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A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20dimCD8+ T cells with a highly inflammatory and central nervous system (CNS)-homing phenotype, were significantly inversely correlated with pretreatment MRI gadolinium-lesion counts, and also predictive of early disease activity observed after anti-CD20 initiation. Direct removal of pretreatment proinflammatory CD20dimCD8+ T cells had a greater contribution to treatment-associated changes in the CD8+ T cell pool than was the case for CD4+ T cells. Early disease activity following anti-CD20 initiation was not associated with reconstituting CD20dimCD8+ T cells, which were less proinflammatory compared with pretreatment. Similarly, this disease activity did not correlate with early reconstituting B cells, which were predominantly transitional CD19+CD24highCD38high with a more anti-inflammatory profile. We provide insights into the mode-of-action of anti-CD20 and highlight a potential role for CD20dimCD8+ T cells in MS relapse biology; their strong inverse correlation with both pretreatment and early posttreatment disease activity suggests that CD20-expressing CD8+ T cells leaving the circulation (possibly to the CNS) play a particularly early role in the immune cascades involved in relapse development.

According to the United Nations, around 53 million metric tons of electronic waste is produced every year, worldwide, the big majority of which goes unprocessed. With the rapid advances in AI technologies and adoption of smart gadgets, the demand for powerful logic and memory chips is expected to boom. Therefore, the development of green electronics is crucial to minimizing the impact of the alarmingly increasing e‐waste. Here, it is shown the application of a green synthesized, chemically stable, carbonyl‐decorated 2D organic, and biocompatible polymer as an active layer in a memristor device, sandwiched between potentially fully recyclable electrodes. The 2D polymer's ultramicro channels, decorated with C═O and O─H groups, efficiently promote the formation of copper nanofilaments. As a result, the device shows excellent bipolar resistive switching behavior with the potential to mimic synaptic plasticity. A large resistive switching window (103), low SET/RESET voltage of ≈0.5/−1.5 V), excellent device‐to‐device stability and synaptic features are demonstrated. Leveraging the device's synaptic characteristics, its applications in image denoising and edge detection is examined. The results show a reduction in power consumption by a factor of 103 compared to a traditional Tesla P40 graphics processing unit, indicating great promise for future sustainable AI‐based applications. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T.sub.FH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T.sub.H1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T.sub.FH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20. SARS-CoV-2-specific antibodies and memory B cells are significantly reduced, but CD4.sup.+ and CD8.sup.+ T cells are robustly activated, in patients with multiple sclerosis on anti-CD20 monotherapy versus healthy controls after BNT162b2 or mRNA-1273 mRNA vaccination., Author(s): Sokratis A. Apostolidis [sup.1] [sup.2] [sup.3] , Mihir Kakara [sup.4] [sup.5] , Mark M. Painter [sup.1] [sup.3] [sup.6] , Rishi R. Goel [sup.1] [sup.3] [sup.6] , Divij Mathew [sup.1] [...]

Observation of nanosilicon-based contributions to the interstellar nanodust is problematic because the indirect-bandgap of silicon makes its optical features wide, while carbon's higher abundancy and ionization potential and the rising slope of extinction curves introduce heavy convolution. Recent macroscopic synthesis and charging of nanosilicon, the coming online of the Webb space telescope with unprecedented spectral resolution, and advances in modeling algorithms, light scattering, and fundamental atomistic computation may open opportunities for effective comparison between laboratory and space observation. Here, we study the transport of charged nanosilicon in electric/magnetic fields. We use high voltage across liquid colloids to charge and propel nanosilicon into external fields and imprint them on metal-coated substrates. We use absorption, luminescence, and light scattering in liquid, flight, and imprinted surfaces to study the field deflection of nanosilicon. We use the Mie/finite-difference time-domain theory to obtain scattering curves of nanosilicon and silica. Nanosilicon-based UV features near the 217.5-nm carbon bump are recorded and calculated using Time-Dependent Density Functional Theory (TDDFT) atomistic theory at 225, 280, and 153 nm resulting from bound–bound, and valence-continuum transitions, respectively. We also show that the constituents of silicates, oxygen and Mg and Fe metal ions, can attach to Si nanoparticles without interrupting luminescence, infrared, or UV signatures, respectively. Because charge defects allow nanosilicon transport over large distances via open B fields of solar holes as well as provide them with narrow "atomic-like" transitions, which are otherwise extended, sightlines with lower carbon and higher resolution afforded by Webb may allow the unmasking of Si-based features. [ABSTRACT FROM AUTHOR]

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF–expressing) and anti-inflammatory (IL-10–expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)–induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases. Editor's summary: Patients with multiple sclerosis (MS) harbor high frequencies of pro-inflammatory B cells, which promote inflammation; yet, it is unclear how cytokine production in B cells is regulated. Li et al. studied cytokine regulation in pro-inflammatory (GM-CSF+) and anti-inflammatory (IL-10+) human B cells, identifying that pro-inflammatory B cells were more metabolically active with increased oxidative phosphorylation (OXPHOS). B cells from patients with MS also had increased OXPHOS, which was required for pro-inflammatory cytokine production, and inhibition of OXPHOS or BTK restored the balance of cytokine production. B cell OXPHOS contributed to the pathogenesis of neuroinflammation in mice by regulating adenosine triphosphate (ATP) signaling. These findings indicate that human B cell cytokine production is metabolically regulated and identify OXPHOS as a potential target for the treatment of MS. —Hannah Isles [ABSTRACT FROM AUTHOR]

A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20dimCD8+ T cells with a highly inflammatory and central nervous system (CNS)-homing phenotype, were significantly inversely correlated with pretreatment MRI gadolinium-lesion counts, and also predictive of early disease activity observed after anti-CD20 initiation. Direct removal of pretreatment proinflammatory CD20dimCD8+ T cells had a greater contribution to treatment-associated changes in the CD8+ T cell pool than was the case for CD4+ T cells. Early disease activity following anti-CD20 initiation was not associated with reconstituting CD20dimCD8+ T cells, which were less proinflammatory compared with pretreatment. Similarly, this disease activity did not correlate with early reconstituting B cells, which were predominantly transitional CD19+CD24highCD38high with a more anti-inflammatory profile. We provide insights into the mode-of-action of anti-CD20 and highlight a potential role for CD20dimCD8+ T cells in MS relapse biology; their strong inverse correlation with both pretreatment and early posttreatment disease activity suggests that CD20-expressing CD8+ T cells leaving the circulation (possibly to the CNS) play a particularly early role in the immune cascades involved in relapse development. [ABSTRACT FROM AUTHOR]