RESUMO
Chemical transformations that introduce, remove or manipulate functional groups are ubiquitous in synthetic chemistry1. Unlike conventional functional-group interconversion reactions that swap one functionality for another, transformations that alter solely the location of functional groups are far less explored. Here, by photocatalytic, reversible C-H sampling, we report a functional-group translocation reaction of cyano (CN) groups in common nitriles, allowing for the direct positional exchange between a CN group and an unactivated C-H bond. The reaction shows high fidelity for 1,4-CN translocation, frequently contrary to inherent site selectivity in conventional C-H functionalizations. We also report the direct transannular CN translocation of cyclic systems, providing access to valuable structures that are non-trivial to obtain by other methods. Making use of the synthetic versatility of CN and a key CN translocation step, we showcase concise syntheses of building blocks of bioactive molecules. Furthermore, the combination of C-H cyanation and CN translocation allows access to unconventional C-H derivatives. Overall, the reported reaction represents a way to achieve site-selective C-H transformation reactions without requiring a site-selective C-H cleavage step.
RESUMO
Polyploids are common and have a wide geographical distribution and environmental adaptability. Allopolyploidy may lead to the activation of transposable elements (TE). However, the mechanism of epigenetic modification of TEs in the establishment and evolution of allopolyploids remains to be explored. We focused on the TEs of model allopolyploid Brassica napus (An An Cn Cn ), exploring the TE characteristics of the genome, epigenetic modifications of TEs during allopolyploidization, and regulation of gene expression by TE methylation. In B. napus, approximately 50% of the genome was composed of TEs. TEs increased with proximity to genes, especially DNA transposons. TE methylation levels were negatively correlated with gene expression, and changes in TE methylation levels were able to regulate the expression of neighboring genes related to responses to light intensity and stress, which promoted powerful adaptation of allopolyploids to new environments. TEs can be synergistically regulated by RNA-directed DNA methylation pathways and histone modifications. The epigenetic modification levels of TEs tended to be similar to those of the diploid parents during the genome evolution of B. napus. The TEs of the An subgenome were more likely to be modified, and the imbalance in TE number and epigenetic modification level in the An and Cn subgenomes may lead to the establishment of subgenome dominance. Our study analyzed the characteristics of TE location, DNA methylation, siRNA, and histone modification in B. napus and highlighted the importance of TE epigenetic modifications during the allopolyploidy process, providing support for revealing the mechanism of allopolyploid formation and evolution.
Assuntos
Brassica napus , Elementos de DNA Transponíveis , Elementos de DNA Transponíveis/genética , Brassica napus/genética , Brassica napus/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , Epigênese Genética/genética , Metilação de DNA/genética , GenômicaRESUMO
The utilization of rice heterosis is essential for ensuring global food security; however, its molecular mechanism remains unclear. In this study, comprehensive analyses of accessible chromatin regions (ACRs), DNA methylation, and gene expression in inter-subspecific hybrid and its parents were performed to determine the potential role of chromatin accessibility in rice heterosis. The hybrid exhibited abundant ACRs, in which the gene ACRs and proximal ACRs were directly related to transcriptional activation rather than the distal ACRs. Regarding the dynamic accessibility contribution of the parents, paternal ZHF1015 transmitted a greater number of ACRs to the hybrid. Accessible genotype-specific target genes were enriched with overrepresented transcription factors, indicating a unique regulatory network of genes in the hybrid. Compared with its parents, the differentially accessible chromatin regions with upregulated chromatin accessibility were much greater than those with downregulated chromatin accessibility, reflecting a stronger regulation in the hybrid. Furthermore, DNA methylation levels were negatively correlated with ACR intensity, and genes were strongly affected by CHH methylation in the hybrid. Chromatin accessibility positively regulated the overall expression level of each genotype. ACR-related genes with maternal Z04A-bias allele-specific expression tended to be enriched during carotenoid biosynthesis, whereas paternal ZHF1015-bias genes were more active in carbohydrate metabolism. Our findings provide a new perspective on the mechanism of heterosis based on chromatin accessibility in inter-subspecific hybrid rice.
Assuntos
Cromatina , Metilação de DNA , Regulação da Expressão Gênica de Plantas , Vigor Híbrido , Oryza , Oryza/genética , Oryza/metabolismo , Vigor Híbrido/genética , Cromatina/genética , Cromatina/metabolismo , Genoma de Planta/genética , Hibridização Genética , Genótipo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Lipid droplets (LDs) are evolutionarily conserved organelles that serve as hubs of cellular lipid and energy metabolism in virtually all organisms. Mobilization of LDs is important in light-induced stomatal opening. However, whether and how LDs are involved in stomatal development remains unknown. We show here that Arabidopsis thaliana LIPID DROPLETS AND STOMATA 1 (LDS1)/RABC1 (At1g43890) encodes a member of the Rab GTPase family that is involved in regulating LD dynamics and stomatal morphogenesis. The expression of RABC1 is coordinated with the different phases of stomatal development. RABC1 targets to the surface of LDs in response to oleic acid application in a RABC1GEF1-dependent manner. RABC1 physically interacts with SEIPIN2/3, two orthologues of mammalian seipin, which function in the formation of LDs. Disruption of RABC1, RABC1GEF1, or SEIPIN2/3 resulted in aberrantly large LDs, severe defects in guard cell vacuole morphology, and stomatal function. In conclusion, these findings reveal an aspect of LD function and uncover a role for lipid metabolism in stomatal development in plants.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Animais , Arabidopsis/metabolismo , Gotículas Lipídicas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Metabolismo dos Lipídeos/genética , Mamíferos/metabolismoRESUMO
Bismuth-based chalcogenides have emerged as promising candidates for next-generation, solution-processable semiconductors, mainly benefiting from their facile fabrication, low cost, excellent stability, and tunable optoelectronic properties. Particularly, the recently developed AgBiS2 solar cells have shown striking power conversion efficiencies. High performance bismuth-based photodetectors have also been extensively studied in the past few years. However, the fundamental properties of these Bi-based semiconductors have not been sufficiently investigated, which is crucial for further improving the device performance. Here, we introduce multiple time-resolved and steady-state techniques to fully characterize the charge carrier dynamics and charge transport of solution-processed Bi-based nanocrystals. It was found that the Ag-Bi ratio plays a critical role in charge transport. For Ag-deficient samples, silver bismuth sulfide thin films behave as localized state induced hopping charge transport, and the Ag-excess samples present band-like charge transport. This finding is crucial for developing more efficient Bi-based semiconductors and optoelectronic devices.
RESUMO
Steroidal saponins are a class of specialized metabolites essential for plant's response to biotic and abiotic stresses. They are also important raw materials for the industrial production of steroid drugs. Steroidal saponins are present in some monocots, such as Dioscorea and Paris, but their distribution, origin, and evolution in plants remain poorly understood. By reconstructing the evolutionary history of the steroidal saponin-associated module (SSAM) in plants, we reveal that the steroidal saponin pathway has its origin in Asparagus and Dioscorea. Through evaluating the distribution and evolutionary pattern of steroidal saponins in angiosperms, we further show that steroidal saponins originated multiple times in angiosperms, and exist in early diverged lineages of certain monocot lineages including Asparagales, Dioscoreales, and Liliales. In these lineages, steroidal saponins are synthesized through the high copy and/or high expression mechanisms of key genes in SSAM. Together with shifts in gene evolutionary rates and amino acid usage, these molecular mechanisms shape the current distribution and diversity of steroidal saponins in plants. Consequently, our results provide new insights into the distribution, diversity and evolutionary history of steroidal saponins in plants, and enhance our understanding of plants' resistance to abiotic and biotic stresses. Additionally, fundamental understanding of the steroidal saponin biosynthesis will facilitate their industrial production and pharmacological applications.
Assuntos
Plantas , Saponinas , Plantas/metabolismoRESUMO
Plant polyploidization increases the complexity of epigenomes and transcriptional regulation, resulting in genome evolution and enhanced adaptability. However, few studies have been conducted on the relationship between gene expression and epigenetic modification in different plant tissues after allopolyploidization. In this study, we studied gene expression and DNA methylation modification patterns in four tissues (stems, leaves, flowers and siliques) of Brassica napusand its diploid progenitors. On this basis, the alternative splicing patterns and cis-trans regulation patterns of four tissues in B. napus and its diploid progenitors were also analyzed. It can be seen that the number of alternative splicing occurs in the B. napus is higher than that in the diploid progenitors, and the IR type increases the most during allopolyploidy. In addition, we studied the fate changes of duplicated genes after allopolyploidization in B. napus. We found that the fate of most duplicated genes is conserved, but the number of neofunctionalization and specialization is also large. The genetic fate of B. napus was classified according to five replication types (WGD, PD, DSD, TD, TRD). This study also analyzed generational transmission analysis of expression and DNA methylation patterns. Our study provides a reference for the fate differentiation of duplicated genes during allopolyploidization.
Assuntos
Brassica napus , Metilação de DNA , Regulação da Expressão Gênica de Plantas , Poliploidia , Brassica napus/genética , Brassica napus/metabolismo , Genes Duplicados/genética , Genes de Plantas , Processamento Alternativo , Duplicação Gênica , Epigênese GenéticaRESUMO
BACKGROUND: Inter-subspecific hybrid rice represents a significant breakthrough in agricultural genetics, offering higher yields and better resilience to various environmental stresses. While the utilization of these hybrids has shed light on the genetic processes underlying hybridization, understanding the molecular mechanisms driving heterosis remains a complex and ongoing challenge. Here, chromatin immunoprecipitation-sequencing (ChIP-seq) was used to analyze genome-wide profiles of H3K4me3 and H3K27me3 modifications in the inter-subspecific hybrid rice ZY19 and its parents, Z04A and ZHF1015, then combined them with the transcriptome and DNA methylation data to uncover the effects of histone modifications on gene expression and the contribution of epigenetic modifications to heterosis. RESULTS: In the hybrid, there were 8,126 and 1,610 different peaks for H3K4me3 and H3K27me3 modifications when compared to its parents, respectively, with the majority of them originating from the parental lines. The different modifications between the hybrid and its parents were more frequently observed as higher levels in the hybrid than in the parents. In ZY19, there were 476 and 84 allele-specific genes with H3K4me3 and H3K27me3 modifications identified, representing 7.9% and 12% of the total analyzed genes, respectively. Only a small portion of genes that showed differences in parental H3K4me3 and H3K27me3 modifications which demonstrated allele-specific histone modifications (ASHM) in the hybrid. The H3K4me3 modification level in the hybrid was significantly lower compared to the parents. In the hybrid, DNA methylation occurs more frequently among histone modification target genes. Additionally, over 62.58% of differentially expressed genes (DEGs) were affected by epigenetic variations. Notably, there was a strong correlation observed between variations in H3K4me3 modifications and gene expression levels in the hybrid and its parents. CONCLUSION: These findings highlight the substantial impact of histone modifications and DNA methylation on gene expression during hybridization. Epigenetic variations play a crucial role in controlling the differential expression of genes, with potential implications for heterosis.
Assuntos
Código das Histonas , Vigor Híbrido , Hibridização Genética , Oryza , Folhas de Planta , Vigor Híbrido/genética , Oryza/genética , Oryza/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Histonas/metabolismo , Histonas/genética , Epigênese Genética , Metilação de DNA , Regulação da Expressão Gênica de PlantasRESUMO
Lighting accounts for one-fifth of global electricity consumption1. Single materials with efficient and stable white-light emission are ideal for lighting applications, but photon emission covering the entire visible spectrum is difficult to achieve using a single material. Metal halide perovskites have outstanding emission properties2,3; however, the best-performing materials of this type contain lead and have unsatisfactory stability. Here we report a lead-free double perovskite that exhibits efficient and stable white-light emission via self-trapped excitons that originate from the Jahn-Teller distortion of the AgCl6 octahedron in the excited state. By alloying sodium cations into Cs2AgInCl6, we break the dark transition (the inversion-symmetry-induced parity-forbidden transition) by manipulating the parity of the wavefunction of the self-trapped exciton and reduce the electronic dimensionality of the semiconductor4. This leads to an increase in photoluminescence efficiency by three orders of magnitude compared to pure Cs2AgInCl6. The optimally alloyed Cs2(Ag0.60Na0.40)InCl6 with 0.04 per cent bismuth doping emits warm-white light with 86 ± 5 per cent quantum efficiency and works for over 1,000 hours. We anticipate that these results will stimulate research on single-emitter-based white-light-emitting phosphors and diodes for next-generation lighting and display technologies.
RESUMO
In addition to genetic mutations, biomechanical factors also affect the structures and functions of the tumors during tumor growth, including solid stress, interstitial fluid pressure, stiffness, and microarchitecture. Solid stress affects tumors by compressing cancer and stromal cells and deforming blood and lymphatic vessels which reduce supply of oxygen, nutrients and drug delivery, making resistant to treatment. Researchers simulate the stress by creating mechanical models both in vitro and in vivo. Cell models in vitro are divided into two dimensions (2D) and three dimensions (3D). 2D models are simple to operate but exert pressure on apical surface of the cells. 3D models, the multicellular tumor spheres, are more consistent with the actual pathological state in human body. However, the models are more difficult to establish compared with the 2D models. Besides, the procedure of the animal models in vivo is even more complex and tougher to operate. Then, researchers challenged to quantify the solid stress through some measurement methods. We compared the advantages and limitations of these models and methods, which may help to explore new therapeutic targets for normalizing the tumor's physical microenvironment. KEY POINTS: â¢This is the first review to conclude the mechanical models and measurement methods in tumors. â¢The merit and demerit of these models and methods are compared. â¢Insights into further models are discussed.
Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Animais , Fenômenos Biomecânicos , Microambiente Tumoral , Modelos Biológicos , Estresse MecânicoRESUMO
CuOx/C catalysts have been used in the selective catalytic reduction of NOx because of the exceptional low-temperature denitration (de-NOx) activity. A fundamental understanding of the reaction between CuO and C is critical for controlling the component of CuOx/C and thus optimizing the catalytic performance. In this study, a transmission electron microscope equipped with an in situ heating device was utilized to investigate the atomic-scale reaction between CuO and C. We report two reaction mechanisms relying on the volume ratio between C and CuO: (1) The reduction from CuO to Cu2O (when the ratio is <â¯â¼31%); (2) the reduction of CuO into polycrystalline Cu (when the ratio is >â¯â¼34%). The atomistic reduction pathway can be well interpreted by considering the diffusion of O vacancy through the first-principle calculations. The atomic-scale exploration of CuO/C offers ample prospects for the design of industrial de-NOx catalysts in the future.
RESUMO
Gallium oxide (Ga2O3) has attracted extensive attention as a potential candidate for low-dimensional metal-oxide-semiconductor field-effect transistors (MOSFETs) due to its wide bandgap, controllable doping, and low cost. The structural stability of nanoscale Ga2O3 is the key parameter for designing and constructing a MOSFET, which however remains unexplored. Using in situ transmission electron microscopy, we reveal the size-dependent phase transition of sub-2 nm Ga2O3 nanowires. Based on theoretical calculations, the transformation pathways from the initial monoclinic ß-phase to an intermediate cubic γ-phase and then back to the ß-phase have been mapped and identified as a sequence of Ga cation migrations. Our results provide fundamental insights into the Ga2O3 phase stability within the nanoscale, which is crucial for advancing the miniaturization, light weight, and integration of wide-bandgap semiconductor devices.
RESUMO
OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14. METHODS: A child who had presented at the Henan Provincial People's Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c.1609G>A (p.V537M) in exon 17 and c.802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+PP3+PP4). CONCLUSION: The c.1609G>A (p.V537M) and c.802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.
Assuntos
Alopecia , Biologia Computacional , Hipotricose , Humanos , Criança , Feminino , Pré-Escolar , Éxons , GenômicaRESUMO
Small nucleic acid drugs mainly include small interfering RNA(siRNA), antisense oligonucleotide(ASO), microRNA(miRNA), messenger RNA(mRNA), nucleic acid aptamer(aptamer), and so on. Its translation or regulation can be inhibited by binding to the RNA of the target molecule. Due to its strong specificity, persistence, and curability, small nucleic acid drugs have received considerable attention in recent years. Recent studies have shown that some miRNAs from animal and plant sources can stably exist in the blood, tissue, and organs of animals and human beings and exert pharmacological action by regulating the expression of various target proteins. This paper summarized the discovery of small nucleic acids derived from traditional Chinese medicine(TCM) and natural drugs and their cross-border regulatory mechanisms and discussed the technical challenges and regulatory issues brought by this new drug, which can provide new ideas and methods for explaining the complex mechanism of TCM, developing new drugs of small nucleic acids from TCM and natural medicine, and conducting regulatory scientific research.
Assuntos
Descoberta de Drogas , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , MicroRNAs/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/química , Ácidos Nucleicos/químicaRESUMO
Herein we demonstrate an effective and facile end-capping technique for ring-opening metathesis polymerization (ROMP) using readily available allyl compounds as a new type of terminating agents. This new type of end-capping reactions, which are based on the base-promoted decomposition of ruthenocyclobutane intermediates, introduce diene moiety onto the chain end of ROMP polymers while simultaneously deactivating the ruthenium complex. These termination reactions are highly efficient, typically completing within 1 minute at 0 °C with >95 % end-capping fidelity.
RESUMO
Fluorescence sensing is crucial to studying biological processes and diagnosing diseases, especially in the second near-infrared (NIR-II) window with reduced background signals. However, it's still a great challenge to construct "off-on" sensors when the sensing wavelength extends into the NIR-II region to obtain higher imaging contrast, mainly due to the difficult synthesis of spectral overlapped quencher. Here, we present a new fluorescence quenching strategy, which utilizes steric hindrance quencher (SHQ) to tune the molecular packing state of fluorophores and suppress the emission signal. Density functional theory (DFT) calculations further reveal that large SHQs can competitively pack with fluorophores and prevent their self-aggregation. Based on this quenching mechanism, a novel activatable "off-on" sensing method is achieved via bio-analyte responsive invalidation of SHQ, namely the Steric Hindrance Invalidation geNerated Emission (SHINE) strategy. As a proof of concept, the ClO--sensitive SHQ lead to the bright NIR-II signal release in epileptic mouse hippocampus under the skull and high photon scattering brain tissue, providing the real-time visualization of ClO- generation process in living epileptic mice.
Assuntos
Teoria da Densidade Funcional , Epilepsia , Corantes Fluorescentes , Imagem Óptica , Animais , Corantes Fluorescentes/química , Epilepsia/diagnóstico por imagem , Camundongos , Raios Infravermelhos , Hipocampo/diagnóstico por imagem , Estrutura MolecularRESUMO
Ciliogenic components, such as the family of intraflagellar transport (IFT) proteins, are recognized to play key roles in endochondral ossification, a critical process to form most bones. However, the unique functions and roles of each IFT during endochondral ossification remain unclear. Here, we show that IFT20 is required for endochondral ossification in mice. Utilizing osteo-chondrocyte lineage-specific Cre mice (Prx1-Cre and Col2-Cre), we deleted Ift20 to examine its function. Although chondrocyte-specific Ift20 deletion with Col2-Cre mice did not cause any overt skeletal defects, mesoderm-specific Ift20 deletion using Prx1-Cre (Ift20:Prx1-Cre) mice resulted in shortened limb outgrowth. Primary cilia were absent on chondrocytes of Ift20:Prx1-Cre mice, and ciliary-mediated Hedgehog signaling was attenuated in Ift20:Prx1-Cre mice. Interestingly, loss of Ift20 also increased Fgf18 expression in the perichondrium that sustained Sox9 expression, thus preventing endochondral ossification. Inhibition of enhanced phospho-ERK1/2 activation partially rescued defective chondrogenesis in Ift20 mutant cells, supporting an important role for FGF signaling. Our findings demonstrate that IFT20 is a critical regulator of temporospatial FGF signaling that is required for endochondral ossification.
Assuntos
Proteínas de Transporte/genética , Condrogênese/genética , Cílios/genética , Deformidades Congênitas dos Membros/genética , Osteogênese/genética , Animais , Osso e Ossos/embriologia , Cartilagem/embriologia , Diferenciação Celular/genética , Condrócitos/fisiologia , Condrogênese/fisiologia , Proteínas Cromossômicas não Histona/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Camundongos , Camundongos Knockout , Osteogênese/fisiologia , Fatores de Transcrição SOX9/biossíntese , Transdução de Sinais/fisiologiaRESUMO
Modification of commodity aromatic polymers is highly desirable for accessing materials with new properties. The long-standing challenge for such approaches lies in the development of catalytic methods that can functionalize the aromatic polymers with high precision while preserving the molecular weight and distribution of the starting polymers without any alteration. Herein, we report a highly efficient AuCl3-catalyzed site-selective aromatic C-H halogenation of polystyrene. The most important feature of this method is that the degree of halogenation can be precisely controlled by simply changing the loading of the halogenating agent, thus allowing the tuning of functional group density in an accurate and predictable manner. Various functional groups, including NH2 and Bpin, can be installed through effective derivatization of the resultant brominated polystyrene, thus making the method a valuable strategy for the synthesis of value-added materials with tailored properties.
RESUMO
Deformation twinning merits attention because of its intrinsic importance as a mode of energy dissipation in solids. Herein, through the atomistic electron microscopy observations, the size-dependent twinning mechanisms in refractory body-centered cubic molybdenum nanocrystals (NCs) under tensile loading are shown. Two distinct twinning mechanisms involving the nucleation of coherent and inclined twin boundaries (TBs) are uncovered in NCs with smaller (diameter < ≈5 nm) and larger (diameter > ≈5 nm) diameters, respectively. Interestingly, the ultrahigh pseudo-elastic strain of ≈41% in sub-5 nm-sized crystals is achieved through the reversible twinning mechanism. A typical TB cross-transition mechanism is found to accommodate the NC re-orientation during the pseudo-elastic deformation. More importantly, the effects of different types of TBs on the electrical conductivity based on the repeatable experimental measurements and first-principles calculations are quantified. These size-dependent mechanical and electrical properties may prove essential in advancing the design of next-generation flexible nanoelectronics.
RESUMO
Dowling-Degos disease (DDD) is an autosomal dominant hereditary skin disease characterized by acquired reticular hyperpigmentation in flexural sites, and one of its causative genes is KRT5 gene. But the effect of KRT5, expressed only in keratinocytes, on melanocytes is unclear. Other pathogenic genes of DDD include POFUT1, POGLUT1 and PSENEN genes, which is involved in posttranslational modification of Notch receptor. In this study, we aim to determine the ablation of keratinocyte KRT5 affect melanogenesis in melanocyte through Notch signalling pathway. Here we found that KRT5 downregulation decreased the expression of the Notch ligand in keratinocytes and Notch1 intracellular domain in melanocytes, by establishing two cell models of ablation of KRT5 in keratinocytes based on CRISPR/Cas9 site-directed mutation and lentivirus-mediated shRNA. Treatment of melanocytes with Notch inhibitors had same effects with ablation of KRT5 on increase of TYR and decrease of Fascin1. Activation of Notch signalling reverses the effect of ablation of KRT5 on melanogenesis. Immunohistochemistry of DDD lesions with KRT5 gene mutation confirmed changes in the expression of relevant molecules in Notch signalling. Our research elucidates molecular mechanism of KRT5-Notch signalling pathway in the regulation of melanocytes by keratinocytes, and preliminary reveal the mechanism of DDD pigment abnormality caused by KRT5 mutation. These findings identify potential therapeutic targets of the Notch signalling pathway for the treatment of skin pigment disorders.