Conventional Type Research Articles

Simulating Error Due to Acquired Thermoelectric Inhomogeneity.

The best method to prevent error due to inhomogeneity is to use a new thermocouple design-the thermocouple with controlled temperature field (TCTF). It uses the auxiliary furnace to control the temperature field along its legs. Such a design allows setting and maintaining the temperature field along the thermocouple (TC) legs for the sensor. Error due to inhomogeneity of TCs cannot appear in a stable temperature field. However, the auxiliary furnace and TCs, to control the temperature field, have errors, so the temperature field along the main TC is maintained with some error. This leads to residual error due to acquired inhomogeneity of the TCTF. We constructed the mathematical models to fit the experimental data of error due to drift for the type K TC. The authors used the constructed models to study error due to inhomogeneity of the TCTF and the conventional type K TC under considerable changes in temperature field. The main results of modelling are as follows: (i) if the changes in temperature field exceed 7 °C, error due to inhomogeneity of the TCTF is lesser than that of the conventional TC; (ii) the maximum error due to inhomogeneity of the conventional type K TC is 10.75 °C; (iii) the maximum error due to inhomogeneity of the TCTF is below 0.2 °C.

Prdm1 positively regulates liver Group 1 ILCs cancer immune surveillance and preserves functional heterogeneity.

Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1-deficient cNK cells and liver ILC1s. Single-cell RNA sequencing (scRNA-seq) data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s, and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.

Prdm1 positively regulates liver Group 1 ILCs cancer immune surveillance and preserves functional heterogeneity

Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1-deficient cNK cells and liver ILC1s. Single-cell RNA sequencing (scRNA-seq) data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s, and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.

Long-Term Bonding Performance of One-Bottle vs. Two-Bottle Bonding Agents to Lithium Disilicate Ceramics.

The aim of this study was to compare the long-term bonding performance to lithium disilicate (LDS) ceramic between one-bottle and two-bottle bonding agents. Bonding performance was investigated under these LDS pretreatment conditions: with hydrofluoric acid (HF) only, without HF, with a two-bottle bonding agent (Tokuyama Universal Bond II) only. Shear bond strengths between LDS and nine resin cements (both self-adhesive and conventional adhesive types) were measured at three time periods: after one-day water storage (Base), and after 5000 and 20,000 thermocycles (TC 5k and TC 20k respectively). Difference in degradation between one- and two-bottle bonding agents containing the silane coupling agent was compared by high-performance liquid chromatography. With HF pretreatment, bond strengths were not significantly different among the three time periods for each resin cement. Without HF, ESTECEM II and Super-Bond Universal showed significantly higher values than others at TC 5k and TC 20k when treated with the recommended bonding agents, especially at TC 20k. Difference in degradation between one- and two-bottle bonding agents containing the silane coupling agent was compared by high-performance liquid chromatography (HPLC). For both cements, these values at TC 20k were also not significantly different from pretreatment with only Tokuyama Universal Bond II. For LDS, long-term bond durability could be maintained by pretreatment with Tokuyama Universal Bond II instead of the hazardous HF.

Vagaries of osteosarcoma at a tertiary care center in Southern India

Background: Osteosarcoma (Os) is the greatest histologic mimicker of all bone tumors. We conducted a retrospective study on its various histopathological patterns, vis-à-vis, clinical and diagnostic features, highlighting its variations. Aims and Objectives: The objective of this study was to study the demographic distribution of Os presenting to our centers and appreciate the histological variations of the disease prevalent in this part of the world as such a study had not been done before. Materials and Methods: Over a period of 25 years, we encountered 100 cases of Os at our institution. The clinical details, investigative findings, gross appearance of tumor tissue obtained, and their hematoxylin and eosin-stained microscopic appearance were studied. Results: The majority were in the 2nd and 3rd decades with a male-to-female ratio of 1.8:1. Long bones were most commonly involved. Microscopically, apart from the conventional type, the histological variants encountered were small cell, soft tissue, malignant fibrous histiocytoma-like, telangiectatic, and juxtacortical including parosteal, periosteal, and dedifferentiated parosteal. Patients were treated with radical amputations, chemo-radiotherapy, and limb salvage surgeries. Conclusion: Being obvious that Os presents with a variety of presentations eluding any prediction regards its biologic behavior, the pathologist should be keen on thorough sampling of tumor tissue and correlate the histologic type with the radiological appearance and clinical presentation.

Multi-dimensional attention-aided transposed ConvBiLSTM network for hyperspectral image super-resolution

Hyperspectral (HS) image always suffers from the deficiency of low spatial resolution, compared with conventional optical image types, which has limited its further applications in remote sensing areas. Therefore, HS image super-resolution (SR) techniques are broadly employed in order to observe finer spatial structures while preserving the spectra of ground covers. In this paper, a novel multi-dimensional attention-aided transposed convolutional long-short term memory (LSTM) network is proposed for single HS image super-resolution task. The proposed network employs the convolutional bi-directional LSTM for the purpose of local and non-local spatial–spectral feature explorations, and transposed convolution for the purpose of image amplification and reconstruction. Moreover, a multi-dimensional attention module is proposed, aiming to capture the salient features on spectral, channel, and spatial dimensions, simultaneously, to further improve the learning abilities of network. Experiments on four commonly-used HS images demonstrate the effectiveness of this approach, compared with several state-of-the-art deep learning-based SR methods.

Boosting Lithium Ion Conduction of Carboxylate‐Type Single‐Ion Conducting Polymers through Complexation with Ionic Liquids for Lithium‐Ion Batteries

AbstractSingle‐ion conducting (SIC) polymers, wherein anions are covalently bonded to the polymer chain, selectively facilitate the movement of lithium ions, making them promising polymer electrolytes for lithium‐ion batteries because only lithium ion acts as a charge carrier. Carboxylate‐type SIC polymers offer cost advantages and are facilely prepared compared to conventional types like sulfonylamide‐type SIC polymers. However, they are known to suffer from inefficient dissociation of lithium ions due to their high basicity. In this study, enhancement of lithium‐ion dissociation in carboxylate‐type SIC polymers is investigated by complexing them with ionic liquid (IL). Incorporation of IL with the SIC polymer significantly improves electrochemical properties, achieving a high ionic conductivity close to 2 mS cm−1 and a critical current density of 2.1 mA cm−2 in a Li symmetric cell at 25 °C. The interaction between the SIC polymer and IL is confirmed through infrared and Raman spectroscopy. Electrochemical tests of the Li/LiFePO4 cell exhibit a high reversible capacity of 128.6 mAh g−1 with a cycle retention of 89.9 % after 100 cycles at 1 C (1 C=170 mA g−1) and an excellent recuperation even after rate tests at 6 C.

A multifunctional PEGylated liposomal-encapsulated sunitinib enhancing autophagy, immunomodulation, and safety in renal cell carcinoma

BackgroundSunitinib is a multikinase inhibitor used to treat patients with advanced renal cell carcinoma (RCC). However, sunitinib toxicity makes it a double-edged sword. Potent immune modulation by sunitinib extends to nuclear interactions. To address these issues, there is an urgent need for delivery vectors suitable for sunitinib treatment.MethodsWe developed PEGylated liposomes as delivery vectors to precisely target sunitinib (lipo-sunitinib) to RCC tumors. Further investigations, including RNA sequencing (RNA-seq), were performed to evaluate transcriptomic changes in these pathways. DiI/DiR-labeled lipo-sunitinib was used for the biodistribution analysis. Flow cytometry and immunofluorescence (IF) were used to examine immune modulation in orthotopic RCC models.ResultsThe evaluation of results indicated that lipo-sunitinib precisely targeted the tumor site to induce autophagy and was readily taken up by RCC tumor cells. In addition, transcriptomic assays revealed that following lipo-sunitinib treatment, autophagy, antigen presentation, cytokine, and chemokine production pathways were upregulated, whereas the epithelial-mesenchymal transition (EMT) pathway was downregulated. In vivo data provided evidence supporting the inhibitory effect of lipo-sunitinib on RCC tumor progression and metastasis. Flow cytometry further demonstrated that liposunitinib increased the infiltration of effector T cells (Teffs) and conventional type 1 dendritic cells (cDC1s) into the tumor. Furthermore, systemic immune organs such as the tumor-draining lymph nodes, spleen, and bone marrow exhibited upregulated anticancer immunity following lipo-sunitinib treatment.ConclusionOur findings demonstrated that lipo-sunitinib is distributed at the RCC tumor site, concurrently inducing potent autophagy, elevating antigen presentation, activating cytokine and chemokine production pathways, and downregulating EMT in RCC cells. This comprehensive approach significantly enhanced tumor inhibition and promoted anticancer immune modulation.Graphical

Geometry Selection in Three-Mirror Freeform Imagers with an Accessible Exit Pupil.

Reimaging telescopes have an accessible exit pupil that facilitates stray light mitigation and matching to auxiliary optical systems. Freeform surfaces present the opportunity for unobscured reflective systems to be folded into geometries that are otherwise impracticable with conventional surface types. It is critical, however, to understand the limitations of the enabled folding geometries and choose the one that best balances the optical performance and mechanical requirements. Here, we used the aberration theory of freeform surfaces to determine the aberration correction potential for using freeform surfaces in reimaging three-mirror telescopes and established a hierarchy for the different folding geometries without using optimization. We found that when using freeform optics, the ideal folding geometry had 9× better wavefront performance compared to the next best geometry. Within that ideal geometry, the system using freeform optics had 39% better wavefront performance compared to a system using off-axis asphere surfaces, thus quantifying one of the advantages of freeform optics in this design space.

Improved time series models for the prediction of lane-change intention

ABSTRACT To improve the accuracy of lane-change intention prediction and analyze the influence of driving styles on prediction outcomes, the T-Encoder-Sequence model is proposed in this paper. It integrates the Transformer’s encoder module with various recurrent neural network (RNN) models and introduces a multimodal fusion input structure. Building on this, a risk indicator model, capable of reflecting driver stress, is established to calculate the model’s input parameters. Consequently, the model can simultaneously capture global information and consider the impact of vehicle classes on drivers. Furthermore, the k-means++ algorithm is employed to categorize vehicle trajectories into conservative, conventional, and aggressive types for further analysis. The results demonstrate that training the model with risk indicator parameters markedly enhances prediction performance. Under identical input parameters, the T-Encoder-Sequence model exhibits notably superior prediction efficacy compared to the original model. The T-Encoder-Sequence model, trained with risk indicator parameters, demonstrates substantial advantages compared to other studies.

Experimental and numerical studies on moisture adsorption/desorption characteristics across the circular fin tube desiccant coated heat exchanger

To improve the energy transfer abilities, enhance the quality of air, and curtail the growth of microorganisms, the desiccant coated heat exchangers are a capable substitute compared to conventional heat exchangers due to their capability of decoupling the sensible and latent loads and utilizing low-grade thermal energy. The concept of desiccant coated heat exchangers (DCHE) can be employed in various heat exchange/transport systems like heat pumps, atmospheric water harvesters, adsorption chillers, and air conditioners. Thus, in this research work, a circular fin tube desiccant coated heat exchanger (DCCHE) has been proposed and designed and a dynamic numerical model is established for simulating the combined heat and mass transport occurring across the adsorption/desorption process of a DCCHE employing finite element approach. The moisture and temperature distribution and flow of fluid are considered in the transient numerical model covering several domains such as water flow, air flow, and the coated desiccant. The desiccant material utilized in the current analysis is silica gel. The validation study showed good agreement, and the maximum error between the experimental result and simulated model for the humidity ratio of air and temperature of outlet air were observed to be ± 8 % and ± 7 %, respectively. A parametric analysis is carried out to assess the effect of varying the different input parameters on DCCHE’s performance. The field emission scanning electron microscopy results concluded that a uniform coating is formed on the circular fin surface. The experimental examination on the sorption kinetics of the silica gel showed that the moisture uptake capability was 0.34 g/g. Moreover, the proposed circular fin tube desiccant coated heat exchanger has been compared with the conventional plate type fin tube DCHE to assess its performance in terms of thermal coefficient of performance and specific dehumidification energy.

Development of an enhanced damage law for typical steel fiber reinforced concrete based on uniaxial compression and tension tests

Understanding the stiffness of a concrete structure is crucial to analyze it, particularly for statically indeterminate structures. Stiffness degradation – commonly referred to as damage – occurs with the onset of cracking or large compressive strains. For most conventional and specialized types of concrete, damage studies and models for predicting damage development are available. However, more information is needed about the damage behavior for the most common steel fiber reinforced concrete in Europe with strength class C30/37 and modern end-anchored high-strength fibers in dosages of 20–40 kg/m3. Therefore, in this study, these common steel fiber concretes were subjected to multiple load cycles in (1) uniaxial compression tests on cylinders and (2) direct tensile tests on bone specimens to investigate their damage behavior. The resulting damage was then compared to known damage laws, but none of the models predicted accurate damage results. Finally, an existing damage law for plain concrete was modified as a function of the residual flexural tensile strength—the relevant parameter for describing the performance of the steel fiber reinforced concrete. Hereby, we were able to decisively improve the agreement between experimental results and the theoretical prognosis by utilizing our modified damage law.

Focus tunable vector autofocusing Airy vortex beams resist atmospheric turbulence.

The rapid increase in orbital angular momentum (OAM) mode size with increasing modal order, given the limited-size of the receiver, is a major impediment to high-capacity OAM mode multiplexing in practice. Based on the Pancharatnam-Berry (PB) phase theory, we correlate the change of the polarization state with the curvature of the wavefront isophase line in the source plane and manipulate the focusing ability of vector autofocusing Airy vortex beam (AAVB) by combining the isophase line curvature and the intensity gradient of the beam, which are two independent degrees of freedom. The present method enables flexible on-demand focusing of vector AAVBs in free space and is more effective in focusing higher order OAM modes, which can reduce the full-width at half maximum (FWHM) of the AAVB with topological charge l= 25 to 1/5 of that of the conventional scalar type. And the modulated vector AAVB is superior to the conventional scalar one in terms of mitigating atmospheric turbulent disturbance. The work provides a potentially useful basis for improving the capability of future free-space OAM systems for large-scale dense communications.

The relationship between psoriasis and vitiligo: From a comprehensive study.

Both psoriasis and vitiligo are autoimmune skin diseases. Previous observational studies have indicated a relationship between the two conditions, and simultaneous onset of both diseases poses increased health risks to patients. However, limited research has explored the causal relationship between psoriasis and vitiligo. To investigate whether a causal association exists between psoriasis and vitiligo. A case of Chinese patients diagnosed with psoriasis and vitiligo has been reported. Transcriptome sequencing was performed on normal, psoriasis, vitiligo, and co-morbid skin tissues of the patients, and single-cell transcriptome sequencing was conducted on the co-morbid skin tissues. A comprehensive Mendelian randomization analysis of Genome-wide association studies (GWAS) was performed on a cohort of 261 018 European individuals with psoriasis from the IEU Open GWAS Project and vitiligo from the National Institutes of Health (NIH) Database of Genotypes and Phenotypes. Case report and transcriptome results showed that skin tissue with vitiligo combined with psoriasis exhibited both vitiligo and psoriasis. Single-cell transcriptome sequencing results showed that in comparison to normal skin and psoriatic skin, the proportions of CD8+ T cells, natural killer cells, naive T cells, T helper cells 17, regulatory T cells, conventional type 1 dendritic cells, Conventional type 2 dendritic cells, and plasmacytoid dendritic cells were all increased in skin tissue with vitiligo combined with psoriasis. Mendelian randomization analysis included 4510 patients with psoriasis and 4680 patients with vitiligo. The results showed no causal relationship between vitiligo and psoriasis in the forward direction (p=0.192; odds ratio [OR], 1.059; 95% confidence interval [CI], 0.971-1.155) or in the reverse direction (p=0.459; OR, 0.927; 95% CI, 0.757-1.134). This study suggests that the association between psoriasis and vitiligo may be closely related to immunity, however, Mendelian randomization studies do not support a causal relationship. These findings hold significant implications for clinicians aiming to enhance their understanding and treatment approaches for psoriasis and vitiligo.

Accuracy and Comparison of Core Needle Biopsy Diagnoses With Excision Specimen for Diagnosing Fibroepithelial Lesions of the Breast.

Background Core needle biopsy (CNB) for fibroepithelial lesions (FELs) of the breast is commonly encountered by histopathologists. The distinction between fibroadenoma (FA) and phyllodes tumor (PT) can be challenging due to overlapping histological features and the limited nature of CNB material. Objective This study aimed to assess the accuracy of CNB diagnosis of FA and PT by comparing it with a diagnosis on subsequent surgical excision specimen. Materials and methods A total of 166 cases of FELs of the breast who underwent CNB and subsequent surgical excision between January 2001 and December 2020 were included in our study. All microscopy glass slides were reviewed, and diagnosis confirmed. Results While 125 (75%) cases based on CNB received a definitive diagnosis of either fibroadenoma or PT, the remaining 41 (25%) cases were better classified on excision specimens and were descriptively diagnosed as fibroepithelial lesions on CNB. Diagnoses on CNB and on subsequent excision specimens were concordant in 113 (90.4%) cases. Among 12 cases that were discordant, three cases diagnosed as FA on CNB were upgraded toPT on excision specimens. Nine cases diagnosed as PT on CNB were diagnosed as FA on excision specimens. These included conventional, cellular, juvenile, and complex FA types. Three PTs, which were reported as FA on CNB, measured 6, 12.5, and 17.5 cm in the greatest dimension. Among 23 cases of PT which were further categorized on CNB, tumor categories changed on excision specimens in three cases. The diagnostic accuracy of CNB diagnosis was 90.4%. Conclusion CNB diagnosis showed good accuracy. PT diagnosis should be strongly considered in all tumors measuring >5 cm, especially those exceeding 10 cm. Cellular, juvenile, and complex FAs can be misdiagnosed as PT on CNB. Correlation with clinical and radiological findings can be helpful in establishing correct diagnosis.

A Review on the Skin Cancer Detection Using Deep Learning Algorithms and LBP

Abstract: Skin cancer development is one of the conventional deadly disease types, with its cases expanding around the whole world. On the off chance that it's not analyzed in the early stages, it can prompt metastases, bringing about high death rates. Skin disease can be relieved whenever it's identified early. Thus, convenient and exact determination of such malignant growths is a key exploration objective. The early and precise identification of skin cancer has been suggested to be aided by deep-learning algorithms. The paper reviews new research articles based on deep learning methods and feature extraction techniques using LBP for skin cancer classification.

Investigation on the Biaxial Flexural Strength of Universal Shade Resin-Based Composites.

The biaxial flexural strength of universal shade and conventional dental resin-based composites before and after alkaline degradation was investigated. Disk samples were prepared from these resin-based composites, and some of the specimens were immersed in 0.1 M NaOH solution to create deteriorated samples. The biaxial flexural strength of the samples before and after the alkaline degradation test was measured and statistically tested. The fracture surfaces after the biaxial flexural test were observed using a scanning electron microscope. The results showed that the biaxial flexural strength of the paste-type universal shade resin-based composite before alkaline degradation was significantly (19%) higher than that of the conventional type, but no difference was observed between the materials after alkaline degradation. On the other hand, the biaxial flexural strength of the flowable universal shade resin-based composites was significantly (around 35%) lower than that of the conventional composite, with or without degradation. Although, for paste-type materials, the biaxial flexural strength of universal shade resin-based composites was higher than that of conventional resin-based composites before alkaline degradation, after degradation the two materials showed similar values. For flowable materials, the biaxial flexural strength of universal shade resin-based composites was lower than that of conventional resin-based composites regardless of the presence or absence of degradation processes. These results suggest that some caution should be used when deciding whether to use flowable universal shade resin-based composite to fill a cavity.

Shear mechanism of RCS joints with whole column-section diaphragm

The authors proposed a new precast RC column-steel beam (RCS) joint with whole column-section diaphragm, aiming to address the shortcomings including bearing failure and difficulty in prefabrication of the RCS joint details available in the existing literature. Due to its unique details, the proposed RCS joint may have a dissimilar force-transferring mechanism from the conventional beam-through type RCS joint. Moreover, the effect of various parameters on this novel joint was still unclear by limited test results. The objective of this study was to clarify the shear mechanism of the proposed joint and the impact of critical parameters. Specimens with different axial load ratios and thickness of parallel FBPs were tested under cyclic loading. The results showed that the increase in axial load ratio and thickness of parallel FBPs improved joint strength in this test. A detailed three-dimensional finite element (FE) model was developed and verified using the experimental results. The difference in the force transferring between the proposed joint and conventional beam-through RCS joints was explained in detail based on the numerical results. The dowel action of longitudinal column bars were evident in the proposed joint and the orthogonal FBPs were ineffective in activating the inner concrete strut. A parametric study was further conducted. The impacts of width of parallel FBPs, thickness of orthogonal FBPs, and axial load ratio were investigated. The joint strength linearly increased with the width of parallel FBPs. A parabolic distribution of shear stress in the parallel FBP section was obtained, while the yield zone was concentrated in the central area of the parallel FBP. The ductility could be improved with the thickness of orthogonal FBPs when the thickness was less than 10 mm. Further increasing the thickness of orthogonal FBP beyond 10 mm did not significantly affect the overall joint behavior. The joint may attain the optimal shear strength when the axial load ratio is between 0.3 and 0.4. The modeling approach in this study could be adopted as an effective tool to assess joint behavior. Moreover, the conclusions obtained by numerical study potentially promoted the application of the proposed joint.

On the future sustainable ultra-high-speed maglev: A superconductor magnet technology enabling high energy efficiency and robustness

The blooming ultrahigh-speed SC maglev (superconducting magnetically levitated train) prompts green travel worldwide. We utilized high-temperature superconductor (HTS) magnets and have developed an energy-economical SC maglev prototype (Energ. Convers. Manage. (291)117247). In this paper, as a continuation, we further improve and maximize the performance of its key part – the HTS magnets, especially in compact high magnetic field and energy density operating conditions, by innovating an HTS magnet technology named the Shunted Extreme-NI Concept. The operational energy-robustness, -density, and -economy of HTS magnets, compared to the conventional type, are improved by 96.8%, 66.7%, and 52.5%, respectively. For a full-scale maglev equipped with this technology, the estimated energy consumption per passenger kilometer can be further reduced to below 20% of that of airplanes under the same cruising speed of 1000 km/h. This work is dedicated to advancing the energy performances of HTS magnets, heading to the future sustainable maglev transportation.

Targeting dendritic cell-specific TNFR2 improves skin and joint inflammation by inhibiting IL-12/ IFN-γ pathways in a mouse model of psoriatic arthritis.

Psoriasis (PsO) and Psoriatic arthritis (PsA) are immune-mediated inflammatory diseases affecting the skin and joints. Approximately, 30% of patients with PsO develop PsA over time with both conditions being associated with elevated tumor necrosis factor-alpha (TNF-α) expression. TNF-α mediates its effect through two membrane receptors, TNFR1 and TNFR2. While current TNF-α-neutralizing agents, targeting both TNFR1 and TNFR2 receptors, constitute the primary treatment for psoriatic diseases, their long-term use is limited due to an increase in opportunistic infections, tuberculosis reactivation and malignancies likely attributed to TNFR1 inactivation. Recent findings suggest a pivotal role of TNFR2 in psoriatic disease, as evidenced by its amelioration in global TNFR2-knockout (TNFR2KO) mice, but not in TNFR1KO mice. The diminished disease phenotype in TNFR2KO mice is accompanied by a decrease in DC populations. However, the specific contribution of TNFR2 in dendritic cells (DCs) remains unclear. Here, utilizing a mannan-oligosaccharide (MOS)-induced PsA model, we demonstrate a significant reduction in PsA-like skin scaling and joint inflammation in dendritic cell-specific TNFR2 knockout mice (DC-TNFR2KO). Notably, MOS treatment in control mice (TNFR2 fl/fl) led to an increase in conventional type 1 dendritic cells (cDC1) population in the spleen, a response inhibited in DC-TNFR2KO mice. Furthermore, DC-TNFR2KO mice exhibited reduced levels of interleukin-12 (IL-12), a Th1 cell activator, as well as diminished Th1 cells, and interferon-gamma (IFN-γ) levels in the serum compared to controls following MOS stimulation. In summary, our study provides compelling evidence supporting the role of TNFR2 in promoting PsA-like inflammation through cDC1/Th1 activation pathways.