Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Microstructure-fracture toughness relationships and toughening mechanism of TC21 titanium alloy with lamellar microstructure

The independent influence of microstructural features on fracture toughness of TC21alloy with lamellar microstructure was investigated.Triple heat treatments were designed to obtain lamellar microstructures with different parameters,which were characterized by OM and SEM.The size and content ofαplates were mainly determined by cooling rate from singleβphase field and solution temperature in two-phase field;while the precipitation behavior of secondaryαplatelets was dominantly controlled by aging temperature in two-phase field.The content and thickness ofαplates and the thickness of secondaryαplatelets were important microstructural features influencing the fracture toughness.Both increasing the content ofαplates and thickeningαplates(or secondaryαplatelets)could enhance the fracture toughness of TC21alloy.Based on energy consumption by the plastic zone of crack tip inαplates,a toughening mechanism for titanium alloys was proposed.

Toughening mechanism of lined Al_2O_3-ZrO_2 multiphaseceramics in SHS composite pipes

Hypoeutectic and hypereutectic Al2O3-ZrO2 multiphase ceramics-lined composite pipes were produced by using the gravitational separation self-propagate high-temperature synthesis （SHS） process. The microstructure of the ceramics was observed by means of SEM and EPMA. The fracture toughness of the multiphase ceramics was tested by using the Vickers indentation method. The fracture toughness of hypoeutectic Al2O3-ZrO2 multiphase ceramics is 15.96 MPa·m^1/2 and that of hypoeutectic Al2O3-ZrO2 multiphase ceramics is 15.23 MPa·m^1/2. The toughening mechanisms were systematically investigated by means of SEM and XRD. The results show that the bridging toughening mechanism, stress induced ZrO2 transformation toughening mechanism, and microcrack toughening mechanism are the predominant toughening mechanism.

FRACTURAL PROCESS AND TOUGHENING MECHANISM OF LAMINATED CERAMIC COMPOSITES

Based on the model of multi-layer beam and the assumption of micro-inhomogeneity of material, the 3D fractural characteristics of laminated ceramic composites have been studied with numerical simulation. Under three-point bending load, crack initiation, coalescence, propagation, tuning off in the weak interface and final rupture have been simulated. The spatial distribution and evolution process of acoustic emission are also presented in the paper. The simulation verifies the primary mechanism of the weak interface inducing the crack to expand along there and absorbing the fractural energy. The disciplinary significance of the effect of strength and properties of material on the toughness and strength of laminated ceramic composites is, therefore, discussed in this paper.

Toughening mechanisms of a high-strength acicular ferrite steel heavy plate

An ultra-low carbon acicular ferrite steel heavy plate was obtained with an advanced thermo-mechanical control process-relaxed precipitation controlled transformation （TMCP-RPC） at Xiangtan Steel, Valin Group. The heavy plate has a tensile strength of approximately 600 MPa with a lower yield ratio. The impact toughness of the heavy plate achieves 280 J at ？40°C. The fine-grained mixed microstructures of the heavy plate mainly consist of acicular ferrite, granular bainite, and polygonal ferrite. The high strength and excellent toughness of the heavy plate are attributed to the formation of acicular ferrite microstructure. The prevention of blocks of martensite/retained austenite （M/A） and the higher cleanness are also responsible for the superior toughness.

A review of the strengthening–toughening behavior and mechanisms of advanced structural materials by multifield coupling treatment

The application of an external field is a promising method to control the microstructure of materials, leading to their improved performance. In the present paper, the strengthening and toughening behavior of some typical high-performance structural materials subjected to multifield coupling treatment, including electrostatic field, electro-pulse current, thermal field, and stress field, are reviewed in detail. In addition to the general observation that the plasticity of materials could be increased by multi-external fields, strength enhancement can be achieved by controlling atomic diffusion or phase transformations. The paper is not limited to the strengthening and toughening mechanisms of the multifield coupling effects on different types of structural materials but is intended to provide a generic method to improve both the strength and ductility of the materials. Finally, the prospects of the applications of multi-external fields have also been proposed based on current works.

Erosion and Toughening Mechanisms of Electroless Ni-P-Nano-NiTi Composite Coatings on API X100 Steel under Single Particle Impact

The addition of superelastic NiTi to electroless Ni-P coating has been found to toughen the otherwise brittle coatings in static loading conditions, though its effect on erosion behaviour has not yet been explored. In the present study, spherical WC-Co erodent particles were used in single particle impact testing of Ni-P-nano-NiTi composite coatings on API X100 steel substrates at two average velocities—35 m/s and 52 m/s. Erosion tests were performed at impact angles of 30°, 45°, 60°, and 90°. The effect of NiTi concentration in the coating was also examined. Through examination of the impact craters and material response at various impact conditions, it was found that the presence of superelastic NiTi in the brittle Ni-P matrix hindered the propagation of cracks and provided a barrier to crack growth. The following toughening mechanisms were identified: crack bridging and deflection, micro-cracking, and transformation toughening.

AN INVESTIGATION OF HIGH-TEMPERATURE DEFORMATION STRENGTHENING AND TOUGHENING MECHANISM OF TITANIUM ALLOY

The high-temperature deformation strengthening and toughening mechanisms of titanium alloys have been investigated in this paper. The materials processed by this method produce a new tri-modal microstrvcture, which consists of 10-20% equiaxed alpha, streaky alpha and transformed beta matrix. It is found that the higher ductility of tri-modal microstructure is attributed to the equiaxed alpha's coopemtive slip and coordinated deformation with the transformed beta matrix. The streaky alpha phases not only increase the strength and creep properties, but also increase the fracture toughness. Propagating along grain boundaries between two neighboring streaky alpha phases, cracks in tri-modal microstructure make a more tortuous way, and then the materials show a higher fracture toughness. This new method is applicable to α, near α,α+β and near β titanium alloys.

Mechanism of toughening and strengthening of Si_3N_4/SiC/ZrO_2 nanocomposites

The Si3N4-based nanocomposites reinforced with micro ZrO2 and nano SiC particles were prepared by polarity dispersant and vacuum-sintering technology. The mechanical properties and microstructures were tested. The results show that appropriate amount of micro ZrO2 and nano SiC particles, not only enhance the microhardness, but also block the excessively growth of β-Si3N4 and β-Si3N4 grains, so they finally all grow up to uniformly pole-shaped grains. This process is similar to the strengthening and toughening mechanism of grain whiskers and makes a remarkable improvement on the toughness. Compared with Si3N4 ceramic, the toughness of Si3N4/SiC/ZrO2 nanocomposites are increased from 6.2 MPa·m1/2 to 11 MPa·m1/2.

Failure mechanism and infrared radiation characteristic of hard siltstone induced by stratification effect

The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and temporal damage mechanism of hard siltstone. The uniaxial compression tests, coupled with acoustic emission(AE) and infrared radiation temperature(IRT) were conducted on siltstones with different stratification effects. The results revealed that the stratigraphic structure significantly affects the stress-strain response and strength degradation characteristics. The mechanical parameters exhibit anisotropy characteristics, and the stratification effect exhibits a negative correlation with the cracking stress and peak stress. The failure modes caused by the stratification effect show remarkable anisotropic features, including splitting failure(Ⅰ: 0°-22.50°, Ⅱ: 90°), composite failure(45°), and shearing failure(67.50°). The AE temporal sequences demonstrate a stepwise response characteristic to the loading stress level. The AE intensity indicates that the stress sensitivity of shearing failure and composite failure is generally greater than that of splitting failure. The IRT field has spatiotemporal migration and progressive dissimilation with stress loading and its dissimilation degree increases under higher stress levels. The stronger the stratification effect, the greater the dissimilation degree of the IRT field. The abnormal characteristic points of average infrared radiation temperature(AIRT) variance at local stress drop and peak stress can be used as early and late precursors to identify fracture instability. Theoretical analysis shows that the competitive relationship between compaction strengthening and fracturing damage intensifies the dissimilation of the infrared thermal field for an increasing stress level. The present study provides a theoretical reference for disaster warnings in hard sedimentary rock mass.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

The underlying mechanism of variety–water–nitrogen–stubble damage interactions on yield formation in ratoon rice with low stubble height under mechanized harvesting

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Hybrid model for BOF oxygen blowing time prediction based on oxygen balance mechanism and deep neural network

The amount of oxygen blown into the converter is one of the key parameters for the control of the converter blowing process,which directly affects the tap-to-tap time of converter. In this study, a hybrid model based on oxygen balance mechanism (OBM) and deep neural network (DNN) was established for predicting oxygen blowing time in converter. A three-step method was utilized in the hybrid model. First, the oxygen consumption volume was predicted by the OBM model and DNN model, respectively. Second, a more accurate oxygen consumption volume was obtained by integrating the OBM model and DNN model. Finally, the converter oxygen blowing time was calculated according to the oxygen consumption volume and the oxygen supply intensity of each heat. The proposed hybrid model was verified using the actual data collected from an integrated steel plant in China, and compared with multiple linear regression model, OBM model, and neural network model including extreme learning machine, back propagation neural network, and DNN. The test results indicate that the hybrid model with a network structure of 3 hidden layer layers, 32-16-8 neurons per hidden layer, and 0.1 learning rate has the best prediction accuracy and stronger generalization ability compared with other models. The predicted hit ratio of oxygen consumption volume within the error±300 m^(3)is 96.67%;determination coefficient (R^(2)) and root mean square error (RMSE) are0.6984 and 150.03 m^(3), respectively. The oxygen blow time prediction hit ratio within the error±0.6 min is 89.50%;R2and RMSE are0.9486 and 0.3592 min, respectively. As a result, the proposed model can effectively predict the oxygen consumption volume and oxygen blowing time in the converter.

Mechanism underlying the effects of exercise against type 2 diabetes:A review on research progress

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes(T2D)in certain nations.The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D.The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D,in addition to identify the limitations of the existing literature,thereby provide direction for future research in this field.