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Rapid tumor growth and insufficient blood supply leads to the development of a hypoxic and nutrient deprived microenvironment. To survive, tumor cells need to tolerate these adverse conditions. Here we found the expression of CD39 was enhanced in necrotic regions distant from blood vessels. We speculate that this is a strategy for tumor cells to actively adapt to the hostile environment. Further studies showed that CD39 was induced by nutrient deprivation through the AMPK signalling pathway. We next explored the significance of CD39 for tumor cells. Our results showed that CD39 reduced cellular oxygen consumption, which could be significant for tumor cells if the available oxygen is limited. Metabolomics analysis showed that overexpression of CD39 significantly altered cellular metabolism, and tricarboxylic acid (TCA) cycle was identified as the most impacted metabolic pathway. In order to explore the molecular mechanism, we performed RNA-seq analysis. The results showed that CD39 significantly up-regulated the expression of pyruvate dehydrogenase kinase isozyme 2 (PDK2), thus inhibiting the activity of pyruvate dehydrogenase (PDH) and TCA cycle. Finally, CD39 was shown to protect tumor cells from hypoxia-induced cell death and reduce intratumoral hypoxia levels. CD39 has attracted a great deal of attention as a newly discovered immune checkpoint molecule in recent years. Our results indicate that CD39 not only plays a role in immune regulation, but also enables tumor cells to tolerate hypoxia by inhibiting TCA cycle and reducing cellular oxygen consumption. This study provides evidence that targeting CD39 may be a novel strategy to prevent adaptation of tumor cells in stressed conditions.
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Apirase , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Apirase/metabolismo , Apirase/genética , Linhagem Celular Tumoral , Nutrientes/metabolismo , Hipóxia Celular , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Ciclo do Ácido Cítrico , Microambiente Tumoral , Animais , Transdução de Sinais , Consumo de Oxigênio , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Tumor cells continue to evolve the metastatic potential in response to signals provided by the external microenvironment during metastasis. Platelets closely interact with tumor cells during hematogenous metastasis and facilitate tumor development. However, the molecular mechanisms underlying this process are not fully understood. METHODS: RNA-sequencing was performed to screen differentially expressed genes mediated by platelets. The effects of platelet and CD39 on tumor metastasis were determined by experimental metastasis models with WT, NCG and CD39-/- mice. RESULTS: RNA-sequencing results showed that platelets significantly up-regulated CD39 expression in tumor cells. CD39 is a novel immune checkpoint molecule and a key driver of immunosuppression. Our data provided evidence that the expression of CD39 was enhanced by platelets in a platelet-tumor cell contact dependent manner. Although the role of CD39 expressed by immune cells is well established, the effect of CD39 expressed by tumor cells on tumor cell behavior, anti-tumor immunity and tumor metastasis is unclear. We found that CD39 promoted tumor cell invasion, but had no effect on proliferation and migration. Notably, we showed that the ability of platelets to prime tumor cells for metastasis depends on CD39 in the experimental tumor metastasis model. CD39 silencing resulted in fewer experimental metastasis formation, and this anti-metastasis effect was significantly reduced in platelet-depleted mice. Furthermore, overexpression of CD39 in tumor cells promoted metastasis. In order to eliminate the effect of CD39 expressed in cells other than tumor cells, we detected tumor metastasis in CD39-/- mice and obtained similar results. Moreover, overexpression of CD39 in tumor cells inhibited antitumor immunity. Finally, the data from human samples also supported our findings. CONCLUSIONS: Our study shows that direct contact with platelets induces CD39 expression in tumor cells, leading to immune suppression and promotion of metastasis.
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Antígenos CD , Apirase , Plaquetas , Metástase Neoplásica , Animais , Apirase/genética , Apirase/metabolismo , Plaquetas/metabolismo , Plaquetas/patologia , Camundongos , Antígenos CD/genética , Antígenos CD/metabolismo , Humanos , Linhagem Celular Tumoral , Feminino , Camundongos Knockout , Movimento Celular , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão GênicaRESUMO
Facile and efficient photocatalysts using sunlight, as well as fast and sensitive surface-enhanced Raman spectroscopy (SERS) substrates, are urgently needed for practical degradation of tetracycline (TC). To meet these requirements, a new paradigm for PI/TiO2/Ag organicâinorganic ternary flexible microfibers based on semiconducting titanium dioxide (TiO2), the noble metal silver (Ag) and the conjugated polymer polyimide (PI) was developed by engineering a simple method. Under sunlight, the photocatalytic characteristics of the PI/TiO2/Ag flexible microfibers containing varying amounts of Ag quantum dots (QDs) were evaluated with photocatalytic degradation of TC in aqueous solution. The results demonstrated that the amount of Ag affected the photocatalytic activity. Among the tested samples, PI/TiO2/Ag-0.07 (93.1%) exhibited a higher photocatalytic degradation rate than PI/TiO2 (25.7%), PI/TiO2/Ag-0.05 (77.7%), and PI/TiO2/Ag-0.09 (63.3%). This observation and evaluation conducted in the present work strongly indicated a charge transfer mechanism. Moreover, the PI/TiO2/Ag-0.07 flexible microfibers exhibited highly sensitive SERS detection, as demonstrated by the observation of the Raman peaks for TC even at an extremely low concentration of 10-10 moles per liter. The excellent photocatalytic performance and SERS detection capability of the PI/TiO2/Ag flexible microfibers arose from the Schottky barrier formed between Ag and TiO2 and also from the outstanding plasmonic resonance and visible light absorptivity of Ag, along with immobilization by the PI. The successful synthesis of PI/TiO2/Ag flexible microfibers holds significant promise for sensitive detection and efficient photocatalytic degradation of antibiotics.
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OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: ⢠The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. ⢠Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. ⢠The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Linfonodos/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologiaRESUMO
Whole-genome duplication is a significant evolutionary mechanism in plants, with polyploid plants often displaying larger organs and enhanced adaptability to unfavorable conditions compared to their diploid counterparts. The cell wall acts as a primary defense for plant cells against external stresses, playing an essential role in the plant's resistance to various stressors. In this study, we utilized both autotetraploid and its donor diploid rice (Oryza sativa L.) to analyze their phenotypic differences comparatively, the composition of key cell wall components, and the expression of related genes under normal conditions, as well as under stress from Magnaporthe oryzae (M. oryzae) and salt. Our findings indicated that autotetraploid rice exhibits significantly larger phenotypic characteristics under normal conditions than diploid rice. At the seedling stage, the lignin, cellulose, hemicellulose, and pectin levels in autotetraploid rice were markedly lower than in diploid rice. Additionally, 24 genes associated with major cell wall components showed differential expression between diploid and tetraploid rice. At the filling stage, the lignin and pectin content in autotetraploid rice were significantly higher than in diploid rice, while the levels of cellulose and hemicellulose were notably lower. Under M. oryzae stress or salt stress, autotetraploid rice showed smaller lesion areas and less wilting than diploid rice. The increased lignin content in autotetraploid rice under M. oryzae stress suggested a stronger adaptive capacity to adverse conditions. Compared to salt stress, M. oryzae stress induced more differential expression of genes related to major cell wall components. In this study, we explored the differences in the major cell wall components of diploid and homologous tetraploid rice under various treatment conditions. This study provides valuable insights into understanding the cell wall's adaptive mechanisms in autotetraploid rice when facing blast disease and salt stress, and it reveals the differential gene expression linked to these adaptive capabilities.
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Quantum vortices in Bose-Einstein condensates (BECs) are essential phenomena in condensed matter physics, and precisely locating their positions, especially the vortex core, is a precondition for studying their properties. With the rise of machine learning, there is a possibility to expedite the localization process and provide accurate predictions. However, traditional machine learning requires particular considerable amount of manual data annotation, leading to uncontrollable accuracy. In this paper, we utilize the U-Net method to detect vortex positions accurately at the pixel level and propose an Automatic Correction Labeling (ACL) approach to optimize the acquisition of data sets for vortex localization in BECs. This approach addresses inaccuracies in the labeled vortex positions and improves the accuracy of vortex localization, especially the vortex core positions, while enhancing the tolerance for human mislabeling. The main process involves Rough Labeling [Formula: see text] Machine Learning [Formula: see text] Probability Region Search [Formula: see text] Data Relabeling [Formula: see text] Machine Learning again. The objective of ACL is to secure more accurate labeled data for model retraining. Through vortex localization experiments conducted in a two-dimensional Bose-Einstein condensate, our results establish the following: 1. Even under conditions of biased and missing manual annotations, U-Net can still accurately locate vortex positions; 2. Vortices exhibit certain regularities, and training U-Net with a small number of samples yields excellent predictive consequences; 3. The machine learning vortex locator based on the ACL method effectively corrects errors in manually annotated data, significantly improving the model's performance metrics, thus enhancing the precision and metrics of vortex localization. This substantial advancement in the application of machine learning in vortex localization provides an effective way for vortex dynamics localization. Furthermore, this method of obtaining more accurate positions of approximate human labels through machine learning offers new insights for machine learning in other types of image recognition problems.
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Herein, a series of polyimide (PI)/titanium dioxide (TiO2) organic-inorganic flexible composite microfibers with high photocatalytic performance and good reusability were prepared by combining electrospinning technology and a hydrothermal method. Under simulated sunlight, the photocatalytic characteristics of the as-prepared PI nanofibers, TiO2 nanorods, and PI/TiO2 microfibers were evaluated with photocatalytic degradation of Rhodamine B (RhB) solution. Among the tested samples, PI/TiO2-3 mL hydrochloric acid-160 °C-14 h (PI/TiO-3-160-14) (100%) exhibited a superior photocatalytic degradation rate compared to pure PI (84.0%) and TiO2 (62.2%). The enhancement of the photocatalytic performance was attributed to the Z-scheme heterojunction mechanism. When the interface was irradiated by simulated sunlight, the band edge bending, built-in electric field, and Coulomb interaction synergistically facilitated the separation and transport of electron-hole pairs in the heterojunction. This enhanced the oxidation and reduction abilities of the valence and conduction bands of PI/TiO2. These results were adequately verified by X-ray photoelectron spectroscopy (XPS) analyses and radical trapping experiments. Additionally, PI/TiO2 microfibers also demonstrated excellent photocatalytic activity toward methylene blue (MB, 81.4%), methyl orange (MO, 95.9%), and malachite green (KG, 98.9%), underscoring the versatile applicability of PI/TiO2. Further supplementary investigations illustrated that PI/TiO2 microfibers also possess excellent photostability during our extensive recycling photocatalytic experiments.
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Saline-alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline-alkali stress than its donor counterparts, which is reflected by differential gene expression between autotetraploid and diploid rice in response to salt, alkali, and saline-alkali stress. In this study, we investigated the expression of the transcription factors (TFs) in the leaf tissues of autotetraploid and diploid rice under different types of saline-alkali stress. Transcriptome analysis identified a total of 1040 genes from 55 TF families that were altered in response to these stresses, with a significantly higher number in autotetraploid rice compared to diploid rice. Contrarily, under these stresses, the number of expressed TF genes in autotetraploid rice was greater than that in diploid rice for all three types of stress. In addition to the different numbers, the differentially expressed TF genes were found to be from significantly distinct TF families between autotetraploid and diploid rice genotypes. The GO enrichment analysis unraveled that all the DEGs were distributed with differentially biological functions in rice, in particular those that were enriched in the pathways of phytohormones and salt resistance, signal transduction, and physiological and biochemical metabolism in autotetraploid rice compared to its diploid counterpart. This may provide useful guidance for studying the biological roles of polyploidization in plant resilience in response to saline-alkali stress.
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Diploide , Oryza , Humanos , Oryza/genética , Fatores de Transcrição/genética , Perfilação da Expressão Gênica , Solução Salina , Cloreto de Sódio , Folhas de Planta/genéticaRESUMO
Water is a key factor limiting plant growth in loess regions. Studying water use by different afforestation species under different water conditions is crucial to understand the drought resistance mechanisms of plants in arid and semi-arid regions. We analyzed water use at different depths by the afforestation species Robinia pseudoacacia and Platycladus orientalis under the drought treatment (100% no throughfall, DT) and the natural rainfall (control, CK) by stable isotope (δ18O, δ2H) technique and explored their drought adaptability. The results showed that R. pseudoacacia mainly absorbed soil water at 0-40 cm soil layer in the wet months (June and September), with a contribution rate of 68.0%±2.4%, and at four layers (0-10, 10-40, 40-60, and 60-120 cm) evenly in the dry months (July and August) in the CK. In contrast, P. orientalis mainly absorbed soil water at 0-40 cm layer in both the wet and dry months, with the contribution rate being 77.0%±2.4% and 57.4%±3.0%, respectively. In the DT, the water-use depths of R. pseudoacacia and P. orientalis tended to move downward with the decreases of soil water content. The water-use depths of R. pseudoacacia changed from 0-40 cm to 60-120 cm, while that of P. orientalis changed from 0-40 cm to the four layers mentioned evenly. R. pseudoacacia and P. orientalis could adjust water-use depths under different water conditions and showed strong drought adaptability, a feature of great significance for evaluating the stress resistance and stability of local plantations.
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Robinia , Thuja , Solo , Água , China , PlantasRESUMO
By using different active materials as gain media, we demonstrate a system aimed to measure the fluorescence lifetime of gain media in the fiber laser by utilizing the correlation between the laser's relaxation oscillation characteristics and the fluorescence lifetime of the active materials. As the advantages of extremely compact configuration, non-destructive and real time of the system, the fluorescence lifetime of gain media composed of materials of erbium-ytterbium-doped or erbium-doped have been measured, whose results are 20.2 µs and 1.62 ms, respectively. The proposed method provides a new, to the best of our knowledge, idea for real-time monitoring of fluorescence lifetime in the fiber laser.
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This Letter proposes an all-fiber self-mixing interferometric method based on laser feedback technology with long transmission distance, which has advantages of high sensitivity and compact structure. We theoretically and experimentally verify that the measurement distance of the self-mixing sensor is not limited to the coherence length of the solitary laser used. In the experiment, the velocity of a non-cooperative target was successfully measured with 40 km transmission distance. Therefore, the all-fiber self-mixing Doppler velocimeter has a great application prospect in the field of remote sensing measurement. Its unique flexibility can be applied to a variety of complex environments of non-cooperative target measurement.
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Molecules in confined spaces exhibit unusual behaviors that are not typically observed in bulk systems. Such behavior can provide alternative strategies for exploring new reaction pathways. Cleavage of the C=N bond of Nile red (NR) in solution is an irreversible reaction. Here, we used spatial confinement within a cationic micelle-confined system to convert this reaction to a reversible process. The fluorescence of NR shifted between red and green for nine cycles. The new chemical pathway based on spatial confinement can be attributed to two factors: increasing the local concentration of reactants and reducing the reaction energy barrier. This effect is supported by both experimental evidence and theoretical calculations. The cross-linked silica shell comprising the confinement chamber stabilizes the enclosed molecules. This reduces fluorophore leakage and maintains fluorescence intensity in most environments, including in solution, on paper, and in hydrogel films, and expands practical applications in encrypted information and multi-informational displays.
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B and T lymphocyte attenuator (BTLA) is one of the most important cosignaling molecules. It belongs to the CD28 superfamily and is similar to programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) in terms of its structure and function. BTLA can be detected in most lymphocytes and induces immunosuppression by inhibiting B and T cell activation and proliferation. The BTLA ligand, herpesvirus entry mediator (HVEM), does not belong to the classic B7 family. Instead, it is a member of the tumor necrosis factor receptor (TNFR) superfamily. The association of BTLA with HVEM directly bridges the CD28 and TNFR families and mediates broad and powerful immune effects. Recently, a large number of studies have found that BTLA participates in numerous physiopathological processes, such as tumor, inflammatory diseases, autoimmune diseases, infectious diseases, and transplantation rejection. Therefore, the present work aimed to review the existing knowledge about BTLA in immunity and summarize the diverse functions of BTLA in various immune disorders.
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Doenças do Sistema Imunitário/etiologia , Doenças do Sistema Imunitário/metabolismo , Imunidade , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Animais , Autoimunidade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Suscetibilidade a Doenças , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Transplante de Órgãos/efeitos adversos , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
The diffusion of target analytes is a determining factor for the sensitivity of a given gas sensor. Surface adsorption results in a low-concentration region near the sensor surface, producing a concentration gradient perpendicular to the surface, and drives a net flux of molecules toward solid reactive reagents on the sensor surface, that is, vertical diffusion. Here, organic semiconductor supramolecules were patterned into micromeshed arrays to integrate vertical and horizontal diffusion pathways. When used as a gas sensor, these arrays have an order of magnitude higher sensitivity than traditional film-based sensors. The sensor sensitivity ramp down with the increase in coverage density of reactive reagents, yielding two linear regions demarcated by 0.3 coverage, which are identified by the experimental results and simulations. The universal nature of template-assisted patterning allows adjustments in the composition, size, and shape of the constituent material, including nanofibers, nanoparticles, and molecules, and thus serves to improve the sensitivity of gas sensors for detecting various volatile organic compounds.
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The engineering of metal-organic frameworks (MOFs) into membranes and films is being investigated, to transform laboratory-synthesized MOFs into industrially viable products for a range of attractive applications. However, rational design and construction of highly permeable MOF thin films, without trade-offs in terms of structural mechanical stability, remains a significant challenge. Herein, a simple, general strategy is reported to prepare thin MOF nanosheet (NS)-assembled frame film via heteroepitaxial growth from metal hydroxide film. As the thin MOF NS-assembled film significantly enhances the permeability of mass though the film, the resultant gold nanoparticle (Au NP)@MOF film exhibits much higher catalytic efficiency than the Au NP@MOF bulk film. Meanwhile, the unique framework of the MOF NS-assembled film resists torsion and collapse, so the composite catalyst exhibits long-term stability.
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Redesigning heterogeneous catalysts so that they can simultaneously integrate the efficiency and durability under reaction environments with respect to gas fuel production, such as hydrogen (H2), oxygen (O2), or carbon monoxide (CO), has proven challenging. In this work, we report the successful template-assisted printing-based assembly of platinum (Pt) nanoparticles (NPs) into striped-pattern (SP) superlattices to produce H2. In comparison to drop-casting flat Pt NPs films, SP superlattices lead to higher mass transference and smaller bubble stretch force, representing a general strategy to improve the efficiency and durability of pre-existed Pt catalysts for the hydrogen evolution reaction (HER), as well as higher current densities than commercial Pt/C, Pt NP films, and many of the other Pt-based or non-Pt-based HER catalysts reported in the literature. The generic nature of template-assisted printing leads to flexibility in the composition, size, and shape of the constituent NPs or molecules, and thus extends such an accelerated technique for producing the oxygen evolution reaction and electrochemical reduction of CO2 to CO.
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In this paper, a vibration-displacement immunization model is proposed to measure the free spectral range of a resonant cavity by using a laser self-mixing velocimeter. The validity of this method is demonstrated by the experimental results, which can effectively get rid of low measurement accuracy related to the self-mixing vibration system due to the vibratory displacement. According to the periodic waveform separation characteristic of the self-mixing velocity signal, the free spectral range of a multilongitudinal mode diode laser is calculated to be 88.24 GHz. Moreover, the influences of different target velocities and signal sampling frequencies on the free spectral range have been analyzed in detail from the theoretical analysis. In the case of high signal sampling rate and low velocity, from which the undistorted velocity signal waveform at the integral order external cavity mode keeps stable, it is possible to obtain relatively accurate measured results.
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Imunização , Lasers , Modelos Teóricos , Reologia/instrumentação , Vibração , Simulação por Computador , Processamento de Sinais Assistido por ComputadorRESUMO
Lamellar nanomaterials with specific architectures and novel properties have received increasing attention from both scientific and technological fields in recent years because of their potential applications in catalysis, energy conversion, and storage devices. Bulk supercluster pellets with well-defined lamellar structures were fabricated by assembling silver clusters and mercaptoalkyl acids (MXA) to investigate the mechanical properties. The relationship between the assembled structure and pressure resistance was surveyed for the first time. The enhanced interlayer interactions were found to increase the elastic modulus of the Ag-MXA supercluster architectures.
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Although the strength of Raman signals can be increased by many orders of magnitude on noble metal nanoparticles, this enhancement is confined to an extremely short distance from the Raman-active surface. The key to the development of Raman spectroscopy for applications in diagnosis and detection of cancer and inflammatory diseases, and in pharmacology, relies on the capability of detecting analytes that are noninteractive with Raman-active surfaces. Here, a new Raman enhancement system is constructed, superficial-layer-enhanced Raman scattering (SLERS), by covering elongated tetrahexahedral gold nanoparticle arrays with a superficial perovskite (CH3 NH3 PbBr3 ) film. Plasmonic decay is depressed along the vertical direction away from the noble metal surface and the penetration depth is increased in the perovskite media. The vertical penetration of SLERS is verified by the spatial distribution of the analytes via Raman imaging in layer-scanning mode.