PoRVA G9P[23] and G5P[7] infections differentially promote PEDV replication by reprogramming glutamine metabolism.

PoRVA and PEDV coinfections are extremely common in clinical practice. Although coinfections of PoRVA and PEDV are known to result in increased mortality, the underlying mechanism remains unknown. Here, we found that PoRVA infection promoted PEDV infection in vivo and in vitro and that PoRVA G9P[23] (RVA-HNNY strain) enhanced PEDV replication more significantly than did PoRVA G5P[7] (RVA-SXXA strain). Metabolomic analysis revealed that RVA-HNNY more efficiently induced an increase in the intracellular glutamine content in porcine small intestinal epithelial cells than did RVA-SXXA, which more markedly promoted ATP production to facilitate PEDV replication, whereas glutamine deprivation abrogated the effect of PoRVA infection on promoting PEDV replication. Further studies showed that PoRVA infection promoted glutamine uptake by upregulating the expression of the glutamine transporter protein SLC1A5. In SLC1A5 knockout cells, PoRVA infection neither elevated intracellular glutamine nor promoted PEDV replication. During PoRVA infection, the activity and protein expression levels of glutamine catabolism-related enzymes (GLS1 and GLUD1) were also significantly increased promoting ATP production through glutamine anaplerosis into the TCA cycle. Consistent with that, siRNAs or inhibitors of GLS1 and GLUD1 significantly inhibited the promotion of PEDV replication by PoRVA. Notably, RVA-HNNY infection more markedly promoted SLC1A5, GLS1 and GLUD1 expression to more significantly increase the uptake and catabolism of glutamine than RVA-SXXA infection. Collectively, our findings illuminate a novel mechanism by which PoRVA infection promotes PEDV infection and reveal that the modulation of glutamine uptake is key for the different efficiencies of PoRVA G9P[23] and PoRVA G5P[7] in promoting PEDV replication.

The key to sustainability: In-depth investigation of environmental quality in G20 countries through the lens of renewable energy, economic complexity and geopolitical risk resilience.

The world is currently facing urgent climate and environmental issues, such as global warming, ecosystem collapse, and energy shortages. In this context, this study selected data from 2000 to 2021 and employed the Method of Moment Quantile Regression (MMQR) to thoroughly investigate the impact of renewable energy consumption, economic complexity, and geopolitical risks on the ecological footprint of the Group of Twenty (G20) countries. The results indicate that in countries with lower quantiles, renewable energy consumption significantly reduces the ecological footprint, whereas its effect is not prominent in countries with higher quantiles. Economic complexity has a negative impact on the ecological footprint, and this impact becomes stronger as the quantile of the ecological footprint rises. Additionally, economic complexity moderates the effect of renewable energy on the ecological footprint. Geopolitical risks facilitate the growth of the ecological footprint. Likewise, robustness tests such as DOLS, FMOLS, and quantile regression confirm these estimates in the same framework. This study has conducted a profound analysis of global environmental issues, offering innovative perspectives and recommendations for achieving goals related to sustainable energy utilization, mitigating climate change, and improving the ecological environment. The findings of this research will guide policymakers in G20 countries to adopt more effective environmental protection measures, thereby contributing to the construction of a sustainable future.

Comparative Analysis of Physicochemical and Functional Properties of Pectin from Extracted Dragon Fruit Waste by Different Techniques.

Dragon fruit peel, often discarded, is a valuable source of commercial pectin. This study investigates different extraction methods, including cold-water (CW), hot-water (HW), ultrasound (US), and novel enzyme extraction (xylanase: EZX), to extract pectins from dragon fruit peel and compare their characteristics. The pectin yield ranged from 10.93% to 20.22%, with significant variations in physicochemical properties across methods (p < 0.05). FTIR analysis revealed that extraction methods did not alter the primary structural configuration of the pectins. However, molecular weights (Mws) varied significantly, from 0.84 to 1.21 × 103 kDa, and the degree of esterification varied from 46.82% to 51.79% (p < 0.05). Monosaccharide analysis identified both homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) pectic configurations in all pectins, predominantly comprising galacturonic acid (77.21-83.12 %mol) and rhamnose (8.11-9.51 %mol), alongside minor side-chain sugars. These properties significantly influenced pectin functionalities. In the aqueous state, a higher Mw impacted viscosity and emulsification performance, while a lower Mw enhanced antioxidant activities and promoted the prebiotic function of pectin (Lactis brevies growth). This study highlights the impact of extraction methods on dragon fruit peel pectin functionalities and their structure-function relationship, providing valuable insights into predicting dragon fruit peel's potential as a food-grade ingredient in various products.

Palliative surgery versus non-surgery of the solitary metastatic lesion in De novo metastatic breast cancer: A SEER based study.

This study aimed to evaluate whether palliative surgery for metastatic lesion could provide a survival benefit in metastatic breast cancer (MBC) patients with solitary metastasis. De novo MBC patients with solitary distant lesions were enrolled utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to form matched pairs of the surgery group and the non-surgery group. The breast cancer-specific survival (BCSS) and overall survival (OS) outcomes between the 2 groups were compared in the following 3 sample models: the entire cohort of MBC (7665 cases); subgroups of patients with different isolated metastatic organs; and subgroups of patients with different molecular subtypes for each isolated metastatic organ. Compared with the Non-surgery group, the surgery group showed better BCSS and OS before PSM (HR = 0.88, 95% CI = 0.79-0.99, P = .04 and HR = 0.85, 95% CI = 0.76-0.95, P = .006, respectively). After PSM, palliative surgery still provided an OS benefit in patients with brain metastasis and lung metastasis (HR = 0.59, 95% CI = 0.37-0.95, P = .01 and HR = 0.64, 95% CI = 0.45-0.90, P = .02, respectively). Likewise, a better BCSS benefit was also found in the subset of patients with brain metastasis (HR = 0.61, 95% CI = 0.38-1.00, P = .01). Further stratification analysis indicated that patients with the luminal A subtype with brain metastasis have a better BCSS (HR = 0.36, 95% CI = 0.16-0.79, P = .04) and OS (HR = 0.37, 95% CI = 0.18-0.75, P = .03) after undergoing palliative surgery than nonsurgical treatment. Our study originality showed that palliative surgery for metastatic lesion could improve survival prognosis in patients with special single-organ metastasis and specific molecular subtypes. More clinical studies are needed to determine whether palliative surgery should be performed in MBC patients.

Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas.

Background: Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy. Methods: We identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves. Results: The levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas. Conclusion: Heightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas.

Plasticity and crosstalk of mesenchymal stem cells and macrophages in immunomodulation in sepsis.

Sepsis is a multisystem disease characterized by dysregulation of the host immune response to infection. Immune response kinetics play a crucial role in the pathogenesis and progression of sepsis. Macrophages, which are known for their heterogeneity and plasticity, actively participate in the immune response during sepsis. These cells are influenced by the ever-changing immune microenvironment and exhibit two-sided immune regulation. Recently, the immunomodulatory function of mesenchymal stem cells (MSCs) in sepsis has garnered significant attention. The immune microenvironment can profoundly impact MSCs, prompting them to exhibit dual immunomodulatory functions akin to a double-edged sword. This discovery holds great importance for understanding sepsis progression and devising effective treatment strategies. Importantly, there is a close interrelationship between macrophages and MSCs, characterized by the fact that during sepsis, these two cell types interact and cooperate to regulate inflammatory processes. This review summarizes the plasticity of macrophages and MSCs within the immune microenvironment during sepsis, as well as the intricate crosstalk between them. This remains an important concern for the future use of these cells for immunomodulatory treatments in the clinic.

Acetylation-dependent deubiquitinase USP26 stabilizes BAG3 to promote breast cancer progression.

Deubiquitylases (DUBs) have emerged as promising targets for cancer therapy due to their role in stabilizing substrate proteins within the ubiquitin machinery. Here, we identified ubiquitin-specific protease 26 (USP26) as an oncogene via screening prognostic DUBs in breast cancer. Through in vitro and in vivo experiments, we found that depletion of USP26 inhibited breast cancer cell proliferation and invasion, and suppressed tumor growth and metastasis in nude mice. Further investigation identified co-chaperone Bcl-2-associated athanogene 3 (BAG3) as the direct substrate of USP26, and ectopic expression of BAG3 partially reversed antitumor effect induced by USP26 knockdown. Mechanistically, the lysine acetyltransferase Tip60 targeted USP26 at K134 for acetylation, which enhanced USP26 binding affinity to BAG3, leading to BAG3 deubiquitination and increased protein stability. Importantly, we employed a structure-based virtual screening and discovered a drug-like molecule called 5813669 that targets USP26, destabilizing BAG3 and effectively mitigating tumor growth and metastasis in vivo. Clinically, high expression levels of USP26 were correlated with elevated BAG3 levels and poor prognosis in breast cancer patients. Overall, our findings highlight the critical role of USP26 in BAG3 protein stabilization and provide a promising therapeutic target for breast cancer.