Pyridoxine-dependent epilepsy due to ALDH7A1 deficiency (PDE-ALDH7A1) is a rare but treatable epileptic encephalopathy caused by disruption of lysine catabolism and secondary depletion of pyridoxal-5'-phosphate (PLP). Although seizures are often controlled with pyridoxine supplementation, many patients continue to experience neurodevelopmental impairment, underscoring the importance of early diagnosis and improved therapeutic strategies. Central to both diagnosis and pathophysiology is the accumulation of lysine-derived metabolites, most notably α-aminoadipate semialdehyde (α-AASA), its cyclic Schiff base Δ[1]-piperideine-6-carboxylate (P6C), and pipecolic acid. These metabolites have become the biochemical hallmarks of PDE-ALDH7A1, linking ALDH7A1 pathogenic variants to PLP inactivation and neuronal dysfunction. However, their chemical instability and analytical requirements pose challenges for universal diagnostics and newborn screening. This review summarizes current understanding of lysine catabolism in health and disease, critically evaluates the diagnostic utility and limitations of classical biomarkers, and discusses emerging insights into their pathophysiological roles. We further highlight recent discoveries of novel, chemically stable biomarkers, including 6-oxopiperidine-2-carboxylic acid (6-oxo-PIP), 2-oxopropylpiperidine-2-carboxylic acid (2-OPP), and 6-hydroxy-2-aminocaproic acid (HACA), identified through advanced metabolomics approaches. These metabolites show promise for newborn screening and provide new mechanistic links between metabolic stress, seizure susceptibility, and ongoing neurological morbidity despite pyridoxine treatment. Collectively, advances in biomarker discovery are reshaping diagnostic strategies for PDE-ALDH7A1 and offering new perspectives on disease mechanisms, paving the way for earlier detection and the development of more effective, mechanism-based therapies.

This study evaluates the rate of von Willebrand disease (vWD) in patients with craniosynostosis and describes the management of patients with vWD who require surgical correction of craniosynostosis (SCC). This is a retrospective cohort study of 190 consecutive patients who underwent initial SCC at a university-affiliated community hospital between January 2016 and May 2024. Before surgery, patients were evaluated by the Pediatric Blood Management Service and underwent laboratory tests for anemia and vWD. Patients who screened positive for vWD received a hematology and oncology (Heme/Onc) referral, preoperative infusion of antihemophilic factor/von Willebrand factor complex (Humate-P), and postoperative administration of aminocaproic acid (Amicar). Univariate analysis was used to compare transfusion volumes between patients with and without vWD. A total of 13.2% of patients were referred to Heme/Onc due to abnormal vWD labs, and 6.8% of patients were ultimately diagnosed with vWD by Heme/Onc. All patients diagnosed with vWD received Humate-P preoperatively, and 77% of patients with vWD also received postoperative Amicar. Compared with all other patients, patients with vWD demonstrated no difference in estimated blood loss (EBL) or intraoperative and total pRBC volumes. There was also no difference in EBL nor pRBC volumes when comparing patients with vWD to anemia protocol-adherent and relative anemia protocol-adherent cohorts. vWD in our craniosynostosis population was higher than in the general American population, which is ∼1%. Preoperative screening for vWD and appropriate perioperative management can effectively address blood loss and transfusion needs for patients undergoing SCC.

Monoclonal antibodies (mAbs) are complex therapeutic proteins exhibiting heterogeneity due to post-translational modifications, making charge variant analysis essential for defining critical quality attributes. Although ion-exchange chromatography and capillary isoelectric focusing are established techniques, they require extensive optimisation, whereas the widely adopted ε-aminocaproic acid-based capillary zone electrophoresis (CZE) (eACA-CZE) method provides a simpler, robust platform. However, its performance can be limited for mAbs whose charge profiles or isoelectric point (pI) values fall outside the method's optimal range. To expand CZE capabilities while maintaining a platform approach, we developed a series of background electrolytes (BGEs) spanning a range of pH values, polyamine concentrations and buffering capacities. These BGEs were formulated for chemical compatibility, long-term stability and fixed-component composition to ensure consistent pH and reproducible currents. Using a pH 5.7 BGE as the starting point, key components were optimised across the full buffer set. A multivariate approach showed that combining these buffers enhanced resolution, resolving additional impurity peaks in 9 of 10 mAbs. This work establishes a flexible toolkit for screening and optimising charge-variant resolution across diverse mAbs.

Thrombin and plasmin both play a central role in hemostasis, regulating coagulation and fibrinolysis, respectively. Conventional hemostatic assays often focus on isolated components or limited phases of hemostasis; for example, activated partial thromboplastin time and prothrombin time evaluate only the initiation of fibrin formation, while factor activity assays assess the function of individual coagulation factors. Although valuable, these assays lack a comprehensive view of the overall process of secondary hemostasis and fibrinolysis, which unfolds dynamically over time. The Nijmegen Hemostasis Assay (NHA) addresses this limitation by enabling simultaneous, time-resolved measurement of thrombin and plasmin generation in a single microplate well. Using two synthetic fluorogenic substrates with distinct excitation and emission spectra and no cross-reactivity, the assay allows accurate quantification of both enzymes in parallel. Hemostasis is initiated in platelet-poor plasma using tissue factor, calcium and tissue-type plasminogen activator, and fluorescence is recorded every 30 s over 70 min at 37 °C. Enzyme activity curves are generated using calibration standards, from which parameters such as lag time, thrombin potential, fibrin lysis time, and plasmin peak height are derived. The assay reliably captures simultaneous thrombin and plasmin generation with good intra- and inter-assay precision, and detects modulation of coagulation and fibrinolysis by effectors such as heparin, activated protein C, and epsilon-aminocaproic acid. In clinical samples, significantly reduced thrombin generation was observed in patients with coagulation factor deficiencies, while patients with fibrinolytic disorders showed elevated plasmin generation profiles. By combining thrombin and plasmin generation measurements, the NHA provides a comprehensive insight into the hemostatic balance beyond conventional assays. This integrated approach holds promise for research and clinical applications, such as the characterization of hemostatic phenotypes, assessment of bleeding and thrombotic risk, and monitoring of targeted therapeutic interventions. This protocol outlines the NHA procedure that aims to enhance the understanding and assessment of hemostatic balance.

Dynamic wet interfaces, exemplified by tooth extraction sockets, demand dressings that can maintain firm adhesion despite constant salivary flushing, suction, and mastication while actively guiding tissue regeneration. Conventional hemostatic materials detach easily under these forces, destabilizing clots and impairing healing. Here, we develop a photocurable wet-adhesive metabolic hydrogel (WAM-Gel) that integrates interfacial stability with bioinstructive metabolic signaling. The hydrogel is formed from N-acryloyl glycinamide (NAGA) and acryloyl-6-aminocaproic acid N-hydroxysuccinimide ester (AANHS), which in situ photo-crosslink into a hydrogen-bond-rich, covalently anchored dual network. This architecture provides high compressive strength, considerable burst pressure, and exceptional shear adhesion, thereby ensuring stable sealing under physiologic suction, chewing, and brushing in daily oral activities. Controlled swelling further ensures conformal socket filling and reliable clot stabilization. Beyond adhesion, the hydrogel incorporates β-hydroxybutyrate (BHB) to endow the construct with metabolic immunoregulatory functionality. As a metabolic regulator, BHB orchestrates osteoimmune programming by coupling macrophage phenotype remodeling with enhanced osteogenic differentiation, thereby fostering a pro-regenerative microenvironment. This dual action suppresses inflammatory cytokines, promotes M2 polarization, augments angiogenesis, and accelerates osteogenesis. In vivo, WAM-Gel enhanced early neovascularization, collagen maturation, and bone formation in rat extraction models, and preserved ridge contour with improved trabecular microarchitecture in beagle sockets compared with standard care. Together, this work supports a bioactive sealing strategy that integrates wet stable adhesion and metabolic regulation for osteoimmune guided regeneration at dynamic oral interfaces.

In this work, 6-aminocaproic acid-modified copper ferrite nanoparticles were synthesized and used as an adsorbent for removing Amaranth dye from water. The modified nanoparticles were easily prepared using a simple and cost-effective method, namely the coprecipitation method. The nanocomposite was characterized by techniques like FTIR, XRD, SEM with EDS, and TEM. To evaluate the adsorption capacity of Amaranth dye, concentrations of Amaranth, contact time, nanocomposite dose, and solution pH were optimized. Further, Langmuir and the Freundlich isotherm models have been investigated. Among these, the Freundlich model showed the most accurate correlation with the experimental result, indicating a multilayer and physico-chemical adsorption of Amaranth dye onto the heterogeneous surface of the prepared nanocomposite. The Langmuir maximum adsorption capacity of this study was ~17 mg g-1. Thermodynamic parameters (∆G° and ∆H°) confirmed that the adsorption process was spontaneous and exothermic. Adsorption kinetic studies showed pseudo second-order fitting with the multi-step adsorption process. The current adsorption performance was best for the first two adsorption-desorption cycles.

Protein lysine methylation is a distinct class of post-translational modifications because it minimally alters the size and positive charge of the lysine side chain. In cellular contexts, the human genome encodes over 60 protein lysine methyltransferases (PKMTs), with the S-adenosyl-l-methionine (SAM) cofactor as the methyl donor, to modify thousands of lysine sites on histones and nonhistone targets in a highly orchestrated manner. The biological roles of protein lysine methylation are increasingly implicated in epigenetic regulation to define diverse cell fates, and their dysregulation is frequently associated with developmental abnormalities and various aspects of cancerous malignancy. However, it has been challenging to annotate the multiple upstream methyltransferase(s) in parallel from known methyllysine marks in the context of over 60 PKMT candidates with redundant and cell-type-dependent activities. We therefore envisioned the technology of Covalent Trapping of Protein Lysine Methyltransferases (CTPM) by assembling the ternary dead-end complex of PKMTs with substrate-cofactor surrogates. With SET-domain-containing PKMTs, the norleucine(Nle)-SAM pair was shown to be a robust structural motif to form such dead-end complexes, likely via harnessing the common feature of the transition state of PKMT-catalyzed lysine methylation. Our CTPM peptidic probes contain the Nle warhead in the place of substrate lysine, the photo-cross-linking residue in proximity of Nle, and the terminal biotin anchor for target enrichment. These CTPM probes, upon pairing with the SAM cofactor, show high efficiency in trapping the upstream PKMTs of the cognate histone and nonhistone substrates.

The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has evaluated the occupational exposure limit value (maximum concentration at the workplace, MAK value) of 6-[(4-methylphenyl)sulfonylamino]hexanoic acid (N-tosyl-6-aminocaproic acid) [78521-39-8] considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. The substance is a complexing agent. As the influence of the complexing effect and the acid effect on the respiratory tract is not known and inhalation studies are not available, a maximum concentration at the workplace (MAK value) cannot be derived. The NOAEL for developmental effects in rats after oral administration was 100 mg/kg body weight and day. In a gavage study in rats that was carried out according to OECD Test Guideline 422, pup mortality was increased and pup body weights were decreased up to postnatal day 4 at 1600 mg/kg body weight and day. The substance is not genotoxic in bacteria or mammalian cells. Carcinogenicity studies are not available. There is no evidence of a contact sensitizing potential. Skin contact is not expected to contribute significantly to systemic toxicity.

ObjectiveTo compare the dose-dependent chondrotoxicity of tranexamic acid (TXA) and aminocaproic acid (ACA) in vitro and in vivo.DesignIn vitro, human chondrocytes were exposed to TXA or ACA (0-50 mg/ml), and cytotoxicity was assessed. In vivo, a rat model of monoiodoacetate-induced osteoarthritis was used to evaluate cartilage damage following intra-articular injections of TXA or ACA.ResultsIn vitro, both TXA and ACA reduced chondrocyte viability in a dose-dependent manner, with significant cytotoxicity observed at concentrations ≥20 mg/ml. TXA was more toxic than ACA at these higher concentrations. Apoptosis increased markedly at 30 mg/ml for both agents. In the rat osteoarthritis model, joints treated with TXA or ACA showed greater cartilage erosion and matrix loss compared to controls, with TXA causing more severe damage.ConclusionBoth TXA and ACA are chondrotoxic in a dose-dependent manner, with TXA demonstrating greater potency. Lower concentrations (≤10 mg/ml) are recommended for topical use in cartilage-preserving surgery to minimize potential damage.