Cell stimulation plays a critical role in regulating essential cellular processes such as differentiation,migration,and apoptosis.Among various stimulation methods,magnetic microano robots(mMNRs)have gained attention ...Cell stimulation plays a critical role in regulating essential cellular processes such as differentiation,migration,and apoptosis.Among various stimulation methods,magnetic microano robots(mMNRs)have gained attention for their ability to precisely stimulate cellular and intracellular structures,owing to their structural flexibility and remote actuation.While much of the research on mMNRs has focused on their use for chemical stimulation of cells,particularly for targeted drug delivery,increasing attention is now given to their potential for physical stimulation of cells.As one form of physical stimulation,mechanical cell stimulation,particularly for cancer therapeutics,has been discussed in existing reviews.This article presents a comprehensive review of the most recent advances in mMNR-mediated physical cell stimulation,including mechanical,thermal,and electrical stimulation,and highlights their emerging roles in cancer therapy,regenerative medicine,neuromodulation,and antimicrobial treatment.The fundamentals of magnetic material-field interactions and actuation mechanisms are discussed,followed by fabrication strategies for structurally diverse mMNRs.Biomedical applications driven by mMNR-mediated cell stimulation are then discussed,along with remaining challenges and opportunities.By highlighting the unique capabilities of mMNRs in physical cell stimulation,this review emphasizes their potential in advancing both biological research and biomedical applications.展开更多
Fracturing operations in shale gas reservoirs of the Sichuan-Chongqing area are frequented by casing deformation,failures in delivery of mechanical staging tools and other down-hole complexities.In addition,limitation...Fracturing operations in shale gas reservoirs of the Sichuan-Chongqing area are frequented by casing deformation,failures in delivery of mechanical staging tools and other down-hole complexities.In addition,limitation in volumes of tail-in proppant in the matrix area significantly restricts the conductivity in the near zones of the wellbore.Eventually,flowback performance and productivity of shale gas horizontal wells are negatively affected.With consideration to the limitations in the implementation of the mechanical staging technique with bridge plug for shale gas development in the Sichuan-Chongqing area,the technique of multi-stage sand filling stimulation in horizontal wells was proposed to solve the above-mentioned problems.By filling sands in fractures,it is possible to divert fluids to maintain long-term high conductivity of fractures,which is the key to satisfactory EOR performances.By introducing the Hertz contact and fractal theory in the analysis of sand plug strength,and in combination of lab engineering simulation test results,the mechanical model for sand plugs in fractures with proppant was constructed.In terms of strength criteria and friction,the stability criteria of sand plug were put forward.Thus,the permeability fractural model for sand plugs in fractures was perfected.Test results show that the stability of sand plug in the earlier stage of production is mainly affected by fluid washing during flowback,so it is necessary to control the flowback rate strictly.In the later stage of production,the stability is mainly affected by fracture closure stress and flow pressure,so it is necessary to enhance the yield strength of proppant to maintain high conductivity of fractures.In conclusion,the multi-stage sand filling stimulation provides a new technique for multi-stage clustering fracturing operations in shale gas horizontal well development.展开更多
The root system actively reacts to mechanical stimuli in its environment,transmitting mechanical signals to optimize the utilization of environmental resources.While the mechanical impedance created by the growth medi...The root system actively reacts to mechanical stimuli in its environment,transmitting mechanical signals to optimize the utilization of environmental resources.While the mechanical impedance created by the growth medium serves as the primary source of stimulation for the roots,extensive research has focused on the roots'response to static mechanical stimulation.However,the impact of dynamic mechanical stimulation on root phenotype remains underexplored.In this study,we utilized a low acyl gellan gum/polyacrylamide(GG/PAM)double network elastic hydrogel as the growth medium for rapeseed.We constructed a mechanical device to investigate the effects of reciprocating extrusion stimulation on the growth of the rapeseed root system.After three weeks of mechanical stimulation,the root system exhibited a significant increase in lateral roots.This branching enhanced the roots'anchoring and penetration into the hydrogel,thereby improving the root system's adaptability to its environment.Our findings offer valuable data and insights into the effects of reciprocating mechanical stimulation on root growth,providing a new way for engineering root phenotype.展开更多
To get a deeper understanding on the formation mechanisms and distribution laws of remaining oil during water flooding, and enhanced oil recovery(EOR) mechanisms by reversing water injection after water flooding, 3D v...To get a deeper understanding on the formation mechanisms and distribution laws of remaining oil during water flooding, and enhanced oil recovery(EOR) mechanisms by reversing water injection after water flooding, 3D visualization models of fractured-vuggy reservoir were constructed based on the elements and configuration of fractures and vugs, and typical fracture-vug structures by using advanced CT scanning and 3D printing technologies. Then, water flooding and reversing water injection experiments were conducted. The formation mechanisms of remaining oil during water flooding include inadequate injection-production well control, gravity difference between oil and water, interference between different flow channels, isolation by low connectivity channel, weak hydrodynamic force at the far end. Under the above effects, 7 kinds of remaining oil may come about, imperfect well-control oil, blind side oil, attic oil at the reservoir top, by-pass residual oil under gravity, by-pass residual oil in secondary channel, isolated oil in low connectivity channel, and remaining oil at far and weakly connected end. Some remaining oil can be recovered by reversing water injection after water flooding, but its EOR is related to the remaining oil type, fracture-cavity structure and reversing injection-production structure. Five of the above seven kinds of remaining oil can be produced by six EOR mechanisms of reversing water injection: gravity displacement, opening new flow channel, rising the outflow point, hydrodynamic force enhancement, vertically equilibrium displacement, and synergistic effect of hydrodynamic force and gravity.展开更多
Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of ost...Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development.In this study,we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication,mimicking the key physiological characteristics of articular cartilage for organ-level OA research.By applying controllable mechanical compression,we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes.We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets.This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions,paving the way for advanced studies on OA pathogenesis and drug screening.展开更多
Osteoarthritis is among the leading causes of disability worldwide,and no pharmacological therapies currently exist to reverse its progression.This lack of therapies is primarily attributed to the inadequacies of conv...Osteoarthritis is among the leading causes of disability worldwide,and no pharmacological therapies currently exist to reverse its progression.This lack of therapies is primarily attributed to the inadequacies of conventional in vitro models of joint physiology and pathology,which significantly hinder advancements in disease mechanism research and drug development.As an emerging in vitro joint model,joint-on-a-chip(JoC)technology allows low-cost,efficient simulation of physiological and pathological joint activities,making it a focal point of current research.Cartilage,subchondral bone,and synovium are among the key tissues required for constructing in vitro joint models,with cartilage playing a central load-bearing role in joint movement.This article provides a detailed overview of the structure and function of these tissues,with an emphasis on the load-bearing mechanisms of cartilage,and identifies the microenvironmental characteristics that JoC should aim to replicate.Subsequently,we review the current types of JoC and highlight their core challenge:the seamless integration of multi-tissue co-culture with specific mechanical stimulation.To address this issue,we propose potential solutions and present a conceptual design for a JoC prototype.Finally,we discuss the challenges and issues related to the outlook for JoC.Our ultimate goal is to develop a JoC capable of replicating the key microenvironments of joints,serving as a high-performance in vitro joint model to advance the study of disease mechanisms and facilitate drug development.展开更多
Tissue-engineered cartilage(TEC)remains a potential alternative for the repair of articular cartilage defects.However,there has been a significant different between the properties of TEC and those of natural cartilage...Tissue-engineered cartilage(TEC)remains a potential alternative for the repair of articular cartilage defects.However,there has been a significant different between the properties of TEC and those of natural cartilage.Studies have shown that mechanical stimulation such as compressive load can help regulate matrix remodelling in TEC,thus affecting its biomechanical properties.However,the influences of shear induced from the tissue fluid phase have not been well studied and may play an important role in tissue regeneration especially when integrated with the compressive load.Therefore,the aim of this study was to quantitatively investigate the effects of combined loading mechanisms on TEC in vitro.A bespoke biosimulator was built to incorporate the coupled motion of compression,friction and shear.The specimens,encapsulating freshly isolated rabbit chondrocytes in a hydrogel,were cultured within the biosimulator under various mechanical stimulations for 4 weeks,and the tissue activity,matrix contents and the mechanical properties were examined.Study groups were categorized according to different mechanical stimulation combinations,including strain(5-20%at 5%intervals)and frequency(0.25 Hz,0.5 Hz,1 Hz),and the effects on tissue behaviour were investigated.During the dynamic culture process,a combined load was applied to simulate the combined effects of compression,friction and shear on articular cartilage during human movement.The results indicated that a larger strain and higher frequency were more favourable for the specimen in terms of the cell proliferation and extracellular matrix synthesis.Moreover,the combined mechanical stimulation was more beneficial to matrix remodelling than the single loading motion.However,the contribution of the combined mechanical stimulation to the engineered cartilaginous tissue matrix was not sufficient to impede biodegradation of the tissue with culture time.展开更多
Background:Scalp combing,as an ancient method of health care,has been used for thousands of years in traditional Chinese medicine.Although this method is considered to be beneficial for the blood circulation of the he...Background:Scalp combing,as an ancient method of health care,has been used for thousands of years in traditional Chinese medicine.Although this method is considered to be beneficial for the blood circulation of the head,the underlying mechanisms remain unclear.Methods:Both human participants and mice were used in this study.In participants,the scalp was stimulated by combing continuously for 5 min,and the temperature was measured using infrared thermal imaging before and after stimulation.In mice,the temperature was determined before and at 5,15,and 30 min after a 5-min scalp mechanical stimulation(SMS).Additionally,the vasculature of the mice was labeled with retro-orbital fluorescein isothiocyanate-dextran injection,and the capillaries were observed directly under a confocal microscope.Using in vivo CLARITY imaging and the spectrofluorometric detection of Evans Blue dye extravasation,the bloodebrain barrier permeability was assessed.Results:SMS increased the temperature of the left ear significantly in human(P=.0247)while can slightly increase the temperature of the right ear and the face without significant difference(P>.05).Moreover,SMS can significantly slow the decrease in the temperature of the external auditory canal at 5 min(P=.0153)and in body temperature at 15 min(P=.0295)after SMS whereas no significant difference in body temperature at 30 min(P>.05)compared with control mice.Furthermore,capillaries of the ear with a diameter of less than 8 mm were significantly dilated(P=.0006)following SMS and the number of dextran dots was higher at 15 min(P>.05)and 30 min(F=10.98,P=.037)after SMS intervention compared with control mice.Conclusion:Our study provides strong evidence to support the notion that scalp combing can improve extra-and intracranial blood circulation under healthy conditions.展开更多
Loss of sensory function for upper-limb amputees inevitably devastates their life qualities, and lack of reliable sensory feedback is the biggest defect to sophisticated prosthetic hands, greatly hindering their usefu...Loss of sensory function for upper-limb amputees inevitably devastates their life qualities, and lack of reliable sensory feedback is the biggest defect to sophisticated prosthetic hands, greatly hindering their usefulness and perceptual embodiment. Thus, it is extremely necessary to accomplish an intelligent prosthetic hand with effective tactile sensory feedback for an upper-limb amputee. This paper presents an overview of three kinds of existing sensory feedback approaches, including cutaneous mechanical stimulation(CMS), transcutaneous electrical nerve stimulation(TENS) and direct peripheral nerve electrical stimulation(DPNES). The emphasis concentrates on major scientific achievements, advantages and disadvantages. The TENS on the skin areas with evoked finger sensation(EFS) at upper-limb amputees' residual limbs might be one of the most promising approaches to realize natural sensory feedback.展开更多
Mechanical stimulation technology is critical in agricultural crop production because it is constantly regarded as a developing green technology to regulate plants to meet people's need for green and healthy agric...Mechanical stimulation technology is critical in agricultural crop production because it is constantly regarded as a developing green technology to regulate plants to meet people's need for green and healthy agricultural products. Various environmental mechanical stimulation impacts seed germination, seedling growth, flowering date, fruit quantity, and fruit quality throughout the life cycle of a horticultural plant. This study first outlines the basic characteristics of six types of common mechanical stimulation in nature:precipitation, wind, gravity,touch, sound, and vibration. The effects of various mechanical stimulation types on the seed, seedling, flowering, and fruit of horticultural plants throughout their whole life cycle are then presented, as reviewed in the recent 100 years of existing literature. Finally, potential future study directions are discussed. The main challenge in mechanical stimulation technology is to uncover its potential capabilities for regulating and controlling plant development and fruit quality in green agriculture instead of agricultural chemicals.展开更多
Mechanical stimulation of plants can be caused by various abiotic and biotic environmental factors.Apart from the negative consequences,it can also cause positive changes,such as acclimatization of plants to stress co...Mechanical stimulation of plants can be caused by various abiotic and biotic environmental factors.Apart from the negative consequences,it can also cause positive changes,such as acclimatization of plants to stress conditions.Therefore,it is necessary to study the physiological and biochemical mechanisms underlying the response of plants to mechanical stimulation.Our aim was to evaluate the response of model plant Arabidopsis thaliana to a moderate force of 5 N(newton)for 20 s,which could be compared with the pressure caused by animal movement and weather conditions such as heavy rain.Mechanically stimulated leaves were sampled 1 h after exposure and after a recovery period of 20 h.To study a possible systemic response,unstimulated leaves of treated plants were collected 20 h after exposure alongside the stimulated leaves from the same plants.The effect of stimulation was assessed by measuring oxidative stress parameters,antioxidant enzymes activity,total phenolics,and photosynthetic performance.Stimulated leaves showed increased lipid peroxidation 1 h after treatment and increased superoxide dismutase activity and phenolic oxidation rate after a 20-h recovery period.Considering photosynthetic performance after the 20-h recovery period,the effective quantum yield of the photosystem II was lower in the stimulated leaves,whereas photochemical quenching was lower in the unstimulated leaves of the treated plants.Nonphotochemical quenching was lower in the stimulated leaves 1 h after treatment.Our study suggested that plants sensed moderate force,but it did not induce pronounced change in metabolism or photosynthetic performance.Principal component analysis distinguished three groups–leaves of untreated plants,leaves analysed 1 h after stimulation,while stimulated and unstimulated leaves of treated plants analysed 20 h after treatment formed together the third group.Observed grouping of stimulated and unstimulated leaves of treated plants could indicate signal transduction from the stimulated to distant leaves,that is,a systemic response to a local application of mechanical stimuli.展开更多
Objective: Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into chondrocytes, it is the ideal seed cells for treating cartilage injury. The purpose of this study was to investigate the i...Objective: Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into chondrocytes, it is the ideal seed cells for treating cartilage injury. The purpose of this study was to investigate the inducible factors that stimulate the differentiation of bone marrow mesenchymal stem cells into chondrocytes. Methods: Rat BMSCs were isolated and subcultured, and then inoculated on PLGA scaffolds after successfully identificating of BMSCs. They were divided into 5 groups. Blank serum group, TGF-β1 + Yougui Yin drug-containing serum induction group, TGF-β1 + mechanical stimulation induction group, Yougui Yin drug-containing serum + mechanical stimulation induction group, TGF-β1 + Yougui Yin drug-containing serum + mechanical stimulation induction group, 4 weeks later, the adhesion status of cells and scaffolds was observed by Scanning Electron Microscopy, and then chondrocyte induction was performed on different treatment groups. After induction, the expression of Aggrecan and Collagen II was detected by immunofluorescence, and the mRNA expression of Aggrecan and Collagen II was detected by qPCR. Results: BMSCs were identified as rat bone marrow mesenchymal stem cells by immunofluorescence CD34 and CD44 cells. Scanning Electron Microscopy observed that BMSCs grew well on PLGA. Compared with PLGA group, the scaffold space of BMSCS-PLGA composite was significantly reduced, and the growth of cell adhesion scaffold was significantly increased. Compared with the blank serum group, the expression of Aggrecan in TGF-β1 + Yougui Yin drug-containing serum group and Yougui Yin drug-containing serum + mechanical stimulation group was significantly increased. The expression of Collagen II in TGF-β1 + Yougui Yin medicated serum group, Yougui Yin medicated serum + mechanical stimulation group, TGF-β1 + mechanical stimulation group and TGF-β1 + Yougui Yin medicated serum + mechanical stimulation group were significantly increased;PCR results showed that compared with blank serum group, the expression of Aggrecan in other groups was significantly increased, except for Collagen II expression in Yougui Yin drug-containing serum + mechanical stimulation group. Conclusion: BMSCs can differentiate into chondrocytes on PLGA scaffold. Compared with blank serum group, BMSCs can be induced to differentiate into chondrocytes in all induction groups, among all induction groups, TGF-β1 + Yougui-yin drug-containing serum group and TGF-β1 + mechanical stimulation group were more significant, and the difference was statistically significant.展开更多
Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to ra...Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.展开更多
In bone tissue engineering microstructure design,adjusting the structural design of biomimetic bone scaffolds can provide distinct differentiation stimuli to cells on the scaffold surface.This study explored the biome...In bone tissue engineering microstructure design,adjusting the structural design of biomimetic bone scaffolds can provide distinct differentiation stimuli to cells on the scaffold surface.This study explored the biomechanical impacts of different biomimetic microstructures on advanced bone tissue engineering scaffolds.Two irregular bone scaffolds(homogeneousadial gradient)based on the Voronoi tesselation algorithm and eight regular lattice scaffolds involving pillar body centered cubic,vintiles,diamond,and cube(homogeneousadial gradient)with constant 80%porosity were constructed.Mechanical stimulation differentiation algorithms,finite element analysis,and computational fluid dynamics were used to investigate the effects of different pore structures on the octahedral shear strain and fluid flow shear stress within the scaffolds,thereby elucidating the differentiation capabilities of the five structural bone/cartilage cell types.The findings demonstrated that irregular structures and radial-gradient designs promoted osteogenic differentiation,whereas regular structures and homogeneous designs facilitated chondrogenic differentiation.The highest percentages of osteoblast and chondrocyte differentiation were observed in radial-gradient irregular scaffolds.This research provides insights into the microstructure design of bone tissue engineering implants.展开更多
Correcting the disordered metabolism and achieving dynamic,comprehensive management of chronic diabetic wounds remains a significant challenge.This study presents a double-network dynamic hydrogel exhibiting longterm ...Correcting the disordered metabolism and achieving dynamic,comprehensive management of chronic diabetic wounds remains a significant challenge.This study presents a double-network dynamic hydrogel exhibiting longterm anti-inflammatory,antioxidant properties,and tunable mechanical strength.The hydrogel is primarily composed of modified chitosan,hyaluronic acid,sodium alginate,and ZnO2/Fe3+nanoparticles.The incorpo-rated ZnO2/Fe3+nanoparticles enable microenvironmental regulation by responding to H+or reactive oxygen species(ROS),while the released Fe3+ions drive hydrogel network reconstruction,thereby enhancing me-chanical properties.In vitro studies demonstrate the hydrogel's efficacy in efficiently scavenging ROS and enhancing Piezo1-mediated macrophage efferocytosis through cell-matrix interactions,accelerating macrophage polarization towards the M2 phenotype and resolving inflammation.In vivo experiments further confirm that the CHS@ZnO2/Fe3+hydrogel significantly promotes re-epithelialization.Mechanical stimulation provided by the hydrogel recruited abundant fibroblasts and endothelial cells to the wound site,facilitating collagen deposition and angiogenesis.This novel hydrogel dressing,combining mechanical and biochemical dual-regulation,pro-vides an advanced therapeutic strategy for the efficient repair of diabetic chronic wounds.展开更多
In recent years,shale oil and gas development has been thriving in China.However,the shale oil and gas production always suffers a rapid decline.Based on the analysis of a large amount of former theories and experienc...In recent years,shale oil and gas development has been thriving in China.However,the shale oil and gas production always suffers a rapid decline.Based on the analysis of a large amount of former theories and experiences,a summary of acid treatment stimulation methods in shale oil and gas is presented,and the acid stimulation mechanism is analyzed.The mainstream technique in acid treatments includes:acid wash,matrix acidizing,prop fracturing with acid preflush,and multi-stage alternate-inject acid fracturing.The main stimulation mechanism of acid treatment can be summarized into 3 categories:a)the influence on shale matrix,namely the acid-induced increase of porosity and permeability,and reduce of wetting property of shale;b)the influence on rock mechanical properties,namely shale brittleness and toughness,and even Young Modulus to some degree;c)the influence on fractures'conductivity,caused by the fact that acid dissolves calcite-enrichment area in priority,and then increases roughness on fracture surface.In room temperature and atmospheric pressure,acid reduces fractures'conductivity,while in pressurized condition,the acid-soaked fractures'conductivity is higher than the conductivity of non-acid-soaked fractures.These knowledges would provide useful reference for furthering stimulation techniques and processes in shale oil and gas development.展开更多
A maritime target saliency detection method inspired by the stimulation competition and selection mechanism of raptor vision is presented for the airborne vision system of unmanned aerial vehicle(UAV)in an unknown mar...A maritime target saliency detection method inspired by the stimulation competition and selection mechanism of raptor vision is presented for the airborne vision system of unmanned aerial vehicle(UAV)in an unknown maritime environment.The stimulation competition and selection mechanism in the visual pathway of raptor vision based on the phenomenon of raptor capturing prey in complex scenes are studied.Then,the mathematical model of the stimulation competition and selection mechanism of raptor vision is established and employed for the salient object detection.Popular image datasets and practical scene datasets are applied to verify the effectiveness of the presented method.Results show that the detection performance of the proposed method is better than that of other comparison methods.The proposed algorithm provides an idea for maritime target salient detection and cross-domain joint mission for UAV or other unmanned equipment.展开更多
In recent years,cardiovascular health problems are becoming more and more serious.At the same time,mechanical stimulation closely relates to cardiovascular health.In this context,Piezo1,which is very sensitive to mech...In recent years,cardiovascular health problems are becoming more and more serious.At the same time,mechanical stimulation closely relates to cardiovascular health.In this context,Piezo1,which is very sensitive to mechanical stimulation,has attracted our attention.Here,we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells,NO production,lipid metabolism,DNA damage protection,the development of new blood vessels and maturation,narrowing of blood vessels,blood pressure regulation,vascular permeability,insulin sensitivity,and maintenance of red blood cell function.Besides,Piezo1 may participate in the occurrence and development of atherosclerosis,diabetes,hypertension,and other cardiovascular diseases.It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health.On the one hand,the function of Piezo1 is necessary to maintain cardiovascular health;on the other hand,under some extreme mechanical stimulation,the overexpression of Piezo1 may bring adverse factors such as inflammation.Therefore,this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.展开更多
Background:We previously confirmed that mechanical stimulation is an important factor in the repair of tendon-bone insertion(TBI)injuries and that mechanoreceptors such as transient receptor potential ion-channel subf...Background:We previously confirmed that mechanical stimulation is an important factor in the repair of tendon-bone insertion(TBI)injuries and that mechanoreceptors such as transient receptor potential ion-channel subfamily V member 4(TRPV4;also known as transient receptor potential vanilloid 4)are key to transforming mechanical stimulation into intracellular biochemical signals.This study aims to elucidate the mechanism of mechanical stimulation regulating TRPV4.Methods:Immunohistochemical staining and western blotting were used to evaluate cartilage repair at the TBI after injury.The RNA expression and protein expression of mechanoreceptors and key pathway molecules regulating cartilage proliferation were analyzed.TBI samples were collected for transcriptome sequencing to detect gene expression.Calcium-ion imaging and flow cytometry were used to evaluate the function of TPRV4 and cellular communication network factor 2(CCN2)after the administration of siRNA,recombinant adenovirus and agonists.Results:We found that treadmill training improved the quality of TBI healing and enhanced fibrochondrocyte proliferation.The transcriptome sequencing results suggested that the elevated expression of the mechanistically stimulated regulator CCN2 and the exogenous administration of recombinant human CCN2 significantly promoted TRPV4 protein expression and fibrochondrocyte proliferation.In vitro,under mechanical stimulation conditions,small interfering RNA(siRNA)-CCN2 not only inhibited the proliferation of primary fibrochondrocytes but also suppressed TRPV4 protein expression and activity.Subsequently,primary fibrochondrocytes were treated with the TRPV4 agonist GSK1016790A and the recombinant adenovirus TRPV4(Ad-TRPV4),and GSK1016790A partially reversed the inhibitory effect of siRNA-CCN2.The phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)signaling pathway participated in the above process.Conclusions:Mechanical stimulation promoted fibrochondrocyte proliferation and TBI healing by activating TRPV4 channels and the PI3K/AKT signaling pathway,and CCN2 may be a key regulatory protein in maintaining TRPV4 activation.展开更多
The ability of the central nervous system(CNS)to clear wastes via cerebrospinal fluid(CSF)outflow is essential for brain health.The cervical lymphatic system is one of the multiple clearance routes for CSF.CSF drains ...The ability of the central nervous system(CNS)to clear wastes via cerebrospinal fluid(CSF)outflow is essential for brain health.The cervical lymphatic system is one of the multiple clearance routes for CSF.CSF drains from the subarachnoid space into the meningeal lymphatic vessels,and subsequently into both superficial and deep cervical lymph nodes.This drainage is not only essential for eliminating metabolic waste such as amyloid-β(Aβ)and tau proteins,but also contributes to immune surveillance and the maintenance of interstitial fluid balance[1,2].Disruption of this pathway—whether due to aging,inflammation,or structural regression of lymphatic vessels—can lead to accumulation of neurotoxic substances and is increasingly associated with neurodegenerative disorders like Alzheimer’s disease(AD)[3].In a recent compelling study,Jin et al.(2025)have pushed the frontier of this field by demonstrating that non-invasive mechanical stimulation of superficial cervical lymphatics(scLVs)can enhance CSF clearance,especially in aged mice.This is a breakthrough with potentially wideranging clinical implications[4](Fig.1).展开更多
基金supported by Fundamental Research Funds for the Central Universities(DUT24RC(3)118 to J.L.,DUT25RC(3)040 to X.D.)the Science Fund for Excellent Research Groups of the National Natural Science Foundation of China(62588301)the Natural Sciences and Engineering Research Council of Canada and the Canada Research Chairs Program to Y.S.
摘要Cell stimulation plays a critical role in regulating essential cellular processes such as differentiation,migration,and apoptosis.Among various stimulation methods,magnetic microano robots(mMNRs)have gained attention for their ability to precisely stimulate cellular and intracellular structures,owing to their structural flexibility and remote actuation.While much of the research on mMNRs has focused on their use for chemical stimulation of cells,particularly for targeted drug delivery,increasing attention is now given to their potential for physical stimulation of cells.As one form of physical stimulation,mechanical cell stimulation,particularly for cancer therapeutics,has been discussed in existing reviews.This article presents a comprehensive review of the most recent advances in mMNR-mediated physical cell stimulation,including mechanical,thermal,and electrical stimulation,and highlights their emerging roles in cancer therapy,regenerative medicine,neuromodulation,and antimicrobial treatment.The fundamentals of magnetic material-field interactions and actuation mechanisms are discussed,followed by fabrication strategies for structurally diverse mMNRs.Biomedical applications driven by mMNR-mediated cell stimulation are then discussed,along with remaining challenges and opportunities.By highlighting the unique capabilities of mMNRs in physical cell stimulation,this review emphasizes their potential in advancing both biological research and biomedical applications.
基金Project supported by the National Major Science and Technology Project“Demonstrative shale gas exploration and development project in Zhaotong”(No.2017ZX05063004).
摘要Fracturing operations in shale gas reservoirs of the Sichuan-Chongqing area are frequented by casing deformation,failures in delivery of mechanical staging tools and other down-hole complexities.In addition,limitation in volumes of tail-in proppant in the matrix area significantly restricts the conductivity in the near zones of the wellbore.Eventually,flowback performance and productivity of shale gas horizontal wells are negatively affected.With consideration to the limitations in the implementation of the mechanical staging technique with bridge plug for shale gas development in the Sichuan-Chongqing area,the technique of multi-stage sand filling stimulation in horizontal wells was proposed to solve the above-mentioned problems.By filling sands in fractures,it is possible to divert fluids to maintain long-term high conductivity of fractures,which is the key to satisfactory EOR performances.By introducing the Hertz contact and fractal theory in the analysis of sand plug strength,and in combination of lab engineering simulation test results,the mechanical model for sand plugs in fractures with proppant was constructed.In terms of strength criteria and friction,the stability criteria of sand plug were put forward.Thus,the permeability fractural model for sand plugs in fractures was perfected.Test results show that the stability of sand plug in the earlier stage of production is mainly affected by fluid washing during flowback,so it is necessary to control the flowback rate strictly.In the later stage of production,the stability is mainly affected by fracture closure stress and flow pressure,so it is necessary to enhance the yield strength of proppant to maintain high conductivity of fractures.In conclusion,the multi-stage sand filling stimulation provides a new technique for multi-stage clustering fracturing operations in shale gas horizontal well development.
基金supporting from Shanghai Pujiang Program(23PJ1400400)DHU startup grant,the Fundamental Research Funds for the Central Universities,DHU Distinguished Young Professor Program.
摘要The root system actively reacts to mechanical stimuli in its environment,transmitting mechanical signals to optimize the utilization of environmental resources.While the mechanical impedance created by the growth medium serves as the primary source of stimulation for the roots,extensive research has focused on the roots'response to static mechanical stimulation.However,the impact of dynamic mechanical stimulation on root phenotype remains underexplored.In this study,we utilized a low acyl gellan gum/polyacrylamide(GG/PAM)double network elastic hydrogel as the growth medium for rapeseed.We constructed a mechanical device to investigate the effects of reciprocating extrusion stimulation on the growth of the rapeseed root system.After three weeks of mechanical stimulation,the root system exhibited a significant increase in lateral roots.This branching enhanced the roots'anchoring and penetration into the hydrogel,thereby improving the root system's adaptability to its environment.Our findings offer valuable data and insights into the effects of reciprocating mechanical stimulation on root growth,providing a new way for engineering root phenotype.
基金National Natural Science Foundation of China Enterprise Innovation and Development Joint Fund(U19B6003-02-06)。
摘要To get a deeper understanding on the formation mechanisms and distribution laws of remaining oil during water flooding, and enhanced oil recovery(EOR) mechanisms by reversing water injection after water flooding, 3D visualization models of fractured-vuggy reservoir were constructed based on the elements and configuration of fractures and vugs, and typical fracture-vug structures by using advanced CT scanning and 3D printing technologies. Then, water flooding and reversing water injection experiments were conducted. The formation mechanisms of remaining oil during water flooding include inadequate injection-production well control, gravity difference between oil and water, interference between different flow channels, isolation by low connectivity channel, weak hydrodynamic force at the far end. Under the above effects, 7 kinds of remaining oil may come about, imperfect well-control oil, blind side oil, attic oil at the reservoir top, by-pass residual oil under gravity, by-pass residual oil in secondary channel, isolated oil in low connectivity channel, and remaining oil at far and weakly connected end. Some remaining oil can be recovered by reversing water injection after water flooding, but its EOR is related to the remaining oil type, fracture-cavity structure and reversing injection-production structure. Five of the above seven kinds of remaining oil can be produced by six EOR mechanisms of reversing water injection: gravity displacement, opening new flow channel, rising the outflow point, hydrodynamic force enhancement, vertically equilibrium displacement, and synergistic effect of hydrodynamic force and gravity.
基金supported by the National Natural Science Foundation of China(Nos.12072010 and 11674019)the Fundamental Research Funds for the Central Universities(No.YWF22-K-101)the National Key Research and Development Program of China(No.2022YFB3804300).
摘要Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development.In this study,we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication,mimicking the key physiological characteristics of articular cartilage for organ-level OA research.By applying controllable mechanical compression,we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes.We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets.This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions,paving the way for advanced studies on OA pathogenesis and drug screening.
基金supported by the National Natural Science Foundation of China(12202302,12272253)Natural Science Foundation of Shanxi Province,China(202403021223002)+1 种基金Sanjin Talents Program for Science and Technology Innovation Teams of Shanxi Province(SJYC2024493)the CUHK Peter Hung Pain Research Institute(PHPRI/2024/122)。
摘要Osteoarthritis is among the leading causes of disability worldwide,and no pharmacological therapies currently exist to reverse its progression.This lack of therapies is primarily attributed to the inadequacies of conventional in vitro models of joint physiology and pathology,which significantly hinder advancements in disease mechanism research and drug development.As an emerging in vitro joint model,joint-on-a-chip(JoC)technology allows low-cost,efficient simulation of physiological and pathological joint activities,making it a focal point of current research.Cartilage,subchondral bone,and synovium are among the key tissues required for constructing in vitro joint models,with cartilage playing a central load-bearing role in joint movement.This article provides a detailed overview of the structure and function of these tissues,with an emphasis on the load-bearing mechanisms of cartilage,and identifies the microenvironmental characteristics that JoC should aim to replicate.Subsequently,we review the current types of JoC and highlight their core challenge:the seamless integration of multi-tissue co-culture with specific mechanical stimulation.To address this issue,we propose potential solutions and present a conceptual design for a JoC prototype.Finally,we discuss the challenges and issues related to the outlook for JoC.Our ultimate goal is to develop a JoC capable of replicating the key microenvironments of joints,serving as a high-performance in vitro joint model to advance the study of disease mechanisms and facilitate drug development.
基金The work was supported by National Key R&D Program of China[2018YFE0207900]Key R&D Program of Guangdong Province[2018B090906001]the Fundamental Research Funds for the Central Universities and the Youth Innovation Team of Shaanxi Universities and the EU via the H2020-MSCA-RISE-2016 program[734156].
摘要Tissue-engineered cartilage(TEC)remains a potential alternative for the repair of articular cartilage defects.However,there has been a significant different between the properties of TEC and those of natural cartilage.Studies have shown that mechanical stimulation such as compressive load can help regulate matrix remodelling in TEC,thus affecting its biomechanical properties.However,the influences of shear induced from the tissue fluid phase have not been well studied and may play an important role in tissue regeneration especially when integrated with the compressive load.Therefore,the aim of this study was to quantitatively investigate the effects of combined loading mechanisms on TEC in vitro.A bespoke biosimulator was built to incorporate the coupled motion of compression,friction and shear.The specimens,encapsulating freshly isolated rabbit chondrocytes in a hydrogel,were cultured within the biosimulator under various mechanical stimulations for 4 weeks,and the tissue activity,matrix contents and the mechanical properties were examined.Study groups were categorized according to different mechanical stimulation combinations,including strain(5-20%at 5%intervals)and frequency(0.25 Hz,0.5 Hz,1 Hz),and the effects on tissue behaviour were investigated.During the dynamic culture process,a combined load was applied to simulate the combined effects of compression,friction and shear on articular cartilage during human movement.The results indicated that a larger strain and higher frequency were more favourable for the specimen in terms of the cell proliferation and extracellular matrix synthesis.Moreover,the combined mechanical stimulation was more beneficial to matrix remodelling than the single loading motion.However,the contribution of the combined mechanical stimulation to the engineered cartilaginous tissue matrix was not sufficient to impede biodegradation of the tissue with culture time.
基金The work was supported by the National Natural Science Foundation of China(81904049 and 81973690)Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(CACM-2018-QNRC2-C06).
摘要Background:Scalp combing,as an ancient method of health care,has been used for thousands of years in traditional Chinese medicine.Although this method is considered to be beneficial for the blood circulation of the head,the underlying mechanisms remain unclear.Methods:Both human participants and mice were used in this study.In participants,the scalp was stimulated by combing continuously for 5 min,and the temperature was measured using infrared thermal imaging before and after stimulation.In mice,the temperature was determined before and at 5,15,and 30 min after a 5-min scalp mechanical stimulation(SMS).Additionally,the vasculature of the mice was labeled with retro-orbital fluorescein isothiocyanate-dextran injection,and the capillaries were observed directly under a confocal microscope.Using in vivo CLARITY imaging and the spectrofluorometric detection of Evans Blue dye extravasation,the bloodebrain barrier permeability was assessed.Results:SMS increased the temperature of the left ear significantly in human(P=.0247)while can slightly increase the temperature of the right ear and the face without significant difference(P>.05).Moreover,SMS can significantly slow the decrease in the temperature of the external auditory canal at 5 min(P=.0153)and in body temperature at 15 min(P=.0295)after SMS whereas no significant difference in body temperature at 30 min(P>.05)compared with control mice.Furthermore,capillaries of the ear with a diameter of less than 8 mm were significantly dilated(P=.0006)following SMS and the number of dextran dots was higher at 15 min(P>.05)and 30 min(F=10.98,P=.037)after SMS intervention compared with control mice.Conclusion:Our study provides strong evidence to support the notion that scalp combing can improve extra-and intracranial blood circulation under healthy conditions.
基金the National Basic Research Program(973) of China(No.2011CB013304)the Medical-Engineering Cross Project of Shanghai Jiao Tong University(No.YG2013MS76)
摘要Loss of sensory function for upper-limb amputees inevitably devastates their life qualities, and lack of reliable sensory feedback is the biggest defect to sophisticated prosthetic hands, greatly hindering their usefulness and perceptual embodiment. Thus, it is extremely necessary to accomplish an intelligent prosthetic hand with effective tactile sensory feedback for an upper-limb amputee. This paper presents an overview of three kinds of existing sensory feedback approaches, including cutaneous mechanical stimulation(CMS), transcutaneous electrical nerve stimulation(TENS) and direct peripheral nerve electrical stimulation(DPNES). The emphasis concentrates on major scientific achievements, advantages and disadvantages. The TENS on the skin areas with evoked finger sensation(EFS) at upper-limb amputees' residual limbs might be one of the most promising approaches to realize natural sensory feedback.
基金supported by a European Marie Curie International Incoming Fellowship (Grant Nos. 326847 and 912847)a Chinese Universities Scientific Fund (Grant No. 2452018313)+1 种基金a High-End Foreign Expert Recruitment Program (Grant No. G2022172006L)an Agricultural Science Innovation and Transformation Project of Shaanxi Province [Grant No. NYKJ2022-YL(XN)12]。
摘要Mechanical stimulation technology is critical in agricultural crop production because it is constantly regarded as a developing green technology to regulate plants to meet people's need for green and healthy agricultural products. Various environmental mechanical stimulation impacts seed germination, seedling growth, flowering date, fruit quantity, and fruit quality throughout the life cycle of a horticultural plant. This study first outlines the basic characteristics of six types of common mechanical stimulation in nature:precipitation, wind, gravity,touch, sound, and vibration. The effects of various mechanical stimulation types on the seed, seedling, flowering, and fruit of horticultural plants throughout their whole life cycle are then presented, as reviewed in the recent 100 years of existing literature. Finally, potential future study directions are discussed. The main challenge in mechanical stimulation technology is to uncover its potential capabilities for regulating and controlling plant development and fruit quality in green agriculture instead of agricultural chemicals.
基金supported by the University of Zagreb Research Grant.
摘要Mechanical stimulation of plants can be caused by various abiotic and biotic environmental factors.Apart from the negative consequences,it can also cause positive changes,such as acclimatization of plants to stress conditions.Therefore,it is necessary to study the physiological and biochemical mechanisms underlying the response of plants to mechanical stimulation.Our aim was to evaluate the response of model plant Arabidopsis thaliana to a moderate force of 5 N(newton)for 20 s,which could be compared with the pressure caused by animal movement and weather conditions such as heavy rain.Mechanically stimulated leaves were sampled 1 h after exposure and after a recovery period of 20 h.To study a possible systemic response,unstimulated leaves of treated plants were collected 20 h after exposure alongside the stimulated leaves from the same plants.The effect of stimulation was assessed by measuring oxidative stress parameters,antioxidant enzymes activity,total phenolics,and photosynthetic performance.Stimulated leaves showed increased lipid peroxidation 1 h after treatment and increased superoxide dismutase activity and phenolic oxidation rate after a 20-h recovery period.Considering photosynthetic performance after the 20-h recovery period,the effective quantum yield of the photosystem II was lower in the stimulated leaves,whereas photochemical quenching was lower in the unstimulated leaves of the treated plants.Nonphotochemical quenching was lower in the stimulated leaves 1 h after treatment.Our study suggested that plants sensed moderate force,but it did not induce pronounced change in metabolism or photosynthetic performance.Principal component analysis distinguished three groups–leaves of untreated plants,leaves analysed 1 h after stimulation,while stimulated and unstimulated leaves of treated plants analysed 20 h after treatment formed together the third group.Observed grouping of stimulated and unstimulated leaves of treated plants could indicate signal transduction from the stimulated to distant leaves,that is,a systemic response to a local application of mechanical stimuli.
摘要Objective: Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into chondrocytes, it is the ideal seed cells for treating cartilage injury. The purpose of this study was to investigate the inducible factors that stimulate the differentiation of bone marrow mesenchymal stem cells into chondrocytes. Methods: Rat BMSCs were isolated and subcultured, and then inoculated on PLGA scaffolds after successfully identificating of BMSCs. They were divided into 5 groups. Blank serum group, TGF-β1 + Yougui Yin drug-containing serum induction group, TGF-β1 + mechanical stimulation induction group, Yougui Yin drug-containing serum + mechanical stimulation induction group, TGF-β1 + Yougui Yin drug-containing serum + mechanical stimulation induction group, 4 weeks later, the adhesion status of cells and scaffolds was observed by Scanning Electron Microscopy, and then chondrocyte induction was performed on different treatment groups. After induction, the expression of Aggrecan and Collagen II was detected by immunofluorescence, and the mRNA expression of Aggrecan and Collagen II was detected by qPCR. Results: BMSCs were identified as rat bone marrow mesenchymal stem cells by immunofluorescence CD34 and CD44 cells. Scanning Electron Microscopy observed that BMSCs grew well on PLGA. Compared with PLGA group, the scaffold space of BMSCS-PLGA composite was significantly reduced, and the growth of cell adhesion scaffold was significantly increased. Compared with the blank serum group, the expression of Aggrecan in TGF-β1 + Yougui Yin drug-containing serum group and Yougui Yin drug-containing serum + mechanical stimulation group was significantly increased. The expression of Collagen II in TGF-β1 + Yougui Yin medicated serum group, Yougui Yin medicated serum + mechanical stimulation group, TGF-β1 + mechanical stimulation group and TGF-β1 + Yougui Yin medicated serum + mechanical stimulation group were significantly increased;PCR results showed that compared with blank serum group, the expression of Aggrecan in other groups was significantly increased, except for Collagen II expression in Yougui Yin drug-containing serum + mechanical stimulation group. Conclusion: BMSCs can differentiate into chondrocytes on PLGA scaffold. Compared with blank serum group, BMSCs can be induced to differentiate into chondrocytes in all induction groups, among all induction groups, TGF-β1 + Yougui-yin drug-containing serum group and TGF-β1 + mechanical stimulation group were more significant, and the difference was statistically significant.
基金funded by the Israeli Ministry of Innovation,Science and Technology(Grant No.3-11873)the Israel Science Foundation(Grant No.1563/10)+1 种基金the Randy L.and Melvin R.Berlin Family Research Center for Regenerative Medicinethe Gurwin Family Foundation.
摘要Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.
基金the National Natural Science Foundation of China(No.52165026)。
摘要In bone tissue engineering microstructure design,adjusting the structural design of biomimetic bone scaffolds can provide distinct differentiation stimuli to cells on the scaffold surface.This study explored the biomechanical impacts of different biomimetic microstructures on advanced bone tissue engineering scaffolds.Two irregular bone scaffolds(homogeneousadial gradient)based on the Voronoi tesselation algorithm and eight regular lattice scaffolds involving pillar body centered cubic,vintiles,diamond,and cube(homogeneousadial gradient)with constant 80%porosity were constructed.Mechanical stimulation differentiation algorithms,finite element analysis,and computational fluid dynamics were used to investigate the effects of different pore structures on the octahedral shear strain and fluid flow shear stress within the scaffolds,thereby elucidating the differentiation capabilities of the five structural bone/cartilage cell types.The findings demonstrated that irregular structures and radial-gradient designs promoted osteogenic differentiation,whereas regular structures and homogeneous designs facilitated chondrogenic differentiation.The highest percentages of osteoblast and chondrocyte differentiation were observed in radial-gradient irregular scaffolds.This research provides insights into the microstructure design of bone tissue engineering implants.
基金supported by the National Natural Science Foundation of China(No.82172378 and 82372363)Shanghai Municipal Health Commission Research Project(20234Z0008)Shanghai Education Commission“Shuguang”project(22SG09).
摘要Correcting the disordered metabolism and achieving dynamic,comprehensive management of chronic diabetic wounds remains a significant challenge.This study presents a double-network dynamic hydrogel exhibiting longterm anti-inflammatory,antioxidant properties,and tunable mechanical strength.The hydrogel is primarily composed of modified chitosan,hyaluronic acid,sodium alginate,and ZnO2/Fe3+nanoparticles.The incorpo-rated ZnO2/Fe3+nanoparticles enable microenvironmental regulation by responding to H+or reactive oxygen species(ROS),while the released Fe3+ions drive hydrogel network reconstruction,thereby enhancing me-chanical properties.In vitro studies demonstrate the hydrogel's efficacy in efficiently scavenging ROS and enhancing Piezo1-mediated macrophage efferocytosis through cell-matrix interactions,accelerating macrophage polarization towards the M2 phenotype and resolving inflammation.In vivo experiments further confirm that the CHS@ZnO2/Fe3+hydrogel significantly promotes re-epithelialization.Mechanical stimulation provided by the hydrogel recruited abundant fibroblasts and endothelial cells to the wound site,facilitating collagen deposition and angiogenesis.This novel hydrogel dressing,combining mechanical and biochemical dual-regulation,pro-vides an advanced therapeutic strategy for the efficient repair of diabetic chronic wounds.
基金supported jointly by the National Natural Science Foundation of China(No.51574197)Educational Commission of Sichuan Province of China(No.16ZA0071).
摘要In recent years,shale oil and gas development has been thriving in China.However,the shale oil and gas production always suffers a rapid decline.Based on the analysis of a large amount of former theories and experiences,a summary of acid treatment stimulation methods in shale oil and gas is presented,and the acid stimulation mechanism is analyzed.The mainstream technique in acid treatments includes:acid wash,matrix acidizing,prop fracturing with acid preflush,and multi-stage alternate-inject acid fracturing.The main stimulation mechanism of acid treatment can be summarized into 3 categories:a)the influence on shale matrix,namely the acid-induced increase of porosity and permeability,and reduce of wetting property of shale;b)the influence on rock mechanical properties,namely shale brittleness and toughness,and even Young Modulus to some degree;c)the influence on fractures'conductivity,caused by the fact that acid dissolves calcite-enrichment area in priority,and then increases roughness on fracture surface.In room temperature and atmospheric pressure,acid reduces fractures'conductivity,while in pressurized condition,the acid-soaked fractures'conductivity is higher than the conductivity of non-acid-soaked fractures.These knowledges would provide useful reference for furthering stimulation techniques and processes in shale oil and gas development.
基金supported by the National Natural Science Foundation of China under grant#62103040,#U1913602,#T2121003,#91948204,#U20B2071,and#U19B2033 and Open Fund/Postdoctoral Fund of the Laboratory of Cognition and Decision Intelligence for Complex Systems,Institute of Automation,Chinese Academy of Sciences under grant CASIA-KFKT-08.
摘要A maritime target saliency detection method inspired by the stimulation competition and selection mechanism of raptor vision is presented for the airborne vision system of unmanned aerial vehicle(UAV)in an unknown maritime environment.The stimulation competition and selection mechanism in the visual pathway of raptor vision based on the phenomenon of raptor capturing prey in complex scenes are studied.Then,the mathematical model of the stimulation competition and selection mechanism of raptor vision is established and employed for the salient object detection.Popular image datasets and practical scene datasets are applied to verify the effectiveness of the presented method.Results show that the detection performance of the proposed method is better than that of other comparison methods.The proposed algorithm provides an idea for maritime target salient detection and cross-domain joint mission for UAV or other unmanned equipment.
基金supported by National Natural Science Foundation of China(No.31971242,and 12032007)the Natural Science Foundation of Chongqing(No.cstc2019jcyjmsxmX0307,cstc2019jcyj-19zdxmx0009,and cstc2019jcyjzdxmX0028).
摘要In recent years,cardiovascular health problems are becoming more and more serious.At the same time,mechanical stimulation closely relates to cardiovascular health.In this context,Piezo1,which is very sensitive to mechanical stimulation,has attracted our attention.Here,we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells,NO production,lipid metabolism,DNA damage protection,the development of new blood vessels and maturation,narrowing of blood vessels,blood pressure regulation,vascular permeability,insulin sensitivity,and maintenance of red blood cell function.Besides,Piezo1 may participate in the occurrence and development of atherosclerosis,diabetes,hypertension,and other cardiovascular diseases.It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health.On the one hand,the function of Piezo1 is necessary to maintain cardiovascular health;on the other hand,under some extreme mechanical stimulation,the overexpression of Piezo1 may bring adverse factors such as inflammation.Therefore,this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.82130071 and 82072516).
摘要Background:We previously confirmed that mechanical stimulation is an important factor in the repair of tendon-bone insertion(TBI)injuries and that mechanoreceptors such as transient receptor potential ion-channel subfamily V member 4(TRPV4;also known as transient receptor potential vanilloid 4)are key to transforming mechanical stimulation into intracellular biochemical signals.This study aims to elucidate the mechanism of mechanical stimulation regulating TRPV4.Methods:Immunohistochemical staining and western blotting were used to evaluate cartilage repair at the TBI after injury.The RNA expression and protein expression of mechanoreceptors and key pathway molecules regulating cartilage proliferation were analyzed.TBI samples were collected for transcriptome sequencing to detect gene expression.Calcium-ion imaging and flow cytometry were used to evaluate the function of TPRV4 and cellular communication network factor 2(CCN2)after the administration of siRNA,recombinant adenovirus and agonists.Results:We found that treadmill training improved the quality of TBI healing and enhanced fibrochondrocyte proliferation.The transcriptome sequencing results suggested that the elevated expression of the mechanistically stimulated regulator CCN2 and the exogenous administration of recombinant human CCN2 significantly promoted TRPV4 protein expression and fibrochondrocyte proliferation.In vitro,under mechanical stimulation conditions,small interfering RNA(siRNA)-CCN2 not only inhibited the proliferation of primary fibrochondrocytes but also suppressed TRPV4 protein expression and activity.Subsequently,primary fibrochondrocytes were treated with the TRPV4 agonist GSK1016790A and the recombinant adenovirus TRPV4(Ad-TRPV4),and GSK1016790A partially reversed the inhibitory effect of siRNA-CCN2.The phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)signaling pathway participated in the above process.Conclusions:Mechanical stimulation promoted fibrochondrocyte proliferation and TBI healing by activating TRPV4 channels and the PI3K/AKT signaling pathway,and CCN2 may be a key regulatory protein in maintaining TRPV4 activation.
基金National Science&Technology Major Program on“Brain Science and Brain-Inspired Research”(2022ZD0211604,2022ZD0211607)National Key Science and Technology Project-Changping National Laboratory Research Project(2025B-07-10)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20251483).
摘要The ability of the central nervous system(CNS)to clear wastes via cerebrospinal fluid(CSF)outflow is essential for brain health.The cervical lymphatic system is one of the multiple clearance routes for CSF.CSF drains from the subarachnoid space into the meningeal lymphatic vessels,and subsequently into both superficial and deep cervical lymph nodes.This drainage is not only essential for eliminating metabolic waste such as amyloid-β(Aβ)and tau proteins,but also contributes to immune surveillance and the maintenance of interstitial fluid balance[1,2].Disruption of this pathway—whether due to aging,inflammation,or structural regression of lymphatic vessels—can lead to accumulation of neurotoxic substances and is increasingly associated with neurodegenerative disorders like Alzheimer’s disease(AD)[3].In a recent compelling study,Jin et al.(2025)have pushed the frontier of this field by demonstrating that non-invasive mechanical stimulation of superficial cervical lymphatics(scLVs)can enhance CSF clearance,especially in aged mice.This is a breakthrough with potentially wideranging clinical implications[4](Fig.1).