Ketogenic diet attenuates cognitive dysfunctions induced by hypoglycemia via inhibiting endoplasmic reticulum stress-dependent pathways.

Hypoglycemia can potentially cause severe damage to the central nervous system. The ketogenic diet (KD), characterized by high-fat and extremely low-carbohydrate content, can modulate homeostasis and nutrient metabolism, thereby influencing body health. However, the effects and underlying mechanisms of KD on hypoglycemia-induced brain injury have not been thoroughly investigated. We aimed to explore the modulating effects of KD on cognitive functions and elucidate the underlying mechanisms. In this study, one-month-old mice were fed with KD for 2 weeks, and the changes in the gut microbiota were detected using the 16S rRNA gene amplicon sequencing method. The hypoglycemic model of mice was established using insulin, and the potential protective effect of KD on hypoglycemia-induced brain injury in mice was evaluated through immunofluorescence staining, western blotting, transmission electron microscopy, and Golgi staining. Our results showed that the intestinal flora of Dorea increased and Rikenella decreased in KD-fed mice. KD can not only alleviate anxiety-like behavior induced by hypoglycemia, but also increase the proportion of mushroom dendritic spines in the hippocampus by modulating changes in the gut microbiota. KD regulated synaptic plasticity by increasing the levels of SPN, PSD95, and SYP, which relieve cognitive impairment caused by hypoglycemia. Moreover, KD can promote the proliferation and survival of adult neural stem cells in the hippocampus, while reducing apoptosis by suppressing the activation of the IRE1-XBP1 and ATF6 endoplasmic reticulum stress pathways in mice with hypoglycemia. This study provides new evidence for demonstrating that KD may alleviate cognitive dysfunctions caused by hypoglycemia by modulating the gut microbiota.

Common and unique testosterone and 17 beta-estradiol degradation mechanisms in Comamonas testosteroni JLU460ET by transcriptome analysis.

Strain C. testosteroni JLU460ET was isolated for testosterone and 17 beta-estradiol degradation by our group. In this study, strain C. testosteroni JLU460ET was induced by testosterone and 17 beta-estradiol and then subjected to transcriptome analysis. There were 2,047 upregulated genes after 3 h of testosterone induction, 2,040 upregulated genes after 13 h of testosterone induction, 2,078 upregulated genes after 3 h of 17 beta-estradiol induction, and 2,095 upregulated genes after 13 h of 17 beta-estradiol induction. Significantly upregulated genes were mainly involved in steroid and aromatic compound degradation. A 100 kb steroid-degrading gene cluster was found by transcriptome analysis, which included 92 annotated genes and 58 novel genes. Among them, MucB/RseB and Fiu are secretory proteins for sensing substrates in the environment. MFS-1 and TonB are transporters of testosterone and 17 beta-estradiol. Ring-cleavage enzymes and beta-oxidation enzymes are important for degradation. The genes upregulated by both substrates were almost the same, but the degree of induction by testosterone was higher than that by 17 beta-estradiol. Nine upregulated genes were selected for verification by quantitative real-time polymerase chain reaction (qRT-PCR). The qRT-PCR results were consistent with the transcriptome sequencing results. In this study, the common and unique metabolic mechanisms of testosterone and 17 beta-estradiol were compared by transcriptome analysis in C. testosteroni JLU460ET for the first time.

Different bacterial and fungal community patterns in restored habitats in coal-mining subsidence areas.

Soil microbiota, which plays a fundamental role in ecosystem functioning, is sensitive to environmental changes. Studying soil microbial ecological patterns can help to understand the consequences of environmental disturbances on soil microbiota and hence ecosystem services. The different habitats with critical environmental gradients generated through the restoration of coal-mining subsidence areas provide an ideal area to explore the response of soil microbiota to environmental changes. Here, based on high-throughput sequencing, we revealed the patterns of soil bacterial and fungal communities in habitats with different land-use types (wetland, farmland, and grassland) and with different restored times which were generated during the ecological restoration of a typical coal-mining subsidence area in Jining City, China. The α-diversity of bacterial was higher in wetland than in farmland and grassland, while that of fungi had no discrepancy among the three habitats. The ß-diversity of bacterial community in the grassland was lower than in the farmland, and fungal community was significant different in all three habitats, showing wetland, grassland, and farmland from high to low. The ß-diversity of the bacterial community decreased with restoration time while that of the fungal community had no significant change in the longer-restoration-time area. Furthermore, soil electrical conductivity was the most important driver for both bacterial and fungal communities. Based on the taxonomic difference among different habitats, we identified a group of biomarkers for each habitat. The study contributes to understand the microbial patterns during the ecological restoration of coal-mining subsidence areas, which has implications for the efficient ecological restoration of subsidence areas.

Deep Learning Model to Classify and Monitor Idiopathic Scoliosis in Adolescents Using a Single Smartphone Photograph.

Importance: Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal disorder. Routine physical examinations by trained personnel are critical to diagnose severity and monitor curve progression in AIS. In the presence of concerning malformation, radiographs are necessary for diagnosis or follow-up, guiding further management, such as bracing correction for moderate malformation and spine surgery for severe malformation. If left unattended, progressive deterioration occurs in two-thirds of patients, leading to significant health concerns for growing children. Objective: To assess the ability of an open platform application (app) using a validated deep learning model to classify AIS severity and curve type, as well as identify progression. Design, Setting, and Participants: This diagnostic study was performed with data from radiographs and smartphone photographs of the backs of adolescent patients at spine clinics. The ScolioNets deep learning model was developed and validated in a prospective training cohort, then incorporated and tested in the AlignProCARE open platform app in 2022. Ground truths (GTs) included severity, curve type, and progression as manually annotated by 2 experienced spine specialists based on the radiographic examinations of the participants' spines. The GTs and app results were blindly compared with another 2 spine surgeons' assessments of unclothed back appearance. Data were analyzed from October 2022 to February 2023. Exposure: Acquisitions of unclothed back photographs using a mobile app. Main Outcomes and Measures: Outcomes of interest were classification of AIS severity and progression. Quantitative statistical analyses were performed to assess the performance of the deep learning model in classifying the deformity as well as in distinguishing progression during 6-month follow-up. Results: The training data set consisted of 1780 patients (1295 [72.8%] female; mean [SD] age, 14.3 [3.3] years), and the prospective testing data sets consisted of 378 patients (279 [73.8%] female; mean [SD] age, 14.3 [3.8] years) and 376 follow-ups (294 [78.2%] female; mean [SD] age, 15.6 [2.9] years). The model recommended follow-up with an area under receiver operating characteristic curve (AUC) of 0.839 (95% CI, 0.789-0.882) and considering surgery with an AUC of 0.902 (95% CI, 0.859-0.936), while showing good ability to distinguish among thoracic (AUC, 0.777 [95% CI, 0.745-0.808]), thoracolumbar or lumbar (AUC, 0.760 [95% CI, 0.727-0.791]), or mixed (AUC, 0.860 [95% CI, 0.834-0.887]) curve types. For follow-ups, the model distinguished participants with or without curve progression with an AUC of 0.757 (95% CI, 0.630-0.858). Compared with both surgeons, the model could recognize severities and curve types with a higher sensitivity (eg, sensitivity for recommending follow-up: model, 84.88% [95% CI, 75.54%-91.70%]; senior surgeon, 44.19%; junior surgeon, 62.79%) and negative predictive values (NPVs; eg, NPV for recommending follow-up: model, 89.22% [95% CI, 84.25%-93.70%]; senior surgeon, 71.76%; junior surgeon, 79.35%). For distinguishing curve progression, the sensitivity and NPV were comparable with the senior surgeons (sensitivity, 63.33% [95% CI, 43.86%-80.87%] vs 77.42%; NPV, 68.57% [95% CI, 56.78%-78.37%] vs 72.00%). The junior surgeon reported an inability to identify curve types and progression by observing the unclothed back alone. Conclusions: This diagnostic study of adolescent patients screened for AIS found that the deep learning app had the potential for out-of-hospital accessible and radiation-free management of children with scoliosis, with comparable performance as spine surgeons experienced in AIS management.

Investigation of enterprise economic management model based on fuzzy logic algorithm.

With the development of modern society and economy, modern business models have changed. Enterprise management is no longer the main function, which requires new management concepts to coordinate production and operation and create new management models. Corporate economic management is one of the main tasks of corporate governance. In order to improve corporate governance, the effective corporate economic evaluation model must be established. The advantage of fuzzy logic algorithm is that it can effectively express fuzzy data and is easy to understand, which is more transparent. The application of fuzzy logic algorithm in the research of enterprise economic management can fully reflect the advantages of fuzzy logic algorithm and improve enterprise governance. In this paper, the fuzzy logic algorithm was used to study the economic management model of enterprises. This paper first introduced the enterprise economic management model, including the definition, characteristics and shortcomings of the enterprise economic management model. The performance evaluation methods of enterprise economic management were introduced, including the clarity of performance evaluation objectives, the optimization of performance evaluation means and the feedback of performance evaluation results. Finally, the fuzzy logic algorithm was used to evaluate the performance of enterprise economic management, and the indicators and performance evaluation model of enterprise economic management were established. In the experimental part, the fuzzy logic algorithm was used to evaluate the economic management of four enterprises. The experimental results showed that Enterprise A had the highest ability to evaluate the economic management of enterprises, and the comprehensive evaluation result of economic management was above 0.9, so it had a very high enterprise economic management ability. The application of fuzzy logic to the study of enterprise economic management could directly show the advantages and disadvantages of the enterprise economic management model through quantitative analysis of the enterprise economic management model. This enabled enterprises to understand the current economic management situation and improve it based on the facts, which helped enterprises to increase their economic management ability.

A clinical experience-based Chinese herbal formula improves ethanol-induced drunken behavior and hepatic steatohepatitis in mice models.

BACKGROUND: Bao-Gan-Xing-Jiu-Wan (BGXJW) is a clinical experience-based Chinese herbal formula. Its efficacy, pharmacological safety, targeted function, process quality, and other aspects have met the evaluation standards and the latest requirements of preparations. It could prevent and alleviate the symptoms of drunkenness and alcoholic liver injury clinically. The present work aims to elucidate whether BGXJW could protect against drunkenness and alcoholic liver disease in mice and explore the associated mechanism. MATERIAL AND METHODS: We used acute-on-chronic (NIAAA) mice model to induce alcoholic steatosis, and alcohol binge-drinking model to reappear the drunk condition. BGXJW at indicated doses were administered by oral gavage respectively to analyze its effects on alcoholic liver injury and the associated molecular mechanisms. RESULTS: BGXJW had no cardiac, hepatic, renal, or intestinal toxicity in mice. Alcoholic liver injury and steatosis in the NIAAA mode were effectively prevented by BGXJW treatment. BGXJW increased the expression of alcohol metabolizing enzymes ADH, CYP2E1, and ALDH2 to enhance alcohol metabolism, inhibited steatosis through regulating lipid metabolism, counteracted alcohol-induced upregulation of lipid synthesis related proteins SREBP1, FASN, and SCD1, meanwhile it enhanced fatty acids ß-oxidation related proteins PPAR-α and CPT1A. Alcohol taken enhanced pro-inflammatory TNF-α, IL-6 and down-regulated the anti-inflammatory IL-10 expression in the liver, which were also reversed by BGXJW administration. Moreover, BGXJW significantly decreased the blood ethanol concentration and alleviated drunkenness in the alcohol binge-drinking mice model. CONCLUSIONS: BGXJW could effectively relieve drunkenness and prevent alcoholic liver disease by regulating lipid metabolism, inflammatory response, and alcohol metabolism.

High-Output Single-Electrode Droplet Triboelectric Nanogenerator Based on Asymmetrical Distribution Electrostatic Induction Enhancement.

Droplet-based triboelectric nanogenerators (D-TENGs) have recently gained much attention due to their great potential in harvesting energy. However, the output performance of conventional single-electrode droplet-based TENGs is limited owing to low induced electrification efficiency. The asymmetric distribution of electric fields on both sides of the electrode edge enhances the electrostatic induction process and improves the output performance of D-TENG. Herein, an induced electrification-enhanced droplet-based triboelectric nanogenerator (IED-TENG) is developed to effectively enhance the output performance by simultaneously optimizing the electrode structure and the dynamics of the water droplet. One droplet falling from a height of 30 cm results in a -70 V output voltage and -6 µA short-circuit current, which is 70 times and 20 times the full-inductive-electrode mode, respectively. The working principle and the relationship between electric signal and droplet dynamics are analyzed in detail. Moreover, the peak output voltage can reach -110 V, and the peak current can get -140 µA by using the power generation of multiple water droplets. The present protocol provides an easy and reproducibility strategy in energy harvesting and sensing areas.

Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila.

The gut microbiota is increasingly considered to play a key role in human immunity and health. The aging process alters the microbiota composition, which is associated with inflammation, reactive oxygen species (ROS), decreased tissue function, and increased susceptibility to age-related diseases. It has been demonstrated that plant polysaccharides have beneficial effects on the gut microbiota, particularly in reducing pathogenic bacteria abundance and increasing beneficial bacteria populations. However, there is limited evidence of the effect of plant polysaccharides on age-related gut microbiota dysbiosis and ROS accumulation during the aging process. To explore the effect of Eucommiae polysaccharides (EPs) on age-related gut microbiota dysbiosis and ROS accumulation during the aging process of Drosophila, a series of behavioral and life span assays of Drosophila with the same genetic background in standard medium and a medium supplemented with EPs were performed. Next, the gut microbiota composition and protein composition of Drosophila in standard medium and the medium supplemented with EPs were detected using 16S rRNA gene sequencing analysis and quantitative proteomic analysis. Here, we show that supplementation of Eucommiae polysaccharides (EPs) during development leads to the life span extension of Drosophila. Furthermore, EPs decreased age-related ROS accumulation and suppressed Gluconobacter, Providencia, and Enterobacteriaceae in aged Drosophila. Increased Gluconobacter, Providencia, and Enterobacteriaceae in the indigenous microbiota might induce age-related gut dysfunction in Drosophila and shortens their life span. Our study demonstrates that EPs can be used as prebiotic agents to prevent aging-associated gut dysbiosis and reactive oxidative stress.

Local Manipulation of Skyrmion Nucleation in Microscale Areas of a Thin Film with Nitrogen-Ion Implantation.

Precise manipulation of skyrmion nucleation in microscale or nanoscale areas of thin films is a critical issue in developing high-efficient skyrmionic memories and logic devices. Presently, the mainstream controlling strategies focus on the application of external stimuli to tailor the intrinsic attributes of charge, spin, and lattice. This work reports effective skyrmion manipulation by controllably modifying the lattice defect through ion implantation, which is potentially compatible with large-scale integrated circuit technology. By implanting an appropriate dose of nitrogen ions into a Pt/Co/Ta multilayer film, the defect density was effectively enhanced to induce an apparent modulation of magnetic anisotropy, consequently boosting the skyrmion nucleation. Furthermore, the local control of skyrmions in microscale areas of the macroscopic film was realized by combining the ion implantation with micromachining technology, demonstrating a potential application in both binary storage and multistate storage. These findings provide a new approach to advancing the functionalization and application of skyrmionic devices.

Effects of plants and soil microorganisms on organic carbon and the relationship between carbon and nitrogen in constructed wetlands.

Constructed wetland is an ideal place for studying the effects of plants and microorganisms on the nutrient cycling and carbon-nitrogen coupling in wetland for their clear background. This study examined both bare plots and others with plants (Phragmites australis or Typha angustifolia) in constructed wetlands and vegetation and soil samples were collected to investigate the effects of plants and soil microorganisms on carbon and nitrogen content. Results showed that the soil organic carbon content was high in plots with high plant biomass, and the increase of soil organic carbon driven by plant biomass was mainly from light fraction organic carbon (LFOC). Correlation analysis and redundancy analysis (RDA) suggested that plants play an important role in the cycle of carbon and nitrogen elements in constructed wetland soils, and that plant nitrogen components were key factors influencing wetland soil carbon and nitrogen. In addition, this study found that most of the main microbial taxa were significantly correlated with dissolved organic carbon (DOC), ammonium nitrogen (NH4+), and nitrate and nitrite nitrogen (NOx-) indicating that microorganisms might play an important role in regulating soil element cycles in constructed wetlands by affecting the metabolism of activated carbon and reactive nitrogen. This study has implications for increasing the carbon sink of constructed wetlands to mitigate the effects of global warming.

Monolayer NbSe2 Favors Ultralow Friction and Super Wear Resistance.

The urgent demand for atomically thin, superlubricating, and super wear-resistant materials in micro/nanoelectromechanical systems has stimulated the research of friction-reducing and antiwear materials. However, the fabrication of subnanometer-thick films with superlubricating and super wear-resistant properties under ambient conditions remains a huge challenge. Herein, high-quality monolayer (ML) NbSe2 (∼0.8 nm) with ultralow friction and super wear resistance in an atmospheric environment was successfully grown by chemical vapor deposition (CVD) for the first time. Moreover, compared with few-layered (FL) NbSe2, ML NbSe2 has a lower friction coefficient and better wear resistance. On the basis of density function theory (DFT) calculations, the adhesion and the degree of charge transfer between ML NbSe2 and the substrate is larger than that of the topmost layer to the underlying layers of NbSe2 with two or more layers, which can be used to explain that the ML NbSe2 favors ultralow friction and super wear resistance.

Habitats generated by the restoration of coal mining subsidence land differentially alter the content and composition of soil organic carbon.

The content and composition of soil organic carbon (SOC) can characterize soil carbon storage capacity, which varies significantly between habitats. Ecological restoration in coal mining subsidence land forms a variety of habitats, which are ideal to study the effects of habitats on SOC storage capacity. Based on the analysis of the content and composition of SOC in three habitats (farmland, wetland and lakeside grassland) generated by different restoration time of the farmland which was destroyed by coal mining subsidence, we found that farmland had the highest SOC storage capacity among the three habitats. Both dissolved organic carbon (DOC) and heavy fraction organic carbon (HFOC) exhibited higher concentrations in the farmland (20.29 mg/kg, 6.96 mg/g) than in the wetland (19.62 mg/kg, 2.47 mg/g) or lakeside grassland (5.68 mg/kg, 2.31 mg/g), and the concentrations increased significantly over time, owing to the higher content of nitrogen in the farmland. The wetland and lakeside grassland needed more time than the farmland to recover the SOC storage capacity. The findings illustrate that the SOC storage capacity of farmland destroyed by coal mining subsidence could be restored through ecological restoration and indicate that the recovery rate depends on the reconstructed habitat types, among which farmland shows great advantages mainly due to the nitrogen addition.

Metabolomic profiling for drug-induced liver injury with autoantibodies.

BACKGROUNDS: Drug induced liver injury (DILI) is sometimes similar to autoimmune hepatitis (AIH) in serology and histology. Clinicians empirically screened DILI with significant autoimmune characteristics to implement clinical intervention. We tried to characterize DILI with autoantibodies by metabolomics. METHODS: Untargeted metabolomics coupled with pattern recognition approaches were performed on sera samples including AIH (n = 59), DILI with autoantibodies (DILIAb+, n = 68), and DILI without autoantibodies (DILIAb-, n = 75). The differential metabolites and fingerprint metabolites between AIH and DILIAb- were screened by orthogonal partial least squares-discriminant analysis and hierarchical clustering respectively. RESULTS: Of the 388 annotated differential metabolites between AIH and DILIAb-, 74 fingerprint metabolites were screened. The eigenmetabolite compressed from the fingerprint possessed high discrimination efficacy (AUC:0.891; 95 %CI, 0.838-0.944). In the fingerprint-based PCA model, AIH and DILIAb- were separated into three regions: the "pure region" of AIH (Region 1), the "pure region" of DILIAb- (Region 3), the mixture region of AIH and DILIAb- (Region 2). After incorporated into the PCA model, DILIAb+ samples were distributed into the three regions, indicating that DILIAb+ samples had different etiological tendencies. Moreover, the fingerprint-based radar model verified the results of PCA model characterizing DILIAb+. Notably, the antibody titers of DILIAb+ in the three regions did not differ significantly, while the response rates for glucocorticoids were obviously different. The metabolic difference among DILIAb+ in different regions mainly lies in energy metabolism. CONCLUSIONS: In terms of metabolic signature, DILIAb+ may not be a community of same pathogenesis, including AIH-inclined parts. Which deserves further study.

Integrated green complexing agent and biochar modified nano zero-valent iron for hexavalent chromium removal: A characterisation and performance study.

In this study, nano zero-valent iron (nZVI) was loaded on biochar (BC) prepared from recycled waste peanut shells. The loaded BC in the nZVI@BC composite was assumed to weaken the agglomeration of nZVI and the environmentally-friendly complexing agents sodium citrate (Cit) and sodium carboxymethyl cellulose (CMC) were used to establish Cit-nZVI@BC and CMC-nZVI@BC for the effective removal of Cr(VI) from aqueous environments. The characterisation results suggested that Cit and CMC not only inhibited the oxidation of nZVI, but also effectively improved its reactivity. The experimental results demonstrated that the Cr(VI) removal efficiency by nZVI was less than 20%, while CMC-nZVI@BC enhanced the Cr(VI) removal efficiency to 80.73%, because CMC was coated on the nZVI surface for anti-passivation and improved the surface activity of nanoparticles. In addition, the Cr(VI) removal efficiency reached almost 100% with Cit-nZVI@BC, and the citrate dissociated the passivation layer on the surface of the zero-valent iron particles to ensure the reactivity of the zero-valent iron. The reaction mechanism of Cit-nZVI@BC includes adsorption, reduction, and co-precipitation, whereas CMC-nZVI@BC also involves surface complexation reactions. The kinetic studies revealed that the removal of Cr(VI) by Cit-nZVI@BC and CMC-nZVI@BC followed the second-order reaction kinetic model, and the reaction rates of Cit-nZVI@BC and CMC-nZVI@BC were both higher than that of nZVI. The results indicate that the prepared systems are promising for Cr(VI) remediation in contaminated environments.

ß-Hydroxybutyric acid attenuates heat stress-induced neuroinflammation via inhibiting TLR4/p38 MAPK and NF-κB pathways in the hippocampus.

Heat stress causes many pathophysiological responses in the brain, including neuroinflammation and cognitive deficits. ß-Hydroxybutyric acid (BHBA) has been shown to have neuroprotective effects against inflammation induced by lipopolysaccharide. The aim of the present study was to evaluate the effects of BHBA on neuroinflammation induced by heat stress, as well as the underlying mechanisms. Mice were pretreated with vehicle, BHBA or minocycline (positive control group) and followed by heat exposure (43°C) for 15 min for 14 days. In mice subjected to heat stress, we found that treatment with BHBA or minocycline significantly decreased the level of serum cortisol, the expressions of heat shock protein 70 (HSP70), and the density of c-Fos+ cells in the hippocampus. Surprisingly, the ethological tests revealed that heat stress led to cognitive dysfunctions and could be alleviated by BHBA and minocycline administration. Further investigation showed that BHBA and minocycline significantly attenuated the activation of microglia and astrocyte induced by heat stress. Pro-inflammatory cytokines were attenuated in the hippocampus by BHBA and minocycline treatment. Importantly, compared with the heat stress group, mice in the BHBA treatment group and positive control group experienced a decrease in the expressions of toll-like receptor 4 (TLR4), phospho-p38 (p-p38), and nuclear factor kappa B (NF-κB). Our results elucidated that BHBA inhibits neuroinflammation induced by heat stress by suppressing the activation of microglia and astrocyte, and modulating TLR4/p38 MAPK and NF-κB pathways. This study provides new evidence that BHBA is a potential strategy for protecting animals from heat stress.

ß-Hydroxybutyric acid improves cognitive function in a model of heat stress by promoting adult hippocampal neurogenesis.

Heat stress has multiple potential effects on the brain, such as neuroinflammation, neurogenesis defects, and cognitive impairment. ß-hydroxybutyric acid (BHBA) has been demonstrated to play neuroprotective roles in various models of neurological diseases. In the present study, we investigated the efficacy of BHBA in alleviating heat stress-induced impairments of adult hippocampal neurogenesis and cognitive function, as well as the underlying mechanisms. Mice were exposed to 43 ℃ for 15 min for 14 days after administration with saline, BHBA, or minocycline. Here, we showed for the first time that BHBA normalized memory ability in the heat stress-treated mice and attenuated heat stress-impaired hippocampal neurogenesis. Consistently, BHBA noticeably improved the synaptic plasticity in the heat stress-treated hippocampal neurons by inhibiting the decrease of synapse-associated proteins and the density of dendritic spines. Moreover, BHBA inhibited the expression of cleaved caspase-3 by suppressing endoplasmic reticulum (ER) stress, and increased the expression of brain-derived neurotrophic factor (BDNF) in the heat stress-treated hippocampus by activating the protein kinase B (Akt)/cAMP response element binding protein (CREB) and methyl-CpG binding protein 2 (MeCP2) pathways. These findings indicate that BHBA is a potential agent for improving cognitive functions in heat stress-treated mice. The action may be mediated by ER stress, and Akt-CREB-BDNF and MeCP2 pathways to improve adult hippocampal neurogenesis and synaptic plasticity.

Sodium citrate and biochar synergistic improvement of nanoscale zero-valent iron composite for the removal of chromium (â ¥) in aqueous solutions.

Sodium citrate (SC) is a widely-used food and industrial additive with the properties of complexation and microbial degradation. In the present study, nano-zero-valent iron reaction system (SC-nZVI@BC) was successfully established by modifying nanoscale zero-valent iron (nZVI) with SC and biochar (BC), and was employed to remove Cr(Ⅵ) from aqueous solutions. The nZVI, SC-nZVI and SC-nZVI@BC were characterized and compared using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analyses (TGA), vibrating sample magnetometer (VSM), scanning electron microscope (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results showed that nZVI was successfully loaded on the biochar, and both the agglomeration and surface passivation problems of nanoparticles were well resolved. The dosage of SC, C:Fe, initial pH and Cr(Ⅵ) concentration demonstrated direct effects on the removal efficiency. The maximum Cr(Ⅵ) removal rate and the removal capacity within 60 min were 99.7% and 199.46 mg/g, respectively (C:Fe was 1:1, SC dosage was 1.12 mol.%, temperature was 25°C, pH = 7, and the original concentration of Cr(Ⅵ) was 20 mg/L). The reaction confirmed to follow the pseudo-second-order reaction kinetics, and the order of the reaction rate constant k was as follows: SC-nZVI@BC > nZVI@BC > SC-nZVI > nZVI. In addition, the mechanism of Cr(Ⅵ) removal by SC-nZVI@BC mainly involved adsorption, reduction and co-precipitation, and the reduction of Cr(Ⅵ) to Cr(Ⅲ) by nano Fe0 played a vital role. Findings from the present study demonstrated that the SC-nZVI@BC exhibited excellent removal efficiency toward Cr(Ⅵ) with an improved synergistic characteristic by SC and BC.

Multidimensional Analyses of Tumor Immune Microenvironment Reveal the Possible Rationality of Immunotherapy and Identify High Immunotherapy Response Subtypes for Renal Papillary Cell Carcinoma.

Kidney renal papillary cell carcinoma (KIRP), the second most common subtype of renal cell carcinoma, still lacks effective treatment regimens for individualized immunotherapy because of the heterogeneity of its elusive immune microenvironment. Therefore, we aimed to comprehensively evaluate the immune microenvironment of KIRP by using the computational biology strategy to analyze the expression profile data of 289 KIRP patients obtained from The Cancer Genome Atlas database. Based on multidimensional, multi-omics bioinformatics analysis, we found that the tumor of patients with KIRP exhibited "hot" tumor characteristics but the CD8+ T cells in the tumor tissues did not limit tumor progression. Thus, patients with KIRP may realize higher clinical benefits by receiving treatment that can reverse CD8+ T-cell exhaustion. Among them, C1 and C3 immune subtypes could realize the best efficacy of reversing CD8+ T-cell exhaustion. Moreover, CCL5 and FASLG expression may be related to the formation of the immunosuppressive microenvironment in the tumors of patients with KIRP. In conclusion, the immune microenvironment landscape presented in this study provides a novel insight for further experimental and clinical exploration of tailored immunotherapy for patients with KIRP.

Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN.

BACKGROUND: MYCN is an oncogenic transcription factor of the MYC family and plays an important role in the formation of tissues and organs during development before birth. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets. METHODS: We utilized network controllability theory, a recent developed powerful tool, to identify the potential drug target around MYCN based on Protein-Protein interaction network of MYCN. First, we constructed a Protein-Protein interaction network of MYCN based on public databases. Second, network control analysis was applied on network to identify driver genes and indispensable genes of the MYCN regulatory network. Finally, we developed a novel integrated approach to identify potential drug targets for regulating the function of the MYCN regulatory network. RESULTS: We constructed an MYCN regulatory network that has 79 genes and 129 interactions. Based on network controllability theory, we analyzed driver genes which capable to fully control the network. We found 10 indispensable genes whose alternation will significantly change the regulatory pathways of the MYCN network. We evaluated the stability and correlation analysis of these genes and found EGFR may be the potential drug target which closely associated with MYCN. CONCLUSION: Together, our findings indicate that EGFR plays an important role in the regulatory network and pathways of MYCN and therefore may represent an attractive therapeutic target for cancer treatment.

TRIB3 Promotes the Malignant Progression of Bladder Cancer: An Integrated Analysis of Bioinformatics and in vitro Experiments.

BACKGROUND: Bladder cancer is a common malignant tumor characterized by high mortality and high management costs; however, it lacks useful molecular prognostic markers. Tribbles pseudokinase 3 (TRIB3) is a pseudokinase that participates in cell tumor progression and metabolism and whose function in bladder cancer is not precisely known. MAIN METHODS: We downloaded transcriptome data and clinical data of bladder cancer from associated databases and extracted the expression matrix of TRIB3 for multiple bioinformatics analysis. RT-PCR detected the expression of TRIB3 in bladder cancer cells. After knockdown of TRIB3 with siRNA, we investigated TRIB3 function using CCK8, Cell Cycle and Transwell assays. KEY FINDINGS: Kaplan-Meier analysis of TRIB3 in the four cohorts showed that high expression of TRIB3 correlated with poor outcome. Expression of TRIB3 positively correlated with stage and grade and down-regulation of TRIB3 expression significantly inhibited proliferation, migration and cell cycle of bladder cancer cells. SIGNIFICANCE: TRIB3 is a potential prognostic marker and therapeutic target. It can be used to individualize the treatment of bladder cancer.