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Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is associated with interstitial lung disease (ILD) in patients with juvenile dermatomyositis (JDM). Although the mechanisms leading to pulmonary involvements remain uncertain, both inflammatory cytokines and autoimmune response between MDA5 and anti-MDA5 antibody could been inferred. The present study examined the roles of MDA5 in an inducible form of lung involvement that develops in autoimmune mice treated with the pristane. MRL/Mp-lpr/lpr mice and wild type controls (+/+) at 5 weeks of age. They received 0.5ml of pristane or an equal volume of PBS IP at the age 7 week (day 1). And 1.2μg of recombinant human MDA5 protein (rMDA5) was instilled IP or PBS at day2 and Day9. The mice were sacrificed on 8 weeks after the intraperitoneal injection. Lung tissue was harvested for histological assessment. MRL/Mp-lpr/lpr mice and wild type controls (+/+) at 5 weeks of age. They received 0.5ml of pristane or an equal volume of PBS IP at the age 7 week (day 1). And 1.2μg of recombinant human MDA5 protein (rMDA5) was instilled IP or PBS at day2 and Day9. The mice were sacrificed on 8 weeks after the intraperitoneal injection. Lung tissue was harvested for histological assessment. Lung involvements did not develop in PBS-treated MRL/lpr mice and WT mice. And Lung involvements did not develop in rMDA5 protein-treated WT mice. H&E staining of lung tissue from MRL/lpr mice and WT mouse with pristane that showed induced bland alveolar hemorrhage. H&E staining of lung from WT mouse compared with lung from a MRL/lpr mouse treated with pristane + rMDA5 protein showing mild thickening of the alveolar septa despite the alveolar hemorrhage. And perivascular lymphocytes infiltrate in a MRL/lpr mouse rather than a WT mouse treated with pristane + rMDA5 protein. CD163 staining of alveolar macrophages were present in the alveolar spaces was more intense in mouse treated with pristane + rMDA5 protein than in mouuse treated with only pristane. The Lymphocyte infiltrations around alveolar macrophages was more prominent in MRL/lpr mouse treated with pristane + rMDA5 protein than other mouse. These results suggest that lung involvements such as the alveolar hemorrhage, are caused by pristeine and rMDA5 prtotein in the pathogenesis of interstitial pneumonia. MRL/lpr mouse treated with pristane + rMDA5 protein showed more alveolar macrophages that had lymphocyte infiltrations. After the alveolar hemorrhage by pritane, the antigen exposure of MDA5 might induce continuously inflammatory response to lymphocytes and macrophages in the alveolar lesions. [1]Sunderrajan VE, McKenzie NW, Lieske RT, et al. Pulmonary inflammation in autoimmune MRL/Mp-lpr/lpr mice. Histopathology and bronchoalveolar lavage evaluation. Am J Pathol. 1986;124: 353–362. [2]Tolga Barker T, Lee YP, Scumpia KK, et al. Pathogenic role of B-cells in the development of diffuse alveolar hemorrhage induced by pristane. Lab Invest. 2011; 91: 1540–1550. None declared [Display omitted]

We consider Fourier multipliers in R 2 with singularities on certain curves, which are closely related to the Bochner–Riesz Fourier multipliers. We prove weighted inequalities and vector valued inequalities for the Fourier multiplier operators which generalize some known results.

Petahertz-bandwidth metrology is demonstrated in the measurement of nonlinear polarization in silica. Petahertz-bandwidth metrology in silica Recent years have seen an increased interest in light–matter interactions in solid-state systems at ultrafast timescales. Ferenc Krausz and colleagues study the nonlinear polarization of silica in response to intense infrared light fields with a spectroscopy method in the attosecond time range. The method makes it possible to unravel details of the reversible and irreversible energy exchange between infrared light and electrons and points to the feasibility of using light-based switching techniques for signal processing in solid-state devices above 100 terahertz. Electric-field-induced charge separation (polarization) is the most fundamental manifestation of the interaction of light with matter and a phenomenon of great technological relevance. Nonlinear optical polarization 1 , 2 produces coherent radiation in spectral ranges inaccessible by lasers and constitutes the key to ultimate-speed signal manipulation. Terahertz techniques 3 , 4 , 5 , 6 , 7 , 8 have provided experimental access to this important observable up to frequencies of several terahertz 9 , 10 , 11 , 12 , 13 . Here we demonstrate that attosecond metrology 14 extends the resolution to petahertz frequencies of visible light. Attosecond polarization spectroscopy allows measurement of the response of the electronic system of silica to strong (more than one volt per ångström) few-cycle optical (about 750 nanometres) fields. Our proof-of-concept study provides time-resolved insight into the attosecond nonlinear polarization and the light–matter energy transfer dynamics behind the optical Kerr effect and multi-photon absorption. Timing the nonlinear polarization relative to the driving laser electric field with sub-30-attosecond accuracy yields direct quantitative access to both the reversible and irreversible energy exchange between visible–infrared light and electrons. Quantitative determination of dissipation within a signal manipulation cycle of only a few femtoseconds duration (by measurement and ab initio calculation) reveals the feasibility of dielectric optical switching at clock rates above 100 terahertz. The observed sub-femtosecond rise of energy transfer from the field to the material (for a peak electric field strength exceeding 2.5 volts per ångström) in turn indicates the viability of petahertz-bandwidth metrology with a solid-state device.

Electron transfer from valence to conduction band states in semiconductors is the basis of modern electronics. Here, attosecond extreme ultraviolet (XUV) spectroscopy is used to resolve this process in silicon in real time. Electrons injected into the conduction band by few-cycle laser pulses alter the silicon XUV absorption spectrum in sharp steps synchronized with the laser electric field oscillations. The observed ∼450-attosecond step rise time provides an upper limit for the carrier-induced band-gap reduction and the electron-electron scattering time in the conduction band. This electronic response is separated from the subsequent band-gap modifications due to lattice motion, which occurs on a time scale of 60 ± 10 femtoseconds, characteristic of the fastest optical phonon. Quantum dynamical simulations interpret the carrier injection step as light-field–induced electron tunneling.

Short, intense laser pulses can be used to access the transition regime between classical and quantum optical responses in dielectrics. In this regime, the relative roles of inter- and intraband light-driven electronic transitions remain uncertain. We applied attosecond transient absorption spectroscopy to investigate the interaction between polycrystalline diamond and a few-femtosecond infrared pulse with intensity below the critical intensity of optical breakdown. Ab initio time-dependent density functional theory calculations, in tandem with a two-band parabolic model, accounted for the experimental results in the framework of the dynamical Franz-Keldysh effect and identified infrared induction of intraband currents as the main physical mechanism responsible for the observations.

Rare diseases are conditions that affect up to 65 people per 100,000 individuals. They are also known as “orphan diseases”, because they attract limited interest from researchers and pharmaceutical industries. Epidermolysis bullosa (EB), ichthyosis, Hailey–Hailey disease (HHD), Darier disease (DD), erythrokeratoderma, porokeratosis, inflammatory linear verrucous epidermal nevus (ILVEN) and piebaldism are examples of rare genetic skin diseases with few approved treatments. Topical treatments are the principal approach for rare dermatological diseases, and it can be useful to manage the symptoms or the patophysiology of these diseases. This study aimed to conduct a comprehensive review of the topical treatments of EB, ichthyosis, HHD, DD, erythrokeratodermias, porokeratosis, ILVEN, and piebaldism. The search was performed across the SciELO, MEDLINE®/PubMed®, Embase and Cochrane databases. This review identified porokeratosis, EB, and congenital ichthyosis as the rare genodermatoses with the highest number of reported studies and topical treatment options. In contrast, conditions such as piebaldism, erythrokeratodermia, and HHD have fewer reported topical interventions. For most rare genetic dermatological diseases, treatment aims to improve quality of life and control clinical signals and symptoms. Creams, gels, and ointments are frequently used as the main pharmaceutical approaches, and several pharmacological classes are employed, including keratolytics, retinoids, vitamin D analogs, topical corticosteroids, calcineurin inhibitors, and cytotoxic or antiproliferative agents. This review highlights the potential of off-label use of topical therapies as cost-effective alternatives in the treatment of rare genetic skin disorders. It also reinforces the critical role of compounded medicines in allowing for dose optimization, drug repurposing, and formulation adjustments, personalizing treatment to achieve improved therapeutic outcomes.

Resolving the fundamental carrier dynamics induced in solids by strong electric fields is essential for future applications, ranging from nanoscale transistors1,2 to high-speed electro-optical switches3. How fast and at what rate can electrons be injected into the conduction band of a solid? Here, we investigate the sub-femtosecond response of GaAs induced by resonant intense near-infrared laser pulses using attosecond transient absorption spectroscopy. In particular, we unravel the distinct role of intra- versus interband transitions. Surprisingly, we found that despite the resonant driving laser, the optical response during the light–matter interaction is dominated by intraband motion. Furthermore, we observed that the coupling between the two mechanisms results in a significant enhancement of the carrier injection from the valence into the conduction band. This is especially unexpected as the intraband mechanism itself can accelerate carriers only within the same band. This physical phenomenon could be used to control ultrafast carrier excitation and boost injection rates in electronic switches in the petahertz regime.

Employing the quantum Liouville equation with phenomenological dissipation, we investigate the transport properties of massless and massive Dirac fermion systems that mimics graphene and topological insulators, respectively. The massless Dirac fermion system does not show an intrinsic Hall effect, but it shows a Hall current under the presence of circularly-polarized laser fields as a nature of a optically-driven nonequilibrium state. Based on the microscopic analysis, we find that the light-induced Hall effect mainly originates from the imbalance of photocarrier distribution in momentum space although the emergent Floquet-Berry curvature also has a non-zero contribution. We further compute the Hall transport property of the massive Dirac fermion system with an intrinsic Hall effect in order to investigate the interplay of the intrinsic topological contribution and the extrinsic light-induced population contribution. As a result, we find that the contribution from the photocarrier population imbalance becomes significant in the strong field regime and it overcomes the intrinsic contribution. This finding clearly demonstrates that intrinsic transport properties of materials can be overwritten by external driving and may open a way to ultrafast optical-control of transport properties of materials.

Transition metals, with their densely confined and strongly coupled valence electrons, are key constituents of many materials with unconventional properties1, such as high-temperature superconductors, Mott insulators and transition metal dichalcogenides2. Strong interaction offers a fast and efficient lever to manipulate electron properties with light, creating promising potential for next-generation electronics3–6. However, the underlying dynamics is a hard-to-understand, fast and intricate interplay of polarization and screening effects, which are hidden below the femtosecond timescale of electronic thermalization that follows photoexcitation7. Here, we investigate the many-body electron dynamics in transition metals before thermalization sets in. We combine the sensitivity of intra-shell transitions to screening effects8 with attosecond time resolution to uncover the interplay of photo-absorption and screening. First-principles time-dependent calculations allow us to assign our experimental observations to ultrafast electronic localization on d orbitals. The latter modifies the electronic structure as well as the collective dynamic response of the system on a timescale much faster than the light-field cycle. Our results demonstrate a possibility for steering the electronic properties of solids before electron thermalization. We anticipate that our study may facilitate further investigations of electronic phase transitions, laser–metal interactions and photo-absorption in correlated-electron systems on their natural timescales.

SummaryRoot amputation, extraction of a single tooth, bone loss or severe tooth mobility, and an unclosed wound were significantly associated with increased risk of developing medication-related osteonecrosis of the jaw (MRONJ). We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates.IntroductionOsteonecrosis of the jaws can occur following tooth extraction in patients receiving bisphosphonate drugs. Various strategies for minimizing the risk of MRONJ have been advanced, but no studies have comprehensively analyzed the efficacy of factors such as primary wound closure, demographics, and drug holidays in reducing its incidence. The purpose of this study was to retrospectively investigate the relationships between these various risk factors after tooth extraction in patients receiving oral bisphosphonate therapy.MethodsRisk factors for MRONJ after tooth extraction were evaluated using univariate and multivariate analysis. All patients were investigated with regard to demographics; type and duration of oral bisphosphonate use; whether they underwent a discontinuation of oral bisphosphonates before tooth extraction (drug holiday), and the duration of such discontinuation; and whether any additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed.ResultsWe found that root amputation (OR = 6.64), extraction of a single tooth (OR = 3.70), bone loss or severe tooth mobility (OR = 3.60), and an unclosed wound (OR = 2.51) were significantly associated with increased risk of developing MRONJ.ConclusionsWe recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. We find no evidence supporting the efficacy of a pre-extraction short-term drug holiday from oral bisphosphonates in reducing the risk of MRONJ.