Good Cycling Stabilities of Sn/SnO2/C/S Composite Electrodes with Introduced Active Tin Atoms in Li-S Batteries.

Polysulfides are easily dissolved in the electrolyte of Li-S batteries after long cycles. Sn atom modification electrodes are beneficial for improving cycling stabilities of Li-S batteries. However, the influence of Sn atoms on the structure and electrochemical performance of SnO2/C composite materials is not explored. Sn/SnO2/C composite materials are developed as sulfur carriers in Li-S batteries in our work. In addition, the cycling stability mechanism of Sn/SnO2/C/S composite electrodes is also elucidated. Results show that introduced Sn/SnO2/C/S composite electrodes display good cycling stability (420.1 mAh·g-1 at 1C after 1000 cycles) in Li-S batteries. The sulfur load of Sn/SnO2/C/S composite electrodes is 80 wt % (2 mg-1·cm-2). The introduction of Sn into Sn/SnO2/C/S composite electrodes plays three roles. The first role is to enhance the structural stability of SnO2. The second role is to help adsorb active sulfur ions. The last role is to promote the electron transportation ability during the initial discharging/charging process. Sn/SnO2/C/S composite electrodes are beneficial for inhibiting the dissolution of polysulfides in electrolytes after long cycles.

ZAP facilitates NLRP3 inflammasome activation via promoting the oligomerization of NLRP3.

The NOD-like receptor family protein 3 (NLRP3) inflammasome is a crucial complex for the host to establish inflammatory immune responses and plays vital roles in a series of disorders, including Alzheimer's disease and acute peritonitis. However, its regulatory mechanism remains largely unclear. Zinc finger antiviral protein (ZAP), also known as zinc finger CCCH-type antiviral protein 1 (ZC3HAV1), promotes viral RNA degradation and plays vital roles in host antiviral immune responses. However, the role of ZAP in inflammation, especially in NLRP3 activation, is unclear. Here, we show that ZAP interacts with NLRP3 and promotes NLRP3 oligomerization, thus facilitating NLRP3 inflammasome activation in peritoneal macrophages of C57BL/6 mice. The shorter isoform of ZAP (ZAPS) appears to play a greater role than the full-length isoform (ZAPL) in HEK293T cells. Congruously, Zap-deficient C57BL/6 mice may be less susceptible to alum-induced peritonitis and lipopolysaccharide-induced sepsis in vivo. Therefore, we propose that ZAP is a positive regulator of NLRP3 activation and a potential therapeutic target for NLRP3-related inflammatory disorders.

The UAF1-USP1 Deubiquitinase Complex Stabilizes cGAS and Facilitates Antiviral Responses.

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) detects cytoplasmic microbial DNA and self-DNA from genomic instability, initiates innate immunity, and plays fundamental roles in defense against viruses and the development of various diseases. The cellular cGAS level determines the magnitude of the response to DNA. However, the underlying mechanisms of the control of cGAS stability, especially its feedback regulation during viral infection, remain largely unknown. In this study, we show that viral infection induces the expression of the UAF1-USP1 deubiquitinase complex in primary peritoneal macrophages (PMs) of C57BL/6J mice. UAF1-USP interacts with cGAS, selectively cleaves its K48-linked polyubiquitination, and thus stabilizes its protein expression in PMs and HEK293T cells. Concordantly, the UAF1-USP1 deubiquitinase complex enhances cGAS-dependent type I IFN responses in PMs. Uaf1 deficiency and ML323 (a specific inhibitor of UAF1-USP1 deubiquitinase complex) attenuates cGAS-triggered antiviral responses and facilitates viral replication both in vitro and in vivo. Thus, our study uncovers a positive feedback mechanism of cGAS-dependent antiviral responses and suggests the UAF1-USP1 complex as a potential target for the treatment of diseases caused by aberrant cGAS activation.

Explosion Strategy Engineering Oxygen-Functionalized Groups and Enlarged Interlayer Spacing of the Carbon Anode for Enhanced Lithium Storage.

Amorphous carbon monoliths with tunable microstructures are candidate anodes for future lithium-based energy storage. Enhancing lithium storage capability and solid-state diffusion kinetics are the precondition for practical applications. Transforming intrinsic oxygen-rich defects into active sites and engineering enlarged interlayer spacing are of great importance. Herein, a novel explosion strategy is designed based on oxalate pyrolysis producing CO and CO2 to successfully prepare lignin-derived carbon monolith (LSCM) with active carbonyl (C═O) groups and enlarged interlayer spacing. Explosion promotes the demethylation of methoxyl groups and cleavage of carboxyl groups to form C═O groups. CO2 etches carbon atoms in a short time to improve the heteroatom level, expanding the interlayer spacing. ZnC2O4 is decomposed at 400 °C, simultaneously producing CO and CO2, which constructs less C═O groups and large interlayer spacing. MgC2O4 is decomposed at 450 and 480 °C, staged-weakly producing CO and CO2, which constructs more C═O groups and larger interlayer spacing. CaC2O4 is decomposed at 480 and 700 °C, staged-uniformly producing CO and CO2, which constructs abundant C═O groups and largest interlayer spacing. The LSCM prepared by staged-uniform explosion exhibits high lithium storage capacity, superior rate capability, and cycling performance. The assembled lithium ion capacitor device achieves excellent energy/power densities of 78 Wh kg-1/100 W kg-1 and superior durability (capacitance retention of 8 4.6% after 20,000 cycles). This work gives a novel insight to engineer advanced oxygen-functionalized carbons for enhanced lithium storage.

Corrigendum: Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/ß-Catenin/ABCG2 Axis.

[This corrects the article DOI: 10.3389/fphar.2021.659297.].

Lignin Derived Porous Carbons: Synthesis Methods and Supercapacitor Applications.

Lignin, one of the renewable constituents in natural plant biomasses, holds great potential as a sustainable source of functional carbon materials. Tremendous research efforts have been made on lignin-derived carbon electrodes for rechargeable batteries. However, lignin is considered as one of the most promising carbon precursors for the development of high-performance, low-cost porous carbon electrode materials for supercapacitor applications. Yet, these efforts have not been reviewed in detail in the current literature. This review, therefore, offers a basis for the utilization of lignin as a pivotal precursor for the synthesis of porous carbons for use in supercapacitor electrode applications. Lignin chemistry, the synthesis process of lignin-derived porous carbons, and future directions for developing better porous carbon electrode materials from lignin are systematically reviewed. Technological hurdles and approaches that should be prioritized in future research are presented.

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/ß-Catenin/ABCG2 Axis.

Accumulating evidence suggests that the root of drug chemoresistance in breast cancer is tightly associated with subpopulations of cancer stem cells (CSCs), whose activation is largely dependent on taxol-promoting autophagy. Our pilot study identified GRP78 as a specific marker for chemoresistance potential of breast CSCs by regulating Wnt/ß-catenin signaling. Ai Du Qing (ADQ) is a traditional Chinese medicine formula that has been utilized in the treatment cancer, particularly during the consolidation phase. In the present study, we investigated the regulatory effects and molecular mechanisms of ADQ in promoting autophagy-related breast cancer chemosensitivity. ADQ with taxol decreasing the cell proliferation and colony formation of breast cancer cells, which was accompanied by suppressed breast CSC ratio, limited self-renewal capability, as well as attenuated multi-differentiation. Furthermore, autophagy in ADQ-treated breast CSCs was blocked by taxol via regulation of ß-catenin/ABCG2 signaling. We also validated that autophagy suppression and chemosensitizing activity of this formula was GRP78-dependent. In addition, GRP78 overexpression promoted autophagy-inducing chemoresistance in breast cancer cells by stabilizing ß-catenin, while ADQ treatment downregulated GRP78, activated the Akt/GSK3ß-mediated proteasome degradation of ß-catenin via ubiquitination activation, and consequently attenuated the chemoresistance-promoted effect of GRP78. In addition, both mouse breast cancer xenograft and zebrafish xenotransplantation models demonstrated that ADQ inhibited mammary tumor growth, and the breast CSC subpopulation showed obscure adverse effects. Collectively, this study not only reveals the chemosensitizating mechanism of ADQ in breast CSCs, but also highlights the importance of GRP78 in mediating autophagy-promoting drug resistance via ß-catenin/ABCG2 signaling.

Corrigendum: Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling.

[This corrects the article DOI: 10.3389/fphar.2020.591400.].

Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling.

Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments-including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection-validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

Treatment of municipal sludge by hydrothermal oxidation process with H2O2.

The recent increase in municipal sludge worldwide has led to a great deal of interest in developing an efficient and environmentally friendly sludge treatment method. In the paper, the treatment of municipal sludge by hydrothermal oxidation (HTO) process with H2O2 as the oxidant was proposed. The impacts of HTO temperature and H2O2 mass fraction on the distribution of products, the moisture content, the migration behaviors of the heavy metals (HMs) of the resulted solid products, the concentration of volatile fatty acids (VFAs) and NH3-N contained in the resulted aqueous phase products and the pH value were investigated. The results indicated that the sludge reduction was achieved by HTO treatment, the increasing H2O2 mass fraction and HTO temperature can significantly improve the dewatering performance of the sludge. The potential toxicity fraction of Pb and Cd contained in the resulted solid residual increased with the increasing HTO severity and the potential toxicity fraction of solid residues was still lower than that of raw material. Acetic acid was the main VFAs produced from HTO treated sludge, and its concentration reached to the maximum value of 2923.41 mg/L at 230 °C under H2O2 mass fraction of 15%. The change in the pH of the resulted aqueous phase products was caused by the competition between the acidic (VFAs or CO2) or alkaline (NH3-N) substances derived from the sludge during HTO process. The HTO process was expected to be an efficient method for municipal sludge treatment due to its mild conditions and high heavy metal safety.

Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. MATERIALS AND METHODS: In vivo OA model was established by intra-articular injection (1.5 mg) of monosodium iodoacetate (MIA) into rats and weekly treated by intra-articular administration of EAA at a dose range from 0.3 to 0.9 g/kg for four weeks. The pain behavior parameters, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were tested before and after the treatment. Then histopathologic, immunohistochemical and TUNEL analyses of the articular cartilage were conducted, followed by Mankin's scoring. In vitro, the effects of EAA on chondrocytes were evaluated via assays of cell viability, immunofluorescence, real time PCR, and Western blot. UPLC-MS was applied to determine the chemical composition of EAA. RESULTS: The animal data showed that EEA not only attenuated the pain hypersensitivity but also blocked the cartilage degeneration by improving chondrocyte survival and suppressing chondrocyte apoptosis at a dose-dependent manner in OA rats. Furthermore, EAA remarkably restored the abnormal expression of collagen type II (Col2) and matrix metalloproteinase-13 (MMP13) in cartilage of OA rats. The cellular data showed that EAA significantly increased the cell viability of chondrocytes against OA-like damage and restored the abnormal expressions of Col2 and MMP13 in damaged chondrocytes. The molecular data showed that EAA significantly restored the abnormal mRNA expressions of Col2, Col10, MMP2 and MMP13 as well as the abnormal protein expressions of MMP13, PARP (total and cleaved) in chondrocytes under pathological condition. UPLC-MS analysis showed the known main components of EAA, including amino acides (glycine, L-aspartic acid, L-glutamic acid, and L-hydroxyproline), nucleoside (uridine), purines (xanthine and hypoxanthine), and pyrimidine (uracil). CONCLUSIONS: Our data demonstrate that EAA exerts antinociceptive and chondroprotective effects on OA through suppressing chondrocyte hypertrophy and apoptosis with restoration of the molecular expressions of anabolism and catabolism in chondrocytes. It provides a promising TCM candidate of novel agent for OA therapy.

Intra-Articular Injection of Fructus Ligustri Lucidi Extract Attenuates Pain Behavior and Cartilage Degeneration in Mono-Iodoacetate Induced Osteoarthritic Rats.

Fructus Ligustri Lucidi (FLL) has been widely used as a traditional Chinese medicine (TCM) for treating soreness and weakness of waist and knees. It has potential for treating OA owing to its kidney-tonifying activity with bone-strengthening effects, but there is so far no report of its anti-OA effect. This study established a rat OA model by intra-articular (IA) injection of mono-iodoacetate (1.5 mg) and weekly treated by IA administration of FLL at 100 µg/mL for 4 weeks. Thermal withdrawal latency, mechanical withdrawal threshold, and spontaneous activity were tested for evaluation of pain behavior, and histopathological (HE, SO, and ABH staining) and immunohistochemical (Col2, Col10, and MMP13) analyses were conducted for observation of cartilage degradation. In vitro effect of FLL on chondrocytes was evaluated by MTT assay and qPCR analysis. Moreover, HPLC analysis was performed to determine its chemoprofile. The pain behavioral data showed that FLL attenuated joint pain hypersensitivity by increasing thresholds of mechanical allodynia and thermal hyperalgesia as well as spontaneous activity. The histopathological result showed that FLL reversed OA cartilage degradation by protecting chondrocytes and extracellular matrix in cartilage, and the immunohistochemical analysis revealed its molecular actions on protein expressions of MMP13, Col2, and Col10 in cartilage. The MTT assay showed its proliferative effects on chondrocytes, and qPCR assay clarified its mechanism associated with gene expressions of Mmp13, Col2, Col10, Adamts5, Aggrecan, and Runx2 in TNF-α treated chondrocytes. Our results revealed an anti-OA effect of FLL on pain behavior and cartilage degradation in OA rats and clarified a molecular mechanism in association with the suppression of chondrocyte hypertrophy and catabolism. IA FLL can be regarded as novel and promising option for OA therapy.

Effect of oxidation processing on the preparation of post-hydrothermolysis acid from cotton stalk.

The typical properties and yield of the refined hydrothermolytic acid (RHTA) and refined hydrothermolytic oxidation acid (RHOA) respectively prepared from cotton stalk by the hydrothermolysis process with and without hydrogen peroxide at 180-280 °C were investigated. The pH of RHOA at 180-260 °C is lower than that of RHTA. The yield of RHOA prepared at 180-280 °C is higher than that of RHTA except 230 °C. Besides, the variation trend of RHOA yield at 180-260 °C is in accordance with that of RHTA yield at 200-280 °C. The composition of RHTA and RHOA were determined using gas chromatography and mass spectrometry. The acids content of RHOA at 200 °C reaches the maximum. The phenols of RHOA at 200-230 °C is significantly higher than that of RHTA. Under oxidation atmosphere, the formation of ketones is inhibited and the secondary reactions of furan derivatives is promoted. Overall, the oxidation processing can alleviate the severe hydrothermolysis conditions for preparing post-hydrothermolysis acid.

Volatility and partitioning of Cd and Pb during sewage sludge thermal conversion.

In this paper, the thermal characteristics of sewage sludge and the transformation behavior of Pb and Cd during the thermal conversion process were addressed. The incineration process and pyrolysis process of the sewage sludge were investigated by thermogravimetric analysis. The results indicated that the thermal conversion process of the sewage sludge could be divided into three stages and the presence of oxygen could accelerate the decomposition of the sewage sludge. Furthermore, the effects of thermal conditions on the concentration ratio of Cd and Pb and their species partitioning in the residual char and ash were investigated. For the pyrolysis process, the maximum concentration ratio of Cd reached 41.64% at 500 °C and the lowest one 2.92% at 700 °C. Contrary, the concentration ratio of Pb remained above 93% as the temperature increased. Thus, the suitable temperature for the sewage sludge pyrolysis was below 500 °C. For the incineration process, the incineration temperature had great influence on the concentration ratio of Cd and Pb. When the incineration temperature increased from 700 °C to 900 °C, the concentration ratio of Cd decreased drastically from 99.32% to 10.96%. The maximum concentration ratio for Pb (95.31%) was reached at 800 °C. Besides, the lowest concentration ratio of Cd and Pb were obtained at a residence time of 30 min. The partitioning analyses of the Cd and Pb contained in the ash showed that the residence time had little effect on the partitioning of Cd and Pb, and the residual fractions of Cd and Pb were both above 90%. It was concluded that Cd and Pb were properly stabilized in the ash. Thus, Cd and Pb in the ash were difficult to be released into the environment and to cause secondary pollution.

Study on an alternative approach for the preparation of wood vinegar from the hydrothermolysis process of cotton stalk.

The yield and pH of the refined aqueous product (RAP) prepared by the hydrothermolysis of cotton stalk (CS) were investigated using response surface methodology with the variation of three parameters: CS/water ratio of 0.05-0.15w/w, temperature of 180-280 °C, and retention time of 0-30 min. At the best formulation (0.05w/w, 264.36 °C and 0 min), the yield and pH of RAP were 82.8% and 3.95, respectively. Additionally, the organic compounds contained in RAP prepared under the respective optimal formulation (pH: 0.05w/w, 251.43 °C and 0 min, yield: 0.05w/w, 280.00 °C and 0 min) were determined by gas chromatography and mass spectrometry. The results show that the kinds of compounds in RAP are identical or similar to those in the wood vinegar (WV), but their contents is slightly higher than that of the WV. In sum, it is feasible that RAP has the enormous potential to be utilized as WV probably because of its higher quality and value than WV.

Sub-T(g) relaxation patterns in Cu-based metallic glasses far from equilibrium.

We investigate the sub-T(g) relaxation patterns (RPs) in binary and quaternary Cu-based glass ribbons (GRs) by using the hyperquenching-sub-T(g) annealing-calorimetric approach. This study contributes to revealing the structural or dynamic evolution in liquids related to the observed three-stage sub-T(g) relaxation processes in GRs. In this work, we have achieved the following three findings. First, the abnormal three-stage relaxation behavior is not a general phenomenon for Cu-based metallic glasses and could not be simply predicted by the large difference in the enthalpy of mixing between different elements in alloys. Second, the abnormal three-stage RP is associated with the non-monotonic change of cluster size with medium range order in supercooled liquids. Third, the existence of the liquid-liquid phase transition depicted by anomalous viscosity drop during cooling in superheated liquids could be a signature of the unusual structural change causing the abnormal three-step sub-T(g) RP in the GRs. This work helps to better understand the complex structural evolution from superheated to supercooled liquids approaching T(g).