Optimized wideband and compact multifunctional photonic device based on Sb2S3 phase change material.

In this paper, a 1 × 2 photonic switch is designed based on a silicon-on-insulator (SOI) platform combined with the phase change material (PCM), Sb2S3, assisted by the direct binary search (DBS) algorithm. The designed photonic switch exhibits an impressive operating bandwidth ranging from 1450 to 1650 nm. The device has an insertion loss (IL) from 0.44 dB to 0.70 dB (of less than 0.7 dB) and cross talk (CT) from -26 dB to -20 dB (of less than -20 dB) over an operating bandwidth of 200 nm, especially an IL of 0.52 dB and CT of -24 dB at 1550 nm. Notably, the device is highly compact, with footprints of merely 3 × 4 µm2. Furthermore, we have extended the device's functionality for multifunctional operation in the C-band that can serve as both a 1 × 2 photonic switch and a 3 dB photonic power splitter. In the photonic switch mode, the device demonstrates an IL of 0.7 dB and a CT of -13.5 dB. In addition, when operating as a 3 dB photonic power splitter, the IL is less than 0.5 dB.

Multifunctional metalens optical tweezers for optical information recognition.

Traditional optical information recognition (OIR), particle capture and manipulation require many optical devices or mechanical moving system components to achieve a specific function, which is difficult to achieve integration. This paper proposes a new method to realize these functions by using multi-focus metalens combining spectrum and polarization selection. The design incorporates three spectral bands, namely 500 nm, 580 nm, and 660 nm, within the visible light range. Additionally, it utilizes either left-handed or right-handed circularly polarized (LCP/RCP) light, resulting in six distinct focus focusing effects on a single focal plane. By analyzing the normalized light intensity (NLI) at the corresponding focus position, the OIR of any wavelength and polarization detection in the design can be realized, and the particle capture at different focusing positions can be realized. Our work can provide a new idea for the high integration of on-chip light recognition and operation and inspire the design of a highly integrated optical system with a smaller size and more substantial function.

Successful Treatment of Refractory Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome with Baricitinib, a Janus Kinase Inhibitor.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a rare immune-mediated inflammatory disease, poses diagnostic and therapeutic challenges owing to its multi-system involvement, high heterogeneity, and lack of specific laboratory tests. Additionally, lacking evidence-based treatment recommendations, with the primary approach focusing on symptomatic relief. Herein, we report the case of a 32-year-old Chinese woman who presented with recurrent, generalized multiple osteoarticular pain lasting over one year and skin erythema pustulosis for 11 months. Traditional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and other traditional approaches, yielded no significant effects. Despite the prior use of adalimumab and acitretin capsules, the treatment remained unsatisfying, especially regarding the skin lesions. Considering the complex pathogenesis of SAPHO syndrome, the patient was orally administered baricitinib (2 mg), a Janus kinase (JAK) inhibitor, twice daily. A notable improvement in both skin lesions and osteoarticular pain was observed within two weeks of treatment initiation. Subsequently, the dosage of baricitinib was halved and continued for an additional three months, during which regular follow-ups revealed neither disease recurrence nor adverse effects. Collectively, the successful treatment of refractory SAPHO syndrome with baricitinib presents a promising implication for addressing the therapeutic challenges of this rare autoimmune condition, offering a potential breakthrough in managing its complex manifestations.

Design and Implementation of a Flexible Electromagnetic Actuator for Tunable Terahertz Metamaterials.

Actuators play a crucial role in microelectromechanical systems (MEMS) and hold substantial potential for applications in various domains, including reconfigurable metamaterials. This research aims to design, fabricate, and characterize structures for the actuation of the EMA. The electromagnetic actuator overcomes the lack of high drive voltage required by other actuators. The proposed actuator configuration comprises supporting cantilever beams with fixed ends, an integrated coil positioned above the cantilever's movable plate, and a permanent magnet located beneath the cantilever's movable plate to generate a static magnetic field. Utilizing flexible polyimide, the fabrication process of the EMA is simplified, overcoming limitations associated with silicon-based micromachining techniques. Furthermore, this approach potentially enables large-scale production of EMA, with displacement reaching up to 250 µm under a 100 mA current, thereby expanding their scope of applications in manufacturing. To demonstrate the function of the EMA, we integrated it with a metamaterial structure to form a compact, tunable terahertz absorber, demonstrating a potential for reconfigurable electromagnetic space.

A Case of Paradoxical Reactions to Biologic Therapy for Psoriasis.

Introduction: Psoriasis is an immune-mediated chronic inflammatory skin disease. As our understanding of the pathogenesis of psoriasis has improved, biologic agents have become increasingly important in the treatment of psoriasis. However, the use of biologic agents is associated with cutaneous side effects. A new type of side effect called paradoxical reactions is an emerging threat arising from the increasing use of biologic agents. Case: Here, we present a case of paradoxical skin reactions - pyoderma gangrenosum (PG) and eczema - induced by biologic therapy. The case was successfully and eventually treated with baricitinib. Discussion: PG is a rare inflammatory disease characterised by painful and necrotic ulcerations containing neutrophils. It has been associated with autoimmune diseases such as inflammatory bowel disease (IBD). TNF (tumor necrosis factor) -α inhibitors can effectively treat refractory PG, while IL (interleukin) -17A inhibitors may worsen IBD symptoms. The cause of PG in this case was believed to be secukinumab, not adalimumab. The patient was diagnosed with eczematous dermatitis due to TNF-α inhibitors, and baricitinib was added to treat eczematous dermatitis. Conclusion: Paradoxical reactions are unpredictable events that may occur during treatment with biologics at anytime. They need further research in order to formulate personalised treatment.

Direct Immunofluorescence of IgG on Formalin-Fixed Paraffin-Embedded Tissue by Heat-Induced Antigen Retrieval as a Sensitive Method for the Diagnosis of Pemphigus.

Purpose: Direct immunofluorescence (DIF) on frozen sections (DIF-F) plays a key role in the identification and differential diagnosis of bullous dermatoses, which are a group of critical autoimmune diseases that include pemphigus, bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). However, this technique requires specialized laboratory equipment conditions, sample acquisition and sample preservation. In this study, the application value of DIF on paraffin-embedded tissue sections (DIF-P) detecting IgG using heat-induced antigen retrieval (HIAR) in the diagnosis of bullous dermatosis was explored. Patients and Methods: Samples from 12 patients with pemphigus vulgaris (PV), 10 patients with pemphigus foliaceus (PF), 17 patients with BP, and 4 patients with EBA were retrospectively studied for DIF-P IgG detection. Formalin-fixed, paraffin-embedded tissue (FFPE) was used, and the antigen retrieval method used in the experiment was HIAR. All patients were diagnosed with the autoimmune bullous disease (AIBD) based on clinical presentation, histopathology, DIF-F, and enzyme-linked immunosorbent assay (ELISA). Results: Intercellular staining for IgG in the epidermis was successful in paraffin-embedded tissue sections in 11 of 12 PV samples and in all 10 PF samples. IgG at the basement membrane zone (BMZ) was not detected by immunofluorescent staining in 17 BP samples and 4 EBA samples. Conclusion: The detection of IgG by DIF-P using HIAR can be used for the diagnosis of pemphigus as an alternative method to DIF-F.

Biallelic mutations in LSS in autosomal-recessive mutilating palmoplantar keratoderma.

Mutilating palmoplantar keratoderma (PPK) is a heterogeneous genetic disease that poses enormous challenges to clinical diagnosis and genetic counselling. Lanosterol synthase (LSS) gene encodes LSS involved in the biosynthesis pathway of cholesterol. Biallelic mutations in LSS were found to be related to diseases such as cataracts, hypotrichosis and palmoplantar keratoderma-congenital alopecia syndrome. The aim of this study was to investigate the contribution of the LSS mutation to mutilating PPK in a Chinese patient. The clinical and molecular characteristics of the patient were evaluated. A 38-year-old male patient with mutilating PPK was recruited in this study. We identified biallelic variants in the LSS gene (c.683C > T, p.Thr228Ile and c.779G > A, p.Arg260His). Immunoblotting revealed that the Arg260His mutant showed a significantly reduced expression level while Thr228Ile showed an expression level similar to that of the wild type. Thin layer chromatography revealed that mutant Thr228Ile retained partial enzymatic activity and mutant Arg260His did not show any catalytic activity. Our findings show the correlation between LSS mutations and mutilating PPK.

A Novel Variant and a Missense Variant Identified in the DKC1 Gene in Three Chinese Familieswith Dyskeratosis Congenita.

Purpose: Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC. Patients and Methods: Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT. Results: There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have "deleterious" and "natural" effects on the function of dyskerin, respectively. Conclusion: The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.

Distinct impact of IgG subclass on autoantibody pathogenicity in different IgG4-mediated diseases.

IgG4 is the least potent human IgG subclass for the FcγR-mediated antibody effector function. Paradoxically, IgG4 is also the dominant IgG subclass of pathogenic autoantibodies in IgG4-mediated diseases. Here, we show that the IgG subclass and Fc-FcγR interaction have a distinct impact on the pathogenic function of autoantibodies in different IgG4-mediated diseases in mouse models. While IgG4 and its weak Fc-FcγR interaction have an ameliorative role in the pathogenicity of anti-ADAMTS13 autoantibodies isolated from thrombotic thrombocytopenic purpura (TTP) patients, they have an unexpected exacerbating effect on anti-Dsg1 autoantibody pathogenicity in pemphigus foliaceus (PF) models. Strikingly, a non-pathogenic anti-Dsg1 antibody variant optimized for FcγR-mediated effector function can attenuate the skin lesions induced by pathogenic anti-Dsg1 antibodies by promoting the clearance of dead keratinocytes. These studies suggest that IgG effector function contributes to the clearance of autoantibody-Ag complexes, which is harmful in TTP, but beneficial in PF and may provide new therapeutic opportunity.

The Pathogenic Role of CD4+ Tissue-Resident Memory T Cells Bearing T Follicular Helper-Like Phenotype in Pemphigus Lesions.

In skin lesions caused by pemphigus, a group of life-threatening autoimmune bullous diseases, an over-representation of CD4+ tissue-resident memory T (TRM) cells was found. We sought to investigate the contributions of CD4+ TRM cells to the severity and refractoriness of pemphigus and their role in local immunological pathogenesis. Our data showed that CD4+ TRM cells accumulated significantly in pemphigus skin lesions. These CD4+ TRM cells expressed a specific set of T follicular helper cell‒related costimulatory molecules. We also found that CD4+ TRM cells remaining in the lesions produced IL-17A and IL-21. In vitro, CD4+ TRM cells exhibited strong support and assistance to autoantibody production. Through transcriptomic sequencing and bioinformatics analysis, we identified that the transcription factor IRF4 was responsible for IL-21 overexpression and autoantibody production. Our results showed that T follicular helper-like CD4+ TRM cells in pemphigus lesions promoted local autoantibody production, resulting in the formation and recurrence of lesions, which supports targeting this cell subset in pemphigus treatment. IRF4 might serve as a potential therapeutic target.

Autoreactive B Cell Differentiation in Diffuse Ectopic Lymphoid-Like Structures of Inflamed Pemphigus Lesions.

Pemphigus is an organ-specific autoimmune disease that targets skin and/or mucous membranes. Our previous study showed that infiltrating lymphocytes in pemphigus vulgaris (PV) lesions produce anti-desmoglein (Dsg) 1/3 antibodies after in vitro culture. In this study, we found diffuse ectopic lymphoid-like structures (ELSs) commonly present in the lesions of both PV and pemphigus foliaceus. Notably, pemphigus lesions contained centroblasts, plasmablasts, and plasma cells, which recapitulated the different stages of B cell differentiation. Elevated mRNA expression levels of the differentiation-related transcription factors BLIMP-1, IRF4, and BCL-6 were observed in pemphigus lesions. Moreover, B cell receptor repertoire analysis revealed the clonal expansion of the lesional B cells. Lesional B cells might recirculate among lesions, lymph nodes, and peripheral blood. Increased mRNA expression levels of multiple chemokines in pemphigus lesions and elevated expression levels of chemokine receptors on lesional B cells were also observed. Collectively, these results show that the ELSs in pemphigus lesions might act as a niche, supporting in situ B cell differentiation and clonal expansion.

Pivotal Role of Lesional and Perilesional T/B Lymphocytes in Pemphigus Pathogenesis.

Pemphigus is a skin and mucosal membrane-targeting autoimmune bullous disease. Previous studies have shown that circulating anti-desmoglein1/3 antibodies are pathogenic and mediate blister formation. However, the role of infiltrating immune cells in lesional skin has not been fully investigated. In this study we showed that there existed a large number of B and T lymphocytes and plasma cells in the skin lesions by immunohistochemistry and immunofluorescence staining. In addition, a significantly increased number of Dsg1- and Dsg3-specific B cells could be identified by flow cytometric analysis or enzyme-linked immunospot technique (i.e., ELISPOT) assay. Furthermore, anti-Dsg1 and Dsg3 antibodies could be detected from the supernatant of in vitro cultures with isolated lymphocytes from lesional skin. We found that most T lymphocytes infiltrating pemphigus vulgaris lesions were CD4+ T helper cells expressing IL-21 and IL-17a but not typical T follicular helper cells expressing CXCR5. Additionally, our microarray assay showed that the level of chemokine CCL19 was significantly elevated, suggesting active T-/B-lymphocyte trafficking and aggregation in the pemphigus vulgaris lesions. Collectively, our results suggest a critical role of locally infiltrating lymphocytes in pemphigus pathogenesis.

[The expression and significance of beta2-AR and VEGFR-2 in infantile hemangioma].

OBJECTIVE: To investigate the significance of beta-adrenergic receptor 2 (beta2-AR) and vascular endothelial growth factor-2 (VEGFR-2) in the occurrence and development of infantile hemangioma through detecting the expression of beta2-AR and VEGFR-2 in the different stages of infantile hemangiomas. METHODS: According to the Mulliken's classification standard, we classified the specimens as proliferating group (32 cases), involuting group (17 cases) and involuted group (11 cases). Normal skin tissue surrounding the hemangioma from 7 cases were chosen as control group. The expression of beta2-AR and VEGFR-2 was detected by immunohistochemical technique in proliferating hemangioma, involuting hemangioma, involuted hemangioma. The mean optical density was measured by image analysis system (Image Pro Plus 6.0) and SPSS 16.0 software was applied for statistical analysis. RESULTS: The expression of beta2-AR and VEGFR-2 was strongly positive in proliferating hemangioma, while positive in involuting hemangioma and weakly positive in the involuted stage. The mean optical density of each phase was 0.064 751 2 +/- 0.012 747, 0.031 6017 +/- 0.006 848,0.011 869 8 +/- 0.039 349 for beta2-AR, and 0.068 940 9 +/- 0.029 274, 0.028 445 5 +/- 0.006 396, 0.011 184 1 +/- 0.004 198 for VEGFR-2. The differences between different stages had a statistically significance (P < 0.05). Correlation analysis on the mean optical density between beta2-AR and VEGFR-2 had a statistically significance (P < 0. 05). CONCLUSIONS: Beta2-AR and VEGFR-2 may be involved in the occurrence and development of infantile hemangioma.