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ETHNOPHARMACOLOGICAL RELEVANCE: Thesium chinense Turcz., a traditional Chinese herbal medicine, displays good therapeutic efficiency against respiratory diseases (e.g. pneumonia, pharyngitis) in clinical applications, however, its effects on COPD and the mechanism of action are still unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic effect of the ethyl acetate fraction of Thesium chinense Turcz. (TCEA) on COPD and reveal the underlying mechanism. MATERIALS AND METHODS: A cigarette smoke (CS)-induced mouse COPD model was established, and the efficacy of TCEA was evaluated using peripheral blood testing, HE and Masson staining, qRT-PCR and ELISA assays. TCEA was analyzed for chemical composition by LC-MS/MS and HPLC. Prediction of major signaling pathways and potential targets was performed by network pharmacology. The molecular mechanism of TCEA was explored by immunoblotting, immunofluorescence staining, flow cytometry, and ubiquitination assay. Finally, potential active small molecules in TCEA were identified by molecular virtual screening. RESULTS: TCEA treatment significantly inhibited the secretion of pro-inflammatory factors and attenuated pathological emphysema. The main chemical constituents of TCEA were identified as flavonoids by UPLC-MS/MS. Network pharmacology analysis enriched the Nrf2 signaling pathway closely related to oxidative stress. Our results suggested that TCEA inhibited ferroptosis by activating Nrf2/SLC7A11/GPX4 axis and inhibiting lipid metabolism-related proteins, ACSL4, ALOX5 and COX2 in vivo and in vitro. Noteworthily, the beneficial impact of TCEA on regulation of SLC7A11 and GPX4 vanished after silencing Nrf2. Moreover, Nrf2 ubiquitination was inhibited by TCEA treatment. Finally, several flavonoids modulating Nrf2 were identified by molecular virtual screening. CONCLUSIONS: TCEA significantly alleviated COPD progression by inhibiting ferroptosis primarily through activation of Nrf2/SLC7A11/GPX4 signaling. Flavonoids are the main active components that exert their effects. These findings shed light on the mechanism of action of TCEA and its potential active components, providing a feasible approach for the treatment of COPD.

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The ring-shaped Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or its paralog SA1), topologically entraps two duplicated sister DNA molecules to establish sister chromatid cohesion in S-phase. It remains largely elusive how the Cohesin release factor Wapl binds the Cohesin complex, thereby inducing Cohesin disassociation from mitotic chromosomes to allow proper resolution and separation of sister chromatids. Here, we show that Wapl uses two structural modules containing the FGF motif and the YNARHWN motif, respectively, to simultaneously bind distinct pockets in the extensive composite interface between Scc1 and SA2. Strikingly, only when both docking modules are mutated, Wapl completely loses the ability to bind the Scc1-SA2 interface and release Cohesin, leading to erroneous chromosome segregation in mitosis. Surprisingly, Sororin, which contains a conserved FGF motif and functions as a master antagonist of Wapl in S-phase and G2-phase, does not bind the Scc1-SA2 interface. Moreover, Sgo1, the major protector of Cohesin at mitotic centromeres, can only compete with the FGF motif but not the YNARHWN motif of Wapl for binding Scc1-SA2 interface. Our data uncover the molecular mechanism by which Wapl binds Cohesin to ensure precise chromosome segregation.

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In this study, we developed a machine learning interatomic potential based on artificial neural networks (ANN) to model carbon-hydrogen (C-H) systems. The ANN potential was trained on a dataset of C-H clusters obtained through density functional theory (DFT) calculations. Through comprehensive evaluations against DFT results, including predictions of geometries and formation energies across 0D-3D systems comprising C and C-H, as well as modeling various chemical processes, the ANN potential demonstrated exceptional accuracy and transferability. Its capability to accurately predict lattice dynamics, crucial for stability assessment in crystal structure prediction, was also verified through phonon dispersion analysis. Notably, its accuracy and computational efficiency in calculating force constants facilitated the exploration of complex energy landscapes, leading to the discovery of a novel C polymorph. These results underscore the robustness and versatility of the ANN potential, highlighting its efficacy in advancing computational materials science by conducting precise atomistic simulations on a wide range of C-H materials.

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Polymer nanocomposites with tuning functions are exciting candidates for various applications, and most current research has focused on static mechanical reinforcement. Actually, under service conditions of complex dynamic interference, stable dynamic mechanical properties with high energy dissipation become more critical. However, nanocomposites often exhibit a trade-off between static and dynamic mechanics, because of their contradictory underlying physics between chain crosslinking and chain relaxation. Here, we report a general strategy for constructing ultra-stable dynamic mechanical complex fluid nanocomposites with high energy dissipation by infusing complex fluids into the nanoconfined space. The key is to tailor full-scale polymer dynamics across an exceptionally broad timescale by single-chain confinement. These materials exhibit stable storage modulus (100 ~ 102 MPa) with high energy dissipation (loss factor > 0.4) over a broad frequency range (10-1 ~ 107 Hz)/temperature range (-35 ~ 85°C). In the loss factor > 0.4 region, their dynamic mechanical stability (rate of modulus change versus temperature (k)) is 10 times higher than that of conventional polymer nanocomposites.

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Dendrobium officinale is a rare and precious medicinal plant. Southern blight is a destructive disease in the artificial cultivation of D. officinale, and one of its pathogens is Sclerotium delphinii. S. delphinii is a phytopathogenic fungus with a wide host range with extremely strong pathogenicity. In this study, S. delphinii was isolated from D. officinale with southern blight. Subsequently, this specific strain underwent thorough whole-genome sequencing using the PacBio Sequel II platform, which employed single-molecule real-time (SMRT) technology. Comprehensive annotations were obtained through functional annotation of protein sequences using various publicly available databases. The genome of S. delphinii measures 73.66 Mb, with an N90 contig size of 2,707,110 bp, and it contains 18,506 putative predictive genes. This study represents the first report on the genome size assembly and annotation of S. delphinii, making it the initial species within the Sclerotium genus to undergo whole-genome sequencing, which can provide solid data and a theoretical basis for further research on the pathogenesis, omics of S. delphinii.

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Influenza infection is associated with a risk of thrombosis. Whether factors associated with reduced thrombosis might also be associated with reduced risk in patients with severe influenza is unknown. To investigate risk factors associated with thrombosis in patients with severe influenza. We used a cohort data set to identify adults diagnosed with severe influenza. Univariable and multivariable logistic regression models explored potential risk factors for thrombosis events in patients with severe influenza. Cox regression analysis was used to examine the risk factors for mortality in patients with severe influenza. A total of 854 patients with severe influenza were included in the analysis. The incidence of VTE was 9.37% (80/854). Multivariable regression analysis showed that previous aspirin medication (OR: 0.37; 95%CI: 0.14-0.84; P = .029) could reduce the risk factor of thrombosis in patients with severe influenza. Compared with patients in the non-thrombosis group, patients in the thrombosis group required more mechanical ventilation (P < .001), tracheostomy (P < .001), ECMO (P = .046), and high-frequency ventilation (P = .004). The incidence of co-infection was higher in the thrombosis group compared to the non-thrombosis group (P = .025). Univariable Cox regression analysis showed that previous aspirin medication (HR 0.52, 95%CI: 0.33-0.82, P = .005) and previous statin medication (HR 0.54, 95%CI: 0.34-0.87, P = .011) were risk factors for 60-day mortality in patients with severe influenza. Patients with severe influenza are at high risk for thrombosis. The effect of aspirin on thrombosis in patients with severe influenza needs further investigation.

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Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges.

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Two-dimensional (2D) nanosheets-based membranes, which have controlled 2D nano-confined channels, are highly desirable for molecular/ionic sieving and confined reactions. However, it is still difficult to develop an efficient method to prepare large-area membranes with high stability, high orientation, and accurately adjustable interlayer spacing. Here, we present a strategy to produce metal ion cross-linked membranes with precisely controlled 2D nano-confined channels and high stability in different solutions using superspreading shear-flow-induced assembly strategy. For example, membranes based on graphene oxide (GO) exhibit interlayer spacing ranging from 8.0±0.1 Što 10.3±0.2 Å, with a precision of down to 1 Å. At the same time, the value of the orientation order parameter (f) of GO membranes is up to 0.95 and GO membranes exhibit superb stability in different solutions. The strategy we present, which can be generalized to the preparation of 2D nano-confined channels based on a variety of 2D materials, will expand the application scope and provide better performances of membranes.

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Sulfide in sediment porewaters, is toxic to rooted macrophytes in both marine and freshwater environments. Current research on sulfide stress in seagrasses primarily focuses on morphological and physiological aspects, with little known about the molecular response and resistance mechanisms. This study first investigated the damage caused by sulfide to eelgrass (Zostera marina L.) using transcriptomic, metabolomic, and other physiological and biochemical indicators and explored the potential resistance of eelgrass at molecular level through laboratory simulated and in-situ sulfide stress experiments. Comprehensive results showed that sulfide stress severely inhibited the growth, photosynthesis, and antioxidant enzyme activities of eelgrass. Importantly, transcriptome analysis revealed significant activation of pathways related to carbohydrate and sulfur metabolism. This activation served a dual purpose: providing an energy source for eelgrass stress response and achieving detoxification through accelerated sulfur metabolism-a potential resistance mechanism. The toxicity of sulfide increased with rising temperature as evidenced by a decrease in EC50. Results from recovery experiments indicated that when Fv/Fm reduced to about 0 under sulfide stress, the growth and photosynthesis of eelgrass recovered to normal level after timely removal of sulfide. However, prolonged exposure to sulfide resulted in failure to recover, leading ultimately to plant death. This study not only enhances our understanding of the molecular-level impacts of sulfide on seagrasses but also provides guidance for the management and ecological restoration of seagrass meadows under sulfide stress.

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The sluggish kinetics of lithium-sulfur (Li-S) batteries severely impedes the application in extreme conditions. Bridging the sulfur cathode and lithium anode, the electrolyte plays a crucial role in regulating kinetic behaviors of Li-S batteries. Herein, we report a multifunctional electrolyte additive of phenyl selenium bromide (PhSeBr) to simultaneously exert positive influences on both electrodes and the electrolyte. For the cathode, an ideal conversion routine with lower energy barrier can be attained by the redox mediator and homogeneous catalyst derived from PhSeBr, thus improving the reaction kinetics and utilization of sulfur. Meanwhile, the presence of Se-Br bond helps to reconstruct a loose solvation sheath of lithium ions and a robust bilayer SEI with excellent ionic conductivity, which contributes to reducing the de-solvation energy and simultaneously enhancing the interfacial kinetics. The Li-S battery with PhSeBr displays superior long cycling stability with a reversible capacity of 1164.7 mAh g-1 after 300 cycles at 0.5 C rate. And the pouch cell exhibits a maximum capacity of 845.3 mAh and a capacity retention of 94.8 % after 50 cycles. Excellent electrochemical properties are also obtained in extreme conditions of high sulfur loadings and low temperature of -20 °C. This work demonstrates the versatility and practicability of the special additive, striking out an efficient but simple method to design advanced Li-S batteries.

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Compounding functional nanoparticles with highly conductive and porous carbon scaffolds is a basic pathway for engineering many important functional devices. However, enabling uniform spatial distribution of functional particles within a massively conjugated, monolithic and mesoporous structure remains challenging, as the high processing temperature for graphitization can arouse nanoparticle ripening, agglomerations and compositional changes. Herein, we report a unique "popcorn-making-mimic" strategy for preparing a highly conjugated and uniformly compounded graphene@NiFe2O4 composite film through a laser-assisted instantaneous compounding method in ambient condition. It can successfully inhibit the unwanted structural disintegration and mass loss during the laser treatment by avoiding oxidation, bursting, and inhomogeneous heat accumulations, thus achieving a highly integrated composite structure with superior electrical conductivity and high saturated magnetization. Such a single-sided film exhibits an absolute shielding effectiveness of up to 20906 dB cm2 g-1 with 75% absorption rate, superior mechanical flexibility and excellent temperature/humidity aging reliability. These performance indexes signify a substantial advance in EMI absorption capability, fabrication universality, small form-factor and device reliability toward commercial applications. Our method provides a paradigm for fabricating sophisticated composite materials for versatile applications.

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Metal selenides have garnered significant attention as promising anode materials for sodium-ion batteries, thanks to their high theoretical capacity, excellent conductivity, and natural abundance. However, their potential is hampered by disappointing capacity retention and unsatisfactory lifespan, primarily attributed to volume expansion and unwanted structural collapse resulting from the insertion and extraction of relatively large Na+ ions during the charge and discharge processes. This feature article provides a brief overview of our endeavors to address the challenges associated with metal selenide-based anode materials, aiming to achieve high-performance electrode materials for sodium-ion batteries. Our strategy encompasses nanostructure design, materials composite engineering, heteroatoms doping, and topography and interface engineering. Additionally, future research directions are also outlined.

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A novel thermosetting preceramic resin called acrylate-grafted liquid polysilazane (ALSZ) was readily synthesized. The curing behaviors of ALSZ were investigated by the techniques of differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and rheological tests. The catalytic thermocuring process was controlled by the addition of a polymerization accelerator composed of a radical initiator (cumene hydroperoxide) and a transition metal catalyst (nickel naphthenate or cobalt naphthenate). Photocuring at room temperature can proceed readily by the addition of photosensitizer 819 (phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide). By combining a radical initiator, a transition metal catalyst, and a photosensitizer, synergistic photothermocuring was achieved, demonstrating advantages such as material shaping at room temperature and low weight loss during curing. The ceramization of the solidified ceramic precursors in an Ar atmosphere was studied using TGA and tube furnace pyrolysis. ALSZs exhibited comparatively high ceramic transformation yields (71-75% at 800 °C). The resulting pyrolytic ceramics maintained their original shape without deformation or foaming expansion. Polysilazanes containing acrylate groups can directly form casting bodies, showing a high static glass transition temperature (>380 °C) by thermomechanical analysis (TMA). FT-IR analyses revealed that multiple reactions are involved in the curing of ALSZ. The results in this paper showed that ALSZ might find prospective applications in material processing, such as additive manufacturing and ceramic-matrix composites.

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BACKGROUND: Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated. METHODS: Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice. RESULTS: Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-ß). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1ß, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic. CONCLUSIONS: The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.

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The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset. This interaction is mediated by binding of the 5-subunit CENP-OPQUR sub-complex of CCAN to the Scc1-SA2 sub-complex of cohesin. Mutation in the CENP-U subunit of the CENP-OPQUR complex that abolishes its binding to the composite interface between Scc1 and SA2 weakens centromeric cohesion, leading to premature separation of sister chromatids during delayed metaphase. We further show that CENP-U competes with the cohesin release factor Wapl for binding the interface of Scc1-SA2, and that the cohesion-protecting role for CENP-U can be bypassed by depleting Wapl. Taken together, this study reveals an inner kinetochore-bound pool of cohesin, which strengthens centromeric sister-chromatid cohesion to resist metaphase spindle pulling forces.

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Currently, it remains challenging to balance intrinsic stiffness with programmability in most vitrimers. Simultaneously, coordinating materials with gel-like iontronic properties for intrinsic ion transmission while maintaining vitrimer programmable features remains underexplored. Here, we introduce a phase-engineering strategy to fabricate bicontinuous vitrimer heterogel (VHG) materials. Such VHGs exhibited high mechanical strength, with an elastic modulus of up to 116 MPa, a high strain performance exceeding 1000%, and a switchable stiffness ratio surpassing 5 × 103. Moreover, highly programmable reprocessing and shape memory morphing were realized owing to the ion liquid-enhanced VHG network reconfiguration. Derived from the ion transmission pathway in the ILgel, which responded to the wide-span switchable mechanics, the VHG iontronics had a unique bidirectional stiffness-gated piezoresistivity, coordinating both positive and negative piezoresistive properties. Our findings indicate that the VHG system can act as a foundational material in various promising applications, including smart sensors, soft machines, and bioelectronics.

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Vibrations with various frequencies in daily life and industry can cause health hazards and fatigue failure of critical structures, which requires the development of elastomers with high energy dissipation at desired frequencies. Current strategies relying on tuning characteristic relaxation time of polymer chains are mostly qualitative empirical methods, and it is difficult to precisely control damping performances. Here, we report a general strategy for constructing dynamic crosslinked polymer fluid gels that provide controllable ultrahigh energy dissipation. This is realized by dynamic-bond-mediated chain reptation of polymer fluids in a crosslinked network, where the characteristic time of chain reptation is dominated by the presence of well-defined dissociation time of dynamic bonds and almost independent of their molar mass. Using prototypical supramolecular polydimethylsiloxane elastomers, we demonstrate that dynamic crosslinked polymer fluid gels exhibit a controllable ultrahigh damping performance at desired frequencies (10-2~102 Hz), exceeding that of typical state-of-the-art silicone damping materials. Their shock absorption is over 300 % higher than that of commercial silicone rubber under the same impact force.

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OBJECTIVE: This review aims to provide a comprehensive summary of the latest research progress regarding the relationship between epilepsy and circular RNA (circRNA). METHODS: Relevant literature from the PubMed database was meticulously searched and reviewed. The selected articles focused on investigating the association between epilepsy and circRNA, including studies on expression patterns, diagnostic markers, therapeutic targets, and functional mechanisms. RESULTS: Epilepsy, characterized by recurrent seizures, is a neurological disorder. Numerous studies have demonstrated significant alterations in the expression profiles of circRNA in epileptic brain tissues, animal models, and peripheral blood samples. These differential expressions of circRNA are believed to be closely linked with the occurrence and development of epilepsy. Moreover, circRNA has shown promising potential as diagnostic markers for epilepsy, as well as prognostic indicators for predicting disease outcomes. Furthermore, circRNA has emerged as a potential therapeutic target for epilepsy treatment, offering prospects for gene therapy interventions. CONCLUSION: The dysregulation of circRNA expression in epilepsy suggests its potential involvement in the pathogenesis and progression of this disorder. Identifying specific circRNA molecules associated with epilepsy may pave the way for novel diagnostic approaches and therapeutic strategies. However, further investigations are imperative to elucidate the precise functional mechanisms of circRNA in epilepsy and validate its clinical utility.

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Piezoelectric hydrogel sensors are becoming increasingly popular for wearable sensing applications due to their high sensitivity, self-powered performance, and simple preparation process. However, conventional piezoelectric hydrogels lack antifreezing properties and are thus confronted with the liability of rupture in low temperatures owing to the use of water as the dispersion medium. Herein, a kind of piezoelectric organohydrogel that integrates piezoelectricity, low-temperature tolerance, mechanical robustness, and stable electrical performance is reported by using poly(vinylidene fluoride) (PVDF), acrylonitrile (AN), acrylamide (AAm), p-styrenesulfonate (NaSS), glycerol, and zinc chloride. In detail, the dipolar interaction of the PVDF chain with the PAN chain facilitates the crystal phase transition of PVDF from the α to ß phase, which endows the organohydrogels with a high piezoelectric constant d33 of 35 pC/N. In addition, the organohydrogels are highly ductile and can withstand significant tensile and compressive forces through the synergy of the dipolar interaction and amide hydrogen bonding. Besides, by incorporating glycerol and zinc chloride, the growth of ice crystals is inhibited, allowing the organohydrogels to maintain stable flexibility and sensitivity even at -20 °C. The real-time monitoring of the pulse signal for up to 2 min indicates that the gel sensor has stable sensitivity. It is believed that our organohydrogels will have good prospects in future wearable electronics.

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INTRODUCTION: Structural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half-life. AIM: Evaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one-stage clotting assays (OSAs) and chromogenic substrate assays (CSAs). METHODS: Human plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full-length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N = 35) tested blinded samples using in-house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed. RESULTS: Efanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under- and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two- to three-fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations. CONCLUSION: Under- or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards.

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