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461 papers

Validation of a Pregnancy-Associated Glycoprotein-Based Lateral Flow Assay for Early Pregnancy Detection in Goats.

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

Circadian-Related Serotonin/Melatonin Level Modulates Cisplatin Ototoxicity Susceptibility Depended on NOS3-NO Pathway.

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

Post-TIPS Dynamics of von Willebrand Factor for Risk Stratification After TIPS Placement.

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

Plasma Aryl Hydrocarbon Receptor Agonist Activity Is Associated With Inflammation and Metabolic Dysregulation in Obesity: A Cross-Sectional Study.

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

Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease.

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

Machine-learning prediction of affinity and epistasis in the bovine pancreatic trypsin inhibitor-chymotrypsin complex.

Tzuri N et al. · Jul 1, 2026

Protein-protein interactions (PPIs) are shaped by evolutionary pressures that fine-tune binding affinities and drive the epistatic relationships that support functional outcomes. Here, we used the complex of bovine pancreatic trypsin inhibitor (BPTI) and chymotrypsin as a model system to study how mutations at one or two positions affect binding affinity and epistasis. To predict the binding affinity landscape of the BPTI-chymotrypsin complex, we combined deep sequencing data, obtained from a saturation scanning mutagenesis BPTI library, with a machine-learning (ML) model. Using this ML model, which was trained on a subset of experimental binding data, we predicted the binding affinities and epistatic interactions across thousands of single and double BPTI mutants, including those not observed in the library. Our predictive approach completed missing data points and enabled us to reveal global trends in affinity changes and mutation couplings within specific binding interface positions. Our analysis revealed that different mutations in the same position may have different effects on affinity, with most double mutations leading to increased epistasis, particularly at hotspot positions, thereby indicating a cooperative binding effect. In most cases, affinity and epistasis were inversely correlated, with affinity enhancement of double-mutant variants being associated with negative epistasis. Our approach can be readily generalized to predict mutation effects in larger combinatorial libraries and in proteins for which structural information is lacking.

Biochemistry, Genetics and Molecular Biology

A Ten-Country Study on Public Perceptions of 5G EMF Emissions: Who Feels Exposed, and Why?

Link SC et al. · Jul 1, 2026

Formal risk assessment considers characteristics such as proximity, dose, and vulnerability. However, public risk perception may also be influenced by other-possibly less relevant-factors such as visibility and novelty. The introduction of 5G and its associated infrastructure and radiofrequency electromagnetic fields (RF-EMF) may therefore change perceptions of RF-EMF from mobile communications in general. To explore this, we conducted an online survey in 10 European countries (n = 10,358) using a picture-based approach. Respondents perceived daily RF-EMF exposures as moderate but expected them to increase with 5G. A mobile phone at the ear was generally associated with higher perceived exposure than multiple base stations. Overall, distance to the RF-EMF source most strongly influenced perceived exposure, followed by the number of sources. 5G reception was linked to higher exposure perception than 4G or Wi-Fi reception. These patterns were consistent across most countries. We conclude that when assessing RF-EMF exposure, people rely on heuristics (e.g., more sources imply more exposure) that often guide them correctly. Understanding when and why people feel particularly exposed can help develop more effective communication about true levels of exposure and risk.

Biochemistry, Genetics and Molecular Biology

Diacylglycerol enantiomer selectivity of diacylglycerol acyltransferases highlights metabolic specialization in triacylglycerol synthesis across the tree of life.

Parchuri P et al. · Jul 1, 2026

Triacylglycerols are the major energy storage lipids in plants, animals, and microorganisms, and are predominantly produced by acyl-CoA:diacylglycerol (DAG) acyltransferases (DGATs). Two enantiomers of the DAG substrate, sn-1,2 and sn-2,3, can be produced by different biological mechanisms; however, little is known about which species produce each enantiomer, the selectivity of DGAT isoforms for either enantiomer, or whether DGAT enantiomer selectivity varies across organisms. Here, DAG enantiomer selectivity of DGAT1 and DGAT2 was measured from eight seed plants, two mammals, one oleaginous yeast, and one photosynthetic microalga using enantiomer-specific in vitro DGAT assays. Across most plants, DGAT1 favored sn-1,2-DAG, whereas DGAT2 preferentially utilized sn-2,3-DAG. However, there were several exceptions. Mammalian DGAT1, DGAT2, and microbial DGAT1s efficiently used both DAG enantiomers, while microbial DGAT2s had unique selectivity. The selectivity of several DGATs for combined acyl-CoA and DAG enantiomer molecular species were also evaluated for biotechnical applications. Therefore, DGAT DAG enantiomer selectivity is common yet strongly dependent on lineage and isoform and likely shaped in part by species-specific metabolic context of triacylglycerol synthesis, turnover, and remodeling. This work expands our understanding of DGAT function and establishes a foundation for leveraging enantiomer-selective acyltransferases in metabolic engineering of tailored lipid products.

Biochemistry, Genetics and Molecular Biology

Association Between Dietary Advanced Glycation End Products (AGEs) and Pancreatic Fat Accumulation: Evidence From a Case-Control Study.

Shahparvari MR et al. · Jul 1, 2026

Background Pancreatic steatosis (PS) is a metabolic condition associated with obesity, insulin resistance, and fatty liver disease. Advanced Glycation End Products (AGEs), abundant in processed and high-temperature-cooked foods, have been linked to several metabolic disorders; however, their relationship with PS has not been previously examined. Methods In this case-control study, 278 individuals with gallstones, aged 55.7 ± 15.1 years, were classified as cases (with PS, n = 89) or controls (without PS, n = 189). PS was defined based on increased echogenicity of the pancreatic parenchyma relative to surrounding structures. Dietary intake was assessed using a food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for PS across quartiles of dietary AGE intake. The fully adjusted model included age, sex, total energy intake, body mass index, smoking status, and alcohol consumption. Results Higher dietary AGE intake was significantly associated with an increased likelihood of PS. In the crude model, odds of PS did not differ significantly across quartiles of dietary AGE intake compared with the lowest quartile. After adjustment for age and sex, individuals in the highest quartile had higher odds of PS (OR = 3.56; CI: 1.1-11.6; p = 0.040). In the fully adjusted model, significant associations were observed for the third (OR = 2.76; CI: 1.69-11.1) and fourth (OR = 3.3; CI: 1.79-13.7) quartiles of dietary AGE intake compared with the lowest quartile. A significant positive trend in the odds of PS was observed across increasing quartiles of dietary AGE intake (p for trend = 0.024). Conclusion Our findings suggest a potential role of dietary AGEs in pancreatic fat accumulation; however, causality cannot be inferred. Larger prospective and interventional studies are needed to confirm these associations and to determine whether reducing dietary AGE exposure can beneficially influence pancreatic fat.

Biochemistry, Genetics and Molecular Biology

Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.

Hammoum T et al. · Jul 1, 2026

Peptide-based nanoparticles (PBN) have emerged as a promising alternative to lipid nanoparticles (LNP) for nucleic acid delivery and efficient cellular uptake. In this study, we evaluated the formulation of WRAP5 (W- and R-rich amphipathic peptide 5)-based PBN using a microfluidic device and assessed the impact of key process parameters, flow rate ratio (FRR), total flow rate (TFR), and mixing channel design, on nanoparticle characteristics. Across 72 formulations encapsulating small interfering RNA (siRNA) or plasmid DNA (pDNA), dynamic light scattering revealed consistent mean sizes ranging from 50 to 70 nm, with a low polydispersity index (PdI < 0.22), independent of FRR, TFR, or mixer type. Stability studies demonstrated that siRNA-loaded PBN exhibited moderate size increases during storage at 4°C, whereas pDNA-loaded PBN remained highly stable for up to 70 days. Biological assays confirmed robust activity: WRAP5:siRNA PBN achieved approximately 50% CDK4 silencing in GIST-T1 cells, and WRAP5:pDNA PBN mediated efficient mCHERRY expression in HeLa cells, regardless of formulation method or storage duration. These findings highlight the robustness and scalability of WRAP5-based PBN, contrasting with LNP systems that require stringent control of FRR and TFR, and partially underscore their potential for nucleic acid delivery applications.

Biochemistry, Genetics and Molecular Biology