffusionless, non-displacive transition.

Interplay Between Mechanochemistry and Sonochemistry.

Ultrasonic irradiation-based mechanochemical strategies have recently been the subject of intensive investigation because of the advantages they offer. These include simplicity, energy savings and wide applicability. Traditional areas of sonoprocessing such as cleaning, efficient mixing and solid activation have been extended to both macromolecular and micro/nanostructures, some of which are biologically significant, ultrasound-responsive actuators and crystal design, among others. Unlike conventional mechanochemical protocols, which require little solvent usage if any at all, mechanical (and chemical) effects promoted by ultrasound are observed in a liquid medium. Tensile forces, which share similarities with solid mechanochemistry, are generated by virtue of nonlinear effects, notably cavitation, when high-amplitude waves propagate in a fluid. This work aims to provide insight into some recent developments in the multifaceted field of sono-mechanochemistry using various examples that illustrate the role of ultrasonic activation, which is capable of boosting hitherto sterile transformations and inventing new crafts in applied chemistry. After a preliminary discussion of acoustics, which is intended to provide a mechanistic background, we mainly focus on experimental developments, while we often mention emerging science and occasionally delve into theoretical models and force simulations.

Mechanism of static loading injury in human skeletal muscle cells.

OBJECTIVE: To establish a cellular-level mechanical injury model for human skeletal muscle cells and investigate changes in the mechanical effect mechanism after such injuries. METHODS: The FX-5000™ Compression System was used to apply constant static mechanical pressure to human skeletal muscle cells. A factorial design analysis was conducted to discover the optimal injury model by evaluating the correlation between the amount of pressure, the duration of mechanical stimulation, and the number of days of observation. Skeletal muscle cell injury was evaluated by measuring cell metabolism, morphology, and calcium homeostasis. RESULTS: Mechanical injury was modeled as continuous pressure of 1 MPa for 2 hours with observation for 3 days. The results show that mechanical injury increased creatine kinase, intracellular Ca2+ concentration, and malondialdehyde content, decreased superoxide dismutase, and caused cell swelling and severe cytoplasmic vacuolization (all P < 0.05). CONCLUSION: This model of mechanically-injured human skeletal muscle cells provides an experimental model for the clinically common skeletal muscle injury caused by static loading pressure. It may be used to study the mechanism of action of treatment methods for mechanically injured skeletal muscle.

Hydro-mechanical effects of vegetation on slope stability: A review.

This study explores the complex interplay between vegetation and soil stability on slopes to enhance soil-bioengineering and slope stabilization techniques. We assess the multifaceted role of vegetation in soil stabilization, examining processes such as canopy interception, stemflow, and the effects of hydrological and mechanical changes induced by root systems and above-ground plant structures. Key underlying mechanisms and their effects on stability are reported, along with the evaluation of significant plant indicators from historical research. Our review revealed that plant coverage and root architecture are critical in reducing soil erosion, with plant roots increasing soil cohesion and reducing soil detachability. Above-ground vegetation provides a protective layer that decreases the kinetic energy of raindrops and allows for higher infiltration. The importance of species-specific root traits is emphasized as pragmatic determinants of erosion prevention. Additionally, the effects of root reinforcement on shallow landslides are dissected to highlight their dualistic nature. While root-soil interactions typically increase soil shear strength and enhance slope stability, it is crucial to discriminate among vegetation types such as trees, shrubs, and grasses due to their distinct root morphology, tensile strength, root area ratio, and depth. These differences critically affect their impact on slope stability, where, for instance, robust shrub roots may fortify soil to greater depths, whereas grass roots contribute significantly to topsoil shear strength. Grasses and herbaceous plants effectively controlled surface erosion, whereas shrubs mainly controlled shallow landslides. Therefore, it is vital to conduct a study that combines shrubs with grasses or herbaceous plants. Both above-ground and below-ground plant indicators, including root and shoot indicators, were crucial for improving slope stability. To accurately evaluate the impact of plant species on slope stability reinforcement, it is necessary to study the combination of hydro-mechanical coupling with both ground plant indicators under specific conditions.

Dynamic single crystals: kinematic analysis of photoinduced crystal jumping (the photosalient effect).

Crystals on the move: If they are subjected to a strong light stimulus, crystals of the cobalt coordination compound [Co(NH3)5(NO2)]Cl(NO3) undergo sudden jumps and leap over distances 10(2)-10(5) times their own size to release the strain that accumulates in their interior. The first quantitative kinematic analysis of this phenomenon is reported. The observed effect could be employed for actuation on the macroscopic scale.

The Interaction of Mechanics and the Hippo Pathway in Drosophila melanogaster.

Drosophila melanogaster has emerged as an ideal system for studying the networks that control tissue development and homeostasis and, given the similarity of the pathways involved, controlled and uncontrolled growth in mammalian systems. The signaling pathways used in patterning the Drosophila wing disc are well known and result in the emergence of interaction of these pathways with the Hippo signaling pathway, which plays a central role in controlling cell proliferation and apoptosis. Mechanical effects are another major factor in the control of growth, but far less is known about how they exert their control. Herein, we develop a mathematical model that integrates the mechanical interactions between cells, which occur via adherens and tight junctions, with the intracellular actin network and the Hippo pathway so as to better understand cell-autonomous and non-autonomous control of growth in response to mechanical forces.

Mechanical effects of needle texture on acupoint tissue.

OBJECTIVE: This study aims to clarify how the stimulation of acupuncture points is achieved by needles with different surface texture during acupuncture; it also seeks to lessen injury at the insertion site and increase the therapeutic efficacy of acupuncture, by simulating the mechanical effects of various needle surface patterns on Zusanli (ST36) without changing the radius of acupuncture needles. METHODS: Five acupuncture needle models with different surface patterns, including the smooth needle, the lined needle, the ringed needle, the left-hand threaded needle and the right-hand threaded needle, and a layered model of the Zusanli acupoint were used to investigate how to reduce tissue damage and increase stimulation during acupuncture treatment. Puncturing of the skin as well as lifting-inserting and twisting needle manipulations were simulated using these models, and the degree of damage and force of stimulation caused by the acupuncture needles with different surface patterns during acupuncture were compared. RESULTS: The smooth needle and the lined needle caused the least tissue damage during insertion, while the left-hand threaded and the right-hand threaded needles caused the most damage. The ringed needle, the left-hand threaded needle and the right-hand threaded needle stimulated the acupoint tissue more during lifting-inserting manipulations, while the lined needle and the smooth needle produced less stimulation. The stimulation of the lined needle on the acupoint tissue was the largest during twisting manipulation, whereas the left-hand threaded needle and the right-hand threaded needle had smaller effects. In lifting-inserting and twisting manipulations, both the left-hand threaded needle and right-hand threaded needle provided more stimulation, but the torsion direction in which they produced better stimulation was the opposite. CONCLUSION: According to the simulation results, the ringed pattern enhances stimulation best in the lifting-inserting manipulation, whereas the lined pattern enhances stimulation best in the twisting manipulation. Both the right-hand and left-hand thread patterns have certain enhancing effects in these two operations. Taking the geometric properties of the pattern into account, the left-hand thread pattern and the right-hand thread pattern have the geometric characteristics of both the lined pattern and the ringed pattern. To conclude, a pattern perpendicular to the movement direction during the acupuncture manipulation creates more stimulation. These results have significance for future needle design. Please cite this article as: Sun MZ, Wang X, Li YC, Yao W, Gu W. Mechanical effects of needle texture on acupoint tissue. J Integr Med. 2023; 21(3): 254-267.

Health Complications of Obesity: 224 Obesity-Associated Comorbidities from a Mechanistic Perspective.

Obesity is associated with a wide range of comorbidities that transverse multiple specialties in clinical medicine. The development of these comorbidities is driven by various mechanistic changes including chronic inflammation and oxidative stress, increased growth-promoting adipokines, insulin resistance, endothelial dysfunction, direct loading and infiltrative effect of adiposity, heightened activities of the renin-angiotensin-aldosterone system and sympathetic nervous system, impaired immunity, altered sex hormones, altered brain structure, elevated cortisol levels, and increased uric acid production, among others. Some of the comorbidities might develop secondary to one or more other comorbidities. Considering the obesity-associated comorbidities in the context of the mechanistic changes is helpful in understanding these conditions and in guiding treatment and future research.

Effect of initial seeding density on cell behavior-driven epigenetic memory and preferential lineage differentiation of human iPSCs.

Understanding the cellular behavioral mechanisms underlying memory formation and maintenance in human induced pluripotent stem cell (hiPSC) culture provides key strategies for achieving stability and robustness of cell differentiation. Here, we show that changes in cell behavior-driven epigenetic memory of hiPSC cultures alter their pluripotent state and subsequent differentiation. Interestingly, pluripotency-associated genes were activated during the entire cell growth phases along with increased active modifications and decreased repressive modifications. This memory effect can last several days in the long-term stationary phase and was sustained in the aspect of cell behavioral changes after subculture. Further, changes in growth-related cell behavior were found to induce nucleoskeletal reorganization and active versus repressive modifications, thereby enabling hiPSCs to change their differentiation potential. Overall, we discuss the cell behavior-driven epigenetic memory induced by the culture environment, and the effect of previous memory on cell lineage specification in the process of hiPSC differentiation.

Linear interband optical refraction and absorption in strained black phosphorene.

Strain effects have been widely addressed in monolayer black phosphorus (MBP) due to its significant influence on the orbital hybridization of atoms. In this theoretical contribution, we use the tight-binding model, the Harrison rule and the Kubo formula to describe the optical refraction and absorption of MBP in detail. The analytical study of the band gap in strained MBP demonstrates electronic phase transitions from semiconductor-to-semimetal/metal and semiconductor-to-insulator, in which both the compressive and tensile strains act linearly on the band gap alterations. The critical strains corresponding to these phase transitions are fully characterized as well. Our calculations show that the variation of the refraction inflections and absorption peaks depends on the strained band gap, however; the band gap changes under out-of-plane strains are different than the in-plane ones. The conditions under which this discrepancy is significant and/or negligible are investigated. Moreover, the dedication of minimal/maximal optical refraction and/or absorption in MBP to both in-plane and out-of-plane strains are fully addressed. Our theoretical results clarify the strain-induced interplay between the band gap and optical properties to propose a wide range of applications in nano-optoelectronics.

Transluminal Approach with Bubble-Seeded Histotripsy for Cancer Treatment with Ultrasonic Mechanical Effects.

Bubble-seeded histotripsy (BSH) is a newly developed ultrasound-based mechanical fractionation technique using locally injected phase change nanodroplets (PCNDs) as sensitizers. The PCNDs are a kind of microbubble precursor compressed into submicron-size in droplets form, which were designed for local administration and will expand into microbubbles under ultrasound exposure. Previously, we reported that a combination of PCNDs injection and pulsed high-intensity focused ultrasound (pHIFU) with an acoustic intensity as low as about 3 kW/cm2 at 1.1 MHz, which is similar to the acoustic intensity of currently available HIFU coagulation therapy, was enough to induce tissue fractionation after significant antitumor effects in an in vivo study. Toward therapeutic application of BSH to deep-seated tissues such as the pancreas, the transluminal approach, using endoscopic ultrasound was thought to be ideal. Therefore, for a preliminary examination, we developed a new transducer with a small aperture (20- × 20-mm square) and long focal length (35 mm), operating at 2.1 MHz that could be attached to an EUS-mimicking probe. With the newly developed transducer and locally injected PCNDs, predictable tissue mechanical fractionation was observed in both ex vivo and in vivo studies at acoustic intensities that were too low to induce any significant bioeffects (around 4 kW/cm2) without using PCNDs. For in situ monitoring of the treatment site during a procedure, the degree of attenuation of microbubble motions after exposing the microbubbles to pHIFU was monitored, using ultrafast echographic imaging. Microbubble movements were observed to be largest at 25-30 s after pHIFU exposure. On the contrary, after 40 s, the movement of microbubbles decreased to the same level as at the start of the procedure, suggesting that an overdose of pHIFU exposure causes coagulation attributable to the thermal effect caused by absorption of the energy. Those results were promising for expanding the application of BSH for a transluminal approach, using a small transducer under real-time monitoring.

Mechanical effects of needle texture on acupoint tissue / 中西医结合学报

OBJECTIVE@#This study aims to clarify how the stimulation of acupuncture points is achieved by needles with different surface texture during acupuncture; it also seeks to lessen injury at the insertion site and increase the therapeutic efficacy of acupuncture, by simulating the mechanical effects of various needle surface patterns on Zusanli (ST36) without changing the radius of acupuncture needles.@*METHODS@#Five acupuncture needle models with different surface patterns, including the smooth needle, the lined needle, the ringed needle, the left-hand threaded needle and the right-hand threaded needle, and a layered model of the Zusanli acupoint were used to investigate how to reduce tissue damage and increase stimulation during acupuncture treatment. Puncturing of the skin as well as lifting-inserting and twisting needle manipulations were simulated using these models, and the degree of damage and force of stimulation caused by the acupuncture needles with different surface patterns during acupuncture were compared.@*RESULTS@#The smooth needle and the lined needle caused the least tissue damage during insertion, while the left-hand threaded and the right-hand threaded needles caused the most damage. The ringed needle, the left-hand threaded needle and the right-hand threaded needle stimulated the acupoint tissue more during lifting-inserting manipulations, while the lined needle and the smooth needle produced less stimulation. The stimulation of the lined needle on the acupoint tissue was the largest during twisting manipulation, whereas the left-hand threaded needle and the right-hand threaded needle had smaller effects. In lifting-inserting and twisting manipulations, both the left-hand threaded needle and right-hand threaded needle provided more stimulation, but the torsion direction in which they produced better stimulation was the opposite.@*CONCLUSION@#According to the simulation results, the ringed pattern enhances stimulation best in the lifting-inserting manipulation, whereas the lined pattern enhances stimulation best in the twisting manipulation. Both the right-hand and left-hand thread patterns have certain enhancing effects in these two operations. Taking the geometric properties of the pattern into account, the left-hand thread pattern and the right-hand thread pattern have the geometric characteristics of both the lined pattern and the ringed pattern. To conclude, a pattern perpendicular to the movement direction during the acupuncture manipulation creates more stimulation. These results have significance for future needle design. Please cite this article as: Sun MZ, Wang X, Li YC, Yao W, Gu W. Mechanical effects of needle texture on acupoint tissue. J Integr Med. 2023; 21(3): 254-267.

Construction of bionic tissue engineering cartilage scaffold based on three-dimensional printing and oriented frozen technology.

Articular cartilage (AC) has gradient features in both mechanics and histology as well as a poor regeneration ability. The repair of AC poses difficulties in both research and the clinic. In this paper, a gradient scaffold based on poly(lactic-co-glycolic acid) (PLGA)-extracellular matrix was proposed. Cartilage scaffolds with a three-layer gradient structure were fabricated by PLGA through three-dimensional printing, and the microstructure orientation and pore fabrication were made by decellularized extracellular matrix injection and directional freezing. The manufactured scaffold has a mechanical strength close to that of real cartilage. A quantitative optimization of the Young's modulus and shear modulus was achieved by material mechanics formulas, which achieved a more accurate mechanical bionic and a more stable interface performance because of the one-time molding process. At the same time, the scaffolds have a bionic and gradient microstructure orientation and pore size, and the stratification ratio can be quantitatively optimized by design of the freeze box and temperature simulation. In general, this paper provides a method to optimize AC scaffolds by both mechanics and histology as well as a bionic multimaterial scaffold. This paper is of significance for cell culture and clinical transplantation experiments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1664-1676, 2018.

Anabolic steroids and tendons: A review of their mechanical, structural, and biologic effects.

One of the suspected deleterious effects of androgenic-anabolic steroids (AAS) is the increased risk for tendon rupture. However, investigations to date have produced inconsistent results and it is still unclear how AAS influence tendons. A systematic review of the literature was conducted to identify studies that have investigated the mechanical, structural, or biologic effects that AAS have on tendons. In total, 18 highly heterogeneous studies were identified. Small animal studies made up the vast majority of published research, and contradictory results were reported frequently. All of the included studies focused on the potential deleterious effects that AAS have on tendon, which is striking given the recent use of AAS in patients following tendon injury. Rather than providing strong evidence for or against the use of AAS, this review highlights the need for additional research. Future studies investigating the use of AAS as a possible treatment for tendon injury/pathology are supported by reports suggesting that AAS may counteract the irreparable structural/functional changes that occur in the musculotendinous unit following rotator cuff tears, as well as studies suggesting that the purported deleterious effects on tendon may be transient. Other possible areas for future research are discussed in the context of key findings that may have implications for the therapeutic application of AAS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2830-2841, 2018.

Numerical investigation of the efficiency of emission reduction and heat extraction in a sedimentary geothermal reservoir: a case study of the Daming geothermal field in China.

The utilization of geothermal energy is clean and has great potential worldwide, and it is important to utilize geothermal energy in a sustainable manner. Mathematical modeling studies of geothermal reservoirs are important as they evaluate and quantify the complex multi-physical effects in geothermal reservoirs. However, previous modeling efforts lack the study focusing on the emission reduction efficiency and the deformation at geothermal wellbores caused by geothermal water extraction/circulation. Emission efficiency is rather relevant in geothermal projects introduced in areas characterized by elevated air pollution where the utilization of geothermal energy is as an alternative to burning fossil fuels. Deformation at geothermal wellbores is also relevant as significant deformation caused by water extraction can lead to geothermal wellbore instability and can consequently decrease the effectiveness of the heat extraction process in geothermal wells. In this study, the efficiency of emission reduction and heat extraction in a sedimentary geothermal reservoir in Daming County, China, are numerically investigated based on a coupled multi-physical model. Relationships between the efficiency of emission reduction and heat extraction, deformation at geothermal well locations, and geothermal field parameters including well spacing, heat production rate, re-injection temperature, rock stiffness, and geothermal well placement patterns are analyzed. Results show that, although large heat production rates and low re-injection temperatures can lead to decreased heat production in the last 8 years of heat extraction, they still improve the overall heat production capacity and emission reduction capacity. Also, the emission reduction capacity is positively correlated with the heat production capacity. Deformation at geothermal wellbore locations is alleviated by smaller well spacing, lower heat production rates, and smaller numbers of injectors in the well pattern, and by placing wells at locations with higher rock stiffness. Compared with the reference case with coal burning for heating purposes, the yearly emission reduction capacity can reach 1 × 107 kg by switching to the direct utilization of geothermal energy in Daming field.

Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression.

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression.