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Abstract Background Failure to restore missing teeth in time can easily lead to the mesial tilting of the distal abutment teeth. However, a fixed partial denture (FPD) can improve stress conduction and distribution and prevent periodontal injuries. In these more complex cases, it is necessary to consider various factors comprehensively to improve conventional treatment planning and achieve better results. Methods We selected a patient with a missing first molar and a mesial inclination of the second molar, leaving inadequate space or bone mass for implant denture restoration, necessitating an FPD for restoration. Three-dimensional finite element analysis (3D-FEA) combined with photoelastic analysis were used to explore how the inclination angle (0 ‒ 30°) and different dental restoration materials (zirconia, lithium disilicate, polymer-infiltrated ceramic network, and resin composite) affect the biomechanical behaviour of FPD‒abutments‒periodontal tissue complex. Results The stress was easily concentrated in the FPD connectors, enamel shoulder collar, periapical area, and root bifurcation. The stress on FPD and the periodontal ligament (PDL) of the second premolar increased with an increase in the elastic modulus of FPD, with an opposite trend in the abutments, the alveolar bone, and the PDL of the second molar. The stress on the FPD and alveolar bone increased with increased inclination angle of the distal abutment. The stress on two abutments and their PDL were positively correlated with the inclination angle in two stages; however, when the inclination angle > 12°, the second premolar and its PDL showed a negative correlation. Conclusions FPDs can be used for restoration within 24° of distal abutment inclination, but protecting the abutments ( 12° especially) must be taken seriously. For this purpose, an FPD material with higher strength is recommended.

Abstract Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC.

Abstract Sleep disturbances profoundly affect the quality of life in individuals with neurological disorders. Closed-loop deep brain stimulation (DBS) holds promise for alleviating sleep symptoms, however, this technique necessitates automated sleep stage decoding from intracranial signals. We leveraged overnight data from 121 patients with movement disorders (Parkinson’s disease, Essential Tremor, Dystonia, Essential Tremor, Huntington’s disease, and Tourette’s syndrome) in whom synchronized polysomnograms and basal ganglia local field potentials were recorded, to develop a generalized, multi-class, sleep specific decoder – BGOOSE. This generalized model achieved 85% average accuracy across patients and across disease conditions, even in the presence of recordings from different basal ganglia targets. Furthermore, we also investigated the role of electrocorticography on decoding performances and proposed an optimal decoding map, which was shown to facilitate channel selection for optimal model performances. BGOOSE emerges as a powerful tool for generalized sleep decoding, offering exciting potentials for the precision stimulation delivery of DBS and better management of sleep disturbances in movement disorders.

In recent years, the application of deep learning in remote-sensing (RS) image change detection (CD) has been deepening, especially in the challenges faced in lightweight model design, that is, how to effectively balance model complexity and detection accuracy. Although some simplified models have achieved compression in existing research, there are shortcomings in maintaining detailed information and improving detection performance. On the other hand, large network architectures limit their actual deployment in resource-limited environments. This article innovatively proposes a lightweight CD network called Multilevel Feature Cross-Fusing Network (MFCF-Net) to address this issue. MFCF-Net uses a lightweight convolutional neural network for feature extraction and introduces the adjacent layer enhancement module in the feature extraction stage to significantly enhance the network's ability to extract high-dimensional features while only moderately increasing parameters. Furthermore, MFCF-Net integrates dense skip connections and cross-attention mechanisms in the decoder to efficiently propagate contextual information and accurately capture and fuse global spatial features, especially for detecting small changes. Experimental results show that on four public RS CD datasets, MFCF-Net achieves excellent detection performance and has a smaller model size (with parameters as low as 1.35M). Particularly on the WHU-CD dataset, compared with the current state-of-the-art method, MFCF-Net achieves significant improvements, with an F1-score increase in 1.4% and an intersection-over-union improvement of 2.45%.

Since 2004, the flourishing two-dimensional graphene has sparked extensive research on graphene-based optical and optoelectronic devices with high performance due to its ultra-fast photoelectric response, broadband, and tunable optical response. However, up until now, graphene-based wire grid polarizers have not been demonstrated to perform excellent characteristics with flat polarization extinction ratio (PER) curves, while they all exhibited narrow peak-shaped working bands. Here, we propose a broadband polarizer based on graphene wire grids with a flat PER curve of up to ∼84.5 dB in the ultrawide range of 1–10 μm. In the range of

Abstract Parkinson’s disease (PD) is associated with excessive beta activity in the basal ganglia. Brain sensing implants aim to leverage this biomarker for demand-dependent adaptive stimulation. Sleep disturbance is among the most common non-motor symptoms in PD, but its relationship with beta activity is unknown. To investigate the clinical potential of beta activity as a biomarker for sleep quality in PD, we recorded pallidal local field potentials during polysomnography in PD patients off dopaminergic medication and compared the results to dystonia patients. PD patients exhibited sustained and elevated beta activity across wakefulness, rapid eye movement (REM), and non-REM sleep, which was correlated with sleep disturbance. Simulation of adaptive stimulation revealed that sleep-related beta activity changes remain unaccounted for by current algorithms, with potential negative outcomes in sleep quality and overall quality of life for patients.

Abstract As a major source of air pollution, particulate matter (PM) and associated toxic trace elements pose potentially serious threats to human health and environmental safety. As is known that plants can reduce air PM pollution. However, the relationship between PM of different sizes and toxic trace elements in foliar PM is still unclear. This study was performed to explore the association between PM of different sizes (PM2.5, PM10, PM>10) and toxic trace elements (As, Al, Cu, Zn, Cd, Fe, Pb) as well as the correlation among toxic trace elements of six roadside plant species (Cinnamomum camphora, Osmanthus fragrans, Magnolia grandiflora, Podocarpus macrophyllus, Loropetalum chinense var. rubrum and Pittosporum tobira) in Changsha, Hunan Province, China. Results showed that P. macrophyllus had the highest ability to retain PM, and C. camphora excelled in retaining PM2.5. The combination of P. macrophyllus and C. camphora was highly recommended to be planted in the subtropical city to effectively reduce PM. The toxic trace elements accumulated in foliar PM varied with plant species and PM size. Two-way ANOVA showed that most of the toxic trace elements were significantly influenced by plant species, PM size, and their interactions (P

Soil and water loss represent a significant environmental challenge in purple soil cropland in China. However, the quantity and mechanism of nutrient loss from purple soil remain unclear. To understand water and soil conservation and address nitrogen (N) and phosphorus (P) mitigation in Camellia oleifera forest stands on purple soil slope farmland, this study aimed to explore the resistance control effect of forest stands on N and P loss in such agricultural landscapes. In the study, a runoff plot experiment was conducted in purple soil slope farmland. The experiment included three distinct treatments: intercropping of oil tea (Camellia oleifera) and ryegrass (Lolium perenne L.), Camellia oleifera monoculture, and barren land served as the control treatment (CK). Water samples were collected and analyzed from the soil surface runoff and the middle soil layer at a depth of 20 cm (interflow) in three treatment plots under natural rainfall conditions in 2023. Various nutrient components, including total nitrogen (TN), dissolved nitrogen (DN), nitrate nitrogen (NO3−-N), ammonium nitrogen (NH4+-N), particulate nitrogen (PN), total phosphorus (TP), dissolved phosphorus (DP), phosphate (PO4+-P), and particulate phosphorus (PP), were measured in the water samples. The results indicated that intercropping effectively mitigated the loss of various forms of N and P in both surface runoff and interflow within purple soil slope farmland. Compared to the CK, the ryegrass intercropping reduced TN and TP loss by 29.3%–37.3% and 25.7%–38.9%, respectively. The ryegrass intercropping led to a decrease in the average total loss of TN, DN, NO3—N, and NH4+-N by 63.0, 24.3, 4.5, and 6.8 g/ha, corresponding to reductions of 33.3%, 47.6%, 58.3%, and 49.1%, respectively, compared to the CK. The average total loss of TP, DP, and PP decreased by 4.4, 1.8, and 1.4 g/hm2 in the intercropping, reflecting reductions of 32.3%, 31.3%, and 31.1%, respectively. The most significant proportion was observed in PN and PP within the runoff water solution, accounting for 53.3%–74.8% and 56.9%–61.0% of the TN and TP, respectively. These findings establish a foundation for purple soil and water conservation. The research provides valuable insights for land management and policymakers in developing erosion prevention and control programs for sloping cultivated land with Camellia oleifera forests in purple soils. Additionally, it offers guidance for soil and water conservation and prevention of surface source pollution in purple soil regions.

Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, reperfusion after an ischemic insult and sudden oxygen exposure lead to the exacerbated synthesis of additional reactive oxidative species and the persistence of increased oxidation levels. Attempts based on antioxidant treatment have failed to achieve an effective therapy for cardiovascular disease patients. The controversial use of vitamin C as an antioxidant in clinical practice is comprehensively systematized and discussed in this review. The dose-dependent adsorption and release kinetics mechanism of vitamin C is complex; however, this review may provide a holistic perspective on its potential as a preventive supplement and/or for combined precise and targeted therapeutics in cardiovascular management therapy.

Postural instability/gait disturbance (PIGD) is very common in advanced Parkinson’s disease, and associated with cognitive dysfunction. Research suggests that low frequency (5–12 Hz) subthalamic nucleus-deep brain stimulation (STN-DBS) could improve cognition in patients with Parkinson’s disease (PD). However, the clinical effectiveness of low frequency stimulation in PIGD patients has not been explored. This study was designed in a double-blinded randomized cross-over manner, aimed to verify the effect of low frequency STN-DBS on cognition of PIGD patients. Twenty-nine PIGD patients with STN-DBS were tested for cognitive at off (no stimulation), low frequency (5 Hz), and high frequency (130 Hz) stimulation. Neuropsychological tests included the Stroop Color-Word Test (SCWT), Verbal fluency test, Symbol Digital Switch Test, Digital Span Test, and Benton Judgment of Line Orientation test. For conflict resolution of executive function, low frequency stimulation significantly decreased the completion time of SCWT-C (p = 0.001) and Stroop interference effect (p

Introduction Class II treatment with mandibular retrusion often involves the Herbst appliance due to its efficiency and low requirement of cooperation. Despite its advantages, it causes side effects concerning the occlusal plane and pogonion in terms of clockwise rotation that hinder the desired mandibular advancement for hyperdivergent patients. In this study, we will use a newly designed Herbst appliance, and a protocol that is accompanied by TADs for vertical control to avoid maxillary clockwise rotation. We hypothesise that the effect of the Herbst appliance with the vertical control approach will be beneficial for maintaining or even decreasing the skeletal divergence in hyperdivergent class II patients compared with conventional Herbst treatment.Methods and analysis This study is a randomised, parallel, prospective controlled trial that will study the efficacy of Herbst with or without vertical control in children with hyperdivergent skeletal class II malocclusion. A total of 44 patients will be enrolled and randomised in a ratio of 1:1 to either Herbst treatment or Herbst treatment with vertical control. Participants will be recruited at the Shanghai Stomatological Hospital, Shanghai, China. The primary endpoint is the change in the angle indicating the occlusal plane and Sella-Nasion plane from baseline (T0) to the primary endpoint (T2) on cephalometric measurements by lateral X-ray examination. Important secondary outcomes include the root length of the anterior teeth, and the assessment score of the Visual Analogue Scale Questionnaire, etc. Safety endpoints will also be evaluated.Ethics and dissemination This study has been approved by the ethics committee of the Shanghai Stomatological Hospital (Approval No. (2021) 012). Before enrolment, a qualified clinical research assistant will obtain written informed consent from both the participants and their guardians after full explanation of this study. The results will be presented at national or international conferences and published in peer-reviewed journals.Trial registration number ChiCTR2100049860, Chinese Clinical Trial Registry

Background: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. Methods: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. Results: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P

Abstract Background Orthodontic treatment is commonly more time-consuming in adults than in teenagers, especially when it comes to the maxillary en-masse retraction, which may take 9 months or even longer. As to solve this concern, orthodontists have been striving to seek new methods for shortening orthodontic treatment time. Piezocision, as a popular alternative treatment, has been widely used in different types of tooth movement. However, its effect on en-masse retraction of maxillary anterior teeth remains unclear. This randomized controlled trial intends to figure out the role piezocision plays in accelerating en-masse retraction. Methods This protocol is designed for a prospective, single-center, assessor-blinded and parallel-group randomized controlled trial. Twenty adult patients aged from 18 to 40 whose orthodontic treatment required bilateral maxillary first premolars extraction will be randomly assigned to the piezocision group and the control group at a ratio of 1:1. The piezocision group will undergo en-masse retraction immediately after the piezo surgery, while the control group will start en-masse retraction directly. Both groups will be followed up every 2 weeks to maintain the retraction force until the end of space closure. The space closing time is set as the primary endpoint. Meanwhile, the secondary endpoints include the change of root length, labial and palatal alveolar bone thickness, vertical bone height, probing depth of maxillary anterior teeth, cephalometric measurements, visual analogue scale, and postoperative satisfaction questionnaire. Discussion This study will attempt to provide more convincing evidence to verify whether piezocision will shorten the time of en-masse retraction or not. Distinguished with previous studies, our study has made some innovations in orthodontic procedure and primary outcome measurement, aiming to clarify the efficacy and safety of piezocision-assisted en-masse retraction in Chinese population. Trial registration Chinese Clinical Trial Registry ChiCTR 1900024297 . Registered on 5 July 2019

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves sleep qualities in Parkinson’s disease (PD) patients; however, it remains elusive whether STN-DBS improves sleep by directly influencing the sleep circuit or alleviates other cardinal symptoms such as motor functions, other confounding factors including stimulation intensity may also involve. Studying the effect of microlesion effect (MLE) on sleep after STN-DBS electrode implantation may address this issue. Objective: To examine the influence of MLE on sleep quality and related factors in PD, as well as the effects of regional and lateral specific correlations with sleep outcomes after STN-DBS electrode implantation. Study Design: Case–control study; Level of evidence, 3. Data Sources and Methods: In 78 PD patients who underwent bilateral STN-DBS surgery in our center, we compared the sleep qualities, motor performances, anti-Parkinsonian drug dosage, and emotional conditions at preoperative baseline and postoperative 1-month follow-up. We determined the related factors of sleep outcomes and visualized the electrodes position, simulated the MLE-engendered volume of tissue lesioned (VTL), and investigated sleep-related sweet/sour spots and laterality in STN. Results: MLE improves sleep quality with Pittsburgh Sleep Quality Index (PSQI) by 13.36% and Parkinson’s Disease Sleep Scale-2 (PDSS-2) by 17.95%. Motor ( P = 0.014) and emotional ( P = 0.001) improvements were both positively correlated with sleep improvements. However, MLE in STN associative subregions, as an independent factor, may cause sleep deterioration ( r = 0.348, P = 0.002), and only the left STN showed significance ( r = 0.327, P = 0.004). Sweet spot analysis also indicated part of the left STN associative subregion is the sour spot indicative of sleep deterioration. Conclusion: The MLE of STN-DBS can overall improve sleep quality in PD patients, with a positive correlation between motor and emotional improvements. However, independent of all other factors, the MLE in the STN associative subregion, particularly the left side, may cause sleep deterioration.

Ledge formation presents a significant challenge in endodontic treatment. Yet, there is still a lack of educational tooth models for hands-on practice. This study aimed to create and evaluate a tooth model for ledge management practice. A natural tooth with curved roots was collected for scientific use under ethics committee approval. Following initial root canal preparation, the tooth was scanned using micro-computed tomography (μCT) and 3D reconstructed. A K-file, created via computer-aided design (CAD), was partly inserted into the root canal wall of the 3D reconstructed tooth. By subtracting the K-file from the tooth, a tooth model with a root canal ledge was produced. The model was then 3D printed for a hands-on workshop. An eight-item Likert-scale questionnaire was administered to 20 postgraduate students and 10 endodontists to assess the model’s quality and training effectiveness. In addition, the success rate of bypassing and correcting the root canal ledge was documented. The feedback from both the students and experts was positive, and the results of the Mann–Whitney U test indicated no statistically significant differences found between the two groups (p > 0.05). The success rate of the students and the experts was 85% and 100%, respectively. In future applications, this novel tooth model is expected to address the existing gap in endodontic education and provide benefits for dental practitioners.

ObjectivesLow-beta oscillation (13–20 Hz) has rarely been studied in patients with early-onset Parkinson’s disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson’s disease (LOPD).MethodsWe enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group.ResultsWe found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500–650 ms, p = 0.008), while LOPD had higher proportion of short burst (200–350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300–460 Hz) amplitude (p = 0.019).ConclusionWe found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.

Introduction In adult patients with thin phenotype, gingival recession is obvious in the mandibular incisors after a large amount of lingual tooth movement. A systematic review indicated that soft tissue augmentation before orthodontic treatment might yield satisfactory results with respect to the progression of gingival recession. However, the studies included had a low-to-moderate level of evidence. This study was designed to investigate the efficacy of soft tissue augmentation prior to orthodontic treatment on the prevention of gingival recession.Method and analysis This is a single-centre, single-blind, randomised controlled, double-armed parallel group comparison trial. This study was initiated in December 2021 and end in December 2025 (anticipated). Patients with mild crowding in the lower arch and a thin gingival type was enrolled and randomly assigned in a 1:1 ratio to either group A (having soft tissue augmentation prior to orthodontic treatment) or group B (having orthodontic treatment only). The planned number of enrolled patients was 48 (24 patients × 2 groups). The primary endpoint was the mean change in recession of the gingival margin. Secondary endpoints included the probing depth, gingival phenotype, frequency of complete root coverage, gingival thickness, width of the keratinised gingiva, clinical attachment level, gingival recession class, full-mouth plaque score, alveolar bone thickness in the faciolingual dimension of the lower anterior teeth and lower incisor inclination.Ethics and dissemination The study protocol was approved by the Ethical Committee of the Shanghai Stomatological Hospital (certificate number (2021)016). The study was conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act and other current legal regulations in China. Written informed consent was obtained from all the participants. The results of this study will be reported in journal publications.Trial registration number ChiCTR2100050892.

Zinc-based nanoparticles, nanoscale metal frameworks and metals have been considered as biocompatible materials for bone tissue engineering. Among them, zinc-based metals are recognized as promising biodegradable materials thanks to their moderate degradation rate ranging between magnesium and iron. Nonetheless, materials’ biodegradability and the related biological response depend on the specific implant site. The present study evaluated the biodegradability, cytocompatibility, and hemocompatibility of a hot-extruded zinc-copper-iron (Zn-Cu-Fe) alloy as a potential biomaterial for craniomaxillofacial implants. Firstly, the effect of fetal bovine serum (FBS) on in vitro degradation behavior was evaluated. Furthermore, an extract test was used to evaluate the cytotoxicity of the alloy. Also, the hemocompatibility evaluation was carried out by a modified Chandler-Loop model. The results showed decreased degradation rates of the Zn-Cu-Fe alloy after incorporating FBS into the medium. Also, the alloy exhibited acceptable toxicity towards RAW264.7, HUVEC, and MC3T3-E1 cells. Regarding hemocompatibility, the alloy did not significantly alter erythrocyte, platelet, and leukocyte counts, while the coagulation and complement systems were activated. This study demonstrated the predictable in vitro degradation behavior, acceptable cytotoxicity, and appropriate hemocompatibility of Zn-Cu-Fe alloy; therefore, it might be a candidate biomaterial for craniomaxillofacial implants.

Genetic Creutzfeldt–Jakob disease (gCJD) characterized by mutations in the prion protein (PrP) gene (PRNP) contributes to approximately 10–15% of the overall human prion diseases. Here, we report a rare mutation in the PRNP gene in a Han-Chinese family. A 36-year-old man initiated with anxiety and depression followed by progressive dementia, cogwheel-like rigidity combined with tremors, and he was diagnosed with frontotemporal lobar dementia in the first 2 years. The disease progression was relatively slow, and the patient developed into akinetic mutism in 4 years. To characterize the disease, following the pedigree studies, neuropsychological examination, neuroimaging studies, real-time quaking-induced conversion (RT-QuIC) examination, and so on were conducted. We eventually identified a rare mutation of G114V combined with one octapeptide repeats deletion (1-ORPD) in the PrP in the patient by DNA sequencing. In addition, the same mutation and deletion were subsequently identified in the patient's mother without any syndromes. His maternal grandmother had a late onset of the disease in her 60s. Given that 1-OPRD has never been reported in human prion disease before, our first report that both G114V mutation and 1-OPRD appear in the family would forward our understanding of the etiological mechanisms of the gCJD.

Carbon nanotubes (CNTs) are a promising bioactive scaffold for bone regeneration because of their superior mechanical and biological properties. Vascularization is crucial in bone tissue engineering, and insufficient vascularization is a long-standing problem in tissue-engineered scaffolds. However, the effect of CNTs on vascularization is still minimal. In the current study, pristine single-walled carbon nanotubes (SWNTs) were purified to prepare different ratios of SWNTs/EDC composites, and their surface morphology and physicochemical properties of SWNTs/EDC were studied. Furthermore, the effect of SWNTs/EDC on vascularization was investigated by inducing the differentiation of bone mesenchymal stem cells (BMSCs) into vascular endothelial cell-like cells (VEC-like cells). Results showed that SWNTs/EDC composite was successfully prepared, and EDC was embedded in the SWNTs matrix and uniformly distributed throughout the composites. The AFM, FTIR spectra, and Raman results confirmed the formation of SWNTs/EDC composites. Besides, the surface topography of the SWNTs/EDC composites presents a rough surface, which may positively affect cell function. In vitro cell culture revealed that SWNTs and SWNTs/EDC composites exhibited excellent biocompatibility and bioactivity. The SWNTs/EDC composite at mass/volume ratios 1:10 had the best enhancement of proliferation and differentiation of BMSCs. Moreover, after culture with SWNTs/EDC composite, approximately 78.3% ± 4.2% of cultured cells are double-positive for FITC-UEA-1 and DiI-Ac-LDL double staining. Additionally, the RNA expression of representative endothelial cell markers VEGF, VEGF-R2, CD31, and vWF in the SWNTs/EDC composite group was significantly higher than those in the control and SWNTs group. With the limitation of our study, the results suggested that SWNTs/EDC composite can promote BMSCs differentiation into VEC-like cells and positively affect angiogenesis and bone regeneration.

Abstract Numerous factors can influence the force exerted by clear aligners on teeth. This study aimed to investigate the stability of the force delivered by two different material appliances. 90 clear aligners with 2 materials and three different activations were designed and fabricated. Then, a device was employed to measure the force generated by the two types of PET-G material appliances immersed in artificial saliva for 0, 3, 7, 10, 14 days. Scanning electron microscopy was applied to observe the morphologic alterations on the aligner surfaces, respectively. The forces generated by different activation appliance exhibited differently, 0.0 mm

Concentrated growth factors (CGFs) are widely used in surgery with bone grafting, but the release of growth factors from CGFs is rapid. RADA16, a self-assembling peptide, can form a scaffold that is similar to the extracellular matrix. Based on the properties of RADA16 and CGF, we hypothesized that the RADA16 nanofiber scaffold hydrogel could enhance the function of CGFs and that the RADA16 nanofiber scaffold hydrogel-wrapped CGFs (RADA16-CGFs) would perform a good osteoinductive function. This study aimed to investigate the osteoinductive function of RADA16-CGFs. Scanning electron microscopy, rheometry, and ELISA were performed, and MC3T3-E1 cells were used to test cell adhesion, cytotoxicity, and mineralization after administration with RADA16-CGFs. We found that RADA16 endowed with the sustained release of growth factors from CGFs, which can help maximize the function of CGFs in osteoinduction. The application of the atoxic RADA16 nanofiber scaffold hydrogel with CGFs can be a new therapeutic strategy for the treatment of alveolar bone loss and other problems that require bone regeneration.

Forests undergo a long-term development process from young to mature stages, yet the variations in soil nutrients, enzyme activities, microbial diversity, and community composition related to forest ages are still unclear. In this study, the characteristics of soil bacterial and fungal communities with their corresponding soil environmental factors in the young, middle, and mature stages (7, 15, and 25-year-old) of Chinese fir plantations (CFP) in the subtropical region of China were investigated in 2021. Results showed that the alpha diversity indices (Chao1 and Shannon) of soil bacteria and fungi were higher in 15 and 25-year-old stands than in 7-year-old stand of CFP, while the soil pH, soil water content, soil organic carbon, total nitrogen, total phosphorus, sucrase, urease, acid phosphatase, catalase, and microbial biomass carbon, nitrogen, and phosphorus showed higher in 7-year-old stand than other two stands of CFP. The nonmetric multidimensional scaling analysis revealed that the soil microbial species composition was significantly different in three stand ages of CFP. The redundancy and canonical correspondence analysis indicated that the soil urease and microbial biomass nitrogen were the main factors affecting soil bacterial and fungal species composition. Our findings suggested that soil microbial diversity and community structure were inconsistent with changes in soil nutrients and enzyme activities during CFP development, and enhancing stand nurturing and soil nutrient accumulation in the mid-development stage were beneficial to the sustainable management of CFP.

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 μg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.

Zinc-based biodegradable metals (BMs) have been developed for biomedical implant materials. However, the cytotoxicity of Zn and its alloys has caused controversy. This work aims to investigate whether Zn and its alloys possess cytotoxic effects and the corresponding influence factors. According to the guidelines of the PRISMA statement, an electronic combined hand search was conducted to retrieve articles published in PubMed, Web of Science, and Scopus (2013.1–2023.2) following the PICOS strategy. Eighty-six eligible articles were included. The quality of the included toxicity studies was assessed utilizing the ToxRTool. Among the included articles, extract tests were performed in 83 studies, and direct contact tests were conducted in 18 studies. According to the results of this review, the cytotoxicity of Zn-based BMs is mainly determined by three factors, namely, Zn-based materials, tested cells, and test system. Notably, Zn and its alloys did not exhibit cytotoxic effects under certain test conditions, but significant heterogeneity existed in the implementation of the cytotoxicity evaluation. Furthermore, there is currently a relatively lower quality of current cytotoxicity evaluation in Zn-based BMs owing to the adoption of nonuniform standards. Establishing a standardized in vitro toxicity assessment system for Zn-based BMs is required for future investigations.

Recognizing the emotional states of humans through EEG signals are of great significance to the progress of human-computer interaction. The present study aimed to perform automatic recognition of music-evoked emotions through region-specific information and dynamic functional connectivity of EEG signals and a deep learning neural network. EEG signals of 15 healthy volunteers were collected when different emotions (high-valence-arousal vs. low-valence-arousal) were induced by a musical experimental paradigm. Then a sequential backward selection algorithm combining with deep neural network called Xception was proposed to evaluate the effect of different channel combinations on emotion recognition. In addition, we also assessed whether dynamic functional network of frontal cortex, constructed through different trial number, may affect the performance of emotion cognition. Results showed that the binary classification accuracy based on all 30 channels was 70.19%, the accuracy based on all channels located in the frontal region was 71.05%, and the accuracy based on the best channel combination in the frontal region was 76.84%. In addition, we found that the classification performance increased as longer temporal functional network of frontal cortex was constructed as input features. In sum, emotions induced by different musical stimuli can be recognized by our proposed approach though region-specific EEG signals and time-varying functional network of frontal cortex. Our findings could provide a new perspective for the development of EEG-based emotional recognition systems and advance our understanding of the neural mechanism underlying emotion processing.

IntroductionHuman gut dysbiosis has been implicated with the onset of many neurodegenerative disorders. However, the current data focused on the gut microbiota of patients with Creutzfeldt-Jakob disease (CJD) are still lacking. In our study, we explored the gut microbiota alteration in patients with CJD.MethodWe performed 16S ribosomal RNA MiSeq sequencing in stool samples of patients with CJD and controls. Functional analysis of the gut microbiota between these two groups was based on Kyoto Encyclopedia of Genes and Genomes and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. Clinical rating scales were used to evaluate the association between cognitive impairment and gut microbiota alteration.ResultWe identified a significant alteration in both the structure and the richness of the CJD group. Function analysis revealed that the gut microbiota of patients with CJD enriched in immune signaling molecule interactions and xenobiotics biodegradation. MoCA and survival times were found to be associated with gut microbiota in patients with CJD.ConclusionWe demonstrated an altered gut microbiota in patients with CJD, which was associated with the cognitive impairment and the survival time of these patients.

The popular trend of today’s music can be obtained by deep excavation, analysis, and prediction of the audience’s preferences. Using huge music library resources and user behavior to form music big data and truly realizing the aggregation of audience preferences determine the popular development trend of music. Therefore, this paper will apply data mining (DM) technology, introduce neural network (NNS) theory, establish a prediction model of music fashion trend, predict and evaluate the music fashion trend according to the selected evaluation index, find the change of music fashion trend in time, and provide decision-making basis for music fashion trend. In this paper, the prediction of music popularity trend based on NNS and DM technology is studied. In the prediction of the number of songs played by 10 artists, the NNS algorithm proposed in this paper reduces the prediction effect from the original 0.074 and 0.045 to 0.044 and 0.032, respectively, and the error rates are reduced by 35.7% and 29.4%, respectively, compared with the learning algorithm and the decision tree algorithm. Among the three methods, the NNS algorithm in this paper has the highest accuracy. Therefore, it can be proved that the model proposed in this paper is more suitable for predicting the trend of music popularity. In the end, it can accurately control the trend of pop music and also realize the aggregation of user preferences to determine the trend of pop music.

Three-dimensionally printed polyetheretherketone (PEEK) materials are promising for fabricating customized dental abutments. This study aimed to investigate the adhesive property of a 3D-printed PEEK material. The effects of surface treatment and temporary crown materials on shear bond strength were evaluated. A total of 108 PEEK discs were 3D printed by fused-filament fabrication. Surface treatments, including sandblasting, abrasive paper grinding, and CO2 laser ablation, were applied to the PEEK discs, with the untreated specimens set as the control. Afterward, the surface topographies of each group were investigated by scanning electron microscopy (SEM, n = 1) and roughness measurements (n = 7). After preparing the bonding specimens with three temporary crown materials (Artificial teeth resin (ATR), 3M™ Filtek™ Supreme Flowable Restorative (FR), and Cool Temp NATURAL (CTN)), the shear bond strength was measured (n = 6), and the failure modes were analyzed by microscopy and SEM. The results showed that ATR exhibited a significantly higher shear bond strength compared to FR and CTN (p < 0.01), and the PEEK surfaces treated by sandblasting and abrasive paper grinding showed a statistically higher shear bond strength compared to the control (p < 0.05). For clinical application, the ATR material and subtractive surface treatments are recommended for 3D-printed PEEK abutments.

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon.

An oronasal fistula (ONF) is an abnormal structure between the oral and nasal cavities, which is a common complication of cleft palate repair due to the failure of wound healing. When some patients with ONF are unsuitable for secondary surgical repair, the obturator treatment becomes a potential method. The objectives of the obturator treatment should be summarized as filling the ONF comfortably and cosmetically restoring the dentition with partial function. The anatomy of patients with cleft palate is complex, which may lead to a more complex structure of the ONF. Thus, the manufacturing process of the obturator for these patients is more difficult. For performing the design and fabrication process rapidly and precisely, digital techniques can help, but limitations still exist. In this review, literature searches were conducted through Medline via PubMed, Wiley Online Library, Science Direct, and Web of Science, and 122 articles were selected. The purpose of this review was to introduce the development of the obturator for treating patients with ONF after cleft palate repair, from the initial achievement of the obstruction of the ONF to later problems such as fixation, velopharyngeal insufficiency, and infection, as well as the application of digital technologies in obturator manufacturing.

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.

Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT2) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells. Functional assays were conducted to determine the role of MALAT1 in regulating the growth and metastasis of parental and DTX-resistant LUAD cells. Investigation revealed the mechanism of the competing endogenous RNA (ceRNA) pathway. MALAT1 regulated miR-200b by acting as a ceRNA. MALAT1 modulated the sensitivity of LUAD cells to DTX. E2F transcription factor 3 (E2F3) and zinc-finger E-box binding homeobox 1 (ZEB1) were two targets of miR-200b and mediated the function of MALAT1 in DTX-resistant LUAD cells. Transcription factor AP-2 gamma (TFAP2C) and ZEB1 activated the MALAT1 transcription. In conclusion, TFAP2C-activated MALAT1 modulated the chemoresistance of LUAD cells by sponging miR-200b to upregulate E2F3 and ZEB1. Our findings may provide novel therapeutic targets and perspectives for LUAD treatment. Keywords: MALAT1, miR-200b, LUAD, chemoresistance

The authors wish to make the following corrections to this paper [...]

It has been proposed that an extended version of the Hubbard model which potentially hosts rich correlated physics may be well simulated by the transition metal dichalcogenide (TMD) moiré heterostructures. Motivated by recent reports of continuous metal-insulator transition (MIT) at half filling, as well as correlated insulators at various fractional fillings in TMD moiré heterostructures, we propose a theory for the potentially continuous MIT with fractionalized electric charges. The charge fractionalization at the MIT will lead to various experimental observable effects, such as a large resistivity as well as large universal resistivity jump at the continuous MIT. These predictions are different from previously proposed theory for interaction-driven continuous MIT. Physics in phases near the MIT will also be discussed.

Brain tumors are the most widespread malignancies in children around the world. Chemotherapy plays a critical role in the treatment of these tumors. Although the current chemotherapy process has a remarkable outcome for a certain subtype of brain tumor, improving patient survival is still a major challenge. Further intensive treatment with conventional non-specific chemotherapy could cause additional adverse reactions without significant advancement in survival. Recently, patient derived brain tumor, xenograft, and whole genome analysis using deep sequencing technology has made a significant contribution to our understanding of cancer treatment. This realization has changed the focus to new agents, targeting the molecular pathways that are critical to tumor survival or proliferation. Thus, many novel drugs targeting epigenetic regulators or tyrosine kinase have been developed. These selective drugs may have less toxicity in normal cells and are expected to be more effective than non-specific chemotherapeutics. This review will summarize the latest novel targets and corresponding candidate drugs, which are promising chemotherapy for brain tumors according to the biological insights.

Soil labile organic carbon fractions (SLOCFs) mainly include microbial biomass carbon (MBC), dissolved organic carbon (DOC), easily oxidized organic carbon (EOC) and light fraction organic carbon (LFOC). The link between bedrock exposure rates with SLOCFs and the carbon pool management index under karst rocky desertification has not been well understood. We selected the bedrock exposure rate and vegetation coverage of 30–50% (light bedrock exposure, LBE), 50–70% (moderate bedrock exposure, MBE) and >70% (intense bedrock exposure, IBE) as the experimental sample plots according to the classification standard of karst rocky desertification, and then selected a sample plot of 0–30% (secondary forest, SF) as the control. This study compared the concentrations and stocks of soil organic carbon (SOC) and SLOCFs and analyzed the relevant carbon pool management index on karst landforms at Anshun, S.W. China. The aims were to determine the relationship between bedrock exposure rates and SLOCFs and to identify the most limiting factors for SLOCFs in karst rocky desertification areas. We found that (1) the concentrations and stocks of SLOCFs declined with increasing soil depth. SOC, DOC and MBC showed IBE > LBE > MBE > SF; LFOC decreased with increasing bedrock exposure rate, and EOC did not show obvious regularity. (2) The carbon pool management index and sensitivity index had significant differences under different bedrock exposure rates. Redundancy analysis and linear regression showed that the increase in bedrock exposure rate had a great impact on MBC, DOC, EOC and SOC. In conclusion, the increase of bedrock exposure rate has no side impact on the DOC, EOC and MBC of the soil, but side effects are exhibited by LFOC. Secondary forest improves the integrity of karst landscapes, and does not change the soil properties as well as the concentrations and stocks of SLOCFs in karst rocky desertification areas.

The rates of translation elongation or termination in eukaryotes are modulated through cooperative molecular interactions involving mRNA, the ribosome, aminoacyl- and nascent polypeptidyl-tRNAs, and translation factors. To investigate the molecular mechanisms underlying these processes, we developed an in vitro translation system from yeast, reconstituted with purified translation elongation and termination factors, utilizing CrPV IGR IRES-containing mRNA, which functions in the absence of initiation factors. The system is capable of synthesizing not only short oligopeptides but also long reporter proteins such as nanoluciferase. By setting appropriate translation reaction conditions, such as the Mg2+/polyamine concentration, the arrest of translation elongation by known ribosome-stalling sequences (e.g., polyproline and CGA codon repeats) is properly recapitulated in this system. We describe protocols for the preparation of the system components, manipulation of the system, and detection of the translation products. We also mention critical parameters for setting up the translation reaction conditions. This reconstituted translation system not only facilitates biochemical analyses of translation but is also useful for various applications, such as structural and functional studies with the aim of designing drugs that act on eukaryotic ribosomes, and the development of systems for producing novel functional proteins by incorporating unnatural amino acids by eukaryotic ribosomes.

Background/Aims: Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. Methods: We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP) -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients’ chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Results: Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Conclusion: Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.

The building damage status is vital to plan rescue and reconstruction after a disaster and is also hard to detect and judge its level. Most existing studies focus on binary classification, and the attention of the model is distracted. In this study, we proposed a Siamese neural network that can localize and classify damaged buildings at one time. The main parts of this network are a variety of attention U-Nets using different backbones. The attention mechanism enables the network to pay more attention to the effective features and channels, so as to reduce the impact of useless features. We train them using the xBD dataset, which is a large-scale dataset for the advancement of building damage assessment, and compare their result balanced F (F1) scores. The score demonstrates that the performance of SEresNeXt with an attention mechanism gives the best performance among single models, with the F1 score reaching 0.787. To improve the accuracy, we fused the results and got the best overall F1 score of 0.792. To verify the transferability and robustness of the model, we selected the dataset on the Maxar Open Data Program of two recent disasters to investigate the performance. By visual comparison, the results show that our model is robust and transferable.

Tyrosine kinases (TKs) play an essential role in regulating various cellular activities and dysregulation of TK signaling contributes to oncogenesis. However, less than half of the TKs have been thoroughly studied. Through a combined use of RNAi and stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics, a global functional proteomic landscape of TKs in breast cancer was recently revealed highlighting a comprehensive and highly integrated signaling network regulated by TKs (Stebbing et al., 2015) [1]. We collate the enormous amount of the proteomic data in an open access platform, providing a valuable resource for studying the function of TKs in cancer and benefiting the science community. Here we present a detailed description related to this study (Stebbing et al., 2015) [1] and the raw data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the identifier http://www.ebi.ac.uk/pride/archive/projects/PXD002065. Keywords: Breast cancer, Cell signaling, Proteomics, SILAC, Tyrosine kinases

LMTK3 is an oncogenic receptor tyrosine kinase (RTK) implicated in various types of cancer, including breast, lung, gastric, and colorectal cancer. It is localized in different cellular compartments, but its nuclear function has not been investigated so far. We mapped LMTK3 binding across the genome using ChIP-seq and found that LMTK3 binding events are correlated with repressive chromatin markers. We further identified KRAB-associated protein 1 (KAP1) as a binding partner of LMTK3. The LMTK3/KAP1 interaction is stabilized by PP1α, which suppresses KAP1 phosphorylation specifically at LMTK3-associated chromatin regions, inducing chromatin condensation and resulting in transcriptional repression of LMTK3-bound tumor suppressor-like genes. Furthermore, LMTK3 functions at distal regions in tethering the chromatin to the nuclear periphery, resulting in H3K9me3 modification and gene silencing. In summary, we propose a model where a scaffolding function of nuclear LMTK3 promotes cancer progression through chromatin remodeling.

Computer-aided design (CAD) and additive manufacturing (AM) have shown promise in facilitating the fabrication of custom trays. Due to the clinical requirements, custom tray materials should achieve good bonding to the impression/adhesive systems. This study evaluated the retention of three fused deposition modeling (FDM) custom tray materials to a silicone impression/adhesive system before and after gritblasting (GB) by peel-off test. CAD-designed experimental test blocks were printed by FDM using acrylonitrile butadiene styrene (ABS), polyethylene terephthalate glycol copolyester (PETG), and high impact polystyrene (HIPS), and the reference test blocks were made of a conventional light-curing resin (n = 11). Before and after GB, the surface topography of all tray materials was analysed, and the maximum strength of the test block peeled off from a silicone impression/adhesive system was measured. After GB, the arithmetic mean height (Sa) and the valley fluid retention index (Svi) of the four material groups declined (p < 0.05). The peel-off strength of each of the four material groups significantly decreased by GB (p < 0.05), but no statistical difference could be found among them before or after GB. In all peel-off tests, adhesive failure occurred at the adhesive-impression material interface. The results indicated ABS, HIPS, and PETG could provide sufficient adhesion to the adhesive as the conventional light-curing resin, and GB could reduce the roughness generated by FDM and weaken the bonding between the adhesive and the silicone impression.