The Mediating Effect of Coping Style in the Relationship Between Sleep Quality and Perceived Cognitive Impairment Among Breast Cancer Patients: A Cross-sectional Study.

BACKGROUND: Perceived cognitive impairment is a significant symptom experienced by breast cancer patients and may be affected by sleep quality. Coping styles have potential relevancies with both sleep quality and perceived cognitive impairment. However, the empirical evidence supporting their association among breast cancer patients is limited. OBJECTIVE: This study explored the associations between sleep quality, coping styles, and perceived cognitive impairment and tested the mediating role of coping styles in breast cancer patients. METHODS: A total of 294 breast cancer patients were included in this cross-sectional study. Patients were assessed using the Pittsburgh Sleep Index Scale, the Simplified Coping Styles Questionnaire, and the Functional Assessment of Cancer Therapy-Cognitive Functioning (Version 3) Scale. The data were analyzed using SPSS and Process macros. RESULTS: The direct effect of sleep quality on reported cognitive impairment was significant (ß = -0.245, P < .001). Furthermore, sleep quality was found to have a significant indirect effect on perceived cognitive impairment through positive coping style (ß = -0.026, P < .05) and negative coping style (ß = -0.131, P < .05). CONCLUSIONS: Our research suggests that sleep quality has both a direct effect on perceived cognitive impairment and an indirect effect through positive and negative coping styles in breast cancer patients. Moreover, negative coping style had a more pronounced mediating effect than positive coping style. IMPLICATIONS FOR PRACTICE: Clinical medical staff could reduce the perceived cognitive impairment of breast cancer patients by improving their sleep quality and encouraging them to adopt a more positive coping style.

Identification of ATM Mutation as a Potential Prognostic Biomarker for Immune Checkpoint Inhibitors Therapy.

BACKGROUND: Ataxia telangiectasia mutated (ATM), an apical DNA damage response gene, is a commonly mutated gene in tumors, and its mutation could strengthen tumor immunogenicity and alter the expression of PD-L1, which potentially contributes to immune checkpoint inhibitors (ICIs) therapy. METHODS: The characteristics of ATM mutation and its relationship with the ICIs-treated clinical prognosis have been analyzed comprehensively in this paper. The overall frequency of ATM mutations has been found to be 4% (554/10953) in the cancer genome atlas (TCGA) cohort. RESULTS: Both the TMB and MSI levels in patients with ATM mutations were significantly higher than those in patients without mutations (P < 0.0001). The median TMB was positively correlated with the frequency of ATM mutations (r = 0.54, P = 0.003). In the TCGA cohort, patients with ATM mutations had better clinical benefits in terms of overall survival (OS, hazard ratio (HR) = 0.736, 95% CI = 0.623 - 0.869), progression-free survival (PFS, HR = 0.761, 95% CI = 0.652 - 0.889), and disease-free survival (DFS, HR = 0.686, 95% CI = 0.512 - 0.919)] than patients without ATM mutations. Subsequently, the verification results showed ATM mutations to be significantly correlated with longer OS in ICIs-treated patients (HR = 0.710, 95% CI = 0.544 - 0.928). Further exploration indicated ATM mutation to be significantly associated with regulated anti-tumor immunity (P < 0.05). CONCLUSION: Our findings highlight the value of ATM mutation as a promising biomarker to predict ICIs therapy in multiple tumors.

Incidence of Cytomegalovirus Infection After Repeat Keratoplasty and Associated Rate of Graft Failure.

INTRODUCTION: The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus-) undergoing repeat keratoplasty. METHODS: This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. RESULTS: Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus- group (29%) (P < 0.001). CMV infection in the cornea increased the risk of repeat graft failure and shortened the median survival time (hazard ratio, 3.876; 95% confidence intervals, 2.554-5.884; P < 0.001). The characteristics of graft failure included exacerbation of ocular surface inflammation, neovascularization, and opacification. Epithelial defects, high IOP, and endothelial decompensation were observed at an increased frequency in the CMV+ group (all P < 0.005). Recurrent CMV infection presented as early endothelial infection in the CMV+ group. Recurrence of CMV infection was confined to the graft endothelium without involving the stroma and epithelium post-repeat endothelial keratoplasty. CONCLUSIONS: CMV infection post-keratoplasty leads to persistent endothelial damage and graft opacification and significantly increases the risk of repeat graft failure. Localized recurrence of CMV infection in the endothelial grafts underscores the importance of monitoring and treatment. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800014684.

Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity.

INTRODUCTION: Metformin (MET), derived from Galega officinalis, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear. OBJECTIVES: This study aimed to elucidate MET's role in inducing plant immunity and investigate the associated mechanisms. METHODS: To investigate the impact of MET on enhancing plant immune responses, we conducted assays measuring defense gene expression, reactive oxygen species (ROS) accumulation, mitogen-activated protein kinase (MAPK) phosphorylation, and pathogen infection. Additionally, surface plasmon resonance (SPR) and microscale thermophoresis (MST) techniques were employed to identify MET targets. Protein-protein interactions were analyzed using a luciferase complementation assay and a co-immunoprecipitation assay. RESULTS: Our findings revealed that MET boosts plant disease resistance by activating MAPKs, upregulating the expression of downstream defense genes, and fortifying the ROS burst. CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) was identified as a target of MET. It inhibited the interaction between BOTRYTIS-INDUCED KINASE 1 (BIK1) and CPK28, blocking CPK28 threonine 76 (T76) transphosphorylation by BIK1, and alleviating the negative regulation of immune responses by CPK28. Moreover, MET enhanced disease resistance in tomato, pepper, and soybean plants. CONCLUSION: Collectively, our data suggest that MET enhances plant immunity by blocking BIK1-mediated CPK28 phosphorylation.

Threatment Strategies for Recurrent Hepatocellular Carcinoma Patients: Ablation and its Combination Patterns.

With the development of guidance technology and ablation equipment, ablative procedures have emerged as important loco-regional alternatives to surgical resection for recurrent hepatocellular carcinoma (rHCC) patients. Currently, ablation modalities used in clinical practice mainly include radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), cryoablation (CRA), high-intensity focused ultrasound (HIFU), and irreversible electroporation (IRE). Accumulated comparative data of ablation versus surgical resection reveal noninferior responses and outcomes but superior adverse effects. Moreover, studies demonstrate that ablation may serve as an excellent procedure for rHCC given its exact minimal invasiveness and immune modulation. We focus on the current status of ablation in clinical practice for rHCC and discuss new research in the field, including ablation combined with these other modalities, such as targeted therapy and immunotherapy.

Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research.

Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; https://ngdc.cncb.ac.cn/lsd/), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.

Janus Membrane with Intrafibrillarly Strontium-Apatite-Mineralized Collagen for Guided Bone Regeneration.

Commercial collagen membranes face difficulty in guided bone regeneration (GBR) due to the absence of hierarchical structural design, effective interface management, and diverse bioactivity. Herein, a Janus membrane called SrJM is developed that consists of a porous collagen face to enhance osteogenic function and a dense face to maintain barrier function. Specifically, biomimetic intrafibrillar mineralization of collagen with strontium apatite is realized by liquid precursors of amorphous strontium phosphate. Polycaprolactone methacryloyl is further integrated on one side of the collagen as a dense face, which endows SrJM with mechanical support and a prolonged lifespan. In vitro experiments demonstrate that the dense face of SrJM acts as a strong barrier against fibroblasts, while the porous face significantly promotes cell adhesion and osteogenic differentiation through activation of calcium-sensitive receptor/integrin/Wnt signaling pathways. Meanwhile, SrJM effectively enhances osteogenesis and angiogenesis by recruiting stem cells and modulating osteoimmune response, thus creating an ideal microenvironment for bone regeneration. In vivo studies verify that the bone defect region guided by SrJM is completely repaired by newly formed vascularized bone. Overall, the outstanding performance of SrJM supports its ongoing development as a multifunctional GBR membrane, and this study provides a versatile strategy of fabricating collagen-based biomaterials for hard tissue regeneration.

Herbicide Safeners: From Molecular Structure Design to Safener Activity.

Herbicide safeners, highly effective antidotes, find widespread application in fields for alleviating the phytotoxicity of herbicides to crops. Designing new herbicide safeners remains a notable issue in pesticide research. This review focuses on discussing and summarizing the structure-activity relationships, molecular structures, physicochemical properties, and molecular docking of herbicide safeners in order to explore how different structures affect the safener activities of target compounds. It also provides insights into the application prospects of computer-aided drug design for designing and synthesizing new safeners in the future.

Non-coding RNAs and leaf senescence: Small molecules with important roles.

Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.

Spliceosomal protein U2B″ delays leaf senescence by enhancing splicing variant JAZ9ß expression to attenuate jasmonate signaling in Arabidopsis.

The regulatory framework of leaf senescence is gradually becoming clearer; however, the fine regulation of this process remains largely unknown. Here, genetic analysis revealed that U2 small nuclear ribonucleoprotein B (U2B″), a component of the spliceosome, is a negative regulator of leaf senescence. Mutation of U2B″ led to precocious leaf senescence, whereas overexpression of U2B″ extended leaf longevity. Transcriptome analysis revealed that the jasmonic acid (JA) signaling pathway was activated in the u2b″ mutant. U2B″ enhances the generation of splicing variant JASMONATE ZIM-DOMAIN 9ß (JAZ9ß) with an intron retention in the Jas motif, which compromises its interaction with CORONATINE INSENSITIVE1 and thus enhances the stability of JAZ9ß protein. Moreover, JAZ9ß could interact with MYC2 and obstruct its activity, thereby attenuating JA signaling. Correspondingly, overexpression of JAZ9ß rescued the early senescence phenotype of the u2b″ mutant. Furthermore, JA treatment promoted expression of U2B″ that was found to be a direct target of MYC2. Overexpression of MYC2 in the u2b″ mutant resulted in a more pronounced premature senescence than that in wild-type plants. Collectively, our findings reveal that the spliceosomal protein U2B″ fine-tunes leaf senescence by enhancing the expression of JAZ9ß and thereby attenuating JA signaling.

Cross-kingdom analyses of transmembrane protein kinases show their functional diversity and distinct origins in protists.

Transmembrane kinases (TMKs) are important mediators of cellular signaling cascades. The kinase domains of most metazoan and plant TMKs belong to the serine/threonine/tyrosine kinase (S/T/Y-kinase) superfamily. They share a common origin with prokaryotic kinases and have diversified into distinct subfamilies. Diverse members of the eukaryotic crown radiation such as amoebae, ciliates, and red and brown algae (grouped here under the umbrella term "protists") have long diverged from higher eukaryotes since their ancient common ancestry, making them ideal organisms for studying TMK evolution. Here, we developed an accurate and high-throughput pipeline to predict TMKomes in cellular organisms. Cross-kingdom analyses revealed distinct features of TMKomes in each grouping. Two-transmembrane histidine kinases constitute the main TMKomes of bacteria, while metazoans, plants, and most protists have a large proportion of single-pass TM S/T/Y-kinases. Phylogenetic analyses classified most protist S/T/Y-kinases into three clades, with clades II and III specifically expanded in amoebae and oomycetes, respectively. In contrast, clade I kinases were widespread in all protists examined here, and likely shared a common origin with other eukaryotic S/T/Y-kinases. Functional annotation further showed that most non-kinase domains were grouping-specific, suggesting that their recombination with the more conserved kinase domains led to the divergence of S/T/Y-kinases. However, we also found that protist leucine-rich repeat (LRR)- and G-protein-coupled receptor (GPCR)-type TMKs shared similar sensory domain architectures with respective plant and animal TMKs, despite that they belong to distinct kinase subfamilies. Collectively, our study revealed the functional diversity of TMKomes and the distinct origins of S/T/Y-kinases in protists.

A Pythium myriotylum Small Cysteine-Rich Protein Triggers Immune Responses in Diverse Plant Hosts.

The oomycete Pythium myriotylum is a necrotrophic pathogen that infects many crop species worldwide, including ginger, soybean, tomato, and tobacco. Here, we identified a P. myriotylum small cysteine-rich protein, PmSCR1, that induces cell death in Nicotiana benthamiana by screening small, secreted proteins that were induced during infection of ginger and did not have a predicted function at the time of selection. Orthologs of PmSCR1 were found in other Pythium species, but these did not have cell death-inducing activity in N. benthamiana. PmSCR1 encodes a protein containing an auxiliary activity 17 family domain and triggers multiple immune responses in host plants. The elicitor function of PmSCR1 appears to be independent of enzymatic activity, because the heat inactivation of PmSCR1 protein did not affect PmSCR1-induced cell death or other defense responses. The elicitor function of PmSCR1 was also independent of BAK1 and SOBIR1. Furthermore, a small region of the protein, PmSCR186-211, is sufficient for inducing cell death. A pretreatment using the full-length PmSCR1 protein promoted the resistance of soybean and N. benthamiana to Phytophthora sojae and Phytophthora capsici infection, respectively. These results reveal that PmSCR1 is a novel elicitor from P. myriotylum, which exhibits plant immunity-inducing activity in multiple host plants. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Corrigendum to "Epigallocatechin-3-gallate/mineralization precursors co-delivery hollow mesoporous nanosystem for synergistic manipulation of dentin exposure" [Bioact. Mater. 23 (2023) 394-408].

[This corrects the article DOI: 10.1016/j.bioactmat.2022.11.018.].

CD39-Expressing CD8+ T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma.

We aimed to explore the effect of CD39 expression on CD8+ T cells and on the diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). The independent prognostic factors for the surgical specimens of the 95 ESCC patients were screened by multivariate Cox regression analysis. Differential gene expression analysis was performed by the NetworkAnalyst platform based on data from the Gene Expression Omnibus (GEO). The expression of CD39 on CD8+ T cells in the CK+ region was higher in cancer tissue than in paracancerous tissue (p = 0.011), and high CD39-expressing CD8+ T cells in the CK+ region (HR, 2.587; p = 0.033) and high CD39-expressing CD8+ T cells in the CK- region (HR, 3.090; p = 0.008) were independent risk factors for prognosis in ESCC patients; the expression of ENTPD1 was upregulated in ESCC tissues compared to normal tissues (adjusted p < 0.001; log2 fold change = 1.99), and its expression was significantly positively correlated with the expression of PDCD1, CTLA4, and HAVCR2. High CD39-expressing CD8+ T cells can be used as a new molecular marker for the diagnosis and prognosis of ESCC, and the restoration of partially exhausted CD8+ T cells by inhibiting CD39 may be a new strategy for treating ESCC.

Research Progress on the Action Mechanism of Herbicide Safeners: A Review.

Herbicide safeners are agricultural chemicals that protect crops from herbicide injury and improve the safety of herbicides and the effectiveness of weed control. Safeners induce and enhance the tolerance of crops to herbicides through the synergism of multiple mechanisms. The principal mechanism is that the metabolic rate of the herbicide in the crop is accelerated by safeners, resulting in the damaging concentration at the site of action being reduced. We focused on discussing and summarizing the multiple mechanisms of safeners to protect crops in this review. It is also emphasized how safeners alleviate herbicide phytotoxicity to crops by regulating the detoxification process and conducting perspectives on future research on the action mechanism of safeners at the molecular level.

Dental plaque-inspired versatile nanosystem for caries prevention and tooth restoration.

Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque. It remains challenges for current practice to specifically identify, intervene and interrupt the development of caries while restoring defects. In this study, inspired by natural dental plaque, a stimuli-responsive multidrug delivery system (PMs@NaF-SAP) has been developed to prevent tooth decay and promote enamel restoration. Classic spherical core-shell structures of micelles dual-loaded with antibacterial and restorative agents are self-assembled into bacteria-responsive multidrug delivery system based on the pH-cleavable boronate ester bond, followed by conjugation with salivary-acquired peptide (SAP) to endow the nanoparticle with strong adhesion to tooth enamel. The constructed PMs@NaF-SAP specifically adheres to tooth, identifies cariogenic conditions and intelligently releases drugs at acidic pH, thereby providing antibacterial adhesion and cariogenic biofilm resistance, and restoring the microarchitecture and mechanical properties of demineralized teeth. Topical treatment with PMs@NaF-SAP effectively diminishes the onset and severity of caries without impacting oral microbiota diversity or surrounding mucosal tissues. These findings demonstrate this novel nanotherapy has potential as a promising biomedical application for caries prevention and tooth defect restoration while resisting biofilm-associated diseases in a controlled manner activated by pathological bacteria.

Epigallocatechin-3-gallate/mineralization precursors co-delivery hollow mesoporous nanosystem for synergistic manipulation of dentin exposure.

As a global public health focus, oral health plays a vital role in facilitating overall health. Defected teeth characterized by exposure of dentin generally increase the risk of aggravating oral diseases. The exposed dentinal tubules provide channels for irritants and bacterial invasion, leading to dentin hypersensitivity and even pulp inflammation. Cariogenic bacterial adhesion and biofilm formation on dentin are responsible for tooth demineralization and caries. It remains a clinical challenge to achieve the integration of tubule occlusion, collagen mineralization, and antibiofilm functions for managing exposed dentin. To address this issue, an epigallocatechin-3-gallate (EGCG) and poly(allylamine)-stabilized amorphous calcium phosphate (PAH-ACP) co-delivery hollow mesoporous silica (HMS) nanosystem (E/PA@HMS) was herein developed. The application of E/PA@HMS effectively occluded the dentinal tubules with acid- and abrasion-resistant stability and inhibited the biofilm formation of Streptococcus mutans. Intrafibrillar mineralization of collagen fibrils and remineralization of demineralized dentin were induced by E/PA@HMS. The odontogenic differentiation and mineralization of dental pulp cells with high biocompatibility were also promoted. Animal experiments showed that E/PA@HMS durably sealed the tubules and inhibited biofilm growth up to 14 days. Thus, the development of the E/PA@HMS nanosystem provides promising benefits for protecting exposed dentin through the coordinated manipulation of dentin caries and hypersensitivity.

Risk of COVID-19 infection, hospitalization and mortality in psoriasis patients treated with interleukin-17 inhibitors: A systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) have brought great disaster to mankind, and there is currently no globally recognized specific drug or treatment. Severe COVID-19 may trigger a cytokine storm, manifested by increased levels of cytokines including interleukin-17 (IL-17), so a new strategy to treat COVID-19 may be to use existing IL-17 inhibitors, which have demonstrated efficacy, safety and tolerability in the treatment of psoriasis. However, the use of IL-17 inhibitors in patients with psoriasis during the COVID-19 pandemic remains controversial due to reports that IL-17 inhibitors may increase the risk of respiratory tract infections. Objectives: The systematic review and meta-analysis aimed to evaluate the effect of IL-17 inhibitors on the risk of COVID-19 infection, hospitalization, and mortality in patients with psoriasis. Methods: Databases (including Embase, PubMed, SCI-Web of Science, Scopus, CNKI, and the Cochrane Library) were searched up to August 23, 2022, for studies exploring differences in COVID-19 outcomes between psoriasis patients using IL-17 inhibitors and those using non-biologics. Two authors independently extracted data and assessed the risk of bias in a double-blind manner. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and heterogeneities were determined by the Q test and I 2 statistic. And the numbers needed to treat (NNTs) were calculated to assess the clinical value of IL-17 inhibitors in preventing SARS-CoV-2 infection and treating COVID-19. Results: Nine observational studies involving 7,106 participants were included. The pooled effect showed no significant differences in the rates of SARS-CoV-2 infection (P = 0.94; I 2 = 19.5%), COVID-19 hospitalization (P = 0.64; I 2 = 0.0%), and COVID-19 mortality (P = 0.32; I 2 = 0.0%) in psoriasis patients using IL-17 inhibitors compared with using non-biologics. Subgroup analyses grouped by age and COVID-19 cases, respectively, revealed consistent results as above. Meanwhile, the pooled NNTs showed no significant differences between the two groups in the clinical value of preventing SARS-CoV-2 infection and treating COVID-19. Conclusion: The use of IL-17 inhibitors in patients with psoriasis does not increase the risk of SARS-CoV-2 infection or worsen the course of COVID-19. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022335195.

Biomineralization-inspired sandwich dentin desensitization strategy based on multifunctional nanocomposite with yolk-shell structure.

Dentin hypersensitivity (DH) treatment is far from being unequivocal in providing a superior strategy that combines immediate and long-term efficiency of dentinal tubule (DT) occlusion and clinical applicability. In order to achieve this aim, a type of multifunctional yolk-shell nanocomposite with acid resistance, mechanical resistance and biomineralization properties was developed in this study, which consists of a silica/mesoporous titanium-zirconium nanocarrier (STZ) and poly(allylamine hydrochloride) (PAH)-stabilized amorphous calcium phosphate (ACP) liquid precursor. First, the nanocomposite, named as PSTZ, immediately occluded DTs and demonstrated outstanding acid and mechanical resistance. Second, the PSTZ nanocomposite induced intrafibrillar mineralization of single-layer collagen fibrils and remineralization of demineralized dentin matrix. Finally, PSTZ promoted the odontogenic differentiation of dental pulp stem cells by releasing ACP and silicon ions. The reconstruction of the dentin-mimicking hierarchical structure and the introduction of newly formed minerals in the upper, middle and lower segments of DTs, defined as sandwich-like structures, markedly reduced the permeability and achieved superior long-term sealing effects. The nanocomposite material based on mesoporous yolk-shell carriers and liquid-phase mineralized precursors developed in this study represents a versatile biomimetic sandwich desensitization strategy and offers fresh insight into the clinical management of DH.