Nardelli D et al. · Jul 1, 2026
Introduction Simonetta Vespucci is the model for the world-renowned Venus painted by Sandro Botticelli at the end of the XV Century. Her unexpected death at the age of 23 remained a mystery for more than 500 years, until we proposed in 2019 that she probably suffered from a pituitary adenoma. Methods We now hypothesize with further evidence from historical descriptions of her last days that an expansion of the adenoma was the cause of her premature death, aged twenty-three. Results Our hypothesis is supported by three elements: (1) tumour characteristics; (2) symptoms presented during her last days; and (3) the historical records of two potential precipitating events. Conclusions We conclude that Simonetta Vespucci, the Venus by Botticelli, died as a consequence of a rapidly expanding pituitary adenoma causing tumour apoplexy, thereby making this endocrine emergency the likeliest cause of her death.
Arts and Humanities
Hanin Z et al. · Jul 1, 2026
Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in patients with diabetes mellitus (DM). Early detection remains difficult, but essential for timely management. In this study, we assessed Peroxidasin (PXDN) gene expression as a biomarker for early detection of DN and for reflection of oxidative stress status. We also compared PXDN and Nuclear factor-κB (NF-κB) expression levels in DN patients, aiming to identify a reliable diagnostic biomarker. Methods This prospective cross-sectional study included 40 patients with T2DM with and without nephropathy, and 20 matched healthy controls. PXDN mRNA expression was quantified by real-time polymerase chain reaction (qRT-PCR). Biochemical analyses of malondialdehyde (MDA) and total antioxidant capacity (TAC) were also done to assess the oxidative stress status. Laboratory parameters, including glycated haemoglobin, urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and microalbuminuria, were measured and correlated with gene expression levels and the oxidative stress status. Results PXDN mRNA expression was significantly upregulated in patients with DN compared to diabetic cases without nephropathy and control subjects. MDA levels were significantly elevated in both diabetic groups relative to controls, but no significant difference was found between DN and DM without renal impairment. TAC was significantly lower in DN cases compared to DM and controls. The NF-κB gene was upregulated in both diabetic groups compared to control subjects, but no significant difference was found between DN and DM without nephropathy. Furthermore, PXDN expression did not correlate with MDA, TAC, or NF-κB levels. Receiver operating characteristic (ROC) analysis identified PXDN as a highly specific and sensitive marker for DN, outperforming conventional oxidative stress biomarkers in distinguishing DN from both diabetic and healthy individuals. Conclusion PXDN is significantly upregulated in DN and may serve as a sensitive and specific molecular marker for early detection of nephropathy compared to NF-κB.
Medicine
Narayan OP et al. · Jul 1, 2026
While recent research shows that biomolecular condensates play important roles in normal cellular processes and diseases, the driving forces in condensate formation are not well understood, especially regarding the role of structured self-associative protein domains. In this work, we study the contribution of a model structured domain, coiled-coil domain, in promoting condensate formation of fusion proteins (FPs). Starting from a large set of ~50,000 FPs, we systematically narrowed down to investigate 14 FPs and their corresponding 18 coiled-coil domains. We showed that all 14 FPs are capable of assembling condensates with high potency. When isolated from the rest of the protein contexts, 11 of the 18 coiled-coil domains can induce condensation on their own, despite their short length compared to their full-length counterparts. To understand the differences between coiled-coils that can drive condensate formation and those that cannot, we developed a "triad-extension" model and found the condensate-sufficient coiled-coil domains have a higher propensity to extend beyond perfectly end-to-end matched dimer/oligomer to promote condensate formation.
Biochemistry, Genetics and Molecular Biology
Bienvenue I et al. · Jul 1, 2026
Background & aims Liver transplantation (LT) is indicated for liver complications related to hepatitis B virus (HBV) infection: acute liver failure (ALF), decompensated cirrhosis or hepatocellular carcinoma (HCC). The present study aimed to describe and evaluate patient survival after LT for HBV-related disease in France and identify the factors influencing survival. Methods The present retrospective cohort study based on medical record information included all adult patients transplanted with positive HBsAg (+/- coinfection with Hepatitis D virus (HDV)) between January 1, 2005 and December 31, 2023 in all French LT centres. Results The study population consisted of 1083 patients, the majority of whom were men (81.5%) with a median [IQR] age at LT listing of 52.8 [42.5-59.8] years. Indications for LT were HBV-related HCC (47.2%), HBV-related cirrhosis (28.5%), HDV-related cirrhosis (11.2%), HBV-related ALF (10.5%), HDV-related HCC (1.4%) and other (0.7%). Median [IQR] post-LT follow-up was 6.0 [2.2-11.1] years. Patient survival at 1, 5, 10 and 15 years after LT was 91.6%, 80.1%, 71.8% and 63.6% respectively. Multivariate analysis showed that independent significant prognostic factors were age at LT (HR: 1.030; 95CI: 1.019-1.042; p Conclusions Survival after LT for HBV-related liver disease is good. NUC type prior to LT seems to be associated with patient survival.
Medicine
Bedoya JU et al. · Jul 1, 2026
Background & aims Transjugular intrahepatic portosystemic shunt (TIPS) improves survival in refractory ascites. A careful patient's selection is mandatory as TIPS can lead to complications. Liver volumetry is predictive of outcomes before hepatic surgery, but data on its role before TIPS placement are scarce. We aimed to evaluate whether liver and spleen volume measurements are associated with prognosis after TIPS placement in patients with ascites. Methods We analysed data from three French centers, treated with TIPS between 2017 and February 2022. Inclusion criteria encompassed a TIPS placement for refractory or recurrent ascites and availability of cross-sectional imaging. Exclusion criteria included non-cirrhotic portal hypertension, other indications for TIPS, hepatocellular carcinoma beyond Milan criteria, and extrahepatic malignancy. Liver and spleen volumes were measured using pre-TIPS CT or MRI scans. The primary endpoint was 1-year transplant-free survival (TFS). Secondary endpoints were overt hepatic encephalopathy (HE), recurrence of ascites, acute variceal bleeding, and jaundice. Results The 160 patients were included (median age 60 years, male gender 83.8%, alcohol-related cirrhosis 58.8%, with active alcohol consumption in 25.6%, Child-Pugh B cirrhosis in 81.2%, median MELD score was 12). The 1-year TFS was 60.1%. Multivariate analysis identified serum creatinine (HR = 1.01 95% CI [1.00-1.01], p = 0.04), total bilirubin (HR = 1.02 95% CI [1.02-1.04], p = 0.004), and portal pressure gradient (HR = 1.09 95% CI [1.01-1.18], p = 0.03) as independent factors associated with TFS. Neither liver-to-spleen volume ratios (LSVR) (p = 0.36) nor liver volume index (p = 0.92) were significantly associated with death or LT. Overall, 38.1% of patients developed overt HE after TIPS, with lower platelet count (HR = 1.01 95% CI [1.00-1.01], p = 0.04) emerging as an independent predictor. No radiological characteristics were associated with the recurrence of ascites. Conclusions In this multicenter study, liver and spleen volumes were not associated with transplant-free survival or liver-related outcomes in patients undergoing TIPS for ascites. These findings suggest that liver volumetry should not be a determining factor in patient selection for TIPS placement.
Medicine
Kara MC et al. · Jul 1, 2026
Background The significant cross-reactivity between bovine, ovine, and caprine pregnancy-associated glycoproteins (PAGs) enables the adaptation of bovine-specific diagnostics for use in other ruminants; consequently, the Alertys OnFarm Pregnancy Test (AOFPT)-a blood-based lateral flow assay-provides a rapid and practical solution for pregnancy detection directly at the animal's head under field conditions. Objectives This study evaluated to assess and validate the performance of AOFPT in goats at days 21 and 28 post-mating, by comparing the results with serum progesterone (P4) analysis and using transabdominal ultrasonography (TAUS) as the gold standard. Methods The study involved 85 Kilis goats, five months post-partum. Estrus was synchronized using an 11-day progestagen device, d-cloprostenol, and PMSG. Whole blood and serum samples were collected on Days 21 and 28 post-mating. AOFPT was performed on-farm immediately after collection. For validation, serum progesterone concentrations were measured via electrochemiluminescence immunoassay, and TAUS was performed on Days 35 and 42, with Day 42 findings serving as the gold standard. Results Results indicated that on Day 21, AOFPT sensitivity, specificity, positive predictive value, and negative predictive value were 79.4%, 93.8%, 98.2%, and 51.7%, respectively. By Day 28, these metrics reached 100%, 81.3%, 95.8%, and 100%. Statistical agreement between AOFPT and the reference method was K = 0.55 (82.14%) on Day 21 and K = 0.87 (96.43%) on Day 28 (p Conclusions AOFPT demonstrated accuracy and reliability closely matching P4 measurements and the reference method. This test provides a practical tool for early on-farm pregnancy diagnosis in goats, potentially enhancing reproductive management and productivity in dairy goat farms and large herds.
Agricultural and Biological Sciences
Qiu S et al. · Jul 1, 2026
Hearing impairment is attributed to factors such as age, genetic predisposition, and environmental influences, among which environmental factors are considered modifiable. Among various environmental factors, the role of poor lifestyle habits is particularly critical, yet the specific mechanisms by which they contribute to hearing damage remain unclear. This study reveals that dysregulated hormone levels due to disrupted light exposure may significantly increase susceptibility to sensorineural hearing loss. In mice, circadian rhythm disruption was found to reduce melatonin and elevate serotonin levels in the inner ear, thereby increasing vulnerability to cisplatin-induced ototoxicity. In both in vivo and in vitro cisplatin-treatment models, we showed that combined treatment with melatonin protected hearing, reduced inner ear cell death, and preserved synaptic connections, whereas serotonin co-administration exacerbated the damage. Using small molecule-protein interaction prediction, we identified NOS3 as a potential target of both melatonin and serotonin, through which they appear to regulate the NO signaling pathway and influence hair cell ferroptosis. Finally, exogenous supplementation of NOS3 in cochlear tissues effectively mitigated cisplatin-induced hair cell damage, even under conditions of circadian rhythm disruption. These findings indicate that the melatonin/serotonin balance modulates susceptibility to sensorineural hearing loss via the NOS3-NO signaling pathway.
Neuroscience
Hintersteininger M et al. · Jul 1, 2026
Background & aims Transjugular intrahepatic portosystemic shunt (TIPS) placement is used to treat complications of portal hypertension. This study aimed to evaluate the prognostic value of von Willebrand factor antigen (VWF) dynamics following TIPS placement. Methods Patients with TIPS placement at the Medical University of Vienna (2018-2025) and University Medical Center Mainz (2022-2025) with available VWF at baseline (BL) were included. Patients from both cohorts with available VWF after 3 months (M3) were included in the combined longitudinal cohort (CLC). Meaningful VWF decrease (VWF-Response) was defined as a relative VWF change (ΔVWF) of at least -5% at M3. Patients were stratified by presence of VWF-Response and interleukin-6 decrease (IL6-Response) into three groups: both (R2), either/or (R1), and neither (R0). Results Overall, 113 and 86 patients were included in the Vienna and Mainz cohorts, respectively. BL VWF was not associated with mortality in both cohorts. 118 patients constituted the CLC, which showed median BL VWF of 313.0% that decreased to 262.0% at M3 (p = 0.007). Fifty-three patients (44.9%) achieved VWF-Response. Both, VWF change (ΔVWF; asHR: 2.75; 95% CI: 1.07-7.11; p = 0.037) and VWF-Response (asHR: 0.24; 95% CI: 0.09-0.61; p = 0.003) were independently associated with survival. According to VWF and IL6 responses, patients were stratified as low-risk (R2), versus intermediate-risk (R1) versus high-risk (R0) with a cumulative incidence of death at 2 years of follow-up of R2: 10.6% versus R1: 23.1% versus R0: 46.7%, respectively. Conclusion After TIPS placement, VWF-Response identifies patients with a favourable prognosis and can be combined with IL6-Response for risk stratification regarding mortality.
Medicine
Bahman F et al. · Jul 1, 2026
Background The aryl hydrocarbon receptor (AhR) is linked to inflammation, but its plasma agonist activity and association with metabolic and inflammatory markers in obesity remain unclear. This cross-sectional study aimed to determine the level of plasma AhR agonistic activity and its association with systemic inflammation and metabolic dysregulation in obesity. Methods Plasma samples were collected from 80 non-diabetic (39-obese, 23-overweight, and 18-normal/healthy weight) individuals. AhR agonist activity was assessed using a cell-based luciferase reporter assay. Plasma AhR was quantified by ELISA. Inflammatory markers were assessed using a multiplex Luminex platform. Results Our findings indicate that plasma AhR agonist activity is elevated in obese (92.77 ± 4.002 fold activation) compared with normal/healthy weight (51.39 ± 2.335) and overweight participants (67.54 ± 5.24 fold activation). Moreover, the AhR protein was also elevated in obese (94.88 ± 7.62 pg/ml) compared to normal/healthy weight (65.88 ± 6.78 pg/ml) and overweight participants (67.54 ± 5.24 pg/ml), which was positively correlated with AhR activity (r = 0.441, p Conclusions Our findings demonstrate that elevated plasma AhR agonist activity is associated with obesity, systemic inflammation, and metabolic dysregulation. These results highlight AhR activity as a biomarker of interest and support further studies to clarify its mechanistic role and potential clinical relevance in metabolic disorders.
Environmental Science
Munro ML et al. · Jul 1, 2026
Aim The ryanodine receptor (RyR2) is an intracellular Ca 2+ release channel which mediates numerous cellular functions across different tissues. Dysregulation of RyR2 channel activity leads to pathological Ca 2+ release, which often underlies disrupted cellular signaling in disease states. In the heart, RyR2 channels forms discrete clusters and calcium release units (CRUs) which control channel activity. These structures demonstrate nanoscale remodeling in disease states associated with pathological Ca 2+ release activity in the heart. Hence, these nanoscale structures are critical in regulating Ca 2+ release in health and disease. RyR2 is also expressed in brain; however, whether analogous clusters and CRUs form in neurons remains unexplored. Methods Using super-resolution imaging, we assessed RyR2 organization in CA1 pyramidal neurons of wild-type mice. Furthermore, we used the APP/PS1 mouse model of Alzheimer's disease (AD) to assess whether there is nanoscale remodeling of RyR2 in a setting associated with pathological Ca 2+ release in neurons. Results Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Moreover, we observed a decrease in RyR2 cluster size and reduced CRU organization in AD mice at an age associated with high plaque burden and cognitive deficits. This remodeling is analogous to that reported in pathological states in the heart. Conclusion Together, these findings implicate the nanoscale remodeling of RyR2 clusters and CRUs as a novel mechanism underlying Ca 2+ channel dysregulation and neuronal dysfunction in AD.
Biochemistry, Genetics and Molecular Biology