Primary Damage Research Articles

Multimodal high-throughput approach assisted by deep learning for the analysis of ceramic saggars

The ceramic saggar is a container utilized in the production process of cathode materials for sodium-ion or lithium-ion batteries, and the characterization of saggar damage mechanisms often relies on the analysis of microstructure and composition of micro-sized areas. However, these results are often unreliable as they derive from a limited amount of data and cannot thus be utilized to perform a comprehensive and accurate analysis of the corrosion resistance mechanism of the saggar. In this study, deep learning combined with multimodal high-throughput in situ characterization methods, including array-SEM, μ-XRF, and μ-XRM, is employed to comprehensively analyze the multiscale characteristics of cordierite–mullite saggars. The 3D distribution of minerals in a 20×13×12 mm3 saggar sample is obtained. The results indicate that the direct dissolution of cordierite corrosion resistance reaction products is the primary damage mechanism of the saggar.

Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion.

To develop a reliable method to generate a mouse model of branch retinal artery occlusion (BRAO) using laser-induced thrombosis of a major artery in the mouse retina. Also, to develop a reliable method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. A reliable and reproducible model of laser-induced BRAO was developed in mouse retina using Rose Bengal. To characterize retinal hypoxia in BRAO, pimonidazole immunostaining and HYPOX-4 molecular imaging methods were used. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used to characterize neuronal cell damage in the BRAO retina. Expression of mRNA in retinal tissues from BRAO and age-matched control retinas were analyzed using qRT-PCR. Occlusion of a branch retinal artery near the optic nerve head (ONH) caused a pattern of retinal tissue hypoxia covering about 12.5% of the entire retina. TUNEL-positive cells were localized in all layers in BRAO retinal tissue cross sections. In addition, qRT-PCR data analysis suggests that BRAO is associated with both inflammation and hypoxia. This study provides a reliable method for BRAO in mouse retina and demonstrates the utility of molecular imaging method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. In addition, our data suggest that BRAO retinas are associated with inflammation and also associated with hypoxia-related neuronal cell damage. Imaging areas of retinal hypoxia may provide accurate diagnosis, evaluating retinal tissue injury from BRAO.

Comparison of fatigue characteristics and failure analysis of Ni-based superalloy subjected to thermomechanical fatigue under different phase conditions

In this research, the thermomechanical fatigue (TMF) characteristics of a second-generation Ni-based single-crystal superalloy were investigated. The combined effects of temperature cycling and mechanical stress were examined using a strain-controlled approach under different TMF testing conditions. The results indicated that cyclic softening occurred during the early stages during in-phase (IP) loading. In contrast, out-of-phase (OP) tests exhibited cyclic hardening, as evidenced by an increase in the stress range, which intensified at higher mechanical strain amplitudes. This resulted in a shorter fatigue life compared to the IP TMF case. The crack distribution patterns and damage mechanisms on the cross-sectional and fracture surfaces of the failed specimens were analyzed. In the OP TMF tests, oxidation-assisted cracking was identified as the primary damage mechanism. The dominance of oxide layers was a key distinguishing feature. Additionally, twinning-related deformation and topologically close-packed (TCP) phase particles were observed in specimens subjected to a higher mechanical strain of 0.6%, where they ran parallel to the main crack, contributing to a reduction in lifetime. Conversely, the IP TMF cases were mainly dominated by creep damage mechanisms, with some signs of oxidation penetration observed during testing. The application of the Ostergren model to the fatigue life prediction of a Ni-based single-crystal superalloy under both conditions was evaluated. As this model was insufficient, a modified Ostergren model was proposed by incorporating the maximum and amplitude stresses in the power law forms.

The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury.

This review explores the complex challenges and advancements in the treatment of traumatic brain injury (TBI) and spinal cord injury (SCI). Traumatic injuries to the central nervous system (CNS) trigger intricate pathophysiological responses, frequently leading to profound and enduring disabilities. This article delves into the dual phases of injury-primary impacts and the subsequent secondary biochemical cascades-that worsen initial damage. Conventional treatments have traditionally prioritized immediate stabilization, surgical interventions, and supportive medical care to manage both the primary and secondary damage associated with central nervous system injuries. We explore current surgical and medical management strategies, emphasizing the crucial role of rehabilitation and the promising potential of stem cell therapies and immune modulation. Advances in stem cell therapy, gene editing, and neuroprosthetics are revolutionizing treatment approaches, providing opportunities not just for recovery but also for the regeneration of impaired neural tissues. This review aims to emphasize emerging therapeutic strategies that hold promise for enhancing outcomes and improving the quality of life for affected individuals worldwide.

Experimental study on overtopping failure of concrete face rockfill dam

With the frequent occurrence of natural disasters, the problem of dam failure with low probability and high risk has gradually attracted people's attention. This paper uses flume model tests to systematically analyze the overtopping failure mechanisms of concrete face rockfill dam (CFRD) and identify its failure modes. The tests reveal that the longitudinal erosion of the CFRD breach progress through stages of soil erosion, panel failures, and water flow stabilization. Meanwhile, the cross-section breach process involves the evolution of breach size in rockfill materials, including traceable erosion, lateral broadening, and breach morphology stabilization. The fracture characteristics of the water-blocking panel are primarily evident in the flow-time curve. By analyzing the breach morphology evolution processes in longitudinal and cross sections, the flow-time curve can be subdivided into stages of burst flow formation, breach expansion with flow increase, rapid increase of breach flow discharge due to panel failures, and stabilization of breach flow and size. The primary damage process of the CFRD occurs in a cyclical stage of breach expansion, flow increase, panel failure, and rapid discharge. The rigid face plate and granular body structure contribute to partial dam failure, showing a tendency for gradual expansion of the breach. The longitudinal section illustrates dam failure resulting from panel fracture and rockfill erosion interaction, while downstream slopes exhibit failure due to lateral intrusion of rockfill and cyclic instability. These research results can serve as a reference for constructing a concrete CFRD failure prediction model and conducting disaster risk assessments.

Simultaneous inhibition of ATM, ATR, and DNA-PK causes synergistic lethality

Here we report that simultaneous inhibition of the three primary DNA damage recognition PI3 kinase-like kinases (PIKKs) —ATM, ATR, and DNA-PK— induces severe combinatorial synthetic lethality in mammalian cells. Utilizing Chinese hamster cell lines CHO and V79 and their respective PIKK mutants, we evaluated effects of inhibiting these three kinases on cell viability, DNA damage response, and chromosomal integrity. Our results demonstrate that while single or dual kinase inhibition increased cytotoxicity, inhibition of all three PIKKs results in significantly higher synergistic lethality, chromosomal aberrations, and DNA double-strand break (DSB) induction as calculated by their synergy scores. These findings suggest that the overlapping redundancy of ATM, ATR, and DNA-PK functions is critical for cell survival, and their combined inhibition greatly disrupts DNA damage signaling and repair processes, leading to cell death. This study provides insights into the potential of multi-targeted DDR kinase inhibition as an effective anticancer strategy, necessitating further research to elucidate underlying mechanisms and therapeutic applications.

Insights into the Mechanical-Structural-Energetic Responses of RDX Nanoparticles from Molecular Dynamics Simulation.

When the particle size of energetic materials is reduced to the nanoscale, significant changes occur in their properties and behavior. In this work, compression processes of three RDX nanoparticles (A, B, and C) were simulated using ReaxFF-lg. The mechanical, structural, and energetic responses of RDX nanoparticles during compression were revealed and characterized. Simulations reveal that the compression process of the nanoparticles can be divided into three stages: elastic stage, primary damage stage, and sustained damage stage. The temperature increase rate in the elastic phase is much lower than in the primary damage phase. In addition, we found that the smaller nanoparticle B presents a smaller elastic modulus and compressive strength, and it has a slower rate of temperature increase during the primary damage phase. Compared to cuboidal nanoparticles (A and B), the spherical nanoparticle C tends to absorb less energy during the elastic stage and exhibits slower damage rate during the primary damage stage. This is a key factor contributing to the low sensitivity of spherical nanoparticles.

Cell-free DNA kinetics in response to muscle-damaging exercise: A drop jump study.

A significant increase in circulating cell-free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96h after muscle-damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low-frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed-onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22±2years; weight, 84.4±11.2kg; height, 184.0±7.4cm) performed 50 intermittent drop jumps at 20s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low-frequency fatigue and delayed-onset muscle soreness before and at several time points up to 96h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72h postexercise (P<0.01). Elevation of postexercise cfDNA was correlated with both more pronounced low-frequency fatigue (r=-0.52, P=3.4×10-11) and delayed-onset muscle soreness (r=0.32, P= 0.00019). Levels of cfDNA change in response to severe primary and secondary muscle damage after exercise. Levels of cfDNA exhibit a stronger correlation with variables related to primary muscle damage than to secondary muscle damage, suggesting that cfDNA is a more sensitive marker of acute loss of muscle function than of secondary inflammation or damaged muscle fibres.

Compression–compression fatigue damage of wrinkled carbon/glass hybrid composite laminates

Compression–compression fatigue tests were carried out to study the compressive fatigue damage mechanisms of a carbon/glass hybrid composite laminate with a manufacturing-induced wrinkle defect. As reported in literature, thin wrinkled composite laminates could show sensibly different fatigue behaviours and damage mechanisms in the presence of tension and compression cyclic loadings. The sensitivities of composites to tension and compression cyclic loadings were not the same. In this study, the damage modes and cracking sequence of a thick wrinkled laminate were identified by the strain fields from digital image correlation (DIC). Acoustic emission (AE) and infrared (IR) thermography were used to detect the damages and explore the potential capabilities of non-destructive evaluation methods when applied to detection of fatigue induced damages in composite structures under operational cyclic loadings. Two primary damage modes were identified and detected before the final failure of the laminate i.e. debonding between the resin-rich layer and the laminate and interlaminar cracks. Debonding occurred earlier than interlaminar cracking. Out-of-plane stresses due to fibre waviness drove the initiation of these damages. Under the settings of AE in this work, AE captured early debonding activities but did not detect the micro damage accumulating before the formation of interlaminar crack. Interlaminar crack initiation was tracked by IR thermography at cross-section of the specimen based on the distinct temperature localisations that occur with this micro damage. No distinct temperature localisations occurred during the formation of debonding as it is mode-I driving under compression–compression cyclic loading, so IR thermography did not detect the debonding crack. The results of this study show the potential of using complementary non-destructive damage evaluation methods to inspect early damages in composite structures. The early detection of damages would give early warning signs before the damages become critical. It is found that AE and IR thermography should be used as complementary tools to detect different damage modes.

Mechanical Behavior of Frozen Soil Subjected to Freeze–Thaw Cycle Under Cyclic Impact Load and Passive Confining Pressure

In this study, the effects of freeze–thaw cycles and cyclic impacts on frozen soil were systematically investigated. With an increase in the number of freeze–thaw cycles, the peak stress of frozen soil decreased until a stable state was achieved. Moreover, subjecting frozen soil to an increased number of cyclic impacts led to notable alterations in mechanical characteristics, including peak stress, critical strain and dynamic elasticity modulus. Both the freeze–thaw cycles and cyclic impacts were identified as primary damage mechanisms in understanding frozen soil degradation processes. Damage resulting from these impacts conformed to the Weibull distribution pattern. Damages induced by freeze–thaw cycles, individual impacts and cyclic impacts were integrated into the Zhu–Wang–Tang viscoelastic model (ZWT model). Relying on principles of elastic mechanics, the role of confining pressure on frozen soil was examined and subsequently integrated into an improved ZWT model. To evaluate the model’s effectiveness, its predictions were compared with experimental results.

Mechanisms of action of microbicides commonly used in infection prevention and control.

SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

Silibinin promotes healing in spinal cord injury through anti-ferroptotic mechanisms.

Pre-clinical animal experiment. In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI. The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe2+ levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso-Beattie-Bresnahan test. Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group (p < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups (p < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group (p < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups (p < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI (p < 0.05). Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.

Neurosurgical Management of Traumatic Brain Injury

The neurosurgical management of traumatic brain injury (TBI) plays a critical role in ensuring acute survival and mitigating secondary brain damage, which significantly impacts patients' quality of life. TBI is defined as an external force impacting the skull, leading to brain injuries and subsequent functional impairments. It is a leading cause of mortality and morbidity, particularly among young individuals. The initial clinical examination is crucial, with external signs like scalp injuries, hematomas, nasal fluid leakage, skull deformities, and neurological deficits providing important clues to injury patterns. Pupil examination is particularly critical, as mydriasis coupled with reduced consciousness may indicate an acute life-threatening increase in intracranial pressure (ICP), necessitating immediate neurosurgical intervention. TBI assessment often utilizes the Glasgow Coma Scale (GCS), classifying injuries as mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS <9). Even mild TBI can lead to long-term complications. TBI should be viewed as a disease process rather than a singular event. Primary brain damage results from shearing forces on the parenchyma, manifesting as contusions, hematomas, or diffuse axonal injury. Secondary brain damage is driven by mechanisms such as inflammation and spreading depolarizations. Treatment aims not only to secure immediate survival but also to reduce secondary injuries, with ICP management being crucial. Neurosurgical interventions are guided by cranial pathologies, with options including ICP monitoring, burr hole trepanation, craniotomy. In severe TBI cases with refractory ICP elevation, decompressive craniectomy may be performed as a last resort, significantly reducing mortality but often resulting in high morbidity and vegetative states, necessitating careful consideration of indications.

Multi-point impact behavior and the relationship between CAI strength and DBIP of PMI foam sandwich structures

Sandwich structures are vulnerable to multi-point impacts, and such impacts can result in a reduction in residual strength even catastrophic accident. Therefore, the multi-point impact behaviors of PMI foam sandwich structure are investigated and studied using experimental and numerical coupled methods. Three impact energy levels and five Distances Between Impact Positions (DBIP) are considered in details, and representative impact characteristics are compared to reveal the association between Compression After Impact (CAI) strength and DBIP. Results indicate that the interference between the multi-point impact events has a dominant effect on CAI strength when DBIP is small, and the variation in bending stiffness induced by the boundary effect is the dominant factor affecting CAI strength when DBIP ranges from 20 mm to 60 mm. In addition, matrix damage represents the primary damage mode in multi-point impact, and the calculated ratio of energy absorbed by the top face sheet and honeycomb core, in relation to the total absorbed energy, serves as a clear indicator of the damage severity experienced by both components. This work is enlightening for the structural design of impact-resistant composites.

Displacement cascade and defect-driven simulations in V-Ti-Ta-Nb high-entropy alloy

High-entropy alloys (HEA) have attracted considerable attention in the development of nuclear materials due to their excellent properties. In this study, the primary irradiation damage and long-term defect evolution of pure V, V-5Ti-5Ta conventional alloy, V-Ti-Ta MEA and V-Ti-Ta-Nb HEA were simulated by molecular dynamics (MD) to understand the irradiation resistance mechanism of these four systems. The primary irradiation damage simulation results indicate that the V-Ti-Ta MEA and V-Ti-Ta-Nb HEA exhibit a delayed thermal peak, a longer defect recombination time and a slightly higher number of final Frenkel pairs (FPs) than pure V and V-5Ti-5Ta alloy. Both primary irradiation damage and long-time defect evolution results show that V-Ti-Ta MEA and V-Ti-Ta-Nb HEA have lower defect clustering fraction, cluster size and dislocation loop size than pure V and V-5Ti-5Ta. This is because V-Ti-Ta MEA and V-Ti-Ta-Nb HEA exhibit lower dislocation loop binding energy and defect mobility compared to pure V and V-5Ti-5Ta alloy. This study investigates the reasons for the better radiation resistance of V-Ti-Ta MEA and V-Ti-Ta-Nb HEA than pure V and V-5Ti-5Ta conventional alloys.

Enhanced irradiation tolerance of the body-centered cubic structured FeCrW medium-entropy alloy as revealed from primary damage process

Multi-principal element alloys have attracted much attention in the development of nuclear reactor materials due to their potentially excellent irradiation resistance. Here, we employed Molecular Dynamics (MD) simulations to investigate displacement cascades resulting from Primary Knock-on Atoms (PKA) energies ranging from 10 to 50 keV in body-centered cubic structured FeCrW, FeCr and α-Fe. The analysis encompasses irradiation-induced defect generation and evolution, aiming to elucidate mechanism of irradiation tolerance. The simulations results indicate that FeCrW medium-entropy alloys generate more Frenkel defects during the thermal spike stage compared to α-Fe, yet fewer residual defects are observed in FeCrW at the end of the cascade. The suppression of the increase in defects number in FeCrW compared to α-Fe is significantly enhanced with the increasing PKA energies. It is foreseeable that the number of residual defects in FeCrW will be much smaller than that of α-Fe with a dramatic increase of PKA energy, which will be attributed to the improved defect self-self-healing ability in FeCrW. Moreover, the mechanism of enhanced defect self-self-healing is attributed to the size of the defect cluster, the formation and distribution of defects, the enhanced thermal spike, and the chemical disorder caused by the increase in composition leading to low thermal conductivity. The spectral energy density (SED) curves spikes of α-Fe, FeCr and FeCrW reveal an important role in the enhanced phonon scattering in improving defect self-repairing ability due to chemical disorder. Our research provides valuable insights for guiding the development of advanced multi-principal element alloy structural materials in nuclear industry, particularly for the fourth-generation fast reactor.

Deformation ability of steel inner sleeve T-joint in modular gymnasia based on 3D-DIC method

Substantial loads the roofs bear exert stringent performance standards on connecting joints in movable modular gymnasiums. Previously, we introduced a novel joint design, utilizing internal sleeves and bolts to integrate the upper and lower columns of modular units. To explore the actual deformation behavior and force distribution of this joint, this study employed a three-dimensional digital image correlation (3D-DIC) measurement method to visualize its full-field displacement and strain distribution. The reliability of the 3D-DIC results was confirmed through comparison with traditional measurement methods. Building upon this solid foundation, this study proceeds to assess the static performance of this innovative joint in two distinct directions, successfully revealing micro-deformation and local buckling phenomena undetectable to the naked eye. Notably, the quality of the welds connecting the beams and columns plays a pivotal role in ensuring the overall structural integrity of the joint. Under lateral loading conditions, the destructive behavior of the joints is primarily governed by material strength. Moment-rotation curves were plotted to delve further into the mechanical characteristics of the joint, revealing that the inner-sleeve T-joint exhibits the attributes of a rigid joint. Moreover, the primary damage modes observed in the specimens were fractures at the beam root or buckling of the column, with the joint area remaining intact. Consequently, this joint qualifies as a full-strength connection. These findings will deepen knowledge and understanding of this novel joint for designers.

Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation

Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional surgical procedures, re-transplantation or die in the absence of a suitable regraft. Here, we investigate the role of the primary cilium, a highly specialised sensory organelle, in biliary injury leading to post-transplant biliary complications. Human biopsies were used to study the structure and function of primary cilia in liver transplant recipients that develop biliary complications (n= 7) in comparison with recipients without biliary complications (n= 12). To study the biological effects of the primary cilia during transplantation, we generated murine models that recapitulate liver procurement and cold storage, and assessed the elimination of the primary cilia in biliary epithelial cells in the K19CreERTKif3afl/fl mouse model. To explore the molecular mechanisms responsible for the observed phenotypes we used invitro models of ischemia, cellular senescence and primary cilia ablation. Finally, we used pharmacological and genetic approaches to target cellular senescence and the primary cilia, both in mouse models and discarded human donor livers. Prolonged ischemic periods before transplantation result in ciliary shortening and cellular senescence, an irreversible cell cycle arrest that blocks regeneration. Our results indicate that primary cilia damage results in biliary injury and a loss of regenerative potential. Senescence negatively impacts primary cilia structure and triggers a negative feedback loop that further impairs regeneration. Finally, we explore how targeted interventions for cellular senescence and/or the stabilisation of the primary cilia improve biliary regeneration following ischemic injury. Primary cilia play an essential role in biliary regeneration and we demonstrate that senolytics and cilia-stabilising treatments provide a potential therapeutic opportunity to reduce the rate of biliary complications and improve clinical outcomes in liver transplantation. Up to 25% of liver transplants result in biliary complications, leading to additional surgery, retransplants, or death. We found that the incidence of biliary complications is increased by damage to the primary cilium, an antenna that protrudes from the cell and is key to regeneration. Here, we show that treatments that preserve the primary cilia during the transplant process provide a potential solution to reduce the rates of biliary complications.

Thermal fatigue behavior of the ZGH451 Ni-based superalloy fabricated by direct energy deposition in the temperature range of 900–1100 °C

In this study, a novel Ni-based superalloy, ZGH451, has been fabricated using direct energy deposition (DED). The thermal fatigue resistance of ZGH451 is systematically evaluated at 900, 1000, and 1100 °C, primarily focusing on the crack initiation and propagation behaviors. The results indicate that higher peak temperatures lead to earlier initiation and more rapid propagation of cracks. Cracks are initiated at the defects and grain boundaries in the vicinity of the notch, and different crack propagation mechanisms (γ' phase slip shearing, γ' phase distortion shearing, and γ' phase rafting shearing at 900, 1000, and 1100 °C, respectively) are the main reason for the different cracks propagation behaviors under the three temperatures. The main crack propagation paths are oriented at approximately 45° with respect to the build direction, suggesting activation of the {111}<110> slip system. Additionally, oxidation reduces the matrix strength and passivates the crack tips, leading to varying rates of crack propagation. At elevated temperatures, the synergistic effects of thermal stress and oxidative erosion are found to be the primary damage mechanisms of thermal fatigue. Overall, the proposed ZGH451 superalloy demonstrates exceptional thermal fatigue resistance, providing a crucial experimental reference for thermal fatigue in additively manufactured superalloys.

Spinal cord injury: pathogenetic principles of molecular and cellular therapy

Spinal cord injury is a prognostically unfavorable condition due to the subsequent development of primary and secondary damage to the nervous structures, leading to various disorders of motor and sensory capabilities, which is also accompanied by dysfunction of the autonomic nervous system. Considering the initial complexities of regeneration processes in the central nervous system, in order to select treatment tactics for patients with spinal cord injury, it is important for doctors to know the cellular basis of the pathophysiological processes occurring in the spinal cord in the acute and chronic phases after injury, including in order to adequately select cells-targets of pharmacological drugs. Existing methods of treating neurotrauma can still do little to help prevent the death of neurons and the formation of glial scars, which make it impossible for the migration of cells involved in the processes of post-traumatic remodeling of the spinal cord and become an obstacle to the sprouting of regenerating axons. Unfortunately, preventing the formation of a glial scar remains an unsolved problem in clinical practice. In addition, in the case of spinal cord injuries in the clinic, it is extremely important to provide humoral stimulation to maintain the viability of nerve structures, for example, using numerous growth factors that are well known today, which have a beneficial effect on the intracellular regeneration of neurons and other cells involved in these processes, but the methodology for their delivery into the central nervous system has only been tested in animal models. That is why there is an urgent need to develop fundamentally new approaches to the treatment of the consequences of spinal cord injury, including cellular technologies based on transplantation of stem or differentiated cells in order to restore nerve structures and secretion of growth factors, the use of genetic constructs carrying genes for neurotrophic factors that can minimize development of post-traumatic destructive processes in the central nervous system. This review is devoted to these issues.