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Both sporadic variably protease-sensitive prionopathy (VPSPr) and familial Creutzfeldt-Jakob disease linked to the prion protein (PrP) V180I mutation (fCJDV180I) have been found to share a unique pathological prion protein (PrPSc) that lacks the protease-resistant PrPSc glycosylated at residue 181 because two of four PrP glycoforms are apparently not converted into the PrPSc from their cellular PrP (PrPC). To investigate the seeding activity of these unique PrPSc molecules, we conducted in vitro prion conversion experiments using serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays with different PrPC substrates. We observed that the seeding of PrPSc from VPSPr or fCJDV180I in the sPMCA reaction containing normal human or humanized transgenic (Tg) mouse brain homogenates generated PrPSc molecules that unexpectedly exhibited a dominant diglycosylated PrP isoform along with PrP monoglycosylated at residue 181. The efficiency of PrPSc amplification was significantly higher in non-CJDMM than in non-CJDVV human brain homogenate, whereas it was higher in normal TgVV than in TgMM mouse brain homogenate. PrPC from the mixture of normal TgMM and Tg mouse brain expressing PrPV180I mutation (Tg180) but not TgV180I alone was converted into PrPSc by seeding with the VPSPr or fCJDV180I. The RT-QuIC seeding activity of PrPSc from VPSPr and fCJDV180I was significantly lower than that of sCJD. Our results suggest that the formation of glycoform-selective prions may be associated with an unidentified factor in the affected brain and the glycoform-deficiency of PrPSc does not affect the glycoforms of in vitro newly amplified PrPSc. [ABSTRACT FROM AUTHOR]

To solve the problem of difficult recovery, high toxicity, serious restraint on reaction pH of traditional catalyst in advanced oxidation processes based on sulfate radical (SO4-), nano-scaled α-Fe2O3 was chosen as novel catalyticmaterial. The effects of different influence factors on the degradation of acid orange (AO) II by activation of hydrogen peroxide with nano α-Fe2O3 were investigated. The results show that the removal rate of organic dyes AO II has positive correlation with oxidant and catalyst dosages, and the corresponding kobs value linearly increases with catalyst dosage, the degradation efficiency of AO II is inhibited in actual waters. The mineralization rate of AO II in α-Fe2O3/PMS system is relatively low, most of the removed AO II is degraded to intermediate products. Nano-scaled α-Fe2O3 is confirmed to be a recyclable catalyst with high catalytic performance and low toxcity. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) was widely used in the plastic products and banned in infant food containers in many countries due to the environmental and biological toxicity. As a common substitute of BPA to manufacture products, Bisphenol C (BPC) is frequently detected in human samples like infants and toddlers' urine, indicating infants and young children are at risk of BPC exposure. However, the understanding of effects of BPC exposure on early development is limited. Herein, we evaluated the early developmental toxicity of BPC and studied the underlying mechanism in a zebrafish model. We found BPC exposure leading to liver and intestinal developmental defects in zebrafish, which occurred via disruption of GPER-AKT-mTOR-RPS6 pathway. Specifically, BPC downregulated phosphorylated and total levels of mTOR, which synergistically reduced the phosphorylation of RPS6, suppressing the translation of genes essential for cell proliferation in liver and intestine such as yap1 and tcf4. Collectively, our results not only observed clear toxicity of BPC during liver and intestinal development but also demonstrated the underlying mechanism of BPC-mediated defects via disrupting the GPER-AKT-mTOR-RPS6 pathway. [Display omitted] • Bisphenol C causes liver and intestinal developmental defects in zebrafish. • Bisphenol C downregulates phosphorylated and total levels of mTOR. • Bisphenol C impacts the translation and cell proliferation in liver and intestine. [ABSTRACT FROM AUTHOR]

The Laves phase will seriously deteriorate the subsequent hot working and welding performance of cast ATI 718Plus. In traditional homogenization annealing, two-stage treatment is used to prevent the formation of harmful eutectic structures due to the initial melting of the low-melting point Laves phase. This has several obvious disadvantages including high processing temperature, long processing time and complicated operation. Electrical pulsed treatment, as a new efficient, feasible and energy-saving green means, has rapidly achieved the dissolution of Laves phase. The increase in diffusion rate of Nb element in Ni matrix by pulsed electric current is due to the enhancement of defect migration and vacancy defect density, leading to a significant enhancement in the diffusion kinetics and accelerating the dissolution of Laves phase. Laves phase dissolution process under the pulsed electric current is from the aggregated state accompanied by dense needle like η phase to the discrete state accompanied by sparse needle like η phase, finally forming a single long strip and being dissolved into an intermittent state until it disappears. In all, using pulsed electric current instead of traditional heat treatment for annealing cast ingots has the potential to achieve one-step homogenization, completely dissolving the Laves phase while eliminating element segregation. • Laves phase will deteriorate the tensile properties of the as-cast structure, and cracks will initiate near the Laves phase in the inter-dendritic regions. • Compared to the traditional heat treatment, the electrical pulsed treatment can accelerate the dissolution of Laves phase and η phase. • The increase in the diffusion rate of Nb element in Ni matrix by EPT leads to a significant enhancement in diffusion kinetics. • Laves phase dissolution process under the EPT is from the aggregated state accompanied by dense needle like η phase to the discrete state accompanied by sparse needle like η phase, finally forming a single long strip and being dissolved into an intermittent state until it disappears. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a commonly used plastic additive. Since BPA has been banned in maternal and infant food containers in many countries, BPA substitutes have been widely introduced to replace it. By systematically assessing the potential developmental toxicity of BPA substitutes, we observed that the 41-150 nM in vivo BPC exposure (around the reported concentration detected in infant urine: 6-186 nM) induced cardiac defects in zebrafish. Mechanistically, BPC disrupted m 6 A homeostasis by downregulation of the key m 6 A methyltransferase, Mettl3, thereby causing the m 6 A reader, Igf2bp2b, to fail in recognizing and stabilizing the inefficiently m 6 A-modified acox1 and tnnt2d mRNA. Then, downregulation of Acox1 (a regulator in cardiac fatty acid metabolism) and Tnnt2d (a component of cardiac troponin for muscle contraction) led to cardiac defects. Indeed, the dual cardiac functional axes regulated by the same m 6 A reader in response to BPC provided new insight into the regulatory mechanisms of epitranscriptomics and cardiac development. Collectively, our study not only presented evidence showing that the internal exposure levels of BPC in humans could lead to cardiac developmental defects but also demonstrated the underlying mechanism of BPC-mediated defects by disrupting the Mettl3-m 6 A-Igf2bp2b-Acox1/Tnnt2d pathways, which provided potential molecular markers associated with BPC exposure.

Objective: Ischemic stroke (IS) is a significant health concern with high disability and fatality rates despite available treatments. Immune cells and cuproptosis are associated with the onset and progression of IS. Investigating the interaction between cuproptosis-related genes (CURGs) and immune cells in IS can provide a theoretical basis for IS treatment., Methods: We obtained IS datasets from the Gene Expression Omnibus (GEO) and employed machine learning to identify CURGs. The diagnostic efficiency of the CURGs was evaluated using receiver operating characteristic (ROC) curves. KEGG and gene set enrichment analysis (GSEA) were also conducted to identify biologically relevant pathways associated with CURGs in IS patients. Single-cell analysis was used to confirm the expression of 19 CURGs, and pathway activity calculations were performed using the AUCell package. Additionally, a risk prediction model for IS patients was developed, and core modules and hub genes related to IS were identified using weighted gene coexpression network analysis (WGCNA). We classified IS patients using a method of consensus clustering., Results: We established a precise diagnostic model for IS. Enrichment analysis revealed major pathways, including oxidative phosphorylation, the NF-kappa B signaling pathway, the apoptosis pathway, and the Wnt signaling pathway. At the single-cell level, compared to those in non-IS samples, 19 CURGs were primarily overexpressed in the immune cells of IS samples and exhibited high activity in natural killer cell-mediated cytotoxicity, steroid hormone biosynthesis, and oxidative phosphorylation. Two clusters were obtained through consensus clustering. Notably, immune cell types including B cells, plasma cells, and resting NK cells, varied between the two clusters. Furthermore, the red module and hub genes associated with IS were uncovered. The expression patterns of CURGs varied over time., Conclusion: This study developed a precise diagnostic model for IS by identifying CURGs and evaluating their interaction with immune cells. Enrichment analyses revealed key pathways involved in IS, and single-cell analysis confirmed CURG overexpression in immune cells. A risk prediction model and core modules associated with IS were also identified., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Plant-based meat analogs have increasingly attracted the attention of the food industry in recent years. However, the digestion behavior of this innovative solid food in human stomach is poorly understood. In this study, plant-based meat analogs with different internal structures were prepared with/without high-moisture extrusion technology and at different temperatures. A semi-dynamic gastric digestion system which involves the mimic processes of the secretion of gastric juice and the gastric emptying was applied. After extrusion treatment at high temperature (150 ℃), the EHT had the highest anisotropic index (H ⊥ /H ∥ =1.90) and an ideal meat-like structure. It was found that particle disintegration and swelling simultaneously occurred in the bolus of the EHT but not in the sample without extrusion treatment (the HLT) in the early stage of gastric digestion. This difference might be attributed to the compact and well-arranged anisotropic structure of the EHT resulting from the extrusion, and leads to difficult enzymatic hydrolyzation unless the particles swell and unfold the polymer chains. The difficulty in particle disintegration in the EHT during gastric digestion is the consequence of the relatively slow gastric emptying rate and the decrease of protein degradation. As a result, the EHT which underwent extrusion treatment at high temperature and possessed the best anisotropic fibrous structure exhibited the slowest gastric digestion. This novel solid food shows good potential as a desired nutritional food for people on diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Breast cancer is one of the most prevalent malignancies in women. Exosomes are important mediators of intercellular communication; however, their regulatory mechanisms in human umbilical vein endothelial cells (HUVECs) angiogenesis in breast cancer remain unknown., Methods: We isolated and characterized breast cancer cell-derived exosomes and investigated their functions. Exosomal sequencing and the TCGA database were used to screen long non-coding RNA (lncRNA). In vitro and in vivo experiments were performed to investigate the role of exosomal lncRNA in HUVEC angiogenesis and tumor growth. Molecular methods were used to demonstrate the molecular mechanism of lncRNA., Results: We demonstrated that breast cancer cell-derived exosomes promoted HUVEC proliferation, tube formation, and migration. Combining exosomal sequencing results with The Cancer Genome Atlas Breast Cancer database, we screened lncRNA small nucleolar RNA host gene 12 (SNHG12), which was highly expressed in breast cancer cells. SNHG12 was also upregulated in HUVECs co-cultured with exosome-overexpressed SNHG12. Moreover, overexpression of SNHG12 in exosomes increased HUVEC proliferation and migration, whereas deletion of SNHG12 in exosomes showed the opposite effects. In vivo experiments showed that SNHG12 knockdown in exosomes inhibited breast cancer tumor growth. Transcriptome sequencing identified MMP10 as the target gene of SNHG12. Functional experiments revealed that MMP10 overexpression promoted HUVEC angiogenesis. Mechanistically, SNHG12 blocked the interaction between PBRM1 and MMP10 by directly binding to PBRM1. Moreover, exosomal SNHG12 promoted HUVEC angiogenesis via PBRM1 and MMP10., Conclusions: In summary, our findings confirmed that exosomal SNHG12 promoted HUVEC angiogenesis via the PBRM1-MMP10 axis, leading to enhanced malignancy of breast cancer. Exosomal SNHG12 may be a novel therapeutic target for breast cancer., (© 2024. The Author(s).)

Objective: This research aims to assess the clinical efficacy of neoadjuvant chemotherapy (NACT) in combination with modified radical mastectomy (MRM) for stage II-III breast cancer (BC) patients and its impact on serum tumor markers (STMs)., Methods: The study included 119 stage II-III BC patients treated between June 2018 and June 2021. Among them, 55 cases underwent MRM (reference group), while 64 cases received NACT followed by MRM (research group). We compared intraoperative parameters (blood loss, operation time, hospital stay), clinical outcomes, the incidence of postoperative adverse events (AEs), changes in STMs (CA125, CA153, CEA), and one-year postoperative quality of life (QOL)., Results: In comparison to the reference group, the research group exhibited significantly lower intraoperative blood loss, shorter operation times, reduced hospital stays, and higher rates of disease remission. Notably, the research group experienced a lower overall incidence of AEs, including skin flap necrosis, subscalp effusion, infection, and upper limb lymphedema. Postoperatively, all STMs in the research group exhibited statistically significant reductions and were lower than those in the reference group. Additionally, all QOL subscales demonstrated improvements and higher scores in the research group., Conclusions: NACT followed by MRM represents an effective approach for enhancing surgical outcomes and clinical efficacy in stage II-III BC patients. This combination therapy also reduces the risk of postoperative AEs and leads to favorable changes in STMs and postoperative QOL levels.

Stable water in water (W/W) emulsions of guar rich droplets dispersed in an amylopectin rich continuous phase (G/A) and the inverse (A/G) can be achieved by adding gelatin and inducing microphase separation of the latter by cooling. In this research, the effect of gelatin on the emulsion stability was further studied by storing the emulsions at 10, 20 and 25 °C. The visual aspect, the microstructure, and the viscosity of the emulsions were investigated at different times during storage at different temperatures and pH. It was found that depending on the conditions, the gelatin phase wetted the interface or formed small discrete microdomains that adsorbed at the interface and dispersed in the bulk phases. The observed differences in morphology and stability are related to the interplay of the rates of aggregation, phase separation of gelatin, which itself depend on the gelatin concentration, temperature and pH. Emulsions could be prepared in this manner that were stable for at least one week and remained visually homogeneous. We believe that this is a promising method to stabilize W/W emulsions as long as the components of the emulsion are incompatible with aggregated gelatin., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90-0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86-0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94-1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association., (© 2023. Springer Nature Limited.)