Characteristics of water-soluble polythiophene: TiO2 composite and its application in photovoltaics

We have studied the characteristics of composites of an environmentally friendly water-soluble polythiophene sodium poly[2-(3-thienyl)-ethoxy-4-butylsulfonate] (PTEBS) and TiO2. We observed that the ultraviolet-visible absorption spectrum of low molecular weight PTEBS is redshifted possibly due to the formation of aggregates. Cyclic voltammetry reveals the values of highest occupied molecular orbitals and lowest unoccupied molecular orbitals for PTEBS. A factor of 7 in photoluminescence quenching indicates that the exciton dissociation and charge separation occur successfully at the PTEBS: TiO2 (1:1 by weight) interface. This enhances the possibility that the separated charges will reach the electrodes before recombining. Scanning electron micrograph images show how the PTEBS and TiO2 are interconnected and form paths to the electrodes to improve charge transport. Photovoltaic devices with TiO2:PTEBS composite achieved an energy conversion efficiency of η=0.015%, a short circuit current of JSC=0.22mA/cm2, an open circuit voltage of VOC=0.72V, and a fill factor of FF=0.29 under ∼300mW/cm2 white light illumination

Synaptic Phospholipids as a New Target for Cortical Hyperexcitability and E/I Balance in Psychiatric Disorders

Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition both rescued schizophrenia-related hyperexcitability syndromes caused by altered bioactive lipid signaling in two genetic mouse models for psychiatric disorders. Interestingly, ATX inhibition did not affect naive animals. However, as our data suggested that pharmacological ATX inhibition is a general method to reverse cortical excitability, we applied ATX inhibition in a ketamine model of schizophrenia and rescued thereby the electrophysiological and behavioral schizophrenia-like phenotype. Our data show that astrocytic ATX is a novel modulator of glutamatergic transmission and that targeting ATX might be a versatile strategy for a novel drug therapy to treat cortical hyperexcitability in psychiatric disorders

Molecular Cause and Functional Impact of Altered Synaptic Lipid Signaling Due to a \u3cem\u3eprg-1\u3c/em\u3e Gene SNP

Loss of plasticity‐related gene 1 (PRG‐1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg‐1 (R345T/mutPRG‐1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss‐of‐PRG‐1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG‐1+/− mice, which are animal correlates of human PRG‐1+/mut carriers, showed an altered cortical network function and stress‐related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA‐synthesizing molecule autotaxin. In line, EEG recordings in a human population‐based cohort revealed an E/I balance shift in monoallelic mutPRG‐1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress‐related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate‐dependent symptoms in psychiatric diseases

The Data-Driven Modeling of Pressure Loss in Multi-Batch Refined Oil Pipelines with Drag Reducer Using Long Short-Term Memory (LSTM) Network

Due to the addition of the drag reducer in refined oil pipelines for increasing the pipeline throughput as well as reducing energy consumption, the classical method based on the Darcy-Weisbach Formula for precise pressure loss calculation presents a large error. Additionally, the way to accurately calculate the pressure loss of the refined oil pipeline with the drag reducer is in urgent need. The accurate pressure loss value can be used as the input parameter of pump scheduling or batch scheduling models of refined oil pipelines, which can ensure the safe operation of the pipeline system, achieving the goal of energy-saving and cost reduction. This paper proposes the data-driven modeling of pressure loss for multi-batch refined oil pipelines with the drag reducer in high accuracy. The multi-batch sequential transportation process and the differences in the physical properties between different kinds of refined oil in the pipelines are taken into account. By analyzing the changes of the drag reduction rate over time and the autocorrelation of the pressure loss sequence data, the sequential time effect of the drag reducer on calculating pressure loss is considered and therefore, the long short-term memory (LSTM) network is utilized. The neural network structure with two LSTM layers is designed. Moreover, the input features of the proposed model are naturally inherited from the Darcy-Weisbach Formula and on adaptation to the multi-batch sequential transportation process in refined oil pipelines, using the particle swarm optimization (PSO) algorithm for network hyperparameter tuning. Case studies show that the proposed data-driven model based on the LSTM network is valid and capable of considering the multi-batch sequential transportation process. Furthermore, the proposed model outperforms the models based on the Darcy-Weisbach Formula and multilayer perceptron (MLP) from previous studies in accuracy. The MAPEs of the proposed model of pipelines with the drag reducer are all less than 4.7% and the best performance on the testing data is 1.3627%, which can provide the calculation results of pressure loss in high accuracy. The results also indicate that the model’s capturing sequential effect of the drag reducer from the input data set contributed to improving the calculation accuracy and generalization ability

Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders

Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition both rescued schizophrenia-related hyperexcitability syndromes caused by altered bioactive lipid signaling in two genetic mouse models for psychiatric disorders. Interestingly, ATX inhibition did not affect naive animals. However, as our data suggested that pharmacological ATX inhibition is a general method to reverse cortical excitability, we applied ATX inhibition in a ketamine model of schizophrenia and rescued thereby the electrophysiological and behavioral schizophrenia-like phenotype. Our data show that astrocytic ATX is a novel modulator of glutamatergic transmission and that targeting ATX might be a versatile strategy for a novel drug therapy to treat cortical hyperexcitability in psychiatric disorders

Additional file 1 of Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model

Additional file 1: Fig. S1. Impact of BBR on body weight and serum albumin levels in FVB Mdr2-/- mice and cholestatic liver injury in C57/BL6 Mdr2-/- mice. Mdr2-/- mice with FVB background (Control) and Mdr2-/- mice with C57BL/6 background (Control BL) were treated with vehicle or BBR (50 mg/kg) via oral gavage once daily for 8 weeks, respectively. a Body weight change during the BBR treatment period of 8 weeks in FVB Mdr2-/- mice. b Serum albumin levels in FVB Mdr2-/- mice. c Liver functional enzyme levels in C57/BL6 Mdr2-/- mice. d Representative images of hematoxylin and eosin (H&E) staining of the liver slides (scale bar, 50 µm for 20x, 20 µm for 40× magnification) in Mdr2-/- BL mice. Data are expressed as the mean ± standard error of the mean (SEM). Statistical significance relative to Control BL: *p < 0.05 (n=9-12). Fig. S2. Comparative analysis of differentially expressed genes (DEGs) in experimental groups. a Hierarchical clustering heatmaps for DEGs in FVBWT, Mdr2-/- and Mdr2-/- mice treated with BBR. RNA-seq data were normalized using a Z-score for tag counts, with red and blue colors representing high and low gene expression, respectively. b Volcano plots for the Mdr2-/- vs. WT group comparison. Red dots represent upregulated genes, green dots represent downregulated genes, and black dots represent genes not differentially expressed. c Venn diagram illustrating the overlap of DEGs between the two comparisons: Mdr2-/- vs. WT and BBR-treated Mdr2-/- vs. Mdr2-/- Control. In Mdr2-/- vs. WT, there were a total of 1937 DEGs, including 1260 upregulated and 677 down-regulated genes. In BBR-treated Mdr2-/- vs. Mdr2-/- Control, there were a total of 587 DEGs, comprising 300 upregulated and 287 down-regulated genes. A total of 373 DEGs were common between the two comparisons. Fig. S3. Ingenuity pathway analysis (IPA) in experimental groups. The DEG data set with FC ≥2 and p-value <0.05 was used for IPA analysis. The top 10 activated pathways in Mdr2-/- control mice compared to WT mice and the top 10 inhibited pathways in BBR-treated Mdr2-/- mice compared to Mdr2-/- control mice are shown. Fig. S4. Impact of BBR on hepatic fibrosis. a Representative images of liver sections stained with Picro-Sirius Red and CK19 IHC (scale bar, 100 µm for 10× magnification) and processed images for quantification. b Hepatic hydroxyproline levels. Data are expressed as the mean ± SEM. Statistical significance relative to control: *p < 0.05 (n=9-12). Fig. S5. Impact of BBR on genes associated with hepatic fibrosis in Mdr2-/- mice. a Representative heatmap of key genes involved in hepatic fibrosis in the liver, comparing the BBR-treated group with the control group. The RNA-seq data were normalized using a Z-score for tag counts, with red and blue colors denoting up- and down-regulated gene expression, respectively. b Relative mRNA expression levels of fibrosis-related genes (Pai1,Col12a1, Sox9, Egr1, Egr2, Egr3, Hbegf, Cyr61, and P4ha1), normalized against HPRT1 as an internal control. Data are expressed as the mean ± SEM. Statistical significance relative to control: *p < 0.05, **p < 0.01, ***p < 0.001(n=9-12). Fig. S6. Impact of BBR on genes associated with inflammation in Mdr2-/- mice. Representative heatmap depicting the expression of key genes involved in hepatic inflammation, comparing the liver tissues of Mdr2-/- mice treated with BBR to the control group. The RNA-seq data were normalized using a Z-score, with red indicating upregulated gene expression and blue indicating downregulated gene expression. Fig. S7. Impact of BBR on NF-kB signaling pathway. KEGG pathway analysis was performed on RNA-seq data to analyze functionally and map genes involved in the NF-kB signaling pathway. a NF-kB signaling pathway in Mdr2-/- vs. WT. b NF-kB signaling pathway in Mdr2-/- treated with BBR vs. Mdr2-/- Control. Red and green colors indicate upregulated and downregulated gene expression, respectively. Fig. S8. Impact of BBR on MAPK signaling pathway. KEGG pathway analysis was performed on RNA-seq data to analyze functionally and map genes involved in the MAPK signaling pathway. a MAPK signaling pathway in Mdr2-/- vs. WT. b MAPK signaling pathway in Mdr2-/- treated with BBR vs. Mdr2-/- Control. Red and green colors indicate upregulated and downregulated gene expression, respectively. Fig. S9. Impact of BBR on Oxidative phosphorylation pathway. KEGG pathway analysis was performed on RNA-seq data to analyze functionally and map genes involved in the Oxidative phosphorylation pathway. a Oxidative phosphorylation pathway in Mdr2-/- vs. WT. b Oxidative phosphorylation pathway in Mdr2-/- treated with BBR vs. Mdr2-/- Control. Red and green colors indicate up- and down-regulated gene expression, respectively. Fig. S10. Impact of BBR on Protein processing in endoplasmic reticulum. RNA-seq data were performed to analyze functionally and map genes involved in the Protein processing in the endoplasmic reticulum pathway using KEGG. a Protein processing in endoplasmic reticulum pathway in Mdr2-/- Control vs. WT. b Protein processing in endoplasmic reticulum pathway in Mdr2-/- treated with BBR vs. Mdr2-/- Control. Red and green colors indicate up- and down-regulated gene expression, respectively. Fig. S11. Impact of BBR on BA Metabolism. Representative heatmap of key genes involved in bile acid metabolism in the liver of BBR-treated vs. Control Mdr2-/- mice. A Z-score is calculated for the RNA-seq data to normalize tag counts. Red and blue colors indicate up- and down-regulated gene expression, respectively. Fig. S12. Impact of BBR on bile acid homeostasis in Mdr2-/- mice. The small intestine and feces were processed for BA analysis using LC-MS/MS. a BA composition profile in the small intestine is expressed as a percentage of total BA. b Total BA, total primary BA, total conjugated BA, and TCA in the small intestine. c BA composition profile in the feces is expressed as a percentage of total BA. d Total BA, total secondary BA, TCA, and LCA in the feces. Data are expressed as the mean ± SEM. Statistical significance relative to control: *p < 0.05 (n=9-12). Fig. S13. Effect of BBR on inflammation and ER stress in the intestine of Mdr2-/- mice. Relative mRNA levels of key genes involved in inflammation and ER stress in the intestine were determined by real-time RT–PCR and normalized with HPRT1 as an internal control. a The relative mRNA levels of Mcp-1, Cd11b, Il-1β, Vcam-1, Il-1α, and Cxcl1. b Relative mRNA levels of Asbt, Chop and H19. Data are expressed as the mean ± SEM. Statistical significance relative to Control: *p < 0.05 (n=9-12). Fig. S14. Tissue distribution of BBR in Mdr2-/- mice. Mdr2-/- mice were treated with BBR (50 mg/kg, n = 3) by intragastric administration after a 12-h fast. Blood, spleen, brain, lung, heart, kidney, liver, stomach contents, intestine contents, and colon feces were collected at 3, 6, and 9 h post-treatment. The concentrations of BBR in the serum and various tissues were quantified using LC-MS/MS. a BBR concentration in the serum. b BBR concentration in the tissues. Data are expressed as the mean ± standard error of the mean (SEM). Fig. S15. Analysis of Fecal Microbiota Diversity in Mdr2-/- Mice Treated with BBR. Fecal samples of FVB Mdr2-/- mice treated with either 50 mg/kg or 100 mg/kg of BBR for 8 weeks were subjected to 16S rRNA gene sequencing to assess microbiota composition. a Alpha diversity of the fecal microbiota, presented through various metrics: Shannon Index (a), observed Amplicon Sequence Variants (ASVs) (b), Faith’s phylogenetic diversity (c), and evenness (d). b Beta diversity analysis using Principal Coordinates Analysis (PCoA) plots, which illustrate variations in microbial communities. These plots are based on different distance metrics: Bray-Curtis distance (a), Jaccard distance (b), Weighted UniFrac distance (c), and Unweighted UniFrac distance (d), with each plot depicting variations along two principal coordinates that account for most of the variation. Fig. S16. Influence of BBR on the Proportions of Firmicutes and Bacteroidetes in the Gut Microbiota of Mdr2-/- mice. The pie chart shows the relative percentages of the Firmicutes and Bacteroidetes phyla in the gut microbiota of Mdr2-/- mice. Comparative analysis is shown across three groups: control, BBR-treated at 50 mg/kg, and BBR-treated at 100 mg/kg. This visualization highlights the specific shifts in these major bacterial phyla due to BBR treatment

Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP

Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases