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In the context of escalating global environmental concerns, the importance of preserving water resources and upholding ecological equilibrium has become increasingly apparent. As a result, the monitoring and prediction of water quality have emerged as vital tasks in achieving these objectives. However, ensuring the accuracy and dependability of water quality prediction has proven to be a challenging endeavor. To address this issue, this study proposes a comprehensive weight-based approach that combines entropy weighting with the Pearson correlation coefficient to select crucial features in water quality prediction. This approach effectively considers both feature correlation and information content, avoiding excessive reliance on a single criterion for feature selection. Through the utilization of this comprehensive approach, a comprehensive evaluation of the contribution and importance of the features was achieved, thereby minimizing subjective bias and uncertainty. By striking a balance among various factors, features with stronger correlation and greater information content can be selected, leading to improved accuracy and robustness in the feature-selection process. Furthermore, this study explored several machine learning models for water quality prediction, including Support Vector Machines (SVMs), Multilayer Perceptron (MLP), Random Forest (RF), XGBoost, and Long Short-Term Memory (LSTM). SVM exhibited commendable performance in predicting Dissolved Oxygen (DO), showcasing excellent generalization capabilities and high prediction accuracy. MLP demonstrated its strength in nonlinear modeling and performed well in predicting multiple water quality parameters. Conversely, the RF and XGBoost models exhibited relatively inferior performance in water quality prediction. In contrast, the LSTM model, a recurrent neural network specialized in processing time series data, demonstrated exceptional abilities in water quality prediction. It effectively captured the dynamic patterns present in time series data, offering stable and accurate predictions for various water quality parameters. [ABSTRACT FROM AUTHOR]

• PEDV E protein inhibits the poly(I:C)-induced IFN-β and ISGs production. • PEDV E protein suppresses the expression of RIG-I signaling-associated molecules. • PEDV E interacts IRF3 and further interferes its nuclear translocation. • PEDV E protein acts as an IFN-β antagonist through blockage of the RIG-I/ IRF3 signaling. Porcine epidemic diarrhea virus (PEDV) encodes many multifunctional proteins that inhibit host innate immune response during virus infection. As one of important structural proteins, PEDV E protein has been found to block the production of type I interferon (IFN) in virus life cycle, but little is known about this process that E protein subverts host innate immune. Thus, in this present study, we initiated the construction of eukaryotic expression vectors to express PEDV E protein. Subsequently, cellular localization analysis was performed and the results showed that the majority of PEDV E protein distributed at cytoplasm and localized in endoplasmic reticulum (ER). Over-expression of PEDV E protein significantly inhibited poly(I:C)-induced IFN-β and IFN-stimulated genes (ISGs) productions. We also found that PEDV E protein remarkably suppressed the protein expression of RIG-I signaling-associated molecules, but all their corresponding mRNA levels remained unaffected and unchanged. Furthermore, PEDV E protein obviously interfered with the translocation of IRF3 from cytoplasm to nucleus through direct interaction with IRF3, which is crucial for the IFN-β production induced by poly(I:C). Taken together, our results suggested that PEDV E protein acts as an IFN-β antagonist through suppression of the RIG-I-mediated signaling. This study will pave the way for the further investigation into the molecular mechanisms by which PEDV E protein evades host innate immune response. [ABSTRACT FROM AUTHOR]

• Chinese1 genotype Wh6 strain (TgCtwh6) infection not only leads to phosphorylation of tau via activating GSK3 β but also promotes hippocampal neuron apoptosis. • The signaling of p -GSK3 β - p -tau might be involved in the hippocampal neuron injury infected by an avirulent cyst-forming TgCtwh6. • These results are helpful for better understanding of mental disorders caused by T. gondii infection. • Prevention TgCtWh6 from infection may be an effective method to reduce the occurrence and delay the development of neurodegenerative diseases. Toxoplasma gondii (T. gondii) is a neurophilic and intracellular parasite that can affect plenty of vertebrate animals, including humans. Recent researches indicate that T. gondii infection is associated with neurodegenerative diseases such as Alzheimer's disease(AD). In addition, tau hyper-phosphorylation is a crucial event leading to the formation of nerve fiber tangles in AD. Despite the efforts to understand the interactions between T. gondii and AD, there are no clear results available so far. Here, we infected mice with the T. gondii of the Chinese 1 genotype Wh6 strain (TgCtwh6) for 60 days. Then we observed the formation of tissue cysts in the brain, the damage of neuron and the increased expression of phosphorylated tau (p -tau) in the hippocampal tissue of the mice. Similarly, we also found that p -tau, glycogen synthase kinase 3 beta (GSK3 β), and phosphorylated GSK3 β (p -GSK3 β) were upregulated in vitro in TgCtwh6 challenged hippocampal neuron cell strain, HT22 cells. We noted a down-regulated expression of GSK3 β , p -GSK3 β , and p -tau in HT22 cells, which were pretreated with LiCl, an inhibitor of GSK3 β. These data suggested that p -GSK3 β may mediate tau phosphorylation after TgCtwh6 infection. Furthermore, TgCtwh6 infection also caused the increased expression of Bax and Caspase3, the decreased expression of Bcl-XL in HT22 cells, which had both early and late apoptosis. In all, our results indicated that TgCtwh6 infection not only led to phosphorylation of tau via activating GSK3 β but also promoted hippocampal neuron apoptosis. Our research may partially reveal the mechanism with which TgCtwh6 induce neurofibrillary pathology. [ABSTRACT FROM AUTHOR]

In the pursuit of high-energy density lithium-ion battery, Li-rich Mn-based oxide cathode has gained great attention with unexpectedly high capacity, low cost and excellent thermal stability. However, the cause for the sluggish kinetics remains a mystery, hindering the application of Li-rich cathode material. Here, we reveal the interfacial instability is the driving force for the sluggish kinetics, which severely blocks the interfacial Li-ion transport and triggers fast battery failure. Through rice-husk carbon (RHC) and spinel phase modification on Li-rich Mn-based oxide Li1.2Ni0.16Mn0.56Co0.08O2 (LNMC), the poor lithium ion diffusion and interfacial degradation can be effectively prevented, delivering a high specific capacity of around 300 mAh/g and excellent rate performance. These findings provide a universal method to prepare high electrochemical performance Li-rich oxide materials. Through synergetic modification, the Li-rich Mn-based cathode delivers a high available capacity of 300 mAh/g via accelerated Li+ intercalation kinetics [ABSTRACT FROM AUTHOR]

To fight the global epidemic of drug-resistant bacteria, essential oils have gained increasing attention as a new source of antibiotics. The antimicrobial activity of Monarda didyma essential oils (MDEO) for the Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were determined by agar disc diffusion assay and broth microdilution assay. To further understand MDEO efficacy, a time-growth curve was performed. The biofilm formation of CRKP were determined by crystalline violet staining method, additionally, changes in intracellular Adenosine triphosphate (ATP), protein, Alkaline phosphatase (AKP) activities, and membrane integrity were investigated to assess the influence of MDEO on cell membrane damage. Finally, the activities of key enzymes in the tricarboxylic acid (TCA) pathways and pentose phosphate (PPP) pathways were examined to determine the effect of MDEO on the respiratory metabolism of CRKP. This study presents the antibacterial mechanism of MDEO against CRKP with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1.25 mg/ml. To understand MDEO efficacy, a time-kill kinetics approach was performed. The bactericidal effect of MDEO was evident at 2 h compared to the control at its MIC and 2MIC. Surface electron microscopic and ATP assay studies provided evidence for the multi-target action of MDEO against CRKP. MDEO could inhibit CRKP biofilm formation. MDEO could also cause irreversible damage to the CRKP cell membrane, resulting in the leakage of biological macromolecules (protein, ATP) and the reduction of intracellular enzymes (AKP) activities. Finally, MDEO affected the pathways of respiratory metabolism, such as PPP and TCA pathways. MDEO could reduce the activity of key enzymes (Glucose-6-phosphate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase) in the PPP and TCA pathways to exert its biological effects against CRKP. These results suggest MDEO can exert inhibitory effects on CRKP, and potential mechanisms of action including inhibition of biofilm formation, damage of cell membrane structure and inhibition of energy metabolism. [ABSTRACT FROM AUTHOR]

Lithium cobalt oxide (LiCoO2) and graphite-based Li-ion batteries have been widely applied for consumer electronics because of the long cycle life and easy preparation. However, the limited capacity for traditional materials hampers the practical application for high energy-density battery. Conventional electrolyte system could not satisfy the need for high-capacity materials. Here, methylene methanedisulfonate (MMDS) was chosen as electrolyte additive for enhancing the available capacity for LiCoO2 and graphite-based battery. The effect of MMDS on the LiCoO2 cathode and graphite anode was investigated via multi electrochemical methods. It was found that the capacity for cells with MMDS electrolyte additive increases (from 142.6 mAh g−1 for pristine to 193.4 mAh g−1 on LiCoO2/Li battery, from 275.5 mAh g−1 for pristine to 407.0 mAh g−1 on graphite/Li battery). The experimental results indicate that improved capacity by MMDS electrolyte additive can be attributable to the stabilized interface on both cathode and anode sides, leading to superior interfacial Li+ kinetics and mitigated bulk structural degradation, which was further confirmed by the ex-situ electrochemical and structural characterization.Graphical abstract: Lithium cobalt oxide (LiCoO2) and graphite-based Li-ion batteries have been widely applied for consumer electronics because of the long cycle life and easy preparation. However, the limited capacity for traditional materials hampers the practical application for high energy-density battery. Conventional electrolyte system could not satisfy the need for high-capacity materials. Here, methylene methanedisulfonate (MMDS) was chosen as electrolyte additive for enhancing the available capacity for LiCoO2 and graphite-based battery. The effect of MMDS on the LiCoO2 cathode and graphite anode was investigated via multi electrochemical methods. It was found that the capacity for cells with MMDS electrolyte additive increases (from 142.6 mAh g−1 for pristine to 193.4 mAh g−1 on LiCoO2/Li battery, from 275.5 mAh g−1 for pristine to 407.0 mAh g−1 on graphite/Li battery). The experimental results indicate that improved capacity by MMDS electrolyte additive can be attributable to the stabilized interface on both cathode and anode sides, leading to superior interfacial Li+ kinetics and mitigated bulk structural degradation, which was further confirmed by the ex-situ electrochemical and structural characterization. [ABSTRACT FROM AUTHOR]

Background: Cardiotoxicity is a common complication following anthracycline chemotherapy and represents one of the serious adverse reactions affecting life, which severely limits the effective use of anthracyclines in cancer therapy. Although some genes have been investigated by individual studies, the comprehensive analysis of key genes and molecular regulatory network in anthracyclines-induced cardiotoxicity (AIC) is lacking but urgently needed. Methods: The present study integrating several transcription profiling datasets aimed to identify key genes associated with AIC by weighted correlation network analysis (WGCNA) and differentially expressed analysis (DEA) and also constructed miRNA-transcription factor-gene regulatory network. A total of three transcription profiling datasets involving 47 samples comprising 41 rat heart tissues and 6 human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) samples were enrolled. Results: The WGCNA and DEA with E-MTAB-1168 identified 14 common genes affected by doxorubicin administrated by 4 weeks or 6 weeks. Functional and signal enrichment analyses revealed that these genes were mainly enriched in the regulation of heart contraction, muscle contraction, heart process, and oxytocin signaling pathway. Ten (Ryr2, Casq1, Fcgr2b, Postn, Tceal5, Ccn2, Tnfrsf12a, Mybpc2, Ankrd23, Scn3b) of the 14 genes were verified by another gene expression profile GSE154603. Importantly, three key genes (Ryr2, Tnfrsf12a, Scn3b) were further validated in a hiPSCMs-based in-vitro model. Additionally, the miRNA-transcription factor-gene regulatory revealed several top-ranked transcription factors including Tcf12, Ctcf, Spdef, Ebf1, Sp1, Rcor1 and miRNAs including miR-124-3p, miR-195-5p, miR-146a-5p, miR-17-5p, miR-15b-5p, miR-424-5p which may be involved in the regulation of genes associated with AIC. Conclusions: Collectively, the current study suggested the important role of the key genes, oxytocin signaling pathway, and the miRNA-transcription factor-gene regulatory network in elucidating the molecular mechanism of AIC. [ABSTRACT FROM AUTHOR]

Background: Cardiotoxicity is a common complication following anthracycline chemotherapy and represents one of the serious adverse reactions affecting life, which severely limits the effective use of anthracyclines in cancer therapy. Although some genes have been investigated by individual studies, the comprehensive analysis of key genes and molecular regulatory network in anthracyclines-induced cardiotoxicity (AIC) is lacking but urgently needed. Methods: The present study integrating several transcription profiling datasets aimed to identify key genes associated with AIC by weighted correlation network analysis (WGCNA) and differentially expressed analysis (DEA) and also constructed miRNA-transcription factor-gene regulatory network. A total of three transcription profiling datasets involving 47 samples comprising 41 rat heart tissues and 6 human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) samples were enrolled. Results: The WGCNA and DEA with E-MTAB-1168 identified 14 common genes affected by doxorubicin administrated by 4 weeks or 6 weeks. Functional and signal enrichment analyses revealed that these genes were mainly enriched in the regulation of heart contraction, muscle contraction, heart process, and oxytocin signaling pathway. Ten (Ryr2, Casq1, Fcgr2b, Postn, Tceal5, Ccn2, Tnfrsf12a, Mybpc2, Ankrd23, Scn3b) of the 14 genes were verified by another gene expression profile GSE154603. Importantly, three key genes (Ryr2, Tnfrsf12a, Scn3b) were further validated in a hiPSCMs-based in-vitro model. Additionally, the miRNA-transcription factor-gene regulatory revealed several top-ranked transcription factors including Tcf12, Ctcf, Spdef, Ebf1, Sp1, Rcor1 and miRNAs including miR-124-3p, miR-195-5p, miR-146a-5p, miR-17-5p, miR-15b-5p, miR-424-5p which may be involved in the regulation of genes associated with AIC. Conclusions: Collectively, the current study suggested the important role of the key genes, oxytocin signaling pathway, and the miRNA-transcription factor-gene regulatory network in elucidating the molecular mechanism of AIC. [ABSTRACT FROM AUTHOR]

Laryngeal cancer is a common type of head and neck malignancy. microRNA is implicated in the development and progression of various tumours. The present study aimed to explore the potential roles and mechanisms of miR‐646 in laryngeal carcinoma cells. We detected the expression of miR‐646 and observed that miR‐646 was reduced in laryngeal cell lines. Subsequently, the proliferation, migration and invasion of TU212 and TU686 cells were evaluated using CCK‐8 assays, cell proliferation ELISA BrdU and transwell assays after transfection with miR‐646 mimic. Overexpression of miR‐646 attenuated the proliferative and invasive abilities of TU212 and TU686 cells. Dual luciferase reporter assay confirmed that glutathione peroxidase 1 (GPX1) is a direct target of miR‐646. Interestingly, restoration of GPX1 promoted cell proliferation and migration, and reversed the biological activities of miR‐646 in cell proliferation and migration. It is worth noting that miR‐646 overexpression blocked the activation of PI3K/AKT pathway, and this was partly abrogated by GPX1. 740Y‐P, a PI3K agonist abolished the effects of miR‐646 on cell proliferation and invasion. Taken together, miR‐646 prohibited the proliferation and invasion of laryngeal carcinoma cells through the PI3K/AKT pathway via targeting GPX1. [ABSTRACT FROM AUTHOR]

• PEDV ORF3 is a transmembrane protein that localizes at endoplasmic reticulum to induce ER stress response. • PEDV ORF3 protein has no effect on apoptosis, but induces autophagy dependent on ER stress response. • This work provides some new findings for the biological function of the PEDV ORF3 protein. Porcine epidemic diarrhea virus (PEDV), the causative agent of PED, is an enveloped, positive-stranded RNA virus in the genus Alphacoronavirus , family Coronaviridae , order Nidovirales. PEDV non-structural accessory protein ORF3 is an ion channel related to viral infectivity and pathogenicity. Our previous study showed that PEDV ORF3 has expression characteristic of aggregation in cytoplasm, but its biological function remains elusive. Thus in this study, we initiated the construction of various vectors to express ORF3, and found ORF3 localized in the cytoplasm in the aggregation manner. Subsequently, confocal microscopy analysis showed that the aggregated ORF3 localized in endoplasmic reticulum (ER) to trigger ER stress response via up-regulation of GRP78 protein expression and activation of PERK-eIF2α signaling pathway. In addition, our results showed that PEDV ORF3 could induce the autophagy through inducing conversion of LC3-I to LC3-II, but couldn't influence the apoptosis. In contrast, conversion of LC3-I/LC3-II could be significantly inhibited by 4-PBA, an ER stress inhibitor, indicating that ORF3-induced autophagy is dependent on ER stress response. This work not only provides some new findings for the biological function of the PEDV ORF3 protein, but also help us for the further understanding the molecular interaction between PEDV ORF3 protein and cells. [ABSTRACT FROM AUTHOR]

Stress granules (SGs) are host translationally silent ribonucleo-proteins formed in cells in response to multiple types of environmental stress, including viral infection. We previously showed that the nuclear protein, 68-kDa Src-associated in mitosis protein (Sam68), is recruited to cytoplasm and form the Sam68-positive SGs at 6 hpi, but the Sam68-positive SGs disassembled beyond 12 hpi, suggesting that the SGs might be inhibited during the late stage of Enterovirus 71 (EV71) infection. However, the mechanism and function of this process remains poorly understood. Thus in this study, we demonstrated that EV71 initially induced SGs formation at the early stage of EV71 infection, and confirmed that 2A pro of EV71 was the key viral component that triggered SG formation. In contrast, SGs were diminished as EV71 infection proceeding. At the same time, arsenite-induced SGs were also blocked at the late stage of EV71 infection. This disruption of SGs was caused by viral protease 3C pro -mediated G3BP1 cleavage. Furthermore, we demonstrated that over-expression of G3BP1-SGs negatively impacted viral replication at the cytopathic effect (CPE), protein, RNA, and viral titer levels. Our novel finding may not only help us to better understand the mechanism how EV71 interacts with the SG response, but also provide mechanistic linkage between cellular stress responses and innate immune activation during EV71 infection. [ABSTRACT FROM AUTHOR]

• Lipid rafts are required for activation of PI3K/Akt signaling both at early and late stages of CA16 infection. • Lipid raft-associated PI3K/Akt plays critical roles in mediating SREBP1 maturation during late stage of CA16 infection. • This finding of lipid raft-associated PI3K/Akt/SREBP1 will deepen our understanding mechanism of CA16 infection. Coxsackievirus A16 (CA16) is one of predominant Enterovirus that possesses high pathogenicity. Lipid rafts, as cholesterol - and sphingolipid - enriched membrane nanodomains, are involved into many aspects of the virus life cycle. Our previous study found that lipid rafts integrity was essential for CA16 replication, but how lipid rafts regulate CA16 replication through activating downstream signaling remains largely unknown. Thus, in this study, we revealed that lipid rafts were required for activation of PI3K/Akt signaling at early stage of CA16 infection. Treatment with wortmannin significantly reduced the expression of virus protein, indicating PI3K/Akt signaling was beneficial for early stage of virus infection. In addition, lipid rafts integrity was also indispensable for PI3K/Akt activation during the late stage of CA16 infection, which played critical functions in mediating sterol regulatory element-binding proteins 1 (SREBP1) maturation. Whereas, over-expression of SREBP1 exhibited inhibition on virus replication, suggesting that PI3K/Akt signaling and SREBP1 might positively and negatively influence virus replication in two different stages of infection, respectively. Taken together, our study demonstrates an important role of the lipid raft-associated PI3K/Akt/SREBP1 signaling in modulating CA16 replication, which will deepen our understanding mechanism of CA16 infection. [ABSTRACT FROM AUTHOR]

• PEDV ORF3 inhibits the productions of pro-inflammatory cytokines IL-6 and IL-8. • PEDV ORF3 inhibits NF-κB activation through blockage of p65 activation. • Our study links PEDV ORF3 to inhibition of pro-inflammatory cytokines. Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positive-sense RNA virus that belongs to a porcine entero-pathogenic alphacoronavirus , causing lethal watery diarrhea in piglets. Despite existing study reports the sole accessory protein ORF3 identified as NF-κB antagonist, the contribution of PEDV ORF3 to production of the pro-inflammatory cytokines mediated by NF-κB signaling remains largely unknown. Thus in this present study, we showed that PEDV ORF3 protein significantly inhibited the productions of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8. The phosphorylation of IκBα was inhibited by ORF3 protein, but no degradation of IκBα was induced in ORF3-expressing cells. Furthermore, PEDV ORF3 inhibited NF-κB activation through preventing nuclear factor p65 phosphorylation and down-regulating p65 expression level, as well as interfering nuclear translocation of p65, eventually resulting into the inhibition of IL-6 and IL-8 production. Our study definitely links PEDV ORF3 to inhibition of pro-inflammatory cytokines production, which will provide new insight into the molecular mechanisms of NF-κB activity inhibited by PEDV proteins to facilitate virus evasion of host innate immune. [ABSTRACT FROM AUTHOR]