Nanoengineered Spintronic-Metasurface Terahertz Emitters Enable Beam Steering and Full Polarization Control.

The demand for emerging applications at the terahertz frequencies motivates the development of novel and multifunctional devices for the generation and manipulation of terahertz waves. In this work, we report the realization of multifunctional spintronic-metasurface emitters, which allow simultaneous beam-steering and full polarization control over a broadband terahertz beam. This is achieved through engineering individual meta-atoms with nanoscale magnetic heterostructures and, thus, implementing microscopical control over the laser-induced spin and charge dynamics. By arranging the spintronic meta-atoms in the metagrating geometry, the generated terahertz beam can be flexibly steered in space between different orders of diffraction. Furthermore, we demonstrate a simultaneous control over the terahertz polarization states at different emission angles and show that the two control capabilities are mutually independent of each other. The nanoengineered multifunctional terahertz emitter demonstrated in this work can provide a solution to the challenge associated with a growing variety of applications of terahertz technology.

A Tissue-Tended Mycophenolate-Modified Nanoparticle Alleviates Systemic Lupus Erythematosus in MRL/Lpr Mouse Model Mainly by Promoting Local M2-Like Macrophagocytes Polarization.

Background: Mycophenolate mofetil (MMF), for which the bioactive metabolite is mycophenolic acid (MPA), is a frequently used immunosuppressant for systemic lupus erythematosus (SLE). However, its short half-life and poor biodistribution into cells and tissues hinder its clinical efficacy. Our dextran mycophenolate-based nanoparticles (MPA@Dex-MPA NPs) have greatly improved the pharmacokinetics of MMF/MPA. We here tested the therapeutic efficacy of MPA@Dex-MPA NPs against SLE and investigated the underlying mechanism. Methods: The tissue and immune cell biodistributions of MPA@Dex-MPA NPs were traced using live fluorescence imaging system and flow cytometry, respectively. Serological proinflammatory mediators and kidney damage were detected to assess the efficacy of MPA@Dex-MPA NPs treatments of MRL/lpr lupus-prone mice. Immune cell changes in the kidney and spleen were further analyzed post-treatment via flow cytometry. Bone marrow-derived macrophages were used to investigate the potential mechanism. Results: MPA@Dex-MPA NPs exhibited superior therapeutic efficacy and safety in the MRL/lpr mice using significantly lower administration dosage (one-fifth) and frequency (once/3 days) compared to MMF/MPA used in ordinary practice. The overall prognosis of the mice was improved as they showed lower levels of serological proinflammatory mediators. Moreover, kidney injury was alleviated with reduced pathological signs and decreased urine protein-creatinine ratio. Further investigations of the underlying mechanism revealed a preferential penetration and persistent retention of MPA@Dex-MPA NPs in the spleen and kidney, where they were mostly phagocytosed by macrophages. The macrophages were found to be polarized towards a CD206+ M2-like phenotype, with a downregulation of surface CD80 and CD40, and reduced TNF-α production in the spleen and kidney and in vitro. The expansion of T cells was also significantly inhibited in these two organs. Conclusion: Our research improved the efficacy of MPA for MRL/lpr mice through synthesizing MPA@Dex-MPA NPs to enhance its tissue biodistribution and explored the possible mechanism, providing a promising strategy for SLE therapy.

Depression and Anxiety in Rosacea Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Depression and anxiety are common among people with rosacea. However, the exact magnitude of the prevalence rate and odds ratios (ORs) for depression and anxiety, respectively, in rosacea patients is unclear, and no systematic review or meta-analysis of published data has yet been performed. We therefore performed as systematic review and meta-analysis to determine the prevalence rates and ORs for depression and anxiety in rosacea patients. METHODS: We performed a systematic search of the PubMed, Embase and Medline databases for all observational studies published up to October 2020 that reported the prevalence rates and ORs for depression and anxiety in patients with rosacea. The primary outcome measures were prevalence rates and ORs for depression and anxiety in patients with rosacea. Heterogeneity across studies was assessed with the I2 statistic. Sources of heterogeneity were explored through subgroup and meta-regression analyses. RESULTS: A total of 14 studies involving 14,134,021 patients with rosacea were included in the systematic review and meta-analysis. The pooled prevalence of depression was 19.6% (95% confidence interval [CI] 15.0-24.3%) and that of anxiety was 15.6% (95% CI 11.8-19.3%). The prevalence of depression and anxiety was significantly lower in studies using clinical criteria to diagnose depression and anxiety (9.2 and 10.2%, respectively) than in those studies using screening tools (26.2% [P < 0.01] and 22.7% [P = 0.03], respectively). The methodological quality of the included studies greatly contributed to the heterogeneity. Patients with rosacea were more likely to experience depression (OR 2.21, 95% CI 1.79-2.72) and anxiety (OR 2.31, 95% CI 1.56-3.44) than healthy controls. CONCLUSIONS: This systematic review and meta-analysis indicates that patients with rosacea are at a higher risk of experiencing depression and anxiety. More efforts are warranted to recognize and manage depression and anxiety in patients with rosacea.

Sialylated immunoglobulin G: a promising diagnostic and therapeutic strategy for autoimmune diseases.

Human immunoglobulin G (IgG), especially autoantibodies, has major implications for the diagnosis and management of a wide range of autoimmune diseases. However, some healthy individuals also have autoantibodies, while a portion of patients with autoimmune diseases test negative for serologic autoantibodies. Recent advances in glycomics have shown that IgG Fc N-glycosylations are more reliable diagnostic and monitoring biomarkers than total IgG autoantibodies in a wide variety of autoimmune diseases. Furthermore, these N-glycosylations of IgG Fc, particularly sialylation, have been reported to exert significant anti-inflammatory effects by upregulating inhibitory FcγRIIb on effector macrophages and reducing the affinity of IgG for either complement protein or activating Fc gamma receptors. Therefore, sialylated IgG is a potential therapeutic strategy for attenuating pathogenic autoimmunity. IgG sialylation-based therapies for autoimmune diseases generated through genetic, metabolic or chemoenzymatic modifications have made some advances in both preclinical studies and clinical trials.

Polysaccharide mycophenolate-based nanoparticles for enhanced immunosuppression and treatment of immune-mediated inflammatory diseases.

Immune-mediated inflammatory diseases (IMIDs) are characterized by immune dysregulation and severe inflammation caused by the aberrant and overactive host immunological response. Mycophenolic acid (MPA)-based immunosuppressive drugs are potential treatments for IMIDs because of their mild side-effect profile; however, their therapeutic effects are limited by the high albumin binding rate, unsatisfactory pharmacokinetics, and undefined cellular uptake selectivity. Methods: Polysaccharide mycophenolate was synthesized by conjugating MPA molecules to dextran (a typical polysaccharide widely used in drug delivery) and encapsulated extra free MPA molecules to fabricate MPA@Dex-MPA nanoparticles (NPs). The efficacy of these NPs for mediating immunosuppression and treatment of IMIDs was evaluated in imiquimod-induced psoriasis-like skin inflammation in Balb/c mice, a representative IMID model. Results: The MPA@Dex-MPA NPs exhibited high MPA loading efficiency, low albumin binding rates, and sustained MPA release, resulting in improved pharmacokinetics in vivo. Compared to free MPA, MPA@Dex-MPA NPs induced more robust therapeutic effects on IMIDs. Mechanistic studies indicated that MPA@Dex-MPA NPs were primarily distributed in dendritic cells (DCs) and significantly suppressed the overactivated DCs in vivo and in vitro. Furthermore, the recovered DCs rehabilitated the IL-23/Th17 axis function and significantly ameliorated imiquimod-induced psoriasis-like skin inflammation. Importantly, MPA@Dex-MPA NPs showed favorable safety and biocompatibility in vivo. Conclusion: Our results indicated the polysaccharide mycophenolate-based NPs to be highly promising for IMID treatment.

5-Aminolevulinic Acid-Loaded Hyaluronic Acid Dissolving Microneedles for Effective Photodynamic Therapy of Superficial Tumors with Enhanced Long-Term Stability.

5-Aminolevulinic acid (5-ALA) is one of the most widely used prodrug in clinical photodynamic therapy of dermatological diseases and cancers; yet, its clinical application is still limited by the shallow skin penetration and unsatisfied stability in any existed formulations. Here, 5-ALA-loaded hyaluronic acid dissolving microneedles (5-ALA@HAMNs) are prepared for photodynamic therapy of superficial tumors. The HAMNs can not only assist the loaded 5-ALA to effectively penetrate the stratum corneum but also provide 5-ALA with an acidic and oxygen-free environment to reduce the dimerization of 5-ALA molecules via Schiff-base bonds and formation of inactive pyrazine derivatives, thus maintaining its chemical structure and biological activity. The chemical stability of 5-ALA in HAMNs is confirmed by UV-vis spectra and mass spectra measurements. The 5-ALA@HAMNs display remarkable tumor elimination both in vitro and in vivo, even after storage at room temperature for nine months, making it a highly potential device for effective delivery of 5-ALA in cancer photodynamic therapy.