Ovarian endometrioma cystectomy may compromise ovarian reserve through inadvertent excision of ovarian cortex. We compared inadvertent cortical removal between robotic-assisted and conventional laparoscopic cystectomy using digital pathology. We retrospectively analyzed 81 patients (40 laparoscopic, 41 robotic) who underwent single-surgeon cystectomy (January 2020-December 2025) with digitized hematoxylin and eosin-stained slides available. Ninety-eight ovary/side specimens were classified as follicle-containing cortex, cortex without follicles, or fibrosis, and excised cortical area (mm²) was quantified. The primary analysis used log-linear regression adjusted for cyst length and width with patient-clustered robust standard errors. Tissue-type distribution did not differ by approach (P = 0.611). Excised cortical area was smaller with robotics (median 34.6 mm², interquartile range 16.9-82.3) than laparoscopy (median 65.4 mm², interquartile range 39.5-81.6; P = 0.011). In the adjusted model, robotics was associated with a smaller excised cortical area (robot-to-laparoscopy ratio 0.55, 95% confidence interval 0.32-0.93; P = 0.029). Follicle counts and antral follicle presence among follicle-containing specimens were comparable. Robotic-assisted cystectomy was associated with less inadvertent excision of ovarian cortex after accounting for cyst dimensions, while follicle-based specimen metrics did not differ.

Duchenne muscular dystrophy (DMD) is a progressive, severe muscle-wasting disease caused by mutations in DMD, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells, and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria support the muscle immune response in the mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. Furthermore, the absence of gut microbes through the generation of mdx germ-free animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD.

Ferroptosis is an iron-dependent form of cell death driven by lipid peroxidation1. Here we identify spermine-a polyamine derived from spermidine2-as an endogenous iron chelator that directly suppresses ferroptosis. Integrating metabolomics, stable isotope tracing and biophysical studies of the interaction between spermine and Fe2+ ions, we demonstrate that aldehyde dehydrogenase 18 family member A1 (ALDH18A1) promotes an alternative glutamine-dependent pathway for de novo spermine synthesis. This process limits iron availability and lipid peroxidation in hepatocellular carcinoma. Genetic or pharmacological inhibition of ALDH18A1-through knockout, short hairpin RNA delivered using adeno-associated virus (AAV), or the small molecule inhibitor YG1702-triggers ferroptosis and impairs both spontaneous and chemically induced hepatocarcinogenesis. Conversely, supplementation of spermine protects against ferroptosis-associated ischaemia-reperfusion injury across multiple tissues, including the liver, intestine and kidneys. These findings uncover a pathophysiologically relevant metabolic circuit in which spermine-mediated iron chelation suppresses ferroptosis.

Degenerative lumbar spinal stenosis (LSS) is driven by fibrosis and hypertrophy of the ligamentum flavum (LF). Oxidative stress-an excess of reactive oxygen species (ROS) over antioxidant defenses-may underlie LF remodeling, but tissue-level evidence is limited. LF from patients with LSS (n = 180) and controls (n = 102) underwent transcriptomic microarray and microRNA (miRNA) profiling, reverse-transcription quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and biochemical assays of thiobarbituric acid-reactive substances (TBARS), total glutathione (GSH), and glutathione peroxidase (GPx) activity. Protein-protein interaction (PPI) and functional enrichment analyses were performed. Among 14,130 oxidative-stress-related transcripts, 8,197 were differentially expressed (p < 0.05). Redox-sensitive inflammatory mediators were upregulated, including tumor necrosis factor (TNF), interleukin-1β (IL-1B), interleukin-6 (IL-6), and C-X-C motif chemokine ligand 8 (CXCL8), alongside mitogen-activated protein kinases (MAPK8/JNK1, MAPK14/p38α, MAPK1/ERK2) and superoxide dismutase 2 (SOD2) and peroxiredoxin-1 (PRDX1). Antioxidant defenses-catalase (CAT), superoxide dismutases SOD1/SOD3, glutathione peroxidase-1 (GPX1), and sirtuin-3 (SIRT3)-were downregulated. RT-qPCR confirmed these trends. ELISA demonstrated higher MAPK8 and IL-6 and lower SIRT3 and GPX1 in hypertrophic LF (all p < 0.05). Biochemically, LSS tissue showed increased TBARS and GPx activity and decreased GSH versus controls; oxidative imbalance intensified with greater pain and higher body mass index. Selected miRNAs (e.g., hsa-miR-3163→MAPK8, hsa-miR-4291→SIRT3) were reduced. PPI networks were highly enriched (p < 1 × 10⁻¹⁶). Notably, MAPK8, SIRT3, GPX1, and IL-6 dysregulation was independent of pain category. LF in LSS exhibits a persistent ROS-driven, MAPK-amplified inflammatory program with mitochondrial vulnerability (SIRT3 loss) and impaired peroxide detoxification (GPX1 decline). This oxidative signature likely sustains fibrosis and LF thickening and nominates MAPK8-SIRT3-GPX1-IL-6 as candidate biomarkers and therapeutic targets.

Acyl-CoA-binding protein (ACBP, encoded by diazepam binding inhibitor, DBI) is an abundant intracellular regulator of lipid metabolism that also circulates systemically, yet the mechanisms governing its release and its relationship to organ injury remain unresolved. Herein, we combine human multi-omics, mechanistic mouse models and controlled cell death assays to identify cell death-driven liberation of intracellular ACBP/DBI as a unifying mechanism underlying its elevation in disease. In a cohort of 1198 hospitalized adults, among whom 75% were acutely infected by SARS-CoV-2, plasma ACBP/DBI tightly correlated with inflammatory markers and biochemical signatures of cardiac, hepatic, renal, metabolic and hematologic dysfunction. SomaScan proteomics further revealed that ACBP/DBI co-varies with organ-enriched proteins, particularly those originating from skeletal muscle and pancreas, implicating tissue injury as a major determinant of its circulating abundance. Multiple forms of acute organ damage in mice, including hepatic or renal ischemia-reperfusion, bile duct ligation, pancreatitis and rhabdomyolysis, triggered rapid and robust increases in plasma ACBP/DBI. Using defined in vitro paradigms, we demonstrate that apoptosis, ferroptosis and necroptosis each cause loss of intracellular ACBP/DBI and its release upon plasma membrane permeabilization, independent of the upstream lethal pathway. These mechanistic insights translated in vivo: hepatocyte apoptosis, ferroptosis and necroptosis each elevated circulating ACBP/DBI in a manner attenuated by pathway-specific inhibitors. Finally, meta-analysis of >100,000 individuals across diverse populations revealed that elevated plasma ACBP/DBI consistently associates with systemic and organ-specific disease and predicts future morbidity. Together, our findings identify cell death-driven ACBP/DBI release as a conserved mechanism linking organ injury to increased plasma ACBP/DBI, positioning this molecule as an integrative biomarker of tissue damage across species, organs, and cell death modalities.

Pulmonary fibrosis is a chronic and progressive lung disease with a high mortality rate. Current conventional therapeutic drugs are limited by problems such as low bioavailability, inadequate pulmonary drug concentration, poor targeting, and significant systemic toxicity, which restrict their clinical efficacy. In recent years, advances in nanotechnology have provided new strategies for its treatment. Nanocarriers have significantly improved drug delivery efficiency and therapeutic outcomes in pulmonary fibrosis, demonstrating promising application prospects. Therefore, this review summarizes the nanocarriers widely used in drug delivery for pulmonary fibrosis in recent years, aiming to provide new insights into drug delivery for this disease.

Hippo signalling is increasingly recognised as an important regulator of metabolic adaptation rather than solely a pathway controlling organ size and growth. This review examines how nutrients, hormones, and energy stress regulate Hippo-Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) activity, and how Hippo signalling, in turn, rewires glucose, lipid, amino acid, and nucleotide metabolism. We highlight emerging concepts, including metabolite-specific checkpoints, tissue-specific Hippo functions across metabolic organs, and the context-dependent roles of Hippo signalling in obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease/steatohepatitis, cardiometabolic disease, and cancer. We also discuss how this bidirectional Hippo-metabolism axis is opening new therapeutic opportunities, while underscoring that effective translation will require cell-type- and disease-stage-specific targeting.

Since 2012, 2 viral causes of hepatitis have been identified in horses. Much remains to be discovered about their transmission, risk factors for clinical disease, diagnosis, and treatment approaches. Equine parvovirus-hepatitis has been identified as the cause of acute hepatic necrosis, previously known as Theiler's disease. Equine hepacivirus is recognized as a cause of chronic fibrosing hepatitis. Diagnosis relies on ruling out other causes of hepatitis and documenting infection by serum or liver polymerase chain reaction. There is no direct antiviral for either condition and treatments are symptomatic or aimed at ameliorating effects of liver failure and encephalopathy if present.

Pelvic exenteration (PE) is a complex, potentially curative option for locally advanced or recurrent pelvic malignancies in which achieving an R0 margin is paramount. This clinical review provides a pragmatic, anatomy-driven framework to optimize preoperative assessment and multidisciplinary planning. Using a compartment-based schema-central, anterior, posterior, and lateral-the article maps tumour spread to structures that determine technical feasibility and functional outcomes. For each compartment, surgical implications and reporting "pearls and pitfalls" are summarized to ensure radiological interpretation directly informs surgical decision-making. Special attention is given to differentiating tumour infiltration from post-treatment fibrosis, particularly following chemoradiotherapy, where diffusion-weighted MRI plays an important role in the attempt to differentiate residual disease from fibrosis and defining safe resection planes. The review outlines assessment of critical anatomical structures or variants that have implications for surgical planning or functional consequences for patients. In addition, reconstructive options and their imaging appearances are briefly discussed to aid postoperative assessment. Through detailed anatomical analysis and structured, compartment-based reporting, radiologists can enhance multidisciplinary communication, refine patient selection, anticipate morbidity, and ultimately increase the likelihood of achieving complete resection in pelvic exenteration.

The identification of clinically predictive serum biomarkers for pulmonary fibrosis is a significant challenge and important goal. Multiple recent proteomic biomarker studies have identified latent transforming growth factor binding protein-2 (LTBP2) as a circulating factor associated with disease progression in fibrotic lung diseases in humans (including IPF), but its role in the development of fibrosis is incompletely defined. LTBP2 competes with the large latent transforming growth factor-beta (TGFβ) complex (LLC) for binding to the N-terminus of fibrillin and is thought to promote the release of active TGFβ. We hypothesized that LTBP2 deficiency would promote LLC sequestration in matrix and reduce TGFβ signaling. We recently reported an LTBP2 knockout (Ltbp2-/-) mouse with no baseline lung abnormalities. Here we show that Ltbp2-/- mice exposed to either bleomycin or silica have a significant reduction in fibrosis compared to wild type controls. Consistent with reduced fibrosis, after bleomycin Ltbp2-/- mouse lungs have reduced TGFβ signaling and isolated fibroblasts from Ltbp2-/- mice exhibit impaired migration in an in vitro wound closure assay. Transcriptomic analysis of bleomycin-treated control and Ltbp2-/-mouse lung tissue identified multiple LTBP2-regulated genes, including the lncRNA antisense of IGFR2 non-coding RNA (Airn) which has reported antifibrotic effects. Interestingly, we also observed that Ltbp2-/-mice had impaired epithelial repair after bleomycin treatment, a phenotype that also occurred in a naphthalene model of club cell injury. These findings provide evidence that LTBP2 is profibrotic and facilitates TGFβ signaling but is also required for normal airway epithelial repair.

Severe asthma is characterized by both steroid resistance and fibrotic remodeling. We hypothesized that myofibroblasts in fibrotic lung tissue acquire glucocorticoid resistance through the upregulation of the anti-apoptotic factor B-cell lymphoma-extra large (Bcl-xL). This study aimed to determine whether myofibroblasts become steroid-resistant via Bcl-xL expression in vivo and in vitro. A steroid-resistant asthma model was developed by repeatedly challenging sensitized BALB/c mice intratracheally with a high dose of ovalbumin (OVA). Myofibroblasts were identified by flow cytometry as α-smooth muscle actin (α-SMA)+ CD31- CD45- CD326- cells. Lung mesenchymal stem cells (MSCs; platelet-derived growth factor receptor α+ CD31- CD45- CD326- cells) were isolated and differentiated into myofibroblasts by culturing them with 15% fetal bovine serum (FBS) for 6 d. In asthmatic lungs, α-SMA+ myofibroblasts showed increased Bcl-xL expression, which was unaffected by dexamethasone (DEX) treatment. However, co-treatment with the Bcl-xL inhibitor navitoclax significantly restored steroid sensitivity. In vitro, MSCs were susceptible to DEX-induced early apoptosis, whereas differentiated myofibroblasts were resistant to DEX-induced apoptosis and strongly expressed Bcl-xL. In other words, navitoclax treatment overcame steroid resistance in cultured myofibroblasts. These findings indicate that Bcl-xL-expressing myofibroblasts contribute to the development of glucocorticoid resistance in fibrotic lungs in severe asthma. Targeting Bcl-xL may provide a novel therapeutic strategy to restore steroid responsiveness in severe asthma.

A recent study by Grippin et al showed that COVID-19 mRNA-lipid nanoparticle vaccines can be strategically implemented to fundamentally reshape the immunosuppressive tumor microenvironment and boost the efficacy of immune checkpoint inhibitors (ICIs) even in patients bearing cancer types that are usually refractory to ICIs. Mechanistically, innate immunological responses elicited by COVID-19 mRNA vaccine negate multiple tumor-associated immune evasion mechanisms and ultimately enable functionally competent polyclonal antitumor CD8+ T responses. As many mRNA vaccines are already, or on the point of being, approved for human use, the translational potential of therapies combining mRNA vaccines with ICIs is unprecedented. Indeed, the strategic repurposing of COVID-19 (and other) mRNA vaccines represents a clinically feasible and immediately translatable approach to potentiate the efficacy of ICI-based cancer immunotherapy.