Mechanoresponsive MiR-138-5p Targets MACF1 to Inhibit Bone Formation

Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.

Machine learning-based real-time visible fatigue crack growth detection

Many large-scale and complex structural components are applied in the aeronautics and automobile industries.However,the repeated alternating or cyclic loads in service tend to cause unexpected fatigue fractures.Therefore,developing real-time and visible monitoring methods for fatigue crack initiation and propagation is critically important for structural safety.This paper proposes a machine learning-based fatigue crack growth detection method that combines computer vision and machine learning.In our model,computer vision is used for data creation,and the machine learning model is used for crack detection.Then computer vision is used for marking and analyzing the crack growth path and length.We apply seven models for the crack classification and find that the decision tree is the best model in this research.The experimental results prove the effectiveness of our method,and the crack length measurement accuracy achieved is 0.6 mm.Furthermore,the slight machine learning models help us realize real-time and visible fatigue crack detection.

Solvent‑aided phase separation in hydrogel towards significantly enhanced mechanoresponsive strength

Understanding working principles and thermodynamics behind phase separations,which have significant influences on condensed molecular structures and their performances,can inspire to design and fabricate anomalously and desirably mechanoresponsive hydrogels.However,a combination of techniques from physicochemistry and mechanics has yet been established for the phase separation in hydrogels.In this study,a thermodynamic model is firstly formulated to describe solvent-aided phase and microphase separations in the hydrogels,which present significantly improved mechanoresponsive strengths.Flory-Huggins theory and interfacial energy equation have further been applied to model the thermodynamics of concentration-dependent and temperature-dependent phase separations.An intricately detailed phase map has finally been formulated to explore the working principle.The thermodynamic methodology of phase separations,combined with the constitutive stress-strain relationships,has a great potential to explore the working mechanisms in mechanoresponsive hydrogels.

ESIPT-regulated Mechanoresponsive Luminescence Process by Introducing Intramolecular Hydrogen Bond in Naphthalimide Derivatives

Herein,two compounds,4-2′-hydroxybenzylidenehydrazinyl-N-butyl-1,8-naphthalimide(BN-1)and 4-benzylidenehydrazinyl-N-butyl-1,8-naphthalimide(BN-2),were synthesized to explore the hydrogen bonding effect on mechanoresponsive luminescent(MRL).The results showed that compound BN-1 exhibited strong emission in solution and solid-state compared with compound BN-2.After grinding,the emission intensity of compound BN-1 sharply decreased by as much as 15 times with an obvious red-shift from 552 nm to 577 nm.The control compound BN-2,by contrast,did not change so much before and after grinding.Single crystal analysis suggests that BN-1 molecule formed strong intramolecular interaction via-N=N⋯H-O hydrogen bond with a distance of 0.2632 nm.An excited-state intramolecular proton transfer(ESIPT)based fluorophore featured this intramolecular hydrogen bond.The intramolecular hydrogen bond as well as other intermolecular interactions can rigidify the molecular conformation of compound BN-1 in solid-state,and thus suppress the nonradiative pathways,resulting in strong emission.These intra-and intermolecular interactions were destroyed by mechanical stimuli,accompanied by molecular conformation change that decreases the luminescence and blocks the ESIPT process.The MRL process was also demonstrated by scanning electron microscopy and powder X-ray diffraction.The molecular stacking mode changed from crystalline to a disordered amorphous state after grinding.