Human recombinant interferon beta-1a (Megavex)

Biotech commercialization should be treated as an engineering discipline.

Shah Shahid N SN

Complement activation linked to type II interferon signaling in Still disease.

Huijsmans Freya M C H FMCH, Thalheim Tabea T, Bodelón Alejandra A, Rogani Greta G et al.

Still disease (SD) is an autoinflammatory syndrome characterized by innate immune dysregulation. While complement can drive inflammation, its involvement in SD remains to be defined. Thus, we aimed to assess complement activation in SD. Complement was assessed using transcriptomic, proteomic, and in vitro approaches. RNA sequencing of monocytes was performed in healthy donors (n=15), non-systemic juvenile idiopathic arthritis (JIA, n=8), and SD patients at onset (n=19), remission (n=18), and macrophage activation syndrome (n=2). Whole-blood NanoString analysis of complement and interferon-related gene expression was conducted in SD (active n=41, inactive n=33) and JIA patients (n>600). Complement products and inflammatory mediators were measured by Luminex and ELISA. Functional complement activity was evaluated in SD (active n=30, inactive n=67) and JIA sera (n=12). In vitro assays examined monocytic C1q induction and complement-mediated CD8+ T cell activation. Transcriptomic analysis of monocytes from SD patients at onset revealed enrichment of the complement cascade compared to patients in remission (Padj=3.7×10-36), ranking among the top ten upregulated pathways. Classical complement genes (C1QB/C1QC) were markedly upregulated in onset SD compared to remission SD and JIA patients. Active SD patients showed increased C1q, C3a, C5a, and terminal complement complex protein levels, with enhanced functional classical complement activity. Whole-blood C1QB/C1QC expression correlated with interferon-related markers, including IL-18, CXCL9 and CXCL10. Recombinant IFN-γ induced monocytic C1q, while C1q enhanced IFN-γ production by CD8+ T cells, supporting a feed-forward loop. SD is characterized by complement activation with marked upregulation of C1q, which is closely linked to IFN-γ/type-II signaling.

An Iridium Distannylidyne - Expanding the Scope of Tetrylidyne Transition Metal Coordination Chemistry.

Holzapfel Lennart G LG, Hinssen Eric E, Miehe Stefan F SF, Eichele Klaus K et al.

Although transition metal tetrylidynes have been known for several decades, analogous heavy ditetrylidynes have not been reported in the literature to this day. In this work we describe the synthesis and characterization of iridium distannylidyne [(Me3P)2Ir(SnAr*)2][WCA] (1a/1b) {[WCA] = [Al(OtBuF)4]- (1a), [BArF 4]- (1b); Ar* = 2,6-bis(2,4,6-tri-iso-propylphenyl)phenyl, tBuF = C(CF3)3, ArF = 3,5-bis(trifluoromethyl)phenyl} as the first transition metal ditetrylidyne. 1 reacts with two equivalents of CO2 to give [(Me3P)2Ir(SnAr*)2(μ3-η3-κ3-O,C,O'-CO2)2][Al(OtBuF)4] (2). In the presence of excess trimethylphosphine, trimethylsilyl azide reacts with 1 to form imido-bridged [(Me3P)3Ir(SnAr*)2(μ2-N-TMS)][BArF 4]  (3) upon extrusion of N2.

Precision Dosing for Pediatric Growth Hormone Deficiency With Daily and Weekly Growth Hormone.

Wu Wei W, Gong Chun-Xiu CX, Mei Jie J, Hou Ling L et al.

Pediatric growth hormone deficiency (GHD) typically requires daily injections of recombinant human growth hormone (rhGH). Long-acting PEGylated recombinant human growth hormone (PEG-rhGH) formulations have been developed to reduce injection frequency and improve adherence and quality of life. However, guidance on switching between short-acting and long-acting regimens during treatment and biomarker-driven precision dose-conversion strategies remains lacking in real-world clinical practice. Therefore, this study analyzed data from two populations comprising healthy adult male subjects (n = 39) and pediatric patients with GHD (n = 408). The analysis used population pharmacokinetic (PopPK) and population pharmacokinetic/pharmacodynamic (PopPK/PD) models. The models showed adequate fit and external predictability. Biomarker-clinical growth endpoint relationship analysis linked changes in insulin-like growth factor-1 standard deviation score (IGF-1 SDS) to growth outcomes, and simulations assessed subgroup responses, missed-dose scenarios, and IGF-1 SDS-guided switching. Simulations enabled subgroup-specific efficacy projections. Missed doses caused a greater loss of benefit with rhGH than with PEG-rhGH. Switching simulations supported IGF-1 SDS-guided conversion within accepted safety limits. The integrated framework provides concise, clinically interpretable rules for individualized titration, adherence-aware care, and safer switching in pediatric GHD. This study supports precision dosing, missed-dose management, and switching between daily rhGH and weekly PEG-rhGH in pediatric GHD.