Metabolic diseases are increasingly linked to dysregulation of the gut-liver axis, highlighting the therapeutic potential of probiotics. Lactococcus lactis subsp. cremoris (LLC) protects against experimental hepatic steatosis, but the mechanisms underlying its benefits remain poorly understood. Here, we integrated untargeted metabolomics, gnotobiotic mouse models, targeted bile acid profiling, and liver injury paradigms to systematically define LLC-mediated metabolic reprogramming. LLC extensively remodeled serum and hepatic metabolomes in Western diet-fed mice, enriching pathways associated with lipid metabolism, xenobiotic biotransformation, and redox homeostasis. LLC attenuated ethanol-induced steatosis and acetaminophen-induced liver injury, accompanied by activation of Nrf2-dependent antioxidant programs and FXR signaling. LLC monocolonization was sufficient to reprogram the hepatic metabolome, revealing direct host metabolic effects. Reduced intestinal bile acid conjugation emerged as a prominent LLC-associated phenotype. Together, these findings identify LLC as a probiotic that reprograms the gut-liver metabolic axis to enhance metabolic resilience and hepatoprotection.

Real-time quality control of pharmaceutical dosage forms requires rapid, non-destructive analytical technologies that provide chemical specificity while maintaining high throughput. Here, an extended short-wave infrared (eSWIR, 1000-2500 nm) line-scan hyperspectral imaging system (L-EOS 2.5e, Photon Etc.) was evaluated for spatially resolved classification of pharmaceutical tablets. The system was evaluated at integration times of 2, 0.2, and 0.02 ms using Standard Normal Variate normalization, Savitzky-Golay second-derivative preprocessing, and an error-correcting output codes support vector machine classifier. Product-level classification of 11 pharmaceutical products achieved accuracies of 99.99%, 100%, and 97.6% at 2, 0.2, and 0.02 ms, respectively. A more challenging manufacturer-level discrimination task involving three 500 mg acetaminophen products containing the same active pharmaceutical ingredient and labeled dose achieved accuracies of 99.7%, 98.6%, and 89.3% at the corresponding integration times. These results demonstrate the potential of eSWIR hyperspectral imaging for rapid, spatially resolved pharmaceutical product discrimination and high-throughput inspection.

Acetaminophen (APAP) induced acute liver injury (ALI) is driven by a self amplifying cascade of reactive oxygen species (ROS) and lipid peroxidation, yet current therapies fail to interrupt this pathological loop. Here we engineer a liver targeted hierarchical nanozyme, SOD@ZIF-8/Mn3O4, which integrates natural superoxide dismutase (SOD) and Mn3O4 nanozymes within a ZIF‑8 nanoplatform. Unlike conventional single step scavengers, this system implements a catalytic hierarchy matching strategy. SOD rapidly converts O2·[-] to H2O2, while Mn3O4 simultaneously decomposes H2O2 and intercepts ·OH, thereby converting the entire ROS cascade into benign water. Density functional theory calculations reveal that the SOD-Mn3O4 interface lowers the energy barriers for catalase like and glutathione peroxidase like steps, establishing a synergistic channeling effect. In APAP injured AML-12 cells and a murine ALI model, the nanozyme not only alleviates oxidative stress and lipid peroxidation but also breaks the ROS inflammation feed forward loop by restoring the Keap1/Nrf2/HO‑1 redox switch and suppressing NF‑κB activation. Transcriptomic and functional analyses confirm that treatment rewires hepatic transcriptional programs associated with lipid metabolism and inflammatory signaling. This work establishes a modular nanozyme natural enzyme hybrid platform where the MOF acts as a spatiotemporal organizer, transforming the pathological ROS chain into a controlled detoxification pathway. The concept is readily extensible to other diseases driven by sequential ROS cascades, offering a paradigm shift from single enzyme mimicry to pathway reprogramming nanobiocatalysis.

Both elevated plasma cell-free hemoglobin (CFH) and heparanase-driven endothelial glycocalyx shedding are contributors to microvascular dysfunction and organ injury in sepsis. However, the mechanisms governing heparanase activation, and the potential role of CFH in this process, are not understood. Utilizing patient samples, mice with cecal slurry-induced (CS) peritonitis and elevated CFH, and human lung microvascular endothelial cells (HLMVECs), we tested the hypothesis that CFH upregulates heparanase production to drive endothelial glycocalyx degradation. In human sepsis, elevated circulating CFH was associated with higher heparanase and heparan sulfate levels, which in turn correlated with adverse clinical outcomes. CS+CFH-treated mice had increased plasma heparanase, glycocalyx degradation, and pulmonary and systemic inflammation; endothelial heparanase deletion abrogated these effects. Additionally, in both pulmonary endothelial cells isolated from CS+CFH-treated mice and HLMVECs exposed to CFH and TNF(?), heparanase transcription and active enzyme production were increased. The deleterious effects of CFH were attenuated by acetaminophen, a hemoprotein reductant. In summary, we demonstrate that CFH oxidation stimulates endothelial heparanase expression and activation during sepsis, leading to endothelial glycocalyx degradation, which may disrupt the endothelial barrier and result in organ injury. Our findings highlight the CFH-heparanase axis as a potential therapeutic target for endothelial glycocalyx preservation in sepsis.

Paracetamol overdose is the leading cause of acute liver failure in many countries, including North America and the United Kingdom. While timely administration with the standard treatment is generally effective, the optimal treatment for scenarios such as "massive" overdose or modified release paracetamol overdose remains unknown. In this work we aim to develop and calibrate a systems pharmacology model for paracetamol-induced hepatotoxicity with the influence of administration of the antidote N-acetylcysteine (NAC). The system model integrates five components, including (1) input of paracetamol, (2) paracetamol metabolism of parent drug and metabolites, (3) physiological turnover of endogenous sulfur-containing substrates, including the metabolism of cysteine to produce glutathione and inorganic sulfate, etc., (4) a general model for the release of biomarkers from injured hepatocytes to blood, and (5) a PK model for NAC and three proposed mechanisms of NAC effect. The final systems model demonstrated a good description of the concentration-time courses of paracetamol, its metabolites and biomarkers after administration of a normal dose to a large overdose of paracetamol. The final model provides a quantitative and comprehensive understanding of the causal pathway of paracetamol-induced liver toxicity and its treatment, which allows the investigation of the 'what if' scenarios in the rescue of paracetamol poisoning.

Renal angiomyolipomas (AMLs) are benign, hypervascular tumors that require transarterial embolization if ruptured or preemptively if at high risk of hemorrhage (>4 cm, intralesional aneurysms, childbearing age, symptomatic, etc.). The embolic materials of choice, in order to produce permanent occlusions of the distal microvasculature bed of the lesion, are microspheres and liquid embolic agents. Embolization may be technically challenging when imaging suggests arteriovenous (AV) communication because rapid flow can compromise controlled delivery of these agents. We report a 30-year-old woman with intermittent right-flank pain and a 5.0-cm right renal AML. Preprocedural computed tomography angiography demonstrated enlarged perilesional veins with early arterial-phase opacification, raising suspicion of intratumoral arteriovenous communication; however, a discrete arteriovenous fistula or high-flow shunt was not directly demonstrated on digital subtraction angiography. These findings prompted a balloon-assisted flow-control strategy to minimize the risk of reflux and non-target embolization. A Scepter™ Mini dual-lumen occlusion balloon microcatheter (Terumo Neuro, Aliso Viejo, CA, USA; balloon size 2.2×9 mm; distal/proximal outer diameter 1.6/2.8 Fr) was advanced into the dominant feeding artery over a 0.008-inch Traxcess™ Mini guidewire (Terumo Neuro, Aliso Viejo, CA, USA). After the 0.44-mL catheter dead space was primed with dimethyl sulfoxide, one 1.5-mL vial of Squid 12 (Balt, Montmorency, France) was injected slowly under temporary flow arrest. Completion angiography demonstrated complete tumor devascularization with preservation of uninvolved renal parenchymal perfusion, and immediate noncontrast computed tomography showed embolic material confined to the target vessels without visible venous migration. Moderate overnight postembolization pain was controlled with intravenous paracetamol, and the patient was discharged the following day. At three-month follow-up, magnetic resonance imaging demonstrated no residual enhancement and a reduction in calculated tumor volume from 49.5 to 11.6 cm[3] (76.5%). This case demonstrates the technical feasibility of balloon-assisted Squid 12 embolization and highlights how preprocedural imaging can directly influence the endovascular strategy in selected complex renal embolization procedures.

Metabolic acidosis is a common finding following cardiac surgery. Although the differential diagnosis of high-anion-gap metabolic acidosis is well established, less common causes may be overlooked, making the diagnosis challenging. We report the case of a 59-year-old patient who developed high-anion-gap metabolic acidosis after surgical treatment for mediastinitis, caused by the concomitant use of flucloxacillin and paracetamol. This drug interaction disrupts the γ-glutamyl cycle, leading to the accumulation of 5-oxoproline (pyroglutamic acid). Although rare, this interaction may cause a severe and potentially fatal reaction, particularly in patients with renal failure, sepsis, or malnutrition. As such, the possible diagnosis of pyroglutamic acidosis should be kept in mind in these settings, and the use of these medications should be discontinued immediately.

Transition metal-mediated activation of sulfite (S(IV)) has garnered substantial interest in advanced oxidation processes (AOPs) for water remediation. Nevertheless, an incomplete understanding of the interfacial activation mechanism limits further improvement and regulation of treatment performance. Herein, a single-atom iron catalyst (Fe1CN) with a well-defined Fe coordination environment is employed as a model platform to investigate coordination-mediated S(IV) activation. The Fe1CN/S(IV) system achieves rapid acetaminophen (ACT) removal, with a reaction rate higher than those of selected benchmark iron-based catalysts under the tested conditions. Mechanistic investigations indicate that oxysulfur radical chemistry, particularly SO4[•-]- and SO5[•-]-related pathways, plays an important role in ACT degradation. Combined in situ spectroscopic analyses and theoretical calculations support preferential interfacial coordination of S(IV) with Fe single-atom sites, promoting inner-sphere electron transfer and subsequent oxysulfur species evolution. Fe sites with an average oxidation state of approximately + 2.4 are associated with Fe(II)- and Fe(III)-involved activation pathways that contribute to sustained S(IV) conversion. The Fe1CN/S(IV) system also maintains effective performance in representative water matrices and during 24 h continuous-flow operation. These findings provide mechanistic insights into coordination-regulated S(IV) activation at Fe single-atom sites and offer valuable guidance for efficient S(IV)-based water treatment.

Understanding the etiologies, clinical characteristics, and outcomes of acute liver failure (ALF) is important for guiding management and evaluating prognosis; however, evidence from Vietnam remains limited. We conducted a prospective single-center cross-sectional observational study involving patients with ALF admitted to Bach Mai Hospital, Vietnam, between January 2020 and July 2021. The study included 60 patients from January 2020 to July 2021 who fulfilled the selection criteria for ALF diagnosis. The mean age of patients was about 53 ± 15 years (range = 21-85 years). Most complications were bleeding (80.0%), metabolic disorders (78.0%), and hypotension (61.6%). The acute subtype was the most common ALF subclassification, accounting for 56.7% of cases. Traditional medicines (21/60 cases) are the most common cause and the leading cause of death, causing 15 out of 45 deaths. Hepatitis B (11/60 cases) and paracetamol (6/60 patients) are the second and third most common causes of ALF, with a mortality rate of 72.7% and 66.7%, respectively. In univariate analyses, older age, higher liver enzyme levels, and more severe clinical complications were significantly associated with mortality (P < .05). In this single-center cohort, traditional medicine was the most frequently identified cause of ALF. Given the small sample size and observational design, these findings should be interpreted cautiously and confirmed in larger multicenter studies. Nevertheless, the findings highlight the importance of improving public awareness regarding the safe use of traditional medicines.

Controlling the material properties of crystalline pharmaceutical materials is essential for developing materials with robust performance and manufacturability. Identification of the crystal facets present in a material opens up the opportunity for developing strategies to control and engineer material to meet manufacturing needs. This proof of concept study presents a workflow for using powder X-ray diffraction (PXRD) and angle resolved polarised Raman spectroscopy (ARPRS), in combination with density functional theory (DFT) calculations, to identify facets in samples unsuitable for single-crystal face indexing with XRD. Using Paracetamol (PCM) form I as a model compound, we demonstrate how preferred orientation effects in PXRD can be used with ARPRS measurements at different sample orientations, obtained by rotating in the plane perpendicular to the laser incidence direction, to define facet assignments from a set of possible planes. PXRD alone cannot distinguish the (011) and (01̄1) facets, but these can be differentiated with ARPRS by analysing the change in normalised band intensity of selected vibrational modes under crystal rotation. Information on the symmetry and orientation of vibrational modes relative to the incident laser can be related to the orientation of functional groups, and this information is consistent with the predicted particle morphology as well as with measurements of the interfacial angle between the facets and corresponding Miller planes.