Effect of repetitive transcranial magnetic stimulation-assisted training on lower limb motor function in children with hemiplegic cerebral palsy.

OBJECTIVE: To explore the effect of repetitive transcranial magnetic stimulation (rTMS)-assisted training on lower limb motor function in children with hemiplegic cerebral palsy (HCP). METHOD: Thirty-one children with HCP who met the inclusion criteria were selected and randomly divided into a control group (n = 16) and an experimental group (n = 15). The control group received routine rehabilitation treatment for 30 min each time, twice a day, 5 days a week for 4 weeks. Based on the control group, the experimental group received rTMS for 20 min each time, once a day, 5 days a week for 4 weeks. The outcome measures included a 10-metre walk test (10MWT), a 6-minute walk distance (6MWD) test, D- and E-zone gross motor function measurements (GMFM), the symmetry ratio of the step length and stance time and the muscle tone of the triceps surae and the hamstrings (evaluated according to the modified Ashworth scale), which were obtained in both groups of children before and after treatment. RESULTS: After training, the 10MWT (P < 0.05), 6MWD (P < 0.01), GMFM (P < 0.001) and the symmetry ratio of the step length and stance time of the two groups were significantly improved (P < 0.05), there was more of an improvement in the experimental group compared with the control group. There was no significant change in the muscle tone of the hamstrings between the two groups before and after treatment (P > 0.05). After treatment, the muscle tone of the triceps surae in the experimental group was significantly reduced (P < 0.05), but there was no significant change in the control group (P > 0.05). CONCLUSION: Repetitive TMS-assisted training can improve lower limb motor function in children with HCP.

Coupling dynamics of locally active memristor based neurons.

Brain-like dynamics require third-order or higher-order complexity. In order to investigate the coupling neuromorphic behaviors of identical third-order memristive neurons, this paper begins with the aim of exploring two identical neuron based dynamics under distinct operating regimes and coupling strengths. Without coupling, the single neuron can exhibit resting states, periodic spikes, or chaos depending on the bias condition. The uncoupled resting neurons can be activated by resistive coupling, inducing inhomogeneous resting states (static Smale paradox) and inhomogeneous spikes (dynamic Smale paradox) due to the edge of chaos regime. Considering the single neuron at the periodic spikes or chaotic states, the coupled neurons can mimic shocking oscillation death, non-periodic asynchronization, and periodic synchronization via the Hopf bifurcation theory. From the above analyses, an artificial ring neural network is constructed using 100 memristive neurons and resistive synapses to further study the coupled mechanism, generating exotic spatiotemporal patterns such as chimera death, amplitude chimera, solitary states, and asynchronization because of symmetry breaking. This sheds new light on exploring exotic spatiotemporal patterns of networks based on memristive neurons from the perspective of the nonlinear circuit theory.

Development of a Pathomics-Based Model for the Prediction of Malignant Transformation in Oral Leukoplakia.

Accurate prognostic stratification of oral leukoplakia (OLK) with risk of malignant transformation into oral squamous cell carcinoma is crucial. We developed an objective and powerful pathomics-based model for the prediction of malignant transformation in OLK using hematoxylin and eosin (H&E)-stained images. In total, 759 H&E-stained images from multicenter cohorts were included. A training set (n = 489), validation set (n = 196), and testing set (n = 74) were used for model development. Four deep learning methods were used to train and validate the model constructed using H&E-stained images. Pathomics features generated through deep learning combined with machine learning algorithms were used to develop a pathomics-based model. Immunohistochemical staining of Ki67, p53, and PD-L1 was used to interpret the black box of the model. Pathomics-based models predicted the malignant transformation of OLK (validation set area under curve [AUC], 0.899; testing set AUC, 0.813) and significantly identified high-risk and low-risk populations. The prediction performance of malignant transformation from dysplasia grading (validation set AUC, 0.743) was lower than that of the pathomics-based model. The expressions of Ki67, p53, and PD-L1 were correlated with various pathomics features. The pathomics-based model accurately predicted the malignant transformation of OLK and may be useful for the objective and rapid assessment of the prognosis of patients with OLK.

Nanosheet-hydrogel composites: from preparation and fundamental properties to their promising applications.

Hydrogels are an important class of soft materials with elastic and intelligent properties. Nevertheless, these traditional hydrogels usually possess poor mechanical properties and limited functions, which greatly restrict their further applications. With the rapid development of nanotechnology, there have been significant advances in the design and fabrication of functional nanocomposite hydrogels with unique properties and functions. Among various materials, nanosheets with planar topography, large specific surface areas, and versatile physicochemical properties have attracted intense research interest. Herein, this review summarises the synthesis mechanisms, fundamental properties, and promising applications of nanosheet-incorporated hydrogels. In particular, how the nanosheet structure is applied to improve the overall performance of the hydrogel in each application is emphasized. Additionally, the current challenges and prospects are briefly discussed in this area. We expect that the combination of nanosheets and hydrogels can attract more researchers' interest and bring new opportunities in the future.

Mapping developmental paths of monkey primordial germ-like cells differentiation from pluripotent stem cells by single cell ribonucleic acid sequencing analysis†.

The induction of primordial germ-like cells (PGCLCs) from pluripotent stem cells (PSCs) provides a powerful system to study the cellular and molecular mechanisms underlying germline specification, which are difficult to study in vivo. The studies reveal the existence of a species-specific mechanism underlying PGCLCs between humans and mice, highlighting the necessity to study regulatory networks in more species, especially in primates. Harnessing the power of single-cell RNA sequencing (scRNA-seq) analysis, the detailed trajectory of human PGCLCs specification in vitro has been achieved. However, the study of nonhuman primates is still needed. Here, we applied an embryoid body (EB) differentiation system to induce PGCLCs specification from cynomolgus monkey male and female PSCs, and then performed high throughput scRNA-seq analysis of approximately 40 000 PSCs and cells within EBs. We found that EBs provided a niche for PGCLCs differentiation by secreting growth factors critical for PGCLC specification, such as bone morphogenetic protein 2 (BMP2), BMP4, and Wnt Family Member 3. Moreover, the developmental trajectory of PGCLCs was reconstituted, and gene expression dynamics were revealed. Our study outlines the roadmap of PGCLC specification from PSCs and provides insights that will improve the differentiation efficiency of PGCLCs from PSCs.

Recent advances in multi-mechanism design of crack-resistant hydrogels.

For conventional hydrogels, the phenomenon of crack generation and propagation caused by high-stress concentration is ubiquitous. However, this phenomenon is unfavorable in many applications, such as wearable electronics, tissue engineering, and tunable adhesion. Fortunately, many hydrogels that can suppress crack growth during deformation and maintain the original mechanical properties during deformation, called crack-resistant hydrogels, have been published. Herein, the state-of-the-art of crack-resistant hydrogels is comprehensively reviewed. Starting from the principle of designing a crack-resistant hydrogel, we first survey the relevant crack-resistant strategies. The latest crack-resistant hydrogels are then categorized according to their crack-resistant mechanisms (including energy dissipation at the molecular level, multiscale structure, crack pinning, crack deflection, and sliding of chain), and their crack-resistant processes are described in detail. Furthermore, we summarize the current challenges and make an outlook for crack-resistant hydrogels, which might lead to substantial progress in the future design and development of these high-performance materials.

Quantitative proteomics reveals stage-specific protein regulation of triple negative breast cancer.

BACKGROUNDS: Triple negative breast cancer (TNBC) is a heterogeneous disease with more aggressive clinical courses than other subtypes of breast cancer. In this study, we performed high-resolution mass spectrometry-based quantitative proteomics with TNBC clinical tissue specimens to explore the early and sensitive diagnostic signatures and potential therapeutic targets for TNBC patients. METHODS: We performed an iTRAQ labeling coupled LC-MS/MS approach to explore the global proteome in tumor tissues and corresponding para-tumor tissues from 24 patients with grade I-II and grade III primary TNBC. Relative peptide quantification and protein identification were performed by Proteome Discoverer™ software with Mascot search engine. Differentially expressed proteins were analyzed by bioinformatic analyses, including GO function classification annotation and KEGG enrichment analysis. Pathway analyses for protein-protein interactions and upstream regulations of differentially expressed candidates were performed by Ingenuity Pathway Analysis (IPA) software. RESULTS: Totally, 5401 unique proteins were identified and quantified in different stage of TNBCs. 845 proteins were changed in patients with grade I or II TNBC, among which 304 were up-regulated and 541 were down-regulated. Meanwhile, for patients with grade III TNBC, 358 proteins were increased and 651 proteins were decreased. Comparing to para-cancerous tissues, various signaling pathways and metabolic processes, including PPAR pathways, PI3K-Akt pathway, one-carbon metabolism, amino acid synthesis, and lipid metabolism were activated in TNBC cancer tissues. Death receptor signaling was significantly activated in grade I-II TNBCs, however, remarkably inhibited in grade III TNBCs. Western blot experiments were conducted to validate expression levels of CYCS, HMGA1 and XIAP with samples from individual patients. CONCLUSIONS: Overall, our proteomic data presented precise quantification of potential signatures, signaling pathways, regulatory networks, and characteristic differences in each clinicopathological subgroup. The proteome provides complementary information for TNBC accurate subtype classification and therapeutic targets research.

Putting the glass down may keep the stroke away: Results from a prospective cohort study in rural China.

BACKGROUND AND AIMS: Most studies assess the relationship between alcohol and stroke at some point. Little is known about the effect on stroke of drinking status changes over time. This study aimed to examine the association of median 2.4-year drinking status changes with risk of stroke. METHODS AND RESULTS: We examined 22,691 adults from rural China. Drinking status was assessed at 2004-2006 and in 2008. Participants were divided into four change patterns: consistent non-drinkers, abstainers, starters, and consistent drinkers. A Cox proportional hazards model were performed. We observed 1215 cases of stroke during a median follow-up period of 11.8 years. A faint J-shaped association between alcohol consumption and risk of stroke was found in this population. Based on the amount of alcohol consumption, only current drinkers with ≥721 g/week at baseline in both males and females had a higher risk of stroke [hazard ratio (HR): 1.342; 95% confidence interval (CI): 1.070-1.683 and HR: 2.130; CI: 1.041-4.357, respectively]. Based on change patterns, Compared with consistent non-drinkers, the HR (95% CI) for consistent drinkers, abstainers and starters was 1.298 (1.070-1.576), 1.093 (0.877-1.362) and 1.263 (1.034-1.543), respectively. The same trend was observed in male. The HR (95% CI) for consistent drinkers, abstainers and starters was 1.360 (1.098-1.685), 1.139 (0.883-1.470) and 1.364 (1.092-1.703), respectively. No difference was observed in females. CONCLUSION: High alcohol consumption was associated with increased risk of stroke in both males and females. However, based on change patterns, consistent drinkers and starters were at higher risk of stroke only in males.

Association of general and abdominal obesity and their changes with stroke in Chinese adults: Results from an 11.8-year follow-up study.

BACKGROUND AND AIMS: Obesity-related diseases play a significant role in the epidemiology of stroke; however, the exact effects of obesity and transitions in obesity status on stroke risk are still unclear. This study was performed to investigate the association of general and abdominal obesity and their changes with stroke in Chinese adults. METHODS AND RESULTS: A total of 26,815 subjects (13,684 men and 13,131 women) aged ≥35 years participated in the study. The association of general and abdominal obesity and their changes with stroke was estimated by Cox proportional hazards models. During a median follow-up period of 11.8 years, 1507 people developed an incident stroke event. The multivariable-adjusted hazard ratios (HRs) (95% CIs) for stroke comparing the highest vs. lowest quartiles of these measurements were 1.276 (1.068-1.524) for BMI, 1.245 (1.035-1.499) for WC, 0.940 (0.786-1.125) for WHR, and 1.221 (1.019-1.464) for WHtR in men. For women, the corresponding values were 1.368 (1.089-1.718), 1.424 (1.119-1.813), 0.971 (0.765-1.232), and 1.341 (1.059-1.699), respectively. C- statistics showed no difference in the predictive value for stroke among various measures of adiposity. Compared with participants who maintained a normal BMI, the HRs for reversed general obesity was 1.272 (95% CI: 1.044-1.550) among men and 1.240 (95% CI: 0.948-1.623) among women. CONCLUSION: Increasing levels of general or abdominal adiposity consistently predict increased risk of stroke, and maintenance of a normal BMI or WC may aid in stroke prevention.

Anisotropic infrared plasmonic broadband absorber based on graphene-black phosphorus multilayers.

Two-dimensional materials (2DMs) such as graphene and black phosphorus (BP) have aroused considerable attentions in the past few years. Engineering and enhancing their light-matter interaction is possible due to their support for localized surface plasmon resonances in the infrared regime. In this paper, we have proposed an infrared broadband absorber consisting of multilayer graphene-BP nanoparticles sandwiched between dielectric layers. Benefiting from the properties of graphene and BP, the absorber exhibits both perfect broadband responses and strong anisotropy beyond individual graphene and BP layers. The absorber is tunable with the variation of geometric parameters as well as the doping levels of graphene and BP. The physical insight is revealed by electric field distributions. Furthermore, the angular robustness for incident wave is investigated. The proposed anisotropic omnidirectional broadband absorber may have promising potential applications in various biosensing, communication and imaging systems.

Temporal relationship between body mass index and triglyceride-glucose index and its impact on the incident of hypertension.

BACKGROUND AND AIMS: Obesity and insulin levels can influence each other by metabolism. However, their temporal sequences and influence on hypertension are generally unknown, especially in Chinese adults. Recently, some scholars have proposed that triglycerides-glucose index (TyG) is an important indicator of insulin resistance. The study aims to describe the relationship between body mass index (BMI) and TyG index and its impact on hypertension. METHODS AND RESULTS: A total of 4081 adults (56.33% women) without antihypertensive, hypoglycemic or lipid-lowering medications were selected for the present study. Measurements of BMI and TyG index were obtained twice from 2012 to 2017. Cross-lagged panel analysis was used to describe the temporal sequences between BMI and TyG index, and the effect of their temporal relationship patterns on hypertension was explored through mediation analysis. After adjusting for confounding factors (age, sex, ethnicity et al.), the cross-lagged path coefficient from baseline BMI to follow-up TyG (ρ2 = 0.135, P < 0.001) was significantly greater than the path coefficient from baseline TyG to follow-up BMI (ρ1 = 0.043, P < 0.001), and P < 0.001 for the difference between ρ1 and ρ2. Furthermore, the sensitivity analyses between women and men revealed identical findings. In addition, TyG index mediation effect on BMI-hypertension was estimated to be 38.45% (P < 0.001) in total population, 25.24% in women and 57.35% in men. CONCLUSION: These results provided evidence that the temporal relationship between BMI and insulin resistance is reciprocal and a higher BMI precedes hyperinsulinemia in Chinese adults. This relationship plays an essential role in the development of hypertension, while there is a difference between women and men.

Sex difference in the incidence of stroke and its corresponding influence factors: results from a follow-up 8.4 years of rural China hypertensive prospective cohort study.

BACKGROUND: Few studies investigate sex difference in stroke incidence in rural China hypertensive population. METHODS: A total of 5097 hypertensive patients aged ≥35 years (mean age, 56.3 ± 11.2 years; 43.8% men) were included in our analysis with a median follow-up 8.4 years in Fuxin county of Liaoning province in China. Cox proportional hazard models were used to analyze the association between the potential factors and incident stroke. RESULTS: We observed 501 new strokes (310 ischemic, 186 hemorrhagic, and 5 unclassified stroke) during the follow-up. The overall incidence of stroke was 1235.21 per 100,000 person-years; for men, the rates were 1652.51 and 920.80 for women. This sex difference in all stroke can be explained by approximately 25% through age, systolic blood pressure, body mass index, low-density lipoprotein-cholesterol, current smoking, current drinking, antihypertensive drugs, education and physical activity. Subgroup analysis indicated that in hemorrhagic stroke this sex difference was more remarkable (63.89% can be explained). CONCLUSIONS: The incidence of stroke was higher in men than that in women and this difference was partly explained by several traditional cardiovascular risk factors.

Potential Application of Electrical Stimulation in Stem Cell-Based Treatment against Hearing Loss.

Deafness is a common human disease, which is mainly caused by irreversible damage to hair cells and spiral ganglion neurons (SGNs) in the mammalian cochlea. At present, replacement of damaged or missing hair cells and SGNs by stem cell transplantation therapy is an effective treatment. However, the survival rate of stem cell transplantation is low, with uncontrollable differentiation hindering its application. Most researchers have focused on biochemical factors to regulate the growth and differentiation of stem cells, whereas little study has been performed using physical factors. This review intends to illustrate the current problems in stem cell-based treatment against deafness and to introduce electric field stimulation as a physical factor to regulate stem cell behavior and facilitate stem cell therapy to treat hearing loss in the future.

Phosphate stable oxygen isotope variability within a temperate agricultural soil.

In this study, we conduct a spatial analysis of soil total phosphorus (TP), acid extractable phosphate (PO4) and the stable oxygen (O) isotope ratio within the PO4 molecule (δ18OPO4 ) from an intensively managed agricultural grassland site. Total P in the soil was found to range from 736 to 1952 mg P kg- 1, of which between 12 and 48% was extractable using a 1 M HCl (HClPO4 ) solution with the two variables exhibiting a strong positive correlation. The δ18OPO4 of the extracted PO4 ranged from 17.0 to 21.6‰ with a mean of 18.8‰ (± 0.8). While the spatial variability of Total P has been researched at various scales, this is the first study to assess the variability of soil δ18OPO4 at a field-scale resolution. We investigate whether or not δ18OPO4 variability has any significant relationship with: (i) itself with respect to spatial autocorrelation effects; and (ii) HClPO4 , elevation and slope - both globally and locally. Results indicate that δ18OPO4 was not spatially autocorrelated; and that δ18OPO4 was only weakly related to HClPO4 , elevation and slope, when considering the study field as a whole. Interestingly, the latter relationships appear to vary in strength locally. In particular, the δ18OPO4 to HClPO4 relationship may depend on the underlying soil class and/or on different field managements that had operated across an historical north-south field division of the study field, a division that had been removed four years prior to this study.

Evolutionary and expression analysis of a MADS-box gene superfamily involved in ovule development of seeded and seedless grapevines.

MADS-box transcription factors are involved in many aspects of plant growth and development, such as floral organ determination, fruit ripening, and embryonic development. Yet not much is known about grape (Vitis vinifera) MADS-box genes in a relatively comprehensive genomic and functional way during ovule development. Accordingly, we identified 54 grape MADS-box genes, aiming to enhance our understanding of grape MADS-box genes from both evolutionary and functional perspectives. Synteny analysis indicated that both segmental and tandem duplication events contributed to the expansion of the grape MADS-box family. Furthermore, synteny analysis between the grape and Arabidopsis genomes suggested that several grape MADS-box genes arose before divergence of the two species. Phylogenetic analysis and comparisons of exon-intron structures provided further insight into the evolutionary relationships between the genes, as well as their putative functions. Based on phylogenetic tree analysis, grape MADS-box genes were divided into type I and type II subgroups. Tissue-specific expression analysis suggested roles in both vegetative and reproductive tissue development. Expression analysis of the MADS-box genes following gibberellic acid (GA3) treatment revealed their response to GA3 treatment and that seedlessness caused by GA3 treatment underwent a different mechanism from that of normal ovule abortion. Expression profiling of MADS-box genes from six cultivars suggests their function in ovule development and may represent potential ovule identity genes involved in parthenocarpy. The results presented provide a few candidate genes involved in ovule development for future study, which may be useful in seedlessness-related molecular breeding programs.

Evolution and expression analysis of the grape (Vitis vinifera L.) WRKY gene family.

WRKY proteins comprise a large family of transcription factors that play important roles in plant defence regulatory networks, including responses to various biotic and abiotic stresses. To date, no large-scale study of WRKY genes has been undertaken in grape (Vitis vinifera L.). In this study, a total of 59 putative grape WRKY genes (VvWRKY) were identified and renamed on the basis of their respective chromosome distribution. A multiple sequence alignment analysis using all predicted grape WRKY genes coding sequences, together with those from Arabidopsis thaliana and tomato (Solanum lycopersicum), indicated that the 59 VvWRKY genes can be classified into three main groups (I-III). An evaluation of the duplication events suggested that several WRKY genes arose before the divergence of the grape and Arabidopsis lineages. Moreover, expression profiles derived from semiquantitative PCR and real-time quantitative PCR analyses showed distinct expression patterns in various tissues and in response to different treatments. Four VvWRKY genes showed a significantly higher expression in roots or leaves, 55 responded to varying degrees to at least one abiotic stress treatment, and the expression of 38 were altered following powdery mildew (Erysiphe necator) infection. Most VvWRKY genes were downregulated in response to abscisic acid or salicylic acid treatments, while the expression of a subset was upregulated by methyl jasmonate or ethylene treatments.

Aqueous phototransformation of bisphenol S: the competitive radical-attack pathway to p-hydroxybenzenesulfonic acid.

The kinetics, environmental influencing factors, products and reaction mechanism of aqueous phototransformation of bisphenol S (BPS), as an alternative to bisphenol A, which is of environmental concern, were investigated. p-Hydroxybenzenesulfonic acid, as the major transformation product was confirmed by gas chromatography - mass spectrometry, electrospray ionization, ¹H nuclear magnetic resonance and fluorescence spectrum analysis. A reaction pathway was proposed based on the reactive oxygen species related results by electron paramagnetic resonance and radical traps. The competition of the excited state of BPS between transferring electron to O2 to •O2(-) and directly oxidizing H2O to •OH was revealed.

Joint optimization of headway and number of stops for bilateral bus rapid transit.

The bilateral Bus Rapid Transit (BRT) system is a kind of BRT system in which the stops are located in the middle of the transit lane. By simultaneously serving transit lines in opposite directions, it is particularly designed to save space resources and enhance service quality. To improve the operational efficiency of the bilateral BRT, this paper optimizes the operational performance of bilateral BRT with elastic demand. The objective is to minimize the generalized time cost per passenger of the system by jointly optimizing the headway and number of stops of bilateral BRT. The cost includes the agency operating and user travel. The optimal design model is formulated as a mixed-integer program and solved using a fuzzy analytic hierarchy process (FAHP) and a genetic algorithm (GA). We conduct a case study and sensitivity analysis to show the effectiveness and reliability of the proposed approach. We conclude that the optimized minimum generalized cost per passenger is lower than the actual case for all demand levels, especially at off-peak hours, by about 22.5%. In addition, we find that the weights of agency and user costs have the most significant impact on headway, whereas the influence of walking, vehicle speed, and route length is minimal. In contrast, the optimal number of BRT stops is mostly influenced by the route length, and walking speed has essentially no effect on the optimal number of stops. Finally, we find that the generalized cost per passenger at peak hours is 10% to 15% smaller than at off-peak hours in various scenarios.

Development of Rules and Algorithms for an Intelligent and Integrated Older Care Model.

To break through the current bottleneck in home-based older care globally, we developed an intelligent and integrated older care model (SMART model) to facilitate integrated care for home-dwelling older people. As a knowledge-based clinical decision support system, the SMART model relies on rules and algorithms to ensure its transparent and well-supported decision-making process with clear rationales. Therefore, we conducted a mixed study combining qualitative research, literature review of the latest literature and guidelines, and expert consultation. Following the intervention mapping framework and nursing process, we determined 138 care problems along with their diagnostic criteria and care goals. Building upon this, we curated 450 evidence-informed methods, each accompanied by at least one implementation approach. Two sets of IF-THEN rules and algorithms including diagnostic rules and method trigger rules were employed to trigger appropriate care problems and customized methods and implementation approaches.

Cucurbitacin B induces ferroptosis in oral leukoplakia via the SLC7A11/mitochondrial oxidative stress pathway.

BACKGROUND: Oral leukoplakia (OLK), characterized by abnormal epithelial hyperplasia, is the most common precancerous oral mucosa lesion and is closely related to oxidative stress. Cucurbitacin B (CuB), a tetracyclic triterpenoid molecule derived from plants, has shown promising anti-proliferative and antioxidant effects in preclinical studies. However, whether CuB can play an antiproliferative role in OLK by regulating oxidative stress remains elusive. PURPOSE: To investigate the role of CuB in inhibiting the malignant progression of oral leukoplakia and to further explore its underlying mechanisms of action. METHODS: In vitro, the effect of CuB on the proliferation, migration, apoptosis, and cell cycle of OLK cells DOK was detected. The core genes and key pathways of OLK and CuB were analyzed in the transcriptome database, by using immunofluorescence, qRT-PCR, and Western blot to evaluate the expression levels of the ferroptosis markers ROS, GSH, MDA, Fe2+, and marker genes SLC7A11, GPX4, and FTH1. Immunohistochemistry of human tissue was performed to investigate the expression of the SLC7A11. In vivo, the model of OLK was established in C57BL/6 mice and the biosafety of CuB treatment for OLK was further evaluated. RESULTS: CuB substantially suppressed the proliferation of DOK cells. Bioinformatics analysis showed that the core targets of OLK crossing with CuB include SLC7A11 and that the essential pathways involve ROS and ferroptosis. In vitro experiments indicated that CuB might promote ferroptosis by down-regulating the expression of SLC7A11. We observed a gradual increase in SLC7A11 expression levels during the progression from normal oral mucosa to oral leukoplakia with varying degrees of epithelial dysplasia. In vivo experiments demonstrated that CuB inhibited the malignant progression of OLK by promoting ferroptosis in OLK mice and exhibited a certain level of biosafety. CONCLUSION: This study demonstrated for the first time that CuB could effectively inhibit the malignant progression of OLK by inducing ferroptosis via activating the SLC7A11/ mitochondrial oxidative stress pathway. These findings indicate that CuB could serve as the lead compound for the future development of anti-oral leukoplakia drugs.