Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Recent Advances and Synergistic Effects of Non-Precious Carbon-Based Nanomaterials as ORR Electrocatalysts: A Review.

The use of platinum-free (Pt) cathode electrocatalysts for oxygen reduction reactions (ORRs) has been significantly studied over the past decade, improving slow reaction mechanisms. For many significant energy conversion and storage technologies, including fuel cells and metal-air batteries, the ORR is a crucial process. These have motivated the development of highly active and long-lasting platinum-free electrocatalysts, which cost less than proton exchange membrane fuel cells (PEMFCs). Researchers have identified a novel, non-precious carbon-based electrocatalyst material as the most effective substitute for platinum (Pt) electrocatalysts. Rich sources, outstanding electrical conductivity, adaptable molecular structures, and environmental compatibility are just a few of its benefits. Additionally, the increased surface area and the simplicity of regulating its structure can significantly improve the electrocatalyst's reactive sites and mass transport. Other benefits include the use of heteroatoms and single or multiple metal atoms, which are capable of acting as extremely effective ORR electrocatalysts. The rapid innovations in non-precious carbon-based nanomaterials in the ORR electrocatalyst field are the main topics of this review. As a result, this review provides an overview of the basic ORR reaction and the mechanism of the active sites in non-precious carbon-based electrocatalysts. Further analysis of the development, performance, and evaluation of these systems is provided in more detail. Furthermore, the significance of doping is highlighted and discussed, which shows how researchers can enhance the properties of electrocatalysts. Finally, this review discusses the existing challenges and expectations for the development of highly efficient and inexpensive electrocatalysts that are linked to crucial technologies in this expanding field.

Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism.

OBJECTIVE: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice. METHODS: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed. RESULTS: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella. CONCLUSIONS: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.

NiFe2O4 Material on Carbon Paper as an Electrocatalyst for Alkaline Water Electrolysis Module.

NiFe2O4 material is grown on carbon paper (CP) with the hydrothermal method for use as electrocatalysts in an alkaline electrolyzer. NiFe2O4 material is used as the anode and cathode catalysts (named NiFe(+)/NiFe(-) hereafter). The results are compared with those obtained using CP/NiFe as the anode and CP/Ru as the cathode (named NiFe)(+)/Ru(-) hereafter). During cell operation with NiFe(+)/Ru(-), the current density reaches 500 mA/cm2 at a cell voltage of 1.79 V, with a specific energy consumption of 4.9 kWh/m3 and an energy efficiency of 66.2%. In comparison, for NiFe(+)/NiFe(-), the current density reaches 500 mA/cm2 at a cell voltage of 2.23 V, with a specific energy consumption of 5.7 kWh/m3 and an energy efficiency of 56.6%. The Faradaic efficiency is 96-99%. With the current density fixed at 400 mA/cm2, after performing a test for 150 h, the cell voltage with NiFe(+)/Ru(-) increases by 0.167 V, whereas that with NiFe(+)/NiFe(-) decreases by only 0.010 V. Good, long-term stability is demonstrated.

TGF-ß1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.

Background: Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-ß and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism. Methods: Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-ß1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-ß1 on breast cancer progression. Results: In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-ß1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-ß1 induced EndMT by activation of TGF-ß and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-ß and Notch signaling pathways. Conclusion: Our findings elucidated the mechanism of TGF-ß1 in the promotion of angiogenesis and progression by EndMT in breast cancer.

Electrolytic Recovery of Metal Cobalt from Waste Catalyst Pickling Solution.

Terephthalic acid production plant uses liquid cobalt-manganese bromide as a catalyst. The waste catalyst is burned with exhaust gas and accumulated in fly ash, which is further pickled and impregnated with a sulfuric acid solution. The resultant solution is rich in cobalt and manganese metal ions with few metal impurities from other petroleum raw materials. An electrochemical reduction method is used to recover cobalt metal from the waste catalyst fly ash pickling solution of terephthalic acid. Various steps have been taken to remove impurities and extract and separate the required pure cobalt metal solution. Afterward, the process of electrolytic reduction smelting is conducted. Variables investigated include current density, electrolyte pH, electrode materials, and electrolytic cell diaphragms, among several others. Results show that the product purity can reach up to 99.84% for the electrolyte feed composition of 21.4 g L-1 Co, 38.2 g L-1 Na, and 2.02 g L-1 Mg.

Corrigendum: TGF-ß1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.

[This corrects the article DOI: 10.3389/fonc.2022.1051148.].

Comprehensive Analysis of the Immune Implication of TEX41 in Skin Cutaneous Melanoma.

Enhancer RNAs (eRNAs), a subclass of noncoding RNAs from enhancers, have been demonstrated to exhibit important regulatory effects on the expressions of various genes. However, the role of eRNAs in skin cutaneous melanoma (SKCM) remained largely unclear. In this study, we aimed to explore the expression and prognostic value of an enhancer RNA TEX41 in SKCM as well as the associations between TEX41 and tumor-infiltrating immune cells (TICs). We observed that TEX41 expression was distinctly increased in SKCM specimens compared with normal skin specimens using GEPIA. Survival assays based on TGCA datasets revealed that patients with low TEX41 expressions displayed a longer overall survival than those with high TEX41 expression. CIBERSORT datasets revealed that TEX41 was related to 8 types of TICs (macrophages M1, T cells regulatory, plasma cells, mast cells resting, T cells CD8, dendritic cells resting, and T cells follicular helper). Three kinds of TICs were negatively related to TEX41 expressions, including macrophages M2, NK cells resting, and macrophages M0. The expressions of TEX41 were involved in five KEGG pathways, including transcriptional misregulation in cancer, SNARE interactions in vesicular transport, mitophagy-animal, melanoma, melanogenesis, and progesterone-mediated oocyte maturation. Overall, TEX41 can be used as a novel biomarker for the prognosis of SKCM patients and is associated with TICs, indicating it as a therapeutic target for SKCM.

Characteristics of Graphite Felt Electrodes Treated by Atmospheric Pressure Plasma Jets for an All-Vanadium Redox Flow Battery.

In an all-vanadium redox flow battery (VRFB), redox reaction occurs on the fiber surface of the graphite felts. Therefore, the VRFB performance highly depends on the characteristics of the graphite felts. Although atmospheric pressure plasma jets (APPJs) have been applied for surface modification of graphite felt electrode in VRFBs for the enhancement of electrochemical reactivity, the influence of APPJ plasma reactivity and working temperature (by changing the flow rate) on the VRFB performance is still unknown. In this work, the performance of the graphite felts with different APPJ plasma reactivity and working temperatures, changed by varying the flow rates (the conditions are denoted as APPJ temperatures hereafter), was analyzed and compared with those treated with sulfuric acid. X-ray photoelectron spectroscopy (XPS) indicated that the APPJ treatment led to an increase in O-/N-containing functional groups on the GF surface to ~21.0% as compared to ~15.0% for untreated GF and 18.0% for H2SO4-treated GF. Scanning electron microscopy (SEM) indicated that the surface morphology of graphite felt electrodes was still smooth, and no visible changes were detected after oxidation in the sulfuric acid or after APPJ treatment. The polarization measurements indicated that the APPJ treatment increased the limiting current densities from 0.56 A·cm-2 for the GFs treated by H2SO4 to 0.64, 0.68, and 0.64 A·cm-2, respectively, for the GFs APPJ-treated at 450, 550, and 650 °C, as well as reduced the activation overpotential when compared with the H2SO4-treated electrode. The electrochemical charge/discharge measurements showed that the APPJ treatment temperature of 550 °C gave the highest energy efficiency of 83.5% as compared to 72.0% with the H2SO4 treatment.

Modifying the Catalyst Layer Using Polyvinyl Alcohol for the Performance Improvement of Proton Exchange Membrane Fuel Cells under Low Humidity Operations.

A proton exchange membrane fuel cell (PEMFC) system for the application of unmanned aerial vehicles is equipped without humidifiers and the cathode channels of the stack are open to the environment due to limited weight available for power sources. As a result, the PEMFC is operated under low humidity conditions, causing membrane dehydration, low performance, and degradation. To keep the generated water within the fuel cell to humidify the membrane, in this study, polyvinyl alcohol (PVA) is employed in the fabrication of membrane electrode assemblies (MEAs). The effect of PVA content, either sprayed on the gas diffusion layer (GDL) or mixed in the catalyst layer (CL), on the MEA performance is compared under various humidity conditions. The results show that MEA performance is increased with the addition of PVA either on the GDL or in the CL, especially for non-humidified anode conditions. The result suggested that 0.03% PVA in the anode CL and 0.1% PVA on the GDL can improve the MEA performance by approximately 30%, under conditions of a non-humidified anode and a room-temperature-humidified cathode. However, MEAs with PVA in the anode CL show better durability than those with PVA on the GDL according to measurement with electrochemical impedance spectroscopy.

Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy.

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic profiling of 29 immune signatures. We named three LUAD subtypes: Immunity High, Immunity Medium, and Immunity Low. The Immunity High subtype was characterized by immune activation, e.g., increased immune scores, elevated stromal scores and the highest infiltration of CD8+ T cells, and decreased tumor purities. Activated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T helper 1 (Th1)/interferon-gamma (IFNγ) gene signature were also observed in the Immunity High subtype. N 6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, was reduced in the Immunity High subtype. Functional and signaling pathway enrichment analysis further showed that differentially expressed genes between the Immunity High subtype and the other subtypes mainly participated in immune response and some cancer-associated pathways. In addition, the Immunity High subtype exhibited more sensitivity to immunotherapy and chemotherapy. Finally, candidate compounds that aimed at LUAD subtype differentiation were identified. Comprehensively characterizing the LUAD subtypes based on immune signatures may help to provide potential strategies for LUAD treatment.

CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer.

The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3ß/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.

Hemin, a heme oxygenase-1 inducer, improves aortic endothelial dysfunction in insulin resistant rats.

BACKGROUND: Under an insulin resistance (IR) state, overproduction of reactive oxygen species (ROS) may be playing a major role in the pathogenesis of endothelial dysfunction, hypertension and atherosclerosis. Recently, increasing attention has been drawn to the beneficial effects of heme oxygenase-1 (HO-1) in the cardiovascular system. This study aimed to investigate the effects of HO-1 on vascular function of thoracic aorta in IR rats and demonstrate the probable mechanisms of HO-1 against endothelial dysfunction in IR states. METHODS: Sprague-Dawley (SD) rats fed with high-fat diet for 6 weeks and the IR models were validated with hyperinsulinemic-euglycemic clamp test. Then the IR rat models (n = 44) were further randomized into 3 subgroups, namely, the IR control group (n = 26, in which 12 were sacrificed immediately and evaluated for all study measures), a hemin treated IR group (n = 10) and a zinc protoporphyrin-IX (ZnPP-IX) treated IR group (n = 8) that were fed with a high-fat diet. Rats with standardized chow diet were used as the normal control group (n = 12). The rats in IR control group, hemin treated IR group and ZnPP-IX treated IR group were subsequently treated every other day with an intraperitoneal injection of normal saline, hemin (inducer of HO-1, 30 micromol/kg) or ZnPP-IX (inhibitor of HO-1, 10 micromol/kg) for 4 weeks. Rats in the normal control group remained on a standardized chow diet and were treated with intraperitoneal injections of normal saline every other day for 4 weeks. Systolic arterial blood pressure (SABP) was measured by tail-cuffed microphotoelectric plethysmography. The blood carbon monoxide (CO) was measured by blood gas analysis. The levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), blood glucose (BG), insulin, total cholesterol (TC) and triglyceride (TG) in serum, and the levels of total antioxidant capacity (TAOC), malondialdehyde (MDA) and superoxide dismutase (SOD) in the aorta were measured. The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreactive tensometry was performed with thoracic aortic rings (TARs). RESULTS: Compared with the normal control group, the levels of SABP, BG, insulin, TC, TG, NO, iNOS and MDA were higher, while the levels of CO, TAOC, SOD and eNOS were lower in IR control rats. After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group. And compared with 4-week IR control rats, the levels of CO, TAOC, SOD and eNOS were increased, while the levels of SABP and iNOS activity were lower in the hemin treated IR group. Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine (ACh). Alternatively, the reverse results of SABP, CO, TAOC, SOD, iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-IX. CONCLUSIONS: The endothelial dysfunction in the aorta is present in the IR state. The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances. It is proposed that hemin, inducer of HO-1, could be a potential therapeutic option for vascular dysfunction in IR states.