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Background: Chronic lung disease of prematurity, called bronchopulmonary dysplasia (BPD), lacks effective therapies, stressing the need for preclinical testing systems that reflect human pathology for identifying causal pathways and testing novel compounds. Alveolar organoids derived from human pluripotent stem cells (hPSC) are promising test platforms for studying distal airway diseases like BPD, but current protocols do not accurately replicate the distal niche environment of the native lung. Herein, we investigated the contributions of cellular constituents of the alveolus and fetal respiratory movements on hPSC-derived alveolar organoid formation. Methods: Human PSCs were differentiated in 2D culture into lung progenitor cells (LPC) which were then further differentiated into alveolar organoids before and after removal of co-developing mesodermal cells. LPCs were also differentiated in Transwell® co-cultures with and without human fetal lung fibroblast. Forming organoids were subjected to phasic mechanical strain using a Flexcell® system. Differentiation within organoids and Transwell® cultures was assessed by flow cytometry, immunofluorescence, and qPCR for lung epithelial and alveolar markers of differentiation including GATA binding protein 6 (GATA 6), E-cadherin (CDH1), NK2 Homeobox 1 (NKX2-1), HT2-280, surfactant proteins B (SFTPB) and C (SFTPC). Results: We observed that co-developing mesenchymal progenitors promote alveolar epithelial type 2 cell (AEC2) differentiation within hPSC-derived lung organoids. This mesenchymal effect on AEC2 differentiation was corroborated by co-culturing hPSC-NKX2-1+ lung progenitors with human embryonic lung fibroblasts. The stimulatory effect did not require direct contact between fibroblasts and NKX2-1+ lung progenitors. Additionally, we demonstrate that episodic mechanical deformation of hPSC-derived lung organoids, mimicking in situ fetal respiratory movements, increased AEC2 differentiation without affecting proximal epithelial differentiation. Conclusion: Our data suggest that biophysical and mesenchymal components promote AEC2 differentiation within hPSC-derived distal organoids in vitro. [ABSTRACT FROM AUTHOR]

Nanoscale-engineered surfaces induce regulated strain in atomic layers of 2D materials that could be useful for unprecedented photonics applications and for storing and processing quantum information. Nevertheless, these strained structures need to be investigated extensively. Here, we present texture-induced strain distribution in single-layer WS2 (1L-WS2) transferred over Si/SiO2 (285 nm) substrate. The detailed nanoscale landscapes and their optical detection are carried out through Atomic Force Microscopy, Scanning Electron Microscopy, and optical spectroscopy. Remarkable differences have been observed in the WS2 sheet localized in the confined well and at the periphery of the cylindrical geometry of the capped engineered surface. Raman spectroscopy independently maps the whole landscape of the samples, and temperature-dependent helicity-resolved photoluminescence (PL) experiments (off-resonance excitation) show that suspended areas sustain circular polarization from 150 K up to 300 K, in contrast to supported (on un-patterned area of Si/SiO2) and strained 1L-WS2. Our study highlights the impact of the dielectric environment on the optical properties of two-dimensional (2D) materials, providing valuable insights into the selection of appropriate substrates for implementing atomically thin materials in advanced optoelectronic devices. [ABSTRACT FROM AUTHOR]

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single‐cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4‐ethylenedioxythiophene) conductive ink, which achieved real‐time quantitation of strain‐induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis. [ABSTRACT FROM AUTHOR]

Background: The periodontal ligament (PDL) experiences considerable mechanical stresses between teeth and bone, vital for tissue adaptation, especially in orthodontic tooth movement (OTM). While recent research emphasizes the role of innate lymphoid cells (ILCs) in regulating sterile inflammation, their involvement in periodontal tissues during OTM remains largely unexplored. Methods: In this study, PDL tissues from orthodontic patients (n = 8) were examined using flow cytometry to detect ILC subtypes. Transwell co-culture systems were used to expose PDL cells to mechanical strain, followed by measuring migration and ratios of sorted ILC subtypes. Statistical analyses were conducted using paired Student's t-test, Kruskal-Wallis test, Dunn's posttest and one-way/two-way ANOVA with Tukey's post-test (p= 0.05; **, p= 0.01; ***, p= 0.001). Results: Our findings demonstrate a significant increase in CD127+ CD161+ ILC frequencies in PDL tissues during OTM, indicating ILC involvement in sterile inflammation induced by orthodontic forces. Co-culture assays show directed migration of ILC subsets towards PDL cells and substantial proliferation and expansion of ILCs. Conclusions: This study is the first to comprehensively investigate the role of ILCs in sterile inflammation during OTM, revealing their presence and distribution within PDL tissues' innate immune response in vivo, and exploring their migratory and proliferative behavior in vitro. The results suggest a crosstalk between ILCs and PDL cells, potentially influencing the inflammatory response and tissue remodeling processes associated with OTM. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic lung disease of prematurity, called bronchopulmonary dysplasia (BPD), lacks effective therapies, stressing the need for preclinical testing systems that reflect human pathology for identifying causal pathways and testing novel compounds. Alveolar organoids derived from human pluripotent stem cells (hPSC) are promising test platforms for studying distal airway diseases like BPD, but current protocols do not accurately replicate the distal niche environment of the native lung. Herein, we investigated the contributions of cellular constituents of the alveolus and fetal respiratory movements on hPSC-derived alveolar organoid formation. Methods Human PSCs were differentiated in 2D culture into lung progenitor cells (LPC) which were then further differentiated into alveolar organoids before and after removal of co-developing mesodermal cells. LPCs were also differentiated in Transwell® co-cultures with and without human fetal lung fibroblast. Forming organoids were subjected to phasic mechanical strain using a Flexcell® system. Differentiation within organoids and Transwell® cultures was assessed by flow cytometry, immunofluorescence, and qPCR for lung epithelial and alveolar markers of differentiation including GATA binding protein 6 (GATA 6), E-cadherin (CDH1), NK2 Homeobox 1 (NKX2-1), HT2-280, surfactant proteins B (SFTPB) and C (SFTPC). Results We observed that co-developing mesenchymal progenitors promote alveolar epithelial type 2 cell (AEC2) differentiation within hPSC-derived lung organoids. This mesenchymal effect on AEC2 differentiation was corroborated by co-culturing hPSC-NKX2-1+ lung progenitors with human embryonic lung fibroblasts. The stimulatory effect did not require direct contact between fibroblasts and NKX2-1+ lung progenitors. Additionally, we demonstrate that episodic mechanical deformation of hPSC-derived lung organoids, mimicking in situ fetal respiratory movements, increased AEC2 differentiation without affecting proximal epithelial differentiation. Conclusion Our data suggest that biophysical and mesenchymal components promote AEC2 differentiation within hPSC-derived distal organoids in vitro.

Abstract Background Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. Results A mechanical tensile strain of 2500 με at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Conclusions In osteocytes, a mechanical tensile strain of 2500 με at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.

Introduction: In native heart tissue, functions of cardiac fibroblasts (CFs) include synthesis, remodeling, and degradation of the extracellular matrix (ECM) as well as secreting factors that regulate cardiomyocyte (CM) function. The influence of direct co-culture and CF-derived ECM on CM mechanical function are not fully understood. Methods: Here we use an engineered culture platform that provides control over ECM geometry and substrate stiffness to evaluate the influence of iPSC-CFs, and the ECM they produce, on the mechanical function of iPSC-CMs. Mechanical analysis was performed using digital image correlation to quantify maximum contractile strain, spontaneous contraction rate, and full-field organization of the contractions. Results: When cultured alone, iPSC-CFs produce and remodel the ECM into fibers following the underlying 15° chevron patterned ECM. The substrates were decellularized and confirmed to have highly aligned fibers that covered a large fraction of the pattern area before reseeding with iPSC-CMs, alone or in co-culture with iPSC-CFs. When seeded on decellularized ECM, larger maximum contractile strains were observed in the co-culture condition compared to the CM Only condition. No significant difference was found in contractile strain between the Matrigel and decellularized ECM conditions; however, the spontaneous contraction rate was lower in the decellularized ECM condition. A methodology for quantifying alignment of cell contraction across the entire field of view was developed based on trajectories approximating the cell displacements during contraction. Trajectory alignment was unaltered by changes in culture or ECM conditions. Conclusions: These combined observations highlight the important role CFs play in vivo and the need for models that enable a quantitative approach to examine interactions between the CFs and CMs, as well as the interactions of these cells with the ECM. [ABSTRACT FROM AUTHOR]

Background: Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. Results: A mechanical tensile strain of 2500 με at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Conclusions: In osteocytes, a mechanical tensile strain of 2500 με at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation. [ABSTRACT FROM AUTHOR]

Alleviating bone loss is an essential way to prevent osteoporotic fractures. Proper exercise improves bone density without the side effects of long‐term medications, but the mechanism is unclear. Our study explored the role of Antxr1/LncRNA H19/Wnt/β‐catenin axis in the process of exercise‐mediated alleviation of bone loss. Here we discovered that moderate‐intensity treadmill exercise alleviates bone loss caused by ovariectomy and ameliorates bone strength accompanied by an increased lncRNA H19 expression. Concomitantly, Antxr1, a mechanosensitive protein was found downregulated by exercise but upregulated by ovariectomy. Interestingly, knockdown expression of Antxr1 increased lncRNA H19 expression and Wnt/β‐catenin signaling pathway in bone marrow mesenchymal stem cells, whereas overexpression of Antxr1 decreased lncRNA H19 expression and Wnt/β‐catenin signaling pathway. Hence, our study demonstrates the regulation of Antxr1/LncRNA H19/Wnt/β‐catenin axis in the process of mechanical strain‐induced osteogenic differentiation, which provides further mechanistic insight into the role of mechanical regulation in bone metabolism. [ABSTRACT FROM AUTHOR]

BackgroundThe periodontal ligament (PDL) experiences considerable mechanical stresses between teeth and bone, vital for tissue adaptation, especially in orthodontic tooth movement (OTM). While recent research emphasizes the role of innate lymphoid cells (ILCs) in regulating sterile inflammation, their involvement in periodontal tissues during OTM remains largely unexplored.MethodsIn this study, PDL tissues from orthodontic patients (n = 8) were examined using flow cytometry to detect ILC subtypes. Transwell co-culture systems were used to expose PDL cells to mechanical strain, followed by measuring migration and ratios of sorted ILC subtypes. Statistical analyses were conducted using paired Student’s t-test, Kruskal-Wallis test, Dunn’s post-test and one-way/two-way ANOVA with Tukey’s post-test (p≤ 0.05; **, p≤ 0.01; ***, p≤ 0.001).ResultsOur findings demonstrate a significant increase in CD127+ CD161+ ILC frequencies in PDL tissues during OTM, indicating ILC involvement in sterile inflammation induced by orthodontic forces. Co-culture assays show directed migration of ILC subsets towards PDL cells and substantial proliferation and expansion of ILCs.ConclusionsThis study is the first to comprehensively investigate the role of ILCs in sterile inflammation during OTM, revealing their presence and distribution within PDL tissues’ innate immune response in vivo, and exploring their migratory and proliferative behavior in vitro. The results suggest a crosstalk between ILCs and PDL cells, potentially influencing the inflammatory response and tissue remodeling processes associated with OTM.

Nanoscale-engineered surfaces induce regulated strain in atomic layers of 2D materials that could be useful for unprecedented photonics applications and for storing and processing quantum information. Nevertheless, these strained structures need to be investigated extensively. Here, we present texture-induced strain distribution in single-layer WS2 (1L-WS2) transferred over Si/SiO2 (285 nm) substrate. The detailed nanoscale landscapes and their optical detection are carried out through Atomic Force Microscopy, Scanning Electron Microscopy, and optical spectroscopy. Remarkable differences have been observed in the WS2 sheet localized in the confined well and at the periphery of the cylindrical geometry of the capped engineered surface. Raman spectroscopy independently maps the whole landscape of the samples, and temperature-dependent helicity-resolved photoluminescence (PL) experiments (off-resonance excitation) show that suspended areas sustain circular polarization from 150 K up to 300 K, in contrast to supported (on un-patterned area of Si/SiO2) and strained 1L-WS2. Our study highlights the impact of the dielectric environment on the optical properties of two-dimensional (2D) materials, providing valuable insights into the selection of appropriate substrates for implementing atomically thin materials in advanced optoelectronic devices.

Purpose: The aim of this study was to evaluate and compare the effect of changing five macrostructural design parameters of dental implants on the peak strains experienced by the interfacial bone. Materials and Methods: Five geometric variables, including three body-related (implant length, diameter, and taper) and two thread-related (thread depth and thread angle) parameters, were defined. The alveolar bone was modeled as a block with anisotropic and linearly elastic properties with 20-mm height and 12-mm buccolingual and mesiodistal dimensions. Oblique occlusal loads (100-N vertical and 20-N horizontal) were applied to the abutment surface. A total of 162 models with different designs were defined by implementation of a full-factorial design. The peak values of the compressive and tensile principal strains in the cortical and cancellous bones were calculated by finite element analysis (FEA). Results: Implant diameter and length had maximum and minimum effects on the peak compressive and tensile strains at the cortical interface, respectively. Implant diameter and thread depth had maximum and minimum effects on the maximum compressive strain at the cancellous interface, while thread angle and length had maximum and minimum significant effects on the maximum tensile strain at the cancellous interface. Conclusion: The interaction of thread parameters and taper has the greatest effect on the peak compressive and tensile strains at the cancellous interface and also on the peak tensile strain at the cortical interface, while body-related parameters are more effective on the peak compressive strain at the cortical interface. [ABSTRACT FROM AUTHOR]

Cleidocranial dysplasia (CCD) is a rare genetic defect caused by a heterozygous mutation of runt-related transcription factor 2 (RUNX2), which is important for osteoblast and skeletal development. RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment. Nicotinamide (NAM) affects bone remodelling processes. As these are crucial for orthodontic therapy, NAM could improve orthodontic treatment in CCD patients. This study investigates the effect of NAM in control and RUNX2-deficient osteoblasts under mechanical strain mimicking orthodontic treatment. First, the optimal NAM concentration and the differences in the expression profile of control and RUNX2-deficient osteoblasts were determined. Subsequently, osteoblasts were exposed to tensile and compressive strain with and without NAM, and the expression of genes critically involved in bone remodelling was investigated. NAM increased the expression of bone remodelling genes. RUNX2-deficient osteoblasts expressed more receptor activator of NFkB ligand (RANKL) and interleukin-6 (IL6), but less colony-stimulating factor-1 (CSF1). Most of the positive effects of NAM on bone remodelling genes were impaired by mechanical loading. In conclusion, NAM stimulated osteoblast differentiation by increasing the expression of RUNX2 and regulated the expression of osteoclastogenic factors. However, the positive effects of NAM on bone metabolism were impaired by mechanical loading and RUNX2 deficiency. [ABSTRACT FROM AUTHOR]

Mechanical stretching is experienced ubiquitously by human tissues and their constituent cells and impacts biochemical and (mechano)biological processes relevant to health and disease. Numerous cell-stretching devices (CSDs) have been developed and used to apply mechanical strain to cells and tissues in in vitro settings, however, few have shown compatibility with live-cell microscopy. In most microscopy-compatible CSDs, imaging is performed post-mechanical stretching while live-cell imaging during cyclic stretching is very rarely shown, especially at high stretching frequencies and for long experiments (i.e., hours long). Live-cell imaging during cell stretching has revealed distinct time-dependent biomechanical features of cells, such as cell fluidization at high amplitudes or frequencies, or cracking followed by recovery of cell monolayers. Basic human functions such as breathing and digestion require mechanical stretching of cells and tissues. However, when it comes to laboratory experiments, the mechanical stretching that cells experience in the body is not often replicated, limiting the biomimetic nature of the studies and the relevance of results. Herein, we establish the importance of mechanical stretching during in vitro investigations by reviewing seminal works performed using cell-stretching platforms, highlighting important outcomes of these works as well as the engineering characteristics of the platforms used. Emphasis is placed on the compatibility of cell-stretching devices (CSDs) with live-cell imaging as well as their limitations and on the research advancements that could arise from live-cell imaging performed during cell stretching. [ABSTRACT FROM AUTHOR]

The effect of strain on the ferroelectricity of HfO _2 thin films after crystallization was investigated by applying uniaxial mechanical strains to Au/HfO _2 /TiN metal–ferroelectric–metal (MFM) capacitors. The remnant polarization (2 P _r ) of MFM capacitors increased when tensile strain was applied during polarization switching. This phenomenon should not be attributed to phase transformation from the non-ferroelectric to the ferroelectric phase, taking account of the fast relaxation of 2 P _r after removal of the mechanical strain and the fact that the crystal structure of HfO _2 thin films evaluated by grazing incidence X-ray diffraction measurement was not changed by the tensile strain.

Mesenchymal stem cells (MSCs) have been proven to promote tissue repair. However, concerns related to their clinical application and regulatory hurdles remain. Recent data has demonstrated the proregenerative secretome of MSCs can result in similar effects in the absence of the cells themselves. Within the secretome, exosomes have emerged as a promising regenerative component. Exosomes, which are nanosized lipid vesicles secreted by cells, encapsulate micro‐RNA (miRNA), RNA, and proteins that drive MSCs regenerative potential with cell specific content. As such, there is an opportunity to optimize the regenerative potential of MSCs, and thus their secreted exosome fraction, to improve clinical efficacy. Exercise is one factor that has been shown to improve muscle progenitor cell function and regenerative potential. However, the effect of exercise on MSC exosome content and function is still unclear. To address this, we used an in vitro culture system to evaluate the effects of mechanical strain, an exercise mimetic, on C2C12 (muscle progenitor cell) exosome production and proregenerative function. Our results indicate that the total exosome production is increased by mechanical strain and can be regulated with different tensile loading regimens. Furthermore, we found that exosomes from mechanically stimulated cells increase proliferation and myogenic differentiation of naïve C2C12 cells. Lastly, we show that exosomal miRNA cargo is differentially expressed following strain. Gene ontology mapping suggests positive regulation of bone morphogenetic protein signaling, regulation of actin‐filament‐based processes, and muscle cell apoptosis may be at least partially responsible for the proregenerative effects of exosomes from mechanically stimulated C2C12 muscle progenitor cells. [ABSTRACT FROM AUTHOR]

The key to hindering the commercial application of Ni-rich layered cathode is its severe structural and interface degradation during the undesired phase transition (hexagonal to hexagonal (H2 → H3)), degenerating from the build-up of mechanical strain and undesired parasitic reactions. Herein, a perovskite Li0.35La0.55TiO3 (LLTO) layer is built onto Ni-rich cathodes crystal to induce layered@spinel@perovskite heterostructure to solve the root cause of capacity fade. Intensive exploration based on structure characterizations, in situ X-ray diffraction techniques, and first-principles calculations demonstrate that such a unique heterostructure not only can improve the ability of the host structure to withstand the mechanical strain but also provides fast diffusion channels for lithium ions as well as provides a protective barrier against electrolyte corrosion. Impressively, the LLTO modified LiNi0.9Co0.05Mn0.05O2 cathode manifests an unexpected cyclability with an extremely high-capacity retention of ≈ 94.6% after 100 cycles, which is superior to the pristine LiNi0.9Co0.05Mn0.05O2 (79.8%). Furthermore, this modified electrode also shows significantly enhanced cycling stability even withstanding a high cut-off voltage of 4.6 V. This surface self-reconstruction strategy provides deep insight into the structure/interface engineering to synergistically stabilize structure stability and regulate the physicochemical properties of Ni-rich cathodes, which will also unlock a new perspective of surface interface engineering for layered cathode materials. [ABSTRACT FROM AUTHOR]

First-principles density functional theory-based calculations have been performed to investigate the strain-induced modifications in the electronic and vibrational properties of monolayer (ML)-ZnO. A wide range of in-plane tensile and compressive strain along different directions are applied to analyse the modifications in detail. The electronic band gap decreases under both tensile and compressive strain, and a direct-to-indirect band gap transition occurs for high values of biaxial tensile strain. The relatively low rate of decrease of band gap and large required strain for direct-to-indirect band gap transition compared to other 2D materials are analysed. Systematic decrease in the frequency of the in-plane and increase in the out-of-plane optical phonon modes with increasing tensile strain are observed. The in-plane acoustic modes show linear dispersion for unstrained as well as strained cases. However, the out-of-plane acoustic mode (ZA), which shows quadratic dispersion in the unstrained condition, turns linear with strain. The dispersion of the ZA mode is analysed using the shell elasticity theory and the possibility of ripple formation with strain is analysed. The strain-induced linearity of the ZA mode indicates the absence of rippling under strain. Finally, the stability limit of ML-ZnO is investigated and found that for 18 % biaxial tensile strain the structure shows instability with the emergence of imaginary phonon modes. Furthermore, the potential of ML-ZnO to be a good thermoelectric material is analysed in an intuitive way based on the calculated electronic and phononic properties. Our results, thus, not only highlight the significance of strain-engineering in tailoring the electronic and vibrational properties but also provide a thorough understanding of the lattice dynamics and mechanical strength of ML-ZnO. [ABSTRACT FROM AUTHOR]

Excessive mechanical strain is the prominent risk factor for osteoarthritis (OA), causing cartilage destruction and degeneration. However, the underlying molecular mechanism contributing to mechanical signaling transduction remains unclear in OA. Piezo type mechanosensitive ion channel component 1 (Piezo1) is a calcium-permeable mechanosensitive ion channel and provides mechanosensitivity to cells, but its role in OA development has not been determined. Herein, we found up-regulated expression of Piezo1 in OA cartilage, and that its activation contributes to chondrocyte apoptosis. The knockdown of Piezo1 could protect chondrocytes from apoptosis and maintain the catabolic and anabolic balance under mechanical strain. In vivo, Gsmtx4, a Piezo1 inhibitor, markedly ameliorated the progression of OA, inhibited the chondrocyte apoptosis, and accelerated the production of the cartilage matrix. Mechanistically, we observed the elevated activity of calcineurin (CaN) and the nuclear transfection of nuclear factor of activated T cells 1 (NFAT1) under mechanical strain in chondrocytes. Inhibitors of CaN or NFAT1 rescued the pathologic changes induced by mechanical strain in chondrocytes. Overall, our findings revealed that Piezo1 was the essential molecule response to mechanical signals and regulated apoptosis and cartilage matrix metabolism via the CaN/NFAT1 signaling axis in chondrocytes, and that Gsmtx4 could be an attractive therapeutic drug for OA treatment. [ABSTRACT FROM AUTHOR]

We present the design of Ge/Si avalanche photodetectors with SiN stressor-induced Ge strain for the C+L band light detection. By optimizing the placement position and thickness of the SiN layer with compressive stress, a uniform strain distribution with a maximum magnitude of 0.59% was achieved in Ge. The surface-illuminated APDs have been studied in respect of the photo-dark current, responsivity, gain, and 3-dB bandwidth. After introducing SiN stressor, the APD exhibits high primary responsivity of 0.80 A/W at 1.55 μm, 0.72 A/W at 1.625 μm, and 3-dB bandwidth of 17.5 GHz. The increased tensile strain in Ge can significantly improve the responsivity and broaden the response band of the device. This work provides a constructive approach to realizing high-responsivity high-speed Ge/Si APD working in the C+L band. [ABSTRACT FROM AUTHOR]

Orthodontic treatment is based on complex strategies and takes up to years until a desired therapeutic outcome is accomplished, implying long periods of high costs and discomfort for the patient. Choosing the optimal settings for force intensities in the initial phase of orthodontic tooth movement is the key to successful orthodontic treatment. It is known that orthodontic tooth movement is mainly mediated by tensile and compressive forces that are communicated to the alveolar bone via the periodontal ligament. While the revelation of the complex molecular network was already approached by transcriptomic analysis of compressed periodontal ligament cells, the entity of molecular key players activated by tensile forces remains elusive. Therefore, the aim of this study was to assess the effect of mechanical tensile forces on the gene expression profile of human primary periodontal ligament stromal cells, mimicking the initial phase of orthodontic tooth movement. A transcriptomic analysis of tension-treated and untreated periodontal ligament stromal cells yielded 543 upregulated and 793 downregulated differentially expressed genes. Finally, six highly significant genes were found in the transcriptome that are related to biological processes with relevance to orthodontic tooth movement, including apelin, fibroblast growth factor receptor 2, noggin, sulfatase 1, secreted frizzled-related protein 4 and stanniocalcin 1. Additionally, differences of gene expression profiles between individual cell donors showed a high effect size. Closer understanding of the roles of the identified candidates in the initial phase of orthodontic tooth movement could help to clarify the underlying mechanisms, which will be essential for the development of personalized treatment strategies in orthodontics.

Cleidocranial dysplasia (CCD) is a rare genetic defect caused by a heterozygous mutation of runt-related transcription factor 2 (RUNX2), which is important for osteoblast and skeletal development. RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment. Nicotinamide (NAM) affects bone remodelling processes. As these are crucial for orthodontic therapy, NAM could improve orthodontic treatment in CCD patients. This study investigates the effect of NAM in control and RUNX2-deficient osteoblasts under mechanical strain mimicking orthodontic treatment. First, the optimal NAM concentration and the differences in the expression profile of control and RUNX2-deficient osteoblasts were determined. Subsequently, osteoblasts were exposed to tensile and compressive strain with and without NAM, and the expression of genes critically involved in bone remodelling was investigated. NAM increased the expression of bone remodelling genes. RUNX2-deficient osteoblasts expressed more receptor activator of NFkB ligand (RANKL) and interleukin-6 (IL6), but less colony-stimulating factor-1 (CSF1). Most of the positive effects of NAM on bone remodelling genes were impaired by mechanical loading. In conclusion, NAM stimulated osteoblast differentiation by increasing the expression of RUNX2 and regulated the expression of osteoclastogenic factors. However, the positive effects of NAM on bone metabolism were impaired by mechanical loading and RUNX2 deficiency.

External stimuli induced effective regulations of luminescent material are of significant interest in the development of smart optical devices. Here, by simply doping with Er3+ in the 0.94Bi0.5Na0.5TiO3-0.06BaTiO3 (BNTBT) ferroelectric host, using the bendable mica substrate, and exerting mechanical strain (bending) or light illumination (via photochromic reaction), the all-inorganic, highly-transparent and flexible Er-doped BNTBT/Mica luminescent-ferroelectric thin films were designed and fabricated, displaying strain-induced dramatically elevation of up-conversion photoluminescence (PL) intensity, suppression of PL concentration quenching, outstanding endurance and durability, convenient illumination-mediated PL quenching. And the strain-induced structural changes and local lattice distortions of the thin films were further explored through theoretical calculations and Raman measurement. Our results can supply the guidance of designing other luminescent-ferroelectric materials with controlled PL properties via easy mechanical/photo stimuli for expanding the application of multifunctional wearable memory devices.

High-temperature superconducting magnets are a system with a complex configuration. In the process of creating such systems, HTSC tapes can be subject to mechanical damage, which leads to a deterioration in the transport characteristics of the tape. This paper presents the results of experimental studies of the effect of mechanical stresses on the transport characteristics of the second-generation HTSC tapes. The volt-ampere characteristics of various samples of second-generation HTSC tapes were measured during their winding on cylindrical formers of various diameters. Winding was carried out at the angles of 22° and 40° relative to the former axis with a force from 10 to 20 N. Different winding options were compared and the optimal set of winding configurations corresponding to the minimum degradation of the critical current of the tape was determined. Scanning Hall magnetometry is used to determine the regions of localization of defects arising at various winding options. All measurements were carried out at the boiling point of liquid nitrogen. The obtained data made it possible to calculate the area of flow of the longitudinal and transverse components of the current in each individual case. [ABSTRACT FROM AUTHOR]

As the main loading‐bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell‐5000™ tension system. We found that CXC‐ ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2‐STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC2 pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling. [ABSTRACT FROM AUTHOR]

The concentration of melatonin is elevated during the night when patients mainly wear removable orthodontic appliances. Next to periodontal ligament fibroblasts and osteoblasts, macrophages react to mechanical strain with an increased expression of inflammatory mediators. Here, we investigated the impact of melatonin on RAW264.7 macrophages exposed to tensile or compressive strain occurring during orthodontic tooth movement in the periodontal ligament. Before exposure to mechanical strain for 4 h, macrophages were pre-incubated with different melatonin concentrations for 24 h, to determine the dependence of melatonin concentration. Afterwards, we performed experiments with and without mechanical strain, the most effective melatonin concentration (25 µM), and the melatonin receptor 2 (MT2) specific antagonist 4P-PDOT. The expression of inflammatory genes and proteins was investigated by RT-qPCR, ELISAs, and immunoblot. Both tensile and compressive strain increased the expression of the investigated inflammatory factors interleukin-1-beta, interleukin-6, tumor necrosis factor alpha, and prostaglandin endoperoxide synthase-2. This effect was inhibited by the addition of melatonin. Incubation with 4P-PDOT blocked this anti-inflammatory effect of melatonin. Melatonin had an anti-inflammatory effect on macrophages exposed to mechanical strain, independent of the type of mechanical strain. As inhibition was possible with 4P-PDOT, the MT2 receptor might be involved in the regulation of the observed effects. [ABSTRACT FROM AUTHOR]

Abstract Background Tenocytes as specialised fibroblasts and inherent cells of tendons require mechanical load for their homeostasis. However, how mechanical overload compared to physiological load impacts on the tenogenic differentiation potential of fibroblasts is largely unknown. Methods Three-dimensional bioartificial tendons (BATs) seeded with murine fibroblasts (cell line C3H10T1/2) were subjected to uniaxial sinusoidal elongation at either overload conditions (0–16%, Ø 8%) or physiological load (0–8%, Ø 4%). This regime was applied for 2 h a day at 0.1 Hz for 7 days. Controls were unloaded, but under static tension. Results Cell survival did not differ among overload, physiological load and control BATs. However, gene expression of tenogenic and extra-cellular matrix markers (Scx, Mkx, Tnmd, Col1a1 and Col3a1) was significantly decreased in overload versus physiological load and controls, respectively. In contrast, Mmp3 was significantly increased at overload compared to physiological load, and significantly decreased under physiological load compared to controls. Mkx and Tnmd were significantly increased in BATs subjected to physiological load compared to controls. Proinflammatory interleukin-6 showed increased protein levels comparing load (both over and physiological) versus unloaded controls. Alignment of the cytoskeleton in strain direction was decreased in overload compared to physiological load, while other parameters such as nuclear area, roundness or cell density were less affected. Conclusions Mechanical overload decreases tenogenic differentiation and increases ECM remodelling/inflammation in 3D-stimulated fibroblasts, whereas physiological load may induce opposite effects.

Abstract Background Organogenesis from tonsil-derived mesenchymal cells (TMSCs) has been reported, wherein tenogenic markers are expressed depending on the chemical stimulation during tenogenesis. However, there are insufficient studies on the mechanical strain stimulation for tenogenic cell differentiation of TMSCs, although these cells possess advantages as a cell source for generating tendinous tissue. The purpose of this study was to investigate the effects of mechanical strain and transforming growth factor-beta 3 (TGF-β3) on the tenogenic differentiation of TMSCs and evaluate the expression of tendon-related genes and extracellular matrix (ECM) components, such as collagen. Results mRNA expression of tenogenic genes was significantly higher when the mechanical strain was applied than under static conditions. Moreover, mRNA expression of tenogenic genes was significantly higher with TGF-β3 treatment than without. mRNA expression of osteogenic and chondrogenic genes was not significantly different among different mechanical strain intensities. In cells without TGF-β3 treatment, double-stranded DNA concentration decreased, while the amount of normalized collagen increased as the intensity of mechanical strain increased. Conclusions Mechanical strain and TGF-β3 have significant effects on TMSC differentiation into tenocytes. Mechanical strain stimulates the differentiation of TMSCs, particularly into tenocytes, and cell differentiation, rather than proliferation. However, a combination of these two did not have a synergistic effect on differentiation. In other words, mechanical loading did not stimulate the differentiation of TMSCs with TGF-β3 supplementation. The effect of mechanical loading with TGF-β3 treatment on TMSC differentiation can be manipulated according to the differentiation stage of TMSCs. Moreover, TMSCs have the potential to be used for cell banking, and compared to other mesenchymal stem cells, they can be procured from patients via less invasive procedures.

We aimed to evaluate the effects of lactoferrin (LF) on the osteogenic differentiation and related gene expressions of mouse embryonic osteoblast precursor cells MC3T3-E1 under mechanical strain. MC3T3-E1 cells were randomly divided into control, strain loading, LF and strain loading + LF groups. Alkaline phosphatase (ALP) activity was measured. Cytoskeletal morphology was measured by rhodamine-phalloidin staining. Formation of mineralized nodules was observed by alizarin red staining. The expressions of differentiation-related genes type I collagen (COL-1), interleukin-6 (IL-6) and osteocalcin (OCN) were determined by RT-PCR, and those of p-Runx2 and p-ERK1/2 proteins were detected by Western blotting. The number of ALP positive cells and expressions of OCN, COL-1 and IL-6 were significantly elevated (P

Calcific aortic valve disease (CAVD) is a serious disease affecting the aging population. A complex interaction between biochemicals, cells, and mechanical cues affects CAVD initiation and progression. In this study, motivated by the progression of calcification in regions of high strain, we developed a finite element method (FEM) based spatial calcification progression model. Several cardiac cycles of transient structural FEM simulations were simulated. After each simulation cycle, calcium deposition was placed in regions of high circumferential strain. Our results show the radial expansion of calcification as spokes starting from the attachment region, agreeing very well with the reported clinical data.

Childhood obesity is a growing problem in industrial societies and associated with increased leptin levels in serum and salvia. Orthodontic treatment provokes pressure and tension zones within the periodontal ligament, where, in addition to fibroblasts, macrophages are exposed to these mechanical loadings. Given the increasing number of orthodontic patients with these conditions, insights into the effects of elevated leptin levels on the expression profile of macrophages during mechanical strain are of clinical interest. Therefore, the aim of this in vitro study was to assess the influence of leptin on the expression profile of macrophages during simulated orthodontic treatment. RAW264.7 macrophages were incubated with leptin and lipopolysaccharides (LPS) from Porphyromonas gingivalis (P. gingivalis) or with leptin and different types of mechanical strain (tensile, compressive strain). Expression of inflammatory mediators including tumor necrosis factor (TNF), Interleukin-1-B (IL1B), IL6, and prostaglandin endoperoxide synthase (PTGS2) was assessed by RT-qPCR, ELISAs, and immunoblot. Without additional mechanical loading, leptin increased Tnf, Il1b, Il6, and Ptgs2 mRNA in RAW264.7 macrophages by itself and after stimulation with LPS. However, in combination with tensile or compressive strain, leptin reduced the expression and secretion of these inflammatory factors. By itself and in combination with LPS from P. gingivalis, leptin has a pro-inflammatory effect. Both tensile and compressive strain lead to increased expression of inflammatory genes. In contrast to its effect under control conditions or after LPS treatment, leptin showed an anti-inflammatory phenotype after mechanical stress. [ABSTRACT FROM AUTHOR]

Recently, studies on low-dimensional conducting domain walls (DWs) in insulating ferroelectrics have opened up new research areas that allow information to be mechanically written and electrically read on the nanoscale. Large strains in thin films can change the polarization gradient across the DW region and thus increasing the DW current significantly. This phenomenon can enable the development of high sensitivity mechanical vibration sensors. In this study, the effects of variable uniaxial strain on the structures of 180° conducting DWs in LiNbO 3 (LNO) single-crystal thin films bonded onto Si/SiO 2 substrates were investigated. After the creation of antiparallel domains within each LNO nanosensor integrated at the film surface, strain modulation of DW currents was observed through simple mechanical bending of the film. The DW current increases under application of tensile strain along the axis of polarization, but decreases under application of in-plane compression by a factor of approximately 25. Phase field simulations showed the dramatic change in polarization gradients around the DW regions under the increase in tensile strain, which reduced the band gap. Repetitive band-gap narrowing/broadening with change in local electric field intensity under vibrating mechanical forces can periodically modulate both the carrier density and the DW conduction in the sensors. This finding not only provides the new fundamental physics to enrich the ferroelectric theory, but also paves the way to the near-future development of bending actuators, piezolighters, and micro-/nano-manipulators, etc. [ABSTRACT FROM AUTHOR]

Exploring efficient storage mediums is the key challenge to accomplish a sustainable hydrogen economy. Material-based hydrogen (H 2) storage is safe, economically viable and possesses high gravimetric density. Here, we have designed a novel H 2 storage architecture by decorating graphene-like haeckelite (r57) sheets with the super-alkali (NLi 4) clusters, which bonded strongly with the r57. We have performed van der Waals corrected density functional theory (DFT) calculations to study the structural, electronic, energetic, charge transfer, and H 2 storage properties of one-sided (r57-NLi 4) and two-sided (r57-2NLi 4) coverage of r57 sheets. Exceptionally high H 2 storage capacities of 10.74%, and 17.01% have been achieved for r57-NLi 4 , and r57-2NLi 4 systems, respectively that comfortably surpass the U.S. Department of Energy's (DOE) targets. Under maximum hydrogenation, the average H 2 adsorption energies have been found as −0.32 eV/H 2 , which is ideal for reversible H 2 storage applications. We have further studied the effects of mechanical strain to explore the H 2 desorption mechanism. Statistical thermodynamic analysis has been employed to study the H 2 storage mechanism at varied conditions of pressures and temperatures. Our findings validate the potential of r 57 -xNLi 4 as efficient H 2 storage materials. [Display omitted] • Pristine r57 weakly adsorb H 2 molecules. • NLi 4 bind strongly to r57 even at higher concentrations. • r57-NLi 4 and r57-2NLi 4 adsorb H 2 with desirable binding energy. • r57-NLi 4 and r57-2NLi 4 yield high storage capacities of 10.74%, and 17.01%, respectively. • Thermodynamic analysis authenticates the H 2 storage at ambient conditions. [ABSTRACT FROM AUTHOR]

Cobalt doped Mg–Zn ferrite (Mg(0.56)Co(0.14)Zn(0.30)Fe2O4) was synthesized by the modified sol–gel auto combustion method (MSG) in which lemon extracts were used as the source of energy. X-ray diffraction (XRD) technique was employed to confirm the formation of cubic spinel ferrite phase. The lattice parameter was evaluated to be 8.39 Å with an average crystallite size ranging from 41–51 nm. Dislocation density, mechanical properties, and hopping length were determined. Crystallite size and strain were evaluated using W–H plot and size–strain plot. [ABSTRACT FROM AUTHOR]

Background: Proposed mechanisms that potentially contribute to polypropylene mesh degradation after in vivo exposure include oxidizing species and mechanical strains induced by normal healing, tissue integration, muscle contraction, and the immediate and chronic inflammatory responses. Methods: This study explores these potential degradation mechanisms using 63 mesh implants retrieved from patients after a median implantation time of 24 months following hernia repair surgery (mesh explants) and analysis of multivariate associations between the material changes and clinical characteristics. Specifically, polypropylene mesh degradation was characterized in terms of material changes in surface oxidation, crystallinity and mechanical properties, and clinical characteristics included mesh placement location, medical history and mesh selection. Results: Compared to pristine control samples, subsets of mesh explants had evidence of surface oxidation, altered crystallinity, or changed mechanical properties. Using multivariate statistical approach to control for clinical characteristics, infection was a significant factor affecting changes in mesh stiffness and mesh class was a significant factor affecting polypropylene crystallinity changes. Conclusions: Highly variable in vivo conditions expose mesh to mechanisms that alter clinical outcomes and potentially contribute to mesh degradation. These PP mesh explants after 0.5 to 13 years in vivo had measurable changes in surface chemistry, crystallinity and mechanical properties, with significant trends associated with factors of mesh placement, mesh class, and infection. [ABSTRACT FROM AUTHOR]

Purpose: The process of osteogenic differentiation hinges upon the pivotal role of mechanical signals. Previous studies found that mechanical tensile strain of 2500 microstrain (με) at a frequency of 0.5 ​Hz promoted osteogenesis in vitro. However, the mechanism of the mechanical strain influencing osteogenesis at the cellular and molecular levels are not yet fully understood. This study aimed to explore the mechanism of mechanical strain on osteogenic differentiation of MC3T3-E1 cells., Materials and Methods: Proteomics analysis was conducted to explore the mechanical strain that significantly impacted the protein expression. Bioinformatics identified important mechanosensitive proteins and the expression of genes was investigated using real-time PCR. The dual-luciferase assay revealed the relationship between the miRNA and its target gene. Overexpression and downexpression of the gene, to explore its role in mechanically induced osteogenic differentiation and transcriptomics, revealed further mechanisms in this process., Results: Proteomics and bioinformatics identified an important mechanosensitive lowexpression protein ATP13A3, and the expression of Atp13a3 gene was also reduced. The dual-luciferase assay revealed that microRNA-3070-3p (miR-3070-3p) targeted the Atp13a3 gene. Furthermore, the downexpression of Atp13a3 promoted the expression levels of osteogenic differentiation-related genes and proteins, and this process was probably mediated by the tumor necrosis factor (TNF) signaling pathway., Conclusion: Atp13a3 responded to mechanical tensile strain to regulate osteogenic differentiation, and the TNF signaling pathway regulated by Atp13a3 was probably involved in this process. These novel insights suggested that Atp13a3 was probably a potential osteogenesis and bone formation regulator., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Infrared transmission characteristics of VO2 thin films synthesized on multiple substrates, using a low-pressure direct oxidation technique, have been characterized. Material characterization of these films indicates high material quality, which resulted in large variation of electrical and optical properties at phase transition. A change in optical transmissivity greater than 80% was observed for these films utilizing infrared (IR) laser illumination at 1550 nm. Phase transition enabled by temperature change induced by a pulsed high-power laser beam resulted in modulated IR laser transmission with a low time constant in VO2 on transparent quartz and muscovite substrates. Investigation of the effect of mechanical strain on phase transition in VO2 grown on flexible muscovite substrate indicate shift in transition temperature to higher for tensile and lower for compressive strains. [ABSTRACT FROM AUTHOR]

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by an arrhythmogenic mechanism involving disruption of calcium handling. This genetic disease can lead to sudden death in children and young adults during physical or emotional stress. Prior CPVT studies have focused on calcium handling, but mechanical functionality has rarely been investigated in vitro. In this research we combine stem cell-derived cardiomyocytes from a CPVT patient (RyR2-H2464D mutation) and a healthy familial control with an engineered culture platform to evaluate mechanical function of cardiomyocytes. Substrates with Young’s modulus ranging from 10 to 50 kPa were used in conjunction with microcontact printing of ECM proteins into defined patterns for subsequent attachment. Digital Image Correlation (DIC) was used to evaluate collections of contracting cells. The amplitude of contractile strain was utilized as a quantitative indicator of functionality and disease severity. We found statistically significant differences: the maximum contractile strain was consistently higher in patient samples compared to control samples on all substrate stiffnesses. Additionally, the patient cell line had a statistically significantly slower intrinsic contraction rate than the control, which agrees with prior literature. Differences in mechanical strain have not been previously reported, and hypercontractility is not a known characteristic of CPVT. However, functional changes can occur as the disease progresses, thus this observation may not represent behavior observed in adolescent and adult patients. These results add to the limited studies of mechanical function of CPVT CMs reported in literature and identify functional differences that should be further explored.

Excessive mechanical strain is the prominent risk factor for osteoarthritis (OA), causing cartilage destruction and degeneration. However, the underlying molecular mechanism contributing to mechanical signaling transduction remains unclear in OA. Piezo type mechanosensitive ion channel component 1 (Piezo1) is a calcium-permeable mechanosensitive ion channel and provides mechanosensitivity to cells, but its role in OA development has not been determined. Herein, we found up-regulated expression of Piezo1 in OA cartilage, and that its activation contributes to chondrocyte apoptosis. The knockdown of Piezo1 could protect chondrocytes from apoptosis and maintain the catabolic and anabolic balance under mechanical strain. In vivo, Gsmtx4, a Piezo1 inhibitor, markedly ameliorated the progression of OA, inhibited the chondrocyte apoptosis, and accelerated the production of the cartilage matrix. Mechanistically, we observed the elevated activity of calcineurin (CaN) and the nuclear transfection of nuclear factor of activated T cells 1 (NFAT1) under mechanical strain in chondrocytes. Inhibitors of CaN or NFAT1 rescued the pathologic changes induced by mechanical strain in chondrocytes. Overall, our findings revealed that Piezo1 was the essential molecule response to mechanical signals and regulated apoptosis and cartilage matrix metabolism via the CaN/NFAT1 signaling axis in chondrocytes, and that Gsmtx4 could be an attractive therapeutic drug for OA treatment.

Background: Tenocytes as specialised fibroblasts and inherent cells of tendons require mechanical load for their homeostasis. However, how mechanical overload compared to physiological load impacts on the tenogenic differentiation potential of fibroblasts is largely unknown. Methods: Three-dimensional bioartificial tendons (BATs) seeded with murine fibroblasts (cell line C3H10T1/2) were subjected to uniaxial sinusoidal elongation at either overload conditions (0–16%, Ø 8%) or physiological load (0–8%, Ø 4%). This regime was applied for 2 h a day at 0.1 Hz for 7 days. Controls were unloaded, but under static tension. Results: Cell survival did not differ among overload, physiological load and control BATs. However, gene expression of tenogenic and extra-cellular matrix markers (Scx, Mkx, Tnmd, Col1a1 and Col3a1) was significantly decreased in overload versus physiological load and controls, respectively. In contrast, Mmp3 was significantly increased at overload compared to physiological load, and significantly decreased under physiological load compared to controls. Mkx and Tnmd were significantly increased in BATs subjected to physiological load compared to controls. Proinflammatory interleukin-6 showed increased protein levels comparing load (both over and physiological) versus unloaded controls. Alignment of the cytoskeleton in strain direction was decreased in overload compared to physiological load, while other parameters such as nuclear area, roundness or cell density were less affected. Conclusions: Mechanical overload decreases tenogenic differentiation and increases ECM remodelling/inflammation in 3D-stimulated fibroblasts, whereas physiological load may induce opposite effects. [ABSTRACT FROM AUTHOR]

In this article, we have comprehensively investigated the electrical properties of split-gate trench (SGT) power MOSFETs under mechanical strains. The static and dynamic electrical properties of SGT power MOSFETs under both uniaxial and biaxial strains are examined thoroughly. It is found that both uniaxial and biaxial compressive strains improve the drain current (${I}_{d}$), while uniaxial and biaxial tensile strains do the opposite. The influence of strain is correlated with drain voltage (${V}_{d}$), and biaxial strains are slightly more effective than uniaxial strains. The mechanical strains do not change the threshold voltage (${V}_{{\mathrm {th}}}$), breakdown voltage (BV), capacitances, and switching characteristics. The piezoresistance coefficients of the SGT power MOSFETs are evaluated. It is also proved that both biaxial and uniaxial compressive strains can effectively decrease the figure-of-merit (FOM) of SGT power MOSFETs. [ABSTRACT FROM AUTHOR]

In this study, the negative bias temperature instability (NBTI) under mechanical strain conditions of low-temperature polycrystalline silicon thin-film transistors (LTPS TFTs) with a stress-release structure was investigated. With both electrical and mechanical stresses simultaneously applied, more significant degradation behaviors will be observed in standard TFT devices because mechanical stress makes it easier to generate strain in Si–H bonds, thus benefiting the process of electrochemical reaction. By employing a stress-release shape in the poly channel, mechanical stress, which mainly accumulates at the width edge of the poly-Si/SiO2 interface, is moved away from the main channel; thus, fewer strained Si–H bonds can participate in the electrochemical reaction compared to the standard structure. Therefore, the degradation of devices under strained NBTI is effectively mitigated, such that the reliability of the devices is enhanced. These observations were obtained using electrical characteristics and extraction of the trap state distribution. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is an important clinical problem. Chronic pressure/volume overload of the atria promotes AF, particularly via enhanced extracellular matrix (ECM) accumulation manifested as tissue fibrosis. Loading of cardiac cells causes cell stretch that is generally considered to promote fibrosis by directly activating fibroblasts, the key cell type responsible for ECM production. The primary purpose of this article is to review the evidence regarding direct effects of stretch on cardiac fibroblasts, specifically: (i) the similarities and differences among studies in observed effects of stretch on cardiac fibroblast function; (ii) the signalling pathways implicated; and (iii) the factors that affect stretch-related phenotypes. Our review summarizes the most important findings and limitations in this area and gives an overview of clinical data and animal models related to cardiac stretch, with particular emphasis on the atria. We suggest that the evidence regarding direct fibroblast activation by stretch is weak and inconsistent, in part because of variability among studies in key experimental conditions that govern the results. Further work is needed to clarify whether, in fact, stretch induces direct activation of cardiac fibroblasts and if so, to elucidate the determining factors to ensure reproducible results. If mechanical load on fibroblasts proves not to be clearly profibrotic by direct actions, other mechanisms like paracrine influences, the effects of systemic mediators and/or the direct consequences of myocardial injury or death, might account for the link between cardiac stretch and fibrosis. Clarity in this area is needed to improve our understanding of AF pathophysiology and assist in therapeutic development. [ABSTRACT FROM AUTHOR]

Mechanical strain regulated osteoclastic differentiation and angiogenesis are crucial for bone modeling and remodeling, and previous data indicate that high-magnitude strain within physiological load regulates osteoclastic differentiation. However, the underlying mechanisms are still not fully understood. In the present study, the RAW264.7 mouse monocyte/macrophage was used as an osteoclast precursor, and the bone marrow-derived macrophages (BMMs) were isolated and cultured in vitro. The above cells were subjected to macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) for the induction of osteoclast differentiation. Subsequently, the above cells were stretched by differential strain magnitudes to simulate the mechanical stimuli in the physiological conditions, and we found that low-magnitude strain (100 με) increased the expression levels of Acp5, Clcn7, MMP9 and Ctsk to promote osteoclastogenesis, while high-magnitude strain (3000 με) had opposite effects. In addition, we noticed that high-magnitude strain upregulated PTEN to inactivate the PI3K/Akt signaling pathway, and silencing of PTEN abrogated the suppressing effects of high-magnitude strain on osteoclastic differentiation. Next, we screened out that high-magnitude strain downregulated miR-21 to promote PTEN expressions in a competing endogenous RNA (ceRNA)-dependent manner. Finally, upregulation of miR-21 recovered osteoclastic differentiation in RAW264.7 and BMMs cells stimulated with high-magnitude strain. Collectively, our findings suggested that high-magnitude mechanical strain affected osteoclastic differentiation through modulating the miR-21/PTEN/PI3K/Akt signaling cascade, which provided potential strategies for the treatment of bone-related diseases. [ABSTRACT FROM AUTHOR]