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Background: Indolent systemic mastocytosis (ISM) is characterized by excessive mast cell accumulation and mast cell-driven signs and symptoms. Currently used therapies are not approved and have limited efficacy. Lirentelimab (AK002) is a monoclonal antibody against sialic acid-binding immunoglobulin-like lectin (Siglec)-8 that inhibits mast cell activation., Objective: To determine the safety, tolerability, and efficacy of lirentelimab in reducing ISM symptoms., Methods: At a specialty center for mastocytosis in Germany, we conducted a phase 1, first-in-human, single-ascending dose and multidose clinical trial of lirentelimab in patients with ISM. Eligible adults had WHO-confirmed ISM and unsatisfactory response to available treatment. In Part A, patients received a single dose of lirentelimab 0.0003, 0.001, 0.003, 0.01, or 0.03 mg/kg; in Part B, patients received 1 lirentelimab dose of 0.3 mg/kg or 1.0 mg/kg; and in Part C, patients received either 1.0 mg/kg lirentelimab every 4 weeks for 6 months or ascending doses of lirentelimab (one 1-mg/kg dose followed by five 3- to 10-mg/kg doses every 4 weeks). The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in Mastocytosis Symptom Questionnaire (MSQ), Mastocytosis Activity Score (MAS), and Mastocytosis Quality of Life Questionnaire (MC-QoL) scores at 2 weeks after the final dose., Results: Across 25 patients with ISM (n=13 Part A+B, n=12 Part C; median age 51 years, 76% female, median 4.6 years from diagnosis), the most common treatment-related adverse events were feeling hot (76%) and headache (48%). No serious adverse events occurred. Part C median MSQ and MAS symptom severity scores improved across all symptoms (MSQ: skin [38%-56% improvement vs baseline], gastrointestinal [49%-60%], neurologic [47%-59%], musculoskeletal [26%-27%]; MAS: skin [53%-59%], gastrointestinal [72%-85%], neurologic [20%-57%], musculoskeletal [25%]). Median MC-QoL scores improved across all domains: symptoms (39%), social life/functioning (42%), emotions (57%), and skin (44%)., Conclusions: Lirentelimab was generally well tolerated and improved symptoms and QoL in patients with ISM. The therapeutic potential of lirentelimab should be considered for ISM., Trial Registration: ClinicalTrials.gov number, NCT02808793., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4 ). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators 5-7 . Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue 1,8,9 . Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

It is important to develop new energy storage and conversion technology to mitigate the energy crisis for the sustainable development of human society. In this study, free-standing porous nitrogen-doped carbon fiber (PN-CF) membranes were obtained from the pyrolysis of Zn-MOF-74/polyacrylonitrile (PAN) composite fibers, which were fabricated in situ by an electrospinning technology. The resulting free-standing fibers can be cut into membrane disks and directly used as an anode electrode without the addition of any binder or additive. The PN-CFs showed great reversible capacities of 210 mAh g -1 at a current density of 0.05 A g -1 and excellent cyclic stability of 170.5 mAh g -1 at a current density of 0.2 A g -1 after 600 cycles in sodium ion batteries (SIBs). The improved electrochemical performance of PN-CFs can be attributed to the rich porous structure derived by the incorporation of Zn-MOF-74 and nitrogen doping to promote sodium ion transportation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xue, Si, Xie, Yang, Mo, Long, Wei, Cao, Wei, Guan, Michaelis, Guo, Yue and Shan.)

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.