Interplay Of Mechanisms Research Articles

Turning foes into permissive hosts: manipulation of macrophage polarization by intracellular bacteria.

Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for intracellular bacteria, such as Salmonella enterica, to persist in infected tissues. Macrophages exhibit heterogeneous activationor polarization, states that are linked to differential antibacterial responses and bacteria permissiveness. Remarkably, recent studies demonstrate that Salmonella and other intracellular bacteria inject virulence effectors into the cellular cytoplasm to skew the macrophage polarization state and reprogram these immune cells into a permissive niche. Here, we review mechanisms of macrophage reprogramming by Salmonella and highlight manipulation of macrophage polarization as a shared bacterial pathogenesis strategy. In addition, we discuss how the interplay of bacterial effector mechanisms, microenvironmental signals, and ontogeny may shape macrophage cell states and functions. Finally, we propose ideas of how further research will advance our understanding of macrophage functional diversity and immunobiology.

MXenes: A comprehensive review of synthesis, properties, and progress in supercapacitor applications

MXenes, a class of two-dimensional materials, have garnered significant attention due to their unique properties and versatile applications in various fields. This review provides a comprehensive overview of MXene synthesis methods, highlighting their distinctive layered structure and tunable properties through surface functionalization. The focus then shifts to their remarkable role in supercapacitor technology. MXenes exhibit high electrical conductivity, large surface areas, and tailored surface chemistry, making them promising candidates for energy storage in supercapacitors. The paper discusses the interplay of electric double-layer capacitance and pseudocapacitance mechanisms within MXene-based electrodes, detailing recent research efforts aimed at optimizing their energy storage performance. Through a combination of theoretical insights and experimental findings, the potential of MXenes to revolutionize supercapacitor technology emerges, offering prospects for high-energy-density and long-lasting energy storage solutions. Additionally, this review highlights recent advances in MXene-based supercapacitors, including novel electrode designs, electrolyte engineering, and hybrid materials, showcasing the dynamic evolution of MXene-based supercapacitor research. This comprehensive overview aims to provide a thorough understanding of MXenes' synthesis, properties, and their pivotal role in advancing supercapacitor technology, while also encompassing the latest breakthroughs in this rapidly evolving field.

Muscle-driven forward dynamic active hybrid model of the lumbosacral spine: combined FEM and multibody simulation.

Most spine models belong to either the musculoskeletal multibody (MB) or finite element (FE) method. Recently, coupling of MB and FE models has increasingly been used to combine advantages of both methods. Active hybrid FE-MB models, still rarely used in spine research, avoid the interface and convergence problems associated with model coupling. They provide the inherent ability to account for the full interplay of passive and active mechanisms for spinal stability. In this paper, we developed and validated a novel muscle-driven forward dynamic active hybrid FE-MB model of the lumbosacral spine (LSS) in ArtiSynth to simultaneously calculate muscle activation patterns, vertebral movements, and internal mechanical loads. The model consisted of the rigid vertebrae L1-S1 interconnected with hyperelastic fiber-reinforced FE intervertebral discs, ligaments, facet joints, and force actuators representing the muscles. Morphological muscle data were implemented via a semi-automated registration procedure. Four auxiliary bodies were utilized to describe non-linear muscle paths by wrapping and attaching the anterior abdominal muscles. This included an abdominal plate whose kinematics was optimized using motion capture data from upper body movements. Intra-abdominal pressure was calculated from the forces of the abdominal muscles compressing the abdominal cavity. For the muscle-driven approach, forward dynamics assisted data tracking was used to predict muscle activation patterns that generate spinal postures and balance the spine without prescribing accurate spinal kinematics. During calibration, the maximum specific muscle tension and spinal rhythms resulting from the model dynamics were evaluated. To validate the model, load cases were simulated from -10° extension to +30° flexion with weights up to 20kg in both hands. The biomechanical model responses were compared with in vivo literature data of intradiscal pressures, intra-abdominal pressures, and muscle activities. The results demonstrated high agreement with this data and highlight the advantages of active hybrid modeling for the LSS. Overall, this new self-contained tool provides a robust and efficient estimation of LSS biomechanical responses under in vivo similar loads, for example, to improve pain treatment by spinal stabilization therapies.

Beyond the state’s reach? Education and citizen making in China

Purpose This special issue aims to address the complexities and dynamics in contemporary China’s citizen-making processes, with a focus on the educational dimension. Design/methodology/approach The four articles in this special issue present citizen-making processes in both educational and cultural arenas. Based on the rich, first-hand data collected inside and outside China, the researchers revealed the dynamics of the educative processes, as the interplay of different mechanisms produces new understandings of citizenship practice. Findings This special issue sheds light on the rise of new types of citizens, who are emerging at the grassroots level in China, beyond the state’s strict direct regulations, along with the rise of market forces and multicultural communities in Chinese society today. Contributors to this special issue have captured an ongoing change, in that the diversified citizen-making mechanisms are, to a certain extent, mitigating the party-state’s definitive monopoly on forging citizens and are creating new spaces for individuals to develop fresh forms of political subjectivity and citizenship practice. In this sense, we argue for the unpacking of the citizen-making processes in present-day China not only from the lens of state-dominated, top-down initiatives but also from that of participatory, bottom-up initiatives performed by grassroots groups with differentiated socio-economic statuses and cultural traditions. Originality/value This special issue can be regarded as a contribution to the growing field of Chinese citizenship studies, which constitutes an integral part of the unfinished project of citizenship after orientalism.

SFAlab: image-based quantification of mechano-active ventral actin stress fibers in adherent cells.

Ventral actin stress fibers (SFs) are a subset of actin SFs that begin and terminate at focal adhesion (FA) complexes. Ventral SFs can transmit forces from and to the extracellular matrix and serve as a prominent mechanosensing and mechanotransduction machinery for cells. Therefore, quantitative analysis of ventral SFs can lead to deeper understanding of the dynamic mechanical interplay between cells and their extracellular matrix (mechanoreciprocity). However, the dynamic nature and organization of ventral SFs challenge their quantification, and current quantification tools mainly focus on all SFs present in cells and cannot discriminate between subsets. Here we present an image analysis-based computational toolbox, called SFAlab, to quantify the number of ventral SFs and the number of ventral SFs per FA, and provide spatial information about the locations of the identified ventral SFs. SFAlab is built as an all-in-one toolbox that besides analyzing ventral SFs also enables the identification and quantification of (the shape descriptors of) nuclei, cells, and FAs. We validated SFAlab for the quantification of ventral SFs in human fetal cardiac fibroblasts and demonstrated that SFAlab analysis i) yields accurate ventral SF detection in the presence of image imperfections often found in typical fluorescence microscopy images, and ii) is robust against user subjectivity and potential experimental artifacts. To demonstrate the usefulness of SFAlab in mechanobiology research, we modulated actin polymerization and showed that inhibition of Rho kinase led to a significant decrease in ventral SF formation and the number of ventral SFs per FA, shedding light on the importance of the RhoA pathway specifically in ventral SF formation. We present SFAlab as a powerful open source, easy to use image-based analytical tool to increase our understanding of mechanoreciprocity in adherent cells.

Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach.

Introduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood. Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach. Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy. Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.

A comprehensive experimental and modelling approach for the evaluation of cross-over fluxes in Vanadium Redox Flow Battery

Vanadium cross-over is a critical issue in Vanadium Redox Flow Battery consisting in a complex interplay of different mechanisms of which a complete comprehension has not been reached yet. Due to the complexity of the involved phenomena, several models have been developed in literature to investigate vanadium cross-over. However, the conventional approaches for model calibration present a limited set of experiments for the validation preventing a complete understanding of cross-over phenomena. In this work a new and comprehensive approach is proposed. It is based on charge-discharge cycles with fixed exchanged capacity, able to isolate the capacity loss induced by cross-over fluxes, and on the measure of the self-discharge of the single electrolyte solutions by exploiting through-plate reference electrodes. Moreover, a 1D physically-based model of the operation of the battery is developed and calibrated on the data of electrolyte imbalance during charge-discharge cycles at three different current densities to obtain model parameters able to accurately describe the involved physics in different operating conditions. The model is then exploited to investigate the main vanadium transport mechanisms through the membrane and to evaluate the influence of the current density on the vanadium cross-over fluxes, net vanadium transport and self-discharge rate of the electrolyte.

Controlling sound waves in gradient spoof-fluid-spoof waveguides

In this work, we theoretically and experimentally demonstrate that effective trapping, guiding, and manipulation of sound waves can be realized in spoof-fluid-spoof acoustic waveguides with gradient index modulation. Empowered by the abundant mode evolution physics between propagation waves and spoof acoustic surface waves in the gradient waveguide structure, various functional sound propagation phenomena, including broadband transmission, broadband reflection, Fabry–Pérot resonances, and Fano resonances, are unveiled. The underlying principle stems from the interplay of various mechanisms composed of gradient mode conversion, high-order mode resonances, and symmetry-protected bound states in the continuum. These effects can be effectively modulated through the manipulation of the fluid gap and doped defects within the waveguide structure. Our findings can offer possibilities for manipulating sound waves in a versatile manner and holding significant potential for various acoustic applications such as sensing, filtering, insulation, and wavefront engineering.

Anomalous Mechanical and Electrical Interplay in a Covalent Organic Framework Monolayer Membrane.

Ion transport through nanoconfinement, driven by both electrical and mechanical forces, has drawn ever-increasing attention, due to its high similarity to stress-sensitive ion channels in biological systems. Previous studies have reported only pressure-induced enhancement in ion conductance in low-permeable systems such as nanotubes, nanoslits, or single nanopores. This enhancement is generally explained by the ion accumulation caused by the capacitive effect in low-permeable systems. Here, we fabricate a highly permeable COF monolayer membrane to investigate ion transport behavior driven by both electrical and mechanical forces. Our results show an anomalous conductance reduction activated by external mechanical force, which is contrary to the capacitive effect-dominated conductance enhancement observed in low-permeable nanopores or channels. Through simulations, we uncovered a distinct electrical-mechanical interplay mechanism that depends on the relative rate between the ion diffusion from the boundary layer to the membrane surface and the ion transport through the membrane. The high pore density of the COF monolayer membrane reduces the charge accumulation caused by the capacitive effect, resulting in fewer accumulated ions near the membrane surface. Additionally, the high membrane permeability greatly accelerates the dissipation of the accumulated ions under mechanical pressure, weakening the effect of the capacitive layer on the streaming current. As a result, the ions accumulated on the electrodes, rather than in the capacitive layer, dominating the streaming current and giving rise to a distinct electrical-mechanical interplay mechanism compared to that in low-permeable nanopores or channels. Our study provides new insights into the interplay between electrical and mechanical forces in ultra-permeable systems.

Time resolved insights into abnormal grain growth by in situ synchrotron measurements

Large oligo-crystalline or single-crystalline metallic materials are of great interest for numerous applications, and a recently developed strategy for promoting abnormal grain growth induced by a cyclic heat treatment opens up new opportunities to manufacture single crystals with a size of several centimeters. So far, the entire available knowledge on this kind of abnormal grain growth has been elaborated based on time discrete observations and, thus, detailed insights into the interplay of elementary mechanisms are still lacking in open literature. The present study reveals time resolved insights into this kind of abnormal grain growth for the first time. It was possible to break down the influence of the individual heat treatment phases by in situ synchrotron high energy X-ray diffraction analysis during cyclic heat treatment. The results obtained not only help to gain a deep understanding of the abnormal grain growth mechanisms, they will also be the basis for an adjustment of the cyclic heat treatment process to improve its efficiency and to eventually obtain even larger single crystals.

The Interplay of Growth Mechanism and Properties of ZnO Nanostructures for Different Applications.

This review provides a background on the structure and properties of ZnO nanostructures. ZnO nanostructures are advantageous for many applications in sensing, photocatalysis, functional textiles, and cosmetic industries, which are described in this review. Previous work using UV Visible (UV-vis) spectroscopy and scanning electron microscopy (SEM) for ZnO nanorod growth analysis in-solution and on a substrate for determination of optical properties and morphology is discussed, as well as their results in determining the kinetics and growth mechanisms. From this literature review, it is understood that the synthesis process greatly affects nanostructures and properties; and hence, their applications. In addition, in this review, the mechanism of ZnO nanostructure growth is unveiled, and it is shown that by having greater control over their morphology and size through such mechanistic understanding, the above-mentioned applications can be affected. The contradictions and gaps in knowledge are summarized in order to highlight the variations in results, followed by suggestions for how to answer these gaps and future outlooks for ZnO nanostructure research.

Comparing energy dissipation mechanisms within the vortex dynamics of gap and gapless nano-sized superconductors

The presence of magnetic fields and/or transport currents can cause penetration of vortices in superconductors. Their motion leads to dissipation and resistive state arises, which in turn strongly affects the performance of superconducting devices such as single-photon and single-electron detectors. Therefore, an understanding of the dissipation mechanisms in mesoscopic superconductors is not only of fundamental value but also very important for further technological advances. In the present work, we analyzed the contributions and interplay of the dissipative mechanisms due to the locally induced electric field and an intrinsic relaxation of the superconducting order parameter, Ψ, in mesoscopic samples by using the time-dependent Ginzburg–Landau theory. Although often neglected, we show that the dissipated energy due to relaxation of Ψ must be taken into account for an adequate description of the total dissipated energy. The local increase of the temperature due to vortex motion and its diffusion in the sample were also analyzed, where the joint effect of thermal relaxation and vortex dynamics plays an important role for the dissipative properties presented by the superconducting systems.

X-photon laser direct write 3D nanolithography

ABSTRACT Multiphoton photopolymerisation (MPP), also known as 3D nanoprinting, was studied using a wavelength-tunable femtosecond laser. The possibility of using any colour of the spectrum from 500 to 1200 nm with a fixed pulse width of 100 fs revealed an interplay of photophysical mechanisms more delicate than just two-photon photopolymerisation. An effective order of absorption, i.e. the X-photon absorption, as well as optimal exposure conditions were assessed for photosensitised and pure SZ2080 pre-polymer. The tunability of wavelength greatly influenced the dynamic fabrication window (DFW), optimised conditions resulting in a 10-fold increase. Furthermore, a non-trivial energy deposition by X-photon absorption was noted with an onset of a strong lateral size increase at longer wavelengths and can be understood as due to reaching epsilon-near-zero conditions. Such a control over the voxel aspect ratio and, consequently, the photopolymerised volume, may boost 3D nanoprinting efficiency. Overall, the results reveal wavelength being an important degree of freedom to tailor the MPP process and, if optimised, benefiting broad applications in areas of micro-optics, nanophotonic devices, metamaterials and tissue engineering.

Coexistence of Bloch and Parametric Mechanisms of High-Frequency Gain in Doped Superlattices

The detailed theoretical study of high-frequency signal gain, when a probe microwave signal is comparable to the AC pump electric field in a semiconductor superlattice, is presented. We identified conditions under which a doped superlattice biased by both DC and AC fields can generate or amplify high-frequency radiation composed of harmonics, half-harmonics, and fractional harmonics. Physical mechanisms behind the effects are discussed. It is revealed that in a general case, the amplification mechanism in superlattices is determined by the coexistence of both the phase-independent Bloch and phase-dependent parametric gain mechanisms. The interplay and contribution of these gain mechanisms can be adjusted by the sweeping AC pump strength and leveraging a proper phase between the pump and strong probe electric fields. Notably, a transition from the Bloch gain to the parametric gain, often naturally occurring as the amplitude of the amplified signal field grows, can facilitate an effective method of fractional harmonic generation in DC–AC-driven superlattices. The study also uncovers that the pure parametric generation of the fractional harmonics can be initiated via their ignition by switching the DC pump electric field. The findings open a promising avenue for the advancement of new miniature GHz–THz frequency generators, amplifiers, and dividers operating at room temperature.

The elasto-plastic nano- and microscale compressive behaviour of rehydrated mineralised collagen fibres.

The hierarchical design of bio-based nanostructured materials such as bone enables them to combine unique structure-mechanical properties. As one of its main components, water plays an important role in bone's material multiscale mechanical interplay. However, its influence has not been quantified at the length-scale of a mineralised collagen fibre. Here, we couple in situ micropillar compression, and simultaneous synchrotron small angle X-ray scattering (SAXS) and X-ray diffraction (XRD) with a statistical constitutive model. Since the synchrotron data contain statistical information on the nanostructure, we establish a direct connection between experiment and model to identify the rehydrated elasto-plastic micro- and nanomechanical fibre behaviour. Rehydration led to a decrease of 65%-75% in fibre yield stress and compressive strength, and 70% in stiffness with a 3x higher effect on stresses than strains. While in agreement with bone extracellular matrix, the decrease is 1.5-3x higher compared to micro-indentation and macro-compression. Hydration influences mineral more than fibril strain with the highest difference to the macroscale when comparing mineral and tissue levels. The effect of hydration seems to be strongly mediated by ultrastructural interfaces while results provide insights towards mechanical consequences of reported water-mediated structuring of bone apatite. The missing reinforcing capacity of surrounding tissue for an excised fibril array is more pronounced in wet than dry conditions, mainly related to fibril swelling. Differences leading to higher compressive strength between mineralised tissues seem not to depend on rehydration while the lack of kink bands supports the role of water as an elastic embedding influencing energy-absorption mechanisms. STATEMENT OF SIGNIFICANCE: Characterising structure-property-function relationships in hierarchical biological materials helps us to elucidate mechanisms that enable their unique properties. Experimental and computational methods can advance our understanding of their complex behaviour with the potential to inform bio-inspired material development. In this study, we close a gap for bone's fundamental mechanical building block at micro- and nanometre length scales. We establish a direct connection between experiments and simulations by coupling in situ synchrotron tests with a statistical model and quantify the behaviour of rehydrated single mineralised collagen fibres. Results suggest a high influence of hydration on structural interfaces, and the role of water as an elastic embedding by outlining important differences between wet and dry elasto-plastic properties of mineral nanocrystals, fibrils and fibres.

Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation.

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.

Velocity field distribution control in antisolvent flow realizing highly stable and efficient perovskite nanocrystals

Achieving highly stable and efficient perovskite nanocrystals (NCs) without applying functional additives or encapsulation, particularly sustaining the stability in ultra-dilute solution, is still a formidable challenge. Here, we show the FAPbI3 perovskite NCs with achieved ∼100 % photoluminescence quantum yield (PLQY) and low defect density (∼0.2 cm−3 per NCs), which is obtained by controlling the velocity field distribution of antisolvent flow in ligand-assisted reprecipitation process. The NCs show incredible reproducibility with narrow deviation of PLQY and linewidth between batch by batch, as well as remarkable stability of maintaining over 80 % PLQY, either in an ultra-diluted solution (9.3 × 10-6 mg/mL), or storing in ambient condition after 90 days with concentration of 0.09 mg/mL. The results in this work demonstrate the interplay of fluid mechanics and crystallization kinetics of perovskite, which pioneers a novel and unprecedent understanding for improving the stability of perovskite NCs for efficient quantum light source.

Improving hydrocarbon toxicity tolerance in poultry: role of genes and antioxidants.

Sustenance of smallholder poultry production as an alternative source of food security and income is imperative in communities exposed to hydrocarbon pollution. Exposure to hydrocarbon pollutants causes disruption of homeostasis, thereby compromising the genetic potential of the birds. Oxidative stress-mediated dysfunction of the cellular membrane is a contributing factor in the mechanism of hydrocarbon toxicity. Epidemiological studies show that tolerance to hydrocarbon exposure may be caused by the activation of genes that control disease defense pathways like aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2p45-related factor 2 (Nrf2). Disparity in the mechanism and level of tolerance to hydrocarbon fragments among species may exist and may result in variations in gene expression within individuals of the same species upon exposure. Genomic variability is critical for adaptation and serves as a survival mechanism in response to environmental pollutants. Understanding the interplay of diverse genetic mechanisms in relation to environmental influences is important for exploiting the differences in various genetic variants. Protection against pollutant-induced physiological responses using dietary antioxidants can mitigate homeostasis disruptions. Such intervention may initiate epigenetic modulation relevant to gene expression of hydrocarbon tolerance, enhancing productivity, and possibly future development of hydrocarbon-tolerant breeds.

Minimal conditions for solidification and thermal processing of colloidal gels

Colloidal gelation is used to form processable soft solids from a wide range of functional materials. Although multiple gelation routes are known to create gels of different types, the microscopic processes during gelation that differentiate them remain murky. A fundamental question is how the thermodynamic quench influences the microscopic driving forces of gelation, and determines the threshold or minimal conditions where gels form. We present a method that predicts these conditions on a colloidal phase diagram, and mechanistically connects the quench path of attractive and thermal forces to the emergence of gelled states. Our method employs systematically varied quenches of a colloidal fluid over a range of volume fractions to identify minimal conditions for gel solidification. The method is applied to experimental and simulated systems to test its generality toward attractions with varied shapes. Using structural and rheological characterization, we show that all gels incorporate elements of percolation, phase separation, and glassy arrest, where the quench path sets their interplay and determines the shape of the gelation boundary. We find that the slope of the gelation boundary corresponds to the dominant gelation mechanism, and its location approximately scales with the equilibrium fluid critical point. These results are insensitive to potential shape, suggesting that this interplay of mechanisms is applicable to a wide range of colloidal systems. By resolving regions of the phase diagram where this interplay evolves in time, we elucidate how programmed quenches to the gelled state could be used to effectively tailor gel structure and mechanics.

The emerging promise of tumour mechanobiology in cancer treatment

Tumour cell biomechanics has lately came to the fore as a disparate feature that fosters cancer development and progression. Tumour mechanosensing entails a mechanical interplay amongst tumour cells, extracellular matrix (ECM) and cells of the tumour microenvironment (TME). Sensory receptors (mechanoceptors) detect changes of extracellular mechanical inputs such as various types of mechanical forces/stress and trigger oncogenic signalling pathways advocating for cancer initiation, growth, survival, angiogenesis, invasion, metastasis, and immune evasion. Moreover, alterations in ECM stiffness and potentiation of mechanostimulated transcriptional regulatory molecules (transcription factors/cofactors) have been shown to strongly correlate with resistance to anticancer drugs. On this basis, new mechanosensitive proteins emerge as potential therapeutic targets and/or biomarkers in cancer. Accordingly, tumour mechanobiology arises as a promising field that can potentially provide novel combinatorial regimens to reverse drug resistance, as well as offer unprecedented targeting approaches that may help to more effectively treat a large proportion of solid tumours and their complications.Here, we highlight recent findings regarding various aspects of tumour mechanobiology in the clinical setting and discuss evidence-based perspectives of developing diagnostic/prognostic tools and therapeutic approaches that exploit tumour−TME physical associations.