Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is among the most common chronic inflammatory skin diseases, usually occurring early in life, and often preceding other atopic diseases such as asthma. TH2 has been believed to play a crucial role in cellular and humoral response in AD, but accumulating evidence has shown that follicular helper T cell (TFH), a critical player in humoral immunity, is associated with disease severity and plays an important role in AD pathogenesis. OBJECTIVES: This study aimed at investigating how TFHs are generated during the pathogenesis of AD, particularly what is the role of keratinocyte-derived cytokine TSLP and Langerhans cells (LCs). METHODS: Two experimental AD mouse models were employed: (1) triggered by the overproduction of TSLP through topical application of MC903, and (2) induced by epicutaneous allergen ovalbumin (OVA) sensitization. RESULTS: This study demonstrated that the development of TFHs and germinal center (GC) response were crucially dependent on TSLP in both the MC903 model and the OVA sensitization model. Moreover, we found that LCs promoted TFH differentiation and GC response in the MC903 model, and the depletion of Langerin+ dendritic cells (DCs) or selective depletion of LCs diminished the TFH/GC response. By contrast, in the model with OVA sensitization, LCs inhibited TFH/GC response and suppressed TH2 skin inflammation and the subsequent asthma. Transcriptomic analysis of Langerin+ and Langerin- migratory DCs revealed that Langerin+ DCs became activated in the MC903 model, whereas these cells remained inactivated in OVA sensitization model. CONCLUSIONS: Together, these studies revealed a dual functionality of LCs in TSLP-promoted TFH and TH2 differentiation in AD pathogenesis.

Semantic Representation and Attention Alignment for Graph Information Bottleneck in Video Summarization.

End-to-end Long Short-Term Memory (LSTM) has been successfully applied to video summarization. However, the weakness of the LSTM model, poor generalization with inefficient representation learning for inputted nodes, limits its capability to efficiently carry out node classification within user-created videos. Given the power of Graph Neural Networks (GNNs) in representation learning, we adopted the Graph Information Bottle (GIB) to develop a Contextual Feature Transformation (CFT) mechanism that refines the temporal dual-feature, yielding a semantic representation with attention alignment. Furthermore, a novel Salient-Area-Size-based spatial attention model is presented to extract frame-wise visual features based on the observation that humans tend to focus on sizable and moving objects. Lastly, semantic representation is embedded within attention alignment under the end-to-end LSTM framework to differentiate indistinguishable images. Extensive experiments demonstrate that the proposed method outperforms State-Of-The-Art (SOTA) methods.

Determination of Johnson-Cook Constitutive of 15-5 PH Steel Processed by Selective Laser Melting.

To obtain a Johnson-Cook model of 15-5 PH steel formed by selective laser melting (SLM), and to determine the difference between the forging process, in this work, mechanical testing, penetration testing and numerical simulations were used to study 15-5 PH steel formed by SLM and forging. Finally, the Johnson-Cook model parameters and failure parameters of the 15-5 PH steel formed by SLM and forging were obtained. We found that the SLM process was beneficial for refining the grain size of 15-5 PH steel and for improving the mechanical properties of 15-5 PH steel, where the yield strength of its specimens increased by 13.1% compared with the forged specimens. The error between the numerical simulations and penetration tests was less than 10%, which verified the validity of the numerical model parameters. It was also found that the penetration ability and abrasion resistance of the SLM-shaped projectiles were slightly superior to those of the forged projectiles.

Split-Hopkinson Pressure Bar Test of Silicone Rubber: Considering Effects of Strain Rate and Temperature.

Using a split-Hopkinson pressure bar test instrument with a temperature control device, in this work, silicone rubber was tested at different temperatures (-40 °C-200 °C) and different strain rates (1.2 × 103 s-1-7.2 × 103 s-1). The results showed that the dynamic mechanical properties of silicone rubber were strain-rate sensitive at different temperatures and the yield strength of the silicone rubber increased with an increase in the strain rate. At a higher strain rate, silicone rubber showed temperature sensitivity. With a decrease in the strain rate, the influence of temperature on silicone rubber gradually decreased. Differential scanning calorimetry analysis showed that silicone rubber had good thermal stability at high temperatures. When the temperature was as low as -40 °C, the silicone rubber underwent a glass transition, showing the characteristics of brittle materials.

Penetration and Cratering of Steel Target by Jets from Titanium Alloy Shaped Charge Liners.

In order to enlarge the crater diameter of shaped charge jet penetration into steel targets, this paper investigates the penetration and cratering characteristics of steel targets by shaped charge jets from titanium alloy liners. Titanium alloy shaped charge liners are prepared separately with mechanical processing and selective laser melting (SLM), and pulsed X-ray radiography is used to identify jet formation characteristics. Jet formation is numerically simulated by AUTODYN-3D, and steel target penetration tests are carried out at a short jet stand-off distance. The results show that AUTODYN-3D can realistically simulate jet formation from titanium alloy liners and that the SLM-processed liner exhibits better penetration performance than the mechanically processed liner. The existing cratering formula of jet penetration is modified to make it consistent with the aperture variations of jet penetration from titanium alloy-lined shaped charges at a short stand-off distance. The findings of this study are expected to provide technical and theoretical support for research on the penetration characteristics of the jets from titanium alloy-lined shaped charges.

Context-dependent function of TSLP and IL-1ß in skin allergic sensitization and atopic march.

Atopic diseases, including atopic dermatitis (AD) and asthma, affect a large proportion of the population, with increasing prevalence worldwide. AD often precedes the development of asthma, known as the atopic march. Allergen sensitization developed through the barrier-defective skin of AD has been recognized to be a critical step leading to asthma, in which thymic stromal lymphopoietin (TSLP) was previously shown to be critical. In this study, using a laser-assistant microporation system to disrupt targeted skin layers for generating micropores at a precise anatomic depth of mouse skin, we model allergen exposure superficially or deeply in the skin, leading to epicutaneous sensitization or dermacutaneous sensitization that is associated with a different cytokine microenvironment. Our work shows a differential requirement for TSLP in these two contexts, and identifies an important function for IL-1ß, which is independent of TSLP, in promoting allergen sensitization and subsequent allergic asthma.

Keratinocyte-derived cytokine TSLP promotes growth and metastasis of melanoma by regulating the tumor-associated immune microenvironment.

Malignant melanoma is a major public health issue displaying frequent resistance to targeted therapy and immunotherapy. A major challenge lies in better understanding how melanoma cells evade immune elimination and how tumor growth and metastasis is facilitated by the tumor microenvironment. Here, we show that expression of the cytokine thymic stromal lymphopoietin (TSLP) by epidermal keratinocytes is induced by cutaneous melanoma in both mice and humans. Using genetically engineered models of melanoma and tumor cell grafting combined with TSLP-KO or overexpression, we defined a crosstalk between melanoma cells, keratinocytes, and immune cells in establishing a tumor-promoting microenvironment. Keratinocyte-derived TSLP is induced by signals derived from melanoma cells and subsequently acts via immune cells to promote melanoma progression and metastasis. Furthermore, we show that TSLP signals through TSLP receptor-expressing (TSLPR-expressing) DCs to play an unrecognized role in promoting GATA3+ Tregs expressing a gene signature including ST2, CCR8, ICOS, PD-1, CTLA-4, and OX40 and exhibiting a potent suppressive activity on CD8+ T cell proliferation and IFN-γ production. An analogous population of GATA3-expressing Tregs was also identified in human melanoma tumors. Our study provides insights into the role of TSLP in programming a protumoral immune microenvironment in cutaneous melanoma.

Compressive Properties and Constitutive Model of Semicrystalline Polyethylene.

The mechanical properties of polyethylene (PE) materials are greatly influenced by their molecular structures, environmental temperature, and strain rate. In this study, static and dynamic compression tests were performed on two semicrystalline PE materials-ultrahigh molecular weight polyethylene (UHMWPE) and high-density polyethylene (HDPE). The stress-strain curves of HDPE and UHMWPE under uniaxial compression at temperatures of -40-120 °C and strain rates of 0.001-5500 s-1 were obtained. The research findings suggest that both the UHMWPE and HDPE showed significant strain rate-strengthening effect and temperature-softening effect. In particular, HDPE exhibited better compression resistance and high-temperature resistance. The relationships between the yield stress and temperature and between the yield stress and strain rate for both materials were fitted, and the Cowper-Symonds constitutive model was built while considering the temperature effect. The parameters of the constitutive model were obtained and input into LS-DYNA software to simulate the dynamic compression process of HDPE. The simulation result was consistent with the test result, validating the accuracy of the constitutive parameters.

Mechanical Properties and Constitutive Model Applied to the High-Speed Impact of Aluminum Foam That Considers Its Meso-Structural Parameters.

In this work, quasistatic mechanical compression experiments were used to study the stress-strain relationship of aluminum foam, and the mechanism of the compressive deformation of aluminum foam under quasistatic compression conditions is discussed based on the experimental observations. Since the interactions among cells of the aluminum foam and differences in compressive strength among cells substantially impacted the mechanical properties of the material, the cellular structural parameters, namely the cell size and cell wall thickness, were defined. Along with the mechanism of deformation of a single cell, the influence of structural parameters on the micro failure mechanism and the stress-strain relationship of the aluminum foam material was analyzed. In combination with the factors influencing the mechanical properties of the aluminum foam, a mechanical constitutive model of aluminum foam suitable for multi-density and multi-impact environments that considers cellular structure density was established to predict the complete stress-strain relationship of aluminum foam under a high strain rate. The coupling function of strain rate and temperature in the original model was verified and the parameters were determined by the compression experiments under different strain rates and different temperatures.

Comparative Study of the Dynamic Deformation of Pure Molybdenum at High Strain Rates and High Temperatures.

To study the dynamic plastic properties of high-purity molybdenum materials at high temperature and high strain rate, we designed tests to compare the mechanical behaviour of two high-purity molybdenum materials with different purities and two with different processing deformation conditions under dynamic impact compression in the temperature range of 297-1273 K. We analysed the molybdenum materials' sensitivities to the strain-hardening effect, strain rate-strengthening effect, and temperature-softening effect as well as the comprehensive response to the combined effect of the strain rate and temperature, the adiabatic impact process, and the microstructure at high temperature and high strain rate. Furthermore, based on a modified Johnson-Cook constitutive model, we quantitatively analysed the flow stresses in these materials. The calculation results strongly agree with the test results. Our findings indicate that the high-purity molybdenum materials show consistent sensitivity to the combined effect of strain rate and temperature regarding the dynamic plastic properties. The materials with higher purity are less sensitive to the combined effect of the strain rate and temperature, and those with less processing deformation experience more pronounced strain-hardening effects. Under high strain rate at room temperature, these materials are highly susceptible to impact embrittlement and decreases in dynamic plastic properties due to intergranular fracture in the internal microstructure. However, increasing the impact environment temperature can significantly improve their plastic properties. The higher the temperature, the better the plastic properties and the higher the impact toughness.

Dynamic Constitutive Model of Ultra-High Molecular Weight Polyethylene (UHMWPE): Considering the Temperature and Strain Rate Effects.

The temperature and strain rate significantly affect the ballistic performance of UHMWPE, but the deformation of UHMWPE under thermo-mechanical coupling has been rarely studied. To investigate the influences of the temperature and the strain rate on the mechanical properties of UHMWPE, a Split Hopkinson Pressure Bar (SHPB) apparatus was used to conduct uniaxial compression experiments on UHMWPE. The stress-strain curves of UHMWPE were obtained at temperatures of 20-100 °C and strain rates of 1300-4300 s-1. Based on the experimental results, the UHMWPE belongs to viscoelastic-plastic material, and a hardening effect occurs once UHMWPE enters the plastic zone. By comparing the stress-strain curves at different temperatures and strain rates, it was found that UHMWPE exhibits strain rate strengthening and temperature softening effects. By modifying the Sherwood-Frost model, a constitutive model was established to describe the dynamic mechanical properties of UHMWPE at different temperatures. The results calculated using the constitutive model were in good agreement with the experimental data. This study provides a reference for the design of UHMWPE as a ballistic-resistant material.

Chromatin remodellers Brg1 and Bptf are required for normal gene expression and progression of oncogenic Braf-driven mouse melanoma.

Somatic oncogenic mutation of BRAF coupled with inactivation of PTEN constitute a frequent combination of genomic alterations driving the development of human melanoma. Mice genetically engineered to conditionally express oncogenic BrafV600E and inactivate Pten in melanocytes following tamoxifen treatment rapidly develop melanoma. While early-stage melanomas comprised melanin-pigmented Mitf and Dct-expressing cells, expression of these and other melanocyte identity genes was lost in later stage tumours that showed histological and molecular characteristics of de-differentiated neural crest type cells. Melanocyte identity genes displayed loss of active chromatin marks and RNA polymerase II and gain of heterochromatin marks, indicating epigenetic reprogramming during tumour progression. Nevertheless, late-stage tumour cells grown in culture re-expressed Mitf, and melanocyte markers and Mitf together with Sox10 coregulated a large number of genes essential for their growth. In this melanoma model, somatic inactivation that the catalytic Brg1 (Smarca4) subunit of the SWI/SNF complex and the scaffolding Bptf subunit of the NuRF complex delayed tumour formation and deregulated large and overlapping gene expression programs essential for normal tumour cell growth. Moreover, we show that Brg1 and Bptf coregulated many genes together with Mitf and Sox10. Together these transcription factors and chromatin remodelling complexes orchestrate essential gene expression programs in mouse melanoma cells.