Thy1-ApoE4/C/EBPß double transgenic mice act as a sporadic model with Alzheimer's disease.

Early onset familial Alzheimer's disease (FAD) with APP, PS1/2 (presenilins) mutation accounts for only a small portion of AD cases, and most are late-onset sporadic. However, majority of AD mouse models are developed to mimic the genetic cause of human AD by overexpressing mutated forms of human APP, PS1/2, and/or Tau protein, though there is no Tau mutation in AD, and no single mouse model recapitulates all aspects of AD pathology. Here, we report Thy1-ApoE4/C/EBPß double transgenic mouse model that demonstrates key AD pathologies in an age-dependent manner in absence of any human APP or PS1/2 mutation. Using the clinical diagnosis criteria, we show that this mouse model exhibits tempo-spatial features in AD patient brains, including progressive cognitive decline associated with brain atrophy, which is accompanied with extensive neuronal degeneration. Remarkably, the mice display gradual Aß aggregation and neurofibrillary tangles formation in the brain validated by Aß PET and Tau PET. Moreover, the mice reveal widespread neuroinflammation as shown in AD brains. Hence, Thy1-ApoE4/C/EBPß mouse model acts as a sporadic AD mouse model, reconstituting the major AD pathologies.

Decoding temporal heterogeneity in NSCLC through machine learning and prognostic model construction.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prevalent and heterogeneous disease with significant genomic variations between the early and advanced stages. The identification of key genes and pathways driving NSCLC tumor progression is critical for improving the diagnosis and treatment outcomes of this disease. METHODS: In this study, we conducted single-cell transcriptome analysis on 93,406 cells from 22 NSCLC patients to characterize malignant NSCLC cancer cells. Utilizing cNMF, we classified these cells into distinct modules, thus identifying the diverse molecular profiles within NSCLC. Through pseudotime analysis, we delineated temporal gene expression changes during NSCLC evolution, thus demonstrating genes associated with disease progression. Using the XGBoost model, we assessed the significance of these genes in the pseudotime trajectory. Our findings were validated by using transcriptome sequencing data from The Cancer Genome Atlas (TCGA), supplemented via LASSO regression to refine the selection of characteristic genes. Subsequently, we established a risk score model based on these genes, thus providing a potential tool for cancer risk assessment and personalized treatment strategies. RESULTS: We used cNMF to classify malignant NSCLC cells into three functional modules, including the metabolic reprogramming module, cell cycle module, and cell stemness module, which can be used for the functional classification of malignant tumor cells in NSCLC. These findings also indicate that metabolism, the cell cycle, and tumor stemness play important driving roles in the malignant evolution of NSCLC. We integrated cNMF and XGBoost to select marker genes that are indicative of both early and advanced NSCLC stages. The expression of genes such as CHCHD2, GAPDH, and CD24 was strongly correlated with the malignant evolution of NSCLC at the single-cell data level. These genes have been validated via histological data. The risk score model that we established (represented by eight genes) was ultimately validated with GEO data. CONCLUSION: In summary, our study contributes to the identification of temporal heterogeneous biomarkers in NSCLC, thus offering insights into disease progression mechanisms and potential therapeutic targets. The developed workflow demonstrates promise for future applications in clinical practice.

Anaerobic oxidation of methane in landfill and adjacent groundwater environments: Occurrence, mechanisms, and potential applications.

Landfills remain the predominant means of solid waste management worldwide. Widespread distribution and significant stockpiles of waste in landfills make them a significant source of methane emissions, exacerbating climate change. Anaerobic oxidation of methane (AOM) has been shown to play a critical role in mitigating methane emissions on a global scale. The rich methane and electron acceptor environment in landfills provide the necessary reaction conditions for AOM, making it a potentially low-cost and effective strategy for reducing methane emissions in landfills. However, compared to other anaerobic habitats, research on AOM in landfill environments is scarce, and there is a lack of analysis on the potential application of AOM in different zones of landfills. Therefore, this review summarizes the existing knowledge on AOM and its occurrence in landfills, analyzes the possibility of AOM occurrence in different zones of landfills, discusses its potential applications, and explores the challenges and future research directions for AOM in landfill management. The identification of research gaps and future directions outlined in this review encourages further investigation and advancement in the field of AOM, paving the way for more effective waste stabilization, greenhouse gas reduction, and pollutant mitigation strategies in landfills.

The dual role of sirtuins in cancer: biological functions and implications.

Sirtuins are pivotal in orchestrating numerous cellular pathways, critically influencing cell metabolism, DNA repair, aging processes, and oxidative stress. In recent years, the involvement of sirtuins in tumor biology has garnered substantial attention, with a growing body of evidence underscoring their regulatory roles in various aberrant cellular processes within tumor environments. This article delves into the sirtuin family and its biological functions, shedding light on their dual roles-either as promoters or inhibitors-in various cancers including oral, breast, hepatocellular, lung, and gastric cancers. It further explores potential anti-tumor agents targeting sirtuins, unraveling the complex interplay between sirtuins, miRNAs, and chemotherapeutic drugs. The dual roles of sirtuins in cancer biology reflect the complexity of targeting these enzymes but also highlight the immense therapeutic potential. These advancements hold significant promise for enhancing clinical outcomes, marking a pivotal step forward in the ongoing battle against cancer.

New insight into the functional group mechanism and structure-activity relationship of the complexation between DOM and Cr(III) in landfill leachate.

Widespread landfills represent a significant source of groundwater contamination. Due to the unique and diverse nature of dissolved organic matter (DOM) in landfill leachate, the interaction between DOM and heavy metals, along with its quantitative evaluation, remains unknown. Consequently, we collected ten samples from various landfill types to serve as representatives for a comprehensive investigation of the mechanism involving functional groups and Cr(III) through the establishment of a quantitative structure-activity relationship (QSAR). We employed ESI FT-ICR MS, (MW) 2D-COS, and DFT calculations for this purpose. Our findings indicate that DOM from landfill leachate contains a higher proportion of CHON molecules on intensity compared to those from natural sources. The maximum complexation capacity was determined by the proportion of proteins (69%), normalized carbon average oxidation state (16%), double bond equivalence (8%), and the number of oxygen atoms (7%) in landfill leachate DOM. Besides, N-containing groups such as N = O and C-N in landfill leachate DOM with lower humification, can exhibit stronger affinities than COOH, ArOH, CO, and polysaccharide C-O groups, which are typically identified as dominant sites in natural DOM. A QSAR model incorporating four parameters demonstrated an impressive accuracy rate of 98.8%, underscoring its reliability in predicting the complexation potential of different landfill leachate DOM with Cr(III).

Effect of combined electrolyzed reduced water and slightly acidic electrolyzed water spraying on the control of Salmonella, eggshell quality, and shelf life of eggs during storage.

Slightly acidic electrolyzed water (SAEW) is a safe and effective disinfectant, but its sterilizing efficiency is compromised by organic matter on the egg surface. Electrolyzed reduced water (ERW) is a harmless cleaner with a decontamination effect on a variety of surfaces and can be used to remove organic matter. This study assesses the effectiveness of a combination of ERW and SAEW in eliminating Salmonella and manure mixture from egg surfaces, as well as its impact on egg quality during storage. The results show that ERW (74.14%) was more effective than deionized water (DW, 64.69%) and SAEW (70.20%) (P < 0.05) in removing manure from egg surfaces. The damage to the cuticle of eggshell treated with ERW for 28 s was similar to that of DW (P > 0.05) and less than that of SAEW (P < 0.05). Spraying ERW for 10 s followed by SAEW for 18 s (ERW + SAEW) completely removed Salmonella from the egg surface, with no bacteria detected in the residual wash solution. Additionally, ERW + SAEW demonstrated superior preservation of egg quality during storage at 25℃ than the control and ERW single treatment (P < 0.05). Moreover, ERW + SAEW resulted in less weight loss compared to SAEW single treatment (P < 0.05). In conclusion, the sequential use of ERW and SAEW appears to be a promising approach for sterilizing eggs. It not only removes organic matter and Salmonella from the egg surface but also improves the preservation quality of the egg at 25 ℃.

Antibiotic resistance genes and heavy metals in landfill: A review.

Landfill is reservoir containing antibiotic resistance genes (ARGs) that pose a threat to human life and health. Heavy metals impose lasting effects on ARGs. This review investigated and analyzed the distribution, composition, and abundance of heavy metals and ARGs in landfill. The abundance ranges of ARGs detected in refuse and leachate were similar. The composition of ARG varied with sampling depth in refuse. ARG in leachate varies with the distribution of ARG in the refuse. The ARG of sulI was associated with 11 metals (Co, Pb, Mn, Zn, Cu, Cr, Ni, Sb, As, Cd, and Al). The effects of the total metal concentration on ARG abundance were masked by many factors. Low heavy metal concentrations showed positive effects on ARG diffusion; conversely, high heavy metal concentrations showed negative effects. Organic matter had a selective pressure effect on microorganisms and could provide energy for the diffusion of ARGs. Complexes of heavy metals and organic matter were common in landfill. Therefore, the hypothesis was proposed that organic matter and heavy metals have combined effects on the horizontal gene transfer (HGT) of ARGs during landfill stabilization. This work provides a new basis to better understand the HGT of ARGs in landfill.

Establishment of a Spontaneous Liver Fibrosis Model in NOD/SCID Mice Induced by Natural Aging.

Liver fibrosis, a critical pathological feature of chronic liver diseases, arises from a multitude of pathogenic factors. Consequently, establishing an appropriate animal model to simulate liver fibrosis holds immense significance for comprehending its underlying pathogenesis. Despite the numerous methodologies available for generating liver fibrosis models, they often deviate substantially from the spontaneous age-related liver fibrosis process. In this study, compared with young (12 weeks) and middle-aged NOD/SCID mice (32 weeks), there were a large number of fibrous septum and collagen in the liver tissue of old NOD/SCID mice (43 weeks, 43 W). Immunohistochemical analysis unequivocally indicated heightened α-SMA content within the liver tissue of the 43 W mice, thereby underscoring aging's role in triggering the epithelial-to-mesenchymal transition. In addition, SA-ß-gal staining as well as P21 expression were increased, and SIRT1 and SIRT3 expression were decreased in 43 W mice. A comprehensive evaluation encompassing transmission electron microscopy and fluorescence quantitative analysis elucidated compromised mitochondrial function and reduced antioxidant capacity in hepatocytes of the 43 W mice. Furthermore, the aging process activated the pro-fibrotic TGF-ß-SMAD pathway, concurrently inducing hepatocellular inflammation. The results of the present study not only validate the successful construction of a spontaneous liver fibrosis mouse model through natural aging induction but also provide initial insights into the mechanisms underpinning age-induced liver fibrosis.

A Glycosyl Hydrolase 30 Family Xylanase from the Rumen Metagenome and Its Effects on In Vitro Ruminal Fermentation of Wheat Straw.

The challenge of wheat straw as a ruminant feed is its low ruminal digestibility. This study investigated the impact of a xylanase called RuXyn, derived from the rumen metagenome of beef cattle, on the in vitro ruminal fermentation of wheat straw. RuXyn encoded 505 amino acids and was categorized within subfamily 8 of the glycosyl hydrolase 30 family. RuXyn was heterologously expressed in Escherichia coli and displayed its highest level of activity at pH 6.0 and 40 °C. RuXyn primarily hydrolyzed xylan, while it did not show any noticeable activity towards other substrates, including carboxymethylcellulose and Avicel. At concentrations of 5 mM, Mn2+ and dithiothreitol significantly enhanced RuXyn's activity by 73% and 20%, respectively. RuXyn's activity was almost or completely inactivated in the presence of Cu2+, even at low concentrations. The main hydrolysis products of corncob xylan by RuXyn were xylopentose, xylotriose, and xylotetraose. RuXyn hydrolyzed wheat straw and rice straw more effectively than it did other agricultural by-products. A remarkable synergistic effect was observed between RuXyn and a cellulase cocktail on wheat straw hydrolysis. Supplementation with RuXyn increased dry matter digestibility; acetate, propionate, valerate, and total volatile fatty acid yields; NH3-N concentration, and total bacterial number during in vitro fermentation of wheat straw relative to the control. RuXyn's inactivity at 60 °C and 70 °C was remedied by mutating proline 151 to phenylalanine and aspartic acid 204 to leucine, boosting activity to 20.3% and 21.8% of the maximum activity at the respective temperatures. As an exogenous enzyme preparation, RuXyn exhibits considerable potential to improve ruminal digestion and the utilization of wheat straw in ruminants. As far as we know, this is the first study on a GH30 xylanase promoting the ruminal fermentation of agricultural straws. The findings demonstrate that the utilization of RuXyn can significantly enhance the ruminal digestibility of wheat straw by approximately 10 percentage points. This outcome signifies the emergence of a novel and highly efficient enzyme preparation that holds promise for the effective utilization of wheat straw, a by-product of crop production, in ruminants.