Primary Damage Research Articles

Synergistic effects of curcumin and stem cells on spinal cord injury: a comprehensive review.

Spinal cord injury (SCI) is damage to the spinal cord that permanently or temporarily disrupts its function, causing considerable autonomic, sensory, and motor disorders, and involves between 10 and 83 cases per million yearly. Traumatic SCI happens following primary acute mechanical damage, leading to injury to the spinal cord tissue and worsening clinical outcomes. The present therapeutic strategies for this complex disease fundamentally rely on surgical approaches and conservative remedies. However, these modalities are not effective enough for neurological recovery. Therefore, it is necessary to discover more efficient methods to treat patients with SCI. Today, considerable attention has been drawn to bioactive compounds-based remedies and stem cell therapy for curing various ailments and disorders, such as neurological diseases. Some researchers have recommended that harnessing curcumin, a polyphenol obtained from turmeric, in combination with stem cells, like mesenchymal stem cells, neural stem cells, and ependymal stem cells, can remarkably improve neurological recovery-related parameters more effective than the treatment with these two methods separately in experimental models. Hereby, this literature review delves into the functionality of curcumin combined with stem cells in treating SCI with a focus on cellular and molecular mechanisms.

Damage features and mechanism of prestressed hollow square piles subjected to non-contact underwater explosion

Critical hydraulic structures are increasingly vulnerable to underwater explosion attacks, with the supporting piles being prime targets for terrorist activities. This study investigates the damage effects and mechanisms of prestressed concrete hollow square (PCHS) piles under non-contact underwater explosions. A series of underwater explosion experiments was conducted on four PCHS piles. The dynamic response of PCHS piles throughout the underwater explosion process was simulated using a coupled fluid-solid numerical model. The mechanisms of dynamic damage to the PCHS piles were elucidated through an integrated analysis of both experimental and numerical results. The research indicates that the damage characteristics of PCHS piles include longitudinal and oblique cracks on the lateral surfaces, transverse cracks on the rear side, and localized fragmentation of concrete. Three primary damage modes have been identified: bending failure(L¯c= 0.59 m/kg1/3), combined bending-shear failure(L¯c= 0.36 m/kg1/3), and punching failure(L¯c= 0.24 m/kg1/3). The local and global responses induced by shock waves are the primary causes of structural damage. Furthermore, as the stand-off distance decreases, the impact of explosive bubbles increases the magnitude of the overall response. A comparative analysis also examined the impact of prestress and axial load on the damage behavior of hollow square piles.

Molecular Dynamic Simulation of Primary Damage with Electronic Stopping in Indium Phosphide

Indium phosphide (InP) is an excellent material used in space electronic devices due to its direct band gap, high electron mobility, and high radiation resistance. Displacement damage in InP, such as vacancies, interstitials, and clusters, induced by cosmic particles can lead to the serious degradation of InP devices. In this work, the analytical bond order potential of InP is modified with the short-range repulsive potential, and the hybrid potential is verified for its reliability to simulate the atomic cascade collisions. By using molecular dynamics simulations with the modified potential, the primary damage defects evolution of InP caused by 1–10 keV primary knock-on atoms (PKAs) are studied. The effects of electronic energy loss are also considered in our research. The results show that the addition of electronic stopping loss reduces the number of point defects and weakens the damage regions. The reduction rates of point defects caused by electronic energy loss at the stable state are 32.2% and 27.4% for 10 keV In-PKA and P-PKA, respectively. In addition, the effects of electronic energy loss can lead to an extreme decline in the number of medium clusters, cause large clusters to vanish, and make the small clusters dominant damage products in InP. These findings are helpful to explain the radiation-induced damage mechanism of InP and expand the application of InP devices.

Local delivery of soluble fractalkine (CX3CL1) peptide restores ribbon synapses after noise-induced cochlear synaptopathy

Cochlear ribbon synapses between sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are vulnerable to rapid and primary damage and/or loss due to noise overexposure. Such damaged ribbon synapses can repair spontaneously in mouse and guinea pig. However, the mechanisms for synaptic repair are unclear. Previously, we have demonstrated a critical role for the fractalkine signaling axis (CX3CL1-CX3CR1) in synaptic repair, wherein noise-damaged ribbon synapses are spontaneously repaired in the presence of fractalkine receptor (CX3CR1) expressed by cochlear macrophages. Here, we examined whether local administration of chemokine fractalkine ligand (CX3CL1 or FKN) in the form of a peptide is effective in restoring synapses and hearing loss after noise-induced cochlear synaptopathy (NICS). Specifically, the efficacy of different isoforms of FKN was evaluated for restoration of loss of IHC ribbon synapses and hearing after NICS. A single transtympanic injection of soluble isoform of FKN (sFKN) peptide at 1 day after synaptopathic noise trauma for 2 hours at 93 decibel sound pressure level led to significant recovery of auditory brainstem response (ABR) thresholds, ABR peak I amplitudes and ribbon synapses in FKN knockout mice when compared to mice injected with membrane-bound FKN peptide (mFKN). Likewise, local treatment with sFKN peptide in FKN wild type mice restored synaptopathic noise-damaged ribbon synapses and ABR peak I amplitudes. Mechanistically, FKN regulates macrophage numbers in the damaged cochlea and in the absence of macrophages, sFKN failed to restore loss of synapses and hearing after NICS. Furthermore, sFKN treatment attenuated cochlear inflammation after NICS without altering the expression of CX3CR1. Finally, injected sFKN peptide was detectable inside the cochlea for 24 h localized to the basilar membrane and spiral lamina near the sensory epithelium. These data provide a proof-of-principle that local delivery of an immune factor, sFKN is effective in restoring ribbon synapses and hearing loss after NICS in a macrophage-dependent manner and highlights the potential of sFKN as an immunotherapy for cochlear synaptopathy due to noise.

Balance of Antioxidants vs. Oxidants in Perinatal Asphyxia

Perinatal asphyxia refers to an acute event of cerebral ischemia and hypoxia during the perinatal period, leading to various degrees of brain injury. The mechanisms involved in perinatal asphyxia include the production of reactive oxygen species (ROS), accumulation of intracellular calcium, lipid peroxidation, excitatory amino acid receptor overactivation, energy failure, and caspase-mediated cell death. Both primary and secondary neuronal damage are caused by the overproduction of ROS following a hypoxic/ischemic event. ROS can react with nearly any type of molecule, including lipids, proteins, polysaccharides, and DNA. Neonates who suffer from perinatal asphyxia are prone to oxidative stress, which is characterized by a disruption in the oxidant/antioxidant balance, favoring oxidants over the intracellular and extracellular antioxidant scavenging mechanisms. Current research has focused on developing treatment strategies that potentially improve the endogenous antioxidant neuroprotective mechanisms or minimize injury resulting from hypoxia/ischemia. In this narrative review, we aim to present evidence regarding the contribution of oxidant/antioxidant balance to the pathogenesis and progression of perinatal asphyxia. Also, we aim to explore the role of potential antioxidant therapies as promising treatment strategies for perinatal asphyxia, especially as an adjunct to therapeutic hypothermia in infants with perinatal asphyxia. The current literature on antioxidant treatments in newborns is limited; however, allopurinol, melatonin, and erythropoietin have shown some positive effects in clinical trials. Inhibitors of nitric oxide synthase, N-acetylcysteine, and docosahexaenoic acid have shown promising neuroprotective effects in preclinical studies. Finally, nanotherapeutics could potentially modulate oxidative stress in hypoxemic/ischemic brain injury by targeted medication delivery. Future research on neuroprotectants and their processes is warranted to develop innovative treatments for hypoxia/ischemia in clinical practice.

FEATURES OF FUNCTIONAL DIAGNOSTICS OF OPTIC NERVE DAMAGE IN CASE OF HEAD INJURY

Introduction. Traumatic optic nerve damage is a rare complication of a head injury. Symptoms of primary damage appear at the time of first diagnostic in the early period and mask TON’s signs. Understanding of visual disturbances for the patient comes in a later period, when recovery is limited due to the irreversibility of the received injuries. Difficulties of early diagnosis of optic nerve damage in case of head trauma encourage the search for new, more informative methods. The aim of the study was to analyze the functional manifestations of the optic nerve damage in case of head injuries with different localization. Materials and methods. 366 cases (732 eyes) of patients with traumatic optic neuropathy (TON) were studied according to archival data in the period from 2014 to 2019. The control group consisted of 58 practically healthy persons (116 eyes). All patients were divided into three groups: A group - patients with traumatic brain injury (TBI) was 120 persons, B group - patients with craniofacial injury (CFI) - 118 persons and C group - with combined injuries - 128 injured. The degree of optic nerve damage was assessed using visometry, pupillometry, and perimetry. Results. In case of craniocerebral injury, decrease of visual acuity with an average value of 0.92±0.06 corresponded to degrees 0 (93%) and I (7%). In the case of craniofacial trauma, according to the research, visual acuity decreased to 0.76±0.13 (by 0.24, 24% compared to the control group, p<0.05). The first degree (23%) and the second degree (7%) were determined. With a combined primary head injury, visual acuity decreased to 0.42±0.21 (by 0.58, 58%, compared to the control group, p<0.05). One third were patients with I, II and III degrees of visual impairment. The use of static perimetry made it possible to detect damage to the optic nerve in patients with 0 degrees of reduced visual acuity. At the same time, 88% of patients of A group (n=120) had 0A class, 23% of B group (n=118) had 0B class, and in C group (n=122) there was almost no. The relative afferent pupillary defect’s test was negative at 0A group of vision loss, but the pupil cycle speed (PSC) was reduced in all patients. This confirms damage to the optic nerve in patients with high visual acuity This study showed that patients with TBI had high visual acuity in 93% of cases, The visual acuity was around 0.5-1.0, but sensitivity in the central part of the visual field decreased by 12 times, and the pupil reaction rate decreased by 55% compared to the control group. In case of craniofacial trauma (B group), visual acuity decreased to 0.76±0.13 (by 0.24, 24% compared to the control group, p<0.05). I degree (23%) and II degree (7%) decrease of visual acuity was determined. As for the sensitivity in the central part of the visual field, it was 46.59% lower than in the A group. In patients with a combined injury of the head and face, a third of the injured had visual acuity less than 0.1, which is not found in other variants of injury. Conclusions. Analysis showed that severity of optic nerve damage depends on localization of the head injury. The use of static perimetry and pupillometry is important for the early diagnosis of TON in conditions with high visual acuity when other symptoms are weak or not amenable to examination.

Seismic behaviour and design of a tall mixed reinforced concrete–steel structure supporting an oil refinery reactor

AbstractThis study investigates the seismic behaviour of a special mixed reinforced concrete-steel structure that supports an oil refinery reactor. The structure is 64.90 m tall and consists of three parts: (a) a reinforced concrete frame basement; (b) a steel braced frame that supports the oil reactor and (c) the steel reactor itself. A three-dimensional model of the structure is created to perform static non-linear (pushover) analyses in order to obtain the capacity curves and understand the overall inelastic behavior of the structure. The results of the pushover analyses reveal that the structure exhibits similar inelastic behavior in both horizontal directions and satisfies the capacity design principles. The structure exhibits limited ductility considering the fact that has been designed with a behavior factor of q = 1.5 and primary damages are expected mainly in concrete members. Subsequently, dynamic non-linear time-history (NLTH) analyses are performed utilizing the three translational components of three seismic motions recorded during past earthquakes. These results involve: (i) the maximum values for displacements, accelerations and base shears; (ii) the maximum stresses at critical points of the oil refining reactor and (iii) the formation of plastic hinges at columns, beams and braces of the structure. Contrary to pushover analyses, NLTH analyses revealed the development of plastic hinges, hence seismic damage, that do not follow the desirable formation pattern. Moreover, the accelerations and displacements observed are expected to cause failure of the piping and mechanical equipment, while local failure of the high-stress areas of the shell of the reactor may be possible. Localized strengthening might be necessary to avoid repair works and downtime after such seismic event.

Cover Image

The cover image is based on the Article Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion by Sara Z. Jamal et al., https://doi.org/10.1111/micc.12883. Created in BioRender. Uddin, M. (2023) BioRender.com/p53i167. image

MORPHOLOGY OF THE HEART IN THE DELAYED PERIOD OF EXPOSURE TO LOW DOSES OF LEAD

The aim of this study was to investigate the delayed effects of low doses of lead exposure on the hart using an original experimental model for studying the delayed effects. Analysis of the obtained morphological picture revealed structural abnormalities affecting both the muscular and stromal-vascular components. The degree of damage is in direct correlation with the received dose of lead. The above indicates that lead loading, even in low doses, is accompanied by structural abnormalities in the heart even after a long time. Most likely, this is due to the ability of lead to accumulate in the body and remain there for a long time. Vascular disorders play a certain, if not the main, role in the damage to muscle cells. However, the presence of a complex mechanism, which also implies primary damage to cardiomyocytes under the influence of lead, cannot be ruled out. Due to the properties of lead and its impact on the body, and also due to the fact that it is impossible to stop the spread of lead in nature, it is important, along with the study of the mechanisms and results of lead exposure, to find prophylactic means that displace lead ions from the body and regulate metabolism, which is affected by their activity.

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.