Melatonin intervention to prevent nanomaterial exposure-induced damages: A systematic review and meta-analysis of in vitro and in vivo studies.

Given its antioxidant, anti-inflammatory, and antiapoptotic properties, melatonin (MEL), a health-caring food to improve sleep disorders, is hypothesized to protect against nanomaterial exposure-induced toxicity. However, the conclusion derived from different studies seemed inconsistent. A meta-analysis of all available preclinical studies was performed to examine the effects of MEL on nanomaterial-induced damages. Eighteen relevant studies were retrieved through searching five electronic databases up to December 2023. The meta-analysis showed that relative to control, MEL treatment significantly increased cell viability (standardized mean difference [SMD = 1.27]) and alleviated liver function (lowered AST [SMD = -3.89] and ALT [SMD = -5.89]), bone formation (enhanced BV/TV [SMD = 4.13] and lessened eroded bone surface [SMD = -5.40]), and brain nerve (inhibition of AChE activity [SMD = -3.60]) damages in animals. The protective mechanisms of MEL against damages caused by nanomaterial exposure were associated with its antiapoptotic (decreased Bax/Bcl-2 ratio [SMD = -4.50] and caspase-3 levels [dose <100 µM: SMD = -3.66]), antioxidant (decreased MDA [in vitro: SMD = -2.84; in vivo: SMD = -4.27]), and anti-inflammatory (downregulated TNF-α [in vitro: SMD = -5.41; in vivo: SMD = -3.21] and IL-6 [in vitro: SMD = -5.90; in vivo: SMD = -2.81]) capabilities. In conclusion, our study suggests that MEL should be supplemented to prevent damages in populations exposed to nanomaterials.

Repeated postnatal sevoflurane exposure impairs social recognition in mice by disrupting GABAergic neuronal activity and development in hippocampus.

BACKGROUND: Repeated exposure to sevoflurane during early developmental stages is a risk factor for social behavioural disorders, but the underlying neuropathological mechanisms remain unclear. As the hippocampal cornu ammonis area 2 subregion (CA2) is a critical centre for social cognitive functions, we hypothesised that sevoflurane exposure can lead to social behavioural disorders by disrupting neuronal activity in the CA2. METHODS: Neonatal mice were anaesthetised with sevoflurane 3 vol% for 2 h on postnatal day (PND) 6, 8, and 10. Bulk RNA sequencing of CA2 tissue was conducted on PND 12. Social cognitive function was assessed by behavioural experiments, and in vivo CA2 neuronal activity was recorded by multi-channel electrodes on PND 60-65. RESULTS: Repeated postnatal exposure to sevoflurane impaired social novelty recognition in adulthood. It also caused a decrease in the synchronisation of neuronal spiking, gamma oscillation power, and spike phase-locking between GABAergic spiking and gamma oscillations in the CA2 during social interaction. After sevoflurane exposure, we observed a reduction in the density and dendritic complexity of CA2 GABAergic neurones, and decreased expression of transcription factors critical for GABAergic neuronal development after. CONCLUSIONS: Repeated postnatal exposure to sevoflurane disturbed the development of CA2 GABAergic neurones through downregulation of essential transcription factors. This resulted in impaired electrophysiological function in adult GABAergic neurones, leading to social recognition deficits. These findings reveal a potential electrophysiological mechanism underlying the long-term social recognition deficits induced by sevoflurane and highlight the crucial role of CA2 GABAergic neurones in social interactions.

A one-stop integrated natural antimicrobial microneedles with anti-inflammatory, pro-angiogenic and long-term moisturizing properties to accelerate diabetic wound healing.

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ±â€¯2.51 %) significantly enhanced cell migration compared to the control group (20.2 ±â€¯1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ±â€¯3.44 %, far surpassing the healing rate of only 40.34 ±â€¯7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds.

Effects of phasic activation of locus coeruleus on cortical neural activity and auditory discrimination behavior.

Although the locus coeruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential (LFP) and single-unit activity (SUA) in multiple cortical regions associated with auditory-motor processing, including the auditory cortex (AC), posterior parietal cortex (PPC), secondary motor cortex (M2), anterior cingulate cortex (ACC), prefrontal cortex (PFC), and orbitofrontal cortex (OFC), in response to optogenetic activation (40Hz and 0.5s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillations (50 - 80Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in NE levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a Go/No-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC, and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.Significance Statement The locus coeruleus (LC) plays a vital role in mediating behaviors related to perception, but the underlying mechanisms remain unclear. Using optogenetic techniques, we selectively activated the neural projections from the norepinephrine (NE) neurons of LC to the orbitofrontal cortex (OFC). We found that phasical activation of LC neurons increased NE levels in the OFC and induced a gamma band neuronal activity, while also shortening the reaction latency of mice in auditory discrimination tasks, but at the cost of increased false alarm rates. These results reveal a neural mechanism involving the LC in auditory-motor processing, providing a new perspective for understanding attention and perception.

Fangchinoline induces antiviral response by suppressing STING degradation.

The stimulator of interferon genes (STING), an integral adaptor protein in the DNA-sensing pathway, plays a pivotal role in the innate immune response against infections. Additionally, it presents a valuable therapeutic target for infectious diseases and cancer. We observed that fangchinoline (Fan), a bis-benzylisoquinoline alkaloid (BBA), effectively impedes the replication of vesicular stomatitis virus (VSV), encephalomyocarditis virus (EMCV), influenza A virus (H1N1), and herpes simplex virus-1 (HSV-1) in vitro. Fan treatment significantly reduced the viral load, attenuated tissue inflammation, and improved survival in a viral sepsis mouse model. Mechanistically, Fan activates the antiviral response in a STING-dependent manner, leading to increased expression of interferon (IFN) and interferon-stimulated genes (ISGs) for potent antiviral effects in vivo and in vitro. Notably, Fan interacts with STING, preventing its degradation and thereby extending the activation of IFN-based antiviral responses. Collectively, our findings highlight the potential of Fan, which elicits antiviral immunity by suppressing STING degradation, as a promising candidate for antiviral therapy.

Undescribed polyketides from endophytes associated with the critically endangered conifer Abies beshanzuensis.

Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.

A Highly Sustainable Supramolecular Bioplastic Film with Superior Hydroplasticity and Biodegradability.

Massive accumulation of postconsumer plastic waste in eco-system has raised growing environmental concerns. Sustainable end-of-life managements of the indispensable plastic are highly demanding and challenging in modern society. To relieve the plastic menace, herein we present a full life cycle sustainable supramolecular bioplastic made from biomass-derived polyelectrolyte (chitosan quaternary ammonium salt, QCS) and natural sodium fatty acid (sodium laurate, SL) through solid-phase molecular self-assembly (SPMSA), by which the QCS-SL complexes, precipitated from mixing the aqueous solutions, self-assemble to form bioplastic film by mildly pressing at room temperature. The QCS-SL bioplastic films display superior hydroplasticity owing to the water-activated molecular rearrangement and electrostatic bond reconstruction, which allows facile self-healing and reprocessing at room temperature to significantly extend the service lifetime of both products and raw materials. With higher water content, the dynamic electrostatic interactions and precipitation-dissolution equilibrium endow the QCS-SL bioplastic films with considerable solubility in water, which is promising to mitigate the plastic accumulation in aquatic environment. Because both QCS and SL are biocompatible and biodegradable, the dissolved QCS-SL films are nontoxic and environmentally friendly. Thus, this novel supramolecular bioplastic is highly sustainable throughout the whole life cycle, which is expected to open a new vista in sustainable plastic materials.

Correction: Wang et al. Visible Light Motivated the Photocatalytic Degradation of P-Nitrophenol by Ca2+-Doped AgInS2. Molecules 2024, 29, 361.

In the original publication [...].

Current trends and perspectives on salty and salt taste-enhancing peptides: A focus on preparation, evaluation and perception mechanisms of salt taste.

Long-term excessive intake of sodium negatively impacts human health. Effective strategies to reduce sodium content in foods include the use of salty and salt taste-enhancing peptides, which can reduce sodium intake without compromising the flavor or salt taste. Salty and salt taste-enhancing peptides naturally exist in various foods and predominantly manifest as short-chain peptides consisting of < 10 amino acids. These peptides are primarily produced through chemical or enzymatic hydrolysis methods, purified, and identified using ultrafiltration + gel filtration chromatography + liquid chromatography-tandem mass spectrometry. This study reviews the latest developments in these purification and identification technologies, and discusses methods to evaluate their effectiveness in saltiness perception. Additionally, the study explores four biological channels potentially involved in saltiness perception (epithelial sodium channel, transient receptor potential vanilloid 1, calcium-sensing receptor (CaSR), and transmembrane channel-like 4 (TMC4)), with the latter three primarily functioning under high sodium levels. Among the channels, salty taste-enhancing peptides, such as γ-glutamyl peptides, may co-activate the CaSR channel with calcium ions to participate in saltiness perception. Salty taste-enhancing peptides with negatively charged amino acid side chains or terminal groups may replace chloride ions and activate the TMC4 channel, contributing to saltiness perception. Finally, the study discusses the feasibility of using these peptides from the perspectives of food material constraints, processing adaptability, multifunctional application, and cross-modal interaction while emphasizing the importance of utilizing computational technology. This review provides a reference for advancing the development and application of salty and salt-enhancing peptides as sodium substitutes in low-sodium food formulations.

A bimetallic sulfide FeCoS4@rGO hybrid as a high-performance anode for potassium-ion batteries.

We synthesized a low metal-to-sulfur atomic ratio (0.5) FeCoS4, exhibiting high reversible specific capacity. Reduced graphene oxide was covered on the surface to improve the cycling stability and rate performance further. Density functional theory calculations show that composite materials can effectively increase the adsorption energy and enhance the diffusion kinetics.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, it is demonstrated that the adaptive microdrugs (even up to 3.0 µm in size) are more efficient than their nanodrugs (less than 200 nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibit enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. It is believed that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors.

Design and application of Cd2+ polypeptide fluorescent probes based on Aggregation Induced Emission (AIE).

Cadmium is a toxic heavy metal, which is both an environmental pollutant, and a threat to human health. A fluorescent probe was developed to detect Cd2+ selectively, sensitively, and quickly. This study reports the successful development of a polypeptide fluorescent probe TPE-HC (TPE-His-Pro-Gly-Cys) which selectively detects Cd2+ by Aggregation-Induced Emission effect. After fluorescence excitation, Cd2+ can be effectively detected based on the change of fluorescence intensity. The detection limit of Cd2+ in buffer solution was determined to be 151 nM (R2 = 0.9933). This probe exhibits high sensitivity, high cell permeabilit y, and low biological toxicity, and can perform live cell imaging under biological conditions. This study indicates that TPE-HC can detect Cd2+ in biological environments.

MultiModRLBP: A Deep Learning Approach for Multi-Modal RNA-Small Molecule Ligand Binding Sites Prediction.

This study aims to tackle the intricate challenge of predicting RNA-small molecule binding sites to explore the potential value in the field of RNA drug targets. To address this challenge, we propose the MultiModRLBP method, which integrates multi-modal features using deep learning algorithms. These features include 3D structural properties at the nucleotide base level of the RNA molecule, relational graphs based on overall RNA structure, and rich RNA semantic information. In our investigation, we gathered 851 interactions between RNA and small molecule ligand from the RNAglib dataset and RLBind training set. Unlike conventional training sets, this collection broadened its scope by including RNA complexes that have the same RNA sequence but change their respective binding sites due to structural differences or the presence of different ligands. This enhancement enables the MultiModRLBP model to more accurately capture subtle changes at the structural level, ultimately improving its ability to discern nuances among similar RNA conformations. Furthermore, we evaluated MultiModRLBP on two classic test sets, Test18 and Test3, highlighting its performance disparities on small molecules based on metal and non-metal ions. Additionally, we conducted a structural sensitivity analysis on specific complex categories, considering RNA instances with varying degrees of structural changes and whether they share the same ligands. The research results indicate that MultiModRLBP outperforms the current state-of-the-art methods on multiple classic test sets, particularly excelling in predicting binding sites for non-metal ions and instances where the binding sites are widely distributed along the sequence. MultiModRLBP also can be used as a potential tool when the RNA structure is perturbed or the RNA experimental tertiary structure is not available. Most importantly, MultiModRLBP exhibits the capability to distinguish binding characteristics of RNA that are structurally diverse yet exhibit sequence similarity. These advancements hold promise in reducing the costs associated with the development of RNA-targeted drugs.

Dynamic molecular signatures of acute myocardial infarction based on transcriptomics and metabolomics.

Acute myocardial infarction (AMI) commonly precedes ventricular remodeling, heart failure. Few dynamic molecular signatures have gained widespread acceptance in mainstream clinical testing despite the discovery of many potential candidates. These unmet needs with respect to biomarker and drug discovery of AMI necessitate a prioritization. We enrolled patients with AMI aged between 30 and 70. RNA-seq analysis was performed on the peripheral blood mononuclear cells collected from the patients at three time points: 1 day, 7 days, and 3 months after AMI. PLC/LC-MS analysis was conducted on the peripheral blood plasma collected from these patients at the same three time points. Differential genes and metabolites between groups were screened by bio-informatics methods to understand the dynamic changes of AMI in different periods. We obtained 15 transcriptional and 95 metabolite expression profiles at three time points after AMI through high-throughput sequencing. AMI-1d: enrichment analysis revealed the biological features of 1 day after AMI primarily included acute inflammatory response, elevated glycerophospholipid metabolism, and decreased protein synthesis capacity. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) might stand promising biomarkers to differentiate post-AMI stage. Anti-inflammatory therapy during the acute phase is an important direction for preventing related pathology. AMI-7d: the biological features of this stage primarily involved the initiation of cardiac fibrosis response and activation of platelet adhesion pathways. Accompanied by upregulated TGF-beta signaling pathway and ECM receptor interaction, GP5 help assess platelet activation, a potential therapeutic target to improve haemostasis. AMI-3m: the biological features of 3 months after AMI primarily showed a vascular regeneration response with VEGF signaling pathway, NOS3 and SHC2 widely activated, which holds promise for providing new therapeutic approaches for AMI. Our analysis highlights transcriptional and metabolomics signatures at different time points after MI, which deepens our understanding of the dynamic biological responses and associated molecular mechanisms that occur during cardiac repair.

Turning Non-Sticking Surface into Sticky Surface: Correlation between Surface Topography and Contact Angle Hysteresis.

We present a surface modification technique that turns CuNi foam films with a high contact angle and non-sticking property into a sticky surface. By decorating with mesh-like biaxially oriented polypropylene (BOPP) and adjusting the surface parameters, the surface exhibits water-retaining capability even when being held upside down. The wetting transition process of droplets falling on its surface were systematically studied using the finite element simulation method. It is found that the liquid filled the surface microstructure and curvy three-phase contact line. Moreover, we experimentally demonstrated that this surface can be further applied to capture underwater air bubbles.

Superstrong Ionogel Enabled by Coacervation-Induced Nanofibril Assembly for Sustainable Moisture Energy Harvesting.

Ionogels have grabbed significant interest in various applications, from sensors and actuators to wearable electronics and energy storage devices. However, current ionogels suffer from low strength and poor ionic conductivity, limiting their performance in practical applications. Here, inspired by the mechanical reinforcement of natural biomacromolecules through noncovalent aggregates, a strategy is proposed to construct nanofibril-based ionogels through complex coacervation-induced assembly. Cellulose nanofibrils (CNFs) can bundle together with poly(ionic liquid) (PIL) to form a superstrong nanofibrous network, in which the ionic liquid (IL) can be retained to form ionogels with high liquid inclusion and ionic conductivity. The strength of the CNF-PIL-IL ionogels can be tuned by the IL content over a wide range of up to 78 MPa. The optical transparency, high strength, and hygroscopicity enabled them to be promising candidates in moist-electricity generation and applications such as energy harvesting windows and wearable power generators. In addition, the ionogels are degradable and the ionogel-based generators can be recycled through dehydration. Our strategy suggests perspectives for the fabrication of high-strength and multifunctional ionogels for sustainable applications.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.

Quality and Flavor Difference in Dry-Cured Meat Treated with Low-Sodium Salts: An Emphasis on Magnesium.

The present study aimed to develop low-sodium curing agents for dry-cured meat products. Four low-sodium formulations (SPMA, SPM, SP, and SM) were used for dry-curing meat. The physicochemical properties and flavor of the dry-cured meat were investigated. The presence of Mg2+ ions hindered the penetration of Na+ into the meat. The weight loss, moisture content, and pH of all low-sodium salt groups were lower than those of S. Mg2+ addition increased the water activity (Aw) of SPMA, SPM, and SM. Dry-curing meat with low-sodium salts promoted the production of volatile flavor compounds, with Mg2+ playing a more prominent role. Furthermore, low-sodium salts also promoted protein degradation and increased the content of free amino acids in dry-cured meat, especially in SM. Principal component analysis (PCA) showed that the low-sodium salts containing Mg2+ were conducive to improving the quality of dry-cured meat products. Therefore, low-sodium salts enriched with Mg2+ become a desirable low-sodium curing agent for achieving salt reduction in dry-cured meat products.

Textured Perovskite/Silicon Tandem Solar Cells Achieving Over 30% Efficiency Promoted by 4-Fluorobenzylamine Hydroiodide.

Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.

Irradiation-Hardening Model of TiZrHfNbMo0.1 Refractory High-Entropy Alloys.

In order to find more excellent structural materials resistant to radiation damage, high-entropy alloys (HEAs) have been developed due to their characteristics of limited point defect diffusion such as lattice distortion and slow diffusion. Specially, refractory high-entropy alloys (RHEAs) that can adapt to a high-temperature environment are badly needed. In this study, TiZrHfNbMo0.1 RHEAs are selected for irradiation and nanoindentation experiments. We combined the mechanistic model for the depth-dependent hardness of ion-irradiated metals and the introduction of the scale factor f to modify the irradiation-hardening model in order to better describe the nanoindentation indentation process in the irradiated layer. Finally, it can be found that, with the increase in irradiation dose, a more serious lattice distortion caused by a higher defect density limits the expansion of the plastic zone.