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Background Diet analysis is essential to understanding the functional role of large bird species in food webs. Morphological analysis of regurgitated bird pellet contents is time intensive and may underestimate biodiversity. DNA metabarcoding has the ability to circumvent these issues, but has yet to be done. Methods We present a pilot study using DNA metabarcoding of MT-RNR1 and MT-CO1 markers to determine the species of origin and prey of 45 pellets collected in Qinghai and Gansu Provinces, China. Results We detected four raptor species [Eurasian Eagle Owl (Bubo bubo), Saker Falcon (Falco cherrug), Steppe Eagle (Aquila nipalensis), and Upland Buzzard (Buteo hemilasius)] and 11 unique prey species across 10 families and 4 classes. Mammals were the greatest detected prey class with Plateau Pika (Ochotona curzoniae) being the most frequent. Observed Shannon’s and Simpson’s diversity for Upland Buzzard were 1.089 and 0.479, respectively, while expected values were 1.312 ± 0.266 and 0.485 ± 0.086. For Eurasian Eagle Owl, observed values were 1.202 and 0.565, while expected values were 1.502 ± 0.340 and 0.580 ± 0.114. Interspecific dietary niche partitioning between the two species was not detected. Conclusions Our results demonstrate successful use of DNA metabarcoding for understanding diet via a novel noninvasive sample type to identify common and uncommon species. More work is needed to understand how raptor diets vary locally, and the mechanisms that enable exploitation of similar dietary resources. This approach has wide ranging applicability to other birds of prey, and demonstrates the power of using DNA metabarcoding to study species noninvasively.

Although our understanding of the molecular and cellular factors involved in the development and growth of glioma has increased, prognosis remains dismal in most patients. The emerging field of cancer neuroscience has revealed the intricate functional interplay between glioma and the cellular architecture of the brain, especially neural circuits. In recent years, studies have revealed that glioma cells integrate and remodel multicellular neural circuits. Neural circuits have thus emerged as critical regulators of glioma from initiation to malignant growth. In the present review, an updated framework was provided for understanding the construction of neuron-glioma networks and the mechanisms by which neurons regulate the malignant phenotype of glioma. Readers will also obtain insights into the construction of glioma-glioma networks formed by tumor microtubes. Furthermore, the present review reveals the complex interconnectivity among the nervous system, immune system and glioma that promotes tumor growth. Finally, some potential areas of clinical translation and new research directions were highlighted.

Background Patients with non–germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) often exhibit suboptimal responses to standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Methods This multicenter, phase II study evaluated the safety and efficacy of zanubrutinib, lenalidomide, and R-CHOP (ZR2-CHOP) in newly diagnosed non-GCB DLBCL. Patients received oral zanubrutinib (160 mg twice daily), lenalidomide (25 mg once daily on Days 1–7), and standard R-CHOP every 21 days for up to six cycles. Results A total of 34 patients were enrolled. The median age was 55 years, with 29.4% over 60 years. Double-expressor lymphoma (DEL) was present in 64.7%, and 39.3% were classified as the MCD genetic subtype. The best overall response rate was 100%. Complete response (CR) was achieved in 70.6% of patients at mid-treatment and 94.1% at end-of-treatment. With a median follow-up of 28 months, the 2-year progression-free survival (PFS) rate was 84.8%, and the 2-year overall survival (OS) rate was 96.8%. In this small cohort, PFS benefit appeared consistent across high-risk subgroups, including those with DEL and MCD subtypes. Plasma ctDNA negativity was achieved in 84% (21/25) of evaluable patients during treatment. Grade 3–4 adverse events occurred in 67.6% of patients, primarily hematologic toxicities. Conclusions ZR2-CHOP demonstrated promising efficacy and manageable toxicity in newly diagnosed non-GCB DLBCL. Trial registration ClinicalTrials.gov Identifier: NCT05200312 (registered January 20, 2022).

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), remains a major clinical challenge due to the limitations of conventional anticoagulant therapies. This study explores tetrahedral DNA nanostructures (TDNs) as a novel therapeutic strategy for DVT by targeting endothelial cell necroptosis and oxidative stress. A mouse DVT model was established via inferior vena cava ligation. TDNs were synthesized from four complementary ssDNA strands and validated via gel electrophoresis and atomic force microscopy. Therapeutic effects were assessed through histopathology, Western blot, qPCR, RNA-seq, and oxidative stress markers (SOD/MDA). Mechanistic insights were explored via transcriptomics, co-immunoprecipitation, and bioinformatics. In a mouse DVT model, TDNs demonstrated remarkable efficacy in mitigating thrombosis, reducing endothelial damage, and restoring vascular homeostasis. Mechanistically, TDNs downregulated the phosphorylation of RIP3 and MLKL, suppressed necroptosis, and modulated inflammatory signaling, specifically via the interaction between PTPRC and CCR9. Transcriptomic analysis confirmed that TDNs ameliorated the dysregulated expression of immune-inflammatory mediators while promoting antioxidative effects by increasing SOD activity and decreasing MDA levels. Bioinformatics and protein interaction assays further unveiled a direct binding between RIP3 and PTPRC, highlighting their roles as molecular targets of TDNs. These findings underscore TDNs' potential as a safe and effective nanotherapeutic platform for managing DVT by simultaneously targeting necroptosis, oxidative stress, and inflammation. Future studies are warranted to optimize dosing strategies and evaluate their long-term safety and synergistic use with established anticoagulants.

Large numbers of lipids exist in the porcine oocytes and early embryos and have the positive effects on their development, suggesting that the lipids may play an important role in pluripotency establishment and maintenance in pigs. However, the effects of lipids and their metabolites, such as fatty acids on reprogramming and the pluripotency gene expression of porcine-induced pluripotent stem cells (iPSCs), are unclear. Here, we generated the porcine iPSCs that resemble the mouse embryonic stem cells (ESCs) under lipid and fatty-acid-enriched cultural conditions (supplement of AlbuMAX). These porcine iPSCs show positive for the ESCs pluripotency markers and have the differentiation abilities to all three germ layers, and importantly, have the capability of aggregation into the inner cell mass (ICM) of porcine blastocysts. We further confirmed that lipid and fatty acid enriched condition can promote the cell proliferation and improve reprogramming efficiency by elevating cAMP levels. Interestingly, this lipids supplement promotes mesenchymal–epithelial transition (MET) through the cAMP/PKA/CREB signal pathway and upregulates the E-cadherin expression during porcine somatic cell reprogramming. The lipids supplement also makes a contribution to lipid droplets accumulation in the porcine iPSCs that resemble porcine preimplantation embryos. These findings may facilitate understanding of the lipid metabolism in porcine iPSCs and lay the foundation of bona fide porcine embryonic stem cell derivation.

A key challenge in electronic skin with dual haptic‐stretch sensing is the interference between force‐sensitive modes. Existing solutions require complex integration processes or mathematical decoupling models. Effectively decoupling stretch and pressure response in flexible force‐sensitive sensors remains a critical task. Herein, a strain redistribution effect (SRE) of composite structural mainframe fulfills the decouple double‐mode force‐sensitive perception by the aid of a lightweight algorithm. The CAD‐assisted design enables the dual‐mode sensing structure to be configured as a three‐layer stacked composite. Utilizing differential Young's modulus distribution, the strain redistribution effect is achieved across the structured frame. Tensile deformation and tactile pressure are measured via resistance from the strain amplification region and capacitance from the strain suppression region, respectively. Digital Image Correlation (DIC) confirms a 53% deformation in the amplification region under 10% tensile strain, demonstrating a fivefold amplification effect. A lightweight random forest algorithm effectively decouples resistance‐capacitance signals, achieving R2 values of 0.99 and 0.75 for tensile deformation, and 0.99 and 0.78 for tactile pressure, respectively. This study leverages the strain redistribution effect of the composite structural frame to provide a novel structured integration scheme for the dual‐mode decoupled force‐sensitive sensing unit, which is expected to be a significant development path. A strain redistribution effect in a composite frame decouples stretch and pressure responses in dual‐mode force‐sensitive sensors. The design uses resistance for tensile deformation and capacitance for pressure. A random forest algorithm effectively decouples the signals, achieving high accuracy. This approach offers a novel solution for improving force‐sensitive sensing performance in electronic skin applications.

Objectives Non-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth. Methods Patients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. NCCT markers were rated by two investigators for heterogeneous density, hypodensity, black hole sign, swirl sign, blend sign, fluid level, island sign, satellite sign, and irregular shape. ICH and IVH volumes were semi-manually segmented. IVH growth was defined as IVH expansion > 1 mL (eIVH) or any delayed IVH (dIVH) on follow-up imaging. Predictors of eIVH and dIVH were explored with multivariable logistic regression. Hypothesized moderators and mediators were independently assessed in PROCESS macro models. Results A total of 731 patients were included, of whom 185 (25.31%) suffered from IVH growth, 130 (17.78%) had eIVH, and 55 (7.52%) had dIVH. Irregular shape was significantly associated with IVH growth (OR 1.68; 95%CI [1.16–2.44]; p  = 0.006). In the subgroup analysis stratified by the IVH growth type, hypodensities were significantly associated with eIVH (OR 2.06; 95%CI [1.48–2.64]; p  = 0.015), whereas irregular shape (OR 2.72; 95%CI [1.91–3.53]; p  = 0.016) in dIVH. The association between NCCT markers and IVH growth was not mediated by parenchymal hematoma expansion. Conclusions NCCT features identified ICH patients at a high risk of IVH growth. Our findings suggest the possibility to stratify the risk of IVH growth with baseline NCCT and might inform ongoing and future studies. Clinical relevance statement Non-contrast CT features identified ICH patients at a high risk of intraventricular hemorrhage growth with subtype-specific differences. Our findings may assist in the risk stratification of intraventricular hemorrhage growth with baseline CT and might inform ongoing and future clinical studies. Key Points • NCCT features identified ICH patients at a high risk of IVH growth with subtype-specific differences. • The effect of NCCT features was not moderated by time and location or indirectly mediated by hematoma expansion. • Our findings may assist in the risk stratification of IVH growth with baseline NCCT and might inform ongoing and future studies.

It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a “dose effect”. Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.

Background: The objective of this study was to assess the performance of the first publicly available automated 3D segmentation for spontaneous intracerebral hemorrhage (ICH) based on a 3D neural network before and after retraining. Methods: We performed an independent validation of this model using a multicenter retrospective cohort. Performance metrics were evaluated using the dice score (DSC), sensitivity, and positive predictive values (PPV). We retrained the original model (OM) and assessed the performance via an external validation design. A multivariate linear regression model was used to identify independent variables associated with the model’s performance. Agreements in volumetric measurements and segmentation were evaluated using Pearson’s correlation coefficients (r) and intraclass correlation coefficients (ICC), respectively. With 1040 patients, the OM had a median DSC, sensitivity, and PPV of 0.84, 0.79, and 0.93, compared to thoseo f 0.83, 0.80, and 0.91 in the retrained model (RM). However, the median DSC for infratentorial ICH was relatively low and improved significantly after retraining, at p < 0.001. ICH volume and location were significantly associated with the DSC, at p < 0.05. The agreement between volumetric measurements (r > 0.90, p > 0.05) and segmentations (ICC ≥ 0.9, p < 0.001) was excellent. Conclusion: The model demonstrated good generalization in an external validation cohort. Location-specific variances improved significantly after retraining. External validation and retraining are important steps to consider before applying deep learning models in new clinical settings.