Explore the vast range of titles available.

Background Muscle-invasive bladder cancer (MIBC) is a prevalent and aggressive malignancy. Ferroptosis and cuproptosis are recently discovered forms of programmed cell death (PCD) that have attracted much attention. However, their interactions and impacts on MIBC overall survival (OS) and treatment outcomes remain unclear. Methods Data from the TCGA-BLCA project (as the training set), cBioPortal database, and GEO datasets (GSE13507 and GSE32894, as the test sets) were utilized to identify hub ferroptosis/cuproptosis-related genes (FRGs and CRGs) and develop a prognostic signature. Differential expression analysis (DEA) was conducted, followed by univariate and multivariate Cox’s regression analyses and multiple machine learning (ML) techniques to select genetic features. The performance of the ferroptosis/cuproptosis-related signature was evaluated using Kaplan–Meier (K–M) survival analysis and receiver-operating characteristics (ROC) curves. Mutational and tumour immune microenvironment landscapes were also explored. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments confirmed the expression patterns of the hub genes, and functional assays assessed the effects of SCD knockdown on cell viability, proliferation, and migration. Results DEA revealed dysregulated FRGs and CRGs in the TCGA MIBC cohort. SCD, DDR2, and MT1A were identified as hub genes. A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets. Nomogram incorporating this signature accurately predicted 1-, 3-, and 5-year survival probabilities in the TCGA cohort and GSE13507 dataset. Copy number variation (CNV) and tumour immune microenvironment analysis revealed that high risk score level groups were associated with immunosuppression and lower tumour purity. The associations of risk scores with immunotherapy and chemical drugs were also explored, indicating their potential for guiding treatment for MIBC patients. The dysregulated expression patterns of three hub genes were validated by RT-qPCR experiments. Conclusions Targeting hub FRGs and CRGs could be a promising therapeutic approach for MIBC. Our prognostic model offers a new framework for MIBC subtyping and can inform personalized therapeutic strategies.

The volume capture ratio of annual rainfall (VCRAR) of low-impact development measures is significantly influenced by its operating characteristics, particularly for residential stormwater detention tanks (SWDTs). The multi-objective operation strategy of SWDTs, encompassing toilet flushing (TF), green space irrigation (GSI), combined TF and GSI (TF-GSI), and peak flow reduction (PFR) rate, were compared using a case study in Beijing based on the stormwater management model. The findings indicate that the VCRAR for TF, GSI, and TF-GSI rainwater harvesting targets was 89.05, 77.16, and 91.21%, respectively. The operating scheme and return periods have a significant impact on the PFR rate's effectiveness. When the return period was lower than 10 years, the SWDT does not reach its maximum storage capacity, and the PFR rate was increased with increasing the return period: the PFR rate was 71.47% when the design return period was 10 years. It will also produce the phenomena of water inrush, and the overflow volume will grow rapidly when the SWDT reaches its maximum storage capacity. Hence, the operation of SWDTs may be integrated with real-time control to optimize the VCRAR for rainwater reuse and flood migration, thereby enhancing the volume utilization efficiency of SWDTs.

Postoperative recurrence of pancreatic adenocarcinoma (PAAD) remains a major challenge. This study aims to establish and validate a lipid metabolism-related prognostic model to predict recurrence in PAAD patients. The TCGA-PAAD database was used to establish a training cohort, which was validated using the ICGC database and multiple center cohorts. A prognostic model based on LASSO Cox regression and a nomogram was developed and further validated. Among 196 lipid metabolism-related genes, four were selected for the prognostic model. Patients were stratified into high- and low-risk groups based on the risk score. Univariate and multivariate Cox regression analyses showed that tumor site, T stage, N stage, M stage, and risk score were significantly associated with progression-free interval (PFI). High-risk patients had worse PFI, overall survival (OS), and disease-specific survival (DSS) (all P  < 0.05). Time-dependent ROC and decision curve analyses confirmed the superior diagnostic capacity of the nomogram. GSEA revealed enrichment in G2M checkpoint, glycolysis, estrogen response, and hypoxia pathways for the high-risk group. Additionally, high-risk scores correlated with poor immune infiltration, gene mutations, and tumor mutational burden (TMB). Single-cell analysis suggested that risk genes interact with various cell types to promote PAAD progression. A novel lipid metabolism-related prognostic model was developed and validated to predict recurrence and survival in PAAD patients, with strong accuracy and stability.

Influenza A virus (IAV) continues to present a threat to public health, highlighting the need for safe and multi-target antivirals. In this study, anti-influenza activity, airborne transmission blocking capacity, and immunomodulatory effects of Cnidium monnieri polysaccharides (CMP) were evaluated. Cytotoxicity in A549 cells was assessed by CCK-8 (CC50 = 8.49 mg/mL), antiviral efficacy against A/California/04/2009 (CA04) by dose–response (EC50 = 1.63 mg/mL), and the stage of action by time-of-addition assays (pre-, co-, post-treatment). A guinea pig model infected with CA04 was used for testing the effect of pre-exposure CMP on transmission, with readouts including nasal-wash titers, seroconversion, lung index, and tissue titers (EID50). RT-qPCR was employed to quantify the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in lung tissue, while Western blot analysis was performed to assess the expression and phosphorylation status of key proteins involved in the NF-κB signaling pathway. CMP suppressed viral replication in vitro within non-cytotoxic ranges, and pre-treatment—rather than co- or post-treatment—significantly reduced titers and cytopathic effect, consistent with effects at pre-entry steps and/or host priming. In vivo, pre-exposure CMP lowered nasal shedding, reduced aerosol transmission (3/6 seroconverted vs. 6/6 controls), decreased lung indices, and diminished tissue viral loads; IAV was undetectable in trachea at 7 days post-infection in pre-exposed animals, and nasal-turbinate titers declined relative to infection controls. Moreover, during in vivo treatment in mice, CMP significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in lung tissue. This effect was mechanistically associated with CMP-mediated regulation of the NF-κB signaling pathway, leading to attenuation of inflammatory responses. These data indicate that CMP combines a favorable in vitro safety and efficacy profile with inhibition of airborne spread in vivo, supporting further mechanistic, pharmacokinetic, and fractionation studies toward translational development.

The tumor necrosis factor (TNF) ligand superfamily plays a critical role in immune regulation and has emerged as a promising target in cancer immunotherapy. By binding to its receptor OX40 (CD134), TNFSF4 promotes the proliferation and survival of T cells and plays an important role in the tumor immune microenvironment, but its role in pancreatic cancer is unclear. This study aimed to investigate the expression patterns and prognostic significance of TNF ligand family members in pancreatic cancer (PC), with a specific focus on TNFSF4. We analyzed single-cell RNA sequencing data from the GSE212966 dataset to assess the expression of TNFSF ligands across immune cell types. TCGA-PAAD bulk RNA-seq data were used for non-negative matrix factorization (NMF) clustering to identify molecular subtypes based on TNFSF ligand expression profiles. Immune infiltration was quantified using single-sample gene set enrichment analysis (ssGSEA), and Kaplan–Meier survival curves were used to compare overall survival (OS) and progression-free survival (PFS) between subtypes. Immunotherapy response prediction was evaluated using tumor mutational burden (TMB), immunophenoscore (IPS), and tumor immune dysfunction and exclusion (TIDE) scores. Gene expression validation was performed using qRT-PCR. TNFSF ligands were predominantly expressed in antigen-presenting cells, particularly B cells and macrophages. NMF clustering identified two molecular subtypes of PC, with cluster 2 associated with significantly better OS and PFS ( p  < 0.05). TNFSF4, highly enriched in B cells, was found to regulate immune-related pathways such as B cell receptor signaling and cytokine–cytokine receptor interaction, as revealed by KEGG pathway analysis. TNFSF4 expression also correlated with favorable immunotherapy markers, suggesting its potential role as a predictive biomarker. These findings were supported by qRT-PCR validation. This study provides a TNFSF ligand-based molecular classification of pancreatic cancer and highlights the immunoregulatory role of TNFSF4. Its association with patient prognosis and immunotherapy responsiveness suggests potential clinical utility in guiding treatment strategies.

Adipose tissue engineering offers a promising approach for breast reconstruction, yet achieving efficient adipose regeneration remains challenging due to poor cell survival and tissue integration. Hence, we developed a three-dimensional (3D) electrospun collagen nanofiber scaffold integrated with adipose-derived mesenchymal stem cells (ADSCs), designed to enhance adipose tissue regeneration by providing a biomimetic extracellular matrix environment. The incorporation of collagen nanofibers enhances cell adhesion and extracellular matrix remodeling, further promoting adipogenic differentiation. Compared to conventional two-dimensional (2D) culture, ADSCs seeded on the scaffold exhibit significantly improved viability and lipid accumulation. In vivo implantation in a rat model demonstrated that the COL-ADSCs composite scaffold increased subcutaneous fat thickness from 2.69 ± 0.10 mm to 3.37 ± 0.11 mm over four weeks, while also promoting collagen remodeling and angiogenesis, as confirmed by CD31-positive staining. Despite these promising outcomes, this study is limited to a small animal model, and further validation in large animal models and clinical settings is necessary. These findings indicate that the COL-ADSCs composite scaffold provides a biomimetic microenvironment that supports ADSC adhesion, differentiation, and tissue remodeling, highlighting its potential as a clinically applicable biomaterial for breast reconstruction.

Volume capture ratio of annual rainfall (VCRAR) is the key parameter of low-impact development (LID) facilities design, which is significantly affected by the rainfall event division method. However, there is no universal agreement on how to determine an optimal division method to achieve it. A modified minimum inter-event time (MIT) method based on MATLAB software was proposed to find an optimal MIT value. The result showed that the optimal MIT value in Beijing is 200 min based on the daily rainfall data from 1987 to 2016, and the annual average rainfall events were 34.2 with an average rainfall depth of 13.7 mm. Taking bioretention facilities as an example, the errors of design VCRAR under different MIT values were compared based on a Stormwater Management Model (SWMM). The results showed that when design VCRAR was ≤50, 55–60, 60–75, 75–80 and >80%, the optimal MIT value for LID facilities design was 60, 120, 200, 360 and 1,440 min, respectively. Therefore, the optimal MIT should be flexibly selected with the changing of design VCRAR, to ensure that LID facilities meet the design goals.

Clade A protein phosphatase 2Cs (PP2C-As) play crucial roles in plant stress responses. Although the ABA receptors PYLs inhibit PP2C-As in an ABA-dependent manner, other modulators of these phosphatases remain largely unknown. Here, we identify the FORKED-LIKE 7 (FL7) protein as a broad PP2C-A interactor that effectively suppresses PP2C activity through an ABA-independent, noncompetitive mechanism. By inhibiting PP2C-A activity, FL7 positively regulates osmotic tolerance and plant immunity in an ABA-independent manner. The N-terminal auxin canalisation (AC) domain of FL7 is required for its PP2C-As inhibitory activity. Further evolutionary analyses reveal that FL7 homologues containing an AC domain belong to an ancient family that emerged in a common ancestor of Klebsormidiophyceae algae and land plants. Genetic analyses indicate that algal FL7 homologues have a conserved function as PP2C-A inhibitors. Our study reveals an ABA-independent layer of PP2C-A modulation that regulates biotic and abiotic stress responses, which is likely conserved across a billion years of streptophyte evolution and predated the PYL-ABA regulation established in the common ancestor of land plants. Li et al. reveal an ABA-independent layer of PP2C-A modulation that regulates both biotic and abiotic stress responses. This mechanism is conserved across approximately a billion years and predates the PYL-ABA regulatory system established in the common ancestor of land plants.

Transformers’ vibration and noise problems are critical to environmental comfort and reliability of equipment. To reduce the vibration and noise of transformers, the vibration and noise of medium and medium-high transformer cores under Maxwell force and magnetostriction were analyzed. A three-dimensional magneto-mechanical-acoustic coupled finite element model was established under sinusoidal and rectangular wave excitation. The deformation, vibration acceleration, and sound pressure distribution were analyzed under the Maxwell force and the magnetostrictive force of medium and medium-high transformers. A vibration noise optimization design architecture for medium and medium-high frequency transformers has been proposed. A transformer core structure with low noise vibration is designed based on the proposed optimization design architecture. The experimental results show that under the sinusoidal excitation, the vibration acceleration in the lamination direction decreases the most, from 18.748 m/s 2 before optimization to 4.89 m/s 2 and under rectangular wave excitation, it decreases from 51.08 m/s 2 before optimization to 13.182 m/s 2 . The proposed method provides a reference for the optimization design of low noise vibration transformers.

Background Cryo-electron microscopy (cryo-EM) has revolutionized protein research by enabling high-resolution structural analysis. However, preparing ultra-large protein complexes (e.g., > 700 kDa) for cryo-EM remains challenging, as it requires preserving both structural integrity and the native state. Conventional isolation methods, such as sucrose density gradient centrifugation, require large sample volumes and provide limited separation resolution. In contrast, native PAGE offers higher resolution; however, no established method exists for extracting protein complexes from gels followed by further purification to achieve high purity. Consequently, no standardized native PAGE-based protocol for cryo-EM sample preparation avoids multiple purification steps. Hence, we aimed to develop a rapid and efficient cryo-EM protein sample preparation method using electroelution with an optimized buffer system that preserves complex integrity to recover target protein complexes after sodium deoxycholate (DOC)-based clear-native PAGE (CN-PAGE). Results We developed an agarose–acrylamide composite gel, which is simpler to prepare and mechanically more robust than conventional linear-gradient acrylamide gels commonly used for CN-PAGE, facilitating precise band excision for efficient electroelution. Cryo-EM structural analysis of the photosystem I–light-harvesting complex I (PSI–LHCI) supercomplex from Arabidopsis thaliana achieved high resolution (2.18 Å) after electroelution from this gel, requiring only buffer exchange by ultrafiltration to remove DOC before grid preparation, without additional chromatographic purification. This finding suggests that DOC may be the main inhibitor of successful grid preparation. Conclusion Our results demonstrate the potential of this method for isolating large protein complexes from small sample volumes for cryo-EM structural analysis. This approach may expand the scope of cryo-EM targets to include some challenging systems previously hindered by purification difficulties.